Bufotenin

Last updated
Bufotenin
Bufotenin2DACS.svg
Bufotenin-3d-sticks.png
Clinical data
Other namesBufotenine; 5-Hydroxy-N,N-dimethyltryptamine; 5-HO-DMT; 5-OH-DMT; N,N-Dimethyl-5-hydroxytryptamine; N,N-Dimethylserotonin; Dimethylserotonin; Dimethyl-5-HT; Cebilcin; Mappine
Routes of
administration 		Oral, intravenous
ATC code
  • None
Legal status
Legal status
Identifiers
  • 3-[2-(Dimethylamino)ethyl]-1H-indol-5-ol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.006.971 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C12H16N2O
Molar mass 204.273 g·mol−1
3D model (JSmol)
Melting point 146 to 147 °C (295 to 297 °F)
Boiling point 320 °C (608 °F)
  • CN(C)CCc1c[nH]c2ccc(O)cc12
  • InChI=1S/C12H16N2O/c1-14(2)6-5-9-8-13-12-4-3-10(15)7-11(9)12/h3-4,7-8,13,15H,5-6H2,1-2H3 Yes check.svgY
  • Key:VTTONGPRPXSUTJ-UHFFFAOYSA-N Yes check.svgY
   (verify)

Bufotenin, also known as dimethylserotonin or as 5-hydroxy-N,N-dimethyltryptamine (5-HO-DMT), is a tryptamine derivative, more specifically, a dimethyltryptamine (DMT) analogue, related to the neurotransmitter serotonin. It is an alkaloid found in some species of mushrooms, plants and toads, especially the skin. It is also found naturally in the human body in small amounts. [1] [2] [3]

Contents

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. [4] Bufotenin is similar in chemical structure to the psychedelics psilocin (4-HO-DMT), 5-MeO-DMT and DMT, chemicals which also occur in some of the same fungus, plant and animal species as bufotenin.

Nomenclature

Bufotenin (bufotenine) is also known by the names 5-hydroxy-N,N-dimethyltryptamine (5-HO-DMT), N,N-dimethyl-5-hydroxytryptamine, dimethylserotonin, and mappine, among others. [5]

History

Bufotenin was isolated from toad skin, and named by the Austrian chemist Handovsky at the University of Prague during World War I. [6] The structure of bufotenine was confirmed in 1934 by Heinrich Wieland's laboratory in Munich, and the first reported synthesis of bufotenine was by Toshio Hoshino and Kenya Shimodaira in 1935. [7]

Sources

Toads

Bufotenin is found in the skin and eggs of several species of toads belonging to the genus Bufo , but is most concentrated in the Colorado River toad (formerly Bufo alvarius, now Incilius alvarius), the only toad species with enough bufotenin for a psychoactive effect. Extracts of toad toxin, containing bufotenin and other bioactive compounds, have been used in some traditional medicines such as ch'an su (probably derived from Bufo gargarizans ), which has been used medicinally for centuries in China. [8]

The toad was "recurrently depicted in Mesoamerican art", [9] which some authors have interpreted as indicating that the effects of ingesting Bufo secretions have been known in Mesoamerica for many years; however, others doubt that this art provides sufficient "ethnohistorical evidence" to support the claim. [8]

In addition to bufotenin, Bufo secretions also contain digoxin-like cardiac glycosides, and ingestion of these toxins can be fatal. Ingestion of Bufo toad poison and eggs by humans has resulted in several reported cases of poisoning, [10] [11] [12] some of which resulted in death. A court case in Spain, involving a physician who dosed people with smoked Mexican Toad poison, one of his customers died after inhaling three doses, instead of the usual of only one, had images of intoxicated with this smoke suffering obvious hypocalcemic hand muscular spasms. [12] [13] [14]

Reports in the mid-1990s indicated that bufotenin-containing toad secretions had appeared as a street drug, supposedly but in fact not an aphrodisiac, [15] ingested orally in the form of ch'an su , [12] 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. [12] [16] The practice of orally ingesting toad poison has been referred to in popular culture and in the scientific literature as toad licking and has drawn media attention. [17] [18] Albert Most, founder of the defunct Church of the Toad of Light and a proponent of spiritual use of Bufo alvarius toxin, published a booklet in 1983 titled Bufo alvarius: The Psychedelic Toad of the Sonoran Desert [19] [20] which explained how to extract and smoke the secretions.

Bufotenin is also present in the skin secretion of three arboreal hylid frogs of the genus Osteocephalus ( Osteocephalus taurinus , Osteocephalus oophagus , and Osteocephalus langsdorfii ) from the Amazon and Atlantic rain forests. [21]

Anadenanthera seeds

Yopo seeds from the perennial Anadenanthera Peregrina tree have a long history of entheogenic use and induce a short but distinct psychedelic experience. Yopo Seeds.jpg
Yopo seeds from the perennial Anadenanthera Peregrina tree have a long history of entheogenic use and induce a short but distinct psychedelic experience.

