5-MEO-DMT is an illicit hallucinogenic drug. Occurring naturally in the venom of some toad species and plants, it was historically used by shamans in South America. However, its recent use by “facilitators” is extremely dangerous and potentially deadly. On the other hand, research teams are exploring how this compound affects mood, anxiety, and mindfulness. Read on to learn about the risks, research, and proposed mechanisms of 5-MEO-DMT.
Disclaimer: 5-MEO-DMT is classified as a Schedule I substance. This means that it is an illegal drug with high potential for harm and no known medical uses. We highly advise against the use of 5-MEO-DMT until future studies determine its safety and efficacy in medically-supervised and safe settings. The only aim of this post is to outline risks and research findings.
What is 5-MEO-DMT?
5-MEO-DMT is an illegal substance. It is naturally found in some species of toads such as the Bufo alvarius toad and may occur in certain plants. It is also produced synthetically.
Scientists describe 5-MEO-DMT as a fast-acting hallucinogen [1, 2, 3].
Unethical and Dangerous Practices
Like its relatives, DMT and bufotenine, it has a history of use in a shamanic and spiritual context. However, its modern-day use by “facilitators,” mostly in Mexico, has been condemned as unethical and reckless .
Dangerous sessions, serious injuries, hospitalizations, and deaths have been reported .
An open letter to two “facilitators” that were leading 5-MEO-DMT sessions, compiled by experts at the World Bufo Alvarius Congress (WBAC), addresses these issues. Briefly, reported malpractices included rape, clandestine drugging, intentional overdosing, psychological manipulation, and financial fraud .
Even if we put these serious allegations aside, it’s important to remember that there is no safe use of 5-MEO-DMT. None of the facilitators have clinical expertise. Plus, the safety and effectiveness of 5-MEO-DMT in certain circumstances has yet to be carefully determined in clinical trials.
With this in mind, let’s take a look at the history of indigenous 5-MEO-DMT use, its scientific discovery, and what emerging research suggests about its effects.
Discovery and History of Use
5-MEO-DMT was initially discovered in the bark of the Dictyoloma incanescens plant. It is also found in the venom of Colorado River Bufo alvarius toads. Smoking its venom is said to cause intense hallucinations [5, 6, 5].
It is also one of the ingredients in South American Virola snuffs and the Ayahuasca drink. However, these also contain greater amounts of other related compounds (bufotenine and DMT, respectively) [5, 6, 5].
5-MeO-DMT was first synthesized in 1936, but its folk use may date centuries back .
According to some reports, plant extracts and other botanical 5-MeO-DMT preparations – such as the Yopo snuff – have historically been used among indigenous cultures in the Americas in pre-Columbian times .
On the other hand, Bufo alvarius toad venom was probably not used historically by indigenous cultures, despite some limited reports claiming otherwise. Based on the existing evidence, scientists think that the use of toad venom is more recent .
Additionally, some researchers have suggested that 5-MEO-DMT is found naturally, in trace amounts, in human bodily fluids such as urine, blood, and cerebrospinal fluid. It appears to be produced in the retina and pineal gland. Its biological function is still unknown .
5-MEO-DMT is classified as a Schedule I drug under the Controlled Substances Act of 2009. Schedule I drugs are considered to have a high potential for abuse, no currently accepted medical use, and lack of accepted safety for use under medical supervision [1, 2, 3].
Since it’s illegal in the US, research on 5-MEO-DMT is limited and ethically and legislatively challenging .
Chemistry & Pharmacology
5-MEO-DMT (5-methoxy-N,N-dimethyltryptamine) is classified as an indolealkylamine. Indolealkylamine drugs are somewhat similar in chemical structure to serotonin, a neurotransmitter implicated in hallucinations, mood, and the control of body temperature [5, 9].
More specifically, 5-MEO-DMT belongs to dimethyltryptamines .
