Bufotenin
Bufotenin, also known as dimethylserotonin or as 5-hydroxy-N,''N-dimethyltryptamine, is a serotonergic psychedelic of the tryptamine family. It is a derivative of the psychedelic dimethyltryptamine and of the neurotransmitter serotonin. The compound is an alkaloid found in some species of mushrooms, plants, and toads. It is also found naturally in the human body in small amounts. Bufotenin, for instance derived from the trees Anadenanthera colubrina and Anadenanthera peregrina, has a long history of entheogenic use as a snuff in South America.
The name bufotenin originates from the toad genus Bufo, which includes several species of psychoactive toads, most notably Incilius alvarius, that secrete bufotoxins from their parotoid glands. However, Bufo and related species like Incilius alvarius'' contain only trace amounts of bufotenin, with their major active component instead being 5-MeO-DMT. In addition to DMT and serotonin, bufotenin is similar in chemical structure to other psychedelics such as 5-MeO-DMT and psilocin. These compounds also occur in some of the same fungus, plant, and animal species as bufotenin.
Bufotenin acts as a potent and non-selective serotonin receptor agonist, including of the serotonin 5-HT1A, 5-HT2A, 5-HT2C, and 5-HT3 receptors, among others. It also acts as a potent and specific serotonin releasing agent. The compound is more hydrophilic than other related tryptamines and consequently is more peripherally selective. In relation to this, bufotenin has been associated with prominent peripheral serotonergic side effects, such as cardiovascular changes. The cardiovascular effects of bufotenin can be powerful and potentially dangerous.
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. Alexander Shulgin was also uncertain whether bufotenin was an active psychedelic. 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. Hamilton Morris has further supported these findings with his own self-experimentation, although bufotenin was reported to be strongly nauseating for himself and many others. According to Morris, the psychedelic effects of bufotenin are like a cross between those of DMT and 5-MeO-DMT. Morris has stated that bufotenin may in fact be the psychedelic with the longest history of human entheogenic use. Bufotenin has also been encountered as a recreational drug in forensic samples, for instance in New York City.
Use and effects
Fabing & Hawkins (1955)
In 1955, Fabing and Hawkins administered bufotenin intravenously at doses of up to 16mg to prison inmates at Ohio State Penitentiary. A toxic effect causing purpling of the face was seen in these tests.A subject given 1mg reported "a tight feeling in the chest" and prickling "as if he had been jabbed by needles." This was accompanied by a "fleeting sensation of pain in both thighs and a mild nausea."
Another subject given 2mg reported "tightness in his throat." He had tightness in the stomach, tingling in pretibial areas, and developed a purplish hue in the face indicating blood circulation problems. He vomited after 3 minutes.
Another subject given 4mg complained of "chest oppression" and that "a load is pressing down from above and my body feels heavy." The subject also reported "numbness of the entire body" and "a pleasant Martini feeling-my body is taking charge of my mind." The subject reported he saw red spots passing before his eyes and red-purple spots on the floor, and the floor seemed very close to his face. Within 2 minutes these visual effects were gone, and replaced by a yellow haze, as if he were looking through a lens filter.
Fabing and Hawkins commented that bufotenin's psychedelic effects were "reminiscent of
Isbell (1956)
In 1956, Harris Isbell at the Public Health Service Hospital in Lexington, Kentucky, experimented with bufotenin as a snuff made from Anadenanthera peregrina. He reported "no subjective or objective effects were observed after spraying with as much as 40 mg bufotenine"; however, subjects who received 10–12mg by intramuscular injection reported "elements of visual hallucinations consisting of a play of colors, lights, and patterns."Turner & Merlis (1959)
Turner and Merlis experimented with intravenous administration of bufotenin to schizophrenics at a New York state hospital. They reported that when one subject received 10mg during a 50-second interval, "the peripheral nervous system effects were extreme: at 17 seconds, flushing of the face, at 22 seconds, maximal inhalation, followed by maximal hyperventilation for about 2 minutes, during which the patient was unresponsive to stimuli; her face was plum-colored." Finally, Turner and Merlis reported:After pushing doses to the morally admissible limit without producing visuals, Turner and Merlis conservatively concluded: "We must reject bufotenine... as capable of producing the acute phase of Cohoba intoxication."
Hofmann (1963)
tried bufotenin orally at doses of up to 50mg but experienced no psychoactive effects.McLeod and Sitaram (1985)
A 1985 study by McLeod and Sitaram in humans reported that bufotenin administered intranasally at a dose of 1–16mg had no effect, other than intense local irritation. When given intravenously at low doses, bufotenin oxalate caused anxiety but no other effects; however, a dose of 8mg 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.Shulgin (1997)
reviewed the literature on bufotenin in his book TiHKAL. However, he and his collaborators did not appear to try it themselves.Ott (2001)
In 2001, ethnobotanist Jonathan Ott published the results of a study in which he self-administered free base bufotenin via insufflation, sublingually, rectally, orally and via vaporization. Ott reported "visionary effects" of intranasal bufotenin and that the "visionary threshold dose" by this route was 40mg, with smaller doses eliciting perceptibly psychoactive effects. He reported that "intranasal bufotenine is throughout quite physically relaxing; in no case was there facial rubescence, nor any discomfort nor disesteeming side effects".At 100mg, effects began within 5minutes, peaked at 35 to 40minutes, and lasted up to 90minutes. Higher doses produced effects that were described as psychedelic, such as "swirling, colored patterns typical of tryptamines, tending toward the arabesque". Free base bufotenin taken sublingually was found to be identical to intranasal use. The potency, duration, and psychedelic action was the same. Ott found vaporized free base bufotenin active from 2 to 8mg with 8mg producing "ring-like, swirling, colored patterns with eyes closed". He noted that the visual effects of insufflated bufotenin were verified by one colleague, and those of vaporized bufotenin by several volunteers.
