Evidence from Human Studies for Utilising Cannabinoids for the Treatment of Substance-Use Disorders: A Scoping Review with a Systematic Approach.

Substance-use disorders are pervasive, comorbid with a plethora of disease and possess limited treatment options. Medicinal cannabinoids have been proposed as a novel potential treatment based on preclinical/animal trials. The objective of this study was to examine the efficacy and safety of potential therapeutics targeting the endocannabinoid system in the treatment of substance-use disorders. We performed a scoping review using a systematic approach of systematic reviews, narrative reviews, and randomised control trials that utilised cannabinoids as treatment for substance-use disorders. For this scoping review we used the PRISMA guidelines, a framework for systematic reviews and meta-analyses, to inform our methodology. We conducted a manual search of Medline, Embase, and Scopus databases in July 2022. Of the 253 results returned by the databases, 25 studies including reviews were identified as relevant, from which 29 randomised controlled trials were derived and analysed via a primary study decomposition. This review captured a small volume of highly heterogenous primary literature investing the therapeutic effect of cannabinoids for substance-use disorders. The most promising findings appeared to be for cannabis-use disorder. Cannabidiol appeared to be the cannabinoid showing the most promise for the treatment of multiple-substance-use disorders.

Implementation of medicinal cannabis in Australia: innovation or upheaval? Perspectives from physicians as key informants, a qualitative analysis.

OBJECTIVE: We sought to explore physician perspectives on the prescribing of cannabinoids to patients to gain a deeper understanding of the issues faced by prescriber and public health advisors in the rollout of medicinal cannabis. DESIGN: A thematic qualitative analysis of 21 in-depth interviews was undertaken to explore the narrative on the policy and practice of medicinal cannabis prescribing. The analysis used the Diffusion of Innovations (DoI) theoretical framework to model the conceptualisation of the rollout of medicinal cannabis in the Australian context. SETTING: Informants from the states and territories of Victoria, New South Wales, Tasmania, Australian Capital Territory, and Queensland in Australia were invited to participate in interviews to explore the policy and practice of medicinal cannabis prescribing. PARTICIPANTS: Participants included 21 prescribing and non-prescribing key informants working in the area of neurology, rheumatology, oncology, pain medicine, psychiatry, public health, and general practice. RESULTS: There was an agreement among many informants that medicinal cannabis is, indeed, a pharmaceutical innovation. From the analysis of the informant interviews, the factors that facilitate the diffusion of medicinal cannabis into clincal practice include the adoption of appropriate regulation, the use of data to evaluate safety and efficacy, improved prescriber education, and the continuous monitoring of product quality and cost. Most informants asserted the widespread assimilation of medicinal cannabis into practice is impeded by a lack of health system antecedents that are required to facilitate safe, effective, and equitable access to medicinal cannabis as a therapeutic. CONCLUSIONS: This research highlights the tensions that arise and the factors that influence the rollout of cannabis as an unregistered medicine. Addressing these factors is essential for the safe and effective prescribing in contemporary medical practice. The findings from this research provides important evidence on medicinal cannabis as a therapeutic, and also informs the rollout of potential novel therapeutics in the future.

The 5-HT2C receptor as a therapeutic target for alcohol and methamphetamine use disorders: A pilot study in treatment-seeking individuals.

Alcohol use disorder (AUD) and methamphetamine use disorder (MUD) are prevalent and have high adverse impacts on both the individual and society. Current treatment strategies for these disorders are ineffective at a population level. Lorcaserin, a 5-HT2C receptor agonist, has shown potential at reducing the symptoms of substance use disorder. This pilot study (initiated prior to market withdrawal) examined feasibility and safety of lorcaserin treatment in people undergoing residential detoxification and treatment for AUD and MUD. This was an open label pilot study of lorcaserin where participants (n = 10 AUD; n = 8 MUD) received 10-mg lorcaserin daily for 4 days then twice daily for 1 month. Primary outcome measures included recruitment and retention rate, incidence of treatment-emergent events, incidence of methamphetamine or alcohol withdrawal-related events, heart rate, and blood pressure. Secondary measures included pharmacokinetic data and self-reported alcohol or methamphetamine use, craving, and psychological distress. AUD participants were recruited faster and had a greater retention rate compared with MUD participants. Lorcaserin did not alter vital signs, was well tolerated, and had a similar pharmacokinetic profile to individuals with obesity. Lorcaserin reduced self-reported alcohol and amphetamine-type substance use and craving in AUD and MUD participants, respectively. Self-reported psychological health also improved over the treatment period for all participants. Despite the pilot nature of this study, our data support the notion of 5-HT2C receptors as a therapeutic target for drug and alcohol abuse.

Medicinal psychedelics for mental health and addiction: Advancing research of an emerging paradigm.

The medical use of psychedelic substances (e.g. psilocybin, ayahuasca, lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine) is attracting renewed interest, driven by a pressing need for research and development of novel therapies for psychiatric disorders, as well as promising results of contemporary studies. In this Viewpoint, we reflect upon the 'Clinical Memorandum on Psychedelics' recently released by the Royal Australian and New Zealand College of Psychiatrists and note subsequent developments including the application for down-scheduling of psilocybin and 3,4-methylenedioxymethamphetamine presently being considered by the Therapeutic Goods Administration and approvals for access via the Special Access Scheme. We suggest that this field is worthy of rigorous research to assess potential benefits, address safety parameters and clarify therapeutic mechanisms. To this end, we outline recent research findings, provide an overview of current knowledge relating to mechanisms of action and discuss salient aspects of the psychedelic-assisted psychotherapy treatment model. The sum of this research points towards medicinal psychedelics as a potential new class of psychiatric treatments when used within a medically supervised framework with integrated psychotherapeutic support. However, before widespread translation into clinical use can occur, appropriately designed and sufficiently powered trials are required to detect both potential positive and negative outcomes. Unique safety and regulatory challenges also need to be addressed. As for any new medical therapy, psychedelic research needs to be conducted in a rigorous manner, through the dispassionate lens of scientific enquiry. Carte blanche availability to practitioners, without specific protocols and appropriate training, would be potentially harmful to individuals and detrimental to the field.