Stereospecific binding ofd-lysergic acid diethylamide (LSD) to brain membranes: Relationship to serotonin receptors
James P. Bennett, Solomon H. Snyder
Brain Research September 1, 1975 DOI: 10.1016/0006-8993(75)90234-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Rat brain membranes; monkey brain |
| Topics | LSD Serotonin |
| Keywords | Stereospecificity 5-HT Receptor Binding site Stereochemistry Neurotransmitter Biochemistry Biophysics |
| Citations | 166 |
| Key findings | D-[3H]LSD binds to post-synaptic serotonin receptors in rat and monkey brain. |
Abstract
D-[3H]LSD binds saturably, reversibly, and with a high affinity (KD = 10 nM) to rat brain membranes. The association and dissociation rates of binding are temperature dependent and fastest at 37 degrees C. Binding is enriched in crude microsomal (P3) membranes. D-[3H]LSD binding is stereospecific as L-LSD, the psychotropically inactive enatiomer, is 1000 times weaker than D-LSD as a displacing agent. The potencies of other LSD analogues parallel their psychotropic activity with the exception of 2-bromo-LSD (psychotropically inactive) which is as potent as D-LSD in displacing bound D-[3H]LSD. Serotonin is the only putative neurotransmitter with affinity (ED50 = 3 muM) for the LSD binding site, and psychotropically active alkylindoleamines are also potent displacing agents. Destruction of presynaptic serotonin neuronal elements by lesioning the midbrain raphe nuclei does not chang the affinity or maximum number of detectable in vitro D-[3H]LSD bindind sites. The regional distribution in monkey brain of D-[3H]LSD binding and high affinity [3h]serotonin uptake, a marker for pre-synaptic serotonin nerve terminal density, shows some correlation. The most notable exceptions are cerebral cortical areas which are highest in D-[3H]LSD binding and only intermediate in [3h]serotonin uptake. Our evidence suggests that D-[3H]LSD binds to post-synaptic serotonin receptors.
Comparable studies
Other observational and cohort studies on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Human participants | 2016 | Observational cohort | |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. USA adult respondents from the National Survey on Drug Use and Health (2008-2012) | 2015 | Observational cohort | n = 190,000 |
| Psychedelics not linked to mental health problems or suicidal behavior: A population study Randomly selected United States adults | 2015 | Observational cohort | n = 135,095 |
| Whole-Brain Multimodal Neuroimaging Model Using Serotonin Receptor Maps Explains Non-linear Functional Effects of LSD. Healthy human participants | 2018 | Observational study with computational modeling |
Citations in the library
Cited by 18
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- Crystal structure of an LSD-bound human serotonin receptor Cell January 26, 2017
- Psychedelics reopen the social reward learning critical period Nature June 14, 2023
- Tritiated LSD Binding in Frontal Cortex in Schizophrenia Archives of General Psychiatry March 1, 1981
- Characterisation of [3H]lysergic acid diethylamide binding to a 5-hydroxytryptamine receptor on human platelet membranes European Journal of Pharmacology 1984
and 13 more in the library
Cites 10
- Lysergic Acid Diethylamide: Sensitive Neuronal Units in the Midbrain Raphe Science August 16, 1968
- Evidence for a central 5‐hydroxytryptamine receptor stimulation by lysergic acid diethylamide British Journal of Pharmacology September 1, 1968
- Antagonism of 5‐hydroxytryptamine by LSD 25 in the central nervous system: a possible neuronal basis for the actions of LSD 25 British Journal of Pharmacology October 1, 1970
- DOM (STP), a New Hallucinogenic Drug, and DOET: Effects in Normal Subjects American Journal of Psychiatry September 1, 1968
- Lysergic acid diethylamide: Role in conversion of plasma tryptophan to brain serotonin (5-hydroxytryptamine) Science 1969
and 5 more in the library