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

Anatomy of a Joint: Comparing Self-Reported and Actual Dose of Cannabis and Tobacco in a Joint, and How These Are Influenced by Controlled Acute Administration

Introduction: Major gaps exist in the measurement of cannabis exposure. The accuracy of self-reported cannabis and tobacco dose per joint is poorly characterized and has never been investigated following acute cannabis/ tobacco exposure. Using an innovative ‘‘Roll a Joint’’ paradigm, this study aims to (1) compare estimated and actual dose of cannabis and tobacco per joint at baseline and (2) examine the acute effects of cannabis and/ or tobacco on estimated and actual dose. Materials and Methods: We investigated this by using a randomized, double-blind, placebo-controlled crossover 2 (active cannabis, placebo cannabis) · 2 (active tobacco, placebo tobacco) design in a laboratory setting. Participants were 24 recreational cousers of cannabis and tobacco. At baseline, they were asked to measure out the amount of cannabis and tobacco they would put in an average joint for themselves (dose per joint). Then, on each of four drug administration sessions, participants were again asked to do this for a joint they would want to smoke ‘‘right now.’’ Self-reported and actual amount was recorded (g). Results: At baseline, the estimated amount of cannabis per joint (0.28 – 0.23 g) was double the actual amount (0.14 – 0.12 g) ( p = 0.003, d = 0.723). No difference emerged between estimated (0.43 – 0.25 g) and actual (0.35 – 0.15 g) ( p = 0.125) amount of tobacco per joint. Compared to placebo, active cannabis reduced the actual dose of both cannabis ( p = 0.035) and tobacco ( p < 0.001) they put in a joint. Participants accurately estimated this reduction for tobacco ( p = 0.014), but not for cannabis ( p = 0.680). Conclusions: Self-reported dose per joint is accurate for tobacco but dramatically overestimates cannabis exposure and therefore should be viewed with caution. Cannabis administration reduced the amount of cannabis and tobacco added to joints, suggesting a reduction in dose during a smoking session. The ‘‘Roll A Joint’’ paradigm should be implemented for better accuracy in assessing dose per joint

Identification of a narrow post-ovulatory window of vulnerability to distressing involuntary memories in healthy women

Psychological disorders characterised by intrusive memories are more prevalent in women than men. The biological, social and cognitive processes underlying this gender-difference have yet to be fully elucidated. Some evidence suggests that (fluctuations in) ovarian hormone levels are responsible for altered sensitivity to emotional stimuli during certain phases in the menstrual-cycle and this may form the basis of a specific vulnerability to psychological disorders in women. The post-ovulatory (luteal) phase has been identified as a period of particular vulnerability to the development of Post-Traumatic Stress Disorder (PTSD). Using an experimental model of PTSD, we examine whether differences are detectable between discrete phases in the menstrual-cycle in the experience of intrusive memories. Women (18-35 years-old) in one of three tightly-defined periods within the menstrual cycle – mid-follicular (n=15), early-luteal (n=15) and late-luteal (n=11) - provided saliva samples for ovarian-hormone assay and watched a distressing film. Subsequent intrusive memories, assessed using a daily online-diary, occurred significantly more frequently in the early-luteal group compared to mid-follicular and late-luteal groups. Intrusion frequency was negatively correlated with the estradiol-to-progesterone ratio, but not estradiol or progesterone alone, suggesting that the interactive effect of low estradiol and high progesterone at encoding contributes to the observed effect. Our results support the need for further research in a clinical context with naturally-cycling women who experience a traumatic event, since assessment of days-since-last-menses and ovarian hormone levels may help to identify those at greatest risk of developing re-experiencing symptoms akin to those seen in psychological disorder such as depression and PTSD