Bufotenin is a constituent of the seeds of Anadenanthera colubrina and Anadenanthera peregrina trees. 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. [22] [23] [24] The oldest archaeological evidence of use of Anadenanthera beans is over 4,000 years old. [23]

Other sources

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, [25] and in the seeds of Mucuna pruriens . [26] Bufotenin has also been identified in Amanita muscaria, Amanita citrina , A. porphyria, and A. tomentella. [27] [28]

Humans

Bufotenin occurs in trace amounts in the human body. [1] [2] [3] [29] It can be biosynthesized from serotonin by indolethylamine N-methyltransferase (INMT) enzymes. [1] [29]

Association with schizophrenia and other mental disorders

A study conducted in the late 1960s reported the detection of bufotenin in the urine of schizophrenic subjects; [30] however, subsequent research failed to confirm these findings until 2010. [31] [32] [33] [34] [35]

Studies have detected endogenous bufotenin in urine specimens from individuals with other psychiatric disorders, [36] such as infant autistic patients. [37] Another study indicated that paranoid violent offenders or those who committed violent behaviour towards family members have higher bufotenin levels in their urine than other violent offenders. [38]

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. [35]

Pharmacology

Pharmacodynamics

Bufotenin is an analogue of the monoamine neurotransmitter serotonin. [39] [40] Similarly to serotonin and related compounds like dimethyltryptamine (DMT), bufotenin is a potent agonist of the serotonin 5-HT2A and 5-HT2C receptors. [39] [40] It is also known to bind with high affinity to other serotonin receptors, including the serotonin 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT3 receptors, and is likely to be a serotonin 5-HT4 receptor agonist. [2] [40] In addition to its serotonin receptor agonism, bufotenin is a potent serotonin releasing agent with an EC50 Tooltip half-maximal effective concentration value of 30.5 nM. [41]

Bufotenin has greatly reduced capacity to cross the blood–brain barrier due to its relatively high hydrophilicity and hence shows prominent peripheral selectivity. [39] As a result, bufotenin has a much greater ratio of peripheral activity to central effect. [39] Studies in humans and animals have found a relative lack of psychedelic effects with bufotenin. [39] However, other studies in humans have reported that the compound can produce psychedelic effects. [42] [43] In any case, bufotenin has often been reported to produce pronounced peripheral serotonergic effects. [39] [2] These have included cardiovascular, gastrointestinal, and other effects, among them increased respiratory rate, chest heaviness, purpling of the head and neck skin (intense skin flushing), nausea, vomiting, and retching. [39] [2] 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. [39]

In contrast to peripheral administration, intracerebroventricular injection of bufotenin in animals produces robust psychedelic-like behavioral effects similar to those of other serotonergic psychedelics like 5-MeO-DMT. [39] In addition, 5-MeO-DMT, the O-methylated analogue of bufotenin, which has much greater lipophilicity, is readily able to cross the blood–brain barrier and produce psychedelic effects. [39] Bufotenin prodrug esters, with greater lipophilicity than bufotenin itself, like O-acetylbufotenin and O-pivalylbufotenin, have also shown psychedelic-like effects in animals. [39] [44] [45]

Psilocin (4-hydroxy-N,N-dimethyltryptamine) is a positional isomer of bufotenin and might be expected to have similarly limited lipophilicity and blood–brain permeability. [39] However, psilocin appears to form a pseudo-ring system wherein its hydroxyl group and amine interact through ionic bonding. [39] [40] This in turn results in psilocin being much less polar, more lipophilic, and more able to cross the blood–brain barrier and exert central actions than it would be otherwise. [39] [40] In contrast, bufotenin is not able to achieve this pseudo-ring system. [39] [40] Accordingly, the experimentally observed partition coefficient of psilocin and 5-MeO-DMT have been reported to both be 3.30, whereas that of bufotenin was reported to be 0.06. [39] A minimum partition coefficient of 1.40 has been proposed for hallucinogenic effects in vivo and an optimal value of 3.14 has been suggested. [39] In any case, bufotenin does still appear to show minor central permeability and some capacity for psychoactive effects. [39] [40]

Effects in humans

Fabing & Hawkins (1955)

In 1955, Fabing and Hawkins administered bufotenin intravenously at doses of up to 16 mg to prison inmates at Ohio State Penitentiary. [46] A toxic effect causing purpling of the face was seen in these tests.

