Evaluating the abuse potential of psychedelic drugs as part of the safety pharmacology assessment for medical use in humans.
David J Heal, Jane Gosden, Sharon L. Smith
Neuropharmacology November 2018 DOI: 10.1016/j.neuropharm.2018.01.049 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Addiction |
| Keywords | 5-ht2a agonist Abuse testing Drug-discrimination Nmda antagonist Psychedelic Self-administration Κ-opioid agonist |
| Key findings | Argues that although psychedelic abuse is documented, no systematic preclinical and clinical evaluation exists of the abuse and dependence risks these drugs pose in a medical-use setting. The authors describe the non-clinical tests regulators require, including drug-discrimination, intravenous self-administration, and physical dependence liability, and critically review FDA's 2017 guidance on abuse/dependence evaluation. |
Abstract
Psychedelics comprise drugs come from various pharmacological classes including 5-HT2A agonists, indirect 5-HT agonists, e.g., MDMA, NMDA antagonists and κ-opioid receptor agonists. There is resurgence in developing psychedelics to treat psychiatric disorders with high unmet clinical need. Many, but not all, psychedelics are schedule 1 controlled drugs (CDs), i.e., no approved medical use. For existing psychedelics in development, regulatory approval will require a move from schedule 1 to a CD schedule for drugs with medical use, i.e., schedules 2-5. Although abuse of the psychedelics is well documented, a systematic preclinical and clinical evaluation of the risks they pose in a medical-use setting does not exist. We describe the non-clinical tests required for a regulatory evaluation of abuse/dependence risks, i.e., drug-discrimination, intravenous self-administration and physical dependence liability. A synopsis of the existing data for the various types of psychedelics is provided and we describe our findings with psychedelic drugs in these models. FDA recently issued its guidance on abuse/dependence evaluation of drug-candidates (CDER/FDA, 2017). We critically review the guidance, discuss the impact this document will have on non-clinical abuse/dependence testing, and offer advice on how non-clinical abuse/dependence experiments can be designed to meet not only the expectations of FDA, but also other regulatory agencies. Finally, we offer views on how these non-clinical tests can be refined to provide more meaningful information to aid the assessment of the risks posed by CNS drug-candidates for abuse and physical dependence. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'.
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
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- Reviewing the Potential of Psychedelics for the Treatment of PTSD The International Journal of Neuropsychopharmacology March 12, 2020
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- Psychedelics, Sociality, and Human Evolution Frontiers in Psychology September 29, 2021
- Positive psychology in the investigation of psychedelics and entactogens: A critical review Neuropharmacology November 1, 2018
and 34 more in the library
Cites 84
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder JAMA Psychiatry April 16, 2014
- Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder The Journal of Clinical Psychiatry July 13, 2010
- A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression American Journal of Psychiatry April 8, 2016
and 79 more in the library