Both the plant and animal worlds are sources of the psychoactive tryptamine compound 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine). It was first described in plants in a member of the family Rutaceae called Dictyoloma incanescens.1 It is also found in high concentrations in the parotid gland secretions of the Colorado River toad Bufo alvarius.2,3 A 2010 review article cites several references indicating 5-MeO-DMT has been detected in human urine, blood, and cerebrospinal fluid and may also be synthesized in the retina and pineal gland.2 In fact, elevated levels of 5-MeO-DMT and its analogs have been detected in the body of fluids of people suffering from psychiatric disorders such as schizophrenia.
Interestingly, researchers are finding that 5-MeO-DMT is only one of many compounds in so-called toad venoms. Just like psilocybin mushrooms, it’s the influence of all the compounds in toad secretions that is responsible for the overall psychedelic experience for the user. For example, a 2018 study found that a 50 mg dose of vaporized bufotoxin secretions (containing about 5-7 mg of 5-MeO-DMT) from B. alvarius gave the same intensity of mystical experience as a high dose (30 mg/70 kg) of pure psilocybin.4 However, there was a significant increase in the intensity of the mystical experience from the vaporized toad secretions compared to a moderate/high dose (20 mg/70kg) of pure psilocybin. The latter result shows that the mixture of compounds in the toad secretions was more potent than the moderate/high dose of pure psilocybin in creating a full mystical experience. Therefore, an experience with 5-MeO-DMT alone would not be expected to have all the effects and possible benefits of the complete, naturally-occurring mixture of compounds in toad secretions.
Here are two examples of the different compounds found in the secretions of B. alvarius. As part of the first study, the researchers analyzed five samples of secretions for the levels of several compounds. The ranges of each compound per 1 gram of dried secretion were:3
- Tryptamines –
- Steroid Lactones –
- Bufogenin = 0.005 – 0.013 mg/g (four samples)
- Tryptophols –
- 5-MeO-tryptophol (5-MTOH or 5-methoxytryptophol) = 0.696 – 3.053 µg/g
Secondly, a 1967 study found the following compounds in the skin of B. alvarius:5
- bufotenin
- bufoviridine
- O-methylbufotenine (another name for 5-MeO-DMT)
- 5-hydroxytryptophol
- 5-hydroxyindoleacetic acid
- 5-methoxytryptophol
- 5-methoxyindoleacetic acid
In addition, Alexander and Ann Shulgin documented that B. alvarius secretions can be up to 15% 5-MeO-DMT.1 Also, they say that 5-MeO-NMT, N-methyl-5-methoxytryptamine, and bufotenine are other components of the secretions of this species.
Evidence Supporting the Entourage Effect in Toad Secretions
The entourage effect is a term that originated in medical marijuana research. It describes a phenomenon where compounds act together synergistically to modulate the overall effects. In other words, compounds can increase (or decrease) the potency of others (and have other influences) by acting as allosteric modulators of receptors, molecular transporters, and enzymes. At this time, there is no direct evidence supporting that the entourage effect is at work with toad secretions. However, there is indirect evidence supporting the hypothesis.
The entourage effect exists in the world of magic mushrooms. In one of his papers, researcher Jochen Gartz saw the entourage effect emerge around the compound aeruginascin when he studied the data from 24 accidental mushroom poisonings.6 He concluded, “Aeruginascin seems to modify the pharmacological action of psilocybin to give an always euphoric mood during ingestion of the mushrooms.”
