The article includes experimental results showing bufotenine activity similar to LSD and other known hallucinogens at the purported hallucinogenic serotonin receptors. Computer modeling of receptors and ligand binding sites gives evidence of bufotenine’s ability to bind and activate those receptors. This evidence supports the rationale that the reported lack of the drug’s classic hallucinogenic response in human experiments results from poor ability to cross the blood brain barrier (BBB), not lack of activation of the appropriate brain receptors. The article also reviews evidence 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 is lacking, the article suggests possible explanations and proposes updated experimental models testing the possible nature of bufotenine’s hallucinogenic potential. Figures, tables, references