Drugs of Abuse Affecting 5-HT_2B Receptors

Stimulant and psychedelic drugs of abuse interact with monoaminergic systems, and the 5-HT_2B receptor is a relatively understudied target of serotonergic drugs. Activation of this receptor has been demonstrated for benzofuran-class stimulants and substituted amphetamines with a serotonergic profile, and may lead to cardiac valvulopathy. Many psychedelic drugs also activate the 5-HT_2B receptor, but the consequences remain unclear. Cardiac valvulopathy is likely not a concern with occasional psychedelic use, but may differ for microdosing regimens involving daily or multiple-times-weekly low doses.

Study at a glance

Abstract

Stimulant and psychedelic drugs of abuse exert their effects through interactions with monoaminergic systems. Compared to other monoaminergic receptors and transporters, the 5-hydroxytryptamine 2B (5-HT_2B) receptor represents a relatively little studied target of serotonergic drugs of abuse. However, studies suggest the involvement of 5-HT_2B receptors in the mechanism of action of serotonergic stimulants and receptor activation may additionally lead to specific adverse effects such as cardiac valvulopathy in users. 5-HT_2B receptor activation has been demonstrated for stimulant-type new psychoactive substances of the benzofuran class and for substituted amphetamines with a distinct serotonergic vs. dopaminergic profile. Besides stimulants, many psychedelic drugs activate the 5-HT_2B receptor but the consequence thereof remains unclear. Cardiac valvulopathy is likely not an adverse effect to consider when psychedelics are used occasionally but this may be different for “microdosing” which involves low doses of psychedelics taken daily or multiple times per week.