Magic mushroom extracts in lipid membranes
Teresa Quynh Tram Nguyen, Frederik W. Lund, Ali Asghar Hakami Zanjani, Himanshu Khandelia
Biochimica et Biophysica Acta (BBA) - Biomembranes May 10, 2022 DOI: 10.1016/j.bbamem.2022.183957 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Computational and experimental study Peer reviewed |
|---|---|
| Topics | Serotonin Psilocybin |
| Keywords | Membrane Tryptamine 5-HT Receptor Stereochemistry Biophysics Biochemistry |
| Citations | 9 |
| Key findings | Both psilocin and serotonin partition into lipid membranes, induce thinning, and depress the melting point, with psilocin's tertiary amine limiting its membrane impact despite greater partitioning. |
Abstract
The active hallucinogen of magic mushrooms, psilocin, is being repurposed to treat nicotine addiction and treatment-resistant depression. Psilocin belongs to the tryptamine class of psychedelic compounds which include the hormone serotonin. It is believed that psilocin exerts its effect by binding to the serotonin 5-HT2A receptor. However, recent in-vivo evidence suggests that psilocin may employ a different mechanism to exert its effects. Membrane-mediated receptor desensitization of neurotransmitter receptors is one such mechanism. We compare the impact of the neutral and charged versions of psilocin and serotonin on the properties of zwitterionic and anionic lipid membranes using molecular dynamics simulations and calorimetry. Both compounds partition to the lipid interface and induce membrane thinning. The tertiary amine in psilocin, as opposed to the primary amine in serotonin, limits psilocin's impact on the membrane although more psilocin partitions into the membrane than serotonin. Calorimetry corroborates that both compounds induce a classical melting point depression like anesthetics do. Our results also lend support to a membrane-mediated receptor-binding mechanism for both psilocin and serotonin and provide physical insights into subtle chemical changes that can alter the membrane-binding of psychedelic compounds.
Comparable studies
Other experimental studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Healthy human volunteers | 1998 | Experimental study | |
| Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | 2000 | Experimental study | |
| Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Rat brain | 1988 | Experimental study | |
| The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Human platelet plasma membrane vesicles and bovine adrenal chromaffin granule membrane... | 1992 | Laboratory study | |
| 5-HT2AReceptor-Mediated Regulation of Brain-Derived Neurotrophic Factor mRNA in the Hippocampus and the Neocortex Rat brain | 1997 | Experimental study |
Citations in the library
Cited by 5
- Interaction of psychedelic tryptamine derivatives with a lipid bilayer Chemistry and Physics of Lipids January 7, 2023
- Molecular insights into the modulation of the 5HT2A receptor by serotonin, psilocin, and the G protein subunit Gqα. FEBS Letters March 1, 2025
- The molecular basis of the antidepressant action of the magic mushroom extract, psilocin. Biochimica et Biophysica Acta. Proteins and Proteomics July 1, 2023
- Spectroscopic behavior of bufotenine and bufotenine N-oxide: Solvent and pH effects and interaction with biomembrane models. Biochimica et Biophysica Acta (BBA) - Biomembranes April 1, 2024
- Psilocybin as serotonergic therapy in epilepsy: Narrative review of potentials and limitations. British Journal of Clinical Pharmacology July 21, 2026
Cites 11
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology November 8, 2017
- Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Proceedings of the National Academy of Sciences April 13, 2021
- Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology May 20, 2016
- Psychedelic Psychiatry's Brave New World. Cell April 1, 2020
and 6 more in the library