Potentiation of 5-methoxy-N,N-dimethyltryptamine-induced hyperthermia by harmaline and the involvement of activation of 5-HT1A and 5-HT2A receptors

Summary & key facts

Researchers gave a fast-acting psychedelic called 5‑MeO‑DMT to animals and measured body temperature. When they gave harmaline, a drug that blocks the enzyme that normally breaks down these psychedelics, the body‑temperature rise got bigger. They also used drugs that block two kinds of serotonin receptors and found that both receptor types helped cause the overheating. The work shows that mixing a monoamine‑oxidase inhibitor like harmaline with a tryptamine such as 5‑MeO‑DMT can greatly increase the risk of dangerous overheating, and that this effect involves activation of two specific serotonin receptors.

Key facts:

• 5‑MeO‑DMT by itself caused a rise in body temperature in the animals used in the study.
• Giving harmaline at the same time made the temperature rise much larger. Harmaline is a drug that blocks the enzyme that normally breaks down compounds like 5‑MeO‑DMT.
• Blocking either of two serotonin receptor types, called 5‑HT1A and 5‑HT2A, reduced the overheating, which means both receptor types help produce the temperature increase.
• The study was done in animals, not people, so the results show a biological risk but do not prove the exact effects or sizes of effects in humans.
• Because harmaline is one ingredient found in traditional plant brews like ayahuasca, the study helps explain why mixing a monoamine‑oxidase inhibitor with a powerful tryptamine can raise safety concerns about overheating.

Topics

Ion channel regulation and function Neurotransmitter Receptor Influence on Behavior Pharmacological Receptor Mechanisms and Effects

Categories

Cellular and Molecular Neuroscience Life Sciences Neuroscience

Tags

5-HT receptor Agonist Antagonist Chemistry Clorgyline Cyproheptadine Endocrinology Harmaline Hyperthermia Hypothermia Internal medicine Ketanserin Medicine Pharmacology Quipazine Receptor Receptor antagonist Serotonin Thermoregulation

Substances

Ayahuasca Other