[12][7][16] For many decades and even into the present, bufotenin has been considered by many experts, such as David E. Nichols, to be either inactive or only weakly active as a psychedelic in humans and to produce robust toxic effects.

[16][5] However, Jonathan Ott found in 2001 via self-experimentation that bufotenin is in fact a potent psychedelic and does not necessarily produce serious adverse effects.

[17] Bufotenin was isolated from toad skin, and named by the Austrian chemist Handovsky at the University of Prague during World War I.

[24][25][26] Reports in the mid-1990s indicated that bufotenin-containing toad secretions had appeared as a street drug, supposedly but in fact not an aphrodisiac,[27] ingested orally in the form of ch'an su,[24] or as a psychedelic, by smoking or orally ingesting Bufo toad secretions or dried Bufo skins.

The use of chan'su and love stone (a related toad skin preparation used as an aphrodisiac in the West Indies) has resulted in several cases of poisoning and at least one death.

Anadenanthera seeds have been used as an ingredient in psychedelic snuff preparations by indigenous cultures of the Caribbean, Central and South America since pre-Columbian times.

[35] Bufotenin has been identified as a component in the latex of the takini (Brosimum acutifolium) tree, which is used as a psychedelic by South American shamans,[37] and in the seeds of Mucuna pruriens.

[6][41] A study conducted in the late 1960s reported the detection of bufotenin in the urine of schizophrenic subjects;[42] however, subsequent research failed to confirm these findings until 2010.

[43][44][45][46][47] Studies have detected endogenous bufotenin in urine specimens from individuals with other psychiatric disorders,[48] such as infant autistic patients.

[50] A 2010 study utilized a mass spectrometry approach to detect levels of bufotenin in the urine of individuals with severe autism spectrum disorder (ASD), schizophrenia, and asymptomatic subjects.

Their results indicate significantly higher levels of bufotenin in the urine of the ASD and schizophrenic groups when compared to asymptomatic individuals.

[47] In 1955, Fabing and Hawkins administered bufotenin intravenously at doses of up to 16 mg to prison inmates at Ohio State Penitentiary.

He had tightness in the stomach, tingling in pretibial areas, and developed a purplish hue in the face indicating blood circulation problems.

"[18][51] Turner and Merlis (1959)[51] experimented with intravenous administration of bufotenin (as the water-soluble creatinine sulfate salt) to schizophrenics at a New York state hospital.

Finally, Turner and Merlis reported: on one occasion, which essentially terminated our study, a patient who received 40 mg intramuscularly, suddenly developed an extremely rapid heart rate; no pulse could be obtained; no blood pressure measured.

"After pushing doses to the morally admissible limit without producing visuals, Turner and Merlis conservatively concluded: "We must reject bufotenine .

"[18] A 1985 study by McLeod and Sitaram in humans reported that bufotenin administered intranasally at a dose of 1–16 mg had no effect, other than intense local irritation.

When given intravenously at low doses (2–4 mg), bufotenin oxalate caused anxiety but no other effects; however, a dose of 8 mg resulted in profound emotional and perceptual changes, involving extreme anxiety, a sense of imminent death, and visual disturbance associated with color reversal and distortion, and intense flushing of the cheeks and forehead.

[1] He reported that "intranasal bufotenine is throughout quite physically relaxing; in no case was there facial rubescence, nor any discomfort nor disesteeming side effects".

[2][1] Higher doses produced effects that were described as psychedelic, such as "swirling, colored patterns typical of tryptamines, tending toward the arabesque".

[2][1] Ott concluded that free base bufotenin taken intranasally and sublingually produced effects similar to those of Yopo without the toxic peripheral symptoms, such as facial flushing, observed in other studies in which the drug was administered intravenously.

[14] Bufotenin is thought to have reduced capacity to cross the blood–brain barrier due to its relatively high hydrophilicity and hence to show significant peripheral selectivity.

[5] In contrast to peripheral administration, intracerebroventricular injection of bufotenin in animals readily produces robust psychedelic-like behavioral effects similar to those of other serotonergic psychedelics like 5-MeO-DMT.

[12] In addition, 5-MeO-DMT, the O-methylated analogue of bufotenin, which has greater lipophilicity, is readily able to cross the blood–brain barrier and produce psychedelic effects.

[12] This is in contrast to its positional isomer psilocin, which is thought to form a pseudo-ring system that limits its susceptibility to metabolism by monoamine oxidase (MAO).

[65] In humans, intravenous administration of bufotenin results in excretion of (70%) of injected drug in the form of 5-HIAA, an endogenous metabolite of serotonin, while roughly 4% is eliminated unmetabolized in the urine.

[78][79][80] Some analogues and derivatives of bufotenin (5-HO-DMT), aside from serotonin and DMT, include psilocin (4-HO-DMT) (a positional isomer), 5-MeO-DMT (O-methylbufotenin), O-acetylbufotenine, O-pivalylbufotenine, bufotenidine (N-methylbufotenin), 5-HO-DiPT, and α-methylserotonin, among others.

[82] A schedule 9 drug is outlined in the Poisons Act 1964 as "Substances which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of the CEO.