Mechanism of Action
Finally, some of the effects may be due to the activation of 5-HT1B, 5-HT3, and GABAA receptors [R].
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 [R].
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 [R].
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) [R, R, R].
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 [R, R].
Health Effects of 5-MEO-DMT
1) 5-MEO-DMT 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) [R].
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) [R, R].
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 [R].
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 [R].
2) 5-MEO-DMT May Decrease Inflammation
3) 5-MEO-DMT 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 the pain relief [R, R].
4) 5-MEO-DMT 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 [R, R].
5) 5-MEO-DMT 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 [R].
Negative Effects of 5-MEO-DMT
1) 5-MEO-DMT 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 [R].
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 [R].
2) 5-MEO-DMT 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) [R].
In mice, 5-MEO-DMT caused hypothermia by stimulating serotonin receptor 5-HT1A, while hyperthermia was caused by stimulating the 5-HT2A receptor [R].
3) 5-MEO-DMT 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 [R].
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) [R, R].
However, another rat study only saw decreased activity after 5-MEO-DMT (due to 5-HT1A activation) [R].
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 [R, R].
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 [R].
6) 5-MEO-DMT May Increase Pain
In rats, low doses of 5-MEO-DMT increased pain [R].
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