On the one hand, naturally-occurring dimethyltryptamines are hypothesized to affect non-ordinary states of consciousness such as dreams, imagination, and creative flow. However, the research is limited. Many of the theories dealing with how the chemicals our bodies produce affect altered states of consciousness have yet to be proven .
On the other hand, ingesting dimethyltryptamines can cause intense hallucinations and psychedelic effects (described as similar to psilocybin), paranoia, “ego-dissolution,” an altered sense of time, and near-death-like experiences. For example, the dimethyltryptamine DMT may model near-death experiences, according to some researchers [11, 12, 13].
5-MEO-DMT specifically causes visual and auditory hallucinations. However, some reports indicate it might be less visual than DMT. Rather, it is described to cause more of an emotional (fear/euphoria) perspective shift, described as overly intense and similar to a near-death experience .
Some studies suggest that the effects of 5-MEO-DMT begin within 3 to 4 minutes, peak at 35 to 40 minutes, and cease at 60 to 70 minutes. Users may lose physical control and coordination and experience nausea and memory loss .
Mechanism of Action
Researchers think that 5-MEO-DMT acts on the serotonin system through the activation of serotonin receptors [5, 15].
5-MEO-DMT seems to exert most of its effects by binding to 5-HT1A and 5-HT2A receptors. It may also bind to 5-HT1B, 5-HT1C (weakly), 5-HT4, and 5-HT1S receptors (in the spinal cord) [16, 15, 16].
There are two types of neurons: presynaptic and postsynaptic. Presynaptic neurons send the signal and postsynaptic neurons receive the signal. Scientists say that activating 5-HT1A receptors in the presynaptic neuron may increase pain, while activating the postsynaptic neuron may decrease pain. How 5-MEO-DMT affects pain remains to be investigated .
Other research teams hypothesize that it may have Its anti-inflammatory and neuro-regenerative effects by activating sigma-1 receptor (SIGMAR1), but this remains unproven [17, 18].
Finally, research suggests that some of the effects may be due to the activation of 5-HT1B, 5-HT3, and GABAA receptors .
Cellular research is determining whether 5-MEO-DMT activates metabotropic glutamate receptor 5 (mGluR5), which, theoretically, may warrant its further research in addiction science [18, 19].
5-MEO-DMT is broken down by MAO-A. Scientists are exploring how and to what extent combining 5-MEO-DMT with MAO-A inhibitors might prolong and increase its effect. For example, plant preparations such as Ayahuasca and Syrian rue seeds contain MAO-A inhibitors [5, 8, 20].
The use of MAO-A inhibitors with 5-MEO-DMT may also increase levels of bufotenine, an active byproduct of 5-MEO-DMT. Harmaline increased levels of 5-MEO-DMT up to 3.6 fold and bufotenin by 9.9 fold in mice. These proposed mechanisms have yet to be investigated in humans [5, 21].
Areas of Research
The studies listed below are highly experimental. We summarized them with the aim of sharing the latest research with the general population. The existing studies should guide further investigation efforts. They should not be interpreted as supportive of any health benefit.
Remember that 5-MEO-DMT is still an illegal drug with a high potential for harm. We highly advise against the use of 5-MEO-DMT until future studies determine its safety and efficacy in medically-supervised and safe settings.
1) Frequency of Use
A recent internet-based survey of over 500 users suggests that 5-MeO-DMT is used infrequently (less than once per year) and predominantly for spiritual exploration. About 90% of users reported mystical-type experiences and about 40% experienced challenging states such as anxiousness or fear .
The authors concluded that future rigorously-designed research in humans should examine the safety of 5-MeO-DMT and how the body processes and breaks it down (pharmacokinetics).
2) Mystical Experiences
One 2018 study collected data from 20 people who were given 5-MeO-DMT as part of a retreat program in Mexico. All participants received 50 mg of inhaled vaporized toad bufotoxin, which contains 5-MeO-DMT, and filled out a questionnaire. Findings suggest that 5-MeO-DMT occasioned “complete mystical experiences” in 75% of individuals and was similar in intensity to high-dose psilocybin .
