Understanding the Risks of 5-MeO-DMT

5-MeO-DMT is widely considered to be the most powerful psychedelic. This is not due to the dosages needed to reach intense altered states – technically, the most potent psychedelic in that respect is LSD, with Salvia divinorum being the most potent naturally occurring psychedelic, given that active doses of Salvinorin A are as low as 200 micrograms. The reason 5-MeO-DMT is reported as the most powerful psychedelic compound is due to its subjective effects, particularly how rapidly ego dissolution and other mystical effects can occur. The potential mental and physical effects of 5-MeO-DMT, as well as the growing literature on potential post-trip effects, mean that those curious about the experience should approach it with care and preparation.

(The purpose of this article is not to create unfounded fear around 5-MeO-DMT. Studies have pointed to its potential to induce rapid and sustained reductions in depression and anxiety, as well as PTSD. Moreover, its short-acting nature – with trips lasting around 20 minutes – means it has practical benefits over compounds like psilocybin, LSD, and mescaline. Nonetheless, its risks must be understood and taken into account to ensure safe usage.)

5-MeO-DMT is not a psychedelic that can be used casually and recreationally like psilocybin mushrooms or LSD. In sufficient doses, it reliably causes profound subjective effects. And for many users, the sheer intensity of these effects, and the rapidity with which they manifest, can be a source of panic or overwhelm. While many people desire and aim for ego dissolution when taking psychedelics, based on reports of its healing potential, there is a dark side to this effect: it is known as dread of ego-dissolution, or anxious ego-dissolution.  

In his book How to Change Your Mind (2018), the journalist Michael Pollan recounts his experiences with various psychedelics, in different settings. In an interview with Nick Hilden for Rolling Stone, he said:

The only one I didn’t like that I tried was 5-MeO-DMT — the venom of the Sonoran Desert Toad, which is incredibly powerful, disorienting, ego dissolving, but not in a happy way, in a frightening way. I had a very frightening experience on that. I’ve since heard from people who are more experienced with 5-MeO-DMT variously that I took too much or I took too little. I don’t know what to do with that.

In an interview for Vice, Pollan underscores the aspect of terror in his psychedelic experiences. But, interestingly, he found that the intense terror induced by 5-MeO-DMT had a silver lining:

“They [the psychedelic experiences] weren’t all sweetness and light. There were episodes of terror in all of them, but there was a particularly terrifying one, and that was the 5-MeO-DMT. That is kind of an overwhelming experience—not only does the ego dissolve, but everything dissolves—all matter dissolves into pure energy, at least in my experience. And that was terrifying.

The best thing about that trip is it only lasted 15 or 20 minutes. And this: When it was over, I had a feeling of gratitude that I’ve never had. Gratitude not just to be alive, but that there is life. That there is anything seemed like a gift—because there could be nothing.”

Indeed, a challenging trip can also entail benefits, as Pollan describes above. However, not everyone finds an immediate or obvious benefit after a terrifying experience, and, in some instances, persisting negative effects occur (more on this in the last section of the article). In any case, those curious about 5-MeO-DMT should be aware of the very real possibility of what is called the ‘whiteout’ experience. Rather than blacking out, users who have a breakthrough 5-MeO-DMT experience report dissolving into bright white light – an infinite, eternal void. Unlike N,N-DMT, 5-MeO-DMT does not typically produce complex, colourful visuals.

Many users also encounter what they call God or the Source during this experience.

This is why 5-MeO-DMT is referred to as the ‘God Molecule’.

The ‘God’ that is encountered is often described not as an entity – the God found in religious texts and religious mysticism – but as an impersonal creative force, although it may also be felt as a loving force.

This fast onset of mystical effects may, for some users, lead to ontological shock and existential distress, so it’s vital to have some form of social support following the experience, such as space to process it with a psychotherapist, an integration coach, an integration group, a support group, or loved ones. Having your sense of self, your beliefs, and your consensus reality rapidly dissolve can be therapeutic and positively transformative, but it can also be destabilising and confusing.

It appears that intense physical reactions are more common with 5-MeO-DMT than other psychedelics, including the similarly short-acting and intense compound N,N-DMT. Possible physical reactions, which have been reported and observed, include shaking, writhing, groaning, screaming, and vomiting. Not everyone experiences such strong physical reactions and releases of energy, however; some users remain still and calm (which is not to say that their subjective experiences are necessarily still and calm).

