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Created page with ''''5-HO-DMT''' TRYPTAMINE, 5-HYDROXY-N,N-DIMETHYL; INDOL-5-OL, 3-[2-(DIMETHYLAMINO)ETHYL]; 5-HYDROXY-N,N-DIMETHYLTRYPTAMINE; 3-(2-DIMETHYLAMINOETHYL)INDOL-5-OL; N,N-DIMETHYLSEROT...'
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'''5-HO-DMT'''
TRYPTAMINE, 5-HYDROXY-N,N-DIMETHYL; INDOL-5-OL, 3-[2-(DIMETHYLAMINO)ETHYL]; 5-HYDROXY-N,N-DIMETHYLTRYPTAMINE; 3-(2-DIMETHYLAMINOETHYL)INDOL-5-OL; N,N-DIMETHYLSEROTONIN; '''BUFOTENINE'''; MAPPINE


{{SummarySheet}}
{{SubstanceBox/Bufotenin}}


'''Bufotenin''' ('''5-HO-DMT''', N,N-dimethylserotonin, bufotenine) is a naturally occurring substituted [[Chemical class::tryptamine]] [[alkaloid]] and a [[serotonergic psychedelic|serotonergic]] [[Psychoactive class::psychedelic]] drug. Bufotenin is a structural derivative of tryptamine and serotonin. Bufotenin is found in a wide array of flora and fauna, including several species of psychoactive toads, most notably the Colorado River toad. The overall effects of bufotenin are generally described as less pleasant than those of other psychedelics such as [[LSD]].


== SYNTHESIS ==
==Chemistry==
A solution of 0.67 g 5-hydroxyindole (indol-5-ol) in 10 mL dry MeOH was treated with a solution of 0.30 g NaOMe in MeOH, followed by 0.70 g benzyl chloride. The mixture was heated on the steam bath for 0.5 h, and the solvent removed under vacuum. The residue was suspended between H2O and CH2Cl2, the organic phase separated and the aqueous phase extracted once with CH2Cl2. The combined organics were stripped of solvent under vacuum, and the residue distilled. A colorless fraction came over at 170-190 °C and spontaneously crystallized in the receiver. There was obtained 0.90 g (80%) 5-benzyloxyindole with a mp 81-86 °C which increased, on recrystallization from toluene / hexane, to 94-96 °C. A sample prepared from the decarboxylation of 5-benzyloxyindole-2-carboxylic acid has been reported to have a mp of 102 °C from benzene.
[[File:Substituted tryptamine.svg|thumb|294px|right|Generic structure of a tryptamine molecule.]]
{{drugbox |
Bufotenin, 5-HO-DMT or 5-hydroxy-N,N-dimethyltryptamine is a ring-substituted indole alkaloid molecule of the [[tryptamine]] class. Tryptamines share a core structure comprised of a bicylic indole heterocycle attached at R<sub>3</sub> to a terminal amine group via an ethyl side chain. Bufotenin is substituted at R<sub>5</sub> of its indole heterocycle with a hydroxy (OH) functional group; it also contains two methyl groups CH<sub>3</sub>- bound to the terminal amine R<sub>N</sub> of its tryptamine backbone (DMT).
| IUPAC_name = 3-(2-dimethylaminoethyl)-1H-indol-5-ol
| image = Bufotenin.png
| image2 = Bufotenin-3d-sticks.png
| width = 140
| width2 = 150
| CAS_number = 487-93-4
| ATC_prefix =
| ATC_suffix =
| PubChem = 10257
| C=12 | H=16 | N=2 | O=1
| molecular_weight = 204.268 g/mol
| smiles = CN(C)CCc1c[nH]c2ccc(O)cc12
| boiling_point = 320
| melting_point = 146
| melting_high = 147
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =
| solubility =
| excretion =
| pregnancy_AU = 
| pregnancy_US =
| pregnancy_category = 
| legal_AU =
| legal_CA =
| legal_UK =
| legal_US = Schedule I
| legal_status =
| routes_of_administration = Parenteral
}}
A solution of 1.0 g 5-benzyloxyindole in 20 mL Et2O was cooled to 0 °C, vigorously stirred, and treated with 0.6 g oxalyl chloride in 10 mL Et2O, added dropwise, over the course of 0.5 h. About half way into the addition a pale red solid appeared. The stirring was continued for an additional 0.5 h and the solids were removed by filtration and washed with a small amount of Et2O. This acid chloride had a mp of 149-151 °C but was used without further purification or characterization in the following reaction. It was added in small increments to 1.2 mL of a 33% aqueous solution of dimethylamine, diluted with acidified H2O, and the resulting solids removed by filtration. These were washed with H2O, and then Et2O and air dried. The product, 5-benzyloxy-N,N-dimethyl-3-indoleglyoxylamide weighed 1.18 g (82%) when dry and had a mp of 185-187 °C.


