Novel, Unifying Mechanism for Mescaline in The Central Nervous System: Electrochemistry, Catechol Redox Metabolite, Receptor, Cell Signaling and Structure Activity Relationships
Peter Kovacic, Ratnasamy Somanathan
Oxidative Medicine and Cellular Longevity 2009 DOI: 10.4161/oxim.2.4.9380 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Intervention | Mescaline |
| Topics | Mescaline Psilocybin |
| Keywords | Metabolite Receptor Signal transduction Mechanism of action Biochemistry Quinone Pharmacology Hallucinogen Biophysics Stereochemistry |
| Citations | 34 |
| Key points | Proposes that mescaline's mechanism of action involves electron transfer via redox cycling of its catechol metabolite with a quinone, aligning with structure-activity relationships of abused drugs and catecholamines. |
Abstract
A unifying mechanism for abused drugs has been proposed previously from the standpoint of electron transfer. Mescaline can be accommodated within the theoretical framework based on redox cycling by the catechol metabolite with its quinone counterpart. Electron transfer may play a role in electrical effects involving the nervous system in the brain. This approach is in accord with structure activity relationships involving mescaline, abused drugs, catecholamines and etoposide. Inefficient demethylation is in keeping with the various drug properties, such as requirement for high dosage and slow acting. There is a discussion of receptor binding, electrical effects, cell signaling and other modes of action. Mescaline is a nonselective, seretonin receptor agonist. 5‐HTP receptors are involved in the stimulus properties. Research addresses the aspect of stereochemical requirements. Receptor binding may involve the proposed quinone metabolite and/or the amino sidechain via protonation. Electroencephalographic studies were performed on the effects of mescaline on men. Spikes are elicited by stimulation of a cortical area. The potentials likely originate in nonsynaptic dendritic membranes. Receptor‐mediated signaling pathways were examined which affect mescaline behavior. The hallucinogen belongs to the class of 2AR agonists which regulate pathways in cortical neurons. The research identifies neural and signaling mechanisms responsible for the biological effects. Recently, another hallucinogen, psilocybin, has been included within the unifying mechanistic framework. This mushroom constituent is hydrolyzed to the phenol psilocin, also active, which is subsequently oxidized to an ET o‐quinone or iminoquinone.
Comparable studies
Other theoretical and historical papers on mescaline, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Schizophrenia: A New Approach. II. Result of a Year's Research | 1954 | Theoretical or philosophical paper | |
| Thought insertion as a self-disturbance: An integration of predictive coding and phenomenological approaches | 2016 | Theoretical or philosophical paper | |
| Entactogens: How the Name for a Novel Class of Psychoactive Agents Originated | 2022 | Theoretical or philosophical paper | |
| Steric and Electronic Relationships among Some Hallucinogenic Compounds | 1970 | Theoretical or philosophical paper | |
| EFFECT OF DRUGS One individual | 1952 | Theoretical or philosophical paper | n = 1 |
Citations in the library
Cited by 11
- Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants. Neuropsychopharmacology October 1, 2023
- Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions Current Molecular Pharmacology October 15, 2018
- Beating pain with psychedelics: Matter over mind? Neuroscience & Biobehavioral Reviews December 16, 2021
- De novo sequencing and analysis of Lophophora williamsii transcriptome, and searching for putative genes involved in mescaline biosynthesis BMC Genomics September 1, 2015
- Abuse of Magic Mushroom, Peyote Cactus, LSD, Khat, and Volatiles Critical Issues in Alcohol and Drugs of Abuse Testing 2019
and 6 more in the library
Cites 11
- The pharmacology of psilocybin Addiction Biology October 1, 2002
- Dihydrobenzofuran Analogues of Hallucinogens. 4. Mescaline Derivatives Journal of Medicinal Chemistry September 1, 1997
- Mescaline effects on rat behavior and its time profile in serum and brain tissue after a single subcutaneous dose Psychopharmacology October 6, 2007
- Blood Flow and Cerebral Laterality in the Mescaline Model of Psychosis Pharmacopsychiatry July 1, 1998
- Involvement of 5-HT receptor subtypes in the discriminative stimulus properties of mescaline European Journal of Pharmacology 1989
and 6 more in the library