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

Hallucinogens are a loosely defined group of compounds including LSD, N,N-dimethyltryptamines, mescaline, psilocybin/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), which can evoke intense visual emotional experiences. We witnessing renaissance research interest in hallucinogens, driven by increasing awareness their psychotherapeutic potential. As such, we now present narrative review the literature on hallucinogen binding vitro ex vivo, various molecular imaging studies with positron emission tomography (PET) or single photon computer (SPECT). In general, depict uptake distribution labelled hallucinogenic congeners brain, as was shown an early PET study N1-([11C]-methyl)-2-bromo-LSD ([11C]-MBL); displacement non-radioactive competitor ketanserin confirmed that majority [11C]-MBL specific to serotonin 5-HT2A receptors. However, interactions at 5HT1A other classes receptors pleotropic effects second messenger pathways may contribute particular experiential phenomenologies LSD compounds. Other salient aspects action include permeability blood–brain barrier, rates metabolism elimination, formation active metabolites. Despite maturation radiochemistry recent years, there has been only handful SPECT radiolabeled most recently using 5-HT2A/2C agonist N-(2[11CH3O]-methoxybenzyl)-2,5-dimethoxy- 4-bromophenethylamine ([11C]Cimbi-36). addition target engagement neuroreceptors transporters, is small number cerebral perfusion ([15O]-water) ([18F]-fluorodeoxyglucose/FDG). There remains considerable scope for basic sites interaction hallucinogens cerebrometabolic effects; expect hybrid conjunction functional magnetic resonance (fMRI) should provide especially useful next phase this research.