The drug may potentially combat addictions, protect the brain, and decrease inflammation and pain. However, 5-MEO-DMT can also cause serious side effects and even be fatal. Read on to learn more about the potential benefits, negatives, and mechanisms of 5-MEO-DMT.
Disclaimer: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it and we are simply providing information that is available in the scientific and clinical literature. Please discuss your medications with your doctor.
What Is 5-MEO-DMT?
5-MEO-DMT (5-methoxy-N,N-dimethyltryptamine) is classified as an indolealkylamine. Indolealkylamine drugs are similar in structure to serotonin, a neurotransmitter that controls mood, behavior, and body temperature [1, 2].
More specifically, 5-MEO-DMT belongs to dimethyltryptamines. Dimethyltryptamines are found naturally in the body and may affect conscious states such as your dreams, imagination, and creativity .
Like its relatives, DMT and bufotenine, it has a history of use in a shamanic and spiritual context.
It was initially discovered from the bark of the Dictyoloma incanescens plant. It is also found in the venom of Colorado River Bufo alvarius toads. Smoking its venom can cause intense hallucinations similar to the Virola snuffs and the Ayahuasca drink [1, 7].
5-MEO-DMT is also one of the ingredients in South American Virola snuffs and Ayahuasca beverages . However, these also contain greater amounts of other related compounds (bufotenine and DMT, respectively).
5-MEO-DMT is found naturally (in trace amounts) in human bodily fluids such as urine, blood, and cerebrospinal fluid. It is produced in the retina and pineal gland. Its biological function is still unknown .
Since it’s illegal in the US, research on 5-MEO-DMT health benefits is limited .
The 5-MEO-DMT Experience
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 .
The drug causes visual and auditory hallucinations. However, users report it to be less visual than DMT. Rather, it seems to cause more of an emotional (fear to euphoria) perspective shift, described as overly intense and similar to a near-death experience. The drug is also reported to cause a “loss of ego” and to distort the perception of time.
While under the drug, users may lose physical control and coordination. The drug was also reported to cause nausea and memory loss.
Mechanism of Action
Finally, some of the effects may be due to the activation of 5-HT1B, 5-HT3, and GABAA receptors .
Activation of the 5-HT1A receptor releases serotonin, which is probably causing many of the effects seen after 5-MEO-DMT use, such as pain relief .
There are two types of neurons: presynaptic and postsynaptic. Presynaptic neurons send the signal and postsynaptic neurons receive the signal. Activating 5-HT1A receptors in the presynaptic neuron may increase pain, while activating the postsynaptic neuron may decrease pain .
5-MEO-DMT is broken down by MAO-A. Combining 5-MEO-DMT with MAO-A inhibitors can prolong and increase its effect (plant preparations such as Ayahuasca and Syrian rue seeds contain MAO-A inhibitors, which increase their effectiveness) [1, 8, 15].
Use of MAO-A inhibitors with 5-MEO-DMT also increases 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 [1, 16].
Positive Effects of 5-MEO-DMT
1) May Protect the Brain and Improve Learning
Cell studies have shown that 5-MEO-DMT may decrease neuron death and brain lesions by inactivating genes that cause cells to die (e.g. Bcl-2). It accomplishes this by activating sigma-1 receptors (σ1R) .
5-MEO-DMT may also regenerate neurons. 5-MEO-DMT increased numbers of dendrites in neurons, which are the parts that receive signals. Increasing dendrites can increase learning capabilities in humans by increasing their excitability (LTP) [13, 17].
5-MEO-DMT may also contribute to brain plasticity. In this case, brain plasticity, as activated through the sigma-1 receptor, can also lead to sensations of novelty and awe .
These are commonly associated with psychedelic drugs.
However, the same study found that 5-MEO-DMT decreased levels of srGAP, a protein that has a role in cognitive function, learning, and memory .
2) May Decrease Inflammation
3) May Reduce Pain
In people with low noradrenaline, 5-MEO-DMT may not produce its pain-relieving effects. This is due to the fact that noradrenaline plays an important role in the serotonin pathway, which is what causes pain relief [19, 20].
4) May Reduce Addiction
5-MEO-DMT works by decreasing the activation of the mGluR5 receptor, which produces rewarding effects in some addictive drugs. Mice without mGluR5 do not consume cocaine due to reduced addiction [13, 14].
5) May Improve Response to Antidepressants
In cell studies, 5-MEO-DMT increased a class of receptors called integrins. Increased integrins are seen in patients who respond better to antidepressants .
Negative Effects of 5-MEO-DMT
1) Can Be Toxic and even Cause 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 .