A subject given 1 mg 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." [46]

Another subject given 2 mg 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. [46]

Another subject given 4 mg 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. [46]

Fabing and Hawkins commented that bufotenin's psychedelic effects were "reminiscent of LSD and mescaline but develop and disappear more quickly, indicating rapid central action and rapid degradation of the drug".[ citation needed ]

Isbell (1956)

In 1956, Harris Isbell at the Public Health Service Hospital in Lexington, Kentucky, experimented with bufotenin as a snuff. He reported "no subjective or objective effects were observed after spraying with as much as 40 mg bufotenine"; however, subjects who received 10–12 mg by intramuscular injection reported "elements of visual hallucinations consisting of a play of colors, lights, and patterns." [6]

Turner & Merlis (1959)

Turner and Merlis (1959) [47] experimented with intravenous administration of bufotenin (as the water-soluble creatinine sulfate salt) to schizophrenics at a New York state hospital. They reported that when one subject received 10 mg 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:

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. There seemed to have been an onset of auricular fibrillation . . . extreme cyanosis developed. Massage over the heart was vigorously executed and the pulse returned to normal . . . shortly thereafter the patient, still cyanotic, sat up saying: "Take that away. I don't like them."

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." [6]

McLeod and Sitaram (1985)

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. [48]

Ott (2001)

In 2001, ethnobotanist Jonathan Ott published the results of a study in which he self-administered free base bufotenin via insufflation (5–100 mg), sublingually (50 mg), intrarectally (30 mg), orally (100 mg) and via vaporization (2–8 mg). [43] Ott reported "visionary effects" of intranasal bufotenin and that the "visionary threshold dose" by this route was 40 mg, 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 100 mg, effects began within 5 minutes, peaked at 35–40 minutes, and lasted up to 90 minutes. 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 2–8 mg with 8 mg 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.

Lethal dose

The acute toxicity (LD50) of bufotenin in rodents has been estimated at 200 to 300 mg/kg. Death occurs by respiratory arrest. [22] In April 2017, a South Korean man died of bufotenin poisoning after consuming toads that had been mistaken for edible Asian bullfrogs, [49] while in Dec. 2019, five Taiwanese men became ill and one man died after eating Central Formosa toads that they mistook for frogs. [50]

Pharmacokinetics

Bufotenin has been reported to undergo a strong first-pass effect [2] and to not be orally active. [39] 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). [39] However, bufotenin actually does show oral activity if sufficiently high doses are taken. [2] About 10-fold higher doses of bufotenin seem to be required orally compared to parenterally for effects. [2]

In rats, subcutaneously administered bufotenin (1–100 μg/kg) distributes mainly to the lungs, heart, and blood, and to a much lesser extent, the brain (hypothalamus, brain stem, striatum, and cerebral cortex), and liver. It reaches peak concentrations at one hour and is nearly eliminated within 8 hours. [51] 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. Orally administered bufotenin undergoes extensive first-pass metabolism by the enzyme monoamine oxidase.

Chemistry

Bufotenin, also known as 5-hydroxy-N,N-dimethyltryptamine (5-HO-DMT), is a substituted tryptamine and a derivative of dimethyltryptamine (DMT; N,N-dimethyltryptamine) and serotonin (5-hydroxytryptamine; 5-HT).

The predicted log P of bufotenin ranges from 0.89 to 2.04. [52] [53] [54] For comparison, the predicted log P of DMT is 2.06 to 2.5 [55] [56] [57] and of serotonin is 0.2 to 0.56. [58] [59] [60]

Analogues and derivatives

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.

Australia

Bufotenin is classified as a Schedule I controlled substance according to the Criminal Code Regulations of the Government of the Commonwealth of Australia. [61] It is also listed as a Schedule 9 substance under the Poisons Standard (October 2015). [62] 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." [63]

Under the Misuse of Drugs Act 1981 6.0 grams (0.21 oz) is determined to be enough for court of trial and 2.0 grams (0.071 oz) is considered intent to sell and supply. [64]

United Kingdom

In the United Kingdom, bufotenin is a Class A drug under the 1971 Misuse of Drugs Act.

United States

Bufotenin (DEA Drug Code 7403) is regulated as a Schedule I drug by the Drug Enforcement Administration at the federal level in the United States and is therefore illegal to buy, possess, and sell. [65]

Sweden

Sweden's public health agency suggested classifying Bufotenin as a hazardous substance, on May 15, 2019. [66]

See also

Related Research Articles

<i>N</i>,<i>N</i>-Dimethyltryptamine Chemical compound

N,N-Dimethyltryptamine is a substituted tryptamine that occurs in many plants and animals, including humans, and which is both a derivative and a structural analog of tryptamine. DMT is used as a psychedelic drug and prepared by various cultures for ritual purposes as an entheogen.