To a well stirred suspension of 1.0 g LAH in 40 mL Et2O there was added a solution of 1.0 g 5-benzyloxy-N,N-dimethyl-3-indoleglyoxamide in 15 mL THF. When the addition was complete, the mixture was held at reflux temperature for 6 h, cooled, the excess hydride and reaction complex cautiously decomposed by the addition of H2O, and when the hydrogen evolution ceased the mixture was made basic with concentrated NH4OH. The solids were removed by filtration and the filter cake washed with THF. The filtrate and washings were combined, and the solvents removed under vacuum to give a clear residue that was dissolved in Et2O and acidified with a solution of oxalic acid in Et2O. The formed crystals were removed by filtration, washed with Et2O and air dried to yield 1.0 g (84%) of 5-benzyloxy-N,N-dimethyltryptamine oxalate with a mp of 178-180 °C after recrystallization from MeOH. The hydrochloride salt has a reported mp of 154-155 °C and of 162-163 °C.
==Pharmacology==
{{Further|Serotonergic psychedelic}}
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 completely eliminated within 8 hours.<ref>{{cite journal | vauthors=((Fuller, R. W.)), ((Snoddy, H. D.)), ((Perry, K. W.)) | journal=Neuropharmacology | title=Tissue distribution, metabolism and effects of bufotenine administered to rats | volume=34 | issue=7 | pages=799–804 | date= July 1995 | url=https://linkinghub.elsevier.com/retrieve/pii/002839089500049C | issn=00283908 | doi=10.1016/0028-3908(95)00049-C}}</ref> 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.


The benzyl group was removed by hydrogenation of a solution of 0.8 g 5-benzyloxy-N,N-dimethyltryptamine oxalate in 5 mL MeOH containing 0.1 g 10% Pd/C catalyst. The mixture was shaken under three atm hydrogen for 6 h, and the solids removed by filtration. Evaporation of the solvent under vacuum gave a residue that was dissolved in anhydrous Et2O and acidified with a solution of oxalic acid in Et2O. There was thus obtained, after filtration, Et2O washing, and air drying, 0.53 g (87%) bufotenine mono-oxalate as pink needles, with a mp 93-94 °C. A mp of 178 °C in the literature may be of the bioxalate. The free base has been reported to have a mp of 125-126 °C or 146-147 °C.
Bufotenin's [[psychedelic]] effects are primarily believed to come from its efficacy at the [[Serotonin#The 5-HT system|5-HT<sub>2A</sub> receptor]] as a [[Agonist#Agonists|partial agonist]]. Specifically, this molecule shows high binding affinity for the 5-HT<sub>2A</sub> and 5-HT<sub>1A</sub> subtypes.<ref name="Krebs-ThomsonRuiz2006">{{cite journal|title=The roles of 5-HT<sub>1A</sub> and 5-HT<sub>2</sub> receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats|pmid=17013638|doi=10.1007/s00213-006-0566-1|year=2006|first1=K.|last1=Krebs-Thomson|first2=E. M.|last2=Ruiz|first3=V.|last3=Masten|first4=M.|last4=Buell|first5=M. A.|last5=Geyer|volume=189|issue=3|pages=319-329|journal=Psychopharmacology|issn=0033-3158|eissn=1432-2072|oclc=2409222}}</ref> However, the role of these interactions and how they result in the [[psychedelic]] experience continues to remain elusive.


Additional mechanisms of action such as [[reuptake inhibition]] of [[neurotransmitters]] such as [[serotonin]], [[noradrenaline]] and [[dopamine]] are also thought to be involved to an extent.<ref name="pmid17223101">{{cite journal|title=The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain|pmid=17223101|volume=559|issue=2–3|year=2007|pages=132-137|first1=F.|last1=Nagai|first2=R.|last2=Nonaka|first3=K.|last3=Satoh|first4=H.|last4=Kamimura|journal=European Journal of Pharmacology|issn=0014-2999|eissn=1879-0712|oclc=01568459|doi=10.1016/j.ejphar.2006.11.075}}</ref> This can result in bufotenin becoming dangerously toxic when combined with [[MAOIs]], [[RIMAs]], [[SSRIs]], [[stimulants]] or any substance which acts as a [[releasing agent]] or [[reuptake inhibitor]] of monoamine [[neurotransmitters]].


== DOSAGE ==
==Subjective effects==
8 - 16 mg, intravenously
{{Preamble/SubjectiveEffects}}
{{effects/base
|{{effects/physical|
The physical effects of Bufotenin can be broken down into several components which progressively intensify proportional to dosage. In comparison to its often relatively mild accompanying cognitive and visual effects, Bufotenin seems to have by far the most proportionally intense and overwhelming physical sensations found within the known psychedelic experience. These individual components are complex, overwhelming and seem to be equally capable of being interpreted as either extremely pleasurable and euphoric or uncomfortable and dysphoric.
*'''[[Effect::Tactile enhancement]]''' - This particular component is perhaps the most overwhelming sensation within the entirety of the Bufotenin experience. It increases the intensity of tactile sensations to such an overwhelming extent that it can induce a sensation of sustained and repeatable full body orgasm within every nerve ending across the entire body to a degree not found within any other psychedelic drug. The experience of this results in the perception of having a difficulty sustaining the act of breathing. It is worth noting, however, that this is not a genuine or dangerous experience of [[respiratory depression]] and is considered to be safe.
*'''[[Effect::Bodily control enhancement]]'''
*'''[[Effect::Bodily pressures]]'''
*'''[[Effect::Changes in gravity]]'''
*'''[[Effect::Physical euphoria|Euphoria]]'''
*'''[[Effect::Motor control loss]]'''
*'''[[Effect::Nausea]]'''
*'''[[Effect::Perception of bodily heaviness]]'''
*'''[[Effect::Pupil dilation]]'''
*'''[[Effect::Skin flushing]]
*'''[[Effect::Temperature regulation suppression]]'''
*'''[[Effect::Vasoconstriction]]'''


