There are over 200 known species under the genus Bufo. These include Bufo marinus-also known as Bufo aqua, the common marine toad, native to the Amazon-and its related species: Bufo vulgaris from Europe, Bufo garganizans, from Asia; and the Colorado River toad Bufo alvarius. While these are the best known of the Bufo toads, there are also Bufo arenarum, Bufo valliceps, Bufo blombergi, Bufo quercicus, Bufo asper, Bufo fowerii, and Bufo formosus (Lyttle et al. 1993, 1996)
All Bufo toads have parotid glands on their backs. The parotid glands produce many different biologically active compounds-such as the neurotransmitters serotonin (5-hydroxy-tryptamine), epinephrine, norepinephrine, and dopamine-which vary from species to species. These glands also often produce analogs of the above neurotransmitters, most notably of serotonin (5-HT), including 5-methoxy-dimethyltryptamine (5-MeO-DMT), N-trimethyl-5-hydroxy-tryptamine (bufotenidine), dehydrobufotenine (a quaternary amine salt of bufotenine), and N,N-dimethylserotonin (bufotenine). Bufotenine is found in all Bufo species (Lyttle 1993).
Bufo toads also excrete from their parotid glands substances called bufodienolides, which are comprised of bufogenins (generally known as bufagins) and bufotoxins, which are extremely toxic cardioactive steroids. Bufogenins are a class of organic molecules that contain 24 carbon atoms in their structure, and they are biosynthesized from cholesterol, and they contain no nitrogen. Bufotoxins do contain nitrogen, however. There are five different kinds of bufotoxins: vulgarobufotoxin, cinobufotoxin, gambabufotoxin, marinobufotoxin and alvarobufotoxin (Lyttle 1993).
As stated above, the toxic venoms found in Bufo toads also consist of tryptamine bases. 5-HT and bufotenine are found in all the Bufo species. Bufo alvarius, actually, is the only known species to contain 5-MeO-DMT. Bufothionine is found in the Bufo gargarizans (Lyttle 1993).
The Bufo toad appears in cultural history as far back as 2000 BC. This may have started with the nature of the toad itself. Its life cycle is such that it tends to be born in the springtime, which is a rainy season in most parts of the world. As a result, frequent associations were made among toads, sexuality, fertility, and rain. This is evident from the fact that the Bufo toad was included (along with other toads and frogs) in the first primitive charms relating to sexuality and rain-fertility in many cultures. Often certain parts of the toad's anatomy were emphasized in these totemic-iconic representations, depending on the goal of the charm (Lyttle et al. 1993, 1996).
The toad's way of life tended to make it a mysterious, other-worldly creature to primitive peoples. The toad's tongue is quick enough that it cannot be followed by the human eye. The way a toad captures an insect with lightening speed can easily seem supernatural. Furthermore, the tongue rests with the tip towards the back of the throat, so that it lashes out like a "spear-throwing stick" to catch its prey (Grant 1980). To make matters all the more bizarre, toads cannot breathe with their mouths open. Toads are born out of (in) the mud, making their birth a mysterious occurrence. The year long life cycle of the toad made it seem as if it was generated out of mud (its birth) and then it would melt back into the mud; it was often seen as if the toads were rising from the dead. Further supernatural characteristics of the Bufo toad include its climbing ability. Toads can climb right-side-up, upside-down, and up over-hanging and outsloping walls. They have no teeth, and they tend to swallow their own skin as they shed it (Lyttle et al. 1996).
Art of the Olmecs, Aztecs, and Mayans depicts the Bufo toad as far back as 2000 BC. It is well known that at an Olmec burial cite in San Lorenzo archaeologists discovered huge numbers of Bufo marinus. It has been documented that these peoples consumed the toads for hallucinogenic purposes. (Lyttle et al. 1996) It is important to note that this particular species' parotid gland does not produce 5-MeO-DMT, a substance with clear hallucinogenic activity (Shulgin 1997; Perrine, 1996; Ciprian-Ollivier and Cetkovich-Bakmas 1997). If the Olmecs were indeed hallucinating from their toad rituals, they must have been doing so due to the presence of bufotenine. Bufotenine's (controversial) psychoactivity will be discussed later in greater detail.
Aztec works from the same period also contain a plethora of toad iconography. Interestingly, depictions of the Bufo toad are specific in their focus. The parotid glands are always emphasized and are represented by three circles drawn on the back of the head (Lyttle et al. 1996). Sometimes there was a reference to a gem being in the middle of the circles. It seems as if the parotid gland's center was the center of the iconographical bullseye, as it were.
