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

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.

Uso da psilocibina no tratamento de transtornos psiquiátricos: Revisão da literatura

“…Foi demonstrado que o coelho é mais sensível, com DL50, por via intravenosa, de 13 mg/kg. Para o rato o valor da DL50, por via intravenosa foi de 280 mg/kg; estima-se que uma pessoa de 60 kg precisaria ingerir até 17 kg de cogumelos frescos para que essa dose fosse alcançada (Henríquez-Hernández et al, 2023).…”

“…Com respeito à espécie humana, 30-40 mg de psilocibina é considerada uma dose elevada, sugerindo que, em comparação com os dados obtidos em animais, somos uma espécie particularmente suscetível. Em voluntários humanos, a dose tóxica não letal (DTL0) de psilocibina foi estabelecida em 60 µg/kg (por via oral), 37 µg/kg (por via intraperitoneal) e 75 µg/kg Research, Society and Development, v. 13, n. 2, e2813244971, 2024 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org /10.33448/rsd-v13i2.44971 (por via intramuscular) (Henríquez-Hernández et al, 2023).…”

“…A psilocibina situa-se entre os psicodélicos mais potentes (apresenta efetividade em doses muito baixas) e, curiosamente, está entre aqueles com maior margem de segurança. No relato histórico por Henríquez-Hernández et al (2023), observa-se que entre humanos, ocorreram muito poucas mortes associadas ao uso de psilocibina.…”

Ayahuasca in the treatment of bipolar disorder with psychotic features–A retrospective case study

“…Also, psilocybin and LSD appear to be relatively safe in combination with ayahuasca. Henríquez-Hernández et al recently discussed general aspects of toxicology of psychedelics (Henríquez-Hernández et al, 2023).…”

The Identification of Drug Abuse

“…The review by Henríquez-Hernández and coll. discusses health-hazardous doses of psychedelic substances, with particular attention paid to ergolamines, simple tryptamines, and phenylethylamines [ 10 ].…”