The Resurgence of Hallucinogen Drugs in Clinical Research.
María T Rivera-García, Silvia L. Cruz
Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion 2023 DOI: 10.24875/ric.23000108 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | LSD Mescaline Psilocybin |
| Keywords | Antidepressant effects N,N-Dimethyltryptamine Psychedelics hallucinogens Entheogens Psychedelic drugs Psychological therapy Drug trials Scientific studies Antidepressants mood enhanc |
| Citations | 8 |
| Key findings | Classic hallucinogens activate 5-HT2A receptors, while ketamine has rapid but short-lasting antidepressant effects and reduces suicidal ideation. |
Abstract
Since the dawn of civilization, ancient cultures have utilized hallucinogens from plants and fungi in the context of religious and healing practices. Recently, their use has expanded to other cultures. Hallucinogens are natural or synthetic substances that alter the perception of reality at nontoxic doses, producing intense psychological and physiological effects. The initial research on hallucinogens began in the 1950s. However, their non-medical use, studies without proper controls, and negative social opinion resulted in legal restrictions that limited their use for clinical and preclinical research for more than two decades. A renewed interest in studying hallucinogens as potential therapeutic agents for treating different psychiatric conditions has recently re-emerged. This review summarizes the effects of main hallucinogen drugs and their therapeutic potential. Classic hallucinogens such as LSD, dimethyltryptamine, psilocin, and mescaline have chemical structures similar to serotonin and directly activate 5-hydroxy-tryptamine (5-HT2A) receptors. Ketamine is a dissociative anesthetic with antagonist effects at the glutamatergic N-methyl-D-aspartate receptor, indirectly activating 5-HT2A receptors. Ketamine has rapid antidepressant effects and reduces suicidal ideation, but its effects are short-lasting. Other hallucinogens are under study. It is necessary to continue this research with a more rigorous methodology and include studying the long-term effects of psychedelics use.
Comparable studies
Other narrative reviews on mescaline, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Study of a New Schizophrenomimetic Drug—Sernyl | 1959 | Review | |
| Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways | 2017 | Review | |
| Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine | 2020 | Review | |
| Legal highs: staying on top of the flood of novel psychoactive substances | 2015 | Review | |
| Psychedelic Drugs in Biomedicine | 2017 | Review |
Citations in the library
Cited by 5
- A Comprehensive Review of the Current Status of the Cellular Neurobiology of Psychedelics Biology October 28, 2023
- New perspective on sustained antidepressant effect: focus on neurexins regulating synaptic plasticity Cell Death Discovery May 1, 2024
- Regulatory Challenges of Integrating Psychedelics into Mental Health Sector Psychoactives April 22, 2025
- The Role of Psychedelics in Contemporary Psychological and Interdisciplinary Inquiry. Journal of Personalized Medicine September 28, 2025
- Regulatory Alignment of Psilocybin Clinical Trials in Major Depressive Disorder on ClinicalTrials.gov: A Cross-Sectional Analysis Pharmacopsychiatry April 17, 2025
Cites 36
- 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
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
and 31 more in the library