From Prohibition to Prescription: The Role of Cannabinoids in Sleep

Insomnia disorder is the most common sleep disorder and is characterised by self-reported difficulties with falling asleep and/or staying asleep and is associated with significant daytime distress. Despite significant advances in the understanding and treatment of insomnia and the availability of effective treatment options, insomnia management remains suboptimal, posing a significant challenge to public health. Anecdotally, cannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are being touted as sleep-promoting drugs. However, evidence for the therapeutic utility of cannabinoids in the treatment of sleep disorders is limited. With increasing consumer interest and uptake of medicinal cannabis globally for the treatment of sleep disorders, it is important that we develop a better understanding of how cannabinoids affect sleep and ‘next day’ function before it becomes routine clinical practice. Therefore, this thesis aims to (1) examine the acute effects of a commonly used ratio of CBD and THC on objective sleep outcomes using polysomnography with high-density EEG in insomnia disorder, (2) determine the ‘next day’ effects of evening administration of CBD and THC on cognitive function, alertness, and driving performance, (3) examine the performance of commonly used point-of collection testing (POCT) devices in detecting individuals who may be under the influence of cannabis. It also provides a comprehensive literature review of the current preclinical and clinical evidence of cannabinoid therapies in the treatment of sleep disorders, and explores the patterns of medicinal cannabis use among a sample of Australians with a self-reported sleep disorder. It is hoped that the work contained in this thesis will advance our understanding of how cannabis impacts sleep and help to guide future research directives and clinical decision making

The safety and efficacy of low oral doses of cannabidiol: An evaluation of the evidence

Abstract Global interest in the non‐intoxicating cannabis constituent, cannabidiol (CBD), is increasing with claims of therapeutic effects across a diversity of health conditions. At present, there is sufficient clinical trial evidence to support the use of high oral doses of CBD (e.g., 10–50 mg/kg) in treating intractable childhood epilepsies. However, a question remains as to whether “low‐dose” CBD products confer any therapeutic benefits. This is an important question to answer, as low‐dose CBD products are widely available in many countries, often as nutraceutical formulations. The present review therefore evaluated the efficacy and safety of low oral doses of CBD. The review includes interventional studies that measured the clinical efficacy in any health condition and/or safety and tolerability of oral CBD dosed at less than or equal to 400 mg per day in adult populations (i.e., ≥18 years of age). Studies were excluded if the product administered had a Δ9‐tetrahydrocannabinol content greater than 2.0%. Therapeutic benefits of CBD became more clearly evident at doses greater than or equal to 300 mg. Increased dosing from 60 to 400 mg/day did not appear to be associated with an increased frequency of adverse effects. At doses of 300–400 mg, there is evidence of efficacy with respect to reduced anxiety, as well as anti‐addiction effects in drug‐dependent individuals. More marginal and less consistent therapeutic effects on insomnia, neurological disorders, and chronic pain were also apparent. Larger more robust clinical trials are needed to confirm the therapeutic potential of lower (i.e., <300 mg/day) oral doses of CBD

Determination of contaminants in artisanal cannabis products used for childhood epilepsy in the Australian community: a sub-analysis of the 'PELICAN' study.

Despite recent approval of pharmaceutical-grade cannabis products for the treatment of childhood epilepsy, some families continue to use artisanal cannabis products as a way to manage seizures in their children. However, such products are typically of unknown composition and quality, and may therefore pose an unpredictable health risk to the child. In the present analysis, 78 samples of cannabis products collected (as part of a previous study) from families of children with epilepsy (average age 8.8 ± 4.6 years) were analyzed for heavy metals (arsenic, cadmium, lead, and mercury), residual solvents (panel of 19 solvents) and pesticides (panel of 57 pesticides). Due to small sample volumes obtained, only a subset of samples was used in each analysis. Results showed that no cannabis sample exceeded the toxicity limits for heavy metals (n = 51 samples tested). Of the 58 cannabis samples tested for residual solvents, 17 (29%) contained concentrations of ethanol or isopropanol above the generally accepted limit of 5000 parts per million. With the volumes consumed, it was thought unlikely that children were consuming hazardous amounts of residual solvents, although this could not be ruled out in every case. Most samples (n = 31 samples tested) yielded inconclusive results for the pesticides, although one sample contained concentrations of bifenthrin that were 4.9 times higher than the acceptable limit. Overall, these results highlight the need for improved access to quality-assured cannabis products and the education of doctors, patients, and artisanal manufacturers around the contaminant exposure risk in unregulated cannabis products

