Publications by year
In Press
Ezquerra-Romano I, lawn W, Krupitsky E, Morgan C (In Press). Ketamine for the treatment of addiction: Evidence and potential mechanisms. Neuropharmacology
Walsh Z, Mollaahmetoglu OM, Rootman J, Golsof S, Keeler J, Marsh BR, Nutt DJ, Morgan C (In Press). Ketamine for the treatment of mental health and substance use disorders: a comprehensive systematic review.
BJPsych OpenAbstract:
Ketamine for the treatment of mental health and substance use disorders: a comprehensive systematic review
Background: in the last two decades, subanaesthetic doses of ketamine have been demonstrated to have rapid and sustained antidepressant effects, and accumulating research has demonstrated ketamine's therapeutic effects for a range of psychiatric conditions.
Aims: in light of these findings surrounding ketamine’s psychotherapeutic potential, we systematically review the extant evidence on ketamine’s effects in treating mental health disorders.
Methods: the systematic review protocol was registered in PROSPERO (CRD42019130636). Human studies investigating the therapeutic effects of ketamine in the treatment of mental health disorders were included. Due to the extensive research in depression, bipolar disorder and suicidal ideation, only systematic reviews & meta-analyses were included. We searched Medline and PsychInfo on the 21st of October 2020. Risk of Bias analysis was assessed using the Cochrane Risk of Bias tools and a Measurement Tool to Assess Systematic Reviews (AMSTAR) Checklist.
Results: 83 published reports were included in the final review, consisting of 33 systematic reviews, 29 RCTs, two-randomised trials without placebo, two non-randomised trials with controls, six open label trials and ten retrospective reviews. The results were presented using narrative synthesis.
Conclusions: Systematic reviews and meta-analyses provide support for robust, rapid, and transient antidepressant and anti-suicidal effects of ketamine. Evidence for other indications is less robust but suggests similarly positive and short-lived effects. The conclusions should be interpreted with caution due to the high risk of bias of included studies. Optimal dosing, modes of administration and the most effective forms of adjunctive psychotherapeutic support needs to be further examined.
Abstract.
2023
Lees R, Hines LA, Hindocha C, Baio G, Shaban NDC, Stothart G, Mofeez A, Morgan CJA, Curran HV, Freeman TP, et al (2023). Effect of four-week cannabidiol treatment on cognitive function: secondary outcomes from a randomised clinical trial for the treatment of cannabis use disorder.
Psychopharmacology,
240(2), 337-346.
Abstract:
Effect of four-week cannabidiol treatment on cognitive function: secondary outcomes from a randomised clinical trial for the treatment of cannabis use disorder
Rationale: Chronic cannabis use is associated with impaired cognitive function. Evidence indicates cannabidiol (CBD) might be beneficial for treating cannabis use disorder. CBD may also have pro-cognitive effects; however, its effect on cognition in people with cannabis use disorder is currently unclear. Objectives: We aimed to assess whether a 4-week CBD treatment impacted cognitive function. We hypothesised that CBD treatment would improve cognition from baseline to week 4, compared to placebo. Methods: Cognition was assessed as a secondary outcome in a phase 2a randomised, double-blind, parallel-group and placebo-controlled clinical trial of 4-week daily 200 mg, 400 mg and 800 mg CBD for the treatment of cannabis use disorder. Participants had moderate or severe DSM-5 cannabis use disorder and intended to quit cannabis use. Our pre-registered primary cognitive outcome was delayed prose recall. Secondary cognitive outcomes were immediate prose recall, stop signal reaction time, trail-making task performance, verbal fluency and digit span. Results: Seventy participants were randomly assigned to placebo (n = 23), 400 mg CBD (n = 24) and 800 mg CBD (n = 23). A 200 mg group was eliminated from the trial because it was an inefficacious dose at interim analysis (n = 12) and was not analysed here. For the primary cognitive outcome, there was no effect of CBD compared to placebo, evidenced by a lack of dose-by-time interaction at 400 mg (0.46, 95%CIs: − 1.41, 2.54) and 800 mg (0.89, 95%CIs: − 0.99, 2.81). There was no effect of CBD compared to placebo on secondary cognitive outcomes, except backwards digit span which increased following 800 mg CBD (0.30, 95%CIs: 0.02, 0.58). Conclusions: in this clinical trial for cannabis use disorder, CBD did not influence delayed verbal memory. CBD did not have broad cognitive effects but 800 mg daily treatment may improve working memory manipulation. Clinical trial registration: the trial was registered with ClinicalTrials.gov (NCT02044809) and the EU Clinical Trials Register (2013–000,361-36).
Abstract.
2022
Grabski M, McAndrew A, Lawn W, Marsh B, Raymen L, Stevens T, Hardy L, Warren F, Bloomfield M, Borissova A, et al (2022). Adjunctive Ketamine with Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder.
Am J Psychiatry,
179(2), 152-162.
Abstract:
Adjunctive Ketamine with Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder.
OBJECTIVE: Early evidence suggests that ketamine may be an effective treatment to sustain abstinence from alcohol. The authors investigated the safety and efficacy of ketamine compared with placebo in increasing abstinence in patients with alcohol use disorder. An additional aim was to pilot ketamine combined with mindfulness-based relapse prevention therapy compared with ketamine and alcohol education as a therapy control. METHODS: in a double-blind placebo-controlled phase 2 clinical trial, 96 patients with severe alcohol use disorder were randomly assigned to one of four conditions: 1) three weekly ketamine infusions (0.8 mg/kg i.v. over 40 minutes) plus psychological therapy, 2) three saline infusions plus psychological therapy, 3) three ketamine infusions plus alcohol education, or 4) three saline infusions plus alcohol education. The primary outcomes were self-reported percentage of days abstinent and confirmed alcohol relapse at 6-month follow-up. RESULTS: Ninety-six participants (35 women; mean age, 44.07 years [SD=10.59]) were included in the intention-to-treat analysis. The treatment was well tolerated, and no serious adverse events were associated with the study drug. Although confidence intervals were wide, consistent with a proof-of-concept study, there were a significantly greater number of days abstinent from alcohol in the ketamine group compared with the placebo group at 6-month follow-up (mean difference=10.1%, 95% CI=1.1, 19.0), with the greatest reduction in the ketamine plus therapy group compared with the saline plus education group (15.9%, 95% CI=3.8, 28.1). There was no significant difference in relapse rate between the ketamine and placebo groups. CONCLUSIONS: This study demonstrated that treatment with three infusions of ketamine was well tolerated in patients with alcohol use disorder and was associated with more days of abstinence from alcohol at 6-month follow-up. The findings suggest a possible beneficial effect of adding psychological therapy alongside ketamine treatment.
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Chesters RA, Pepper F, Morgan C, Cooper JD, Howes OD, Vernon AC, Stone JM (2022). Brain volume in chronic ketamine users - relationship to sub-threshold psychotic symptoms and relevance to schizophrenia.
Psychopharmacology (Berl),
239(11), 3421-3429.
Abstract:
Brain volume in chronic ketamine users - relationship to sub-threshold psychotic symptoms and relevance to schizophrenia.
RATIONALE: Ketamine may model aspects of schizophrenia arising through NMDA receptor activity deficits. Although acute ketamine can induce effects resembling both positive and negative psychotic symptoms, chronic use may be a closer model of idiopathic psychosis. OBJECTIVES: We tested the hypotheses that ketamine users had lower brain volumes, as measured using MRI, and greater sub-threshold psychotic symptoms relative to a poly-drug user control group. METHODS: Ketamine users (n = 17) and poly-drug using controls (n = 19) were included in the study. All underwent volumetric MRI imaging and measurement of sub-threshold psychotic symptoms using the Comprehensive Assessment of At-Risk Mental State (CAARMS). Freesurfer was used to analyse differences in regional brain volume, cortical surface area and thickness between ketamine users and controls. The relationship between CAARMS ratings and brain volume was also investigated in ketamine users. RESULTS: Ketamine users were found to have significantly lower grey matter volumes of the nucleus accumbens, caudate nucleus, cerebellum and total cortex (FDR p
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Grabski M, Morgan C (2022). Ketamine. In (Ed) Reference Module in Neuroscience and Biobehavioral Psychology.
Walsh Z, Mollaahmetoglu OM, Rootman J, Golsof S, Keeler J, Marsh B, Nutt DJ, Morgan CJA (2022). Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review (vol 8, e19, 2021).
BJPSYCH OPEN,
8(1).
Author URL.
Moss M, Edelblute A, Sinn H, Torres K, Forster J, Adams T, Morgan C, Henry M, Reed K (2022). The Effect of Creative Arts Therapy on Psychological Distress in Health Care Professionals.
American Journal of Medicine,
135(10), 1255-1262.e5.
Abstract:
The Effect of Creative Arts Therapy on Psychological Distress in Health Care Professionals
Background: Work-related psychological distress is common among health care professionals. We determined whether 4 creative arts therapy (CAT) programs were acceptable, feasible, and improved psychological distress and job turnover intention in health care professionals with burnout symptoms. Methods: Health care professionals were enrolled during the coronavirus disease (COVID-19) pandemic from September 2020 until July 2021. Participants attended in-person weekly 90-minute group session for 12 consecutive weeks. Intervention and control subjects completed surveys before the beginning and after the end of their cohort. The study outcomes were session attendance (feasibility), program satisfaction (acceptability), and change in symptoms of anxiety, depression, burnout, posttraumatic stress disorder (PTSD), and job turnover intention. Results: We randomized 165 participants into 4 CAT interventions and 1 common control group across 3 sequential cohorts. Thirty-five randomized participants dropped out before the start of the cohort, and 16 were replaced from a waiting list. Therefore, the cohort consisted of 146 participants. On average, participants were 35 years old, white (85%), and female (92%). Overall, 52% were nurses, 10% were doctors, and 16% were behavioral health specialists. Participants attended a median of 9.5 [8-11] sessions. Program satisfaction was high with a median Client Satisfaction Questionnaire (CSQ-8) score of 31 [17-32] out of a possible score of 32. Participants randomized to the intervention had improvements in anxiety (P <. 0001) and depression scores (P =. 0007), total posttraumatic stress disorder score (P =.0002), burnout scores (P =. 001. 003. 008), and turnover intention (P =. 001). Conclusions: a CAT program is feasible, acceptable, and may reduce psychological distress and turnover intention for health care professionals.
Abstract.
2021
Carlyle M, Broomby R, Simpson G, Hannon R, Fawaz L, Mollaahmetoglu OM, Drain J, Mostazir M, Morgan CJA (2021). A randomised, double-blind study investigating the relationship between early childhood trauma and the rewarding effects of morphine.
Addict Biol,
26(6).
Abstract:
A randomised, double-blind study investigating the relationship between early childhood trauma and the rewarding effects of morphine.
Experiences of childhood trauma (abuse and neglect) are disproportionately higher in those with opioid use disorder (OUD). Childhood trauma may affect the reinforcing and rewarding properties of opioid drugs and responses to pain, potentially via developmental changes to the endogenous opioid system. This has been supported by preclinical research, yet this has not been investigated in non-addicted humans. Physically healthy participants with either a history of severe childhood trauma or no previous history of childhood trauma attended two sessions where they received either an intramuscular active dose of morphine (0.15 mg/kg) or a very low dose control (0.01 mg/kg) in a randomised, double-blind crossover design. Sessions were held 1 week apart. Participants' physical pain threshold and tolerance were measured pre- and post-drug administration using the cold water pressor test, alongside acute subjective and behavioural responses over 2.5 h. The trauma group reported liking the effects of morphine, feeling more euphoric and wanting more of the drug over the session, as well as feeling less nauseous, dizzy, and dislike of the effects of morphine compared to the non-trauma comparison group. Morphine increased pain threshold and tolerance, yet this did not differ between the groups. Childhood trauma may therefore sensitise individuals to the pleasurable and motivational effects of opioids and reduce sensitivity to the negative effects, providing compelling evidence for individual differences in opioid reward sensitivity. This may explain the link between childhood trauma and vulnerability to OUD, with consequent implications on interventions for OUD, the prescribing of opioids, and reducing stigmas surrounding OUD.
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Borissova A, Ferguson B, Wall MB, Morgan CJ, Carhart-Harris RL, Bolstridge M, Bloomfield MA, Williams TM, Feilding A, Murphy K, et al (2021). Acute effects of MDMA on trust, cooperative behaviour and empathy: a double-blind, placebo-controlled experiment.
J Psychopharmacol,
35(5), 547-555.
Abstract:
Acute effects of MDMA on trust, cooperative behaviour and empathy: a double-blind, placebo-controlled experiment.
BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA) is being actively researched as an adjunct to psychotherapy. It may be beneficial to trust, empathy and cooperative behaviour due to its acute prosocial effects. AIM: to test (a) the acute effects of MDMA on measures of empathy, trust and cooperative behaviour, and (b) subacute changes in mood three days after MDMA administration. METHODS: Twenty-five participants (n=7 female), participated in this double-blind, repeated-measures, placebo-controlled experiment. Participants attended two acute sessions, one week apart. Each acute session was followed by a subacute session three days later. Participants received placebo (100 mg ascorbic acid) during one acute session, and MDMA (100 mg MDMA-HCl) at the other, with order counterbalanced. Participants completed the following tasks assessing prosocial behaviour: a trust investment task, a trustworthy face rating task, an empathic stories task, a public project game, a dictator game and an ultimatum game. Participants reported subjective effects. Blood was taken pre-drug, 2 and 4 hours post-drug, and tested for plasma MDMA levels. RESULTS: MDMA acutely increased self-reported 'closeness to others' and 'euphoria' and increased plasma concentrations of MDMA. MDMA did not significantly change task-based empathy, trust or cooperative behaviour. Using Bayesian analyses, we found evidence that MDMA and placebo did not differ in their effects on empathy and cooperative behaviour. MDMA did not significantly change subacute mood and this was supported by our Bayesian analyses. CONCLUSION: Despite augmentation in plasma MDMA levels and subjective drug effects, we found no increase in prosocial behaviour in a laboratory setting.
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Mokrysz C, Shaban NDC, Freeman TP, Lawn W, Pope RA, Hindocha C, Freeman A, Wall MB, Bloomfield MAP, Morgan CJA, et al (2021). Acute effects of cannabis on speech illusions and psychotic-like symptoms: two studies testing the moderating effects of cannabidiol and adolescence.
Psychol Med,
51(12), 2134-2142.
Abstract:
Acute effects of cannabis on speech illusions and psychotic-like symptoms: two studies testing the moderating effects of cannabidiol and adolescence.
BACKGROUND: Acute cannabis administration can produce transient psychotic-like effects in healthy individuals. However, the mechanisms through which this occurs and which factors predict vulnerability remain unclear. We investigate whether cannabis inhalation leads to psychotic-like symptoms and speech illusion; and whether cannabidiol (CBD) blunts such effects (study 1) and adolescence heightens such effects (study 2). METHODS: Two double-blind placebo-controlled studies, assessing speech illusion in a white noise task, and psychotic-like symptoms on the Psychotomimetic States Inventory (PSI). Study 1 compared effects of Cann-CBD (cannabis containing Δ-9-tetrahydrocannabinol (THC) and negligible levels of CBD) with Cann+CBD (cannabis containing THC and CBD) in 17 adults. Study 2 compared effects of Cann-CBD in 20 adolescents and 20 adults. All participants were healthy individuals who currently used cannabis. RESULTS: in study 1, relative to placebo, both Cann-CBD and Cann+CBD increased PSI scores but not speech illusion. No differences between Cann-CBD and Cann+CBD emerged. In study 2, relative to placebo, Cann-CBD increased PSI scores and incidence of speech illusion, with the odds of experiencing speech illusion 3.1 (95% CIs 1.3-7.2) times higher after Cann-CBD. No age group differences were found for speech illusion, but adults showed heightened effects on the PSI. CONCLUSIONS: Inhalation of cannabis reliably increases psychotic-like symptoms in healthy cannabis users and may increase the incidence of speech illusion. CBD did not influence psychotic-like effects of cannabis. Adolescents may be less vulnerable to acute psychotic-like effects of cannabis than adults.
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Ruffell SGD, Netzband N, Tsang W, Davies M, Butler M, Rucker JJH, Tofoli LF, Dempster EL, Young AH, Morgan CJA, et al (2021). Ceremonial Ayahuasca in Amazonian Retreats-Mental Health and Epigenetic Outcomes from a Six-Month Naturalistic Study.
FRONTIERS IN PSYCHIATRY,
12 Author URL.
Freeman AM, Mokrysz C, Hindocha C, Lawn W, Morgan CJA, Freeman TP, Saunders R, Curran HV (2021). Does variation in trait schizotypy and frequency of cannabis use influence the acute subjective, cognitive and psychotomimetic effects of delta-9-tetrahydrocannabinol? a mega-analysis.
Journal of Psychopharmacology,
35(7), 804-813.
Abstract:
Does variation in trait schizotypy and frequency of cannabis use influence the acute subjective, cognitive and psychotomimetic effects of delta-9-tetrahydrocannabinol? a mega-analysis
Background: While the acute effects of cannabis are relatively benign for most users, some individuals experience significant adverse effects. This study aimed to identify whether variation in schizotypal personality traits and frequency of cannabis use influence the acute effects of delta-9-tetrahydrocannabinol (THC). Methods: Individual participant data from four double-blind, randomised, placebo-controlled, acute crossover studies involving 128 cannabis users were combined for a mega-analysis. Using multilevel linear models and moderation analyses, frequency of cannabis use and schizotypal personality traits were investigated as potential moderators of the subjective, cognitive and psychotomimetic effects of acute THC. Results: There was evidence of a moderating effect where increased frequency of cannabis use was associated with reduced intensity of subjective (changes in alertness and feeling stoned) and psychosis-like effects following THC when compared with placebo. Moderating effects of cannabis use frequency on acute memory impairment were weak. Trait schizotypy did not moderate the acute psychosis-like effects of THC compared with placebo. Conclusions: Our results suggest that a pattern of domain-specific tolerance develops to the acute effects of THC. Tolerance to the alertness-reducing effects occurred more readily than tolerance to psychotomimetic effects. Only partial tolerance to feeling stoned was found, and there was weak evidence for tolerance to memory impairment. Trait schizotypy did not moderate THC’s effects on psychotomimetic symptoms.
Abstract.
(2021). Safety Concerns with Ketamine and Esketamine. In (Ed) Ketamine, the MIT Press, 121-140.
Mollaahmetoglu OM, Palmer E, Maschauer E, Nolan MC, Stevens T, Carlyle M, Hardy L, Watkins ER, Morgan CJA (2021). The acute effects of alcohol on state rumination in the laboratory.
Psychopharmacology (Berl),
238(6), 1671-1686.
Abstract:
The acute effects of alcohol on state rumination in the laboratory.
RATIONALE: Rumination is a repetitive, negative, self-focused thinking style associated with various forms of psychopathology. Recent studies suggest that rumination increases craving for alcohol and predicts harmful drinking and alcohol-related problems. However, the acute effects of alcohol on rumination have not been previously studied. It is proposed that alcohol may reduce ruminative thinking through decreasing negative mood. OBJECTIVES: in the present study, we aimed to test the previously unexplored effects of acute alcohol consumption on rumination in a hazardous drinking population. METHODS: We conducted a randomised placebo-controlled laboratory study to examine the effect of low (0.4 g kg-1) and high doses (0.8 g kg-1) of alcohol on state rumination compared to placebo. Participants completed a rumination induction task prior to receiving drinks. We then measured state rumination and mood at repeated time points; 30 min, 60 min and 90 min post-drinks consumption. RESULTS: We found a significant decrease in state rumination in the low-dose alcohol group compared to placebo at 30 min post-alcohol consumption, but no difference was observed between the high-dose alcohol and placebo groups. Mediation analysis provided evidence for an indirect effect of alcohol on state rumination through concurrent changes in negative mood. CONCLUSIONS: These findings suggest that acute alcohol consumption can regulate negative mood and concurrently rumination, providing preliminary evidence for the role of rumination in alcohol use disorders. Rumination may be a treatment target in alcohol use disorders.
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Hale E (2021). “My best card against my mental health”: a Qualitative Analysis of Blue Space and the Self-Management of Mental Health Symptoms.
Abstract:
“My best card against my mental health”: a Qualitative Analysis of Blue Space and the Self-Management of Mental Health Symptoms.