<span class="mw-page-title-main">Psilocybin</span> Chemical compound found in some species of mushrooms

Psilocybin, also known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT), and formerly sold under the brand name Indocybin, is a naturally occurring psychedelic prodrug compound produced by more than 200 species of fungi. Psilocybin is itself biologically inactive but is quickly converted by the body to psilocin, which has mind-altering effects similar, in some aspects, to those of other classical psychedelics. Effects include euphoria, visual and mental hallucinations, changes in perception, a distorted sense of time, and perceived spiritual experiences. It can also cause adverse reactions such as nausea and panic attacks.

<span class="mw-page-title-main">Tryptamine</span> Metabolite of the amino acid tryptophan

Tryptamine is an indolamine metabolite of the essential amino acid, tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon. The structure of tryptamine is a shared feature of certain aminergic neuromodulators including melatonin, serotonin, bufotenin and psychedelic derivatives such as dimethyltryptamine (DMT), psilocybin, psilocin and others.

<span class="mw-page-title-main">5-MeO-DMT</span> Chemical compound

5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), also known as O-methylbufotenin or mebufotenin, is a psychedelic of the tryptamine family. It is found in a wide variety of plant species, and also is secreted by the glands of at least one toad species, the Colorado River toad. Like its close relatives dimethyltryptamine (DMT) and bufotenin (5-HO-DMT), it has been used as an entheogen in South America. Slang terms include Five-methoxy, the power, bufo, and toad venom.

<i>Anadenanthera peregrina</i> Species of plant

Anadenanthera peregrina, also known as yopo, jopo, cohoba, parica or calcium tree, is a perennial tree of the genus Anadenanthera native to the Caribbean and South America. It grows up to 20 m (66 ft) tall, and has a thorny bark. Its flowers grow in small, pale yellow to white spherical clusters resembling Acacia inflorescences. It is an entheogen which has been used in healing ceremonies and rituals for thousands of years in northern South America and the Caribbean. Although the seeds of the yopo tree were originally gathered from the wild, increased competition between tribes over access to the seeds led to it being intentionally cultivated and transported elsewhere, expanding the plant's distribution through introduction to areas beyond its native range.

<span class="mw-page-title-main">5-Hydroxytryptophan</span> Chemical compound

5-Hydroxytryptophan (5-HTP), used medically as oxitriptan, is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitter serotonin.

<span class="mw-page-title-main">Psilocin</span> Chemical compound

Psilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin. Psilocin is a Schedule I drug under the Convention on Psychotropic Substances. Acting on the serotonin 5-HT2A receptors, psilocin's psychedelic effects are directly correlated with the drug's occupancy at these receptor sites. The subjective mind-altering effects of psilocin are highly variable and are said to resemble those of lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DMT).

<span class="mw-page-title-main">Cohoba</span> Taíno term for a ceremony in which the ground seeds of the cojóbana tree were inhaled

Cohoba is a Taíno transliteration for a ceremony in which the ground seeds of the cojóbana tree were inhaled, the Y-shaped nasal snuff tube used to inhale the substance, and the psychoactive drug that was inhaled. Use of this substance produced a hallucinogenic, entheogenic, or psychedelic effect. The cojóbana tree is believed by some to be Anadenanthera peregrina although it may have been a generalized term for psychotropics, including the quite toxic Datura and related genera (Solanaceae). The corresponding ceremony using cohoba-laced tobacco is transliterated as cojibá. This was said to have produced the sense of a visionary journey of the kind associated with the practice of shamanism.

<span class="mw-page-title-main">Diethyltryptamine</span> Chemical compound

DET, also known under its chemical name N,N-diethyltryptamine and as T-9, is a psychedelic drug closely related to DMT and 4-HO-DET. However, despite its structural similarity to DMT, its activity is induced by an oral dose of around 50–100 mg, without the aid of MAO inhibitors, and the effects last for about 2–4 hours.

Bufotoxins are a family of toxic steroid lactones or substituted tryptamines of which some are toxic. They occur in the parotoid glands, skin, and poison of many toads and other amphibians, and in some plants and mushrooms. The exact composition varies greatly with the specific source of the toxin.

<span class="mw-page-title-main">Colorado River toad</span> Species of amphibian

The Colorado River toad, also known as the Sonoran Desert toad, is a toad species found in northwestern Mexico and the southwestern United States. It is well known for its ability to exude toxins from glands within its skin that have psychoactive properties.

<i>N</i>-Methyltryptamine Chemical compound

N-Methyltryptamine (NMT), also known as monomethyltryptamine, is a chemical compound of the tryptamine family and a naturally occurring compound found in the human body and certain plants.

