Figure 1.
The multiple targets of serotonergic psychedelic drugs. Among the major anatomic targets for serotonergic psychedelics are cortical areas, such as the PFC, where serotonergic receptors are located in pyramidal neurons. Although activation of 5-HT2A receptors is an integral element of the hallucinogenic experience and may contribute to some of the proposed therapeutic effects of these class of drugs, other receptors of the same family (5-HT2C and 5-HT1A) or even the TrkB receptor of the neurotrophin, BDNFs are involved in the therapeutic effects of psychedelic drugs. This suggests a potential to dissociate psychedelics from therapeutic effects. a, Several psychedelic drugs may also induce their effects (psychedelic and or therapeutic) via a biased activation of signaling pathways (G-protein-mediated vs β-arrestin). b, Alternatively, serotonergic psychedelics may target intracellular 5-HT2A receptors to induce therapeutic effects because of their lipophilicity, which allows them to traverse the cell membrane. c, Some derivatives, such as 2-Br-LSD, also target 5-HT2A receptors as partial agonists, inducing synaptic plasticity but lacking hallucinogenic effects. d, Finally, it is also conceivable that several psychedelics and entactogens can be a substrate for TGM2 to monoamylate glutamine restudies in proteins, such as Rac1 or histones, to alter cytoskeleton function or gene expression, respectively, in the induction of lasting therapeutic effects.