Acute and non-acute effects of cannabis in adolescents and adults

Preclinical research demonstrates that cannabinoids have differing effects in adolescent and adult animals, and human epidemiological research suggests that adolescent cannabis use has greater potential for harm than adult use. In chapters 1 and 2, I review this literature, describing the acute and non-acute effects of cannabis on memory, response inhibition and psychotic-like symptoms, with a focus on findings relating to adolescent populations and age of cannabis use onset. In chapter 3, I describe associations between adolescent cannabis use, IQ and educational performance, demonstrating that adjustment for potential confounders – most notably cigarette use – leaves cannabis use not associated with lower performance. In chapter 4, I describe 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 vaporised active or placebo cannabis, participants completed tasks assessing memory, inhibition, alongside physiological measures and subjective drug effects (e.g. “stoned”). Results showed contrasting profiles of adolescent resilience (blunted subjective, physiological and memory effects) and vulnerability (lack of satiety, impaired inhibitory processes). In chapter 5, in the same sample, I describe the acute psychotic-like effects of cannabis. Cannabis increased psychotic-like symptoms and the incidence of speech illusions in both adolescents and adults, though some self-rated effects were heightened in adults. In chapter 6, in a reduced sample, I describe the acute effects of cannabis on anhedonia (as indexed by reward responsivity, hedonic capacity and self-rated anhedonia) in adolescents (n=13) and adults (n=13). Cannabis did not affect reward responsivity or hedonic capacity in either group, though adults but not adolescents reported self-rated increases in anhedonia. In chapter 7, I integrate my findings, discuss their implications, consider limitations and suggest directions for future research into the effects of cannabis use in adolescence

Are IQ and educational outcomes in teenagers related to their cannabis use? A prospective cohort study

The UK Medical Research Council (MRC), Wellcome Trust and University of Bristol provide core support for ALSPAC. This research was specifically funded by an MRC Studentship awarded to the first autho

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

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

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 (CBD), which may offset cannabis-related harms. Methods: Across three sessions, sixteen cannabis users inhaled cannabis with CBD, cannabis without CBD, and placebo. We compared their response to music relative to control excerpts of scrambled sound during functional Magnetic Resonance Imaging (fMRI) within regions identified in a meta-analysis of music-evoked reward and emotion. All results were False Discovery Rate corrected (p<0.05). Results: Compared to placebo, cannabis without CBD dampened response to music in bilateral auditory cortex (right: p=0.005, left: p=0.008), right hippocampus/parahippocampal gyrus (p=0.025), right amygdala (p=0.025) and right ventral striatum (p=0.033). Across all sessions, the effects of music in this ventral striatal region correlated with pleasure ratings (p=0.002) and increased functional connectivity with auditory cortex (right: p=0.000, left: p=0.000), supporting its involvement in music reward. Functional connectivity between right ventral striatum and auditory cortex was increased by CBD (right: p=0.003, left: p=0.030), and cannabis with CBD did not differ from placebo on any fMRI measures. Both types of cannabis increased ratings of wanting to listen to music (p<0.002) and enhanced sound perception (p<0.001). 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

Attentional bias and treatment adherence in substitute-prescribed opiate users

BACKGROUND: Attentional bias (AB) is implicated in the development and maintenance of substance dependence and in treatment outcome. We assessed the effects of attentional bias modification (ABM), and the relationship between AB and treatment adherence in opiate dependent patients. METHOD: An independent groups design was used to compare 23 opiate dependent patients with 21 healthy controls. Participants completed an AB task before either a control or an ABM task designed to train attention away from substance-related stimuli. Pre- and post-ABM AB and craving were assessed to determine any changes. Relationships between treatment adherence (‘using on top’ of prescribed opiates or not) and AB, craving and psychopathology were also examined. RESULTS: There was no baseline difference in AB between patients and controls, and no significant effect of ABM on AB or substance craving. However, treatment adherent patients who did not use illicit opiates on top of their prescribed opiates had statistically significantly greater AB away from substance-related stimuli than both participants using on top and controls, and reported significantly lower levels of craving than non-treatment adherent patients. CONCLUSION: Whilst we did not find any significant effects of ABM on AB or craving, patients who were treatment adherent differed from both those who were not and from controls in their attentional functioning and substance craving. These findings are the first to suggest that AB may be a within-treatment factor predictive of adherence to pharmacological treatment and potentially of recovery in opiate users

