Growing up as a kid in Phoenix, Arizona, I’d often hear my classmates gossip about a rare type of desert toad that would bestow its magical powers on anyone brave enough to lick it. This was just a perversion of an old Brothers Grimm fairytale, “The Frog and the Prince,” but as with most fairy tales, more than a grain of truth was embedded in the fiction. Phoenix and the surrounding Sonoran desert are home to a toad endowed with the ability to transport humans to other realities that would make even the most outlandish fairy tales seem utterly mundane—and you don’t even have to lick it. 

I’m speaking, of course, of the Sonoran Desert toad, which is the only amphibian in North America that produces a natural psychedelic. The glands on each side of the toad’s neck are filled with a venom that contains a powerful psychoactive chemical called 5-MeO-DMT. When the toad’s venom is collected and allowed to dry, it can be vaporized and inhaled to produce one of the most intense psychedelic experiences known to humans. Like its cousin N-N-DMT, the effects of smoked 5-MeO-DMT last only a few minutes, but are liable to transport the user to a place far removed from base reality. 

5-MeO-DMT is also naturally produced in a number of plants, but despite its prevalence in nature and powerful psychoactive effects, it remains woefully understudied compared to other psychedelics. Although intrepid psychonauts have been smoking toad venom for decades, it wasn’t until 1994 that the psychedelic effects of 5-MeO-DMT were formally described in a scientific journal. Even the U.S. government was slow to catch on—the substance wasn’t scheduled by the Drug Enforcement Administration (DEA) until 2011.

Despite its legal status and relative obscurity in the psychonaut community, a growing contingent of psychedelic researchers believes it’s time to pay 5-MeO-DMT more attention. At the forefront of this push to revisit 5-MeO-DMT is Alan Davis, an assistant professor of social work at Ohio State University and an adjunct professor in the psychedelic research department at Johns Hopkins University, arguably the world’s leading psychedelic research lab. 

PRØHBTD caught up with Davis to learn more about the promises and perils of nature’s least understood psychedelic.

How did you become interested in 5-MeO-DMT?

I first became aware of 5-MeO-DMT when I was doing an ibogaine study in Mexico. We were tracking outcomes for a clinic that was treating patients with opiate use disorder. As I started working on that, I discovered that they were also administering 5-MeO-DMT later on in the treatment. That was the first time I’d ever heard of it, so I went to see if there was any research on the topic and there really wasn’t any. That prompted the first large-scale survey study on 5-MeO-DMT to try to understand how it’s being used. What are some of the potential benefits? What are the potential consequences? 

How does 5-MeO-DMT compare to the more common N-N-DMT?

The 5-MeO-DMT experience is far less visual than the N-N-DMT experience. I think that’s probably the main difference. On N-N-DMT, people report these profoundly visual and immersive experiences that often involve contact with seemingly autonomous entities and other types of experiences that also can be deeply meaningful and therapeutic. 5-MeO-DMT seems to be less visual and less immersive. We get far fewer reports of entity encounters, and when there is some type of entity encounter, it’s usually almost ubiquitously reported as some type of God, so not necessarily these kinds of alien or other types of entities that are more frequently described with N-N-DMT. When they are encountered with 5-MeO-DMT, it’s more of a felt sense or presence, as opposed to a visual entity that they might see. 5-MeO-DMT experiences seem to be more profoundly spiritual. 

People have been smoking 5-MeO-DMT collected from toads for decades. Why do you think science ignored it?

I think in part it’s a numbers game. There are only so many psychedelic researchers out there. More of them are going into this field each year, but 5 or 10 years ago, there really weren’t that many of us out there. Also, funding was really terrible back then and not so great now, although it’s getting better, and a lot more things are opening up. 5-MeO-DMT seems to be very, very rare in terms of the overall landscape of psychedelics that are used. Of course, that is increasing, especially over the last couple years, but even then it’s in the same essential category in terms of prevalence as something like N-N-DMT, which is much less commonly used than something like psilocybin or LSD. I have noticed there’s been a steadily increasing swell of interest from other scientists whom I’ve started working with as well as some organizations working towards a kind of medicalization of psychedelics, in part because it has some unique properties that could potentially be an advantage over something like psilocybin or LSD. I think that interest will continue to grow, and more research will continue to be published on the topic going forward.

Everything I’ve heard about 5-MeO-DMT focuses on how intense an experience it is. 

This is not a substance to be taken lightly. I think most people who are thoughtful about approaching psychedelic experiences have recognized that, and I think in part that’s because of how potent it is. It’s somewhere around four or more times more potent than N-N-DMT, which means that the dosing needs to be very specific. The hard part with the toad in particular is that the relative percentage of 5-MeO-DMT in any specific secretion of toad venom is going to vary from toad to toad and season to season. So it’s really difficult to dose people correctly with the venom. Not to mention the number of practitioners or facilitators out there who aren’t even trying to do that. They’re just throwing a bunch of medicine into a pipe and not really even taking any of that into consideration. It’s much different than synthetic 5-MeO-DMT, which can be very precise assuming that a facilitator is willing to do so, and you can control some of the risk that way. 