Objective: Theoretical and empirical evidence suggests a relationship between exposure to blue space (outdoor water environments) and positive mental health and wellbeing. To date, studies indicate that people’s proximity to and use of blue space is associated with good mental health, but additional exploratory research is required to understand interactions between blue space and mental health outcomes in people with mental health difficulties. This study explores how people with mental health difficulties experience blue spaces in a non-clinical, non-intervention context. A broader aim of this research is to consider the mechanisms/pathways connecting blue space and mental health outcomes.
Methods: the population of interest in this study were adult men and women living in British coastal communities who self-identified with having a mental health difficulty. Data consisted of semi-structured interviews from primary (N=6) and secondary (N=7) data sets. The data was analysed using constructivist grounded theory.
Results: Findings indicate that blue spaces provide conditions where people can gauge their mental health, assess their needs, and get them met. The analysis highlighted that blue space exposure has both a reactive and preventative impact on mental health symptoms and suggested that this may be mediated by the severity of mental health difficulties. This study supports the notion that social (i.e. meaningful relationships with others) and attentional (i.e. mindfulness and gratitude) mechanisms are important in explicating the relationship between blue space and mental health but highlights occasions where blue space exposure can worsen (i.e. heightened anxiety related to the perception of threat from others on beaches at night) or have no effect on mental health symptoms (i.e. the persistence of suicidal ideation).
Conclusion: Overall, this study suggests that an added value of blue space environments specifically for people living with mental health difficulties is that they provide the necessary conditions that empower people to feel able to self-manage their mental health symptoms.
Abstract.
Mollaahmetoglu OM, Keeler J, Ashbullby KJ, Ketzitzidou-Argyri E, Grabski M, Morgan CJA (2021). “This is Something That Changed My Life”: a Qualitative Study of Patients' Experiences in a Clinical Trial of Ketamine Treatment for Alcohol Use Disorders. Frontiers in Psychiatry, 12, 1-17.
2020
Hindocha C, Freeman TP, Schafer G, Gardner C, Bloomfield MAP, Bramon E, Morgan CJA, Curran HV (2020). Acute effects of cannabinoids on addiction endophenotypes are moderated by genes encoding the CB1 receptor and FAAH enzyme.
Addict Biol,
25(3).
Abstract:
Acute effects of cannabinoids on addiction endophenotypes are moderated by genes encoding the CB1 receptor and FAAH enzyme.
Understanding genetic factors that contribute to cannabis use disorder (CUD) is important, but to date, findings have been equivocal. Single-nucleotide polymorphisms (SNPs) in the cannabinoid receptor 1 gene (CNR1; rs1049353 and rs806378) and fatty acid amide hydrolase (FAAH) gene (rs324420) have been implicated in CUD. Their relationship to addiction endophenotypes such as cannabis-related state satiety, the salience of appetitive cues, and craving after acute cannabinoid administration has not been investigated. Forty-eight cannabis users participated in a double-blind, placebo-controlled, four-way crossover experiment where they were administered treatments in a randomized order via vaporization: placebo, Δ9 -tetrahydrocannabinol (THC) (8 mg), THC + cannabidiol (THC + CBD) (8 + 16 mg), and CBD (16 mg). Cannabis-related state satiety, appetitive cue salience (cannabis and food), and cannabis craving were assessed each day. Participants were genotyped for rs1049353, rs806378, and rs324420. Results indicated that CNR1 rs1049353 GG carriers showed increased state satiety after THC/THC + CBD administration in comparison with placebo and reduced the salience of appetitive cues after THC in comparison with CBD administration; a carriers did not vary on either of these measures indicative of a vulnerability to CUD. CNR1 rs806378 CC carriers showed greater salience to appetitive cues in comparison with T carriers, but there was no evidence for changes in state satiety. FAAH rs324420 a carriers showed greater bias to appetitive cues after THC, in comparison with CC carriers. FAAH CC carriers showed reduced bias after THC in comparison with CBD. No SNPs modulated craving. These findings identify candidate neurocognitive mechanisms through which endocannabinoid system genetics may influence vulnerability to CUD.
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Morgan C, Freeman T, Baio G, Shaban N, Thomas EM, Astbury D, Freeman AM, Craft S, Morrison PD, Bloomfield MAP, et al (2020). Cannabidiol for the treatment of cannabis use disorder: Phase IIa double-blind placebo-controlled randomised adaptive Bayesian dose-finding trial. Lancet Psychiatry, 7(10), 865-874.
Hindocha C, Quattrone D, Freeman TP, Murray RM, Mondelli V, Breen G, Curtis C, Morgan CJA, Valerie Curran H, Di Forti M, et al (2020). Do AKT1, COMT and FAAH influence reports of acute cannabis intoxication experiences in patients with first episode psychosis, controls and young adult cannabis users?.
Transl Psychiatry,
10(1).
Abstract:
Do AKT1, COMT and FAAH influence reports of acute cannabis intoxication experiences in patients with first episode psychosis, controls and young adult cannabis users?
Epidemiological and biological evidence support the association between heavy cannabis use and psychosis. However, it is unclear which cannabis users are susceptible to its psychotogenic effect. Therefore, understanding genetic factors contributing to this relationship might prove an important strategy to identify the mechanisms underlying cannabis-associated psychotic experiences. We aimed to determine how variation in AKT1, COMT and FAAH genotypes, and their interaction with three different groups (first episode psychosis (FEP) patients (n = 143), controls (n = 92) and young adult (YA) cannabis users n = 485)) influenced cannabis experiences, in those who had used cannabis at least once. We investigated the role of AKT1 (rs2494732), COMT Val158Met (rs4680) and FAAH (rs324420) on cannabis experiences by combining data from a large case-control study of FEP patients, with a naturalistic study of YA cannabis users (n = 720). Outcome measures were cannabis-induced psychotic-like experiences (cPLEs) and euphoric experiences (cEEs). We used linear mixed effects models to assess the effects of each genotype and their interaction with group, adjusting for age, sex, ethnicity, age of first cannabis use, years of use and frequency. cPLEs were more frequent in FEP patients than controls and YA cannabis users. cEEs were more prevalent in YA cannabis users than FEP patients or controls. Variation in AKT1, COMT or FAAH was not associated with cPLEs/cEEs. There was no interaction between genotype and group (FEP cases, controls and YA cannabis users) on cPLEs/cEEs. In conclusion, AKT1, COMT or FAAH did not modulate specific psychotomimetic response to cannabis and did not interact with group, contrary to previous research.
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Carlyle M, Rowley M, Stevens T, Karl A, Morgan CJA (2020). Impaired empathy and increased anger following social exclusion in non-intoxicated opioid users.
Psychopharmacology (Berl),
237(2), 419-430.
Abstract:
Impaired empathy and increased anger following social exclusion in non-intoxicated opioid users.
RATIONALE: Social functioning is modulated by the endogenous opioid system. In opioid use disorder, social functioning appears disrupted, but little research has delineated the nature of these deficits and their relationship to acute opioid use. OBJECTIVES: the current study aimed to assess both emotional and cognitive empathy, along with subjective and physiological responses to social exclusion in opioid users who were either acutely intoxicated or non-intoxicated from using opioids. METHODS: Individuals on an opioid substitution medication (OSM) were divided into 'intoxicated users' (had taken their OSM the same day as testing, n = 20) and 'non-intoxicated users' (had taken their OSM > 12 h ago, n = 20) and compared with opioid-naïve controls (n = 24). Empathy was assessed using the multifaceted empathy test and self-report questionnaire. Participants also underwent a period of social exclusion (Cyberball Game) and completed measures of mood and physiological responses (salivary cortisol and heart rate). RESULTS: Non-intoxicated users had significantly lower emotional empathy (the ability to experience others' emotions), as well as greater anger after social exclusion when compared with the intoxicated users and controls. Anger did not change with social exclusion in the intoxicated user group and cortisol levels were lower overall. CONCLUSIONS: Reduced ability to spontaneously share the emotions of others was reported in non-intoxicated users, particularly regarding positive emotions. There was some support for the idea of hyperalgesia to social pain, but this was restricted to an enhanced anger response in non-intoxicated users. Equivalent rates of empathy between the intoxicated users and controls could indicate some remediating effects of acute opioids.
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Grabski M, Borissova A, Marsh B, Morgan CJA, Curran HV (2020). Ketamine as a mental health treatment: Are acute psychoactive effects associated with outcomes? a systematic review.
Behav Brain Res,
392Abstract:
Ketamine as a mental health treatment: Are acute psychoactive effects associated with outcomes? a systematic review.
Esketamine was recently licensed by the US Food and Drug Administration (FDA) and European Drug Agency (EDA) for use in treatment resistant depression (TRD), and further research indicates ketamine as a possible treatment in other mental health conditions. While the underlying mechanisms remain unclear, it has been hypothesised that ketamine's acute psychoactive effects may be associated with psychiatric treatment efficacy. We systematically reviewed the evidence for this association. The databases Medline, Embase and PsychInfo were searched up to June 2019. Studies were included if they enrolled adults with a psychiatric diagnosis, assessed acute psychoactive effects using a quantitative measure, and reported on the relationship between acute effects and treatment outcome. We included 21 studies, involving 891 patients. Seventeen studies assessed patients with depression (TRD [k = 14]), three assessed substance use disorders, and one assessed social anxiety disorder. Overall, 41 associations were assessed, of which 26 % were significant. The studies reviewed displayed great variability in terms of methodology and quality of reporting. The most commonly assessed effect was dissociation, measured by the CADSS. Our results suggest that the CADSS total is not consistently associated with antidepressant outcomes. Apart from this, the current literature is too limited to draw definite conclusions on the presence of an association between acute psychoactive effects and mental health outcomes. The field would benefit from consistently employing a priori hypotheses, more transparent reporting and sufficiently powered statistical analyses. Furthermore, the use of a broader range of assessments tools of acute psychoactive effects during ketamine administration would be beneficial.
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Rossi GN, Osório FL, Morgan CJA, Crippa JAS, Bouso JC, Rocha JM, Zuardi AW, Hallak JEC, Santos RGD (2020). The effects of Cannabidiol (CBD) and Delta-9-Tetrahydrocannabinol (THC) on the recognition of emotions in facial expressions: a systematic review of randomized controlled trials.
Neurosci Biobehav Rev,
118, 236-246.
Abstract:
The effects of Cannabidiol (CBD) and Delta-9-Tetrahydrocannabinol (THC) on the recognition of emotions in facial expressions: a systematic review of randomized controlled trials.
Tetrahydrocannabinol (THC) and cannabidiol (CBD) are phytocannabinoids being linked with modulation of anxiety and depression. The recognition of emotions in facial expressions (REFE) is impaired in these disorders. Both drugs could modulate anxiety and mood by interfering with REFE. Thus, a systematic review of controlled trials assessing the effects of THC and CBD on REFE was performed. Ten studies describing seven distinct experiments were found (n = 170). THC (7.5-15 mg) did not alter REFE in three experiments, but reduced task performance in other three experiments. CBD did not alter REFE in two experiments, but improved task performance and counteracted the effects of THC in one experiment. THC (≥ 10 mg) and CBD (600 mg) showed opposite effects on brain activation, skin conductance, and anxiety measures with negative/threatening faces. The limited number of studies precludes firm conclusions on the effects of these substances on REFE. Further controlled trials are needed to elucidate the effects of THC and CBD on REFE. The PROSPERO ID for this study is CRD42019135085.
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Lawn W, Mithchener L, Freeman TP, Benattayallah A, Bisby JA, Wall MB, Dodds CM, Curran HV, Morgan CJA (2020). Value-based decision-making of cigarette and nondrug rewards in dependent and occasional cigarette smokers: an FMRI study.
Addict Biol,
25(4).
Abstract:
Value-based decision-making of cigarette and nondrug rewards in dependent and occasional cigarette smokers: an FMRI study.
Little is known about the neural functioning that underpins drug valuation and choice in addiction, including nicotine dependence. Following ad libitum smoking, 19 dependent smokers (smoked≥10/day) and 19 occasional smokers (smoked 0.5-5/week) completed a decision-making task. First, participants stated how much they were willing-to-pay for various amounts of cigarettes and shop vouchers. Second, during functional magnetic resonance imaging, participants decided if they wanted to buy these cigarettes and vouchers for a set amount of money. We examined decision-making behaviour and brain activity when faced with cigarette and voucher decisions, purchasing (vs not purchasing) cigarettes and vouchers, and "value signals" where brain activity correlated with cigarette and voucher value. Dependent smokers had a higher willingness-to-pay for cigarettes and greater activity in the bilateral middle temporal gyrus when faced with cigarette decisions than occasional smokers. Across both groups, the decision to buy cigarettes was associated with activity in the left paracingulate gyrus, right nucleus accumbens, and left amygdala. The decision to buy vouchers was associated with activity in the left superior frontal gyrus, but dependent smokers showed weaker activity in the left posterior cingulate gyrus than occasional smokers. Across both groups, cigarette value signals were observed in the left striatum and ventromedial prefrontal cortex. To summarise, nicotine dependence was associated with greater behavioural valuation of cigarettes and brain activity during cigarette decisions. When purchasing cigarettes and vouchers, reward and decision-related brain regions were activated in both groups. For the first time, we identified value signals for cigarettes in the brain.
Abstract.
Author URL.
2019
Hindocha C, Freeman T, Bloomfield M, Bramon E, Morgan C, Curran HV (2019). Acute effects of cannabinoids on addiction endophenotypes are moderated by genes encoding the cannabinoid receptor 1 and FAAH enzyme.
Author URL.
Carlyle M, Stevens T, Fawaz L, Marsh B, Kosmider S, Morgan CJ (2019). Greater empathy in MDMA users.
J Psychopharmacol,
33(3), 295-304.
Abstract:
Greater empathy in MDMA users.
BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA) is widely known for its positive acute effects on social behaviour, such as increasing empathy, whilst also attenuating the negative impact of social exclusion. However there is a scarcity of research that investigates the long-term impact of recreational MDMA use on these fundamental social processes. METHOD: Sixty-seven individuals were split into three groups based on their drug-use history: poly-drug MDMA users ( n = 25), poly-drug users who do not use MDMA ( n = 19), alcohol-only users ( n = 23), and were tested in an independent groups design. Participants completed both a self-report measure of emotional and cognitive empathy, along with the Multifaceted Empathy Task - a computerised assessment of empathy - and the Cyberball Game - a social exclusion paradigm. RESULTS: MDMA users had significantly greater subjective emotional empathy, and greater cognitive empathy on the computer task compared with the poly-drug users who do not use MDMA. There were no significant differences in subjective responses to social exclusion between the groups. Indices of MDMA use did not correlate with empathy. CONCLUSIONS: Long-term MDMA users in this sample exhibited normal psychosocial functioning in regard to empathy and social pain and had higher subjective emotional empathy. This conflicts with previous suggestions that moderate, long-term MDMA use may cause heightened social distress, and is further evidence of the safety of the drug, which is relevant to considerations of its therapeutic use.
Abstract.
Author URL.
Curran V, Mokrysz C, Freeman T, Hindocha C, Lawn W, Das R, Morgan C (2019). How do different cannabinoids in cannabis influence vulnerability to mental health problems?.
Author URL.
Carlyle M, Rockliff H, Edwards R, Ene C, Karl A, Marsh B, Hartley L, Morgan CJ (2019). Investigating the Feasibility of Brief Compassion Focused Therapy in Individuals in Treatment for Opioid Use Disorder.
Subst Abuse,
13Abstract:
Investigating the Feasibility of Brief Compassion Focused Therapy in Individuals in Treatment for Opioid Use Disorder.
Opioid use disorder (OUD) is reaching epidemic proportions worldwide, and is notoriously difficult to treat. Compassion focused therapy (CFT) has emerged as therapeutic tool for treating individuals exhibiting high levels of self-criticism and low self-esteem, both of which are common in OUD. Until now, however, there had been no research investigating this therapy in patients with OUD. Before running a premature clinical trial, it is important to fully assess the feasibility and acceptability of this treatment in this group of individuals. We aimed to assess the feasibility of CFT treatment in individuals with OUD in a short group intervention, which was co-created by the research team, service users and a local drugs service. The intervention involved three 2-hour sessions held over 3 weeks, where participants engaged in compassion-orientated psychoeducation and self-compassionate exercises. Individuals were randomly assigned to either the CFT group (n = 15), the active control (relaxation) group (n = 12) or the waitlist control group (n = 11). of 103 individuals approached, 45% attended a baseline visit suggesting the treatment was acceptable to this group. A relatively low attrition rate across the 3 groups was found for CFT (21.1%), with no difference in drop-out between the groups. Qualitative analysis of interviews with participants identified a desire for more sessions. Compassion focused therapy was thus feasible and well-tolerated in those with OUD, and a further trial to evaluate any clinical differences may be warranted.
Abstract.
Author URL.
Curran HV, Hindocha C, Morgan C, Shaban NDC, Das R, Freeman TP (2019). Reply to Vadhan et al. - Correspondence on Curran et al. (2018) 'Which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like response'. Psychological Medicine, 49(10), 1759-1760.
Marsh B, Carlyle M, Carter E, Hughes P, McGahey S, Lawn W, Stevens T, McAndrew A, Morgan CJA (2019). Shyness, alcohol use disorders and ‘hangxiety’: a naturalistic study of social drinkers.
Personality and Individual Differences,
139, 13-18.
Abstract:
Shyness, alcohol use disorders and ‘hangxiety’: a naturalistic study of social drinkers
Social anxiety disorder (SAD) has been related to alcohol use disorder (AUD). Shyness can be considered a subclinical analogue of SAD, yet there is little research into the effect of alcohol on anxiety levels in highly-shy individuals. This naturalistic study investigated acute and sub-acute effects of alcohol in high and low shy social drinkers. 97 individuals were tested at home and assigned to either consume alcohol to normal levels (n = 50) or to remain sober (n = 47). Baseline measures of AUD symptoms, shyness and social phobia were taken. Measures of state anxiety were taken at baseline, following a period of alcohol consumption or sobriety, and the following morning. Marginally decreased acute anxiety resulting from alcohol consumption in high shyness was observed. A significant increase in anxiety the day following drinking was observed in highly-shy participants. There was a significant correlation between anxiety elevation on the second day and AUDIT scores in highly-shy participants. This study suggests anxiety during hangover is linked to AUD symptoms in highly-shy individuals, providing a potential marker for increased AUD risk, which could inform prevention and treatment.
Abstract.
Carlyle M (2019). Social risk factors in the aetiology, maintenance and treatment of opioid use disorder.
Abstract:
Social risk factors in the aetiology, maintenance and treatment of opioid use disorder
Opioid use disorder (OUD) is a growing global concern as overdoses have drastically increased over recent years. There is an urgent requirement for novel and more effective treatments. Investigating the role of social factors in the onset and maintenance of OUD may be a promising approach. In Chapter 1, I review the role of social vulnerability factors in OUD, and how social functioning may be altered in opioid drug users via changes to the endogenous opioid system. In Chapter 2, I report greater pleasurable effects and reduced aversive effects of an acute dose of morphine in individuals with histories of childhood trauma (without histories of OUD). This suggested history of childhood trauma may increase the rewarding value of opioids, and therefore be a major vulnerability factor preceding OUD. Impairments to social functioning in those with OUD is then investigated in Chapter 3, where I report reduced empathy for others’ emotions alongside greater anger following social exclusion. These findings indicate social risk factors and impaired social functioning as an important area that should be considered in the search for novel treatments for OUD. In Chapter 4 I report on a brief intervention of compassion-focused therapy (CFT) for OUD, showing that this novel treatment is feasible and tolerable in this population. Another potential therapeutic avenue to improve social functioning is by using MDMA adjunct to psychotherapy, therefore in Chapter 5 I examined whether social functioning is negatively affected by MDMA use. Low level, repeated MDMA use was associated with improved empathy and did not affect social distress, highlighting it as potentially suitable for treating social impairments in OUD. In Chapter 6, I discuss the wider theoretical implications and propose a social risk factor model for OUD. I also discuss the clinical implications of the findings, potential limitations to the work, and suggestions for future directions for improving social functioning in OUD. In conclusion, social functioning is disrupted in OUD, and experiences of childhood trauma and social stressors may prime people to the addictive effects of these drugs; however, CFT or MDMA-assisted psychotherapy may be beneficial for treating OUD.
Abstract.
Freeman TP, Morgan C, Hindocha C (2019). Strengthening the evidence for medicinal cannabis and cannabinoids. BMJ, l5871-l5871.
Morgan C, Ene C (2019). The prescribing of cannabis-derived medications by medical doctors in the United Kingdom.
