Neuroscience study compares new psychedelic drugs with classic hallucinogens like LSD

New psychoactive tryptamine drugs predict hallucinogenic effects that are similar to classic hallucinogens but also have MDMA-like properties, according to a study published online this August in European Neuropsychopharmacology.

Classic hallucinogens can be grouped into different chemical groups, these include: tryptamines (e.g., psilocin and DMT), ergolines (LSD), and phenethylamines (e.g., mescaline). Psychoactive tryptamines are naturally found in toads, plants, and mushrooms. However, many new types of tryptamine have been created and are recreationally used as psychoactive substances.

The neurotransmitter serotonin (5-HT) has a similar core structure to tryptamines. Therefore, the psychoactive effects of hallucinogens, including those of tryptamines, are thought to be mediated mainly by the serotonin receptor, 5-HT2A. In addition, they may be modulated by interactions with other targets, including other serotonin receptors, monoamine transporters, and trace amine-associated receptors.

Structural alterations of tryptamines have been shown to result in different pharmacological and psychoactive profiles. For example, many classic drugs produce hallucinogenic effects with relatively low potency when compared to these new drugs, with the new versions also having stimulant-type activation and less visual perceptual alterations.

The study, led by Anna Rickli of the University Hospital Basel and University of Basel, compared the effects of the new psychoactive tryptamines DiPT,  4-OH-DiPT, 4-OH-MET, 5-MeO-AMT, and 5-MeO-MiPT with the classic hallucinogens LSD, psilocin, DMT, mescaline, and MDMA, on incubated human cells. More specifically, they investigated the level of binding between the drugs and a number of brain receptors, including monoamine receptors, and determined functional serotonin activation for the receptors 5- HT2A and 5-HT2B.

The results showed that all of the new tryptamines interacted with 5-HT2A receptors and were partial or full 5-HT2A agonists (i.e. they increase the receptor physiological response for serotonin within the brain). The level of binding to the 5-HT2A receptor was lower for all of the tryptamines when compared with LSD, suggesting a lower effect on serotonin release. Many of the tryptamines (psilocin, DMT, DiPT, 4-OH-DiPT, and 4-OH-MET) interacted with a transporter of serotonin and partially with a transporter of norepinephrine (which increases arousal and alertness) – this is similar to MDMA but in contrast to LSD and mescaline. In contrast to LSD, the tryptamines had minimal effects on adrenergic (related to adrenaline) and dopaminergic (related to reward-motivated behavior) receptors.

The researchers concluded, “The receptor interaction profiles of the tryptamines predict hallucinogenic effects that are similar to classic serotonergic hallucinogens but also MDMA-like psychoactive properties.”