The authors believe that the short duration of action may be advantageous for clinical interventions and for studying mystical-type experiences. And although the results look promising, this study had several limitations.
For one, it didn’t include a placebo group. As such, both the participants and investigators knew what was being administered, which makes the placebo effect likely. Also, the first author of the study is affiliated with several treatment centers in Mexico and the US.
Additionally, the sample size was small and mostly consisted of white men. Larger, better-designed, multi-center trials on more diverse populations are needed.
3) Mood & Mindfulness
A single inhalation of vapor from dried toad secretion containing 5-MeO-DMT was related to sustained improvements in satisfaction with life, mindfulness capacities, and mental health symptoms, according to a widely-discussed study published in 2019 .
The study, conducted in the Netherlands, assessed 42 people who inhaled vapor from dried toad secretion at several European locations.
Findings suggest a link between 5-MeO-DMT and higher ratings of satisfaction with life, mindfulness, and problem-solving capacities (convergent thinking) for up to 4 weeks after inhalation. Ratings of depression, anxiety, and stress also decreased within 4 weeks .
The authors also found that participants who experienced high levels of ego dissolution or “oceanic boundlessness” during the session were more satisfied with life and had better mood and felt less stress afterward .
However, this study had design flaws, a small sample, and no placebo control. It was a so-called “naturalistic observational study,” which means that the researchers simply took note of what was happening during the sessions and gave the participants questionnaires after.
In a previous study with similar naturalistic design, 5-MeO-DMT was associated with unintended improvements in depression and anxiety in 362 people who completed an internet-based survey .
Scientists behind these two studies concluded that future, higher-quality trials should explore potential therapeutic applications of 5-MeO-DMT .
Additionally, cellular studies are examining whether 5-MEO-DMT impacts a class of receptors called integrins, which may be important for antidepressant response .
4) Neuronal Health and Learning
Scientists are investigating whether 5-MEO-DMT affects the following pathways and processes in cells:
- Reducing neuron death and brain lesions by inactivating certain genes(e.g. Bcl-2) and activating sigma-1 receptors (σ1R) .
- Regenerating neurons and increasing the numbers of dendrites in neurons, which are the parts that receive signals and have been implicated in learning (LTP) [18, 24].
- Increasing brain plasticity via sigma-1 receptor, which has been linked with sensations of novelty and awe .
However, one study found that 5-MEO-DMT decreased levels of srGAP, a protein that has a role in cognitive function, learning, and memory .
This compound is hypothesized to cause hallucinations by affecting the prefrontal cortex (sensory, visual, and associated areas) of the brain .
None of these mechanisms have been explored in humans. It’s impossible to draw conclusions from cellular studies. Animal studies and clinical trials would need to determine how 5-MEO-DMT impacts learning and brain health.
Researchers are exploring whether 5-MEO-DMT:
- Decreases the production of inflammatory molecules IL-1β, IL-6, IL-8, and TNF-α while increasing anti-inflammatory molecule IL-10 in cells .
- Decreases nuclear factor kappa B (NF-κB), which theoretically reduces the activation of inflammatory cytokines [18, 17].
- Reduces the ability of white blood cells to activate other immune cells such as Th1 and Th17 T-cells. Some scientists believe these are overactive in autoimmune and chronic inflammatory diseases .
The effects of 5-MEO-DMT on inflammation in humans are unknown.
In rats, high doses (1.6 – 25µg) of 5-MEO-DMT reduced pain. The researchers hypothesize this was due to increased activation of serotonin receptors (5-HT1A) [26, 15].
5-MEO-DMT in low doses may also increase pain, according to other animal studies. In theory, activation of serotonin receptors (e.g. 5-HT2B and/or 5-HT7) can lead to pain, as in migraines [26, 27].
Much more research is needed before we understand how 5-MEO-DMT may impact pain pathways.
Some scientists think that 5-MEO-DMT might work by decreasing the activation of the mGluR5 receptor, which produces rewarding effects in some addictive drugs. For example, mice without mGluR5 do not consume cocaine due to reduced addiction [18, 19].