Curran HV, Hindocha C, Morgan CJA, Shaban N, Das RK, Freeman TP (2019). Which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like effects?.
Psychological medicine,
49(9), 1574-1580.
Abstract:
Which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like effects?
BACKGROUND: Changes in cannabis regulation globally make it increasingly important to determine what predicts an individual's risk of experiencing adverse drug effects. Relevant studies have used diverse self-report measures of cannabis use, and few include multiple biological measures. Here we aimed to determine which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like symptoms. METHOD: in a naturalistic study, 410 young cannabis users were assessed once when intoxicated with their own cannabis and once when drug-free in counterbalanced order. Biological measures of cannabinoids [(Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN) and their metabolites)] were derived from three samples: each participant's own cannabis (THC, CBD), a sample of their hair (THC, THC-OH, THC-COOH, CBN, CBD) and their urine (THC-COOH/creatinine). Comprehensive self-report measures were also obtained. Self-reported and clinician-rated assessments were taken for cannabis dependency [Severity of Dependence Scale (SDS), DSM-IV-TR] and acute psychotic-like symptoms [Psychotomimetic State Inventory (PSI) and Brief Psychiatric Rating Scale (BPRS)]. RESULTS: Cannabis dependency was positively associated with days per month of cannabis use on both measures, and with urinary THC-COOH/creatinine for the SDS. Acute psychotic-like symptoms were positively associated with age of first cannabis use and negatively with urinary THC-COOH/creatinine; no predictors emerged for BPRS. CONCLUSIONS: Levels of THC exposure are positively associated with both cannabis dependency and tolerance to the acute psychotic-like effects of cannabis. Combining urinary and self-report assessments (use frequency; age first used) enhances the measurement of cannabis use and its association with adverse outcomes.
Abstract.
2018
Lawn W, Hallak JE, Crippa JA, Dos Santos R, Porffy L, Barratt MJ, Ferris JA, Winstock AR, Morgan CJA (2018). Author Correction: Well-being, problematic alcohol consumption and acute subjective drug effects in past-year ayahuasca users: a large, international, self-selecting online survey.
Sci Rep,
8(1).
Abstract:
Author Correction: Well-being, problematic alcohol consumption and acute subjective drug effects in past-year ayahuasca users: a large, international, self-selecting online survey.
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Abstract.
Author URL.
Hindocha C, Freeman TP, Grabski M, Stroud JB, Crudgington H, Davies AC, Das RK, Lawn W, Morgan CJA, Curran HV, et al (2018). Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal.
Addiction,
113(9), 1696-1705.
Abstract:
Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal.
BACKGROUND AND AIMS: Cannabidiol (CBD), a non-intoxicating cannabinoid found in cannabis, may be a promising novel smoking cessation treatment due to its anxiolytic properties, minimal side effects and research showing that it may modify drug cue salience. We used an experimental medicine approach with dependent cigarette smokers to investigate if (1) overnight nicotine abstinence, compared with satiety, will produce greater attentional bias (AB), higher pleasantness ratings of cigarette-related stimuli and increased craving and withdrawal; and (2) CBD in comparison to placebo, would attenuate AB, pleasantness of cigarette-related stimuli, craving and withdrawal and not produce any side effects. DESIGN: Randomized, double-blind cross-over study with a fixed satiated session followed by two overnight abstinent sessions. SETTING: UK laboratory. PARTICIPANTS: Thirty non-treatment-seeking, dependent cigarette smokers recruited from the community. INTERVENTION AND COMPARATOR: 800 mg oral CBD, or matched placebo (PBO) in a counterbalanced order MEASUREMENTS: AB to pictorial tobacco cues was recorded using a visual probe task and an explicit rating task. Withdrawal, craving, side effects, heart rate and blood pressure were assessed repeatedly. FINDINGS: When participants received PBO, tobacco abstinence increased AB (P = 0.001, d = 0.789) compared with satiety. However, CBD reversed this effect, such that automatic AB was directed away from cigarette cues (P = 0.007, d = 0.704) and no longer differed from satiety (P = 0.82). Compared with PBO, CBD also reduced explicit pleasantness of cigarette images (P = 0.011; d = 0.514). Craving (Bayes factor = 7.08) and withdrawal (Bayes factor = 6.95) were unaffected by CBD, but greater in abstinence compared with satiety. Systolic blood pressure decreased under CBD during abstinence. CONCLUSIONS: a single 800-mg oral dose of cannabidiol reduced the salience and pleasantness of cigarette cues, compared with placebo, after overnight cigarette abstinence in dependent smokers. Cannabidiol did not influence tobacco craving or withdrawal or any subjectively rated side effects.
Abstract.
Author URL.
Freeman TP, Pope RA, Wall MB, Bisby JA, Luijten M, Hindocha C, Mokrysz C, Lawn W, Moss A, Bloomfield MAP, et al (2018). Cannabis Dampens the Effects of Music in Brain Regions Sensitive to Reward and Emotion.
Int J Neuropsychopharmacol,
21(1), 21-32.
Abstract:
Cannabis Dampens the Effects of Music in Brain Regions Sensitive to Reward and Emotion.
BACKGROUND: Despite the current shift towards permissive cannabis policies, few studies have investigated the pleasurable effects users seek. Here, we investigate the effects of cannabis on listening to music, a rewarding activity that frequently occurs in the context of recreational cannabis use. We additionally tested how these effects are influenced by cannabidiol, which may offset cannabis-related harms. METHODS: Across 3 sessions, 16 cannabis users inhaled cannabis with cannabidiol, cannabis without cannabidiol, and placebo. We compared their response to music relative to control excerpts of scrambled sound during functional Magnetic Resonance Imaging within regions identified in a meta-analysis of music-evoked reward and emotion. All results were False Discovery Rate corrected (P
Abstract.
Author URL.
Morgan C, Freeman T, Hindocha C, Schafer G, Gardner C, Curran HV (2018). Individual and combined effects of acute delta-9-tetrahydrocannabinol and cannabidiol on psychotomimetic symptoms and memory function. Translational Psychiatry, 8, 181-181.
Lawn W, Freeman TP, East K, Gaule A, Aston ER, Bloomfield MAP, Das RK, Morgan CJA, Curran HV (2018). The Acute Effects of a Dopamine D3 Receptor Preferring Agonist on Motivation for Cigarettes in Dependent and Occasional Cigarette Smokers.
Nicotine Tob Res,
20(7), 800-809.
Abstract:
The Acute Effects of a Dopamine D3 Receptor Preferring Agonist on Motivation for Cigarettes in Dependent and Occasional Cigarette Smokers.
BACKGROUND: Dopaminergic functioning is thought to play critical roles in both motivation and addiction. There is preliminary evidence that dopamine agonists reduce the motivation for cigarettes in smokers. However, the effects of pramipexole, a dopamine D3 receptor preferring agonist, have not been investigated. The aim of this study was to examine the effects of an acute dose of pramipexole on the motivation to earn cigarettes and nondrug rewards. METHODS: Twenty dependent and 20 occasional smokers received 0.5 mg pramipexole using a double-blind, placebo-controlled crossover design. Motivation for cigarettes and consummatory nondrug rewards was measured using the DReaM-Choice task, in which participants earned, and later "consumed," cigarettes, music, and chocolate. Demand for cigarettes was measured using the Cigarette Purchase Task (CPT). Self-reported craving, withdrawal, and drug effects were also recorded. RESULTS: Dependent smokers chose (p <. 001) and button-pressed for (p <. 001) cigarettes more, and chose chocolate less (p <. 001), than occasional smokers. Pramipexole did not affect the number of choices for or amount of button-pressing for any reward including cigarettes, which was supported by a Bayesian analysis. The dependent smokers had greater demand for cigarettes than occasional smokers across all CPT outcomes (ps <. 021), apart from elasticity. Pramipexole did not affect demand for cigarettes, and this was supported by Bayesian analyses. Pramipexole produced greater subjective "feel drug" and "dislike drug" effects than placebo. CONCLUSIONS: Dependent and occasional cigarette smokers differed in their motivation for cigarettes but not for the nondrug rewards. Pramipexole did not acutely alter motivation for cigarettes. These findings question the role of dopamine D3 receptors in cigarette-seeking behavior in dependent and occasional smokers. IMPLICATIONS: This study adds to the growing literature about cigarette versus nondrug reward processing in nicotine dependence and the role of dopamine in cigarette-seeking behavior. Our results suggest nicotine dependence is associated with a hypersensitivity to cigarette rewards but not a hyposensitivity to nondrug rewards. Furthermore, our results question the importance of dopamine D3 receptors in motivational processing of cigarettes in occasional and dependent smokers.
Abstract.
Author URL.
Hindocha C, Freeman TP, Grabski M, Crudgington H, Davies AC, Stroud JB, Das RK, Lawn W, Morgan CJA, Curran HV, et al (2018). The effects of cannabidiol on impulsivity and memory during abstinence in cigarette dependent smokers.
Sci Rep,
8(1).
Abstract:
The effects of cannabidiol on impulsivity and memory during abstinence in cigarette dependent smokers.
Acute nicotine abstinence in cigarette smokers results in deficits in performance on specific cognitive processes, including working memory and impulsivity which are important in relapse. Cannabidiol (CBD), the non-intoxicating cannabinoid found in cannabis, has shown pro-cognitive effects and preliminary evidence has indicated it can reduce the number of cigarettes smoked in dependent smokers. However, the effects of CBD on cognition have never been tested during acute nicotine withdrawal. The present study therefore aimed to investigate if CBD can improve memory and reduce impulsivity during acute tobacco abstinence. Thirty, non-treatment seeking, dependent, cigarette smokers attended two laboratory-based sessions after overnight abstinence, in which they received either 800 mg oral CBD or placebo (PBO), in a randomised order. Abstinence was biologically verified. Participants were assessed on go/no-go, delay discounting, prose recall and N-back (0-back, 1-back, 2-back) tasks. The effects of CBD on delay discounting, prose recall and the N-back (correct responses, maintenance or manipulation) were null, confirmed by a Bayesian analysis, which found evidence for the null hypothesis. Contrary to our predictions, CBD increased commission errors on the go/no-go task. In conclusion, a single 800 mg dose of CBD does not improve verbal or spatial working memory, or impulsivity during tobacco abstinence.
Abstract.
Author URL.
Lawn W, Freeman T, Benattayallah A, Bisby J, Mitchener L, Curran V, Dodds C, Morgan C (2018). Value-Based Decision-Making of Cigarettes and Non-Drug Rewards in Dependent and Occasional Smokers: an fMRI Study.
Author URL.
2017
McAndrew A, Lawn W, Stevens T, Porffy L, Brandner B, Morgan CJA (2017). A proof-of-concept investigation into ketamine as a pharmacological treatment for alcohol dependence: study protocol for a randomised controlled trial.
Trials,
18(1).
Abstract:
A proof-of-concept investigation into ketamine as a pharmacological treatment for alcohol dependence: study protocol for a randomised controlled trial.
BACKGROUND: Worldwide, alcohol abuse is a burgeoning problem. Abstinence is key to allow recovery of physical and mental health as well as quality of life, but treatment for alcohol dependence is associated with high relapse rates. Preliminary data have suggested that a combined repeated ketamine and psychological therapy programme may be effective in reducing relapse in severe alcohol use disorder. This non-commercial proof-of-concept trial is aimed at making a preliminary assessment of the effectiveness of this combined treatment in this patient group. METHODS/DESIGN: This is a phase II, randomised, double-blind, placebo-controlled, parallel-group clinical trial taking place in two sites in the UK: the South West of England and London. Ninety-six recently detoxified alcoholics, with comorbid depressive symptoms, will be randomised to one of four treatment arms. Patients will receive either three sessions of ketamine (0.8 mg/kg administered intravenously (IV) over 40 minutes) or placebo (50 ml saline 0.9% IV over 40 minutes) plus either seven sessions of manualised psychological therapy or an alcohol education control. Patients will be assessed at 3 and 6 months on a range of psychological and biological variables. The primary endpoints are (1) relapse rates at 6 months and (2) percentage days abstinent at 6 months. Secondary endpoints include 3 and 6 month percentage days abstinence, tolerability (indicated by dropout), adverse events, depressive symptoms, craving and quality of life. DISCUSSION: This study will provide important information on a new combined psychological and pharmacological intervention aimed at reducing relapse rates in alcoholics. The findings would have broad application given the worldwide prevalence of alcoholism and its associated medical, psychological and social problems. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02649231. Registered on 5 January 2016.
Abstract.
Author URL.
Freeman TP, Pope R, Wall M, Bisby J, Luijten M, Hindocha C, Mokrysz C, Lawn W, Moss A, Bloomfield M, et al (2017). Cannabis increases wanting but not liking of music and dampens its rewarding effects on the brain.
Author URL.
Carlyle M, Dumay N, Roberts K, McAndrew A, Stevens T, Lawn W, Morgan CJA (2017). Improved memory for information learnt before alcohol use in social drinkers tested in a naturalistic setting.
Scientific Reports,
7(1).
Abstract:
Improved memory for information learnt before alcohol use in social drinkers tested in a naturalistic setting
Alcohol is known to facilitate memory if given after learning information in the laboratory; we aimed to investigate whether this effect can be found when alcohol is consumed in a naturalistic setting. Eighty-eight social drinkers were randomly allocated to either an alcohol self-dosing or a sober condition. The study assessed both retrograde facilitation and alcohol induced memory impairment using two independent tasks. In the retrograde task, participants learnt information in their own homes, and then consumed alcohol ad libitum. Participants then undertook an anterograde memory task of alcohol impairment when intoxicated. Both memory tasks were completed again the following day. Mean amount of alcohol consumed was 82.59 grams over the evening. For the retrograde task, as predicted, both conditions exhibited similar performance on the memory task immediately following learning (before intoxication) yet performance was better when tested the morning after encoding in the alcohol condition only. The anterograde task did not reveal significant differences in memory performance post-drinking. Units of alcohol drunk were positively correlated with the amount of retrograde facilitation the following morning. These findings demonstrate the retrograde facilitation effect in a naturalistic setting, and found it to be related to the self-administered grams of alcohol.
Abstract.
Singh I, Morgan C, Curran V, Nutt D, Schlag A, McShane R (2017). Ketamine treatment for depression: opportunities for clinical innovation and ethical foresight.
The Lancet Psychiatry,
4(5), 419-426.
Abstract:
Ketamine treatment for depression: opportunities for clinical innovation and ethical foresight
We present a review and analysis of the ethical considerations in off-label ketamine use for severe, treatment-resistant depression. The analysis of ethical considerations is contextualised in an overview of the evidence for ketamine use in depression, and a review of the drug's safety profile. We find that, based on current evidence, ketamine use for severe, treatment-resistant depression does not violate ethical principles; however, clinicians and professional bodies must take steps to ensure that guidelines for good practice are enacted, that all experimental and trial data are made available through national registries, and that the risk potential of ketamine treatment continues to be monitored and modelled. We conclude with a set of key recommendations for oversight bodies that would support safe, effective, and ethical use of ketamine in depression.
Abstract.
Lawn W, Morgan C (2017). Motivational processing of cigarette and music reward in dependent and occasional smokers: an fMRI and behavioural study.
Author URL.
Freeman TP, Pope R, Wall M, Bisby J, Luijten M, Hindocha C, Mokrysz C, Lawn W, Moss A, Bloomfield M, et al (2017). P.4.012 Cannabis increases wanting but not liking of music and dampens its rewarding effects on the brain. European Neuropsychopharmacology, 27, s92-s93.
Ranganathan M, Morgan C, Di Forti M, Curran H, Dsouza D (2017). PREDICTORS OF CANNABIS-INDUCED PSYCHOSIS.
Author URL.
Bloomfield M, McCutcheon R, Dahoun T, Kempton M, Valmaggia L, Freeman T, Glover V, Pruesner J, Morgan C, Kapur S, et al (2017). The effects of long-term psychosocial adversity on dopaminergic function and the acute stress response.
Author URL.
Morgan C, McAndrew A, Stevens T, Nutt D, Lawn W (2017). Tripping up addiction: the use of psychedelic drugs in the treatment of problematic drug and alcohol use.
Current Opinion in Behavioral Sciences,
13, 71-76.
Abstract:
Tripping up addiction: the use of psychedelic drugs in the treatment of problematic drug and alcohol use
Psychedelic drugs have been used as treatments in indigenous cultures for thousands of years. Yet, due to their legal status, there has been limited scientific research into the therapeutic potential of these compounds for psychiatric disorders. In the absence of other effective treatments however, researchers have begun again to systematically investigate such compounds and there is now evidence pointing to the use of psychedelic drugs in the treatment of addiction. In this review we focus on human evidence for the effectiveness of preparations used by indigenous cultures in the Amazon (ayahausca) and Africa (ibogaine) and worldwide (psilocybin), and more recently synthetised drugs such as the serotonergic hallucinogen LSD and the dissociative anaesthetic ketamine. Potential mechanisms explored are anti-depressant effects, changes in neuroplasticity and existential psychological effects of these drugs.
Abstract.
Lawn W, Hallak JE, Crippa JA, Dos Santos R, Porffy L, Barratt MJ, Ferris JA, Winstock AR, Morgan CJA (2017). Well-being, problematic alcohol consumption and acute subjective drug effects in past-year ayahuasca users: a large, international, self-selecting online survey.
Sci Rep,
7(1).
Abstract:
Well-being, problematic alcohol consumption and acute subjective drug effects in past-year ayahuasca users: a large, international, self-selecting online survey.
Ayahuasca is a natural psychedelic brew, which contains dimethyltryptamine (DMT). Its potential as a psychiatric medicine has recently been demonstrated and its non-medical use around the world appears to be growing. We aimed to investigate well-being and problematic alcohol use in ayahuasca users, and ayahuasca's subjective effects. An online, self-selecting, global survey examining patterns of drug use was conducted in 2015 and 2016 (n = 96,901). Questions were asked about: use of ayahuasca, lysergic acid diethylamide (LSD) and magic mushrooms; demographics, current well-being and past-year problematic alcohol use of past-year ayahuasca users and comparison drug users; and subjective effects of ayahuasca and comparison drugs. Ayahuasca users (n = 527) reported greater well-being than both classic psychedelic users (n = 18,138) and non-psychedelic drug-using respondents (n = 78,236). Ayahuasca users reported less problematic drinking than classic psychedelic users, although both groups reported greater problematic drinking than the other respondents. Ayahuasca's acute subjective effects usually lasted for six hours and were most strongly felt one hour after consumption. Within our online, self-selecting survey, ayahuasca users reported better well-being than comparison groups and less problematic drinking than classic psychedelic users. Future longitudinal studies of international samples and randomised controlled trials are needed to dissect the effects of ayahuasca on these outcomes.
Abstract.
Author URL.
2016
Morgan CJA, Freeman TP, Powell J, Curran HV (2016). AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers.
Transl Psychiatry,
6(2).
Abstract:
AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers.
Smoking cannabis daily doubles an individual's risk of developing a psychotic disorder, yet indicators of specific vulnerability have proved largely elusive. Genetic variation is one potential risk modifier. Single-nucleotide polymorphisms in the AKT1 and catechol-O-methyltransferase (COMT) genes have been implicated in the interaction between cannabis, psychosis and cognition, but no studies have examined their impact on an individual's acute response to smoked cannabis. A total 442 healthy young cannabis users were tested while intoxicated with their own cannabis-which was analysed for delta-9-tetrahydrocannbinol (THC) and cannabidiol content-and also ± 7 days apart when drug-free. Psychotomimetic symptoms and working memory were assessed on both the sessions. Variation at the rs2494732 locus of the AKT1 gene predicted acute psychotic response to cannabis along with dependence on the drug and baseline schizotypal symptoms. Working memory following cannabis acutely was worse in females, with some suggestion of an impact of COMT polymorphism on working memory when drug-free. These findings are the first to demonstrate that AKT1 mediates the acute response to cannabis in otherwise healthy individuals and implicate the AKT1 pathway as a possible target for prevention and treatment of cannabis psychosis.
Abstract.
Author URL.
Lawn W, Freeman TP, Pope RA, Joye A, Harvey L, Hindocha C, Mokrysz C, Moss A, Wall MB, Bloomfield MA, et al (2016). Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis 'amotivational' hypotheses.
Psychopharmacology (Berl),
233(19-20), 3537-3552.
Abstract:
Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis 'amotivational' hypotheses.
