Clinical Trial Design Challenges and Opportunities for Emerging Treatments for Opioid Use Disorder: A Review.
Brian D Kiluk, Bethea A Kleykamp, Sandra D Comer, Roland R. Griffiths, Andrew S Huhn, Matthew W Johnson, Kyle M Kampman, Marco Pravetoni, Kenzie L Preston, Ryan Vandrey, Cecilia L Bergeria, Michael P. Bogenschutz, Randall Brown, Kelly E Dunn, Robert H. Dworkin, Patrick H. Finan, Peter S. Hendricks, Elisabeth J Houtsmuller, Thomas R Kosten, Dustin C Lee, Frances R. Levin, Aimee Mcrae-Clark, Charles L. Raison, Kurt Rasmussen, Dennis C Turk, Roger D Weiss, Eric C. Strain
JAMA Psychiatry 2023 DOI: 10.1001/jamapsychiatry.2022.4020 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Addiction |
| Citations | 22 |
| Key findings | Consensus recommendations for clinical trial design of novel OUD treatments targeting non-MOR systems emphasize specifying treatment stage, role, patient-informed outcomes, and safety monitoring. |
Abstract
Novel treatments for opioid use disorder (OUD) are needed to address both the ongoing opioid epidemic and long-standing barriers to existing OUD treatments that target the endogenous μ-opioid receptor (MOR) system. The goal of this review is to highlight unique clinical trial design considerations for the study of emerging treatments for OUD that address targets beyond the MOR system. In November 2019, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the US Food and Drug Administration sponsored a meeting to discuss the current evidence regarding potential treatments for OUD, including cannabinoids, psychedelics, sedative-hypnotics, and immunotherapeutics, such as vaccines. Consensus recommendations are presented regarding the most critical elements of trial design for the evaluation of novel OUD treatments, such as: (1) stage of treatment that will be targeted (eg, seeking treatment, early abstinence/detoxification, long-term recovery); (2) role of treatment (adjunctive with or independent of existing OUD treatments); (3) primary outcomes informed by patient preferences that assess opioid use (including changes in patterns of use), treatment retention, and/or global functioning and quality of life; and (4) adverse events, including the potential for opioid-related relapse or overdose, especially if the patient is not simultaneously taking maintenance MOR agonist or antagonist medications. Applying the recommendations provided here as well as considering input from people with lived experience in the design phase will accelerate the development, translation, and uptake of effective and safe therapeutics for individuals struggling with OUD.
Comparable studies
Other narrative reviews on addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Mindfulness meditation–based pain relief: a mechanistic account | 2016 | Review | |
| Psychedelics as anti-inflammatory agents Animal models and cellular studies | 2018 | Review | |
| A narrative review of yoga and mindfulness as complementary therapies for addiction. | 2013 | Review | |
| The neuropsychopharmacology of cannabis: A review of human imaging studies | 2018 | Review |
Citations in the library
Cited by 4
- From taboo to treatment: The emergence of psychedelics in the management of pain and opioid use disorder. British Journal of Clinical Pharmacology December 1, 2024
- Effects of psychedelics on opioid use disorder: a scoping review of preclinical studies. Cellular and Molecular Life Sciences January 21, 2025
- The therapeutic effects of psychedelics for opioid use disorder: A systematic review of clinical studies. Psychiatry Research June 1, 2025
- Effects of Psychedelics Lysergic Acid Diethylamide and R (–)-2,5-Dimethoxy-4-Iodoamphetamine on Oral Opioid Consumption and Naloxone-Precipitated Withdrawal in Male C57Bl/6J Mice Psychedelic Medicine March 28, 2026
Cites 13
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials Journal of Psychopharmacology March 8, 2012
- Psychedelics as Medicines: An Emerging New Paradigm Clinical Pharmacology & Therapeutics November 4, 2016
- Clinical applications of hallucinogens: A review. Experimental and Clinical Psychopharmacology August 1, 2016
- Psychedelics: Where we are now, why we got here, what we must do Neuropharmacology February 21, 2018
and 8 more in the library