In this video blog, we will delve into the pharmacologic mechanisms of 5-MeO-DMT compared to classic psychedelic tryptamines such as LSD, psilocybin, and DMT.
- All psychedelic tryptamines stimulate serotonin 2A (5HT2A) receptors.
- Classic tryptamines have a ‘ceiling effect’ due to partial agonism, while 5-MeO-DMT is a full agonist.
- Classic tryptamines have limited effects on other serotonin receptors and enzymes, while 5-MeO-DMT can activate additional serotonin receptors and increase intrasynaptic serotonin levels.
- 5-MeO-DMT carries the risk of serotonergic toxicity and should be used with caution, especially in combination with monoamine oxidase inhibitors (MAOIs).
Psychedelic Tryptamines are Serotonin 2A Stimulating Substances
All psychedelic tryptamines, including 5-MeO-DMT, have the ability to bind and stimulate serotonin 2A (5HT2A) receptors. Studies have shown that when these receptors are blocked, the psychedelic effects are significantly reduced or eliminated. This common mechanism is shared by both classic psychedelic tryptamines and 5-MeO-DMT.
Classic Psychedelics vs. 5-MeO-DMT at Serotonin 2A Receptors
While classic psychedelic tryptamines and 5-MeO-DMT both bind to 5HT2A receptors, there may be different pharmacological properties that distinguish them. Classic tryptamines can only partially activate the receptor compared to serotonin, resulting in a ‘ceiling effect’ on the response they can produce. This explains why classic psychedelics do not have lethal doses. On the other hand, 5-MeO-DMT is a full agonist and can produce supraphysiologic responses compared to serotonin.
Pharmacology Beyond Serotonin 2A Receptors
Classic psychedelic tryptamines primarily interact with various serotonin receptors, similar to their interaction with 5HT2A receptors. They have limited activity on targets outside of serotonin receptors, such as serotonin packaging proteins (VMAT2), the serotonin reuptake pump (SERT), and the serotonin breakdown enzyme Monoamine Oxidase (MAO). This means that classic tryptamines do not significantly increase serotonin levels in synapses, which limits their potential for serotonin toxicity. In contrast, 5-MeO-DMT can fully activate other serotonin receptors, such as 5HT1A, and can also bind to SERT, potentially increasing intrasynaptic serotonin levels.
What’s the Bottom Line?
While 5-MeO-DMT shares many pharmacological similarities with classic psychedelic tryptamines, it is a stronger serotonergic substance overall and has the potential to increase intrasynaptic serotonin levels. This suggests that there may be an overdose point where toxic serotonergic responses can occur, especially when combined with other substances that increase serotonin. The combination of 5-MeO-DMT with monoamine oxidase inhibitors (MAOIs) has been reported to be fatal.
Want More Information on 5-MeO-DMT?
Download your copy of the FIVE Guide for a more comprehensive discussion of the pharmacology and drug interaction potential of 5-MeO-DMT.
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