RATIONALE: Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence. OBJECTIVES: the objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning. METHODS: in study 1, 17 participants each received three acute vaporized treatments, namely Cann-CBD (8 mg THC), Cann + CBD (8 mg THC + 10 mg CBD) and matched placebo, followed by a 50 % dose top-up 1.5 h later, and completed the Effort Expenditure for Rewards Task (EEfRT). In study 2, 20 cannabis-dependent participants were compared with 20 non-dependent, drug-using control participants on the EEfRT and the Probabilistic Reward Task (PRT) in a non-intoxicated state. RESULTS: Cann-CBD reduced the likelihood of high-effort choices relative to placebo (p = 0.042) and increased sensitivity to expected value compared to both placebo (p = 0.014) and Cann + CBD (p = 0.006). The cannabis-dependent and control groups did not differ on the EEfRT. However, the cannabis-dependent group exhibited a weaker response bias than the control group on the PRT (p = 0.007). CONCLUSIONS: Cannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. In contrast, cannabis dependence was associated with preserved motivation alongside impaired reward learning, although confounding factors, including depression, cannot be disregarded. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC.
Abstract.
Author URL.
Freeman TP, Pope RA, Wall MB, Bisby J, Luijten M, Hindocha C, Lawn W, Mokrysz C, Moss A, Bloomfield MAP, et al (2016). Dissociable effects of cannabinoids on anticipatory and consummatory reward processing.
Author URL.
Curran HV, Freeman TP, Mokrysz C, Lewis DA, Morgan CJA, Parsons LH (2016). Keep off the grass? Cannabis, cognition and addiction.
Nat Rev Neurosci,
17(5), 293-306.
Abstract:
Keep off the grass? Cannabis, cognition and addiction.
In an increasing number of states and countries, cannabis now stands poised to join alcohol and tobacco as a legal drug. Quantifying the relative adverse and beneficial effects of cannabis and its constituent cannabinoids should therefore be prioritized. Whereas newspaper headlines have focused on links between cannabis and psychosis, less attention has been paid to the much more common problem of cannabis addiction. Certain cognitive changes have also been attributed to cannabis use, although their causality and longevity are fiercely debated. Identifying why some individuals are more vulnerable than others to the adverse effects of cannabis is now of paramount importance to public health. Here, we review the current state of knowledge about such vulnerability factors, the variations in types of cannabis, and the relationship between these and cognition and addiction.
Abstract.
Author URL.
Morgan PG, Sedensky MM, Kayser E-B (2016). Ketamine and Mitochondrial Function. Anesthesia & Analgesia, 122(3), 917-918.
Morgan C (2016). NEUROBIOBEHAVIOURAL CHANGES FOLLOWING KETAMINE USE: INSIGHTS FOR ADDICTION.
Author URL.
Tang WK, Lin Y, Zhang C, Liang H, Lai WY, Morgan C, Fan N, Davidson C, Ren Q, Hashimoto K, et al (2016). NEUROBIOLOGY AND NEUROPHARMACOLOGY OF PSYCHOTROPIC DRUG ABUSE.
Author URL.
Freeman TP, Pope RA, Wall MB, Bisby J, Luijten M, Hindocha C, Lawn W, Mokrysz C, Moss A, Bloomfield MAP, et al (2016). PM298. Dissociable effects of cannabinoids on anticipatory and consummatory reward processing. The International Journal of Neuropsychopharmacology, 19(Suppl_1), 6-7.
Bloomfield MAP, Mouchlianitis E, Morgan CJA, Freeman TP, Curran HV, Roiser JP, Howes OD (2016). Salience attribution and its relationship to cannabis-induced psychotic symptoms.
Psychological Medicine,
46(16), 3383-3395.
Abstract:
Salience attribution and its relationship to cannabis-induced psychotic symptoms
Background Cannabis is a widely used drug associated with increased risk for psychosis. The dopamine hypothesis of psychosis postulates that altered salience processing leads to psychosis. We therefore tested the hypothesis that cannabis users exhibit aberrant salience and explored the relationship between aberrant salience and dopamine synthesis capacity. Method We tested 17 cannabis users and 17 age- and sex-matched non-user controls using the Salience Attribution Test, a probabilistic reward-learning task. Within users, cannabis-induced psychotic symptoms were measured with the Psychotomimetic States Inventory. Dopamine synthesis capacity, indexed as the influx rate constant K i cer, was measured in 10 users and six controls with 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine positron emission tomography. Results There was no significant difference in aberrant salience between the groups [F 1,32 = 1.12, p = 0.30 (implicit); F 1,32 = 1.09, p = 0.30 (explicit)]. Within users there was a significant positive relationship between cannabis-induced psychotic symptom severity and explicit aberrant salience scores (r = 0.61, p = 0.04) and there was a significant association between cannabis dependency/abuse status and high implicit aberrant salience scores (F 1,15 = 5.8, p = 0.03). Within controls, implicit aberrant salience was inversely correlated with whole striatal dopamine synthesis capacity (r = -0.91, p = 0.01), whereas this relationship was non-significant within users (difference between correlations: Z = -2.05, p = 0.04). Conclusions Aberrant salience is positively associated with cannabis-induced psychotic symptom severity, but is not seen in cannabis users overall. This is consistent with the hypothesis that the link between cannabis use and psychosis involves alterations in salience processing. Longitudinal studies are needed to determine whether these cognitive abnormalities are pre-existing or caused by long-term cannabis use.
Abstract.
2015
Bloomfield M, Mouchlianitis E, Morgan C, Egerton A, Kapur S, Curran HV, Roiser J, Howes OD (2015). ABERRANT SALIENCE AND ITS RELATIONSHIP TO CANNABIS-INDUCED PSYCHOTIC SYMPTOMS.
Author URL.
Hindocha C, Freeman TP, Schafer G, Gardener C, Das RK, Morgan CJA, Curran HV (2015). Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: a randomised, double-blind, placebo-controlled study in cannabis users.
European Neuropsychopharmacology,
25(3), 325-334.
Abstract:
Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: a randomised, double-blind, placebo-controlled study in cannabis users
Acute administration of the primary psychoactive constituent of cannabis, δ-9-tetrahydrocannabinol (THC), impairs human facial affect recognition, implicating the endocannabinoid system in emotional processing. Another main constituent of cannabis, cannabidiol (CBD), has seemingly opposite functional effects on the brain. This study aimed to determine the effects of THC and CBD, both alone and in combination on emotional facial affect recognition. 48 volunteers, selected for high and low frequency of cannabis use and schizotypy, were administered, THC (8. mg), CBD (16. mg), THC+CBD (8. mg+16. mg) and placebo, by inhalation, in a 4-way, double-blind, placebo-controlled crossover design. They completed an emotional facial affect recognition task including fearful, angry, happy, sad, surprise and disgust faces varying in intensity from 20% to 100%. A visual analogue scale (VAS) of feeling 'stoned' was also completed. In comparison to placebo, CBD improved emotional facial affect recognition at 60% emotional intensity; THC was detrimental to the recognition of ambiguous faces of 40% intensity. The combination of THC+CBD produced no impairment. Relative to placebo, both THC alone and combined THC+CBD equally increased feelings of being 'stoned'. CBD did not influence feelings of 'stoned'. No effects of frequency of use or schizotypy were found. In conclusion, CBD improves recognition of emotional facial affect and attenuates the impairment induced by THC. This is the first human study examining the effects of different cannabinoids on emotional processing. It provides preliminary evidence that different pharmacological agents acting upon the endocannabinoid system can both improve and impair recognition of emotional faces.
Abstract.
Hindocha C, Freeman TP, Schafer G, Gardener C, Das RK, Morgan CJA, Curran HV (2015). Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: a randomised, double-blind, placebo-controlled study in cannabis users.
Eur Neuropsychopharmacol,
25(3), 325-334.
Abstract:
Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: a randomised, double-blind, placebo-controlled study in cannabis users.
Acute administration of the primary psychoactive constituent of cannabis, Δ-9-tetrahydrocannabinol (THC), impairs human facial affect recognition, implicating the endocannabinoid system in emotional processing. Another main constituent of cannabis, cannabidiol (CBD), has seemingly opposite functional effects on the brain. This study aimed to determine the effects of THC and CBD, both alone and in combination on emotional facial affect recognition. 48 volunteers, selected for high and low frequency of cannabis use and schizotypy, were administered, THC (8mg), CBD (16mg), THC+CBD (8mg+16mg) and placebo, by inhalation, in a 4-way, double-blind, placebo-controlled crossover design. They completed an emotional facial affect recognition task including fearful, angry, happy, sad, surprise and disgust faces varying in intensity from 20% to 100%. A visual analogue scale (VAS) of feeling 'stoned' was also completed. In comparison to placebo, CBD improved emotional facial affect recognition at 60% emotional intensity; THC was detrimental to the recognition of ambiguous faces of 40% intensity. The combination of THC+CBD produced no impairment. Relative to placebo, both THC alone and combined THC+CBD equally increased feelings of being 'stoned'. CBD did not influence feelings of 'stoned'. No effects of frequency of use or schizotypy were found. In conclusion, CBD improves recognition of emotional facial affect and attenuates the impairment induced by THC. This is the first human study examining the effects of different cannabinoids on emotional processing. It provides preliminary evidence that different pharmacological agents acting upon the endocannabinoid system can both improve and impair recognition of emotional faces.
Abstract.
Author URL.
Hindocha C, Shaban NDC, Freeman TP, Das RK, Gale G, Schafer G, Falconer CJ, Morgan CJA, Curran HV (2015). Associations between cigarette smoking and cannabis dependence: a longitudinal study of young cannabis users in the United Kingdom.
Drug Alcohol Depend,
148, 165-171.
Abstract:
Associations between cigarette smoking and cannabis dependence: a longitudinal study of young cannabis users in the United Kingdom.
AIMS: to determine the degree to which cigarette smoking predicts levels of cannabis dependence above and beyond cannabis use itself, concurrently and in an exploratory four-year follow-up, and to investigate whether cigarette smoking mediates the relationship between cannabis use and cannabis dependence. METHODS: the study was cross sectional with an exploratory follow-up in the participants' own homes or via telephone interviews in the United Kingdom. Participants were 298 cannabis and tobacco users aged between 16 and 23; follow-up consisted of 65 cannabis and tobacco users. The primary outcome variable was cannabis dependence as measured by the Severity of Dependence Scale (SDS). Cannabis and tobacco smoking were assessed through a self-reported drug history. RESULTS: Regression analyses at baseline showed cigarette smoking (frequency of cigarette smoking: B=0.029, 95% CI=0.01, 0.05; years of cigarette smoking: B=0.159, 95% CI=0.05, 0.27) accounted for 29% of the variance in cannabis dependence when controlling for frequency of cannabis use. At follow-up, only baseline cannabis dependence predicted follow-up cannabis dependence (B=0.274, 95% CI=0.05, 0.53). At baseline, cigarette smoking mediated the relationship between frequency of cannabis use and dependence (B=0.0168, 95% CI=0.008, 0.288) even when controlling for possible confounding variables (B=0.0153, 95% CI=0.007, 0.027). CONCLUSIONS: Cigarette smoking is related to concurrent cannabis dependence independently of cannabis use frequency. Cigarette smoking also mediates the relationship between cannabis use and cannabis dependence suggesting tobacco is a partial driver of cannabis dependence in young people who use cannabis and tobacco.
Abstract.
Author URL.
Curran HV, Morgan CJA (2015). Declarative and Nondeclarative Memory. In (Ed) Encyclopedia of Psychopharmacology, 462-468.
Morgan CJA, Noronha LA, Muetzelfeldt M, Feilding A, Curran HV (2015). Erratum: Harms and benefits associated with psychoactive drugs: Findings of an international survey of active drug users (Journal of Psychopharmacology 27 (497-506) DOI: 10.1177/0269881113477744). Journal of Psychopharmacology, 29(9).
Morgan CJA, Curran HV (2015). Inhibition of Memory. In (Ed) Encyclopedia of Psychopharmacology, 808-812.
Tang WK, Morgan CJA, Lau GC, Liang HJ, Tang A, Ungvari GS (2015). Psychiatric Morbidity in Ketamine Users Attending Counselling and Youth Outreach Services.
Substance AbuseAbstract:
Psychiatric Morbidity in Ketamine Users Attending Counselling and Youth Outreach Services
Background: No study has examined ketamine users’ psychiatric morbidity using structured diagnostic instruments. The aim of this study was thus to determine the psychiatric comorbidity of community-based ketamine users using the Structured Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), Axis I Disorders (SCID). Methods: a convenience sample of 200 frequent ketamine users was recruited from community organizations in Hong Kong. Participants were screened with the Severity of Dependence Scale (SDS), Beck Depression Inventory (BDI), Anxiety subscale of the Hospital Anxiety Depression Scale (HADSA), and SCID psychotic symptoms. Those who scored above the threshold (cutoff point of 8/9 on the BDI and 4/5 on HADSA) or displayed evidence of psychotic symptoms were referred for a structured clinical interview conducted by a psychiatrist. Results: One hundred and seventy participants scored above the cutoff point on 1 or more of the scales, and 115 participants attended the SCID interview. Fifty-one of these 115 participants received a psychiatric diagnosis of 1 or more comorbidities for the month preceding the interview. Mood disorders accounted for 80.4% of the diagnoses, anxiety disorders for 33.3%, and psychotic disorders for 7.8%. Conclusions: Female gender and history of psychiatric/psychological clinic attendance were significantly associated with comorbid psychiatric disorders, whereas ketamine dependence had a borderline association.
Abstract.
Tang WK, Morgan CJA, Lau GC, Liang HJ, Tang A, Ungvari GS (2015). Psychiatric morbidity in ketamine users attending counselling and youth outreach services.
Substance Abuse,
36(1), 67-74.
Abstract:
Psychiatric morbidity in ketamine users attending counselling and youth outreach services
Background: No study has examined ketamine users psychiatric morbidity using structured diagnostic instruments. The aim of this study was thus to determine the psychiatric comorbidity of community-based ketamine users using the Structured Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), Axis I Disorders (SCID). Methods: a convenience sample of 200 frequent ketamine users was recruited from community organizations in Hong Kong. Participants were screened with the Severity of Dependence Scale (SDS), Beck Depression Inventory (BDI), Anxiety subscale of the Hospital Anxiety Depression Scale (HADSA), and SCID psychotic symptoms. Those who scored above the threshold (cutoff point of 8/9 on the BDI and 4/5 on HADSA) or displayed evidence of psychotic symptoms were referred for a structured clinical interview conducted by a psychiatrist. Results: One hundred and seventy participants scored above the cutoff point on 1 or more of the scales, and 115 participants attended the SCID interview. Fifty-one of these 115 participants received a psychiatric diagnosis of 1 or more comorbidities for the month preceding the interview. Mood disorders accounted for 80.4% of the diagnoses, anxiety disorders for 33.3%, and psychotic disorders for 7.8%. Conclusions: Female gender and history of psychiatric/psychological clinic attendance were significantly associated with comorbid psychiatric disorders, whereas ketamine dependence had a borderline association.
Abstract.
Carhart-Harris RL, Murphy K, Leech R, Erritzoe D, Wall MB, Ferguson B, Williams LTJ, Roseman L, Brugger S, De Meer I, et al (2015). The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level-Dependent Resting State Functional Connectivity.
BIOLOGICAL PSYCHIATRY,
78(8), 554-562.
Author URL.
MBSc EN, Joshua N, Morgan C, Rossell SL (2015). The effect of ketamine on configural facial processing.
J Clin Psychopharmacol,
35(2), 188-191.
Abstract:
The effect of ketamine on configural facial processing.
Ketamine can induce a transient psychosis via its influence on ionotropic N-methyl-d-aspartate receptors. Unlike dopamine agonists, which specifically mimic the positive symptoms seen in psychotic illnesses such as schizophrenia, ketamine may provide a better model because it is able to induce not only positive symptoms but also schizophrenia-like cognitive and negative symptoms. To test the veracity of the ketamine model further, research is attempting to replicate a range of cognitive deficits associated with schizophrenia in healthy controls under the influence of ketamine. Facial processing is one area that is impaired in schizophrenia. More specifically, research suggests that schizophrenia is associated with a reduced facial inversion effect reflecting abnormalities in configural face processing. The purpose of the current study was to determine whether ketamine would also reduce the facial inversion effect. This study was a double-blind, placebo-controlled repeated-measures design in which data are presented for 14 participants who received ketamine on one occasion and saline on another. The results supported the ketamine model, with the participants demonstrating an intact inversion effect in the placebo condition but no inversion effect under the influence of ketamine. Further, participants' self-reported deficits in visual processing correlated with their inversion score and errors on the faces task. Future studies should examine a wider range of facial processing tasks with a larger sample to confirm the current results and to determine the specificity of ketamine's ability to mimic schizophrenia facial processing deficits. The current study is supportive of the role of glutamate system in the processing of configural face information.
Abstract.
Author URL.
Lawn W, Freeman TP, Hindocha C, Mokrysz C, Das RK, Morgan CJA, Curran HV (2015). The effects of nicotine dependence and acute abstinence on the processing of drug and non-drug rewards.
Psychopharmacology,
232(14), 2503-2517.
Abstract:
The effects of nicotine dependence and acute abstinence on the processing of drug and non-drug rewards
Rationale: Drug addiction may be characterised by a hypersensitivity to drug rewards and a hyposensitivity to non-drug rewards. This imbalance may become further polarised during acute abstinence. Objectives: (i) Examine the differences between dependent and occasional smokers in choices for, motivation for and self-reported wanting and liking of cigarette and non-drug rewards. (ii) Examine the effects of 12-h nicotine abstinence on these metrics. Methods: Dependent (n=20) and occasional, non-dependent smokers (n=20) were tested after ad libitum smoking and ≥12-h of nicotine abstinence. A novel task was developed (Drug, Reward and Motivation-Choice (DReaM-Choice)) in which different rewards (cigarettes, music and chocolate) could be won. In each trial, participants chose between two rewards and then could earn the chosen reward via repeated button-pressing. Participants subsequently 'consumed' and rated subjective liking of the rewards they had won. Results: Compared with occasional smokers, dependent smokers made more choices for (p
Abstract.
Lawn W, Freeman TP, Hindocha C, Mokrysz C, Das RK, Morgan CJA, Curran HV (2015). The effects of nicotine dependence and acute abstinence on the processing of drug and non-drug rewards.
PsychopharmacologyAbstract:
The effects of nicotine dependence and acute abstinence on the processing of drug and non-drug rewards
Rationale: Drug addiction may be characterised by a hypersensitivity to drug rewards and a hyposensitivity to non-drug rewards. This imbalance may become further polarised during acute abstinence.
Abstract.
2014
Edward Roberts R, Curran HV, Friston KJ, Morgan CJA (2014). Abnormalities in white matter microstructure associated with chronic ketamine use.
Neuropsychopharmacology,
39(2), 329-338.
Abstract:
Abnormalities in white matter microstructure associated with chronic ketamine use
Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been found to induce schizophrenia-type symptoms in humans and is a potent and fast-acting antidepressant. It is also a relatively widespread drug of abuse, particularly in China and the UK. Acute administration has been well characterized, but the effect of extended periods of ketamine use-on brain structure in humans-remains poorly understood. We measured indices of white matter microstructural integrity and connectivity in the brain of 16 ketamine users and 16 poly-drug-using controls, and we used probabilistic tractography to quantify changes in corticosubcortical connectivity associated with ketamine use. We found a reduction in the axial diffusivity profile of white matter in a right hemisphere network of white matter regions in ketamine users compared with controls. Within the ketamine-user group, we found a significant positive association between the connectivity profile between the caudate nucleus and the lateral prefrontal cortex and dissociative experiences. These findings suggest that chronic ketamine use may be associated with widespread disruption of white matter integrity, and white matter pathways between subcortical and prefrontal cortical areas may in part predict individual differences in dissociative experiences due to ketamine use. © 2014 American College of Neuropsychopharmacology.
Abstract.
Curran HV, Morgan CJA (2014). Desired and Undesired Effects of Cannabis on the Human Mind and Psychological Well-Being. In (Ed) Handbook of Cannabis, 647-660.
Bloomfield MAP, Morgan CJA, Egerton A, Kapur S, Curran HV, Howes OD (2014). Dopaminergic Function in Cannabis Users and its Relationship to Cannabis-Induced Psychotic Symptoms.
BIOLOGICAL PSYCHIATRY,
75(6), 470-478.
Author URL.
