Hofmann vs. Paracelsus: Do Psychedelics Defy the Basics of Toxicology?—A Systematic Review of the Main Ergolamines, Simple Tryptamines, and Phenylethylamines
Luis Alberto Henríquez-Hernández, Jaime Rojas-Hernández, Domingo Jesús Quintana Hernández, Lucas F Borkel
Toxics February 3, 2023 DOI: 10.3390/toxics11020148 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Topics | MDMA Psilocybin |
| Keywords | Toxicology Pharmacology Tryptamines Hallucinogen Recreational use |
| Citations | 21 |
| Key findings | For LSD and psilocybin, no dose has been established above which users' lives are endangered, while MDMA appears the most dangerous, though reports are biased by recreational misuse. |
Abstract
Psychedelics are experiencing a strong renaissance and will soon be incorporated into clinical practice. However, there is uncertainty about how much harm they can cause at what doses. This review aimed to collect information on the health-hazardous doses of psychedelic substances, to be aware of the risks to which patients may be subjected. We focused on ergolamines, simple tryptamines, and phenylethylamines. We reviewed articles published in major medical and scientific databases. Studies reporting toxic or lethal doses in humans and animals were included. We followed PRISMA criteria for revisions. We identified 3032 manuscripts for inclusion. Of these, 33 were ultimately useful and gave relevant information about effects associated with high psychedelics doses. Despite having different molecular structures and different mechanisms of action, psychedelics are effective at very low doses, are not addictive, and are harmful at extremely high doses. For LSD and psilocybin, no dose has been established above which the lives of users are endangered. In contrast, MDMA appears to be the most dangerous substance, although reports are biased by recreational missuses. It seems that it is not only the dose that makes the poison. In the case of psychedelics, the set and setting make the poison.
Comparable studies
Other systematic reviews and meta-analyses on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A review of the acute subjective effects of MDMA/ecstasy | 2006 | Systematic review | |
| Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review Patients in clinical trials with MDMA or serotonergic psychedelics | 2022 | Systematic review | n = 598 |
| Treating posttraumatic stress disorder with MDMA-assisted psychotherapy: A preliminary meta-analysis and comparison to prolonged exposure therapy Patients with PTSD | 2016 | Meta-analysis | |
| The neuropsychology of ecstasy (MDMA) use: a quantitative review MDMA users | 2007 | Meta-analysis | |
| Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review | 2022 | Systematic review |
Citations in the library
Cited by 19
- Set and setting predict psychopathology, wellbeing and meaningfulness of psychedelic experiences: a correlational study. Expert Review of Clinical Pharmacology 2024
- Cognitive functioning associated with acute and subacute effects of classic psychedelics and MDMA - a systematic review and meta-analysis. Scientific Reports June 26, 2024
- Therapeutic Potential of Psilocybin for Treating Psychological Distress among Survivors of Adverse Childhood Experiences: Evidence on Acceptability and Potential Efficacy of Psilocybin Use Journal of Psychoactive Drugs October 10, 2023
- Pattern of psychedelic substance use: a comparison between populations in Spain and South America using the Psychedelic Use Scale (PUS) Current Psychology November 21, 2024
- Therapeutic benefit versus epistemic risk: Need for empirical research in psychedelic epistemology. Journal of Psychiatric Research August 1, 2025
and 14 more in the library
Cites 29
- Subjective Reports of the Effects of MDMA in a Clinical Setting Journal of Psychoactive Drugs October 1, 1986
- Adverse effects of psychedelics: From anecdotes and misinformation to systematic science. Journal of Psychopharmacology February 2, 2022
- Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects Neuropsychopharmacology October 15, 2020
- The Background and Chemistry of MDMA Journal of Psychoactive Drugs October 1, 1986
- Modern Clinical Research on LSD Neuropsychopharmacology April 27, 2017
and 24 more in the library