<span class="mw-page-title-main">Indole alkaloid</span> Class of alkaloids

Indole alkaloids are a class of alkaloids containing a structural moiety of indole; many indole alkaloids also include isoprene groups and are thus called terpene indole or secologanin tryptamine alkaloids. Containing more than 4100 known different compounds, it is one of the largest classes of alkaloids. Many of them possess significant physiological activity and some of them are used in medicine. The amino acid tryptophan is the biochemical precursor of indole alkaloids.

<i>O</i>-Acetylpsilocin Semi-synthetic psychoactive drug

Psilacetin, also known as O-acetylpsilocin or as 4-acetoxy-N,N-dimethyltryptamine, is a semi-synthetic serotonergic psychedelic drug that has been suggested by David Nichols to be a potentially useful alternative to psilocybin for pharmacological studies, as they are both believed to be prodrugs of psilocin. However, some users report that O-acetylpsilocin's subjective effects differ from those of psilocybin and psilocin. Additionally, some users prefer 4-AcO-DMT to natural psilocybin mushrooms due to feeling fewer adverse side effects such as nausea and heavy body load, which are more frequently reported in experiences involving natural mushrooms. It is the acetylated form of the psilocybin mushroom alkaloid psilocin and is a lower homolog of 4-AcO-MET, 4-AcO-DET, 4-AcO-MiPT and 4-AcO-DiPT.

<span class="mw-page-title-main">5-MeS-DMT</span> Chemical compound

5-MeS-DMT (5-methylthio-N,N-dimethyltryptamine) is a lesser-known psychedelic drug. It is the 5-methylthio analog of dimethyltryptamine (DMT). 5-MeS-DMT was first synthesized by Alexander Shulgin. In his book TiHKAL, the minimum dosage is listed as 15-30 mg. The duration listed as very short, just like DMT. 5-MeS-DMT produces similar effects to DMT, but weaker. Shulgin describes his feelings while on a low dose of this drug as "pointlessly stoned", although at a higher dose of 20 mg he says it is "quite intense" and suggests that a higher dose still might have full activity.

<span class="mw-page-title-main">4-PrO-DMT</span> Chemical compound

4-Propionoxy-N,N-dimethyltryptamine is a synthetic psychedelic drug from the tryptamine family with psychedelic effects, and is believed to act as a prodrug for psilocin. It produces a head-twitch response in mice. It has been sold online as a designer drug since May 2019. It was first identified as a new psychoactive substance in Sweden, in July 2019. A number of related derivatives have been synthesized as prodrugs of psilocin for medical applications.

<i>O</i>-Acetylbufotenine Psychedelic tryptamine

O-Acetylbufotenine, or bufotenine O-acetate, also known as 5-acetoxy-N,N-dimethyltryptamine (5-AcO-DMT) or O-acetyl-N,N-dimethylserotonin, is a synthetic tryptamine derivative and putative serotonergic psychedelic. It is the O-acetylated analogue of the naturally occurring peripherally selective serotonergic tryptamine bufotenine and is thought to act as a centrally penetrant prodrug of bufotenine.

<i>O</i>-Pivalylbufotenine Tryptamine serotonergic psychedelic

O-Pivalylbufotenine, or bufotenine O-pivalate, also known as 5-pivaloxy-N,N-dimethyltryptamine or O-pivalyl-N,N-dimethylserotonin, is a synthetic tryptamine derivative and putative serotonergic psychedelic. It is the O-pivalyl analogue of the naturally occurring but peripherally selective serotonergic tryptamine bufotenine and is thought to act as a centrally penetrant prodrug of bufotenine.