Freeman TP, Morgan CJA, Hindocha C, Schafer GL, Das RK, Curran HV (2014). Effects of delta-9-tetrahydrocannabinol and cannabidiol on estimated cannabis potency and actual titration.
Author URL.
Stewart LH, Ferguson B, Morgan CJA, Swaboda N, Jones L, Fenton R, Wall MB, Curran HV (2014). Effects of ecstasy on cooperative behaviour and perception of trustworthiness: a naturalistic study.
J Psychopharmacol,
28(11), 1001-1008.
Abstract:
Effects of ecstasy on cooperative behaviour and perception of trustworthiness: a naturalistic study.
BACKGROUND: Acute recreational use of 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') can promote pro-social effects which may alter interpersonal perceptions. AIMS: to explore such effects, this study investigated whether acute recreational use of ecstasy was associated with changes in individual perception of trustworthiness of people's faces and co-operative behaviours. METHOD: an independent group, repeated measures design was used in which 17 ecstasy users were tested on the night of drug use (day 0) and again three days later (day 3); 22 controls were tested on parallel days. On each day, participants rated the trustworthiness of 66 faces, carried out three co-operative behaviour tasks (public good; dictator; ultimatum game) and completed mood self-ratings. RESULTS: Acute ecstasy use was associated with increased face trustworthiness ratings and increased cooperative behaviour on the dictator and ultimatum games; on day 3 there were no group differences on any task. Self-ratings showed the standard acute ecstasy effects (euphoria, energy, jaw clenching) with negative effects (less empathy, compassion, more distrust, hostility) emerging on day 3. CONCLUSIONS: Our findings of increased perceived trustworthiness and co-operative behaviours following use of ecstasy suggest that a single dose of the drug enhances aspects of empathy. This may in turn contribute to its popularity as a recreational drug and potentially to its enhancement of the therapeutic alliance in psychotherapy.
Abstract.
Author URL.
Stone JM, Pepper F, Fam J, Furby H, Hughes E, Morgan C, Howes OD (2014). Erratum: Glutamate, N-acetyl aspartate and psychotic symptoms in chronic ketamine users (Psychopharmacology DOI: 10.1007/s00213-013-3354-8). Psychopharmacology, 231(10), 2117-2118.
Stone JM, Pepper F, Fam J, Furby H, Hughes E, Morgan C, Howes OD (2014). Glutamate, N-acetyl aspartate and psychotic symptoms in chronic ketamine users.
PSYCHOPHARMACOLOGY,
231(10), 2107-2116.
Author URL.
Hindocha C, Freeman TP, Schafer G, Gardener C, Morgan CJA, Curran HV (2014). Individual and combined effects of delta-9-tetrahydrocannabinol and cannabidiol on model psychosis and memory function.
Author URL.
Morgan CJA (2014). Inhibition of Memory. In (Ed) Encyclopedia of Psychopharmacology, 1-6.
Freeman TP, Morgan CJA, Hindocha C, Schafer G, Das RK, Curran HV (2014). Just say 'know': How do cannabinoid concentrations influence users' estimates of cannabis potency and the amount they roll in joints?.
AddictionAbstract:
Just say 'know': How do cannabinoid concentrations influence users' estimates of cannabis potency and the amount they roll in joints?
Aims: (1) to determine whether measured concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in individuals' own cannabis predict their estimates of drug potency and actual titration; and (2) to ascertain if these effects are influenced by frequency of use and cannabis type. Design: Cross-sectional, naturalistic. Setting: Participants' own homes. Participants: a total of 247 cannabis users in the United Kingdom: 152 'recreational' (1-24 days/month) and 95 'daily' (≥25 days/month). Methods: Participants rated their own cannabis for its potency (1-10) and type ('resin', 'herbal', 'skunk') before smoking it in front of the researcher. The amount of cannabis (g) used in their joints was recorded and an additional sample was analysed for THC and CBD concentrations (%). Findings: THC concentrations were related negatively to the amount of cannabis used [unstandardized regression coefficient: b=-0.009, 95% confidence interval (CI)=-0.017, -0.002]. Potency estimates were predicted by increasing THC (b=0.055, 95% CI=0.020, 0.090) and decreasing CBD (b=-0.160, 95% CI=-0.284, -0.062), and both of these associations were mediated by cannabis type (THC: b=0.018, 95% CI=0.006, 0.037; CBD: b=-0.105, 95% CI=-0.198, -0.028). Potency estimates were more reflective of THC as frequency of use increased (b=0.004, 95% CI=0.001 . 0.007) and were 7.3 times more so in daily (partial r=0.381) than recreational users (r=0.052). Conclusions: When using their own cannabis in a naturalistic setting, people titrate the amount they roll in joints according to concentrations of delta-9-tetrahydrocannabinol (THC) but not cannabidiol (CBD). Recreational users thus show poor understanding of cannabis potency. © 2014 Society for the Study of Addiction.
Abstract.
Neill E, Rossell SL, Morgan CJA, Carter O, Joshua N (2014). KETAMINE AS a MODEL FOR SCHIZOPHRENIA DEFICITS.
Author URL.
Morgan CJA, Dodds CM, Furby H, Pepper F, Fam J, Freeman TP, Hughes E, Doeller C, King J, Howes O, et al (2014). Long-term heavy ketamine use is associated with spatial memory impairment and altered hippocampal activation.
Frontiers in Psychiatry,
5(OCT).
Abstract:
Long-term heavy ketamine use is associated with spatial memory impairment and altered hippocampal activation
Ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist, is rising in popularity as a drug of abuse. Preliminary evidence suggests that chronic, heavy ketamine use may have profound effects on spatial memory but the mechanism of these deficits is as yet unclear. This study aimed to examine the neural mechanism by which heavy ketamine use impairs spatial memory processing. In a sample of 11 frequent ketamine users and 15 polydrug controls, matched for IQ, age, years in education. We used fMRI utilising an ROI approach to examine the neural activity of three regions known to support successful navigation; the hippocampus, parahippocampal gyrus and the caudate nucleus during a virtual reality task of spatial memory. Frequent ketamine users displayed spatial memory deficits, accompanied by and related to, reduced activation in both the right hippocampus and left parahippocampal gyrus during navigation from memory, and in the left caudate during memory updating, compared to controls. Ketamine users also exhibited schizotypal and dissociative symptoms that were related to hippocampal activation. Impairments in spatial memory observed in ketamine users are related to changes in medial temporal lobe activation. Disrupted medial temporal lobe function may be a consequence of chronic ketamine abuse and may relate to schizophrenia-like symptomatology observed in ketamine users.
Abstract.
Neill E, Rossell SL, Morgan CJA, Carter O, Joshua N (2014). Poster #M234 KETAMINE AS a MODEL FOR SCHIZOPHRENIA DEFICITS. Schizophrenia Research, 153, S275-S275.
Carhart-Harris RL, Wall MB, Erritzoe D, Kaelen M, Ferguson B, De Meer I, Tanner M, Bloomfield M, Williams TM, Bolstridge M, et al (2014). The effect of acutely administered MDMA on subjective and BOLD-fMRI responses to favourite and worst autobiographical memories.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY,
17(4), 527-540.
Author URL.
Bloomfield MAP, Morgan CJA, Kapur S, Curran HV, Howes OD (2014). The link between dopamine function and apathy in cannabis users: an [ <sup>18</sup>F]-DOPA PET imaging study.
Psychopharmacology,
231(11), 2251-2259.
Abstract:
The link between dopamine function and apathy in cannabis users: an [ 18F]-DOPA PET imaging study
Rationale: Cannabis is the most widely used illicit drug in the world, and regular use has been associated with reduced motivation, i.e. Apathy. Regular long-term cannabis use has been associated with reduced dopamine synthesis capacity. The mesolimbic dopaminergic system mediates the processing of incentive stimuli by modifying their motivational value, which in turn is modulated by endocannabinoid signalling. Thus, it has been proposed that dopaminergic dysfunction underlies the apathy associated with chronic cannabis use. Objectives: the aim of this study was to examine the relationship between dopaminergic function and subjective apathy in cannabis users. Methods: We measured dopamine synthesis capacity (indexed as the influx rate constant K icer) via 3,4-dihydroxy-6-[18F]-fluoro-l- phenylalanine positron emission tomography and subjective apathy using the self-rated Apathy Evaluation Scale (AES-S) in 14 regular cannabis users. Results: all subjects scored in excess of 34 points on the AES-S (median [interquartile range] 59.5 [7.5]), indicative of significant apathy based on normative data. K icer was inversely correlated to AES-S score in the whole striatum and its associative functional subdivision (Spearman's rho=-0.64, p=0.015 [whole striatum]; rho=-0.69, p=0.006 [associative]) but not in the limbic or sensorimotor striatal subdivisions. There were no significant relationships between AES-S and current cannabis consumption (rho=0.28, p=0.34) or age of first cannabis use (rho=0.25, p=0.40). Conclusions: These findings indicate that the reduction in striatal dopamine synthesis capacity associated with chronic cannabis use may underlie reduced reward sensitivity and amotivation associated with chronic cannabis use. © 2014 Springer-Verlag Berlin Heidelberg.
Abstract.
Bloomfield MAP, Morgan CJA, Kapur S, Curran HV, Howes OD (2014). The link between dopamine function and apathy in cannabis users: an [18F]-DOPA PET imaging study. Psychopharmacology
Bloomfield MAP, Morgan CJA, Kapur S, Curran HV, Howes OD (2014). The link between dopamine function and apathy in cannabis users: an [F-18]-DOPA PET imaging study.
Author URL.
Rossell S, Curran V, Morgan C (2014). Using ketamine to model thought disorder in schizophrenia. Acta Neuropsychiatrica, 18(6), 268-269.
2013
Edward Roberts R, Curran HV, Friston KJ, Morgan CJA (2013). Abnormalities in White Matter Microstructure Associated with Chronic Ketamine Use. Neuropsychopharmacology
Freeman TP, Morgan CJA, Pepper F, Howes OD, Stone JM, Curran HV (2013). Associative blocking to reward-predicting cues is attenuated in ketamine users but can be modulated by images associated with drug use.
Psychopharmacology (Berl),
225(1), 41-50.
Abstract:
Associative blocking to reward-predicting cues is attenuated in ketamine users but can be modulated by images associated with drug use.
RATIONALE: Blocking is an associative learning process that is attenuated in schizophrenia, can be modulated by cue salience and is accompanied by changes in selective attention. Repeated exposure to ketamine can model aspects of schizophrenia, and frequent users selectively attend to images of the drug. OBJECTIVES: This study aimed to establish whether (1) ketamine users show attenuated blocking to reward-predicting cues and (2) drug cues can modulate blocking and cause overshadowing of neutral cues that are equally predictive of reward in these individuals. METHODS: Ketamine users (n = 18) and polydrug controls (n = 16) were assessed on the Drug Cue Reward Prediction Error Task, which indexes blocking and overshadowing to neutral and drug-related cues following Pavlovian reward conditioning. Schizotypy, depression, drug history and ketamine dependence were also assessed. RESULTS: Compared to controls, ketamine users showed elevated delusional, schizotypal and depressive symptoms, and a reduction in blocking as evidenced by higher accuracy to blocked cues. Drug-related cues were resistant to blocking and seen as more important for earning money by ketamine users compared to controls. Both groups showed overshadowing of neutral cues by drug cues, and ketamine users gave both of these cues higher importance ratings than controls. CONCLUSIONS: These findings provide the first evidence that (1) glutamatergic perturbation is linked to a reduction in blocking and (2) blocking can be modulated by the presence of drug-related cues. The ability of drug cues to bias selective learning about 'alternative rewards' has implications for contingency management based addiction treatments.
Abstract.
Author URL.
Das RK, Kamboj SK, Ramadas M, Yogan K, Gupta V, Redman E, Curran HV, Morgan CJA (2013). Cannabidiol enhances consolidation of explicit fear extinction in humans.
Psychopharmacology,
226(4), 781-792.
Abstract:
Cannabidiol enhances consolidation of explicit fear extinction in humans
Rationale: Whilst Cannabidiol (CBD), a non-psychotomimetic cannabinoid, has been shown to enhance extinction learning in rats, its effects on fear memory in humans have not previously been studied. Objectives: We employed a Pavlovian fear-conditioning paradigm in order to assess the effects of CBD on extinction and consolidation. Method: Forty-eight participants were conditioned to a coloured box (CS) with electric shocks (UCS) in one context and were extinguished in a second context. Participants received 32 mg of CBD either following before or after extinction in a double-blind, placebo-controlled design. At recall, 48 h later, participants were exposed to CSs and conditioning contexts before (recall) and after (reinstatement) exposure to the UCS. Skin conductance and shock expectancy measures of conditioned responding were recorded throughout. Results: Successful conditioning, extinction and recall were found in all three treatment groups. CBD given post-extinction enhanced consolidation of extinction learning as assessed by shock expectancy. CBD administered at either time produced trend level reduction in reinstatement of autonomic contextual responding. No acute effects of CBD were found on extinction. Conclusions: These findings provide the first evidence that CBD can enhance consolidation of extinction learning in humans and suggest that CBD may have potential as an adjunct to extinction-based therapies for anxiety disorders. © 2013 Springer-Verlag Berlin Heidelberg.
Abstract.
Morgan CJA, Das RK, Joye A, Curran HV, Kamboj SK (2013). Cannabidiol reduces cigarette consumption in tobacco smokers: preliminary findings.
Addict Behav,
38(9), 2433-2436.
Abstract:
Cannabidiol reduces cigarette consumption in tobacco smokers: preliminary findings.
The role of the endocannabinoid system in nicotine addiction is being increasingly acknowledged. We conducted a pilot, randomised double blind placebo controlled study set out to assess the impact of the ad-hoc use of cannabidiol (CBD) in smokers who wished to stop smoking. 24 smokers were randomised to receive an inhaler of CBD (n=12) or placebo (n=12) for one week, they were instructed to use the inhaler when they felt the urge to smoke. Over the treatment week, placebo treated smokers showed no differences in number of cigarettes smoked. In contrast, those treated with CBD significantly reduced the number of cigarettes smoked by ~40% during treatment. Results also indicated some maintenance of this effect at follow-up. These preliminary data, combined with the strong preclinical rationale for use of this compound, suggest CBD to be a potential treatment for nicotine addiction that warrants further exploration.
Abstract.
Author URL.
Morgan CJA, Page E, Schaefer C, Chatten K, Manocha A, Gulati S, Curran HV, Brandner B, Leweke FM (2013). Cerebrospinal fluid anandamide levels, cannabis use and psychotic-like symptoms.
Br J Psychiatry,
202(5), 381-382.
Abstract:
Cerebrospinal fluid anandamide levels, cannabis use and psychotic-like symptoms.
Anandamide is a ligand of the endocannabinoid system. Animals show a depletion following repeated Δ(9)-tetrahydrocannabinol (THC) administration but the effect of cannabis use on central nervous system levels of endocannabinoids has not been previously examined in humans. Cerebrospinal fluid (CSF) levels of the endocannabinoids anandamide, 2-arachidonoylglycerol (2-AG) and related lipids were tested in 33 volunteers (20 cannabis users). Lower levels of CSF anandamide and higher levels of 2-AG in serum were observed in frequent compared with infrequent cannabis users. Levels of CSF anandamide were negatively correlated with persisting psychotic symptoms when drug-free. Higher levels of anandamide are associated with a lower risk of psychotic symptoms following cannabis use.
Abstract.
Author URL.
Freeman TP, Morgan CJA, Brandner B, Almahdi B, Curran HV (2013). Dopaminergic involvement in effort-based but not impulsive reward processing in smokers.
Drug Alcohol Depend,
130(1-3), 109-114.
Abstract:
Dopaminergic involvement in effort-based but not impulsive reward processing in smokers.
BACKGROUND: a reduction in reward responsivity and an increase in temporal discounting of rewards are both evident in smokers during acute abstinence compared to satiation. However, it is not yet known whether these processes can be modulated pharmacologically in smokers, other than with nicotine or tobacco. METHODS: a double-blind placebo controlled crossover design assessed the effects of 0.5 mg pramipexole, a dopamine D₂/D₃ agonist, in smokers following 2 h of abstinence. Reward responsivity was measured using an effort-based card sorting task. Temporal discounting of monetary reward was assessed using Area Under the Curve (AUC) analysis, and affective and subjective effects were indexed. RESULTS: on placebo, smokers showed an equivalent speed of card sorting when a financial incentive was provided compared to when it was not. Conversely, more cards were sorted under rewarded compared to non-rewarded trials after pramipexole, indicating an improvement in reward responsivity. Temporal discounting of monetary reward was not affected by pramipexole. Drug treatment also decreased positive affect and increased drowsiness. CONCLUSIONS: a single dose of pramipexole can enhance effort-based reward responsivity, but does not alter temporal discounting in smokers. These findings highlight pharmacological correlates of reward processing deficits in nicotine dependence and offer potential targets for their treatment.
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Author URL.
Morgan CJA, Noronha LA, Muetzelfeldt M, Fielding A, Curran HV (2013). Harms and benefits associated with psychoactive drugs: findings of an international survey of active drug users.
JOURNAL OF PSYCHOPHARMACOLOGY,
27(6), 497-506.
Author URL.
Morgan CJA, Noronha LA, Muetzelfeldt M, Feilding A, Curran HV (2013). Harms and benefits associated with psychoactive drugs: findings of an international survey of active drug users.
J Psychopharmacol,
27(6), 497-506.
Abstract:
Harms and benefits associated with psychoactive drugs: findings of an international survey of active drug users.
There have been several recent efforts in the UK and the Netherlands to describe the harms of psychoactive substances based on ratings of either experts or drug users. This study aimed to assess the perceived benefits as well as harms of widely used recreational drugs, both licit and illicit, in an international sample of drug users. The survey was hosted at https://www.internationaldrugsurvey.org/ and was available in three languages. Residents reported their experience of 15 commonly used drugs or drug classes; regular users then rated their harms and benefits. In all, 5791 individuals from over 40 countries completed the survey, although the majority were from English speaking countries. Rankings of drugs differed across 10 categories of perceived benefits. Skunk and herbal cannabis were ranked consistently beneficial, whilst alcohol and tobacco fell below many classified drugs. There was no correlation at all between users' harm ranking of drugs and their classification in schedules of the USA or ABC system in the UK. Prescription analgesics, alcohol and tobacco were ranked within the top 10 most harmful drugs. These findings suggest that neither the UK nor US classification systems act to inform users of the harms of psychoactive substances. It is hoped the results might inform health professionals and educators of what are considered to be both the harms and benefits of psychoactive substances to young people.
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Author URL.
2012
Freeman T, Morgan CJA, Pepper F, Howes OD, Stone JM, Curran HV (2012). Associative blocking to reward-predicting cues is attenuated in ketamine users but can be modulated by images associated with drug use.
Author URL.
Bloomfield MAP, Morgan CJA, Egerton A, Kapur S, Curran HV, Howes OD (2012). Chronic cannabis use and dopamine synthesis capacity: an [18F]-DOPA positron emission tomography study.
Author URL.
Freeman TP, Morgan CJA, Vaughn-Jones J, Hussain N, Karimi K, Curran HV (2012). Cognitive and subjective effects of mephedrone and factors influencing use of a 'new legal high'.
Addiction,
107(4), 792-800.
Abstract:
Cognitive and subjective effects of mephedrone and factors influencing use of a 'new legal high'.
AIMS: Use of the stimulant drug mephedrone increased dramatically in 2009, and it is still available in the United Kingdom after being controlled in April 2010. This study aimed to assess mephedrone's acute cognitive and subjective effects. DESIGN: a mixed within- and between-subjects design compared 20 mephedrone users, first while intoxicated (T1) and secondly drug free (T2); and 20 controls twice when drug free (T1 and T2). SETTINGS: Participants' own homes. PARTICIPANTS: Healthy adults recruited from the community. MEASUREMENTS: Subjective effects, episodic and working memory, phonological and semantic fluency, psychomotor speed and executive control at were assessed at T1 and T2. Trait schizotypy, depression, changes in mephedrone use since the ban and attitudes influencing use of a hypothetical new legal high were indexed at T2 only. FINDINGS: Compared with controls, mephedrone users had generally impaired prose recall (P = 0.037) and higher scores in schizotypy (P < 0.001) and depression (P = 0.01). Mephedrone acutely primed a marked 'wanting' for the drug (P < 0.001), induced stimulant-like effects, impaired working memory (P < 0.001) and enhanced psychomotor speed (P = 0.024). Impulsivity in mephedrone users correlated with the number of hours in an average (nearly 8 hour) mephedrone session (r = 0.6). Users would be drawn to use a new legal high if it were pure, had no long/short term harms, and was positively rated by friends or on the internet. CONCLUSIONS: Mephedrone impairs working memory acutely, induces stimulant-like effects in users and is associated with binge use. Factors that influence users' attitudes to new drugs might help to predict future trends in use of the many new psychoactive substances emerging on the internet.