The Mayans, like the Olmecs, also used the Bufo in their funerary practices. Thousands of toads were found in their burial vessels in Seibal, Mexico. The Mayans were also known to use the toads for ritual hallucinogenic purposes. The Potomam Maya used a drink called Chicha in their rituals. Chicha consisted of sugar fermented with a live toad and toad poisons (Lyttle et al. 1996). It is unlikely that the Mayans were using the Bufo alvarius-the only Bufo species that has 5-MeO-DMT in its venom-in their practices, as it is native to North America, not Mexico. Again, it seems as if we are presented with an example of historical hallucinogenic consumption of toads where the only possible psychoactive ingredient is bufotenine.
Meso American and South American tribes used toad excretions and extractions in tribal practices. Curanderos (shamanic healers) and brujos (sorcerers) made medicinal preparations and potions using the Bufo venom. First, they would irritate the toad gently-picking the toad up by hand could do the trick-so as to cause the toad to release its poison from the parotid glands. The poison was then collected in small bowls and subjected to secret techniques. These techniques were passed on from generation to generation of curanderos. The Bufo venom (in whatever capacity) was then repeatedly treated over a fire, so as to remove the harmful elements, presumably the bufotoxins. The remaining substance was left to harden, when it could be rolled into pills for future use, i.e., as a "love magic" (Lyttle et al. 1996).
Peruvian Indians and Guyana peoples also used Bufo toad poisons in their medicinal practices. The venom was rubbed into people's skin through cuts and put into their eyes, in order to allow their skills to be received by the "Toad Mother." Ancient Tanani peoples of Bolivia also showed their "Earth Mother" motif as a monstrous toad (Lyttle et al. 1996).
For thousands of years, Chinese healers have used Bufo extractions in a medicinal preparation called ch'an su. The Bufo toad has played a role in the medicinal, cultural, and religious histories of Tibet, Nepal, India, Germany, and Africa for centuries. Even greek mythology contains countless toad references. The Greek gods Dionysus, Zeus, Diana, and Hera were all associated with Bufo toads. The Temple of Sparta and the Temple of Delphi both have may sculpted toads on the buildings themselves.
The seeds of a South American legume, Anadenanthera colombrina, are used by the Argentine Shamans in Chaco Central, and have been shown to be dramatically psychedelic. However, extremely sophisticated spectroscopic analysis has shown bufotenine to be their only alkaloid component (Shulgin 1997).
Bufotenine has also been found in several species of Amanita mushrooms, notably Amanita mappa, Amanita muscaria, and Amanita pantherina. Amanita mushrooms have been known for centuries to be psychoactive. Although the main psychoactive alkaloid in psychedelic mushrooms is psilocybin, the fact that these particular species also contain bufotenine has probably added to the notion that bufotenine is itself psychedelic.
Toads' relationship to mushrooms has infiltrated the language of cultures across the globe for centuries. The English word "toad stool" dates back to 1398. The Welsh use the expression "bwyd y llfant" (toad's bread), and "caws llfant" (toad's cheese). The Dutch word "paddestoel" (toad's stool) is nearly identical to the English expression. The Norweigians use the word "paddehatt" (toad's hat), while the French say "pain de crapaud" (toad's bread), the Ukrainians use "zhabjachi hyrb" to mean "toadlike mushroom", the Basque expression "amoroto" means "toadlike thing", and for the Chinese, it's "ha-ma chun" (toad mushroom) (Lyttle et al. 1996).
Clearly the cross cultural abundance of the link between toads and mushrooms is significant. It would make complete sense to argue that the word "toad stool" for a mushroom has an etimology that is related to the similarities between the toads and the mushrooms. As the alkaloids of both had not yet been isolated in 1398, it is most probably the mind-altered state induced by both the amphibian and fungus that was perceived to be similar enough to warrant the coining of such an expression.
It seems appropriate here to discuss what (if any) chemicals found in Bufo toads are psychedelic, or mind-manifesting. 5-MeO-DMT has effects that are said to resemble those of N,N-dimethyltryptamine (DMT) and psilocybin when smoked (Perrine 1996; Shulgin 1997). 5-MeO-DMT is a member of the group called methylated indoolealkylamines (MIAs). On pharmacologic testing, all MIAs were found to have strong hallucinogenic properties (Ciprian-Ollivier and Cetkovich-Bakmas 1997). 5-MeO-DMT was found to elicit an intermediate substituion of LSD-trained stimulus in LSD-trained rats (Helsley et al. 1998). In other words, rats which were trained to be able to tell the difference between LSD and saline pushed the "LSD button" more than 750f the time when they were given 5-MeO-DMT. Its probably safe to assume that the rats were pushing this button based on some experience of a substitution that was distinct from that of saline. Furthermore, 5-MeO-DMT was also found to elicit a head-twitch response when administered to mice (Matsumoto et al. 1996). While this may not be indicative that the mice were "tripping" (having a psychedelic experience), it does show that 5-MeO-DMT is not an inactive substance. However, it is not active orally (Lyttle et al. 1996). The most common mode of administration is smoking, although the animal studies have proven activity upon injection as well.
