Psychoactive substances, known for their acute impact on perception and cognition, are gaining attention for their potential therapeutic applications. Many of these substances are plant-derived with deep-rooted histories of use in non-medical contexts, where they have been viewed as either tools for social cohesion or sources of discord, depending on cultural and societal contexts. This review explores psychoactive substances; psychedelics, cannabis, and stimulants, in a legitimized medical context, focusing on the ethical considerations shaping research and the regulatory and prescribing challenges involved in translating these compounds into viable clinical treatments. It highlights the diverse voices; Indigenous, philosophical, psychiatric, and using communities advocating for careful consideration of their broader implications. Key issues include navigating the blurred boundaries between therapeutic benefit and potential misuse, ensuring rigorous scientific methodologies, and addressing the sociopolitical factors shaping public perception and policy. The article emphasizes the need for evidence-based frameworks that balance innovation with patient safety and calls for approaches that recognize the social and commercial determinants of health, extending ethical considerations beyond merely prescribing. By critically assessing the promise and limitations of repurposing these substances, the article contributes to the ongoing discourse on their role in contemporary psychiatric practice.

There has been substantial recent renewed interest and investment to assess the therapeutic potential of psychedelic compounds in addiction disorders. This editorial discusses the available evidence from randomised trials and future research directions in the field, together with potential implications for patients, professionals and the wider addiction treatment system.

What happens when an emerging programme of medical research overlaps with a surging social movement? In this article we draw on the anthropological term ‘chemosociality’ to describe forms of sociality born of shared chemical exposure. Psychedelic administration in the context of recent clinical trials appears to have been particularly chemosocial in nature. We argue that one consequence is that psychedelic-assisted therapy (PAT) clinical research trials tend to breach key assumptions underlying the logic of causal inference used to establish efficacy. We propose the concept of dark loops to describe forms of sociality variously emerging from, and impacting participant experiences in, PAT trials. These dark loops are not recorded, let alone incorporated into the causal pathways in the interpretation of psychedelic trial data to date. We end with three positions which researchers might adopt in response to these issues: chemosocial minimisation where research is designed to attenuate or eliminate the effects of dark loops in trials; chemosocial description where dark loops (and their impacts) are openly and candidly documented and chemosocial valorisation where dark loops are hypothesised to contribute to trial outcomes and actively drawn upon for positive effect. Our goal is to fold in an appreciation of how the increasingly-discussed hype surrounding psychedelic research and therapeutics continues to shape the phenomena under study in complex ways, even as trials become larger and more rigorous in their design.