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Author URL.
Kamboj SK, Joye A, Das RK, Gibson AJW, Morgan CJA, Curran HV (2012). Cue exposure and response prevention with heavy smokers: a laboratory-based randomised placebo-controlled trial examining the effects of D-cycloserine on cue reactivity and attentional bias.
PSYCHOPHARMACOLOGY,
221(2), 273-284.
Author URL.
Bloomfield MAP, Morgan CJA, Egerton A, Kapur S, Curran HV, Howes OD (2012). DOPAMINE SYNTHESIS CAPACITY IN REGULAR CANNABIS USERS WHO EXPERIENCE TRANSIENT PSYCHOTIC SYMPTOMS ON CANNABIS: AN [F-18]-DOPA PET IMAGING STUDY.
Author URL.
Bloomfield MAP, Morgan CJA, Egerton A, Kapur S, Curran HV, Howes OD (2012). Dopaminergic function in cannabis users: an [F-18]-DOPA positron emission tomography study of dopamine synthesis capacity.
Author URL.
Freeman TP, Morgan CJA, Beesley T, Curran HV (2012). Drug cue induced overshadowing: selective disruption of natural reward processing by cigarette cues amongst abstinent but not satiated smokers.
PSYCHOLOGICAL MEDICINE,
42(1), 161-171.
Author URL.
Freeman TP, Morgan CJA, Beesley T, Curran HV (2012). Erratum: Drug cue induced overshadowing: Selective disruption of natural reward processing by cigarette cues amongst abstinent but not satiated smokers (Psychological Medicine (2011) 42 (161-171)). Psychological Medicine, 42(6).
Schafer G, Feilding A, Morgan CJA, Agathangelou M, Freeman TP, Valerie Curran H (2012). Investigating the interaction between schizotypy, divergent thinking and cannabis use.
Conscious Cogn,
21(1), 292-298.
Abstract:
Investigating the interaction between schizotypy, divergent thinking and cannabis use.
Cannabis acutely increases schizotypy and chronic use is associated with elevated rates of psychosis. Creative individuals have higher levels of schizotypy, however links between cannabis use, schizotypy and creativity have not been investigated. We investigated the effects of cannabis smoked naturalistically on schizotypy and divergent thinking, a measure of creativity. One hundred and sixty cannabis users were tested on 1 day when sober and another day when intoxicated with cannabis. State and trait measures of both schizotypy and creativity were administered. Quartile splits compared those lowest (n=47) and highest (n=43) in trait creativity. Cannabis increased verbal fluency in low creatives to the same level as that of high creatives. Cannabis increased state psychosis-like symptoms in both groups and the high creativity group were significantly higher in trait schizotypy, but this does not appear to be linked to the verbal fluency change. Acute cannabis use increases divergent thinking as indexed by verbal fluency in low creatives.
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Author URL.
Morgan CJA, Curran HV, ISCD (2012). Ketamine use: a review.
ADDICTION,
107(1), 27-38.
Author URL.
Morgan CJA, Duffin S, Hunt S, Monaghan L, Mason O, Curran HV (2012). Neurocognitive Function and Schizophrenia-Proneness in Individuals Dependent on Ketamine, on High Potency Cannabis ('Skunk') or on Cocaine.
PHARMACOPSYCHIATRY,
45(7), 269-274.
Author URL.
Bloomfield MAP, Morgan CJA, Egerton A, Kapur S, Curran HV, Howes OD (2012). P.3.029 Chronic cannabis use and dopamine synthesis capacity: an [18F]-DOPA positron emission tomography study. European Neuropsychopharmacology, 22, s76-s77.
Rossell SL, Neill E, Morgan C (2012). Poster #164 THE COGNITIVE SUBSTRATES OF THOUGHT DISORDER USING ANALOGUE MODELING. Schizophrenia Research, 136
Griffiths A, Hill R, Morgan C, Rendell PG, Karimi K, Wanagaratne S, Curran HV (2012). Prospective memory and future event simulation in individuals with alcohol dependence.
Addiction,
107(10), 1809-1816.
Abstract:
Prospective memory and future event simulation in individuals with alcohol dependence.
AIM: to assess objectively prospective memory (PM) performance of individuals with alcohol dependence and determine whether the use of an imagery technique at the point of encoding can enhance their performance. DESIGN: an independent group design was used to compare individuals with alcohol dependence with social drinkers. SETTING: One UK residential substance misuse service. PARTICIPANTS: Twenty-four abstinent 'individuals with alcohol dependence' and 24 social drinkers matched on age, gender and years of education. MEASUREMENTS: the virtual week (VW); story recall; a category fluency task; trail-making test (TMT); a single digit cancellation task (SDCT); spot-the-word; State-Trait Anxiety Inventory (STAI); Beck Depression Inventory (BDI-II); and the Severity of Alcohol Dependence Questionnaire (SAD-Q) FINDINGS: Event-based PM task performance of individuals with alcohol dependence was associated strongly with indices of alcohol usage (P < 0.001), and was impaired significantly compared to that of social drinkers (P < 0.001). Imagining improved social drinkers' time-based PM but not that of individuals with alcohol dependence. CONCLUSIONS: Individuals with alcohol dependence may experience prospective memory deficits which may be due to difficulties with effective strategy application.
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Author URL.
Battistella S, Constantinou N, Morgan CJA, Davis P, O'Ryan D, Curran HV (2012). Semantic priming and verbal learning in current opiate users, ex-users and non-user controls.
HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL,
27(5), 499-506.
Author URL.
Morgan CJA, Gardener C, Schafer G, Swan S, Demarchi C, Freeman TP, Warrington P, Rupasinghe I, Ramoutar A, Tan N, et al (2012). Sub-chronic impact of cannabinoids in street cannabis on cognition, psychotic-like symptoms and psychological well-being.
Psychological Medicine,
42(2), 391-400.
Abstract:
Sub-chronic impact of cannabinoids in street cannabis on cognition, psychotic-like symptoms and psychological well-being
Background Cannabis varies considerably in levels of its two major constituent cannabinoids-(delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Recently, we found evidence that those who smoked cannabis containing detectable levels of CBD had fewer psychotic-like symptoms than those whose cannabis had no CBD. The present study aimed, first, to replicate those findings and, second, to determine whether protective effects of CBD may extend to other harms of cannabis, such as memory impairment and reduced psychological well-being.Method a total of 120 current cannabis smokers, 66 daily users and 54 recreational users were classified into groups according to whether analysis of their hair revealed the presence or absence of CBD and high versus low levels of THC. All were assessed on measures of psychosis-like symptoms, memory (prose recall; source memory) and depression/anxiety.Results Lower psychosis-like symptoms were found in those whose hair had CBD compared with those without. However, this was seen only in recreational users, who had higher levels of THC in their hair. Higher THC levels in hair were associated with increased depression and anxiety. Prose recall and source memory were poorer in daily users with high THC levels in hair while recognition memory was better in individuals with CBD present in hair.Conclusions CBD attenuates the psychotic-like effects of cannabis over time in recreational users. Higher THC negatively impacts on memory and psychological well-being. These findings raise concerns for the harms stemming from use of varieties such as 'skunk' (sensimillia), which lack any CBD but currently dominate the supply of cannabis in many countries. © 2011 Cambridge University Press.
Abstract.
Morgan CJA, Gardener C, Schafer G, Swan S, Demarchi C, Freeman TP, Warrington P, Rupasinghe I, Ramoutar A, Tan N, et al (2012). Sub-chronic impact of cannabinoids in street cannabis on cognition, psychotic-like symptoms and psychological well-being.
Psychol Med,
42(2), 391-400.
Abstract:
Sub-chronic impact of cannabinoids in street cannabis on cognition, psychotic-like symptoms and psychological well-being.
BACKGROUND: Cannabis varies considerably in levels of its two major constituent cannabinoids - (delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Recently, we found evidence that those who smoked cannabis containing detectable levels of CBD had fewer psychotic-like symptoms than those whose cannabis had no CBD. The present study aimed, first, to replicate those findings and, second, to determine whether protective effects of CBD may extend to other harms of cannabis, such as memory impairment and reduced psychological well-being. METHOD: a total of 120 current cannabis smokers, 66 daily users and 54 recreational users were classified into groups according to whether analysis of their hair revealed the presence or absence of CBD and high versus low levels of THC. All were assessed on measures of psychosis-like symptoms, memory (prose recall; source memory) and depression/anxiety. RESULTS: Lower psychosis-like symptoms were found in those whose hair had CBD compared with those without. However, this was seen only in recreational users, who had higher levels of THC in their hair. Higher THC levels in hair were associated with increased depression and anxiety. Prose recall and source memory were poorer in daily users with high THC levels in hair while recognition memory was better in individuals with CBD present in hair. CONCLUSIONS: CBD attenuates the psychotic-like effects of cannabis over time in recreational users. Higher THC negatively impacts on memory and psychological well-being. These findings raise concerns for the harms stemming from use of varieties such as 'skunk' (sensimillia), which lack any CBD but currently dominate the supply of cannabis in many countries.
Abstract.
Author URL.
Rossell SL, Neill E, Morgan C (2012). THE COGNITIVE SUBSTRATES OF THOUGHT DISORDER USING ANALOGUE MODELING.
Author URL.
2011
Taylor EM, Greene NMP, Morgan CJA, Munafo MR (2011). Association of study characteristics with estimates of effect size in studies of ecstasy use.
JOURNAL OF PSYCHOPHARMACOLOGY,
25(11), 1573-1577.
Author URL.
Das RK, Gupta V, Ramadas M, Yogan K, Morgan CJA, Kamboj S (2011). CANNABIDIOL POTENTIATES THE CONSOLIDATION OF CONDITIONED FEAR MEMORY IN HUMANS.
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Morgan CJA, Schafer G, Gardener C, Curran HV (2011). CBD VS. THC: HOW DO EFFECTS DIFFER IN USERS PRONE TO PSYCHOSIS, ACUTELY AND CHRONICALLY, AND NATURALISTICALLY AND IN THE LABORATORY?.
Author URL.
Kamboj SK, Massey-Chase R, Rodney L, Das R, Almahdi B, Curran HV, Morgan CJA (2011). Changes in cue reactivity and attentional bias following experimental cue exposure and response prevention: a laboratory study of the effects of D-cycloserine in heavy drinkers.
Psychopharmacology (Berl),
217(1), 25-37.
Abstract:
Changes in cue reactivity and attentional bias following experimental cue exposure and response prevention: a laboratory study of the effects of D-cycloserine in heavy drinkers.
RATIONALE: the effects of D-cycloserine (DCS) in animal models of anxiety disorders and addiction indicate a role for N-methyl D-aspartate (NMDA) receptors in extinction learning. Exposure/response prevention treatments for anxiety disorders in humans are enhanced by DCS, suggesting a promising co-therapy regime, mediated by NMDA receptors. Exposure/response prevention may also be effective in problematic drinkers, and DCS might enhance habituation to cues in these individuals. Since heavy drinkers show ostensible conditioned responses to alcohol cues, habituation following exposure/response prevention should be evident in these drinkers, with DCS enhancing this effect. OBJECTIVES: the objective of this study is to investigate the effect of DCS on exposure/response prevention in heavy drinkers. METHODS: in a randomised, double-blind, placebo-controlled study, heavy social drinkers recruited from the community received either DCS (125 mg; n = 19) or placebo (n = 17) 1 h prior to each of two sessions of exposure/response prevention. Cue reactivity and attentional bias were assessed during these two sessions and at a third follow-up session. Between-session drinking behaviour was recorded. RESULTS: Robust cue reactivity and attentional bias to alcohol cues was evident, as expected of heavy drinkers. Within- and between-session habituation of cue reactivity, as well as a reduction in attentional bias to alcohol cues over time was found. However, there was no evidence of greater habituation in the DCS group. Subtle stimulant effects (increased subjective contentedness and euphoria) which were unrelated to exposure/response prevention were found following DCS. CONCLUSIONS: DCS does not appear to enhance habituation of alcohol cue reactivity in heavy non-dependent drinkers. Its utility in enhancing treatments based on exposure/response prevention in dependent drinkers or drug users remains open.
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Joye A, Morgan C, McEvoy S, Curran HV (2011). DEPENDENCY, PSYCHOSIS AND FREQUENCY OF USE IN HIGH VS. LOW POTENCY CANNABIS PREFERENCE.
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Freeman TP, Morgan CJA, Beesley T, Curran HV (2011). DRUG-CUE INDUCED OVERSHADOWING: SELECTIVE DISRUPTION OF NATURAL REWARD PROCESSING BY CIGARETTE CUES AMONGST ABSTINENT BUT NOT SATIATED SMOKERS.
Author URL.
Freeman TP, Morgan CJA, Beesley T, Curran HV (2011). Drug cue induced overshadowing: disruption of natural reward processing by cigarette cues amongst abstinent but not satiated smokers.
Author URL.
Carroll EMA, Kamboj SK, Conroy L, Tookman A, Williams ACDC, Jones L, Morgan CJA, Curran HV (2011). Facial Affect Processing in Patients Receiving Opioid Treatment in Palliative Care: Preferential Processing of Threat in Pain Catastrophizers.
JOURNAL OF PAIN AND SYMPTOM MANAGEMENT,
41(6), 975-985.
Author URL.
Gardener C, Morgan CJA, Curran HV (2011). IMPACT OF CANNABINOIDS ON COGNITION, PSYCHOTIC-LIKE SYMPTOMS AND PSYCHOLOGICAL WELL BEING.
Author URL.
Morgan CJA (2011). NEUROLOGICAL CONSEQUENCES OF HEAVY KETAMINE USE.
Author URL.
Neill E, Rossell SL, McDonald S, Joshua N, Jansen N, Morgan CJA (2011). Using Ketamine to Model Semantic Deficits in Schizophrenia.
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY,
31(6), 690-697.
Author URL.
2010
Leitz J, Morgan CJ, Bisby JA, Paraskevaides T, Rendell PG, Curran HV (2010). Acute alcohol globally impairs prospective memory but future event simulation partially overcomes this deficit.
Author URL.
Morgan C, Corlett P, Roiser J, Fletcher P, Friston KJ, Curran V (2010). An fMRI study of associative learning and prediction error signalling in daily ketamine abusers.
Author URL.
Constantinou N, Morgan CJA, Battistella S, O'Ryan D, Davis P, Curran HV (2010). Attentional bias, inhibitory control and acute stress in current and former opiate addicts.
DRUG AND ALCOHOL DEPENDENCE,
109(1-3), 220-225.
Author URL.
Schafer G, Morgan CJA, Freeman TP, Curran HV (2010). CANNABIDIOL WEAKENS THE APPETITIVE EFFECTS OF DELTA-9-TETRAHYDROCANNABINOL: a NATURALISTIC STUDY OF CANNABIS SMOKERS.
Author URL.
Morgan CJA, Freeman TP, Schafer GL, Curran HV (2010). Cannabidiol attenuates the appetitive effects of Delta 9-tetrahydrocannabinol in humans smoking their chosen cannabis.
Neuropsychopharmacology,
35(9), 1879-1885.
Abstract:
Cannabidiol attenuates the appetitive effects of Delta 9-tetrahydrocannabinol in humans smoking their chosen cannabis.
Worldwide cannabis dependence is increasing, as is the concentration of Delta(9)-tetrahydrocannabinol (THC) in street cannabis. At the same time, the concentration of the second most abundant cannabinoid in street cannabis, cannabidiol (CBD), is decreasing. These two cannabinoids have opposing effects both pharmacologically and behaviorally when administered in the laboratory. No research has yet examined how the ratio of these constituents impacts on the appetitive/reinforcing effects of cannabis in humans. A total of 94 cannabis users were tested 7 days apart, once while non-intoxicated and once while acutely under the influence of their own chosen smoked cannabis on dependence-related measures. Using an unprecedented methodology, a sample of cannabis (as well as saliva) was collected from each user and analyzed for levels of cannabinoids. On the basis of CBD : THC ratios in the cannabis, individuals from the top and bottom tertiles were directly compared on indices of the reinforcing effects of drugs, explicit liking, and implicit attentional bias to drug stimuli. When intoxicated, smokers of high CBD : THC strains showed reduced attentional bias to drug and food stimuli compared with smokers of low CBD : THC. Those smoking higher CBD : THC strains also showed lower self-rated liking of cannabis stimuli on both test days. Our findings suggest that CBD has potential as a treatment for cannabis dependence. The acute modulation of the incentive salience of drug cues by CBD may possibly generalize to a treatment for other addictive disorders.
Abstract.
Author URL.
Morgan C, Schafer G, Freeman T, Curran HV (2010). Cannabidiol attenuates the appetitive effects of delta-9-tetrahydrocannabinol: a naturalistic study of cannabis smokers.
Author URL.
DE LA TORRE R (2010). Commentary on Morgan etâal. (2010): Ketamine abuse: first medical evidence of harms we should confront. Addiction, 105(1), 134-135.
Morgan CJA, Muetzelfeldt L, Curran HV (2010). Consequences of chronic ketamine self-administration upon neurocognitive function and psychological wellbeing: a 1-year longitudinal study.
Addiction,
105(1), 121-133.
Abstract:
Consequences of chronic ketamine self-administration upon neurocognitive function and psychological wellbeing: a 1-year longitudinal study.
BACKGROUND: 'Recreational' use of ketamine is spreading rapidly among young people. In healthy individuals an acute dose of the N-methyl D-aspartate (NMDA) receptor antagonist ketamine induces marked psychosis-like effects and cognitive impairments, but little is known about the long-term effects of the drug. AIMS: to evaluate the long-term neuropsychiatric or cognitive consequences. METHODS: a total of 150 individuals were assessed, 30 in each of five groups: frequent ketamine users, infrequent ketamine users, abstinent users, polydrug controls and non-users of illicit drugs. Twelve months later, 80% of these individuals were re-tested. RESULTS: Cognitive deficits were mainly observed only in frequent users. In this group, increasing ketamine use over the year was correlated with decreasing performance on spatial working memory and pattern recognition memory tasks. Assessments of psychological wellbeing showed greater dissociative symptoms in frequent users and a dose-response effect on delusional symptoms, with frequent users scoring higher than infrequent, abstinent users and non-users, respectively. Both frequent and abstinent using groups showed increased depression scores over the 12 months. CONCLUSIONS: These findings imply that heavy use of ketamine is harmful to aspects of both cognitive function and psychological wellbeing. Health education campaigns need to raise awareness among young people and clinicians about these negative consequences of ketamine use.
Abstract.
Author URL.
Morgan CJA, Curran HV (2010). DIFFERENTIAL EFFECTS OF CANNABINOIDS IN CANNABIS SMOKERS.
Author URL.
Curran HV, Morgan CJA (2010). Declarative and Non-Declarative Memory. In (Ed) Encyclopedia of Psychopharmacology, 366-370.
Bisby JA, Leitz JR, Morgan CJA, Curran HV (2010). Decreases in recollective experience following acute alcohol: a dose-response study.
Psychopharmacology (Berl),
208(1), 67-74.
Abstract:
Decreases in recollective experience following acute alcohol: a dose-response study.
RATIONALE: Acute alcohol intoxication induces a selective impairment of recognition memory associated with conscious recollection whilst recognition based on familiarity is left intact. OBJECTIVES: We aimed to further elucidate the acute effects of alcohol on recognition memory by assessing three different doses of alcohol and examining the way in which this affected the recollection and familiarity components of recognition memory in comparison to a placebo group. METHODS: a double-blind independent design was used, and participants received either alcohol (0.4, 0.6 or 0.8 g/kg) or a placebo drink. Participants encoded word pairs with depth of processing manipulated under generate and read conditions. Recognition memory was assessed and recollective awareness was examined through use of the remember-know procedure. RESULTS: Alcohol produced a dose-dependent reduction in recognition memory associated with recollection, evidenced by decreases in the number of correctly recognised items with 'remember' responses compared to placebo. Recognition based on a familiarity, evidenced by 'know' responses, showed no differences between groups or pattern of reduction compared to the placebo group. However, a negative correlation was found between recognition based on familiarity and levels of intoxication. CONCLUSIONS: Alcohol-induced impairments in recognition memory occur in a dose-dependent manner, specifically driven by reductions in recognition associated with conscious awareness.
