Harnessing Pharmacogenomics in Clinical Research on Psychedelic‐Assisted Therapy
Andreas Halman, Rachel Conyers, Claire Moore, Dhrita Khatri, Jerome Sarris, Daniel Perkins
Clinical Pharmacology & Therapeutics September 30, 2024 DOI: 10.1002/cpt.3459 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | MDMA Psilocybin Psychedelic-assisted therapy |
| Keywords | Pharmacology Pharmacogenomics Hallucinogen Pharmacodynamics Dosing Cyp2d6 Pharmacokinetics |
| Citations | 13 |
| Key findings | Genetic variants in drug-metabolizing enzymes impact the intensity of acute psychedelic effects for LSD and ibogaine, and a dose reduction for CYP2D6 poor metabolizers may be appropriate. |
Abstract
Psychedelics have recently re‐emerged as potential treatments for various psychiatric conditions that impose major public health costs and for which current treatment options have limited efficacy. At the same time, personalized medicine is increasingly being implemented in psychiatry to provide individualized drug dosing recommendations based on genetics. This review brings together these topics to explore the utility of pharmacogenomics (a key component of personalized medicine) in psychedelic‐assisted therapies. We summarized the literature and explored the potential implications of genetic variability on the pharmacodynamics and pharmacokinetics of psychedelic drugs including lysergic acid diethylamide (LSD), psilocybin, N,N ‐dimethyltryptamine (DMT), 5‐methoxy‐ N,N ‐dimethyltryptamine (5‐MeO‐DMT), ibogaine and 3,4‐methylenedioxymethamphetamine (MDMA). Although existing evidence is limited, particularly concerning pharmacodynamics, studies investigating pharmacokinetics indicate that genetic variants in drug‐metabolizing enzymes, such as cytochrome P450, impact the intensity of acute psychedelic effects for LSD and ibogaine, and that a dose reduction for CYP2D6 poor metabolizers may be appropriate. Furthermore, based on the preclinical evidence, it can be hypothesized that CYP2D6 metabolizer status might contribute to altered acute psychedelic experiences with 5‐MeO‐DMT and psilocybin when combined with monoamine oxidase inhibitors. In conclusion, considering early evidence that genetic factors can influence the effects of certain psychedelics, we suggest that pharmacogenomic testing should be further investigated in clinical research. This is necessary to evaluate its utility in improving the safety and therapeutic profile of psychedelic therapies and a potential future role in personalizing psychedelic‐assisted therapies, should these treatments become available.
Comparable studies
Other narrative reviews on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Human Pharmacology of MDMA | 2004 | Review | |
| Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research | 2001 | Review | |
| 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans | 1994 | Review | |
| (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals | 2000 | Review | |
| Amphetamine toxicities | 2010 | Review |
Citations in the library
Cited by 11
- Population pharmacokinetic-pharmacodynamic modeling of co-administered N,N-dimethyltryptamine and harmine in healthy subjects. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie July 9, 2025
- Rare but relevant: Ibogaine and cardiovascular complications-prolonged QT interval and ventricular arrhythmias. Addiction January 20, 2026
- Commentary on Methods for Addressing Functional Unblinding and Mechanistic Uncertainty in Clinical Trials of Psychedelic-Assisted Treatments Current Treatment Options in Psychiatry November 11, 2025
- Subjective and neurocognitive profiling of clinical doses of 3,4-methylenedioxymethamphetamine (MDMA) in healthy volunteers: implications for therapeutic use Molecular Psychiatry April 8, 2026
- Optimized Parenteral and Intranasal Formulations of Tryptamine Psychedelics for Rapid-Acting Antidepressant Therapy. ACS Medicinal Chemistry Letters June 12, 2025
and 6 more in the library
Cites 47
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Global Street Food: la cocina de la calle Diseño interior 2009
and 42 more in the library