Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens

Abstract

Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) and psilocybin. Despite their differences in chemical structure, the two classes of hallucinogens produce remarkably similar subjective effects in humans, and induce cross-tolerance. The phenylalkylamine hallucinogens are selective 5-HT2 receptor agonists, whereas the indoleamines are relatively non-selective for serotonin (5-HT) receptors. There is extensive evidence, from both animal and human studies, that the characteristic effects of hallucinogens are mediated by interactions with the 5-HT2A receptor. Nevertheless, there is also evidence that interactions with other receptor sites contribute to the psychopharmacological and behavioral effects of the indoleamine hallucinogens. This article reviews the evidence demonstrating that the effects of indoleamine hallucinogens in a variety of animal behavioral paradigms are mediated by both 5-HT2 and non-5-HT2 receptors.

Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs)

“…We The 5-HT 2A receptor mediates hallucinogenic drug properties (Halberstadt and Geyer, 2011;Nelson et al, 1999;Nichols, 2004;Vollenweider et al, 1998) and is therefore considered the key target of hallucinogenic phenethylamines, including 2C…”

“…Accordingly, 5-HT 1A receptor stimulation has been hypothesized to counteract hallucinogenic activity (Halberstadt and Geyer, 2011;Nichols, 2004), and lower 5-HT 1A receptor stimulation for the NBOMe drugs may further enhance their hallucinogenic drug properties. N-2-methoxybenzyl substitution increased 5-HT 2B…”

Reproductive Aging: Perimenopause and Psychopathological Symptoms

“…There is extensive evidence, from both animal and human studies, that the characteristic effects of hallucinogens are mediated by their agonistic interactions with the 5-HT 2A receptor [125]. The loss of estrogen in perimenopause leads to a decreased density of 5-HT 2A receptors and a lower activity of serotonin, which could explain aberrant temperature regulation, including hot flashes and night sweats [114,126].…”

The effects of benzofury (5-APB) on the dopamine transporter and 5-HT2-dependent vasoconstriction in the rat

“…The hallucinogen LSD appears to act as a partial agonist of both 5-HT 2A and 5-HT 1A receptors (Halberstadt and Geyer, 2011;Passie et al, 2008), with effects via 5-HT 2A receptors predominating. The two main receptors expressed by vascular smooth muscle are 5-HT 2A and…”