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Paraskevaides T, Morgan CJA, Leitz JR, Bisby JA, Rendell PG, Curran HV (2010). Drinking and future thinking: acute effects of alcohol on prospective memory and future simulation.
PSYCHOPHARMACOLOGY,
208(2), 301-308.
Author URL.
Morgan CJA, Curran VH (2010). Episodic Memory. In (Ed) Encyclopedia of Psychopharmacology, 489-489.
Morgan CJA, Muetzelfeldt L, Curran HV (2010). Erratum: Consequences of chronic ketamine self-administration upon neurocognitive function and psychological wellbeing: a 1-year longitudinal study (Addiction). Addiction, 105(4).
Bisby JA, Leitz JR, Morgan CJA, Rendell PG, Paraskevaides T, Curran HV (2010). FUTURE EVENT SIMULATION IMPROVES ALCOHOL-INDUCED PROSPECTIVE MEMORY IMPAIRMENTS.
Author URL.
Morgan CJA, Muetzelfeldt L, Muetzelfeldt M, Nutt DJ, Curran HV (2010). Harms associated with psychoactive substances: findings of the UK National Drug Survey.
J Psychopharmacol,
24(2), 147-153.
Abstract:
Harms associated with psychoactive substances: findings of the UK National Drug Survey.
Nutt and colleagues' 'rational' scale to assess the harms of commonly used drugs was based on ratings by a panel of experts. This survey aimed to assess drug users' views of the harms of drugs using the same scale. As users' drug choices are not solely based on harms, we additionally assessed perceived benefits. The survey was hosted at http://www.nationaldrugsurvey.org. UK residents reported their experience of 20 commonly used substances; those with direct experience of a substance rated its physical, dependence-related and social harms as well as benefits. A total of 1501 users completed the survey. There was no correlation between the classification of the 20 drugs under the Misuse of Drugs Act and ranking of harms by users. Despite being unclassified substances, alcohol, solvents and tobacco were rated within the top ten most harmful drugs. There was a remarkably high correlation (r = 0.896) overall between rankings by users' and by experts. Ecstasy, cannabis and LSD were ranked highest by users on both acute and chronic benefits. These findings imply that users are relatively well informed about the harms associated with the drugs they use. They also suggest that the current UK legal classification system is not acting to inform users of the harms of psychoactive substances.
Abstract.
Author URL.
Morgan CJA, Rothwell E, Atkinson H, Mason O, Curran HV (2010). Hyper-priming in cannabis users: a naturalistic study of the effects of cannabis on semantic memory function.
Psychiatry Res,
176(2-3), 213-218.
Abstract:
Hyper-priming in cannabis users: a naturalistic study of the effects of cannabis on semantic memory function.
Psychotic symptoms have theoretically been linked to semantic memory impairments in patients with schizophrenia. Little is known of the effects of cannabis, the world's most popular illicit drug, on semantic memory and whether they are linked to the psychotomimetic states elicited by the drug. Thirty-six cannabis users were tested whilst under the influence of cannabis. They were then tested again when not intoxicated and compared with 38 non-drug using controls. Semantic memory was assessed using a semantic priming task with a long and short stimulus onset asynchrony (SOA) to differentiate automatic and controlled processing. Under the influence of cannabis, users showed increases in both automatic semantic priming and schizotypal symptoms compared with controls. When abstinent, cannabis users exhibited hyper-priming at long SOAs. Cannabis users did not differ from controls in either trait schizotypy or state schizotypy when not intoxicated. Acute cannabis use increases schizotypyal symptoms and may increase automatic semantic priming in recreational users of this drug. When drug-free, cannabis users did not differ from controls in schizotypy but did show hyper-priming at the long SOA. The acute increase in automatic semantic priming may be one factor contributing to the psychotomimetic effects of cannabis.
Abstract.
Author URL.
Rossell SL, Stefanovic A, Roiser JP, Joshua NR, Neill E, Morgan CJA, Curran V (2010). IMAGING THE DELUDED BRAIN IN SCHIZOPHRENIA.
AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY,
44, A38-A38.
Author URL.
Freeman TP, Morgan CJA, Schafer GL, Curran HV (2010). IN SMOKED CANNABIS, CANNABIDIOL ATTENUATES THE ACUTE MEMORY IMPAIRING EFFECTS OF DELTA 9-TETRAHYDROCANNABINOL (THC).
Author URL.
Morgan CJA, Schafer G, Freeman TP, Curran HV (2010). Impact of cannabidiol on the acute and psychotomimetic effects of smoked cannabis: naturalistic study.
BRITISH JOURNAL OF PSYCHIATRY,
197(4), 285-290.
Author URL.
Curran V, Schafer G, Freeman T, Morgan C (2010). In smoked cannabis, cannabidiol attenuates the acute memory impairing effects of delta 9-tetrahydrocannabinol (THC).
Author URL.
Morgan CJA, Curran VH (2010). Inhibition of Memory. In (Ed) Encyclopedia of Psychopharmacology, 632-636.
Morgan C, Curran V (2010). Priming. In (Ed) Encyclopedia of Psychopharmacology, 1073-1073.
Morgan C, Curran V (2010). Procedural Memory. In (Ed) Encyclopedia of Psychopharmacology, 1073-1073.
Platt B, Kamboj S, Morgan CJA, Curran HV (2010). Processing dynamic facial affect in frequent cannabis-users: Evidence of deficits in the speed of identifying emotional expressions.
DRUG AND ALCOHOL DEPENDENCE,
112(1-2), 27-32.
Author URL.
Morgan C, Curran V (2010). Prospective Memory. In (Ed) Encyclopedia of Psychopharmacology, 1075-1075.
Morgan CJA, Curran VH (2010). Semantic Memory. In (Ed) Encyclopedia of Psychopharmacology, 1202-1202.
Morgan CJA, Curran VH (2010). State-Dependent Retrieval. In (Ed) Encyclopedia of Psychopharmacology, 1283-1283.
Das R, Kamboj S, Morgan C, Curran V (2010). The Effects of D-cycloserine and cue exposure on the processing of alcohol-relevant cues in hazardous recreational drinkers.
Author URL.
2009
Stefanovic A, Brandner B, Klaassen E, Cregg R, Nagaratnam M, Bromley LM, Das RK, Rossell SL, Morgan CJA, Curran HV, et al (2009). Acute and chronic effects of ketamine on semantic priming: modeling schizophrenia?.
J Clin Psychopharmacol,
29(2), 124-133.
Abstract:
Acute and chronic effects of ketamine on semantic priming: modeling schizophrenia?
Acute administration of the N-methyl-D-aspartate receptor antagonist ketamine induces schizophrenia-like symptoms in healthy volunteers; furthermore, a window on ketamine's chronic effects is provided by regular recreational users. The current study utilized both acute ketamine administration in healthy volunteers and chronic ketamine abusers to investigate semantic processing, one of the key cognitive deficits in schizophrenia. Semantic processing was examined using a semantic priming paradigm. In experiment 1, acute effects of low (75 ng/mL) and high (150 ng/mL) ketamine doses were compared in a placebo-controlled double-blind independent group design with 48 participants. In experiment 2, 19 regular recreational ketamine users were compared with 19 ketamine-naive polydrug controls and 26 non-drug-using controls. In both experiments, semantic priming parameters were manipulated to distinguish between ketamine's effects on (1) automatic and strategic processing and (2) the facilitation and inhibition components of semantic priming for strongly (directly) related primes and targets. Acute effects of ketamine on semantic priming for weakly (indirectly) related primes and targets were also assessed in experiment 1. Acutely, ketamine impaired the employment of strategic mechanisms but not automatic processing within both the direct and indirect semantic priming tasks. Acute ketamine administration also induced clear schizophrenia-like symptoms. Schizotypy traits in the cognitive and perceptual domains tended to correlate with increased semantic priming in long-term ketamine users. In summary, acute and chronic ketamine-induced changes partially mirrored the findings on semantic priming in schizophrenia.
Abstract.
Author URL.
Freeman TP, Morgan CJA, Schafer G, Curran HV (2009). Acute and chronic effects of naturalistically smoked cannabis on depression and anxiety.
EUROPEAN NEUROPSYCHOPHARMACOLOGY,
19, S376-S376.
Author URL.
Mason O, Morgan CJA, Dhiman SK, Patel A, Parti N, Patel A, Curran HV (2009). Acute cannabis use causes increased psychotomimetic experiences in individuals prone to psychosis.
PSYCHOLOGICAL MEDICINE,
39(6), 951-956.
Author URL.
Morgan C (2009). DIFFERENTIAL EFFECTS OF THC AND CBD IN CANNABIS SMOKERS.
EUROPEAN PSYCHIATRY,
24 Author URL.
Leitz JR, Morgan CJA, Bisby JA, Rendell PG, Curran HV (2009). Global impairment of prospective memory following acute alcohol.
PSYCHOPHARMACOLOGY,
205(3), 379-387.
Author URL.
Morgan CJA, Bedford NJ, O'Regan A, Rossell SL (2009). Is Semantic Processing Impaired in Individuals with High Schizotypy?.
JOURNAL OF NERVOUS AND MENTAL DISEASE,
197(4), 232-238.
Author URL.
Morgan CJA, Huddy V, Lipton M, Curran HV, Joyce EM (2009). Is persistent ketamine use a valid model of the cognitive and oculomotor deficits in schizophrenia?.
Biol Psychiatry,
65(12), 1099-1102.
Abstract:
Is persistent ketamine use a valid model of the cognitive and oculomotor deficits in schizophrenia?
BACKGROUND: Acute ketamine has been shown to model features of schizophrenia such as psychotic symptoms, cognitive deficits and smooth pursuit eye movement dysfunction. There have been suggestions that chronic ketamine may also produce an analogue of the disorder. In this study, we investigated the effect of persistent recreational ketamine use on tests of episodic and working memory and on oculomotor tasks of smooth pursuit and pro- and antisaccades. METHODS: Twenty ketamine users were compared with 1) 20 first-episode schizophrenia patients, 2) 17 polydrug control subjects who did not use ketamine but were matched to the ketamine users for other drug use, and 3) 20 non-drug-using control subjects. All groups were matched for estimated premorbid IQ. RESULTS: Ketamine users made more antisaccade errors than both control groups but did not differ from patients. Ketamine users performed better than schizophrenia patients on smooth pursuit, antisaccade metrics, and both memory tasks but did not differ from control groups. CONCLUSIONS: Problems inhibiting reflexive eye movements may be a consequence of repeated ketamine self-administration. The absence of any other oculomotor or cognitive deficit present in schizophrenia suggests that chronic self-administration of ketamine may not be a good model of these aspects of the disorder.
Abstract.
Author URL.
Morgan CJA, Muetzelfeldt L, Curran HV (2009). Ketamine use, cognition and psychological wellbeing: a comparison of frequent, infrequent and ex-users with polydrug and non-using controls.
Addiction,
104(1), 77-87.
Abstract:
Ketamine use, cognition and psychological wellbeing: a comparison of frequent, infrequent and ex-users with polydrug and non-using controls.
INTRODUCTION: Preliminary research has indicated that recreational ketamine use may be associated with marked cognitive impairments and elevated psychopathological symptoms, although no study to date has determined how these are affected by differing frequencies of use or whether they are reversible on cessation of use. In this study we aimed to determine how variations in ketamine use and abstention from prior use affect neurocognitive function and psychological wellbeing. METHOD: We assessed a total of 150 individuals: 30 frequent ketamine users, 30 infrequent ketamine users, 30 ex-ketamine users, 30 polydrug users and 30 controls who did not use illicit drugs. Cognitive tasks included spatial working memory, pattern recognition memory, the Stockings of Cambridge (a variant of the Tower of London task), simple vigilance and verbal and category fluency. Standardized questionnaires were used to assess psychological wellbeing. Hair analysis was used to verify group membership. RESULTS: Frequent ketamine users were impaired on spatial working memory, pattern recognition memory, Stockings of Cambridge and category fluency but exhibited preserved verbal fluency and prose recall. There were no differences in the performance of the infrequent ketamine users or ex-users compared to the other groups. Frequent users showed increased delusional, dissociative and schizotypal symptoms which were also evident to a lesser extent in infrequent and ex-users. Delusional symptoms correlated positively with the amount of ketamine used currently by the frequent users. CONCLUSIONS: Frequent ketamine use is associated with impairments in working memory, episodic memory and aspects of executive function as well as reduced psychological wellbeing. 'Recreational' ketamine use does not appear to be associated with distinct cognitive impairments although increased levels of delusional and dissociative symptoms were observed. As no performance decrements were observed in the ex-ketamine users, it is possible that the cognitive impairments observed in the frequent ketamine group are reversible upon cessation of ketamine use, although delusional symptoms persist.
Abstract.
Author URL.
Morgan CJA, Duffen S, Hunt S, Monaghan L, Mason OJ, Curran HV (2009). PRODROMAL SYMPTOMS IN CANNABIS, KETAMINE AND COCAINE USERS.
SCHIZOPHRENIA BULLETIN,
35, 22-22.
Author URL.
Morgan C, Mason O, Duffen S, Hunt S, Monaghan L, Curran HV (2009). Prodromal symptoms and neurocognitive profile of 3 groups of dependent drug users: cannabis, ketamine and cocaine.
EUROPEAN NEUROPSYCHOPHARMACOLOGY,
19, S657-S657.
Author URL.
Freeman TP, Morgan CJA, Klaassen E, Das RK, Stefanovic A, Brandner B, Curran HV (2009). Superstitious conditioning as a model of delusion formation following chronic but not acute ketamine in humans.
Psychopharmacology (Berl),
206(4), 563-573.
Abstract:
Superstitious conditioning as a model of delusion formation following chronic but not acute ketamine in humans.
BACKGROUND: Ketamine has previously been shown to induce delusion-like or referential beliefs, both acutely in healthy volunteers and naturalistically among nonintoxicated users of the drug. Delusions are theoretically underpinned by increased superstitious conditioning or the erroneous reinforcement of random events. MATERIALS AND METHODS: Using a novel and objectively measured superstitious conditioning task, experiment 1 assessed healthy volunteers before and during placebo (n = 16), low-dose (n = 15), and high-dose ketamine (n = 16) under randomized and double-blind conditions. Experiment 2 used the same task to compare ketamine users (n = 18), polydrug controls (n = 19), and nondrug-using controls (n = 17). RESULTS: in experiment 1, ketamine produced dose-dependent psychotomimetic effects but did not cause changes in superstitious conditioning. Experiment 2 found increased levels of superstitious conditioning among ketamine users compared to polydrug and nondrug-using controls, respectively, as evidenced by both objective task responses and subjective beliefs following the task. CONCLUSIONS: Results indicate that chronic but not acute exposure to ketamine may increase the propensity to adopt superstitious conditioning. These findings are discussed in terms of acute and chronic ketamine models of delusion-like belief formation in schizophrenia.
Abstract.
Author URL.
Blagrove M, Morgan CJA, Curran HV, Bromley L, Brandner B (2009). The incidence of unpleasant dreams after sub-anaesthetic ketamine.
PSYCHOPHARMACOLOGY,
203(1), 109-120.
Author URL.
2008
Friswell J, Phillips C, Holding J, Morgan CJA, Brandner B, Curran HV (2008). Acute effects of opioids on memory functions of healthy men and women.
Psychopharmacology,
198(2), 243-250.
Abstract:
Acute effects of opioids on memory functions of healthy men and women
Introduction: Although several psychotropic drugs can acutely induce an anterograde impairment of memory which impedes new learning, they do not produce retrograde impairments, reducing memory for information learned prior to the drug being administered. However, both anterograde and retrograde memory impairments have been reported following an acute dose of morphine in palliative care patients (Kamboj et al. Pain 117:388-395, 2005). Objective: the present study was designed to determine: (1) whether similar amnestic effects would be found after a single oral dose of either morphine or oxycodone in healthy volunteers, (2) how generalisable such effects were across a broader range of memory tasks and (3) whether men and women showed a differential response. Materials and methods: a double-blind, placebo-controlled crossover design was used with 18 participants (nine men, nine women) who were administered 10 mg morphine, 5 mg oxycodone and placebo on three separate test days. Results: on a working memory task, subtle impairments were found in women following both opioids whilst in men only following morphine. On an episodic memory task, women made significantly more source attribution errors after oxycodone and men made more after placebo. Most gender differences were weight related and a range of other measures showed no drug-induced impairments. Conclusion: We conclude that these standard doses of opioids have only marginal effects on memory. If these findings can be extrapolated to patients with pain, then clinicians can feel confident in prescribing them on an outpatient basis without impacting on patients' daily functioning. © 2008 Springer-Verlag.
Abstract.
Morgan CJA, Rees H, Curran HV (2008). Attentional bias to incentive stimuli in frequent ketamine users.
Psychol Med,
38(9), 1331-1340.
Abstract:
Attentional bias to incentive stimuli in frequent ketamine users.
BACKGROUND: the attention-grabbing properties of drugs to drug-using individuals have been well documented and recent research has begun to suggest that such attentional bias may be related to the severity of drug dependency. Dependence on ketamine has been reported anecdotally but no systematic study has investigated this phenomenon. We aimed to explore attentional biases to incentive stimuli in different populations of ketamine users. METHOD: Using a dot-probe paradigm, attentional bias to both drug-related and money-related stimuli was investigated in 150 participants: 30 frequent ketamine users, 30 infrequent ketamine users, 30 ex-ketamine users, 30 poly-drug users and 30 non-drug-using controls. Two stimulus presentation times were used (200 and 2000 ms) to investigate whether attentional bias was as a result of an automatic or a more conscious attentional shift. Participants also rated the degree to which stimuli used in the dot-probe paradigm were pleasurable. RESULTS: Frequent ketamine users demonstrated an attentional bias to both types of incentive stimuli only at the short stimulus presentation interval and this was significantly correlated with degree of ketamine use. No attentional biases were observed in any of the other groups. All groups rated money stimuli as more pleasurable than neutral stimuli. CONCLUSIONS: These data support incentive models of drug use and demonstrate the ability of the attentional bias paradigm to discriminate recreational drug users from those with more dependent patterns of use. Ketamine is a potentially dependence-forming drug.
Abstract.
Author URL.
Morgan CJA, Curran HV (2008). Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis.
Br J Psychiatry,
192(4), 306-307.
Abstract:
Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis.
Cannabis contains various cannabinoids, two of which have almost opposing actions: Delta9-tetrahydrocannabinol (Delta9-THC) is psychotomimetic, whereas cannabidiol (CBD) has antipsychotic effects. Hair samples were analysed to examine levels of Delta9-THC and CBD in 140 individuals. Three clear groups emerged: ;THC only', ;THC+CBD' and those with no cannabinoid in hair. The THC only group showed higher levels of positive schizophrenia-like symptoms compared with the no cannabinoid and THC+CBD groups, and higher levels of delusions compared with the no cannabinoid group. This provides evidence of the divergent properties of cannabinoids and has important implications for research into the link between cannabis use and psychosis.
Abstract.
Author URL.
Muetzelfeldt L, Kamboj SK, Rees H, Taylor J, Morgan CJA, Curran HV (2008). Journey through the K-hole: phenomenological aspects of ketamine use.
Drug Alcohol Depend,
95(3), 219-229.
Abstract:
Journey through the K-hole: phenomenological aspects of ketamine use.
Although recreational use of the dissociative anaesthetic drug ketamine is currently increasing, little is known about the phenomenological aspects of its use. We therefore designed a structured interview to examine initiation experiences, positive and negative effects of ketamine use, and concerns about the drug and its long-term effects. Ninety participants (30 frequent users, 30 infrequent 'recreational' users and 30 ex-users who had abstained from use for at least 3 months) were interviewed and reported drug use was verified by hair sample analysis. The most appealing aspects of ketamine for two-thirds of users were "melting into the surrounding", "visual hallucinations", "out-of-body experiences" and "giggliness". Unappealing effects for half of users were "memory loss" and "decreased sociability". Frequent ketamine users expressed more concerns than other groups about long-term effects on physical health problems, especially K-cramps and cystitis, whereas ex-users were more concerned about mental health problems. Addictive/dependent patterns of behaviour were also a concern: the majority of frequent users reported using the drug without stopping until supplies ran out and the mean increase in dosage in this group was six-fold from initiation to current use. We have identified specific health issues which seem uniquely related to ketamine use. Additionally, the dependence on ketamine frequently reported by users may be a cause for concern as its popularity grows and substance misuse services should be made aware of this when clients present in the future.
