Hallucinogenic drugs are partial agonists of the human platelet shape change response: a physiological model of the 5-HT2 receptor.
S J McClue, C Brazell, S M Stahl
Biological Psychiatry July 1, 1989 DOI: 10.1016/0006-3223(89)90042-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro pharmacological assay study Peer reviewed |
|---|---|
| Population | Human blood platelets |
| Interventions | Lysergic acid diethylamide (LSD-25) N N-dimethyltryptamine (N N-DMT) 5-methoxy-N N-dimethyltryptamine (5-MeODMT) 4-iodo-2 5-dimethoxyphenylisopropylamine (DOI) bufotenine mescaline lisuride methysergide lysergic acid cocaine amphetamine phencyclidine |
| Measures | platelet shape change |
| Topics | LSD Serotonin |
| Keywords | Brain Blood platelets Humans Receptors, serotonin Hallucinogens Platelet aggregation Dose-response relationship, drug |
| Key points | Hallucinogens including LSD, N,N-DMT, 5-MeODMT, DOI, bufotenine, and mescaline acted as partial agonists at the platelet 5-HT2 receptor model, whereas structurally similar nonhallucinogens did not. The authors propose that some behavioral effects of LSD-type hallucinogens in humans are due to their actions at 5-HT2 receptors. |
Abstract
We have assayed several phenylalkylamine and indolealkylamine hallucinogens, as well as structurally similar nonhallucinogens, for their effect on human platelet shape change, a physiological model for the central serotonergic 5-HT2 receptor. The hallucinogenic drugs lysergic acid diethylamide (LSD-25), N,N-dimethyltryptamine (N,N-DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), 4-iodo-2,5-dimethoxyphenylisopropylamine (DOI), bufotenine, and mescaline all showed a characteristic 5-HT2 partial agonist effect on platelet shape change. Nonhallucinogens with structural similarity to hallucinogens did not share this profile. Lisuride, methysergide, and lysergic acid showed antagonism of 5-HT-induced shape change, but none were shape change agonists. Other "psychoactive" or mood-altering drugs (cocaine, amphetamine, phencyclidine) showed poor antagonism of 5-HT-induced platelet shape change. This work refines recent ideas that some of the behavioral effects of LSD-type hallucinogens in humans are due to their actions at 5-HT2 receptors and suggests that these hallucinogens are partial 5-HT2 agonists.
Comparable studies
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| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 8
- DOI-Induced Activation of the Cortex: Dependence on 5-HT2AHeteroceptors on Thalamocortical Glutamatergic Neurons Journal of Neuroscience December 1, 2000
- The roles of 5-HT1A and 5-HT2 receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats. Psychopharmacology December 1, 2006
- Bufotenine: toward an understanding of possible psychoactive mechanisms. Journal of Psychoactive Drugs 2000
- Cardiovascular safety of psychedelic medicine: current status and future directions Pharmacological Reports October 24, 2023
- Exploring novel therapeutic strategies: Could psychedelic perspectives offer promising solutions for Alzheimer's disease comorbidities? Dialogues in Clinical Neuroscience March 19, 2025
and 3 more in the library
Cites 4
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- On the Use and Abuse of LSD Archives of General Psychiatry March 1, 1968
- SHAPE CHANGE OF BLOOD PLATELETS—A MODEL FOR CEREBRAL 5‐HYDROXYTRYPTAMINE RECEPTORS? British Journal of Pharmacology April 1, 1979
- Effects of LSD-25 on brain serotonin. Journal of Pharmacology and Experimental Therapeutics November 1, 1961