}}


== DURATION ==
{{effects/visual|
1 - 2 hrs
The visual effects of Bufotenin can be broken down into several components which progressively intensify proportional to dosage. In comparison to its consistently overwhelming and intense accompanying cognitive and physical effects, bufotenin seems to have some of the most proportionally underwhelming visual effects found within the known psychedelic experience.
*'''[[Effect::Visual acuity enhancement]] and [[Effect::Visual acuity suppression]]''' - Bufotenin is equally capable of both decreasing and increasing visual acuity. The outcome of which effect will manifest seems to be chosen almost entirely at random and is largely setting dependent.
*'''[[Effect::Drifting]]''' ([[Drifting#Morphing|Morphing]], [[Drifting#Breathing|Breathing]], [[Drifting#Melting|Melting]], [[Drifting#Flowing|Flowing]]) - In comparison to other psychedelics, this effect can be described as identical to DMT in its style, highly detailed, slow and smooth in motion and static in appearance.
*'''[[Effect::Colour enhancement]]'''
*'''[[Effect::Colour shifting]]'''
*'''[[Effect::Environmental orbism]]'''
*'''[[Effect::Recursion]]'''


====[[Effect::Geometry]]====
The visual geometry that is present throughout this trip does not usually occur and never extends beyond level 7 at its highest state. It is very similar to [[DMT]] although significantly smaller in size and more likely to manifest in darkness or without distractions. In terms of appearance, it can be comprehensively described through its [[Geometry#Variations|variations]] as intricate in complexity, abstract in form, equally organic and digital in feel, structured in organization, brightly lit, multicoloured in scheme, glossy in shading, equal in sharp and soft edges, small in size, fast in speed, smooth in motion, equal in rounded and angular corners, immersive in depth and consistent in its intensity.


== QUALITATIVE COMMENTS ==
}}
(with 1 mg, intravenously, over a three minute period) "Within a minute (from the start of the injection) I had a tight feeling in my chest and my face felt as if it had been jabbed by nettles and this lasted for about 6 minutes. I had fleeting nausea."


(with 2 mg, intravenously, over a 3 minute period) "I felt a tightness in my throat and stomach and it seemed that my pulse was racing, although apparently there was no change in either my pulse or blood pressure."
|{{effects/cognitive|
*'''[[Effect::Amnesia]]'''
*'''[[Effect::Analysis enhancement]]'''
*'''[[Effect::Anxiety]]'''
*'''[[Effect::Conceptual thinking]]'''
*'''[[Effect::Delusion]]'''
*'''[[Effect::Autonomous voice communication]]'''
*'''[[Effect::Emotion enhancement]]'''
*'''[[Effect::Increased music appreciation]]'''
*'''[[Effect::Memory suppression]]'''
**'''[[Effect::Ego death]]'''
*'''[[Effect::Mindfulness]]'''
*'''[[Effect::Thought connectivity]]'''
*'''[[Effect::Time distortion]]'''
*'''[[Effect::Unity and interconnectedness]]'''
*'''[[Effect::Wakefulness]]'''


(with 4 mg, intravenously, over a 3 minute period) "During the injection, I first felt a burning sensation in my face, then a load pressing down from above, and then a numbness of the entire body. I saw red and black spots -- a vivid orange-red -- moving around. Apparently my purplish face color lasted some 15 minutes, well after my visual things had disappeared."
}}


(with 8 mg, intravenously, over a 3 minute period) "I became lightheaded as soon as the injection started, and then my face turned purple and I became nauseated and I felt I couldn't breathe. I see white, straight lines with a black background. I can't trace a pattern. Now there are red, green and yellow dots, very bright like they were made out of fluorescent cloth, moving like blood cells through capillaries, weaving in and out of the white lines. I another two minutes, everything was pretty much gone."
{{effects/auditory|
*'''[[Effect::Auditory enhancement|Enhancements]]'''
*'''[[Effect::Auditory distortion|Distortions]]'''
*'''[[Effect::Auditory hallucinations|Hallucinations]]'''
}}


(with 10 mg, intravenously, over a 50 second period) "My face was suddenly very hot. I could not breathe fast enough."
}}
 
(with 10 mg, intravenously, over a 77 minute period) "There were no psychological changes."
 
(with 16 mg, intravenously, over a 3 minute period) "Almost immediately I felt a burning sensation in the roof of my mouth and I felt a tingling all over my body. My face turned purple, and my chest feels crushed. Everything has a yellow haze, and I was sweating heavily and I vomited. Words can't come. My mind feels crowded. When I start on a thought, another one comes along and clashes with it. I can't express myself clearly. I am here and not here. It has now been forty minutes and I feel better, but I still feel like I would like to walk it off, like a hang-over."
 