References

  1. 1 2 3 Barker SA, McIlhenny EH, Strassman R (2012). "A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans: 1955-2010". Drug Test Anal. 4 (7–8): 617–635. doi:10.1002/dta.422. PMID   22371425.
  2. 1 2 3 4 5 6 7 8 Neumann J, Dhein S, Kirchhefer U, Hofmann B, Gergs U (2024). "Effects of hallucinogenic drugs on the human heart". Front Pharmacol. 15: 1334218. doi: 10.3389/fphar.2024.1334218 . PMC   10869618 . PMID   38370480.
  3. 1 2 Kärkkäinen J, Forsström T, Tornaeus J, Wähälä K, Kiuru P, Honkanen A, Stenman UH, Turpeinen U, Hesso A (2005). "Potentially hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine and dimethyltryptamine in blood and tissues". Scand J Clin Lab Invest. 65 (3): 189–199. doi:10.1080/00365510510013604. PMID   16095048.
  4. ↑ Bufo Alvarius. AmphibiaWeb. Accessed on May 6, 2007.
  5. ↑ "DEA Drug Scheduling". U.S. Drug Enforcement Administration. Archived from the original on 2008-10-20. Retrieved 2007-08-11.
  6. 1 2 3 Chilton WS, Bigwood J, Jensen RE (1979). "Psilocin, bufotenine and serotonin: historical and biosynthetic observations". Journal of Psychedelic Drugs. 11 (1–2): 61–69. doi:10.1080/02791072.1979.10472093. PMID   392119.
  7. ↑ Hoshino T, Shimodaira K (1935). "Synthese des Bufotenins und über 3-Methyl-3-β-oxyäthyl-indolenin. Synthesen in der Indol-Gruppe. XIV". Justus Liebig's Annalen der Chemie. 520 (1): 19–30. doi:10.1002/jlac.19355200104.
  8. 1 2 Davis W, Weil A (1992). "Identity of a New World Psychoactive Toad". Ancient Mesoamerica. 3: 51–9. doi:10.1017/s0956536100002297. S2CID   162875250.
  9. ↑ Yao B, Wang L, Wang H, Bao J, Li Q, Yu F, et al. (April 2021). "Seven interferon gamma response genes serve as a prognostic risk signature that correlates with immune infiltration in lung adenocarcinoma". Aging. 13 (8): 11381–11410. doi:10.1086/202831. PMC   8109098 . PMID   33839701. S2CID   143698915.
  10. ↑ Hitt M, Ettinger DD (June 1986). "Toad toxicity". The New England Journal of Medicine. 314 (23): 1517–1518. doi:10.1056/NEJM198606053142320. PMID   3702971.
  11. ↑ Ragonesi DL (1990). "The boy who was all hopped up". Contemporary Pediatrics. 7: 91–4.
  12. 1 2 3 4 Brubacher JR, Ravikumar PR, Bania T, Heller MB, Hoffman RS (November 1996). "Treatment of toad toxin poisoning with digoxin-specific Fab fragments". Chest. 110 (5): 1282–1288. doi:10.1378/chest.110.5.1282. PMID   8915235.
  13. ↑ Gowda RM, Cohen RA, Khan IA (April 2003). "Toad venom poisoning: resemblance to digoxin toxicity and therapeutic implications". Heart. 89 (4): 14e–14. doi:10.1136/heart.89.4.e14. PMC   1769273 . PMID   12639891.
  14. ↑ Lever, Christopher (2001). The Cane Toad: The History and Ecology of a Successful Colonist. Westbury Academic & Scientific Publishing. ISBN   978-1-84103-006-7.
  15. ↑ Rodrigues, R.J. Aphrodisiacs through the Ages: The Discrepancy Between Lovers' Aspirations and Their Desires. ehealthstrategies.com
  16. ↑ Centers for Disease Control and Prevention (CDC) (November 1995). "Deaths associated with a purported aphrodisiac--New York City, February 1993-May 1995". MMWR. Morbidity and Mortality Weekly Report. 44 (46): 853–5, 861. PMID   7476839.
  17. ↑ The Dog Who Loved to Suck on Toads. NPR. Accessed on May 6, 2007.
  18. ↑ Psychoactive toad: Cultural references
  19. ↑ Most, A. "Bufo avlarius: The Psychedelic Toad of the Sonoran Desert". erowid.org. Retrieved 2007-08-12.
  20. ↑ How 'bout them toad suckers? Ain't they clods? Archived September 28, 2011, at the Wayback Machine Smoky Mountain News. Accessed on May 6, 2007
  21. ↑ Costa TO, Morales RA, Brito JP, Gordo M, Pinto AC, Bloch C (September 2005). "Occurrence of bufotenin in the Osteocephalus genus (Anura: Hylidae)". Toxicon. 46 (4): 371–375. Bibcode:2005Txcn...46..371C. doi:10.1016/j.toxicon.2005.02.006. PMID   16054186.
  22. 1 2 Repke DB, Torres CM (2006). Anadenanthera: visionary plant of ancient South America. New York: Haworth Herbal Press. ISBN   978-0-7890-2642-2.
