Localization of serotonin 5‐HT2 receptors in living human brain by positron emission tomography using N1‐([11C]‐methyl)‐2‐BR‐LSD
Dean F. Wong, John R. Lever, Paul R. Hartig, Robert F. Dannals, Victor L. Villemagne, Beth J. Hoffman, Alan A. Wilson, Hayden T. Ravert, Jonathan M. Links, Ursula Scheffel, Henry N. Wagner
Study at a glance
AI-extracted from the abstract| Characteristics | Clinical trial Peer reviewed |
|---|---|
| Sample size | 7 |
| Population | Normal human volunteers |
| Topics | Serotonin LSD |
| Keywords | Ketanserin Radioligand 5-HT Receptor Putamen Human brain Temporal cortex Binding potential Endocrinology |
| Citations | 93 |
| Key findings | [11C]-MBL selectively labels serotonin 5-HT2 receptors in human brain, with highest binding in cortical regions and lower ratios in older volunteers. |
Abstract
Abstract N1‐([ 11 C]‐Methyl)‐2‐Br‐LSD ([ 11 C]‐MBL) has been developed as a positron emission tomography (PET) imaging agent for serotonin 5‐HT 2 receptors. In vitro receptor binding assays with nonradioactive MBL show high‐affinity binding to serotonin 5‐HT 2 receptors (K i = 0.5 nM), a secondary interaction of 8‐fold lower affinity with dopamine D 2 receptors, and low‐affinity interactions with α 1 ‐adrenergic as well as serotonin 5‐HT 1 receptors. Intravenous injection of [ 11 C]‐MBL in a baboon led to selective labeling of cortical regions that was markedly blocked by prior administration of ketanserin, a selective 5‐HT 2 receptor antagonist. Clinical trials with [ 11 C]‐MBL have been conducted in seven normal human volunteers, and the regional distribution of radioactivity in the brain was distinctly serotonergic. Labeling was highest in frontal, temporal, and parietal cortex with lower levels observed in caudate and putamen. The tracer rapidly washed from the cerebellum and the low levels of activity in this brain region were used to define nonspecific binding. The maximum specificity was reached between 30 and 60 minutes postinjection when frontal cortex to cerebellum ratios ranged from 1.7 for a 52‐year‐old male to 2.7 for a 30‐year‐old male. In agreement with previous studies, a trend towards lower ratios (lower serotonin 5‐HT 2 receptor levels) was observed in older volunteers. These studies indicate that [ 11 C]‐MBL is a selective radioligand that can be used to monitor serotonin 5‐HT 2 receptor densities in vivo in most regions of the human brain.
Comparable studies
Other non-randomized and open-label trials on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The paradoxical psychological effects of lysergic acid diethylamide (LSD) Healthy volunteers | 2016 | Within-subjects controlled trial | n = 20 |
| Study of Lysergic Acid Diethylamide as an Analgesic Agent Hospital patients | 1964 | Clinical trial | n = 50 |
| Psychedelic Therapy Utilizing LSD in the Treatment of the Alcoholic Patient: A Preliminary Report Alcoholic patients | 1967 | Pilot study | n = 69 |
| LSD-induced hallucinogen persisting perception disorder treatment with clonidine: an open pilot study Patients with LSD-induced hallucinogen persisting perception disorder (HPPD) | 2000 | Open-label pilot study | n = 8 |
| DOET(2,5-Dimethoxy-4-Ethylamphetamine), a New Psychotropic Drug Normal male subjects | 1971 | Controlled trial |
Citations in the library
Cited by 17
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- Psychedelics and Other Psychoplastogens for Treating Mental Illness Frontiers in Psychiatry October 4, 2021
- Psilocybin links binocular rivalry switch rate to attention and subjective arousal levels in humans Psychopharmacology September 13, 2007
- Modulating the Rate and Rhythmicity of Perceptual Rivalry Alternations with the Mixed 5-HT2A and 5-HT1A Agonist Psilocybin Neuropsychopharmacology January 26, 2005
- LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1 Scientific Reports September 5, 2021
and 12 more in the library