The NBOMe compounds are a novel series of hallucinogenic drugs that are potent agonists of the 5-HT2A receptor, have a short history of human consumption and are available to buy online, in most ...countries. In this study, we sought to investigate the patterns of use, characteristics of users and self-reported effects. A cross-sectional anonymous online survey exploring the patterns of drug use was conducted in 2012 (n = 22,289), including questions about the use of 25B-NBOMe, 25C-NBOMe, and 25I-NBOMe and comparison drugs. We found that 2.6% of respondents (n = 582) reported having ever tried one of the three NBOMe drugs and that at 2.0%, 25I-NBOMe was the most popular (n = 442). Almost all (93.5%) respondents whose last new drug tried was a NBOMe drug, tried it in 2012, and 81.2% of this group administered the drug orally or sublingually/buccally. Subjective effects were similar to comparison serotonergic hallucinogens, though higher ‘negative effects while high’ and greater ‘value for money’ were reported. The most common (41.7%) drug source was via a website. The NBOMe drugs have emerged recently, are frequently bought using the internet and have similar effects to other hallucinogenic drugs; however, they may pose larger risks, due to the limited knowledge about them, their relatively low price and availability via the internet.
Abstract
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<.05).
Results
Compared with placebo, cannabis without cannabidiol dampened response to music in bilateral auditory cortex (right: P=.005, left: P=.008), right hippocampus/parahippocampal gyrus (P=.025), right amygdala (P=.025), and right ventral striatum (P=.033). Across all sessions, the effects of music in this ventral striatal region correlated with pleasure ratings (P=.002) and increased functional connectivity with auditory cortex (right: P< .001, left: P< .001), supporting its involvement in music reward. Functional connectivity between right ventral striatum and auditory cortex was increased by cannabidiol (right: P=.003, left: P=.030), and cannabis with cannabidiol did not differ from placebo on any functional Magnetic Resonance Imaging measures. Both types of cannabis increased ratings of wanting to listen to music (P<.002) and enhanced sound perception (P<.001).
Conclusions
Cannabis dampens the effects of music in brain regions sensitive to reward and emotion. These effects were offset by a key cannabis constituent, cannabidol.
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.
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.
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.
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.
ClinicalTrials.gov, NCT02649231 . Registered on 5 January 2016.
Cannabis use is common in people with psychotic disorders and is associated with the exacerbation of symptoms, poor treatment adherence, and an increased risk of relapse. Accurate assessment of ...cannabis use is thus critical to the clinical management of psychosis.
Cannabis use is usually assessed with self-report questionnaires that were originally developed for healthy individuals or people with a cannabis use disorder. Compared to these groups, the pattern of cannabis use and the associated harms in patients with psychosis are quite different. Moreover, in people with psychosis, the accuracy of self-reported use may be impaired by psychotic symptoms, cognitive deficits, and a desire to conceal use when clinicians have advised against it. Although urinary screening for delta-9-tetrahydrocannabinol is sometimes used in the assessment of acute psychotic episodes, it is not used in routinely. Cannabis use could be assessed by measuring the concentration of cannabinoids in urine and blood, but this is rarely done in either clinical settings or research.
Using quantitative biological measures could provide a more accurate guide to the effects of use on the disorder than asking patients or using questionnaires.
Abstract
Background
COVID-19 lockdown measures have caused severe disruptions to work and education and prevented people from engaging in many rewarding activities. Cannabis users may be especially ...vulnerable, having been previously shown to have higher levels of apathy and anhedonia than non-users.
Methods
In this survey study, we measured apathy and anhedonia, before and after lockdown measures were implemented, in n = 256 adult and n = 200 adolescent cannabis users and n = 170 adult and n = 172 adolescent controls. Scores on the Apathy Evaluation Scale (AES) and Snaith-Hamilton Pleasure Scale (SHAPS) were investigated with mixed-measures ANCOVA, with factors user group, age group, and time, controlling for depression, anxiety, and other drug use.