Abstract.
Author URL.
Mason OJ, Morgan CJM, Stefanovic A, Curran HV (2008). The psychotomimetic states inventory (PSI): measuring psychotic-type experiences from ketamine and cannabis.
Schizophr Res,
103(1-3), 138-142.
Abstract:
The psychotomimetic states inventory (PSI): measuring psychotic-type experiences from ketamine and cannabis.
BACKGROUND: This study reports a new measure of psychotomimetic states in the context of cannabis and ketamine use. The Psychotomimetic States Inventory (PSI) has sub-scales of Delusory Thinking, Perceptual Distortions, Cognitive Disorganization, Anhedonia, Mania and Paranoia. METHODS: the PSI was administered in two independent group, repeated measures designs: an experimental study of ketamine and a naturalistic study of cannabis. RESULTS: Both cannabis and ketamine produced reliable increases in ratings of psychotomimetic state effects across several sub-scales. CONCLUSIONS: the PSI is a potentially useful measure of the nature and extent of the phenomenological effects of psychotropic drugs in schizophrenia-related research.
Abstract.
Author URL.
2007
Uhlhaas PJ, Millard I, Muetzelfeldt L, Curran HV, Morgan CJA (2007). Perceptual organization in ketamine users: Preliminary evidence of deficits on night of drug use but not 3 days later.
Journal of Psychopharmacology,
21(3), 347-352.
Abstract:
Perceptual organization in ketamine users: Preliminary evidence of deficits on night of drug use but not 3 days later
N-methyl-D-aspartate (NMDA)-receptor antagonists such as ketamine can induce transient schizophrenia-Like symptoms and cognitive dysfunctions in heaLthy voLunteers simiLar to those observed in patients with schizophrenia. PerceptuaL organization deficits have been documented in schizophrenia and are thought to be reLated to some symptoms associated with the iLLness. The current study was designed to determine whether peopLe who repeatedLy seLf-administer ketamine wouLd aLso show deficits in perceptuaL organization. Using a psychophysicaLLy weLL-controLLed measure of contour integration, we compared a group of recreationaL users (n = 16) to a group of poLy-drug using controLs (n = 16). Contour integration performance was measured on the night of drug use and 3 days Later when drug free. The resuLts showed that on the night of drug use, ketamine produced a dysfunction in contour integration however, this was not present 3 days Later when drug free. LeveLs of dissociation were aLso higher in ketamine users onLy on the night of drug use. These preLiminary data provide some support for the roLe of NMDA-receptor hypofunctioning in dysfunctional coordination of cognitive activity. © 2007 British Association for Psychopharmacology.
Abstract.
Klaassen E, Morgan CJA, Cregg R, Nagaratnam M, Brandner B, Curran HV (2007). The role of dopamine and glutamate in superstition: an investigation using ketamine.
Author URL.
2006
Morgan CJA, Curran HV (2006). Acute and chronic effects of ketamine upon human memory: a review.
Psychopharmacology (Berl),
188(4), 408-424.
Abstract:
Acute and chronic effects of ketamine upon human memory: a review.
INTRODUCTION: Ketamine is attracting increasing research interest not only because of its powerful amnestic effects but also as a putative model of schizophrenia and as a substance with an expanding following of recreational users. OBJECTIVE: This article reviews the existing literature on the effects of acute ketamine on the memory of healthy volunteers and of repeated doses of ketamine in recreational users. CURRENT TRENDS: Although there have been relatively few, often methodologically diverse, studies to date of the mnemonic effects of ketamine, there is an emerging consensus that an acute dose of the drug impairs the manipulation of information in working memory and produces decrements in the encoding of information into episodic memory. Preliminary evidence suggests that ketamine may differ from other classic amnestic drugs in impairing aspects of semantic memory. Acute-on-chronic effects in ketamine users generally mimic the pattern seen in controlled studies with healthy volunteers. However, chronic ketamine use may be associated with a more specific pattern of memory decrements and with episodic memory impairment, which might not abate following cessation of use. FUTURE TRENDS: an important aim of future research should be to detail the specificity of ketamine's amnestic effects on both a neuropharmacological and a cognitive level.
Abstract.
Author URL.
Morgan C, Bedford N, Rossell SL (2006). Evidence of semantic disorganisation using semantic priming in individuals with high schizotypy.
Schizophr Res,
84(2-3), 272-280.
Abstract:
Evidence of semantic disorganisation using semantic priming in individuals with high schizotypy.
Semantic processing deficits are present in schizophrenia and are particularly evident on semantic priming tasks. Using high schizotypes (psychosis-prone individuals) can overcome some confounds involved in studying actively symptomatic schizophrenics. In the current study, 26 high and 32 low scorers on the O-LIFE schizotypy scale (from a sample of 251 students) were selected for testing. All subjects were administered a lexical-decision semantic priming task where half the stimuli had a short 200 ms stimulus onset asynchrony (SOA, length of time from onset of prime to onset of target) and half the stimuli had a long 750 ms SOA. In addition, half the words were of high frequency and half of a low frequency. There were no group differences in priming for words of different frequencies. Low schizotypes showed greater priming at the 200 ms SOA than at the 750 ms SOA, whilst individuals with high schizotypy showed the opposite pattern. The pattern shown by the low schizotypes replicates earlier work by the authors using other normal control samples; establishing that there is greater priming under conditions of automatic spreading of activation. Furthermore, the data shows there is not an increase in automatic spreading of activation in individuals with high schizotypy. There has been controversy in the schizophrenia literature over whether there is increased priming under automatic conditions. The current study suggests that, when confounds are controlled for, schizophrenia-like symptoms are not related to an increase in automatic spreading of activation.
Abstract.
Author URL.
Morgan CJA, Perry EB, Cho H-S, Krystal JH, D'Souza DC (2006). Greater vulnerability to the amnestic effects of ketamine in males.
PSYCHOPHARMACOLOGY,
187(4), 405-414.
Author URL.
Morgan CJA, Rossell SL, Pepper F, Smart J, Blackburn J, Brandner B, Curran HV (2006). Semantic priming after ketamine acutely in healthy volunteers and following chronic self-administration in substance users.
Biol Psychiatry,
59(3), 265-272.
Abstract:
Semantic priming after ketamine acutely in healthy volunteers and following chronic self-administration in substance users.
BACKGROUND: Ketamine is used acutely as a model of schizophrenia. It has been suggested that chronic ketamine may also mimic aspects of this disorder, in particular impaired cognitive function. As semantic processing deficits are considered central to cognitive impairments in schizophrenia, this study aimed to characterize semantic impairments following both acute and chronic ketamine. METHODS: We examined the acute effects of two doses of ketamine (Experiment 1) using a double-blind, placebo-controlled, independent group design with 48 volunteers. Ketamine's chronic effects (Experiment 2) were explored in 16 ketamine users and 16 poly-drug controls. A semantic priming task with a frequency (high and low) and stimulus onset asynchrony (SOA: short-200 msec, long-750 msec) manipulation was used. RESULTS: in Experiment 1, acute ketamine produced inverse priming at the long SOA. In Experiment 2, ketamine users showed inverse priming for low-frequency words at the long SOA compared to poly-drug controls. CONCLUSIONS: the inverse priming effect at the long SOA induced by acute ketamine was indicative of controlled processing impairments. In ketamine users, there was also an indication of controlled processing impairments. Decreased priming for low-frequency words suggested that long-term ketamine abuse results in damage to the semantic store.
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Author URL.
2005
Morgan CJA, Lippett R, Pepper F, Blackburn J, Brandner B, Curran HV (2005). 'Me-pulse' inhibition: a novel self-monitoring task piloted in high schizotypy scorers, healthy volunteers following an acute dose of ketamine and ketamine users.
Author URL.
2004
Morgan CJA, Mofeez A, Brandner B, Bromley L, Curran HV (2004). Acute effects of ketamine on memory systems and psychotic symptoms in healthy volunteers.
Neuropsychopharmacology,
29(1), 208-218.
Abstract:
Acute effects of ketamine on memory systems and psychotic symptoms in healthy volunteers.
N-methyl-D-aspartate (NMDA) receptor antagonists have been demonstrated to induce schizophrenia-like symptoms and cognitive impairment in humans. The NMDA receptor has been strongly implicated in memory, but research to date on the effects of NMDA antagonists has examined only some aspects of human memory functions. This study used a double-blind, placebo-controlled, independent groups design with 54 healthy volunteers to examine the effects of infusions of two doses (0.4, 0.8 mg/kg) of the NMDA antagonist ketamine upon the five human memory systems, aspects of executive functioning and schizophrenia-like and dissociative symptoms. Ketamine produced a dose-dependent impairment to episodic and working memory and a slowing of semantic processing. Ketamine also impaired recognition memory and procedural learning. Attention, perceptual priming and executive functioning were not affected following the drug. In addition, ketamine induced schizophrenia-like and dissociative symptoms, which were not correlated with the cognitive measures. These data suggest that, in humans, ketamine produces a selective pattern of impairments to working, episodic, and procedural memory but not to perceptual priming, attention or aspects of executive functioning.
Abstract.
Author URL.
Morgan CJA, Monaghan L, Curran HV (2004). Beyond the K-hole: a 3-year longitudinal investigation of the cognitive and subjective effects of ketamine in recreational users who have substantially reduced their use of the drug.
Addiction,
99(11), 1450-1461.
Abstract:
Beyond the K-hole: a 3-year longitudinal investigation of the cognitive and subjective effects of ketamine in recreational users who have substantially reduced their use of the drug.
RATIONALE: Ketamine is a dissociative anaesthetic that is also a drug of abuse. Previous studies have demonstrated persisting episodic and semantic memory impairments in recreational ketamine users 3 days after taking ketamine. However, the degree to which these deficits might be reversible upon reduction or cessation of ketamine use was not known. OBJECTIVE: to follow-up a population of ketamine users tested 3 years previously and examine whether impairments observed 3 days after drug use are enduring or reversible. METHODS: Eighteen ketamine users and 10 polydrug controls from studies conducted between 3 and 4 years earlier were re-tested on the same battery of cognitive tasks and subjective measures. These tapped episodic, semantic and working memory and executive and attentional functioning. Subjective schizotypal, dissociative, mood and bodily symptoms were also examined and a drug use history recorded. RESULTS: the ketamine users had reduced their frequency of use of ketamine by an average of 88.3%. Performance of ketamine users on tasks tapping semantic memory had improved and this improvement was correlated with their reduction in ketamine use. On tasks tapping episodic memory and attentional functioning, ketamine users still showed deficits compared to polydrug controls. Higher levels of schizotypal symptoms and perceptual distortions were exhibited by the ketamine group, although dissociative symptoms were similar to controls. CONCLUSIONS: These findings indicate that semantic memory impairments associated with recreational ketamine are reversible upon marked reduction of use; however, impairments to episodic memory and possibly attentional functioning appear long-lasting. In addition, schizotypal symptoms and perceptual distortions may persist after cessation of ketamine use. Ketamine users, or potential users, should be aware of the enduring effects of this drug on aspects of memory and subjective experience.
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Author URL.
Morgan CJA, Mofeez A, Brandner B, Bromley L, Curran HV (2004). Ketamine impairs response inhibition and is positively reinforcing in healthy volunteers: a dose-response study.
Psychopharmacology (Berl),
172(3), 298-308.
Abstract:
Ketamine impairs response inhibition and is positively reinforcing in healthy volunteers: a dose-response study.
RATIONALE: Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has medical indications but is also used as a recreational drug. Previous research has found persisting cognitive and psychotogenic effects of ketamine in chronic abusers of this drug 3 days after an acute dose. OBJECTIVE: the present study aimed to investigate the effects of ketamine on two processes related to drug abuse, response inhibition and reinforcement, and to examine whether an acute dose of ketamine produced residual cognitive effects in healthy volunteers. METHODS: Fifty-four healthy volunteers were given an 80-min infusion of one of two doses (0.4, 0.8 mg kg(-1)) of ketamine or placebo. Subjects completed a battery of tests at three time points: pre-infusion, during the infusion and 3 days later at follow-up. The battery consisted of tests of episodic and semantic memory, schizophrenic-like and dissociative symptoms, response inhibition and measures of subjective effects, including mood, bodily symptoms and enjoyment of and desire for the drug. RESULTS: Ketamine acutely impaired response inhibition and had related biphasic effects on the subjective reinforcing effects of the drug. Ketamine also acutely impaired episodic but not semantic memory and increased schizophrenic-like and dissociative symptoms. No residual cognitive effects were observed 3 days following an acute dose. CONCLUSIONS: the lack of residual effects in healthy volunteers on day 3 indicates that impairments found on day 3 in ketamine abusers are chronic effects. The abuse of ketamine may be related to its capacity both to reinforce and to decrease response inhibition.
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Author URL.
Bedford NJ, Morgan C, Rossell SL (2004). Lack of self-serving bias and excessive internalising of blame in the attributional style of schizophrenia-prone individuals.
Author URL.
MORGAN C (2004). Long-term effects of ketamine: evidence for a persisting impairment of source memory in recreational users. Drug and Alcohol Dependence
Morgan CJA, Riccelli M, Maitland CH, Curran HV (2004). Long-term effects of ketamine: evidence for a persisting impairment of source memory in recreational users.
Drug Alcohol Depend,
75(3), 301-308.
Abstract:
Long-term effects of ketamine: evidence for a persisting impairment of source memory in recreational users.
RATIONALE: Ketamine is an N-methyl-d-aspartate (NMDA)-receptor antagonist that is increasingly being used as a recreational drug. Previous research has shown gross generalised verbal memory impairments persisting 3 days after ketamine use in chronic users, however episodic memory has not specifically investigated in this population. OBJECTIVE: to determine whether ketamine, on the night of drug use (day 0) and 3 days later, is associated with impaired episodic memory as assessed by a source memory task. METHODS: Twenty ketamine users and 20 poly-drug controls were compared on a source memory task both on day 0 and 3. Participants also completed questionnaires on both days indexing schizophrenic-like and dissociative symptoms. RESULTS: on day 0, ketamine abusers were impaired on both source memory and item recognition and scored more highly on schizophrenic and dissociative symptom scales compared to poly-drug controls. On day 3 ketamine abusers only displayed source memory impairments and these positively correlated with the level of schizophrenic-like symptoms on day 0. No differences on day 3 in schizophrenic-like or dissociative symptoms were observed. CONCLUSIONS: Ketamine abusers exhibit a persisting deficit in source memory on day 3 but not in item recognition. These findings suggest that repeated use of ketamine produces chronic impairments to episodic memory.
Abstract.
Author URL.
2003
Morgan CJA, Mofeez A, Brandner B, Bromley L, Curran HV (2003). Human memory systems and ketamine.
Author URL.
2002
Pilling S, Bebbington P, Kuipers E, Garety P, Geddes J, Orbach G, Morgan C (2002). Psychological treatments in schizophrenia: I. Meta-analysis of family intervention and cognitive behaviour therapy.
Psychological Medicine,
32(5), 763-782.
Abstract:
Psychological treatments in schizophrenia: I. Meta-analysis of family intervention and cognitive behaviour therapy
Background. While there is a growing body of evidence on the efficacy of psychological interventions for schizophrenia, this meta-analysis improves upon previous systematic and meta-analytical reviews by including a wider range of randomized controlled trials and providing comparisons against both standard care and other active interventions. Method. Literature searches identified randomized controlled trials of four types of psychological interventions: family intervention, cognitive behavioural therapy (CBT), social skills training and cognitive remediation. These were then subjected to meta-analysis on a variety of outcome measures. This paper presents results relating to the first two. Results. Family therapy, in particular single family therapy, had clear preventative effects on the outcomes of psychotic relapse and readmission, in addition to benefits in medication compliance. CBT produced higher rates of 'important improvement' in mental state and demonstrated positive effects on continuous measures of mental state at follow-up. CBT also seems to be associated with low drop-out rates. Conclusions. Family intervention should be offered to people with schizophrenia who are in contact with carers. CBT may be useful for those with treatment resistant symptoms. Both treatments, in particular CBT, should be further investigated in large trials across a variety of patients, in various settings. The factors mediating treatment success in these interventions should be researched.
Abstract.
Pilling S, Bebbington P, Kuipers E, Garety P, Geddes J, Martindale B, Orbach G, Morgan C (2002). Psychological treatments in schizophrenia: II. Meta-analyses of randomized controlled trials of social skills training and cognitive remediation.
Psychological Medicine,
32(5), 783-791.
Abstract:
Psychological treatments in schizophrenia: II. Meta-analyses of randomized controlled trials of social skills training and cognitive remediation
Background. Social skills training and cognitive remediation are psychological techniques with considerable face validity for the treatment of negative symptoms of schizophrenia and their consequences. This paper provides a meta-analytical review of these treatments. It includes an appreciable number of randomized controlled trials, using comparisons against both standard care and other active interventions. However, the assessment of particular outcomes sometimes had to be based on single studies. Method. A detailed search strategy was used to identify randomized controlled trials of social skills training and cognitive remediation, primarily employing electronic databases. Randomized controlled trials (RCTs) that met predefined criteria were then subjected to meta-analysis on a variety of outcome measures. Results. There was no clear evidence for any benefits of social skills training on relapse rate, global adjustment, social functioning, quality of life or treatment compliance. Cognitive remediation had no benefit on attention, verbal memory, visual memory, planning, cognitive flexibility or mental state. Conclusions. Social skills training and cognitive remediation do not appear to confer reliable benefits for patients with schizophrenia and cannot be recommended for clinical practice.
Abstract.
2000
Curran HV, Morgan C (2000). Cognitive, dissociative and psychotogenic effects of ketamine in recreational users on the night of drug use and 3 days later.
Addiction,
95(4), 575-590.
Abstract:
Cognitive, dissociative and psychotogenic effects of ketamine in recreational users on the night of drug use and 3 days later.
AIMS: Recreational use of the N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, is increasing. The present study aimed to examine both the acute and residual effects of this drug on cognitive function, dissociation and schizotypal symptomatology in recreational users. DESIGN AND PARTICIPANTS: a parallel group design was used to compare 20 volunteers who reported having taken ketamine with 19 volunteers who reported no consumption of ketamine on the relevant night (day 0). All 39 participants were tested on day 0 and again 3 days later. On each test occasion a battery of tests was administered which tapped a wide range of memory functions, attention, dissociation, schizotypal symptomatology and mood. FINDINGS: Groups were broadly matched for polydrug use apart from ketamine. Acute effects on day 0 replicated previous laboratory studies showing a broad spectrum of cognitive impairments following ketamine administration as well as marked dissociative effects and schizotypal symptomatology. Three days later, ketamine users had significantly higher scores than controls on both dissociation and schizotypal symptomatology. On some cognitive measures there were no group differences on day 3; however, on tests tapping semantic memory, the ketamine users showed persisting impairments compared with controls. CONCLUSIONS: Ketamine appears to induce acute and severe impairments of working, episodic and semantic memory as well as psychotogenic and dissociative effects. Three days after drug ingestion, recreational users display semantic memory impairment and dissociative and schizotypal symptomatology which could reflect chronic or residual effects of taking the drug or pre-existing differences in ketamine users.
Abstract.
Author URL.
Webb Y, Clifford P, Fowler V, Morgan C, Hanson M (2000). Comparing patients' experience of mental health services in England: a five-Trust survey.
International Journal of Health Care Quality Assurance,
13(6), 273-281.
Abstract:
Comparing patients' experience of mental health services in England: a five-Trust survey
The implementation of the Care Programme Approach (CPA) in English mental health services has been slow to proceed despite general support, both in England and in other countries, of its principles of good practice. This study set out to evaluate the implementation of the CPA directly from patients' experience using the "Your Treatment and Care" assessment tool. The results of a survey of 503 patients across five NHS Trusts in England showed that many patients did not have a copy of their care plan and had not been involved in the care planning procedure. Many reported shortcomings in their experience of their key worker and their psychiatrist. However, there was substantial variation in experience across services. "Your Treatment and Care" showed good internal reliability, was acceptable to users, and appeared to be able to access actual experiences better than a traditional "satisfaction" item. It appears to be very useful as a benchmarking tool and is now being used in services across the UK, the USA and Australia. © MCB University Press.
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