The CannTeen study: verbal episodic memory, spatial working memory, and response inhibition in adolescent and adult cannabis users and age-matched controls

BACKGROUND: Preclinical and human studies suggest that adolescent cannabis use may be associated with worse cognitive outcomes than adult cannabis use. We investigated the associations between chronic cannabis use and cognitive function in adolescent and adult cannabis users and controls. We hypothesised user-status would be negatively associated with cognitive function and this relationship would be stronger in adolescents than adults. METHODS: As part of the 'CannTeen' project, this cross-sectional study assessed cognitive performance in adolescent cannabis users (n = 76; 16-17-year-olds), adolescent controls (n = 63), adult cannabis users (n = 71; 26-29-year-olds) and adult controls (n = 64). Users used cannabis 1-7 days/week. Adolescent and adult cannabis users were matched on cannabis use frequency (4 days/week) and time since last use (2.5 days). Verbal episodic memory (VEM) was assessed using the prose recall task, spatial working memory (SWM) was assessed using the spatial n-back task, and response inhibition was assessed with the stop-signal task. Primary outcome variables were: delayed recall, 3-back discriminability, and stop signal reaction time, respectively. RESULTS: Users had worse VEM than controls (F(1,268) = 7.423, p = 0.007). There were no significant differences between user-groups on SWM or response inhibition. Null differences were supported by Bayesian analyses. No significant interactions between age-group and user-group were found for VEM, SWM, or response inhibition. CONCLUSIONS: Consistent with previous research, there was an association between chronic cannabis use and poorer VEM, but chronic cannabis use was not associated with SWM or response inhibition. We did not find evidence for heightened adolescent vulnerability to cannabis-related cognitive impairment

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

Drug Use Changes at the Individual Level: Results from a Longitudinal, Multisite Survey in Young Europeans Frequenting the Nightlife Scene

Background: Monitoring emerging trends in the increasingly dynamic European drug market is vital; however, information on change at the individual level is scarce. In the current study, we investigated changes in drug use over 12 months in European nightlife attendees. / Method: In this longitudinal online survey, changes in substances used, use frequency in continued users, and relative initiation of use at follow-up were assessed for 20 different substances. To take part, participants had to be aged 18–34 years; be from Belgium, Italy, the Netherlands, Sweden, or the UK; and have attended at least 6 electronic music events in the past 12 months at baseline. Of 8,045 volunteers at baseline, 2,897 completed the survey at both time points (36% follow-up rate), in 2017 and 2018. / Results: The number of people using ketamine increased by 21% (p < 0.001), and logarithmized frequency of use in those continuing use increased by 15% (p < 0.001; 95% CI: 0.07–0.23). 4-Fluoroamphetamine use decreased by 27% (p < 0.001), and logarithmized frequency of use in continuing users decreased by 15% (p < 0.001, 95% CI: −0.48 to −0.23). The drugs with the greatest proportion of relative initiation at follow-up were synthetic cannabinoids (73%, N = 30), mephedrone (44%, N = 18), alkyl nitrites (42%, N = 147), synthetic dissociatives (41%, N = 15), and prescription opioids (40%, N = 48). / Conclusions: In this European nightlife sample, ketamine was found to have the biggest increase in the past 12 months, which occurred alongside an increase in frequency of use in continuing users. The patterns of uptake and discontinuation of alkyl nitrates, novel psychoactive substances, and prescription opioids provide new information that has not been captured by existing cross-sectional surveys. These findings demonstrate the importance of longitudinal assessments of drug use and highlight the dynamic nature of the European drug landscape