Hallucinogenic potential: a review of psychoplastogens for the treatment of opioid use disorder

The opioid epidemic in the United States persists, with opioid use disorder (OUD) at its core, involving physical addiction, psychological issues, and social-legal problems. Existing treatments have limited effectiveness due to access barriers, strict regimens, and failure to address non-pharmacological aspects. A growing body of research suggests hallucinogens, particularly psychoplastogens like ibogaine, ketamine, and classic psychedelics, may offer a unique, holistic alternative by combining pharmacological, neuroplasticity, and psychological mechanisms. However, legal, social, and safety concerns have hindered research. This review examines preclinical and clinical evidence for these compounds in treating OUD, while noting that further research is needed to establish long-term efficacy and proper safety and ethical guidelines.

Study at a glance

Abstract

The United States is entering its fourth decade of the opioid epidemic with no clear end in sight. At the center of the epidemic is an increase in opioid use disorder (OUD), a complex condition encompassing physical addiction, psychological comorbidities, and socioeconomic and legal travails associated with the misuse and abuse of opioids. Existing behavioral and medication-assisted therapies show limited efficacy as they are hampered by lack of access, strict regimens, and failure to fully address the non-pharmacological aspects of the disease. A growing body of research has indicated the potential of hallucinogens to efficaciously and expeditiously treat addictions, including OUD, by a novel combination of pharmacology, neuroplasticity, and psychological mechanisms. Nonetheless, research into these compounds has been hindered due to legal, social, and safety concerns. This review will examine the preclinical and clinical evidence that psychoplastogens, such as ibogaine, ketamine, and classic psychedelics, may offer a unique, holistic alternative for the treatment of OUD while acknowledging that further research is needed to establish long-term efficacy along with proper safety and ethical guidelines.