Cannabis constituents modulate ∆9-tetrahydrocannabinol-induced hyperphagia in rats

Rationale The hyperphagic effect of ∆9-tetrahydrocannabinol (∆9THC) in humans and rodents is well known. However, no studies have investigated the importance of ∆9THC composition and any influence other non-∆9THC cannabinoids present in Cannabis sativa may have. We therefore compared the effects of purified ∆9THC, synthetic ∆9THC (dronabinol), and ∆9THC botanical drug substance (∆9THC-BDS), a ∆9THC-rich standardized extract comparable in composition to recreationally used cannabis. Methods Adult male rats were orally dosed with purified ∆9THC, synthetic ∆9THC, or ∆9THC-BDS, matched for ∆9THC content (0.34–2.68 mg/kg). Prior to dosing, subjects were satiated, and food intake was recorded following ∆9THC administration. Data were then analyzed in terms of hourly intake and meal patterns. Results All three ∆9THC substances tested induced significant hyperphagic effects at doses ≥0.67 mg/kg. These effects included increased intake during hour one, a shorter latency to onset of feeding and a greater duration and consumption in the first meal. However, while some differences in vehicle control intakes were observed, there were significant, albeit subtle, differences in pattern of effects between the purified ∆9THC and ∆9THC-BDS. Conclusion All ∆9THC compounds displayed classical ∆9THC effects on feeding, significantly increasing short-term intake whilst decreasing latency to the first meal. We propose that the subtle adjustment to the meal patterns seen between the purified ∆9THC and ∆9THC-BDS are due to non-∆9THC cannabinoids present in ∆9THC-BDS. These compounds and other non-cannabinoids have an emerging and diverse pharmacology and can modulate ∆9THC-induced hyperphagia, making them worth further investigation for their therapeutic potential.

A low delta-9-tetrahydrocannabinol cannabis extract induces hyperphagia in rats

Appetite stimulation via partial agonism of cannabinoid type 1 receptors by Δ9tetrahydrocannabinol (Δ9THC) is well documented and can be modulated by non-Δ9THC phytocannabinoids. Δ9THC concentrations sufficient to elicit hyperphagia induce changes to both appetitive (reduced latency to feed) and consummatory (increased meal one size and duration) behaviours. Here, we show that a cannabis extract containing too little Δ9THC to stimulate appetite can induce hyperphagia solely by increasing appetitive behaviours. Twelve, male Lister hooded rats were presatiated before treatment with a low-Δ9THC cannabis extract (0.5, 1.0, 2.0 and 4.0 mg/kg). Hourly intake and meal pattern data were recorded and analyzed using one-way analyses of variance followed by Bonferroni post-hoc tests. The cannabis extract significantly increased food intake during the first hour of testing (at 4.0 mg/kg) and significantly reduced the latency to feed versus vehicle treatments (at doses ≥1.0 mg/kg). Meal size and duration were unaffected. These results show only the increase in appetitive behaviours, which could be attributed to non-Δ9THC phytocannabinoids in the extract rather than Δ9THC. Although further study is required to determine the constituents responsible for these effects, these results support the presence of non-Δ9THC cannabis constituent(s) that exert a stimulatory effect on appetite and likely lack the detrimental psychoactive effects of Δ9THC.

Cannabis sativa and the endogenous cannabinoid system: therapeutic potential for appetite regulation

The herb Cannabis sativa (C. sativa) has been used in China and on the Indian subcontinent for thousands of years as a medicine. However, since it was brought to the UK and then the rest of the western world in the late 19th century, its use has been a source of controversy. Indeed, its psychotropic side effects are well reported but only relatively recently has scientific endeavour begun to find valuable uses for either the whole plant or its individual components. Here, we discuss evidence describing the endocannabinoid system, its endogenous and exogenous ligands and their varied effects on feeding cycles and meal patterns. Furthermore we also critically consider the mounting evidence which suggests non‐tetrahydrocannabinol phytocannabinoids play a vital role in C. sativa‐induced feeding pattern changes. Indeed, given the wide range of phytocannabinoids present in C. sativa and their equally wide range of intra‐, inter‐ and extra‐cellular mechanisms of action, we demonstrate that non‐Δ9tetrahydrocannabinol phytocannabinoids retain an important and, as yet, untapped clinical potential.

Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB 1 receptor-independent mechanism

BACKGROUND AND PURPOSE Epilepsy is the most prevalent neurological disease and is characterized by recurrent seizures. Here, we investigate (i) the anticonvulsant profiles of cannabis-derived botanical drug substances (BDSs) rich in cannabidivarin (CBDV) and containing cannabidiol (CBD) in acute in vivo seizure models and (ii) the binding of CBDV BDSs and their components at cannabinoid CB 1 receptors. EXPERIMENTAL APPROACH The anticonvulsant profiles of two CBDV BDSs (50–422 mg·kg −1 ) were evaluated in three animal models of acute seizure. Purified CBDV and CBD were also evaluated in an isobolographic study to evaluate potential pharmacological interactions. CBDV BDS effects on motor function were also investigated using static beam and grip strength assays. Binding of CBDV BDSs to cannabinoid CB 1 receptors was evaluated using displacement binding assays. KEY RESULTS CBDV BDSs exerted significant anticonvulsant effects in the pentylenetetrazole (≥100 mg·kg −1 ) and audiogenic seizure models (≥87 mg·kg −1 ), and suppressed pilocarpine-induced convulsions (≥100 mg·kg −1 ). The isobolographic study revealed that the anticonvulsant effects of purified CBDV and CBD were linearly additive when co-administered. Some motor effects of CBDV BDSs were observed on static beam performance; no effects on grip strength were found. The Δ 9 -tetrahydrocannabinol and Δ 9 -tetrahydrocannabivarin content of CBDV BDS accounted for its greater affinity for CB 1 cannabinoid receptors than purified CBDV. CONCLUSIONS AND IMPLICATIONS CBDV BDSs exerted significant anticonvulsant effects in three models of seizure that were not mediated by the CB 1 cannabinoid receptor and were of comparable efficacy with purified CBDV. These findings strongly support the further clinical development of CBDV BDSs for the treatment of epilepsy.

Three dimensions of the male gender role as correlates of alcohol and cannabis involvement in young Australian men

This study examined 3 aspects of the male gender role and their relationship to alcohol and cannabis involvement in young adult Australian men (N = 160) aged between 18 and 25 years. Higher scores on the Restrictive Emotionality scale, which assessed gender ,role conflict, were found to relate to both alcohol-related problems and cannabis use. Higher scores on the Antifemininity scale, which assessed traditional attitudes toward men, were also found to be associated with alcohol-related problems. However, lower scores on another aspect of gender role conflict, Restrictive Affectionate Behavior Between Men, and lower scores on one aspect of traditional attitudes toward men, Status Rationality, correlated with higher frequency levels of alcohol and cannabis use.

Family risk factors for cannabis use: a population-based survey of Australian secondary school students

The objective of this study was to investigate relationships between adolescent cannabis use and indices of parent - child attachment, family functioning and parent attitudes to drugs and delinquency. A total of 2848 year 9 and 2363 year 11 students participated in the Victorian Adolescent Health and Well-Being Survey (1999). The study was a school-based random sample of 535 metropolitan and rural, government and non-government secondary schools throughout Victoria, Australia. Cannabis use was defined as 'any' and 'weekly' use in the last 30 days. Multivariate logistic regression was used to identify independent associations between cannabis use and parent - child attachment, family functioning and parent attitudes to drugs and delinquency. Cannabis use in year 9 was associated with permissive parent attitudes to drugs and delinquency (any use: adjusted odds ratio (OR) = 8.1; weekly use: adjusted OR = 7.6), and was particularly sensitive to small changes in the quality of the parent - child relationship with risk increasing threefold for those describing their attachment as 'good' compared with 'very good' (any use: adjusted OR = 2.8, weekly use adjusted OR = 2.9). A similar, but more moderate pattern association was evident in year 11. After adjusting for other family and background factors, poor family functioning showed minimal association with level of cannabis use at both year levels. Results suggest that intervention efforts might sensibly target strengthening parent - children relationships and promoting less permissive parent attitudes to drug use.