Subjective experiences of 5-MeO-DMT all invariably attest to its psychoactivity. Comments include "It was a glimpse into my future," "a merely intense psychedelic state," "a kind of cosmic consciousnesss type of experience," and "I remember switching to a perception where the endless and intricate phosphene was love and the energy of light. I called upon those forces within my being to realign and submit, to let go of all of the cogent fears and just exist ... and that innate decision saved me a lot of psychic damage" (Shulgin 1997). There is no question as to the psychedelic nature of the drug. Interestingly, it is not a scheduled drug on the Federal Controlled Substances Act, but as an analog of both DMT and bufotenine, prosecution could still legally occur under the Controlled Substances Analog Act.
The MIAs include DMT and bufotenine as well. So already, according to Ciprian-Ollivier and Cetkovich-Bakmas, bufotenine has "strong hallucinogenic properties." In the LSD-trained rat study, bufotenine elicited an LSD stimulus response only 25.80f the time (Helsley et al. 1998). However, although statistically this is not a huge number, it is a lot more than the 0 0.000000e+00licited by saline. Something is going on in the rat's brain, otherwise the response should be zero. Regardless, this experiment is problematic. The LSD trained rats were given alot of LSD per kg body weight, in fact 50 times the average human dose. Furthermore, human experience with LSD is not so intense as to cause head-twitching. The rats were sensitive to such large doses of LSD, that they may well have been unable to be sensitive to the more subtle bufotenine. Furthermore, the dosage and best modes of administration of bufotenine remain unknown. Another analysis could be that the psychedelic state induced by bufotenine is not as intense as either 5-MeO-DMT or LSD. This hypothesis is consistent with subjective reports, described below.
In 1956, Fabing and Hawkins experimented on human subjects in the Ohio Penitentiary. Four White male murderers were administered bufotenine at doses of .06 to .25 mg/kg (body weight) intravenously over three minutes (Fabing and Hawkins 1956). The following was observed: (1) tingling from head and neck to extremities; (2) constriction of the chest; (3) color hallucinations and visual disturbances; (4) mental confusion and mild disorientation; (5) purpling of skin in head and neck as "the diluted color of eggplant"; and (6) nausea, retching, vomiting, nystagmus (Lyttle et al. 1996). Qualitative comments included the following: (with 1 mg) "... my face felt as if it had been jabbed by nettles ...", (with 2 mg) "I felt a tightness ... my body feels heavy", (with 4 mg) "I saw red and black spots-a vivid orange-red-moving around", (with 8 mg) "Now there are red, green and yellow dots, very bright like they were made out of flourescent cloth, moving like blood cells through capillaries, weaving in and out of the white lines", and (with 16 mg) "Words can't come. My mind feels crowded. When I start on a thought, another one comes along and clashes with it.... I am here and not here" (Fabing and Hawkins 1956). A few minutes after cessation of the injection was a slow relaxation and withdrawal, then a gradual return to mental awareness and significant euphoria lasting several hours (Lyttle et al. 1996). Lower doses and slower administration of bufotenine reduced the unpleasant initial symptoms without reducing the euphoria. "... Its effects are reminiscent of LSD-25 and mescaline" (Fabing and Hawkins 1956). In TIKHAL, Shulgin states, "Some clinicians declare that the compound is unquestioningly psychotomimetic and it must be catalogued right up there along with LSD and psilocybin."
Regardless of the psychoactivity of bufotenine when administered intravenously, it is inactive orally (Lyttle et al. 1993, 1996; Shulgin 1997; Perrine 1996). "Toad-licking," and the hallucinations that it allegedly produces, remain an urban myth. The practice of "toad-licking" in the United States started in the 1960's, when drug users learned of the Bufo toad's historical role in visionary experiences. But it was the Drug Enforcement Administration (DEA) that was actually responsible for the explosion of the practice in the mid-1980's. Media sensationalization ensued, spreading word about "psychedelic toads" across the nation. George Root, a former administrator at SP Labs in Miami, Florida, said on the subject in 1990, "... there has been much speculation in the anthropological literature regarding the possible hallucinogenic uses Bufo. This debate is largely based on the fact that Bufo is a common representation in the art of some Meso American peoples ... and the fact that Bufo skeletal remains have been discovered at archaeological sites. ... Speculations aside ... there is a very good reason why licking toads will not get you high. The toxic compounds are likely to kill you before you could possibly consume enough bufotenine to have any hallucinogenic effect" (Lyttle et al. 1996).