Encoding of Marginal Utility across Time in the Human Brain

Marginal utility theory prescribes the relationship between the objective property of the magnitude of rewards and their subjective value. Despite its pervasive influence, however, there is remarkably little direct empirical evidence for such a theory of value, let alone of its neurobiological basis. We show that human preferences in an intertemporal choice task are best described by a model that integrates marginally diminishing utility with temporal discounting. Using functional magnetic resonance imaging, we show that activity in the dorsal striatum encodes both the marginal utility of rewards, over and above that which can be described by their magnitude alone, and the discounting associated with increasing time. In addition, our data show that dorsal striatum may be involved in integrating subjective valuation systems inherent to time and magnitude, thereby providing an overall metric of value used to guide choice behavior. Furthermore, during choice, we show that anterior cingulate activity correlates with the degree of difficulty associated with dissonance between value and time. Our data support an integrative architecture for decision making, revealing the neural representation of distinct subcomponents of value that may contribute to impulsivity and decisiveness

Dopamine, urges to smoke, and the relative salience of drug versus non-drug reward

When addicted individuals are exposed to drug-related stimuli, dopamine release is thought to mediate incentive salience attribution, increasing attentional bias, craving and drug seeking. It is unclear whether dopamine acts specifically on drug cues versus other rewards, and if these effects correspond with craving and other forms of cognitive bias. Here, we administered the dopamine D 2 /D 3 agonist pramipexole (0.5 mg) to 16 tobacco smokers in a double-blind placebo-controlled crossover design. Visual fixations on smoking and money images were recorded alongside smoking urges and fluency tasks. Pramipexole attenuated a marked bias in initial orienting towards smoking relative to money but did not alter a maintained attentional bias towards smoking. Pramipexole decreased urges to smoke retrospectively after the task but not on a state scale. Fewer smoking words were generated after pramipexole but phonological and semantic fluency were preserved. Although these treatment effects did not correlate with each other, changes in initial orienting towards smoking and money were inversely related to baseline scores. In conclusion, pramipexole can reduce the salience of an addictive drug compared with other rewards and elicit corresponding changes in smoking urges and cognitive bias. These reward-specific and baseline-dependent effects support an ‘inverted-U’ shaped profile of dopamine in addiction

AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers.

This is the final version of the article. Available from Springer Nature via the DOI in this record.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.This research was funded by grants to HVC and CJAM from the Medical Research Council UK (G0800268/P4844; MRCL023032/1)

Prospective memory impairments in heavy social drinkers are partially overcome by future event simulation

BACKGROUND: Recent research suggests that alcohol acutely impairs prospective memory (PM), and this impairment can be overcome using a strategy called 'future event simulation' (FES). Impairment in event-based PM found in detoxifying alcohol-dependent participants is reversed through FES. However, the impact of the most common problematic drinking patterns that do not involve alcohol dependence on PM remains unclear. AIMS: Here, we examine the impact of frequent heavy drinking on PM and the degree to which any impairments can be reversed through FES. METHODS: PM was assessed in 19 heavy drinkers (AUDIT scores ≥15) and 18 matched control participants (AUDIT scores ≤7) using the 'Virtual Week' task both at baseline and again following FES. RESULTS: Heavy drinkers performed significantly worse than controls on regular and irregular time-based PM tasks. FES improved the performance of controls but not of heavy drinkers on time-based tasks. In contrast, FES improved heavy drinkers' performance on event-based PM tasks. CONCLUSIONS: These findings suggest that heavy drinkers experience deficits in strategic monitoring processing associated with time-based PM tasks which do not abate after FES. That the same strategy improves their event-based PM suggests that FES may be helpful for individuals with problematic drinking patterns in improving their prospective memory

Acute memory and psychotomimetic effects of cannabis and tobacco both 'joint' and individually: a placebo-controlled trial