 
== EXTENSIONS AND COMMENTARY ==
This is a presentation of the very earliest studies done with bufotenine with human subjects, studies with 14 schizophrenic patients at a state mental hospital and with two convicts in a state prison. Two convicts at a state prison were injected over the course of three minutes, with a solution of bufotenine as the salt. This single observation, a description of hyperserotoninemia (a release of serotonin in the blood, called a carcinoid flush) was all it took, at the right time and the right place, to put bufotenine on the books as a "dangerous drug" by FDA classification. And with the passage of the Controlled Substance Act of 1970, it was placed in Schedule I as a hallucinogen, with a high abuse potential and no accepted medical utility. Whatever the actual activity of bufotenine might be, and what role it could play in explaining the complex role of serotonin in the human animal, today it would be extremely difficult to study, because of the flushing of the face of an experimental subject in a prison in Maryland in study that occurred at just the wrong time.
 
But that is the politics of the drug. I cannot help but comment on some aspects of the medical ethics that accompanied these studies. Here were a collection of 14 schizophrenic patients, experimental cattle is the analogy that comes to mind, into which the researching physicians injected their drug. Listen to the account of one lady, following a rapid intravenous injection of bufotenine. "There was intense salivation. She could easily have drowned in her own saliva, and she had to be turned on her side. The pulse rate rose slightly during the period extending from the end of the injection until some 10 minutes later, but without much change in blood pressure. Responsiveness returned in about 23 minutes, at which time the patient was entirely lucid and, in response to a query related to a preinjection suggestion, spoke of a long repressed memory from the age of three years, when she came into the bathroom and saw her mother dying of a uterine hemorrhage. This was told without affect and had no therapeutic consequences." HOLY COW! A schizophrenic victim volunteers a long-repressed memory of her mother's traumatic death. And with the state of the healing art in the mental hospitals of that time, two physicians effectively ignore what today would be considered a dramatic break-through in therapy. Another of their trials was acknowledged as being nearly fatal, requiring artificial respiration as intervention. This is research in the healing art of medicine?
 
So much for the politics, and for the medical ethics lecture. What can one say about the drug itself? This is an example of a very rare breed of active compounds, one that can be found in both the animal and the vegetable kingdoms. From toads to toadstools. There are a number of extremely close structural relatives out there in the wild world. Bufotenine must first and foremost be seen as an extremely close relative to serotonin (one of our principal neurotransmitter) of which it is the N,N-dimethyl homologue). There are many modifications of it in nature (found most frequently in the skins of frogs), and these all have deceptively similar names. It is helpful to me to tally them.
 
Bufoviridine: This is the 1:1 ester of bufotenine with sulfuric acid. It is yet more polar than bufotenine, and correspondingly less likely to get into the brain. If the bisulfate acid position were itself esterified in some biologically stable manner, then this compound just might be centrally active, but probably only via a parenteral route as seen with 5-MeO-DMT. The exposed dimethylamino group would still make it an easy substrate for MAO's.
 
Bufotenidine or Cinobufagine: This is the quaternary amine internal salt, 5-hydroxy-N,N,N-trimethyltryptammonium salt. It also is frequently found as a hydrogen sulfate ester, but this latter has no trivial name. Mention has been made of bufotenidine and its sulfate ester as a occasional companion of histamine analogues found in frog skins. See the appendix on histamines.


Dehydrobufotenine: There is a covalent bond formed between the dimethylated nitrogen atom and the indolic 4-position, by the theoretical removal of a molecule of hydrogen. It is no longer a simple tryptamine but as it is a commonly found component of the chemistry of several toads, and a few giant reeds as well, it is included here. It is, by definition, a quaternary amine salt. The original structure assigned it was that of a vinylamine (with the loss of a hydrogen molecule from the alpha/beta chain positions. This was shown to be incorrect.
===Experience reports===
There are currently no anecdotal reports which describe the effects of this compound within our [[experience index]]. Additional experience reports can be found here:


Bufothionine: This is the hydrogen sulfate ester of dehydrobufotenine.
*[https://erowid.org/experiences/subs/exp_Bufotenin.shtml Erowid Experience Vaults: Bufotenin]


O-Methylnordehydrobufotenine: This is a rearrangement product of dehydrobuftenine, which may be a natural product or it may be an artifact of analysis.
==Natural sources==
===Colorado River toad===
[[File:Bufo alvarius1.jpg|thumbnail|235px|
<center>[[File:Status iucn3.1 LC.svg.png|frameless|220px]]</center>
]]
The Colorado River toad (Incilius alvarius), also known as the Sonoran Desert toad, is a psychoactive toad found in northern Mexico and the southwestern United States. Its skin and venom contain [[5-MeO-DMT]] and bufotenin.


O-Methylbufotenine: This represents a true crossover alkaloid, found in many plants as well as in the toad family, It is entered as a recipe under the synonym, 5-MeO-DMT.
The toad's primary defense system are glands that produce a poison that may be potent enough to kill a grown dog.<ref name="desertmuseum">{{cite book|author=Steven J. Phillips|editor=Patricia Wentworth Comus|year=2000|title=A Natural History of the Sonoran Desert|publisher=University of California Press|page=537|isbn=0-520-21980-5|oclc=837703609}}</ref> These parotoid glands also produce the 5-MeO-DMT<ref>{{cite web|url=http://www.erowid.org/archive/sonoran_desert_toad/erspamer.htm|publisher=Erowid|title=The Sonoran Desert Toad: Bufo alvarius|access-date=August 27, 2020}}</ref> and bufotenin for which the toad is known. Fresh venom can easily be collected from these glands without harm to the toad. To do this, obtain a flat glass plate or any other smooth, nonporous surface of at least 12-inches square and hold the toad in front of the plate (which is fixed in a vertical position). When the desert toad is stroked near the parotid glands in the neck region, there is a squirting out of this venom. When it is allowed to dry on a hard surface it takes on the texture of rubber cement. It contains up to 15% 5-MeO-DMT, as well as [[N-methyl-5-methoxytryptamine]], [[5-MeO-NMT]] and Bufotenin, which have their own entries. In this manner, the venom can be collected on the glass plate, free of dirt and liquid released when the toad is handled.


Norbufotenine (5-hydroxy-N-methyltryptamine, N-methylserotonin, 5-OH-NMT): This base is scattered in both the animal and the plant kingdoms. It has been found in quite a few toads and in barley shoots. It has been isolated from the herb Desmodium pulchellum. This is an interesting twilight compound lying half way between a notorious toxin (bufotenine) and a vital neurotransmitter (serotonin). And it is unexplored, for shame. It has been detected in the urine of schizophrenic subjects, but that doesn't say anything about its potential activity. That bare hydroxyl group may make it difficult to get into the brain. Probably as difficult as bufotenine itself proved to be. The removal of the second methyl group reveals serotonin.
==Toxicity and harm potential==
{{Further|Responsible use#Hallucinogens}}
The toxicity and long-term health effects of recreational bufotenin do not seem to have been studied in any scientific context and the exact [[Toxicity::toxic dose is unknown]]. This is because bufotenin is a [[research chemical]] with very little history of human usage. Anecdotal evidence from people within the psychonaut community who have tried bufotenin suggests that there are no negative health effects attributed to simply trying the drug by itself at low to moderate doses and using it very sparingly (but nothing can be completely guaranteed). [https://www.google.com/ Independent research] should always be done to ensure that a combination of two or more substances is safe before consumption.


Bufogenins or Bufagins: These are nitrogen-free steroidal lactones that are heart toxins found in toad venom. They have no chemical resemblance to bufotenine whatsoever. Examples are bufogenin B, bufotalin and bufotalinin.
It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug.
===Tolerance and addiction potential===
Bufotenin is [[Addiction potential::not habit-forming]] and the desire to use it can actually decrease with use. It is most often self-regulating.  


Bufotoxins: These are steroidal bufagins, usually linked via an hydroxyl suberic acid which is, in turn, bound by a peptide link to arginine.
Tolerance to the effects of bufotenin is built [[Time to full tolerance::almost immediately after ingestion]]. After that, it takes about [[Time to half tolerance::1 hour]] for the tolerance to be reduced to half and [[Time to zero tolerance::2 hours]] to be back at baseline (in the absence of further consumption). Bufotenin does not have a cross-tolerance with other [[psychedelics]], meaning that after the consumption of bufotenin psychedelics will not have a reduced effect.


The are two structural variations of bufotenine that I feel would be interesting to explore. One deals with the ethers of the 5-hydroxyl group. The O-methyl ether is, of course, 5-MeO-DMT. It is mentioned above under the name O-methylbufotenine. What about the very obvious O-ethylbufotenine, 5-EtO-DMT? It had once been synthesized from 5-ethoxytryptophol in a physostigmine study, and had been converted to bufotenine with aluminum chloride. If the analogy from the phenethylamines applies here (MEM is as potent as TMA-2) then 5-EtO-DMT should be as potent as 5-MeO-DMT. And probably would have to be smoked for the very same reasons. Another variation deals with possible esters on that 5-hydroxyl group. Finding activity in things like the bisulfate bufoviridine would be unlikely, but perhaps an acetate ester (easily made from bufotenine and acetic anhydride) would allow it to make it into the CNS, in a manner similar to the acetate of the 4-hydroxy analogue, psilocin.
===Dangerous Interactions===
{{DangerousInteractions/Intro}}
{{DangerousInteractions/Psychedelics}}


There once was (and maybe still is) a group called The Institute of Current World Affairs who gave grants to people to allow them to travel and write on topics of cultural interest. I was on their mailing list, which gave me a fabulous collection of essays and vignettes written by Andy Weil, who later spun some of them together into a book called The Marriage of the Sun and Moon. In trying to organize and understand the pharmacology of bufotenine I was pleasantly reminded of the essays Andy devoted to the magic of Uri Geller.
Deaths from bufotenin are rare but, as a powerful [[monoamine]] [[reuptake inhibitor]] (MRI), injury can occur when excessive doses are taken or when taken with drugs such as [[MAOIs]], [[RIMAs]], [[stimulants]] and any substance which act as a [[releasing agent]] or [[reuptake inhibitor]] of [[neurotransmitters]] such as [[serotonin]] and [[dopamine]]. This has resulted in well documented deaths<ref>{{cite journal|pmid=15214625|doi=10.1081/clt-120030949|year=2004|volume=42|issue=2|pages=191-195|first1=D. E.|last1=Brush|first2=S. B.|last2=Bird|first3=E. W.|last3=Boyer|journal=Journal of Toxicology: Clinical Toxicology|issn=1556-3650|eissn=1556-9519|title=Monoamine oxidase inhibitor poisoning resulting from Internet misinformation on illicit substances}}</ref><ref>{{cite journal|pmid=16356341|doi=10.1093/jat/29.8.838|title=A fatal intoxication following the ingestion of 5-methoxy-N,N-dimethyltryptamine in an ayahuasca preparation|volume=29|issue=8|year=2005|pages=838-841|journal=Journal of Analytical Toxicology|issn=0146-4760|eissn=1945-2403|oclc=02942106|first1=J.|last1=Sklerov|first2=B.|last2=Levine|first3=K. A.|last3=Moore|first4=T.|last4=King|first5=D.|last5=Fowler}}</ref> that are easily avoidable and could have been otherwise prevented.