Ayahuasca has the potential ability to reduce addiction. Some people have suggested that its effects, in part, may be due to 5-MEO-DMT. However, such claims are still completely ungrounded. Nobody has yet examined the effectiveness and safety of 5-MEO-DMT in people with addiction [28, 29, 30].
Dangers of 5-MEO-DMT
If you have been exposed to 5-MEO-DMT and experience poisoning, urgently contact a poison control center near you (call 1-800-222-1222).
Severe Poisoning and Death
One user combined 5-MEO-DMT with an MAO-A inhibitor (harmaline), which led to severe poisoning and death .
A separate account of a 25-year-old man who made an Ayahuasca preparation containing harmaline, 5-MEO-DMT, and DMT was found dead the morning after ingestion .
Due to 5-MEO-DMT’s ability to raise levels of serotonin and decrease its reuptake, it may lead to a condition called serotonin syndrome. Serotonin syndrome, which is a group of symptoms that can occur (e.g. fever, diarrhea, sweating) due to the combined use of certain drugs, can lead to death due to excessive serotonin-induced toxicity [33, 34].
In one case study, a 5-year-old boy licked a Bufo alvarius toad leading to the ingestion of 5-MEO-DMT. The boy was sent to the hospital with seizures and took a week to fully recover .
Toxicity in Animals
Body Temperature Fluctuations
In rats, 5-MEO-DMT lowered body temperature drastically (hypothermia) in low doses, while higher doses raised body temperature (hyperthermia) .
In mice, 5-MEO-DMT caused hypothermia by stimulating serotonin receptor 5-HT1A, while hyperthermia was caused by stimulating the 5-HT2A receptor .
Hyper- or Hypoactivity
In rats, 5-MEO-DMT with an MAO-A inhibitor decreased movement in the first 30 minutes and increased it in the next 30. 5-MEO-DMT alone only decreased movement .
Other animal studies show similar results. A rat and a mouse study saw that low doses of 5-MEO-DMT with an MAO-A inhibitor caused extreme hyperactivity in 45 minutes to three hours (due to 5-HT2A activation) [38, 39].
However, another rat study only saw decreased activity after 5-MEO-DMT (due to 5-HT1A activation) .
In rats, low doses of 5-MEO-DMT increased pain .
Safety, Drug Interactions & Dosage
5-MEO-DMT use is dangerous. This compound is described as 4- to 10-fold more potent than DMT and it may also cause strong side effects .
Research suggests it causes extreme serotonin reuptake inhibition and serotonin toxicity in combinations with MAO-A inhibitor is likely and potentially fatal [5, 8].
Some users reported that this drug caused panic attacks and anxiety that lasted up to a few weeks after use.
Additionally, licking Bufo alvarius toads to ingest 5-MEO-DMT is extremely dangerous. There are other chemicals on the toads’ skin that are highly toxic to the heart and can lead to death. There have been numerous accounts of people dying after toad-licking, many of which came into contact with the wrong toad and died or suffered permanent paralysis.
5-MEO-DMT causes hallucinations. Self-reported human experiments have shown that 5-MEO-DMT distorts sound, vision, and time. These side effects were seen when taken orally, through the nose, or under the tongue .
Keep in mind that the drug interactions of 5-MEO-DMT are unknown, given the lack of well-designed clinical studies.
Taking 5-MEO-DMT with an MAO-A inhibitor (e.g. harmaline, harmine, clorgyline) can be particularly dangerous. MAO-A inhibitors such as harmaline increase serotonin activity, and when coupled with 5-MEO-DMT, excess serotonin can be toxic and deadly [2, 41].
There is no safe dosage of 5-MEO-DMT. 5-MEO-DMT is an illegal drug that can cause serious side effects. Therefore, we strictly advise against taking it.
This section summarizes research data.
One clinical study used 0 mg of inhaled vaporized toad bufotoxin, which contains 5-MeO-DMT .
