Neurobiological research on N,N-dimethyltryptamine (DMT) and its potentiation by monoamine oxidase (MAO) inhibition: from ayahuasca to synthetic combinations of DMT and MAO inhibitors.
Klemens Egger, Helena Aicher, Paul Cumming, Milan Scheidegger
Cellular and Molecular Life Sciences September 10, 2024 DOI: 10.1007/s00018-024-05353-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Peer reviewed |
|---|---|
| Topics | Ayahuasca DMT 5-MeO-DMT |
| Keywords | Psychedelics entheogens Hallucinogens Harmine Mao inhibition Β-carbolines Psychoactive substances Neuroscience brain chemistry Neuropharmacology Traditional medicine ethnobotany Indigenous healing Plant medicine |
| Citations | 30 |
| Key findings | DMT's psychoactive effects arise from serotonin receptor agonism, and its oral bioavailability is greatly increased by co-administration with MAO-A inhibitors, with synergistic effects that may promote neuroplasticity and therapeutic efficacy. |
Abstract
The potent hallucinogen N,N-dimethyltryptamine (DMT) has garnered significant interest in recent years due to its profound effects on consciousness and its therapeutic psychopotential. DMT is an integral (but not exclusive) psychoactive alkaloid in the Amazonian plant-based brew ayahuasca, in which admixture of several β-carboline monoamine oxidase A (MAO-A) inhibitors potentiate the activity of oral DMT, while possibly contributing in other respects to the complex psychopharmacology of ayahuasca. Irrespective of the route of administration, DMT alters perception, mood, and cognition, presumably through agonism at serotonin (5-HT) 1A/2A/2C receptors in brain, with additional actions at other receptor types possibly contributing to its overall psychoactive effects. Due to rapid first pass metabolism, DMT is nearly inactive orally, but co-administration with β-carbolines or synthetic MAO-A inhibitors (MAOIs) greatly increase its bioavailability and duration of action. The synergistic effects of DMT and MAOIs in ayahuasca or synthetic formulations may promote neuroplasticity, which presumably underlies their promising therapeutic efficacy in clinical trials for neuropsychiatric disorders, including depression, addiction, and post-traumatic stress disorder. Advances in neuroimaging techniques are elucidating the neural correlates of DMT-induced altered states of consciousness, revealing alterations in brain activity, functional connectivity, and network dynamics. In this comprehensive narrative review, we present a synthesis of current knowledge on the pharmacology and neuroscience of DMT, β-carbolines, and ayahuasca, which should inform future research aiming to harness their full therapeutic potential.
Comparable studies
Other narrative reviews on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Neuropharmacology of N,N-dimethyltryptamine | 2016 | Review | |
| N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function Humans and animals (general) | 2018 | Review | |
| Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Humans (pharmacokinetics) | 2010 | Review | |
| Dark Classics in Chemical Neuroscience:N,N-Dimethyltryptamine (DMT) | 2018 | Review | |
| A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity. | 2013 | Review |
Citations in the library
Cited by 22
- Exploring DMT: Endogenous role and therapeutic potential. Neuropharmacology May 1, 2025
- Examining the pharmacokinetic and pharmacodynamic interaction of N,N-dimethyltryptamine and harmine in healthy volunteers: Α factorial dose-escalation study. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie March 1, 2025
- Pharmacokinetics and pharmacodynamics of an innovative psychedelic N,N-dimethyltryptamine/harmine formulation in healthy participants: a randomized controlled trial. The International Journal of Neuropsychopharmacology December 28, 2024
- An overview of psilocybin, LSD, MDMA, and ketamine in revitalizing psychedelic-assisted therapy: Insights, limitations and future directions. Progress in Neuro-Psychopharmacology and Biological Psychiatry July 25, 2025
- Clinical Pharmacokinetics of N,N-Dimethyltryptamine (DMT): A Systematic Review and Post-hoc Analysis. Clinical Pharmacokinetics February 1, 2025
and 17 more in the library
Cites 167
- Meditation experience is associated with differences in default mode network activity and connectivity Proceedings of the National Academy of Sciences November 23, 2011
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
and 162 more in the library