He was initially completely entranced by the way this young man from Israel could muster the psychic energy of an audience to bring about some remarkable phenomenon. It was not just the bending of keys and spoons, but it was remote viewing and mind-reading as well. It was the stuff of the miraculous.
==Legal status==


Andy was a total convert, but then there was an abrupt erosion of certainty that began with Andy's meeting with a skeptic called the Amazing Randi, who could duplicate most of the illusions with his sleight of hand mastery. Andy went from total belief to total disbelief in a very short period of time. It seemed that his earlier conviction was wrong and that all was indeed misrepresentation. This change in position of course managed to offend both camps. Then he came finally to a middle ground. The status of Uri Geller may be essentially unanswerable. Psychic phenomena are believed if that is needed. Are these things factual? Who is judging it all, and from what point of view?
*'''Germany''': Bufotenin is controlled under the NpSG<ref>{{cite web|url=https://www.gesetze-im-internet.de/npsg/anlage.html|title=Anlage NpSG|publisher=Bundesamt für Justiz [Federal Office of Justice]|access-date=December 10, 2019|language=de}}</ref> (''New Psychoactive Substances Act'') as of July 18, 2019.<ref>{{cite web|url=http://www.bgbl.de/xaver/bgbl/start.xav?startbk=Bundesanzeiger_BGBl&jumpTo=bgbl119s1083.pdf|title=Verordnung zur Änderung der Anlage des Neue-psychoaktive-Stoffe-Gesetzes und von Anlagen des Betäubungsmittelgesetzes|publisher=Bundesanzeiger Verlag|work=Bundesgesetzblatt Jahrgang 2019 Teil I Nr. 27|pages=1083-1094|publication-date=July 17, 2019|language=de|issn=0341-1095}}</ref> Production and import with the aim to place it on the market, administration to another person, placing it on the market and trading is punishable. Possession is illegal but not punishable.<ref>{{cite web|url=https://www.gesetze-im-internet.de/npsg/__4.html|title=§ 4 NpSG|publisher=Bundesamt für Justiz [Federal Office of Justice]|access-date=December 10, 2019|language=de}}</ref><ref>{{cite web|url=https://www.gesetze-im-internet.de/npsg/__3.html|title=§ 3 NpSG|publisher=Bundesamt für Justiz [Federal Office of Justice]|access-date=December 10, 2019|language=de}}</ref> The legislator considers it possible that orders of Bufotenin are punishable as an incitement to place it on the market.<ref>{{cite web|url=http://dip21.bundestag.de/dip21/btd/18/085/1808579.pdf|title=Gesetzentwurf der Bundesregierung: Entwurf eines Gesetzes zur Bekämpfung der Verbreitung neuer psychoaktiver Stoffe|page=20|date=May 30, 2016|id=Drucksache 18/8579|publisher=Deutscher Bundestag|language=de}}</ref>
*'''Switzerland''': Bufotenin is not controlled under Buchstabe A, B, C and D. It could be considered legal.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>
*'''United Kingdom''': Bufotenin is a Class A drug.<ref>{{cite web|title=Schedule 2: Part I: Class A Drugs|url=http://www.legislation.gov.uk/ukpga/1971/38/schedule/2/part/I|work="Misuse of Drugs Act 1971"|access-date=August 20, 2020|publisher=UK Government}}</ref>
*'''United States''': Bufotenin is a Schedule I substance.{{citation needed}}


And so it is with bufotenine. Is it an active [[psychedelic]]? Absolutely yes, absolutely no, and maybe yes and maybe no.
==See also==


The early reports used the "psychotomimetic" term and pushed for a psychedelic interpretation of the observations. Observers saw colored spots, straight lines against a black background. Words can't come. My mind feels crowded. These and similar descriptions are often encountered as components of psychedelic experiences. And yet a skeptic would point to the terms that are closely associated with toxic effects, and peripheral poisoning: my face turned purple and I became nauseated, I could not breathe fast enough. Lactimation and tachycardia. These all are exerpts from the small selection of comments given above. In the period that has followed the earliest studies described in the "Qualitative Comments" section above, there have been about a dozen additional reports that could be offered that describe the same scatter of ups and downs, employing different modes of delivery. With insuflation, I have one that claims a feeling of fear, a flushing of the face, lacrimation and tachycardia, with ten milligrams. Another report states that after snorting forty milligrams, observed neither objective nor subjective effects. Some clinicians demand that the compound is unquestionably a psychotomimetic and it must be catalogued right up there along with LSD and psilocybin. Others, equally sincere, present human trials that suggest only peripheral toxicity and conclude that there is no central action to be seen. And there are many who state that there are no effects for it at all, either inside or outside the CNS. The psychopharmacological status of bufotenine, like that of Uri Geller, may be essentially unanswerable.
*[[Responsible use]]
*[[Psychoactive substance index]]
*[[Psychedelics]]
*[[DMT]]
*[[5-MeO-DMT]]