  23. 1 2 Pochettino ML, Cortella AR, Ruiz M (1999). "Hallucinogenic Snuff from Northwestern Argentina: Microscopical Identification of Anadenanthera colubrina var. cebil (Fabaceae) in Powdered Archaeological Material". Economic Botany. 53 (2): 127–132. Bibcode:1999EcBot..53..127P. doi:10.1007/BF02866491. ISSN   0013-0001. JSTOR   4256172. S2CID   13153575.
  24. ↑ Miller MJ, Albarracin-Jordan J, Moore C, Capriles JM (June 2019). "Chemical evidence for the use of multiple psychotropic plants in a 1,000-year-old ritual bundle from South America". Proceedings of the National Academy of Sciences of the United States of America. 116 (23): 11207–11212. Bibcode:2019PNAS..11611207M. doi: 10.1073/pnas.1902174116 . PMC   6561276 . PMID   31061128.
  25. ↑ Moretti C, Gaillard Y, Grenand P, Bévalot F, Prévosto JM (June 2006). "Identification of 5-hydroxy-tryptamine (bufotenine) in takini (Brosimumacutifolium Huber subsp. acutifolium C.C. Berg, Moraceae), a shamanic potion used in the Guiana Plateau". Journal of Ethnopharmacology. 106 (2): 198–202. doi:10.1016/j.jep.2005.12.022. PMID   16455218.
  26. ↑ Chamakura RP (1994). "Bufotenine—a hallucinogen in ancient snuff powders of South America and a drug of abuse on the streets of New York City". Forensic Sci Rev. 6 (1): 2–18.
  27. ↑ Rumack BH, Spoerke DG (1994). Handbook of Mushroom Poisoning: Diagnosis and Treatment. CRC Press. p. 208. ISBN   978-0849301940.
  28. ↑ Buck, Robert W. (1963-08-24). "Toxicity of Amanita muscaria". JAMA. 185 (8): 663–664. doi:10.1001/jama.1963.03060080059020. ISSN   0098-7484. PMID   14016551.
  29. 1 2 Jiménez JH, Bouso JC (August 2022). "Significance of mammalian N, N-dimethyltryptamine (DMT): A 60-year-old debate". J Psychopharmacol. 36 (8): 905–919. doi:10.1177/02698811221104054. PMID   35695604.
  30. ↑ Faurbye A, Pind K (November 1968). "Occurrence of bufotenin in the urine of schizophrenic patients and normal persons". Nature. 220 (5166): 489. Bibcode:1968Natur.220..489F. doi: 10.1038/220489a0 . PMID   5686166. S2CID   4192320.
  31. ↑ Siegel M (October 1965). "A sensitive method for the detection of n,n-dimethylserotonin (bufotenin) in urine; failure to demonstrate its presence in the urine of schizophrenic and normal subjects". Journal of Psychiatric Research. 3 (3): 205–211. doi:10.1016/0022-3956(65)90030-0. PMID   5860629.
  32. ↑ Pomilio AB, Vitale AA, Ciprian-Ollivier J, Cetkovich-Bakmas M, Gómez R, Vázquez G (April 1999). "Ayahoasca: an experimental psychosis that mirrors the transmethylation hypothesis of schizophrenia". Journal of Ethnopharmacology. 65 (1): 29–51. doi:10.1016/S0378-8741(98)00163-9. PMID   10350367.
  33. ↑ Ciprian-Ollivier J, Cetkovich-Bakmas MG (December 1997). "Altered consciousness states and endogenous psychoses: a common molecular pathway?". Schizophrenia Research. 28 (2–3): 257–265. doi:10.1016/S0920-9964(97)00116-3. PMID   9468359. S2CID   20830063.
  34. ↑ Carpenter WT, Fink EB, Narasimhachari N, Himwich HE (October 1975). "A test of the transmethylation hypothesis in acute schizophrenic patients". The American Journal of Psychiatry. 132 (10): 1067–1071. doi:10.1176/ajp.132.10.1067. PMID   1058643.
  35. 1 2 Emanuele E, Colombo R, Martinelli V, Brondino N, Marini M, Boso M, et al. (2010). "Elevated urine levels of bufotenine in patients with autistic spectrum disorders and schizophrenia". Neuro Endocrinology Letters. 31 (1): 117–121. PMID   20150873.
  36. ↑ Takeda N, Ikeda R, Ohba K, Kondo M (November 1995). "Bufotenine reconsidered as a diagnostic indicator of psychiatric disorders". NeuroReport. 6 (17): 2378–2380. doi:10.1097/00001756-199511270-00024. PMID   8747157.
  37. ↑ Takeda N (February 1994). "Serotonin-degradative pathways in the toad (Bufo bufo japonicus) brain: clues to the pharmacological analysis of human psychiatric disorders". Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology. 107 (2): 275–281. doi:10.1016/1367-8280(94)90051-5. PMID   7749594.
  38. ↑ Räisänen MJ, Virkkunen M, Huttunen MO, Furman B, Kärkkäinen J (September 1984). "Increased urinary excretion of bufotenin by violent offenders with paranoid symptoms and family violence". Lancet. 2 (8404): 700–701. doi:10.1016/S0140-6736(84)91263-7. PMID   6147728. S2CID   33258299.
