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
Summary
Psychedelics like Psilocybin and other Tryptamines may be safer than commonly perceived. A review of 3032 manuscripts, distilling 33 useful articles, found no established lethal dose for common hallucinogens such as LSD. While MDMA appears more dangerous, often linked to recreational use, its toxicology is complicated by context. These substances, pivotal in Drug Studies and emerging Medicine, influence neurotransmitter receptors, showing promise in Psychology and Psychiatry. Pharmacology suggests danger lies less in chemical synthesis and alkaloids, and more in "set and setting" than dose alone.
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.