Two recent publications provide new and provocative input to this dialogue. One of these involved a series of appearances of a reddish substance on the East Coast called Chinese Love Stone, Black Stone, Rock Hard or Stud 100, being sold as aphrodisiacs. They were to be moistened and rubbed on the genitals, but as might be expected, quite a few were eaten and eventually smoked. They contained steroidal toxins, and were possibly related to some frog origins, but they were claimed to be bufotenine and indeed contained bufotenine in addition to several cardiotoxins as well as 5-MeO-DMT.
==External links==


A second report carries, at least for me, much more impact. A study of the use of the seeds of a South American legume, Anadenanthera colubrina var. Cebil by the Argentine Shamans in Chaco Central, shows then to be dramatically psychedelic. And yet, extremely sophisticated spectroscopic analysis has shown them to contain bufotenine and only bufotenine as their alkaloid component.
*[https://en.wikipedia.org/wiki/Bufotenin Bufotenin (Wikipedia)]
*[https://erowid.org/chemicals/bufotenin/bufotenin.shtml Bufotenin (Erowid Vault)]
*[https://isomerdesign.com/PiHKAL/read.php?domain=tk&id=19 Bufotenin (TiHKAL / Isomer Design)]
*[https://go.drugbank.com/drugs/DB01445 Bufotenin (DrugBank)]


At the bottom line, I do not really know of bufotenine is a psychedelic drug. Maybe yes and maybe no.
==References==
[[Category:Tryptamines]]
<references />
[[Category:Drugs]]
[[Category:TiHKAL]]
[[Category:Shulgin]]


{{TiHKAL}}
[[Category:Alkaloid]]
[[Category:Tryptamine]]
[[Category:Psychedelic]]
[[Category:Entheogen]]

Revision as of 19:54, 7 April 2024

Summary sheet: Bufotenin

Template:SubstanceBox/Bufotenin

Bufotenin (5-HO-DMT, N,N-dimethylserotonin, bufotenine) is a naturally occurring substituted Chemical class::tryptamine alkaloid and a serotonergic Psychoactive class::psychedelic drug. Bufotenin is a structural derivative of tryptamine and serotonin. Bufotenin is found in a wide array of flora and fauna, including several species of psychoactive toads, most notably the Colorado River toad. The overall effects of bufotenin are generally described as less pleasant than those of other psychedelics such as LSD.

Chemistry

File:Substituted tryptamine.svg
Generic structure of a tryptamine molecule.

Bufotenin, 5-HO-DMT or 5-hydroxy-N,N-dimethyltryptamine is a ring-substituted indole alkaloid molecule of the tryptamine class. Tryptamines share a core structure comprised of a bicylic indole heterocycle attached at R3 to a terminal amine group via an ethyl side chain. Bufotenin is substituted at R5 of its indole heterocycle with a hydroxy (OH) functional group; it also contains two methyl groups CH3- bound to the terminal amine RN of its tryptamine backbone (DMT).

Pharmacology

Further information: Serotonergic psychedelic

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 completely eliminated within 8 hours.[1] 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.

Bufotenin's psychedelic effects are primarily believed to come from its efficacy at the 5-HT2A receptor as a partial agonist. Specifically, this molecule shows high binding affinity for the 5-HT2A and 5-HT1A subtypes.[2] However, the role of these interactions and how they result in the psychedelic experience continues to remain elusive.

Additional mechanisms of action such as reuptake inhibition of neurotransmitters such as serotonin, noradrenaline and dopamine are also thought to be involved to an extent.[3] This can result in bufotenin becoming dangerously toxic when combined with MAOIs, RIMAs, SSRIs, stimulants or any substance which acts as a releasing agent or reuptake inhibitor of monoamine neurotransmitters.

Subjective effects

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.

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Experience reports

There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:

Natural sources

Colorado River toad

File:Status iucn3.1 LC.svg.png

The Colorado River toad (Incilius alvarius), also known as the Sonoran Desert toad, is a psychoactive toad found in northern Mexico and the southwestern United States. Its skin and venom contain 5-MeO-DMT and bufotenin.

The toad's primary defense system are glands that produce a poison that may be potent enough to kill a grown dog.[4] These parotoid glands also produce the 5-MeO-DMT[5] and bufotenin for which the toad is known. Fresh venom can easily be collected from these glands without harm to the toad. To do this, obtain a flat glass plate or any other smooth, nonporous surface of at least 12-inches square and hold the toad in front of the plate (which is fixed in a vertical position). When the desert toad is stroked near the parotid glands in the neck region, there is a squirting out of this venom. When it is allowed to dry on a hard surface it takes on the texture of rubber cement. It contains up to 15% 5-MeO-DMT, as well as N-methyl-5-methoxytryptamine, 5-MeO-NMT and Bufotenin, which have their own entries. In this manner, the venom can be collected on the glass plate, free of dirt and liquid released when the toad is handled.

Toxicity and harm potential

Further information: Responsible use § Hallucinogens

The toxicity and long-term health effects of recreational bufotenin do not seem to have been studied in any scientific context and the exact Toxicity::toxic dose is unknown. This is because bufotenin is a research chemical with very little history of human usage. Anecdotal evidence from people within the psychonaut community who have tried bufotenin suggests that there are no negative health effects attributed to simply trying the drug by itself at low to moderate doses and using it very sparingly (but nothing can be completely guaranteed). Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

It is strongly recommended that one use harm reduction practices when using this drug.

