Bufotenine: toward an understanding of possible psychoactive mechanisms.

Bufotenine shows activity similar to LSD, psilocin, and 5-MeO-DMT at serotonin receptors 5-HT2A and 5-HT2C, which are linked to hallucinogenic effects. Computer modeling indicates bufotenine can bind and activate these receptors. The lack of classic hallucinogenic response in human experiments likely results from poor blood-brain barrier penetration, not from failure to activate brain receptors. Under certain physiological conditions, similar drugs that normally do not cross the blood-brain barrier can enter the brain. While direct human evidence of hallucinogenic activity is absent, these factors suggest possible psychoactivity, and updated experimental models are proposed to test bufotenine's hallucinogenic potential.

Study at a glance

Abstract

A review of the neuropharmacology of the alleged hallucinogen bufotenine is presented, including recent experimental results showing activity similar to LSD and other known hallucinogens (psilocin and 5-MeO-DMT) at the purported hallucinogenic serotonin (5-HT) receptors, 5-HT2A and 5-HT2C. In addition, current reports of computer modeling of the receptors and ligand binding sites give evidence of bufotenine's ability to bind and activate these receptors. While binding and activation of the purported hallucinogenic receptors are not the full extent of the hallucinogenic signature, this evidence shows support for the rationale that the reported lack of the drug's classic hallucinogenic response in human experiments is due to poor ability to cross the blood brain barrier (BBB), not lack of activation of the appropriate brain receptors. Further evidence is reviewed that in some physiological states, some drugs with characteristics similar to bufotenine which do not normally cross the BBB, cross it and enter the brain. While direct human experimental evidence of bufotenine's hallucinogenic activity seems lacking, the above combined factors are considered, and possible explanations of bufotenine's reported psychoactivity are suggested. Additionally, updated experimental models testing the possible nature of bufotenine's hallucinogenic potential are proposed.