Search

Aims: The aims of this study were to present an enhanced cannabis timeline followback (EC‐TLFB) enabling comprehensive assessment of cannabis use measures, including standard tetrahydrocannabinol (THC) units, and to validate these against objectively indexed urinary 11‐nor‐9‐carboxy‐tetrahydrocannabinol (THC‐COOH) concentrations. Design: We used cross‐sectional baseline data from the 'CannTeen' observational longitudinal study. Setting: The study was conducted in London, UK. Participants: A total of 147 participants who used cannabis regularly took part in the study (n = 71 female, n = 76 male; mean age = 21.90, standard deviation = 5.32). Measurements The EC‐TLFB was used to calculate frequency of cannabis use, method of administration, including co‐administration with tobacco, amount of cannabis used (measured with unaided self‐report and also using pictorial aided self‐report) and type of cannabis product (flower, hash) which was used to estimate THC concentration (both from published data on THC concentration of products and analysis of cannabis samples donated by participants in this study). We calculated total weekly standard THC units (i.e. 5 mg THC for all cannabis products and methods of administration) using the EC‐TLFB. The outcome variable for validation of past week EC‐TLFB assessments was creatinine‐normalized carboxy‐tetrahydrocannabinol (THC‐COOH) in urine. Findings All measures of cannabis exposure included in this analysis were positively correlated with levels of THC‐COOH in urine (r = 0.41–0.52). Standard THC units, calculated with average concentrations of THC in cannabis in the UK and unaided self‐report measures of amount of cannabis used in grams showed the strongest correlation with THC‐COOH in urine (r = 0.52, 95% bias‐corrected and accelerated = 0.26–0.70). Conclusions: The enhanced cannabis timeline followback (EC‐TLFB) can provide a valid assessment of a comprehensive set of cannabis use measures including standard tetrahydrocannabinol units as well as and traditional TLFB assessments (e.g. frequency of use and grams of cannabis use). [ABSTRACT FROM AUTHOR]

Background and Aims: Long‐term harms of cannabis may be exacerbated in adolescence, but little is known about the acute effects of cannabis in adolescents. We aimed to (i) compare the acute effects of cannabis in adolescent and adult cannabis users and (ii) determine if cannabidiol (CBD) acutely modulates the effects of delta‐9‐tetrahydocannabinol (THC). Design: Randomised, double‐blind, placebo‐controlled, crossover experiment. The experiment was registered on ClinicalTrials.gov (NCT04851392). Setting: Laboratory in London, United Kingdom. Participants: Twenty‐four adolescents (12 women, 16‐ to 17‐year‐olds) and 24 adults (12 women, 26‐ to 29‐year‐olds) who used cannabis 0.5–3 days/week and were matched on cannabis use frequency (mean = 1.5 days/week). Intervention: We administered three weight‐adjusted vaporised cannabis flower preparations: 'THC' (8 mg THC for 75 kg person); 'THC + CBD' (8 mg THC and 24 mg CBD for 75 kg person); and 'PLA' (matched placebo). Measurements Primary outcomes were (i) subjective 'feel drug effect'; (ii) verbal episodic memory (delayed prose recall); and (iii) psychotomimetic effect (Psychotomimetic States Inventory). Findings Compared with 'PLA', 'THC' and 'THC + CBD' significantly (P < 0.001) increased 'feel drug effect' (mean difference [MD] = 6.3, 95% CI = 5.3–7.2; MD = 6.8, 95% CI = 6.0–7.7), impaired verbal episodic memory (MD = –2.7, 95% CI = −4.1 to −1.4; MD = −2.9, 95% CI = −4.1 to −1.7) and increased psychotomimetic effects (MD = 7.8, 95% CI = 2.8–12.7; MD = 10.8, 95% CI = 6.2–15.4). There was no evidence that adolescents differed from adults in their responses to cannabis (interaction P ≥ 0.4). Bayesian analyses supported equivalent effects of cannabis in adolescents and adults (Bayes factor [BF01] >3). There was no evidence that CBD significantly modulated the acute effects of THC. Conclusions: Adolescent cannabis users are neither more resilient nor more vulnerable than adult cannabis users to the acute psychotomimetic, verbal memory‐impairing or subjective effects of cannabis. Furthermore, in adolescents and adults, vaporised cannabidiol does not mitigate the acute harms caused by delta‐9‐tetrahydocannabinol. [ABSTRACT FROM AUTHOR]

Background: Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the two major constituents of cannabis with contrasting mechanisms of action. THC is the major psychoactive, addiction-promoting, and psychotomimetic compound, while CBD may have opposite effects. The brain effects of these drugs alone and in combination are poorly understood. In particular, the striatum is implicated in the pathophysiology of several psychiatric disorders, but it is unclear how THC and CBD influence striato-cortical connectivity. Aims: To examine effects of THC, CBD, and THC + CBD on functional connectivity of striatal sub-divisions (associative, limbic and sensorimotor). Method: Resting-state functional Magnetic Resonance Imaging (fMRI) was used across two within-subjects, placebo-controlled, double-blind studies, with a unified analysis approach. Results: Study 1 (N = 17; inhaled cannabis containing 8 mg THC, 8 mg THC + 10 mg CBD or placebo) showed strong disruptive effects of both THC and THC + CBD on connectivity in the associative and sensorimotor networks, but a specific effect of THC in the limbic striatum network which was not present in the THC + CBD condition. In Study 2 (N = 23, oral 600 mg CBD, placebo), CBD increased connectivity in the associative network, but produced only relatively minor disruptions in the limbic and sensorimotor networks. Outcomes: THC strongly disrupts striato-cortical networks, but this effect is mitigated by co-administration of CBD in the limbic striatum network. Oral CBD administered has a more complex effect profile of relative increases and decreases in connectivity. The insula emerges as a key region affected by cannabinoid-induced changes in functional connectivity, with potential implications for understanding cannabis-related disorders, and the development of cannabinoid therapeutics. [ABSTRACT FROM AUTHOR]

Background: The lack of an agreed international minimum approach to measuring cannabis use hinders the integration of multidisciplinary evidence on the psychosocial, neurocognitive, clinical and public health consequences of cannabis use. Methods: A group of 25 international expert cannabis researchers convened to discuss a multidisciplinary framework for minimum standards to measure cannabis use globally in diverse settings. Results: The expert‐based consensus agreed upon a three‐layered hierarchical framework. Each layer—universal measures, detailed self‐report and biological measures—reflected different research priorities and minimum standards, costs and ease of implementation. Additional work is needed to develop valid and precise assessments. Conclusions: Consistent use of the proposed framework across research, public health, clinical practice and medical settings would facilitate harmonisation of international evidence on cannabis consumption, related harms and approaches to their mitigation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The iCannToolkit is a first important step to systematically gather evidence regarding the health effects of contemporary medical and non-medical cannabis use—over time, among licit and illicit settings, cultures and age groups—in order to inform policy development and to raise awareness concerning cannabis use-related risks and benefits. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]