These physical effects can be related to the physiological effects of the compound, subjective effects (e.g. the experience of terror), therapeutic effects (e.g. emotional catharsis, or the release of pent-up emotions and tension), or a combination of these factors. Because of the possibility of strong physical reactions – particularly uncontrollable physical movements – it’s crucial to only use 5-MeO-DMT in the presence of a well-trained guide, who understands how to support someone experiencing these reactions. Otherwise, there is the potential risk of injury.

All psychedelics can potentially result in extended difficulties, that is, post-trip emotional distress that outlasts the acute subjective effects of the compound. These extended difficulties can be short-, medium-, or long-term. Nevertheless, it appears that not all psychedelics are equal when it comes to the frequency at which these extended difficulties occur, and there also seem to be differences in the type of extended difficulty that is more likely to occur from using one psychedelic than another.

The use of 5-MeO-DMT, according to current research, appears to be associated with a higher incidence of extended difficulties than other psychedelics. ‘Reactivations’ (or ‘flashbacks’) are frequently reported following 5-MeO-DMT use. This refers to re-experiencing the effects of the compound, without the compound being present in one’s system. It is a form of hallucinogen persisting perception disorder (HPPD): Type 1 HPPD, characterised by short-lasting, episodic effects, in contrast to Type 2 HPPD, which is marked by more persisting visual effects. A 2020 study published in the Journal of Psychedelic Studies found that nearly 69% of participants who vaporised 5-MeO-DMT experienced reactivations (this figure dropped to 21% for those who received an intramuscular injection of the compound).

It should be noted that Type 1 HPPD is often referred to as a ‘benign’ form of HPPD. Indeed, researchers have found that most people who experience 5-MeO-DMT reactivations report that it is a neutral or positive experience (it may be a way of recalling the experience, which can be helpful for integrating it). Nonetheless, a minority of users do feel that these reactivations are troubling and disruptive. 

Reactivations may be the least of one’s concerns after a 5-MeO-DMT journey. In addition to ontological or existential distress, it’s also possible to experience persisting depersonalisation and/or derealisation. The comedian Neal Brennan has described on various podcasts (e.g. Depresh Mode and Mental Illness Happy Hour) and interviews how it took 18 months to recover from his 5-MeO-DMT trip, during which he experienced extreme emotional distress. In an interview for Big Think, Brennan recounted his attempts to heal his depression:

“I tried transcranial magnetic stimulation. Ketamine, that was not helpful. And then ring the bell. Ayahuasca. I went from being an atheist to I believe I have a connection to a central creation force. And then 5-MeO-DMT. Bufo alvarius [the toad from which natural 5-MeO-DMT is extracted]. It is widely considered the most potent psychedelic you can do. It lived up to the hype. I was so disoriented I thought I might have to kill myself.

But not from depression. It was from disorientation. Straight up, I had thoughts like, “Am I in God's imagination?” Too far out. Let's put it that way. What I endured was almost unbearable. But I was better in my body, felt better, funnier, kinder, more loving, more apt to fall in love than I'd ever been.”

(Brennan experienced reactivations, too, which were also distressing – they were connected to his disorientation – feeling detached from reality, intense anxiety, and like he was losing his sanity.) Like Pollan, Brennan found a silver lining in his distress. He said on the Depresh Mode podcast that he cannot, due to the distress and suicidal ideation he experienced, recommend 5-MeO-DMT, nor does he think he would repeat the experience if given the chance. Nonetheless, he credits the compound with being mostly responsible for resolving his chronic depression. It seems that while 5-MeO-DMT may involve a greater risk of extended difficulties than other psychedelics, alongside this is the potential for long-term therapeutic benefits, after just a single experience. 

Because of the unique power and risks of 5-MeO-DMT, it’s important to only use the compound in a controlled, supervised, safe, and comfortable setting. This is not a compound you want to use on your own, in an uncontrolled setting, or with those inexperienced with it acting as a trip sitter. The doses of 5-MeO-DMT are low (6–20 mg of the compound can produce profound effects), so it’s critical to only use it if you can trust that the dose being administered is accurate. With these points in mind, seeking out a reputable, well-reviewed 5-MeO-DMT retreat would be the safest option. (Joining a clinical trial is a safe option, too, if a retreat is unaffordable, but these are few and far between, they’re more difficult to join, and many wouldn’t want to have their experience in a clinical setting.)