2) May Cause 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 .
3) May Cause 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) [30, 31].
However, another rat study only saw decreased activity after 5-MEO-DMT (due to 5-HT1A activation) .
4) 5-MEO-DMT May Cause Serotonin Syndrome
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 excessive serotonin-affecting drug use, can lead to death due to excessive serotonin-induced toxicity [33, 34].
5) 5-MEO-DMT Can Cause Seizures
In one case study, a 5-year-old boy licked a Bufo alvarius toad leading to ingestion of 5-MEO-DMT. The boy was sent to the hospital with seizures and took a week to fully recover .
6) 5-MEO-DMT May Increase Pain
In rats, low doses of 5-MEO-DMT increased pain .
5-MEO-DMT is more potent than DMT, and may also cause stronger side effects.
Those with hyperserotonergic (high serotonin) disorders (e.g. autism spectrum disorder) should stay clear of 5-MEO-DMT. The drug causes extreme serotonin reuptake inhibition and may cause serotonin toxicity when taken with an MAO-A inhibitor [1, 8].
When ingesting 5-MEO-DMT, it is advised to take the drug with an experienced user who may be able to help in the case of an emergency.
The drug was reported, by some users, to cause panic attacks and anxiety that lasted up to a few weeks after use.
Do not lick Bufo alvarius toads to ingest 5-MEO-DMT. There are other chemicals on the toads’ skin that are toxic to the heart and can lead to death. There are also numerous accounts of people dying after toad-licking as licking the wrong toad can cause death or permanent paralysis.
5-MEO-DMT can cause 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 .
5-MEO-DMT causes hallucinations by affecting the prefrontal cortex (the sensory, visual, and associated areas) of the brain. Rat studies show that 5-MEO-DMT with an MAO-A inhibitor increased the firing rate of 51% of neurons in the prefrontal cortex .
Taking 5-MEO-DMT with an MAO-A inhibitor (e.g. harmaline, harmine, clorgyline) can be dangerous. MAO-A inhibitors such as harmaline already increase serotonin activity by themselves. When coupled with 5-MEO-DMT, excess serotonin activity can be extremely toxic and lead to death [5, 36].
In cell studies, MAO-A inhibitors prolonged 5-MEO-DMT exposure 24-fold .
5-MEO-DMT is taken by inhalation, injection, under the tongue or through the nose. Doses range from under 1 to 20 mg, depending on the mode of use. Ingestion requires an MAO-A inhibitor, and may also be the least safe way of using the drug [1, 4].
Ingesting the drug without an MAO-A inhibitor will either produce no effect or only ⅓ the strength .
It is important to note that people seem to respond differently to different doses.
Users report 1 to 2 mg inhaled as threshold dose, while 5 to 10 mg would already be a stronger dose.
Having an experienced user around can increase safety.
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. People with schizophrenia and other psychotic disorders usually have elevated levels of bufotenine in their bodily fluids [39, 1].
As bufotenine binds to serotonin receptors (5-HT2A) at 10-fold higher rates, exposure to bufotenin can contribute significantly 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 can produce opposite effects by decreasing the production of bufotenine .
On the other hand, ultra-rapid metabolizers (with extra copies of the gene) may have higher levels of bufotenine upon 5-MEO-DMT use.
5-MEO-DMT is inactivated by MAO-A .
Lower activity of this enzyme (and variants that cause low activity) may increase the effect of this drug, as it may stay in the body longer. These are the variants linked to low MAO-A levels:
On the other hand, people with variants that produce more MAO-A may inactivate the drug faster, and may experience less effect from the same dosage:
Drugs Similar to 5-MEO-DMT
There are many drugs 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 concentrations to toxic levels.
Often, 5-MEO-DMT is found with other drugs such as DMT and monoamine oxidase A (MOA-A) inhibitors (e.g. harmaline). Combining these can increase toxicity as harmaline increases exposure to both 5-MEO-DMT and bufotenine .
5-MEO-DMT is 4- to 10-fold more potent than DMT in humans .
Limitations and Caveats
Because of a lack of human studies, and the scarcity of animal ones, it is impossible to pinpoint exactly the benefits and side effects of 5-MEO-DMT. Only self-reported drug use provides some insight as to the effects in humans.
User experiences are plentiful and many of them are positive. 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.
However, there are many negative experiences as well. 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.
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.
5-MEO-DMT is a drug that affects your neurotransmitters. Want to understand your variants in these genes and how they affect your mood and tendency to respond to such drugs? Check out the mood DNA Wellness Report here.