Results
Adolescent cannabis users had significantly higher SHAPS scores before lockdown, indicative of greater anhedonia, compared with adolescent controls (P = .03, η p2 = .013). Contrastingly, adult users had significantly lower scores on both the SHAPS (P < .001, η p2 = .030) and AES (P < .001, η p2 = .048) after lockdown compared with adult controls. Scores on both scales increased during lockdown across groups, and this increase was significantly smaller for cannabis users (AES: P = .001, η p2 = .014; SHAPS: P = .01, η p2 = .008). Exploratory analyses revealed that dependent cannabis users had significantly higher scores overall (AES: P < .001, η p2 = .037; SHAPS: P < .001, η p2 = .029) and a larger increase in scores (AES: P = .04, η p2 =.010; SHAPS: P = .04, η p2 = .010), compared with non-dependent users.
Conclusions
Our results suggest that adolescents and adults have differential associations between cannabis use as well as apathy and anhedonia. Within users, dependence may be associated with higher levels of apathy and anhedonia regardless of age and a greater increase in levels during the COVID-19 lockdown.
Rationale
Cannabis and tobacco are often smoked simultaneously in joints, and this practice may increase the risks of developing tobacco and/or cannabis use disorders. Currently, there is no human ...experimental research on how these drugs interact on addiction-related measures.
Objectives
This study aimed to investigate how cannabis and tobacco, each alone and combined together in joints, affected individuals’ demand for cannabis puffs and cigarettes, explicit liking of drug and non-drug-related stimuli and craving.
Method
A double-blind, 2 (active cannabis, placebo cannabis) × 2 (active tobacco, placebo tobacco) crossover design was used with 24 non-dependent cannabis and tobacco smokers. They completed a pleasantness rating task (PRT), a marijuana purchase task (MPT) and a cigarette purchase task (CPT) alongside measures of craving pre- and post-drug administration.
Results
Relative to placebo cannabis, active cannabis reduced liking of cannabis-associated stimuli and increased response time to all stimuli except cigarette-related stimuli. Relative to placebo cannabis, active cannabis decreased demand for cannabis puffs (trends for breakpoint and elasticity) and cigarettes (breakpoint,
P
max
,
O
max
) on several characteristics of the purchase tasks. We found no evidence that active tobacco, both alone or combined with cannabis, had an effect on liking, demand or craving.
Conclusions
Acutely, cannabis reduced liking of cannabis-related stimuli and demand for cannabis itself. Acute cannabis also reduced demand for cigarettes on the CPT. Acute tobacco administration did not affect demand or pleasantness ratings for cigarettes themselves or cannabis. In non-dependent cannabis and tobacco co-users, tobacco did not influence the rewarding effects of cannabis.
•There are 31 studies examining cannabis use and reward processing using questionnaire, behavioural, or functional neuroimaging methods.•There is evidence that cannabis use is associated with ...anhedonia during adolescence.•Problematic cannabis use may be associated with apathy during young adulthood, but this remains to be confirmed by future research.•Longitudinal and acute neuroimaging studies find a link between cannabis and blunted neural reward responses, not observed cross-sectionally.•There is large variability in study methodology, and adolescents and female cannabis users are currently underrepresented in the literature.
Cannabis use has historically been thought to cause amotivation, but the relationship between cannabis and apathy, anhedonia, and reward processing remains poorly characterised. In this systematic review, we evaluated whether cannabis exposure acutely and/or non-acutely was associated with altered reward processing using questionnaire, behavioural, or functional neuroimaging measures. Questionnaire studies demonstrated greater anhedonia in adolescent cannabis users, and some indication of greater apathy in young adult cannabis users. Behavioural studies yielded some evidence of reduced reward learning in adolescent cannabis users, though there were too few studies in this category for reliable conclusions. Finally, longitudinal and acute functional neuroimaging studies showed an association between cannabis and blunted neural responses to reward, which did not emerge consistently in cross-sectional studies. The current results suggest that cannabis use is associated with specific impairments in reward and motivation. Future large-scale, longitudinal studies which use multiple behavioural and neuroimaging measures of reward processing may further clarify the impact of cannabis use on motivational and reward processes, and neural networks.
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.
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.
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.
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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