Adolescent pre-treatment with oxytocin protects against adult methamphetamine-seeking behavior in female rats

The neuropeptide oxytocin (OT), given acutely, reduces self-administration of the psychostimulant drug methamphetamine (METH). Additionally, chronic OT administration to adolescent rats reduces levels of alcohol consumption in adulthood, suggesting developmental neuroplasticity in the OT system relevant to addiction-related behaviors. Here, we examined whether OT exposure during adolescence might subsequently inhibit METH self-administration in adulthood. Female Sprague-Dawley rats were administered vehicle or OT (1 mg/kg, i.p.) once daily from postnatal days (PND) 28 to 37 (adolescence). At PND 62 (adulthood), rats were trained to self-administer METH (intravenous, i.v.) in daily 2-hour sessions for 10 days under a fixed ratio 1 (FR1) reinforcement schedule, followed by determination of dose-response functions (0.01-0.3 mg/kg/infusion, i.v.) under both FR1 and progressive ratio (PR) schedules of reinforcement. Responding was then extinguished, and relapse to METH-seeking behavior assessed following priming doses of non-contingent METH (0.1-1 mg/kg, i.p.). Finally, plasma was collected to determine pre-treatment effects on OT and corticosterone levels. Results showed that OT pre-treatment did not significantly inhibit the acquisition of METH self-administration or FR1 responding. However, rats pre-treated with OT responded significantly less for METH under a PR reinforcement schedule, and showed reduced METH-primed reinstatement with the 1 mg/kg prime. Plasma OT levels were also significantly higher in OT pre-treated rats. These results confirm earlier observations that adolescent OT exposure can subtly, yet significantly, inhibit addiction-relevant behaviors in adulthood.12 page(s

Driving-related behaviors, attitudes, and perceptions among Australian medical cannabis users: results from the CAMS 20 survey

Abstract Road safety is an important concern amidst expanding worldwide access to legal cannabis. The present study reports on the driving-related subsection of the Cannabis as Medicine Survey 2020 (CAMS-20) which surveyed driving-related behaviors, attitudes, and perceptions among Australian medical cannabis (MC) users. Of the 1063 respondents who reported driving a motor vehicle in the past 12 months, 28% (297/1063) reported driving under the influence of cannabis (DUIC). Overall, 49–56% of respondents said they typically drive within 6 h of MC use, depending on the route of administration (oral or inhaled). Non-medical cannabis (NMC) was perceived to be more impairing for driving than MC. Binary logistic regression revealed associations between likelihood of DUIC and (1) inhaled routes of cannabis administration, (2) THC-dominant products, (3) illicit rather than prescribed use, (4) believing NMC does not impair driving, and (5) not being deterred by roadside drug testing. Overall, these findings suggest there is a relatively low perception of driving-related risk among MC users. Targeted education programs may be needed to highlight the potential risks associated with DUIC, and further research is needed to determine whether driving performance is differentially affected by MC and NMC

Other medication used versus prescribed cannabinoids.

Other medication used versus prescribed cannabinoids.</p

MacPhail vs CAMS approximate (%) S8 approval in Jan 2021 for most common indications.

MacPhail vs CAMS approximate (%) S8 approval in Jan 2021 for most common indications.</p

Main reasons for use of prescribed medicinal cannabis users by cannabinoid product production composition.

Main reasons for use of prescribed medicinal cannabis users by cannabinoid product production composition.</p