G-protein coupled receptors (GPCRs) are some of the most ubiquitous receptors in nature, and the scientific literature is brimming with studies that show their role in the allosteric modulation of cellular functions. The compounds in marijuana, magic mushrooms, and toad secretions all have an affinity for GPCRs, some more than others. In particular, magic mushroom compounds bind to serotonin 5-HT2A receptors which elicits their psychedelic effects,7 5-MeO-DMT is also known to work primarily via 5-HT2A,8 and there is experimental evidence that shows cannabidiol (CBD) interacts with GPCRs.9 And, other compounds in toad secretions like bufotenin are agonists of 5-HT2A receptors.2
To sum it up, the entourage effect almost certainly plays a role in the effects of toad secretions. This is because several of the compounds are known to be agonists of the serotonin 5-HT2A receptor, which is subject to allosteric modulation like other GPCRs. Also, studies have shown that the effects of chemically similar compounds like serotonin and other tryptamines can be changed through allosteric modulation of GPCRs like 5-HT2A. The fact that the entourage effect has been documented in nature for other compounds like those found in magic mushrooms and cannabis also adds credence to extrapolating this theory to toad secretions.
Conclusion
Ingesting 5-MeO-DMT alone is not the same as the complete, naturally-occurring cocktail of compounds in toad secretions. Researchers are finding more compounds in the secretions of B. alvarius, including steroid lactones, tryptophols, and additional tryptamines. The consistencies that scientists see in the natural world suggest the entourage effect that modulates the effects of compounds in marijuana and psilocybin mushrooms is probably also at work in toad secretions.
Barbara E. Bauer, MS
Barb is the former Editor and one of the founders of Psychedelic Science Review. She is currently a contributing writer. Her goal is making accurate and concise psychedelic science research assessable so that researchers and private citizens can make informed decisions.
This article provides zero evidence whatsoever to support its repeated assertion that Bufo alvarius toad secretion produces a different experience than pure synthetic 5-MeO due to an entourage effect. It is simply speculation. Also, comparing the experience of the toad secretion with the isolated alkaloid from psilocybin mushrooms and extrapolating that to a comparison between toad and synthetic 5-MeO is nonsensical. Apples and oranges. While there are undoubtedly other psychoactive compounds in the toad secretion, including bufotenin, it is unclear if those are even active when vaporized. Moreover, if there’s any difference at all experientially, it would seem to be… Read more »
Hi Matt – Thanks for your comments. The concept of pure 5-MeO-DMT having different effects than whole toad secretions (the entourage effect) is not speculation. As I said in the article, it is based on indirect experimental evidence we have from other naturally occurring organisms, e.g., cannabis, magic mushrooms. The subjective experiences you describe provide some insight, but they are influenced by many variables including set and setting, purity, potency, etc.
Check out this article that discusses the effects of 5-MeO-DMT versus toad secretions.
https://psychedelicreview.com/scientist-test-the-effects-of-inhaling-synthetic-5-meo-dmt/
The link leads to an article that states that there is no noticeable entourage effect, at least with the methodology used.
Thanks for your comment. Would you please point me to where the authors say that in the paper?
Rick must’ve just scanned over it instead of doing actual reading from a basis of intellect, instead of “I already know this” ego… “After analyzing the data, the researchers noticed differences in the subjective effects the participants experienced after inhaling vaporized 5-MeO-DMT compared to a previous study they did where people inhaled vaporized toad secretions, which contain a cocktail of compounds.4 They found the moderate levels of ego dissolution and altered states of consciousness experienced in this research were similar to the previous study using toad secretions but 20-30% lower in magnitude. Also, the percentage of participants who achieved maximum… Read more »
Matt. Might wanna stick to things you have experience with. If you haven’t, yourself, then your opinion is irrelevant about it. Might wanna at least observe every report achieved through the scientific method instead of listening to recreational hearsay and pharmaceutical propaganda for synthetics. No need to try to bash legitimate hypothesis with your mundane defense of pride and refusal to admit that it might just be the best thing to have to humble oneself enough to make a deal with (so called “inferior”) plants and animals. Survival of the most indispensable, and humans are becoming more and more disposable… Read more »
I just stumbled across this article again for the first time in a few years and saw your comment. I now have extensive experience with both toad secretion and pure molecule, so here are my observations. At full-release dose I find the two forms indistinguishable from one another aside from the duration of time it takes to inhale one versus the other. Set and setting play a role in any psychedelic journey–and each is unique–but there’s just no discernible experiential difference between toad secretion and pure molecule. The only thing that stands out to me is that it takes much… Read more »