The possible place for psychedelics in pharmacotherapy of mental disorders.
Pharmacological Reports December 1, 2023 DOI: 10.1007/s43440-023-00550-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | LSD psilocybin DMT 5-MeO-DMT |
| Topics | 5-MeO-DMT DMT Ketamine LSD Psilocybin |
| Keywords | Fast-acting antidepressant drugs Mood disorders Psychedelics Mental health treatment Antidepressants Psychiatric medicine Therapeutic compounds |
| Citations | 10 |
| Key findings | Psychedelic drugs such as LSD, psilocybin, DMT, and 5-MeO-DMT show clinical efficacy and rapid onset after a single administration with fewer side effects than current antidepressants. |
Abstract
Since its emergence in the 1960s, the serotonergic theory of depression bore fruit in the discovery of a plethora of antidepressant drugs affecting the lives of millions of patients. While crucial in the history of drug development, recent studies undermine the effectiveness of currently used antidepressant drugs in comparison to placebo, emphasizing the long time it takes to initiate the therapeutic response and numerous adverse effects. Thus, the scope of contemporary pharmacological research shifts from drugs affecting the serotonin system to rapid-acting antidepressant drugs. The prototypical representative of the aforementioned class is ketamine, an NMDA receptor antagonist capable of alleviating the symptoms of depression shortly after the drug administration. This discovery led to a paradigm shift, focusing on amino-acidic neurotransmitters and growth factors. Alas, the drug is not perfect, as its therapeutic effect diminishes circa 2 weeks after administration. Furthermore, it is not devoid of some severe side effects. However, there seems to be another, more efficient, and safer way to target the glutamatergic system. Hallucinogenic agonists of the 5-HT2A receptor, commonly known as psychedelics, are nowadays being reconsidered in clinical practice, shedding their infamous 1970s stigma. More and more clinical studies prove their clinical efficacy and rapid onset after a single administration while bearing fewer side effects. This review focuses on the current state-of-the-art literature and most recent clinical studies concerning the use of psychedelic drugs in the treatment of mental disorders. Specifically, the antidepressant potential of LSD, psilocybin, DMT, and 5-MeO-DMT will be discussed, together with a brief summary of other possible applications.
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 9
- Psilocybin in pharmacotherapy of obsessive-compulsive disorder Pharmacological Reports August 1, 2024
- Psychedelic therapy - refining the claim of a paradigm shift. International Review of Psychiatry December 1, 2024
- Novel mechanisms underlying rapid-acting antidepressants: ketamine-like compounds, neurosteroid GABAkines, and psychedelics. Drug Discovery Today June 1, 2025
- Perceptual Modifying Compounds and Their Potential Therapeutic Applications in Neuropsychiatric Disorders. ACS Medicinal Chemistry Letters January 11, 2024
- Psilocybin induces stereotyped movements and reduces defensive responding in planarians through 5-hydroxytryptamine mechanisms. Behavioural Pharmacology July 1, 2026
and 4 more in the library
Cites 100
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
and 95 more in the library