Semantic priming and verbal learning in current opiate users, ex-users and non-user controls.

OBJECTIVE: Despite a growing interest in memory functions of chronic drug users, investigation of semantic and episodic memory in opiate users is limited, and findings of studies have been inconsistent. The present study aimed to assess semantic memory and episodic memory for both drug-related and neutral stimuli in current and ex-users of opiates. METHODS: Using an independent group design, we assessed semantic priming and verbal learning in 16 current opiate users on a methadone maintenance programme, 16 ex-opiate users in rehabilitation programmes and 16 healthy controls. The groups were matched on verbal IQ, age and employment status. RESULTS: We found that current and ex-users showed intact automatic and controlled semantic priming. Ex-users who had been abstinent for an average of 19 months showed a verbal learning impairment compared with controls. Both current and ex-users were impaired in recalling semantically unrelated words but unimpaired in recalling semantically related words. CONCLUSION: The findings suggest a relative lack of spontaneous use of mnemonic strategies and imply that highly structured information would help opiate-using clients in treatment.

Cannabidiol for the treatment of cannabis use disorder: a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial.

Background A substantial and unmet clinical need exists for pharmacological treatment of cannabis use disorders. Cannabidiol could offer a novel treatment, but it is unclear which doses might be efficacious or safe. Therefore, we aimed to identify efficacious doses and eliminate inefficacious doses in a phase 2a trial using an adaptive Bayesian design. METHODS: We did a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial at the Clinical Psychopharmacology Unit (University College London, London, UK). We used an adaptive Bayesian dose-finding design to identify efficacious or inefficacious doses at a-priori interim and final analysis stages. Participants meeting cannabis use disorder criteria from DSM-5 were randomly assigned (1:1:1:1) in the first stage of the trial to 4-week treatment with three different doses of oral cannabidiol (200 mg, 400 mg, or 800 mg) or with matched placebo during a cessation attempt by use of a double-blinded block randomisation sequence. All participants received a brief psychological intervention of motivational interviewing. For the second stage of the trial, new participants were randomly assigned to placebo or doses deemed efficacious in the interim analysis. The primary objective was to identify the most efficacious dose of cannabidiol for reducing cannabis use. The primary endpoints were lower urinary 11-nor-9-carboxy-δ-9-tetrahydrocannabinol (THC-COOH):creatinine ratio, increased days per week with abstinence from cannabis during treatment, or both, evidenced by posterior probabilities that cannabidiol is better than placebo exceeding 0·9. All analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov (NCT02044809) and the EU Clinical Trials Register (2013-000361-36). FINDINGS: Between May 28, 2014, and Aug 12, 2015 (first stage), 48 participants were randomly assigned to placebo (n=12) and to cannabidiol 200 mg (n=12), 400 mg (n=12), and 800 mg (n=12). At interim analysis, cannabidiol 200 mg was eliminated from the trial as an inefficacious dose. Between May 24, 2016, and Jan 12, 2017 (second stage), randomisation continued and an additional 34 participants were allocated (1:1:1) to cannabidiol 400 mg (n=12), cannabidiol 800 mg (n=11), and placebo (n=11). At final analysis, cannabidiol 400 mg and 800 mg exceeded primary endpoint criteria (0·9) for both primary outcomes. For urinary THC-COOH:creatinine ratio, the probability of being the most efficacious dose compared with placebo given the observed data was 0·9995 for cannabidiol 400 mg and 0·9965 for cannabidiol 800 mg. For days with abstinence from cannabis, the probability of being the most efficacious dose compared with placebo given the observed data was 0·9966 for cannabidiol 400 mg and 0·9247 for cannabidiol 800 mg. Compared with placebo, cannabidiol 400 mg decreased THC-COOH:creatinine ratio by -94·21 ng/mL (95% interval estimate -161·83 to -35·56) and increased abstinence from cannabis by 0·48 days per week (0·15 to 0·82). Compared with placebo, cannabidiol 800 mg decreased THC-COOH:creatinine ratio by -72·02 ng/mL (-135·47 to -19·52) and increased abstinence from cannabis by 0·27 days per week (-0·09 to 0·64). Cannabidiol was well tolerated, with no severe adverse events recorded, and 77 (94%) of 82 participants completed treatment. INTERPRETATION: In the first randomised clinical trial of cannabidiol for cannabis use disorder, cannabidiol 400 mg and 800 mg were safe and more efficacious than placebo at reducing cannabis use. FUNDING: Medical Research Council.