BACKGROUND: Cannabis and tobacco have contrasting cognitive effects. Smoking cannabis with tobacco is prevalent in many countries and although this may well influence cognitive and mental health outcomes, the possibility has rarely been investigated in human experimental psychopharmacological research. METHOD: The individual and interactive effects of cannabis and tobacco were evaluated in 24 non-dependent cannabis and tobacco smokers in a randomized, placebo-controlled, double-blind, 2 (cannabis, placebo) × 2 (tobacco, placebo) crossover design. Verbal memory (prose recall), working memory (WM) performance including maintenance, manipulation and attention (N-back), psychotomimetic, subjective and cardiovascular measures were recorded on each of four sessions. RESULTS: Cannabis alone impaired verbal memory. A priori contrasts indicated that tobacco offset the effects of cannabis on delayed recall. However, this was not supported by linear mixed model analysis. Cannabis load-dependently impaired WM. By contrast, tobacco improved WM across all load levels. The acute psychotomimetic effects and ratings of 'stoned' and 'dizzy' induced by cannabis were not altered by tobacco. Cannabis and tobacco had independent effects on increasing heart rate and interacting effects on increasing diastolic blood pressure. CONCLUSIONS: Relative to placebo, acute cannabis impaired verbal memory and WM. Tobacco enhanced performance on WM, independently of cannabis. Moreover, we found some preliminary evidence that tobacco may offset the effects of cannabis on delayed, but not immediate, verbal recall. In contrast, the psychotomimetic and subjective effects of cannabis were unaffected by tobacco co-administration. By reducing the cognitive impairment from cannabis, tobacco co-administration may perpetuate use despite adverse health consequences

Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males

Preclinical research demonstrates that cannabinoids have differing effects in adolescent and adult animals. Whether these findings translate to humans has not yet been investigated. Here we believe we conducted the first study to compare the acute effects of cannabis in human adolescent (n=20; 16-17 years old) and adult (n=20; 24-28 years old) male cannabis users, in a placebo-controlled, double-blind cross-over design. After inhaling vaporized active or placebo cannabis, participants completed tasks assessing spatial working memory, episodic memory and response inhibition, alongside measures of blood pressure and heart rate, psychotomimetic symptoms and subjective drug effects (for example, 'stoned', 'want to have cannabis'). Results showed that on active cannabis, adolescents felt less stoned and reported fewer psychotomimetic symptoms than adults. Further, adults but not adolescents were more anxious and less alert during the active cannabis session (both pre- and post-drug administration). Following cannabis, cognitive impairment (reaction time on spatial working memory and prose recall following a delay) was greater in adults than adolescents. By contrast, cannabis impaired response inhibition accuracy in adolescents but not in adults. Moreover, following drug administration, the adolescents did not show satiety; instead they wanted more cannabis regardless of whether they had taken active or placebo cannabis, while the opposite was seen for adults. These contrasting profiles of adolescent resilience (blunted subjective, memory, physiological and psychotomimetic effects) and vulnerability (lack of satiety, impaired inhibitory processes) show some degree of translation from preclinical findings, and may contribute to escalated cannabis use by human adolescents

What are the psychological effects of using synthetic cannabinoids? A systematic review

Background: Synthetic cannabinoids are, typically, full agonists at the cannabinoid CB1 receptor, and therefore considerably more potent than natural cannabis and may have correspondingly more serious psychological effects. Despite government sanctions against their production they continue to be available in ever-increasing varieties over the Internet. The psychological consequences of synthetic cannabinoid use are relatively unknown. Aim: The purpose of this study was to synthesise the available research on the psychological consequences of synthetic cannabinoid use. Method: A literature search of three databases was conducted in February 2018, including the following keywords: Spice, synthetic cannabis, cognition, affect, behaviour, psychosis, depression and anxiety. Results: Seventeen studies involving a variety of participants were eligible for inclusion: one controlled administration study, seven cross-sectional studies, five Internet surveys and four qualitative studies. The controlled administration study showed that, compared to placebo, synthetic cannabinoids acutely affected some aspects of cognitive functioning and subjective psychological ratings. Non-controlled, cross-sectional studies generally showed that synthetic cannabinoid users had lower performance on cognitive tasks and showed elevated symptomatology (e.g. paranoia) compared to both natural cannabis and non-cannabis users. Methodological limitations were noted across different study designs. There is limited research on how doses, frequency or type of synthetic cannabinoid influence outcomes. Conclusions: Acute synthetic cannabinoid use can result in a range of psychological outcomes and, when non-intoxicated, synthetic cannabinoid users appear to differ from natural cannabis and non-users on various affective and cognitive domains. As synthetic cannabinoid use is increasing in at-risk populations there is an urgent need for more and better research to inform users, professionals and policymakers