Did your research uncover any ways that tended to make people have a more positive 5-MeO-DMT trip?

People are reporting more positive experiences when they’re in a supportive setting where there is proper care placed on dosing of the synthetic molecule. They’re reporting things like deeply mystical experiences and deeply positive mood. We get a lot of reports of individuals who are saying that it’s one of the single most profound experiences of their entire life. Although there are some challenges, in those types of settings the challenges are significantly less than in settings where those things aren’t being carefully attended to. There’s something about this supportive context where there is some attention to what someone is getting in terms of the substance, how it’s being administered and all that. Maybe the more ritualistic or ceremonial experience provides some type of context to understand what to expect and how to navigate it, but also how to make sense of it afterward. I think people are more at risk of having a challenging experience without those parameters in place because the drug is so potent and the experience can be so difficult to predict

What were people’s more challenging experiences like?

We’ve had some people report, regardless of the context, that they were having traumatizing anxiety-producing experiences. They’re pretty rare from what I can tell from our research, but they do happen. At worst, I’ve had people report having to go to the emergency department because of paralyzing panic attacks that persist for weeks and months after. Recently I had someone email me and say that they had a friend who has been committed to a psychiatric hospital because they were suicidal after these panic attacks persisted. Someone came into their community and dosed them and then just left without giving them any kind of preparation or integration. 

Despite this, do you still think 5-MeO-DMT may have medicinal value?

I think that the potential benefits of this medicine when used appropriately and perhaps even medically in the future, in a clinical trial setting, override minimal risks. Like any other psychedelic, when we administer a little bit in the lab, we don’t have the types of adverse effects that are more common in the community. 

Was the group you studied that took 5-MeO-DMT in a more ceremonial or structured context or was it an underground affair?

My understanding is this is an underground group with no formal religious exemption. This group predated that [DEA] scheduling, but I don’t think that they ever transitioned to any type of formal religious exemption after it became illegal. I think they just continued on with their group as it was.

One of your studies focuses on “benefit enhancement” strategies that people who take 5-MeO-DMT use to improve the experience. What were some of the more prevalent strategies?

We chose to call them benefit enhancement strategies as opposed to harm reduction strategies in part because we kind of felt like the term harm reduction was a little bit pejorative. Some people might argue that point, but harm reduction kind of seems to assume that drugs are harmful to begin with, and we didn’t want to make that same bias going into it. 

In this study, we looked at these different benefit enhancement strategies, and a lot of them are things people would assume, like a safe set and setting. So we were looking at having an intention for the 5-MeO experience, having a safe space, having music for their session, comfortable spaces, no distractions. Then we included some things that are more from an indigenous perspective, so things like abstaining from sex, alcohol or other substances prior to the experience. We also had some items in there about integration and having a friend they can talk to after the session. We found that having an intention, utilizing ceremonial techniques, having a guide present for the session, meditating prior to the session,  were all predictive of having more intensely positive experiences for those who use these strategies compared to those who did not. 

Maybe a lot of people in the psychedelic community will say “no shit, that’s what we’ve been saying for decades about these experiences,” but to our knowledge, this is the first empirical test of that. We haven’t found anything in the literature that actually tested that as a scientific question. So that’s kind of exciting. 

Were there any strategies that people reliably used to improve a challenging experience?

There was really just one strategy that predicted less challenging experiences when it was used: having music playing during the session. This has been a mainstay since the ’50s and ’60s, but again, I don’t think it had been tested [before]. So even though we might have accepted these as truths prior to the study, we now have some empirical evidence suggesting that these strategies seem to predict increases in positive experiences and decreases in challenging experiences.

Now that you’ve done several studies on how people use 5-MeO-DMT outside of the lab, do you have any plans to do a clinical trial?

Well, with survey work, you can answer questions that can’t be answered in clinical studies, so I do think there can be more of those done. I’m working with some folks from Imperial [College London] on developing a new study, and I’m collaborating with some people in Wisconsin, Ohio State and my colleagues at Hopkins on a new study for people who are native Spanish speakers on the topic of 5-MeO-DMT and other psychedelics. However, I think there needs to be a clinical trial at some point soon if we want to proceed with the idea that this molecule might potentially have the capacity to not only enhance and heal, but to help healthy volunteers understand different aspects of their consciousness or explore their own kind of psycho-spiritual human-ness. 

I know that there have been some conversations about pursuing a clinical trial, but as with everything else in this space, funding is the main limitation. A lot of the funds right now are going into psilocybin and MDMA work because those seem to be the most likely to get FDA approval. But because the funds are all going into those types of studies, everything else is being pushed to the back burner. So it’ll be difficult, I think. Hopefully in the next year or two or three, we might be able to get one of these clinical trials up and running.

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