Enhanced recognition of facial expressions of disgust in opiate users receiving maintenance treatment.

AIMS: Accurate recognition of facial expressions of emotion is critical in interpersonal interaction but is impaired in alcoholics, even after a period of abstinence. Little is known of whether other drug-dependent populations also show these impairments. This study aimed to investigate facial expression recognition by chronic opiate users. DESIGN: An independent group design was used to compare 20 participants receiving opiate substitution treatment, 20 ex-opiate users in rehabilitation (average abstinence of 6 months) and 21 unemployed healthy controls. MEASUREMENTS: The accuracy and speed of recognizing morphed emotional facial expressions were assessed using an emotional hexagon task. FINDINGS: Current opiate users were significantly more accurate than ex-users at recognizing expressions of disgust. They were also generally slower than controls in recognizing all expressions, and slower than ex-opiate users in recognizing surprise, happy and fearful expressions. CONCLUSIONS: Opiate users in maintenance treatment show a heightened ability to recognize facial expressions of disgust. We suggest that this may reflect increased exposure to other people's expressions of disgust and/or priming by the physical and social environments encountered by opiate-dependent individuals. Further, opiate maintained individuals' global slowness in processing emotional expressions may reflect the sedative effects of methadone.

Attentional bias, inhibitory control and acute stress in current and former opiate addicts.

BACKGROUND: Drug dependence is associated with both attentional biases to drug-related cues and inhibitory control deficits. Although acute stress is known to increase craving, it is not known whether this effect is mediated via changes in attentional bias and inhibitory control. OBJECTIVES: To examine the effect of a mild stressor on inhibitory control, attentional bias and craving in current opiate users (methadone maintained), ex-users (currently abstinent) and non-users (healthy controls). METHOD: Forty-eight participants (16 in each group) were exposed to both stress and non-stress conditions, after which inhibitory control and attentional bias was assessed using a Go-No-go and dot probe task respectively. Subjective ratings of stress levels and drug craving were repeatedly monitored. RESULTS: Current opiate users had significantly higher cravings ratings than both other groups at all times, and their craving tended to increase following the stress task. Current users had a greater attentional bias towards drug-related stimuli than the ex-users. Interestingly, ex-users showed a bias away from drug-related stimuli in the stress condition and this correlated positively with their length of abstinence. On the Go/No-go task, all groups had fewer false alarms in the stress condition. CONCLUSIONS: These results indicate that successful treatment is associated with a bias away from drugs, and that this bias may be protective against the effects of stress.

Long-term effects of psychological trauma on psychosocial functioning.

BACKGROUND: Most studies of the effects of trauma on mental health have generally not separately assessed psychosocial functioning, and in those that have key issues have received little attention, such as the relation between the time courses of the two kinds of outcome, and detailed assessment of social functioning in a range of domains. The present study made separate assessments with a view to testing four hypotheses. First, that the experience of trauma itself (independently of effects on mental health) has a negative effect on psychosocial functioning; second, that psychopathology following trauma is associated with poorer psychosocial functioning; third, that psychosocial functioning recovers when psychiatric conditions remit; fourth, that post-traumatic stress and depression have different associations with impairments of psycho-social functioning. METHOD: One hundred and fifteen young adults who had survived a shipping disaster (the sinking of the Jupiter in 1988) between 5 and 8 years previously, and 50 control participants were assessed for psychopathology, and for psychosocial functioning using the Adolescent to Adult Personality Functioning Assessment (ADAPFA). RESULTS: Results did not support the first hypothesis: survivors who, although experiencing a traumatic event, did not develop Post Traumatic Stress Disorder or other psychopathology warranting diagnosis, when compared with Controls who had no psychopathology since the time of the disaster, showed no significant differences on any ADAPFA domains or on total score. There was partial support for the second hypothesis: survivors with diagnosable disorder during the rating period showed poorer psychosocial functioning in total ADAPFA score and in the domains of Education/Work, Love Relationships, and Non-specific Social Contacts, though not in other domains. The third hypothesis was supported: recovered Survivors showed no psychosocial impairments compared with unaffected Controls. Results also supported the fourth hypothesis, showing differential effects of post traumatic stress and depression in relation to the extent and kind of psycho-social impairments. CONCLUSIONS: The results lend support to the general model that effects on psychosocial functioning following traumatic experience are mediated by psychopathology, though further research is needed to establish whether the present pattern of findings applies to other kinds of trauma.