Psychedelics as pharmacotherapeutics for substance use disorders: a scoping review on clinical trials and perspectives on underlying neurobiology
Lucas M Wittenkeller, Gary A. Gudelsky, John T. Winhusen, Davide Amato
medRxiv April 6, 2025 preprint DOI: 10.1101/2025.04.04.25324315 via OpenAlex
Summary
Psychedelics are being tested for treating substance use disorders (SUDs) due to their potential to alter consciousness and cognitive processes. Current clinical trials and literature suggest that psychedelics may restore dopamine homeostasis, which could reduce drug-seeking behavior and encourage abstinence. However, the neurobiological mechanisms behind their therapeutic effects remain largely uncharacterized.
Study at a glance
| Design | scoping review |
|---|---|
| Population | clinical trials utilizing classic psychedelics as interventions for substance use disorders |
| Key finding | Psychedelics may blunt drug-seeking behavior and promote drug abstinence by restoring dopamine homeostasis. |
Abstract
Abstract Psychedelics have garnered great attention in recent years as treatments for major depressive disorder and treatment-resistant depression due to their ability to alter consciousness and afflicted cognitive processes with lasting effects. Given these unique characteristics and the urgent need for efficacious treatments, psychedelics are being tested for a variety of psychiatric conditions, including substance use disorders (SUDs). Despite promising results and growing interest, the neurobiological mechanisms underlying therapeutic efficacy of psychedelics remain uncharacterized. Using a scoping review approach, we summarize current clinical trials registered at ClinicalTrials.gov that utilize classic psychedelics as interventions for SUDs with the goal of understanding the current state and outlook of the field. A second scoping review was conducted using PubMed and SCOPUS databases to identify the relevant publications addressing the pharmacotherapeutic potential of restoring dopamine homeostasis as a novel neurobiological mechanism of psychedelics. This mechanism may blunt drug-seeking behavior, promote drug abstinence, and underlie their clinical relevance for SUD in addition to previously characterized mechanisms.