  39. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 McBride MC (2000). "Bufotenine: toward an understanding of possible psychoactive mechanisms". J Psychoactive Drugs. 32 (3): 321–331. doi:10.1080/02791072.2000.10400456. PMID   11061684.
  40. 1 2 3 4 5 6 7 Plazas E, Faraone N (February 2023). "Indole Alkaloids from Psychoactive Mushrooms: Chemical and Pharmacological Potential as Psychotherapeutic Agents". Biomedicines. 11 (2): 461. doi: 10.3390/biomedicines11020461 . PMC   9953455 . PMID   36830997.
  41. ↑ Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB (October 2014). "Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes". Psychopharmacology (Berl). 231 (21): 4135–4144. doi:10.1007/s00213-014-3557-7. PMC   4194234 . PMID   24800892.
  42. ↑ Shen HW, Jiang XL, Winter JC, Yu AM (October 2010). "Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions". Curr Drug Metab. 11 (8): 659–666. doi:10.2174/138920010794233495. PMC   3028383 . PMID   20942780.
  43. 1 2 Ott J (2001). "Pharmañopo-psychonautics: human intranasal, sublingual, intrarectal, pulmonary and oral pharmacology of bufotenine". Journal of Psychoactive Drugs. 33 (3): 273–281. doi:10.1080/02791072.2001.10400574. PMID   11718320. S2CID   5877023.
  44. ↑ Glennon RA, Gessner PK, Godse DD, Kline BJ (November 1979). "Bufotenine esters". J Med Chem. 22 (11): 1414–1416. doi:10.1021/jm00197a025. PMID   533890.
  45. ↑ Gessner PK, Dankova J (1975). "Brain bufotenine from administered acetylbufotenine: Comparison of its tremorgenic activity with that of N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine". Pharmacologist. 17: 259.
  46. 1 2 3 4 Fabing HD, Hawkins JR (May 1956). "Intravenous bufotenine injection in the human being". Science. 123 (3203): 886–887. Bibcode:1956Sci...123..886F. doi:10.1126/science.123.3203.886. PMID   13324106.
  47. ↑ Turner WJ, Merlis S (January 1959). "Effect of some indolealkylamines on man". A.M.A. Archives of Neurology and Psychiatry. 81 (1): 121–129. doi:10.1001/archneurpsyc.1959.02340130141020. PMID   13605329.
  48. ↑ McLeod WR, Sitaram BR (November 1985). "Bufotenine reconsidered". Acta Psychiatrica Scandinavica. 72 (5): 447–450. doi:10.1111/j.1600-0447.1985.tb02638.x. PMID   4091027. S2CID   9578617.
  49. ↑ "South Korean man dies after eating toads". BBC. 21 April 2017.
  50. ↑ "Taiwanese dies from eating toads, 5 injured". Taiwan News. 17 December 2019. Retrieved 2019-12-18.
  51. ↑ Fuller RW, Snoddy HD, Perry KW (July 1995). "Tissue distribution, metabolism and effects of bufotenine administered to rats". Neuropharmacology. 34 (7): 799–804. doi:10.1016/0028-3908(95)00049-C. PMID   8532147. S2CID   23801665.
  52. ↑ "Bufotenine". PubChem. Retrieved 11 September 2024.
  53. ↑ "Bufotenine: Uses, Interactions, Mechanism of Action". DrugBank Online. 31 July 2007. Retrieved 12 September 2024.
  54. ↑ "BUFOTENINE". ChemSpider. 12 September 2024. Retrieved 12 September 2024.
  55. ↑ "Dimethyltryptamine". PubChem. Retrieved 11 September 2024.
  56. ↑ "Dimethyltryptamine: Uses, Interactions, Mechanism of Action". DrugBank Online. 31 July 2007. Retrieved 12 September 2024.
  57. ↑ "Dimethyltryptamine". ChemSpider. 12 September 2024. Retrieved 12 September 2024.
  58. ↑ "Serotonin". PubChem. Retrieved 11 September 2024.
  59. ↑ "Serotonin: Uses, Interactions, Mechanism of Action". DrugBank Online. 21 February 2013. Retrieved 12 September 2024.
  60. ↑ "Serotonin". ChemSpider. 12 September 2024. Retrieved 12 September 2024.
  61. ↑ Criminal Code Regulation 2005 (SL2005-2) (rtf), Australian Capital Territory, May 1, 2005, retrieved 2007-08-12
  62. ↑ Poisons Standard October 2015 https://www.comlaw.gov.au/Details/F2015L01534
  63. ↑ Poisons Act 1964 Archived 2015-12-22 at the Wayback Machine . slp.wa.gov.au
  64. ↑ Misuse of Drugs Act 1981 (2015) Archived 2015-12-22 at the Wayback Machine . slp.wa.gov.au
  65. ↑ §1308.11 Schedule I. Archived 2009-08-27 at the Wayback Machine deadiversion.usdoj.gov
  66. ↑ "Folkhälsomyndigheten föreslår att 20 ämnen klassas som narkotika eller hälsofarlig vara" (in Swedish). Folkhälsomyndigheten. 15 May 2019. Archived from the original on 20 October 2021. Retrieved 11 November 2019.