Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 9; p. 2451
• Main Authors: Cumming, Paul, Scheidegger, Milan, Dornbierer, Dario, Palner, Mikael, Quednow, Boris B, Martin-Soelch, Chantal
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.04.2021; MDPI
• Subjects: Auditory evoked potentials; Binding; Binding sites; Blood-brain barrier; Brain mapping; Brain research; Computed tomography; Congeners; Dopamine; Drugs; Emission analysis; Functional magnetic resonance imaging; Hallucinations; Hallucinogens; Ketanserin; Ligands; Literature reviews; LSD; Lysergic acid diethylamide; Lysergide; Magnetic resonance imaging; Medical imaging; Membrane permeability; Mescaline; Metabolism; Metabolites; Methamphetamine; molecular imaging; Nervous system; Neuroimaging; Perfusion; PET; Phenomenology; Photon emission; Physiology; Positron emission; Positron emission tomography; Proteins; Psilocybin; Psychedelic drugs; Psychopharmacology; Radiochemistry; Review; Serotonin; serotonin receptors; Serotonin S2 receptors; Signal transduction; Single photon emission computed tomography; SPECT; Tomography; serotonin receptors; hallucinogens; molecular imaging; PET; SPECT
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26092451

Hallucinogens are a loosely defined group of compounds including LSD, -dimethyltryptamines, mescaline, psilocybin/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), which can evoke intense visual and emotional experiences. We are witnessing a renaissance of research interest in hallucinogens, driven by increasing awareness of their psychotherapeutic potential. As such, we now present a narrative review of the literature on hallucinogen binding in vitro and ex vivo, and the various molecular imaging studies with positron emission tomography (PET) or single photon emission computer tomography (SPECT). In general, molecular imaging can depict the uptake and binding distribution of labelled hallucinogenic compounds or their congeners in the brain, as was shown in an early PET study with -([ C]-methyl)-2-bromo-LSD ([ C]-MBL); displacement with the non-radioactive competitor ketanserin confirmed that the majority of [ C]-MBL specific binding was to serotonin 5-HT receptors. However, interactions at serotonin 5HT and other classes of receptors and pleotropic effects on second messenger pathways may contribute to the particular experiential phenomenologies of LSD and other hallucinogenic compounds. Other salient aspects of hallucinogen action include permeability to the blood-brain barrier, the rates of metabolism and elimination, and the formation of active metabolites. Despite the maturation of radiochemistry and molecular imaging in recent years, there has been only a handful of PET or SPECT studies of radiolabeled hallucinogens, most recently using the 5-HT agonist -(2[ CH O]-methoxybenzyl)-2,5-dimethoxy- 4-bromophenethylamine ([ C]Cimbi-36). In addition to PET studies of target engagement at neuroreceptors and transporters, there is a small number of studies on the effects of hallucinogenic compounds on cerebral perfusion ([ O]-water) or metabolism ([ F]-fluorodeoxyglucose/FDG). There remains considerable scope for basic imaging research on the sites of interaction of hallucinogens and their cerebrometabolic effects; we expect that hybrid imaging with PET in conjunction with functional magnetic resonance imaging (fMRI) should provide especially useful for the next phase of this research.