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Background Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several centres have reported that one dose of the serotonergic psychedelic psilocybin, combined with therapeutic support, improves these symptoms for up to 6 months in this patient group. Drawing upon related therapeutic mechanisms, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy may have the potential to achieve similar, positive mental health outcomes in this group. Preliminary evidence also supports the tolerability of MDMA-assisted therapy for anxiety and depression in advanced-stage cancer. Methods Up to 32 participants with advanced-stage cancer and associated depression and anxiety will be randomised in a 1:1 ratio into one of two blinded parallel treatment arms. The intervention group will receive 120 mg (+ 60 mg optional supplemental dose) MDMA-assisted therapy. The psychoactive control group will receive 20 mg oral (+ 10 mg optional supplemental dose) methylphenidate-assisted therapy. For each medication-assisted therapy session, participants will undergo two 90-min therapeutic support sessions in the week preceding, and one 90-min support session the day after the experimental session. A battery of measures (mood, anxiety, quality of life, mystical experience, spiritual wellbeing, attitudes towards death, personality traits, holistic health and wellbeing, connectedness, demoralisation, expectations, qualitative data and safety measures) will be assessed at baseline and through to the end of the protocol. Participants will be followed up until either 12 months post-randomisation or death, whichever occurs first. Discussion This study will examine the effect of MDMA-assisted therapy on symptoms of anxiety and depression in advanced-stage cancer. Potential therapeutic implications include establishing the safety and effectiveness of a novel treatment that may relieve mental suffering in patients with life-threatening illness. Trial registration Trial registered on Australian New Zealand Clinical Trials Registry. Registration number: ACTRN12619001334190p. Date registered: 30/09/2019. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378153&showOriginal=true&isReview=true

Background There has been a resurgence of research into the potential therapeutic benefits of psychedelics for neuropsychiatric disorders. Classic psychedelics, such as psilocybin, exert complex effects on higher cognitive functions such as perception and awareness, but their impact on motor function remains unexplored. Moreover, there is a theoretical rationale for using psychedelics to promote motor retraining in certain neuropsychiatric conditions associated with motor dysfunction. This protocol paper outlines the first study to investigate the feasibility and safety of performing movement tasks during the acute effects of psilocybin in healthy participants. The findings from this study will further our understanding of the impact of psychedelics on motor function, and inform future studies that combine classic psychedelics with motor retraining in clinical populations. Methods 12 healthy participants will each receive three doses of psilocybin (between 5 and 20 mg) in a randomized order, with each dose administered at least 1 week apart. Participants, the trial physiotherapists, and statisticians will remain blinded to the psilocybin dose. A battery of measures assessing motor function will be completed during the acute drug effects. In addition, measures of safety, pre‐ and post‐dose resting‐state brain activity via functional magnetic resonance imaging, and participants' subjective experience will be assessed. Highlights Psychedelics may promote motor retraining in certain neuropsychiatric disorders. No clinical studies have investigated the impact of psychedelics on motor function. This study will assess the performance of movement tasks during the acute effects of psilocybin in healthy participants. This will inform the design of a follow‐up study of psilocybin‐assisted physiotherapy in motor functional neurological disorder. The findings will inform future trials exploring psychedelics to assist motor retraining in other neuropsychiatric disorders with associated motor dysfunction.

Background Insomnia is associated with significant comorbidity, disability and impact on quality of life and, despite advances in pharmacotherapy and psychotherapy, remains a significant burden to society. Cannabinoids are gaining acceptance for use as medicines in the treatment of insomnia disorder. Objective We conducted a systematic review and meta-analysis to evaluate the efficacy of cannabinoids in the treatment of insomnia disorder. Methods We performed a systematic review of the PubMed, Cochrane Library, MEDLINE, and Cumulative Index to Nursing and Allied Health Literature Complete databases from inception to 5 December 2019, and again prior to data abstraction, for studies of cannabis-based products for the treatment of insomnia disorder in adults. Inclusion criteria were (1) clinical studies, (2) participants aged ≥ 18 years, (3) insomnia disorder either formally diagnosed against contemporaneous diagnostic criteria or quantified with validated instruments and (4) compared cannabis-based products with the standard of care, placebo or a sedative. No language restrictions were imposed. Non-primary research, animal studies and studies of cannabis-induced insomnia were excluded. Risk of bias was assessed using the RoB 2 tool for randomised controlled trials (RCTs) and Risk of Bias in Non-randomized Studies—of Interventions (ROBINS-I) tool for non-randomized trials. Heterogeneity was assessed with the I 2 statistic . Results A total of five studies (two RCTs and three non-randomised studies) with 219 study participants were included, of which three could be combined. The three non-randomised studies contributed data on the Pittsburgh Sleep Quality Index Questionnaire score, showing a favourable effect of cannabinoids at ≤ 4 weeks of follow-up (mean difference − 1.89 [95% confidence interval {CI} − 2.68 to − 1.10]; n  = 176) and at 8 weeks of follow-up (mean difference − 2.41 [95% CI − 3.36 to − 1.46]; n  = 166). One double-blind crossover RCT ( n  = 32) reported that, compared with amitriptyline, nabilone—a synthetic analogue to tetrahydrocannabinol (THC)—improved Insomnia Severity Index scores after 2 weeks of treatment (adjusted difference − 3.25 [95% CI − 5.26 to − 1.24]) and resulted in a more restful sleep as a sub-measure of the Leeds Sleep Evaluation Questionnaire (LSEQ) (difference 0.48 [95% CI 0.01–0.95]) but with no effect on overall sleep quality as measured by the LSEQ. In a single ascending-dose RCT ( n  = 9), THC reduced sleep-onset latency compared with placebo at 10 mg, 20 mg and 30 mg doses (mean difference − 43.00 min [95% CI − 82.76 to − 3.24], − 62.00 [95% CI − 103.60 to − 20.40] and − 54.00 [95% CI − 103.93 to − 4.07], respectively). All the included studies were assessed as poor quality, mainly due to small sample sizes, short treatment periods, uncertain clinical significance and high risk of bias. Conclusions Few studies have examined the efficacy of cannabinoids in the treatment of insomnia disorder. Despite some possible signals for efficacy, the heterogeneity of participants, interventions, efficacy outcomes and results, and the high risk of bias across included trials, do not reliably inform evidence-based practice. This review highlights shortcomings in the existing literature, including lack of diagnostic clarity, poorly defined participant groups, non-standardised interventions and studies of inappropriate design, duration and power to detect clinically meaningful outcomes. Further research in the form of high-quality RCTs are required before drawing any conclusions about the efficacy of cannabinoids in the treatment of insomnia disorder. Trial Registration PROSPERO registration number, CRD42020161043.