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.
Morris (2020s)
, a psychoactive drug journalist, the creator of Hamilton's Pharmacopeia, and a pharmacologist, has experimented with bufotenin and found that it was an active psychedelic. He has claimed that its effects are like a cross between those of DMT and 5-MeO-DMT, being less visual than DMT but more visual than 5-MeO-DMT. Morris has also stated that bufotenin is very nauseating and this has made it unpleasant for himself and other people. By insufflation, he has said that its duration is about 1hour and is longer than that of DMT or 5-MeO-DMT.Morris and others have suggested use of the serotonin 5-HT3 receptor antagonist ondansetron to prevent nausea and vomiting with especially nauseating or serotonin 5-HT3 receptor agonistic serotonergic psychedelics like bufotenin.
Side effects
s of bufotenin include nausea and vomiting, among others. It can also produce powerful and potentially dangerous and frightening cardiovascular side effects at doses that allow for hallucinogenic effects.Overdose
The acute toxicity of bufotenin in rodents has been estimated at 200 to 300mg/kg. Death occurs by respiratory arrest. In April 2017, a South Korean man died after consuming bufotenin-containing toads that had been mistaken for edible Asian bullfrogs, while in Dec. 2019, five Taiwanese men became ill and one man died after eating bufotenin-containing Central Formosa toads that they mistook for frogs.Interactions
Pharmacology
Pharmacodynamics
Bufotenin is an analogue of the monoamine neurotransmitter serotonin. Similarly to serotonin and related compounds like dimethyltryptamine, bufotenin is an agonist of the serotonin 5-HT1A, 5-HT2A, 5-HT2C, 5-HT3, and 5-HT4 receptors. It is also known to bind with high affinity to other serotonin receptors, including the serotonin 5-HT1B, 5-HT1D, 5-HT1F, 5-HT6, and 5-HT7 receptors. Bufotenin has about 5- to 10-fold higher affinity for the serotonin 5-HT2A receptor than 5-MeO-DMT, about the same activational potency as 5-MeO-DMT at the receptor in vitro, and about 3-fold higher in-vivo potency than 5-MeO-DMT when they are in the brain. In contrast to many other psychedelic tryptamines, bufotenin shows high affinity for the serotonin 5-HT3 receptors, similar to or higher than that of serotonin, and this receptor is strongly associated with production of nausea and vomiting. In addition to its serotonin receptor agonism, bufotenin is a potent serotonin releasing agent with an value of 30.5nM, whereas it is inactive as a releaser of dopamine or norepinephrine.A special property of 5-MeO-DMT is that it has much higher affinity for and activational potency at the serotonin 5-HT1A receptor compared to other psychedelic tryptamines such as DMT and this is thought to confer it with unique and distinct hallucinogenic effects. Similarly, bufotenin has also shown greatly increased affinity for the serotonin 5-HT1A receptor. Whereas the serotonin 5-HT1A receptor affinities of tryptamine and DMT were 125nM and 170nM, respectively, the affinities of serotonin, 5-methoxytryptamine, bufotenin, and 5-MeO-DMT were 3nM, 9nM, 4.9nM, and 6.5nM, respectively. Comparing bufotenin to DMT, it had 35-fold higher affinity for the serotonin 5-HT1A receptor in comparison. Findings were very similar in another study not only in terms of affinities but also activational potencies. Bufotenin had a similar at the serotonin 5-HT1A receptor as serotonin, 5-MeO-T, and 5-MeO-DMT, and a far greater value than tryptamine or DMT.
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. As a result, bufotenin has a greater ratio of peripheral activity to central effect. Bufotenin produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents. However, it requires doses about 10-fold higher than those of psilocybin to produce behavioral responses in rats. Conversely, unlike other psychedelics, bufotenin fails to substitute for LSD, psilocybin, or 5-MeO-DMT in rodent drug discrimination tests. Relatedly, findings on the effects of bufotenin in animals have been described as "equivocal". Studies have been similarly mixed on the psychedelic effects of bufotenin in humans, with some finding a relative lack of psychedelic effects and pronounced toxic effects, while others have found psychedelic effects without major adverse effects. In any case, bufotenin has often been reported to produce pronounced peripheral serotonergic effects. These have included cardiovascular, gastrointestinal, and other effects, among them increased respiratory rate, chest heaviness, purpling of the head and neck skin, nausea, vomiting, and retching. It is possible that in addition to its limited central permeation, the peripheral effects of bufotenin have served to mask its central and hallucinogenic effects. The adverse effects of bufotenin may be more pronounced with intravenous injection compared to other routes such as insufflation.
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. 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. Bufotenin prodrug esters, with greater lipophilicity than bufotenin itself, like O-acetylbufotenin and O-pivalylbufotenin, have also shown robust psychedelic-like effects in animals.