Tolerance and addiction potential

Bufotenin is Addiction potential::not habit-forming and the desire to use it can actually decrease with use. It is most often self-regulating.

Tolerance to the effects of bufotenin is built Time to full tolerance::almost immediately after ingestion. After that, it takes about Time to half tolerance::1 hour for the tolerance to be reduced to half and Time to zero tolerance::2 hours to be back at baseline (in the absence of further consumption). Bufotenin does not have a cross-tolerance with other psychedelics, meaning that after the consumption of bufotenin psychedelics will not have a reduced effect.

Dangerous Interactions

Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).

Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit. Template:DangerousInteractions/Psychedelics

Deaths from bufotenin are rare but, as a powerful monoamine reuptake inhibitor (MRI), injury can occur when excessive doses are taken or when taken with drugs such as MAOIs, RIMAs, stimulants and any substance which act as a releasing agent or reuptake inhibitor of neurotransmitters such as serotonin and dopamine. This has resulted in well documented deaths[6][7] that are easily avoidable and could have been otherwise prevented.

Legal status

  • Germany: Bufotenin is controlled under the NpSG[8] (New Psychoactive Substances Act) as of July 18, 2019.[9] Production and import with the aim to place it on the market, administration to another person, placing it on the market and trading is punishable. Possession is illegal but not punishable.[10][11] The legislator considers it possible that orders of Bufotenin are punishable as an incitement to place it on the market.[12]
  • Switzerland: Bufotenin is not controlled under Buchstabe A, B, C and D. It could be considered legal.[13]
  • United Kingdom: Bufotenin is a Class A drug.[14]
  • United States: Bufotenin is a Schedule I substance.[citation needed]

See also

External links

References

  1. ↑ Fuller, R. W., Snoddy, H. D., Perry, K. W. (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. ISSN 0028-3908. 
  2. ↑ Krebs-Thomson, K.; Ruiz, E. M.; Masten, V.; Buell, M.; Geyer, M. A. (2006). "The roles of 5-HT1A and 5-HT2 receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats". Psychopharmacology. 189 (3): 319–329. doi:10.1007/s00213-006-0566-1. eISSN 1432-2072. ISSN 0033-3158. OCLC 2409222. PMID 17013638. 
  3. ↑ Nagai, F.; Nonaka, R.; Satoh, K.; Kamimura, H. (2007). "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain". European Journal of Pharmacology. 559 (2–3): 132–137. doi:10.1016/j.ejphar.2006.11.075. eISSN 1879-0712. ISSN 0014-2999. OCLC 01568459. PMID 17223101. 
  4. ↑ Steven J. Phillips (2000). Patricia Wentworth Comus. ed. A Natural History of the Sonoran Desert. University of California Press. p. 537. ISBN 0-520-21980-5. OCLC 837703609. 
  5. ↑ "The Sonoran Desert Toad: Bufo alvarius". Erowid. Retrieved August 27, 2020. 
  6. ↑ Brush, D. E.; Bird, S. B.; Boyer, E. W. (2004). "Monoamine oxidase inhibitor poisoning resulting from Internet misinformation on illicit substances". Journal of Toxicology: Clinical Toxicology. 42 (2): 191–195. doi:10.1081/clt-120030949. eISSN 1556-9519. ISSN 1556-3650. PMID 15214625. 
  7. ↑ Sklerov, J.; Levine, B.; Moore, K. A.; King, T.; Fowler, D. (2005). "A fatal intoxication following the ingestion of 5-methoxy-N,N-dimethyltryptamine in an ayahuasca preparation". Journal of Analytical Toxicology. 29 (8): 838–841. doi:10.1093/jat/29.8.838. eISSN 1945-2403. ISSN 0146-4760. OCLC 02942106. PMID 16356341. 
  8. ↑ "Anlage NpSG" (in Deutsch). Bundesamt für Justiz [Federal Office of Justice]. Retrieved December 10, 2019. 
  9. ↑ "Verordnung zur Änderung der Anlage des Neue-psychoaktive-Stoffe-Gesetzes und von Anlagen des Betäubungsmittelgesetzes" (PDF). Bundesgesetzblatt Jahrgang 2019 Teil I Nr. 27 (in Deutsch). Bundesanzeiger Verlag. July 17, 2019. pp. 1083–1094. ISSN 0341-1095. 
  10. ↑ "§ 4 NpSG" (in Deutsch). Bundesamt für Justiz [Federal Office of Justice]. Retrieved December 10, 2019. 
  11. ↑ "§ 3 NpSG" (in Deutsch). Bundesamt für Justiz [Federal Office of Justice]. Retrieved December 10, 2019. 
  12. ↑ "Gesetzentwurf der Bundesregierung: Entwurf eines Gesetzes zur Bekämpfung der Verbreitung neuer psychoaktiver Stoffe" (PDF) (in Deutsch). Deutscher Bundestag. May 30, 2016. p. 20. Drucksache 18/8579. 
  13. ↑ "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in Deutsch). Bundeskanzlei [Federal Chancellery of Switzerland]. Retrieved January 1, 2020. 
  14. ↑ "Schedule 2: Part I: Class A Drugs". "Misuse of Drugs Act 1971". UK Government. Retrieved August 20, 2020. 
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