However, many scientists claim bufotenine is not at all psychoactive (Shulgin 1997; Lyttle et al. 1993, 1996; Perrine 1996). Bufotenine is often discounted as a psychedelic because it is said to not cross the blood-brain barrier at all (Lyttle et al. 1996) The basis for this hypothesis is that it has low lipid solubiliity and is a very polar molecule. The fact is, 5-MeO-DMT and DMT both share these characteristics, and yet both are psychoactive. It may well be that only a small amount of bufotenine in the brain is necessary to produce hallucinations. It has actually been proven that bufotenine does penetrate the blood-brain barrier (Fuller et al. 1994). It does so relatively poorly, but as compared with the other MIAs, there is little difference. The degree to which it can penetrate the phospholipid bilayer may well be somewhat irrelevant.
Fuller et al. Injected bufotenine (at 1, 30, or 100 mg/kg) into rats and, at varying time intervals, decapitated them and studied their tissues to see the distribution of bufotenine. It was found that bufotenine concentrations were highest in lung, heart, and blood, and lower in brain and liver. In the central nervous system, concentrations of bufotenine were highest in the hypothalamus and brain stem and slightly lower in the striatum and cortex. Concentrations of 5-hydroxyindoleacetic acid (5-HIAA) were increased significantly due to bufotenine metabolism, specifically in the four brain regions where bufotenine was found. According to Fuller et al., the fact that the brain and liver may be able to metabloize bufotenine more rapidly than the lung and heart may be dependant on the amount of bufotenine present. It also appears that MAO-A, and not MAO-B, is involved in bufotenine metabolism (Fuller et al. 1995).
Bufotenine has been shown to have a high affinity for 5-HT1D and 5-HT1B receptors. Both are G-protein-coupled receptors and are negatively coupled to adenylate cyclase. It has also been shown that bufotenine is an efficacious agonist at 5-HT1D, meaning that its agonist potency is close to its binding affinity (Pauwels et al. 1996). At the 5-HT6 receptor, bufotenine is a more potent agonist than 5-HT, but less potent than LSD. It seems that the hydroxyl gorup at position 5 of the indole ring is important for full agonist activity. Here again, bufotenine's affinity corresponds with its potency of activation (Boess et al. 1997). Interestingly, although bufotenine shows high affinity agonist binding at the 5-HT2A receptor, it lacks detectable agonist activity. Apparently, high affinity at this receptor is not correlated with receptor activation (Roth et al. 1997). It is interesting that bufotenine has such a high affinity for the 5-HT2A receptor because it is well known that hallucinogenic drugs, such as LSD, also have a high affinity for this receptor. It is unlikely that bufotenine's shared trait with other psychedelics is meaningless.
Recent studies have found MIAs in the urine and other body fluids of psychotic patients, specifically those with schizophrenia. Normal patients do not show any MIAs in their bodily fluids. These findings support the transmethylation hypothesis, which suggests that an inborn error of metabolism might cause some cases of schizophrenia by producing a hallucinogenic substance in the body (Ciprian-Ollivier & Cetkovich-Bakmas 1997, Takeda et al. 1995). Normal metabolic pathways from serotonin are as follows: 5-HT->5-HIAA and 5HT->N-acetyl-5-HT->melatonin. However, the theory states that in psychiatric patients, the pathway may be as follows: 5HT->N-methyl-5-HT->bufotenine. This serotonin-degredative pathway is not associated with normal homeostasis. Takeda et al. detected bufotenine and N-methyl-5-HT in nearly all of the psychiatric patients tested (including autistic, epileptic, mentally retarded, depressed, schizophrenic and Alzheimer's patients). The methylation theory of psychatric disorders suggests that the body is capable of producing toxic methylated substances that induce psychotic behavior (Takeda et al. 1995). This is not necessarily a causal relationship that has been found between the presence of bufotenine and psychosis, but a correlation between the two is clear. Interestingly, new generation anti-psychotics have an impact on 5-HT activity. This may be yet another indication of some relationship between bufotenine and psychosis (which would lead to a correlation between bufotenine and hallucinations).
Bufo toads have been extremely important to cultures around the world for thousands of years. They have been valuable to medicine and could continue to be. Today, the Drug Enforcement Administration continues to arrest people caught licking toads, charging them with the ingestion of bufotenine. While "toad licking" cannot cause hallucinations, recent literature indicates that bufotenine (found in all Bufo toads) is psychedelic. Furthermore, it may be a useful drug for diagnosis, treatment, and research on psychosis.
References
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