Modelling the public health consequences of cannabis use in Australia

Aims: To detail and validate a simulation model that describes the dynamics of cannabis use, including its probable causal relationships with schizophrenia, road traffic accidents (RTA) and heroin/poly-drug use (HPU).

Methods: A Markov model with 17 health-states was constructed. Annual cycles were used to simulate the initiation of cannabis use, progression in use, reduction and complete remission. The probabilities of transition between health-states were derived from observational data. Following 10-year-old Australian children for 90 years, the model estimated age-specific prevalence for cannabis use. By applying the relative risks according to the extent of cannabis use, the age-specific prevalence of schizophrenia and HPU, and the annual RTA incidence and fatality rate were also estimated. Predictive validity of the model was tested by comparing modelled outputs with data from other credible sources. Sensitivity and scenario analyses were conducted to evaluate technical validity and face validity.

Results: The estimated cannabis use prevalence in individuals aged 10-65 years was 12.2% which comprised 27.4% weekly and 18.0% daily users. The modelled prevalence and age profile were comparable to the reported cross-sectional data. The model also provided good approximations to the prevalence of schizophrenia (Modelled: 4.75/1,000 persons vs Observed: 4.6/1,000 persons), HPU (3.2/1,000 vs 3.1/1,000) and the RTA fatality rate (8.1 per 100,000 vs 8.2 per 100,000). Sensitivity analyses and scenario analysis provided expected and explainable trends.

Conclusions: The validated model provides a valuable tool to assess the likely effectiveness and cost-effectiveness of interventions designed to affect patterns of cannabis use. It can be updated as new data becomes available and/or applied to other countries.

MAKINGtheLINK : a school-based health promotion programme to increase help-seeking for cannabis and mental health issues among adolescents

Aim: There is increasing concern regarding the use of cannabis among adolescents, especially given recent evidence highlighting its link with later mental disorders. Encouraging young people with mental health or drug issues to seek professional help is an important early intervention strategy; however, adolescents are typically reluctant to do so and instead turn to their peers for help. Peers may not have the skills or knowledge required to assist their friends to access professional help. This paper describes the development and evaluation of MAKINGtheLINK, a school-based health promotion programme that promotes help-seeking behaviour for mental health and cannabis use issues among young people.

Methods: The MAKINGtheLINK programme was piloted with 182 Year 10 students at a secondary school in Melbourne, Australia. Forty teachers received the MAKINGtheLINK staff professional development session.

Results: The delivery of the MAKINGtheLINK programme was found to be both acceptable and feasible within a school setting. Students and teachers described it as a fun, engaging, helpful and important programme. Students reported increased confidence and awareness of how to seek help for themselves or a friend, and teachers indicated increased confidence and awareness of how to assist students to seek help for cannabis use and/or mental health problems.

Conclusions: MAKINGtheLINK was successfully implemented within the school curriculum. We believe this is the first school-based programme that specifically focuses on facilitating professional help-seeking for cannabis use and mental health problems among young people, and demonstrates that utilizing peer models for help-seeking is a valuable resource for early intervention initiatives.

Cannabis use and related harms in the transition to young adulthood: a longitudinal study of Australian secondary school students

The current study documents the changing rates of cannabis use, misuse and cannabis-related social harms among Australian adolescents as they grow into young adulthood. It utilised data from a longitudinal study of young people at ages 15, 16, 17, and 19. The rates of cannabis use were found to increase as participants aged; past year use increased from 7.5% at age 15 to 29.8% at age 19. Further, at ages 17 and 19, cannabis use was more prevalent among males than females. Among those who reported cannabis use, the rates of cannabis-related harms were low to moderate, and did not increase with age in the same manner as rates of cannabis use. The most prevalent self-reported cannabis-related harm was anxiety/depression; affecting between 20–30% of the cannabis users at each age. These findings may assist in understanding the extent of cannabis-related problems among youth, and in planning relevant services.