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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.

Psychedelic and mindfulness interventions have been shown to improve mental ill-health and wellbeing, with a range of clinical processes and effects in common. However, each appear to contain specific challenges in the context of mental health treatment. In this Perspective, we focus on a set of distinct affordances, “useful differences”, within psychedelic and mindfulness interventions that might address common challenges within the other intervention. Accordingly, we propose a set of applied synergies, indicating specific ways in which these two promising interventions might be combined for greater benefit. Metaphorically, on the journey toward mental health and wellbeing, we propose that psychedelic treatments may serve the role of Compass (initiating, motivating, and steering the course of mindfulness practice), with mindfulness interventions serving the role of Vehicle (integrating, deepening, generalizing, and maintaining the novel perspectives and motivation instigated by psychedelic experience). We outline a set of testable hypotheses and future research associated with the synergistic action of psychedelic and mindfulness interventions toward improved clinical outcomes.

Background Mobile apps for problematic substance use have the potential to bypass common barriers to treatment seeking. Ten years following the release of the first app targeting problematic tobacco, alcohol, and illicit drug use, their effectiveness, use, and acceptability remains unclear. Objective This study aims to conduct a systematic literature review of trials evaluating mobile app interventions for problematic tobacco, alcohol, and illicit drug use. Methods The review was conducted according to recommended guidelines. Relevant databases were searched, and articles were included if the mobile app study was a controlled intervention trial and reported alcohol, tobacco, or illicit drug consumption as outcomes. Results A total of 20 studies met eligibility criteria across a range of substances: alcohol (n=11), tobacco (n=6), alcohol and tobacco (n=1), illicit drugs (n=1), and illicit drugs and alcohol (n=1). Samples included the general community, university students, and clinical patients. The analyzed intervention sample sizes ranged from 22 to 14,228, and content was considerably diverse, from simple stand-alone apps delivering self-monitoring or psychoeducation to multicomponent apps with interactive features and audio content, or used as adjuncts alongside face-to-face treatment. Intervention duration ranged from 1 to 35 weeks, with notifications ranging from none to multiple times per day. A total of 6 of the 20 app interventions reported significant reductions in substance use at post or follow-up compared with a comparison condition, with small to moderate effect sizes. Furthermore, two other app interventions reported significant reductions during the intervention but not at post treatment, and a third reported a significant interaction of two app intervention components. Conclusions Although most app interventions were associated with reductions in problematic substance use, less than one-third were significantly better than the comparison conditions at post treatment. A total of 5 out of the 6 apps that reported intervention effects targeted alcohol (of those, one targeted alcohol and illicit drugs and another alcohol and tobacco) and 1 targeted tobacco. Moreover, 3 out of 6 apps included feedback (eg, personalized) and 2 had high risk of bias, 1 some risk, and 3 low risk. All 6 apps included interventions of 6 weeks or longer. Common study limitations were small sample sizes; risk of bias; lack of relevant details; and, in some cases, poorly balanced comparison conditions. Appropriately powered trials are required to understand which app interventions are most effective, length of engagement required, and subgroups most likely to benefit. In sum, evidence to date for the effectiveness of apps targeting problematic substance use is not compelling, although the heterogeneous comparison conditions and trial designs across studies limit the ability to compare efficacy between apps. We discuss potential approaches that can help ascertain whether the promise of mobile app interventions for problematic substance use can be fulfilled.

Anorexia nervosa (AN) has the highest mortality rate of any psychiatric disease, yet available pharmacological treatments are largely ineffective due, in part, to an inadequate understanding of the neurobiological drivers that underpin the condition. The recent resurgence of research into the clinical applications of psychedelic medicine for a range of mental disorders has highlighted the potential for classical psychedelics, including psilocybin, to alleviate symptoms of AN that relate to serotonergic signaling and cognitive inflexibility. Clinical trials using psychedelics in treatment-resistant depression have shown promising outcomes, although these studies are unable to circumvent some methodological biases. The first clinical trial to use psilocybin in patients with AN commenced in 2019, necessitating a better understanding of the neurobiological mechanisms through which psychedelics act. Animal models are beneficial in this respect, allowing for detailed scrutiny of brain function and behavior and the potential to study pharmacology without the confounds of expectancy and bias that are impossible to control for in patient populations. We argue that studies investigating the neurobiological effects of psychedelics in animal models, including the activitybased anorexia (ABA) rodent model, are particularly important to inform clinical applications, including the subpopulations of patients that may benefit most from psychedelic medicine.

Thanks to Mark Yates and Melissa Latham for reading earlier versions of the manuscript.

In the quest for new treatment options for depression, attention is being paid to the potential role of psychedelic drugs. Psilocybin is of particular interest given its mechanism of action, its benefits in early trials and its relatively low side effects burden. This viewpoint outlines a number of key issues that remain to be elucidated about its potential use in the clinical environment, including clarification of the profile of people most likely to benefit and those who might experience adverse effects, longer-term outcomes and the role of psychotherapeutic input alongside the drug itself. There are also opportunities to understand better, the neurobiology underpinning its effects.