From taboo to treatment: The emergence of psychedelics in the management of pain and opioid use disorder.

Chronic pain and opioid use disorder (OUD) are two interconnected public health crises that lack effective treatments. This review examines whether psychedelics could serve as novel therapeutics by acting on shared brain mechanisms underlying both conditions. Preclinical and human evidence suggests psychedelics may reverse pain- and opioid-induced neuroadaptations like central sensitization. The authors map how psychedelics could modulate overlapping dimensions of pain (sensory, affective, cognitive) and opioid-related phenomena (craving, withdrawal). They note a scarcity of controlled studies but propose mechanistic insights and methodological guidelines for future clinical trials. The goal is to accelerate development of alternatives to opioids amid the escalating crisis.

Study at a glance

Abstract

The rise of psychedelics in contemporary medicine has sparked interest in their potential therapeutic applications. While traditionally associated with countercultural movements and recreational use, recent research has shed light on the potential benefits of psychedelics in various mental health conditions. In this review, we explore the possible role of psychedelics in the management of chronic pain and opioid use disorder (OUD), 2 critical areas in need of innovative treatment options. Pain control remains a significant clinical challenge, particularly for individuals with OUD and those who receive long-term opioid therapy who develop marked tolerance to opioid-induced analgesia. Despite the magnitude of this problem, there is a scarcity of controlled studies investigating pain management alternatives for these populations. Drawing from preclinical and human evidence, we highlight the potential of psychedelics to act on shared neurobiological substrates of chronic pain and OUD, potentially reversing pain- and opioid-induced neuroadaptations, such as central sensitization. We elaborate on the multifaceted dimensions of the pain experience (sensory, affective and cognitive) and their intersections that overlap with opioid-related phenomena (opioid craving and withdrawal), hypothesizing how these processes can be modulated by psychedelics. After summarizing the available clinical research, we propose mechanistic insights and methodological considerations for the design of future translational studies and clinical trials, building on a shared clinical and neurobiological understanding of chronic pain and OUD. Our intention is to provide timely perspectives that accelerate the development and exploration of novel therapeutics for chronic pain and OUD amidst the escalating opioid crisis.