Hofmann vs. Paracelsus: Do Psychedelics Defy the Basics of Toxicology?—A Systematic Review of the Main Ergolamines, Simple Tryptamines, and Phenylethylamines

This review (s=33) of psychedelic compounds (e.g. LSD & psilocybin) finds that they aren’t addictive or toxic at low doses, but can be harmful at high doses. Physiologically the biggest risk was identified for MDMA, though psychological (relating to set & setting) risks may be more critical.

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.

Authors: Luis A. Henríquez-Hernández, Jaime Rojas-Hernández, Domingo J. Quintana-Hernández & Lucas F. Borkel

Summary of Hofmann vs. Paracelsus

Psychedelics are back in the spotlight, and scientific research needs to be effectively focused. Basic research is needed, as well as translational and clinical research, which constitutes the main body of knowledge on these substances.

The toxicity of a drug can be calculated mathematically as the specific ratio between the active dose and the lethal dose, and the lethal dose 50 (LD50 ) is the most important indices. The relationship between effectiveness and toxicity must be well studied to understand the risks and benefits of a medicine.

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