According to survey data, users reported taking 5-MEO-DMT by inhalation, injection, under the tongue, or through the nose. Doses ranged from under 1 to 20 mg, depending on the mode of use. Those who ingested it used a MAO-A inhibitor, which may be the most dangerous combination [5, 1, 2].
Many drugs are chemically similar to 5-MEO-DMT (dimethyltryptamines and/or indolealkylamines). Some of them include :
- DMT or “the spirit molecule” (N,N-Dimethyltryptamine)
- Bufotenine or 5-HO-DMT (5-hydroxy-N,N-dimethyltryptamine)
- 5-MEO-DiPT or “Foxy”(5-methoxy-N,N-diisopropyltryptamine).
These drugs all act on the serotonin system, often increasing serotonin to toxic levels.
5-MEO-DMT can be converted into bufotenine, but both drugs are hallucinogenic on their own. Scientists think that bufotenine may bind to serotonin receptors (5-HT2A) better [5, 42, 10].
Often, 5-MEO-DMT is found with other drugs such as DMT and monoamine oxidase A (MOA-A) inhibitors (e.g. harmaline). These combinations can increase toxicity as harmaline increases exposure to both 5-MEO-DMT and bufotenine .
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Do not consider user experiences as medical advice. Never delay or disregard seeking professional medical advice from your doctor or another qualified healthcare provider because of something you have read on SelfHacked. We understand that reading individual, real-life experiences can be a helpful resource, but it is never a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
There are many negative experiences with 5-MEO-DMT. Some users have noted cognitive disruptions such as anxiety and paranoia that can last up to weeks after taking the drug. Other symptoms like the disruption of sleep and panic attacks can also occur.
One user felt like he had been thrown into a “boiling vat of murky white liquid where he wasn’t sure if he had a physical body.” As bubbles would touch his skin, he would receive memories and emotions.
Another user noted complete euphoria after taking the drug. During the trip, he said that “the whole of my being and the world’s existence and history had suddenly made sense to me.” He felt the effects for 30 minutes.
Users often lose their sense of time and space and see vivid colors and imagery. One user said that matrix-like colors gave birth in “non-time” to explosions of sparks which were galactic in the inward scope and scale.
Almost all users detail a phenomenon called “breaking through,” which is when the body and the mind become separated letting the mind wander into whatever imaginary world it can envision. The physical senses/constraints of our world become lifted and oftentimes the user is brought over to an entirely separate world.
During the psychoactive periods, there can be bouts of vomiting and muscle tremors. You may shake and move around uncontrollably. Some users say they moved from one area of the room to another, but do not remember moving. This loss of memory is called a “white-out” and may decrease your ability to form memories of the experience in the short term.
The impact of 5-MEO-DMT on genetics – as well as the impact of genetics on 5-MEO-DMT production in the body is unknown. This section is purely theoretical and outlines early scientific research.
5-MEO-DMT is reduced to bufotenine by CYP2D6. Bufotenine is an active byproduct of 5-MEO-DMT and binds to serotonin receptors better than 5-MEO-DMT. Limited research suggested that people with schizophrenia and other psychotic disorders may have elevated levels of bufotenine in their bodily fluids, but large studies have not verified this [43, 5].
As bufotenine binds to serotonin receptors (5-HT2A) at 10-fold higher rates, exposure to bufotenin may theoretically contribute to the effects of 5-MEO-DMT .
Mouse models show that certain variations of the CYP2D6 gene can increase exposure to bufotenine by 60% .
Other variations of the gene are hypothesized to produce opposite effects by decreasing the production of bufotenine .
For example, a link has been suggested between lower bufotenine conversion and rs3892097 (a nonfunctional variant), rs28371706, or rs1065852.
On the other hand, ultra-rapid metabolizers (with extra copies of the gene) may have higher levels of bufotenine after 5-MEO-DMT.
5-MEO-DMT is inactivated by MAO-A .
These variants have been linked to lower MAO-A levels:
On the other hand, the following have been linked with higher MAO-A: