What is the Closest Drug to DMT?: A Pharmacological Comparison

October 9, 2025 •

3 min read

Tryptamine derivatives are a class of compounds chemically related to the monoamine alkaloid tryptamine, and they often act as agonists at serotonin receptors. Among the most well-known is DMT, but this raises the question: what is the closest drug to DMT in terms of chemical structure and effect?

Quick Summary

Pharmacologically, 5-MeO-DMT and psilocybin are the most frequently compared drugs to N,N-DMT. While all are tryptamines that act on serotonin receptors, their potency, duration, and subjective effects differ significantly.

Key Points

Closest Relatives: 5-MeO-DMT and psilocybin are considered the closest, most common relatives to DMT, all belonging to the tryptamine class.
Chemical Similarity: 5-MeO-DMT is structurally the most similar to DMT, with a simple addition of a methoxy group on the indole ring.
Pharmacological Action: DMT and psilocin (from psilocybin) both primarily act as agonists on the 5-HT2A serotonin receptor to produce their classic psychedelic effects.
Potency and Effects: 5-MeO-DMT is 4-20 times more potent than DMT and often produces less visual, more 'ego-dissolving' experiences described as 'whiteouts'.
Duration is Key: A major difference is duration; smoked DMT lasts about 20 minutes, whereas psilocybin's effects last 4-6 hours.
Legal Status: DMT and its primary analogues like psilocybin and 5-MeO-DMT are Schedule I controlled substances in the U.S., making them illegal outside of approved research.
Mechanism of Action: The psychedelic effects of tryptamines are largely attributed to their ability to stimulate 5-HT2A receptors, disrupting normal brain network connectivity.

Understanding DMT and its Pharmacological Neighbors

N,N-Dimethyltryptamine (DMT) is a potent, naturally occurring psychedelic found in various plants and animals. It is a tryptamine, sharing a structural similarity with serotonin. DMT's rapid and profound effects are primarily mediated through its interaction with brain serotonin receptors, particularly the 5-HT2A subtype. Identifying the closest drug to DMT involves examining other tryptamines with similar structures and mechanisms.

The Prime Candidates: 5-MeO-DMT and Psilocybin

When considering substances most similar to DMT, 5-MeO-DMT and psilocybin are frequently mentioned.

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT): This compound is structurally very close to DMT, differing by a methoxy group. It is found in plants and the venom of the Incilius alvarius toad. 5-MeO-DMT is significantly more potent than DMT, up to 20 times stronger. While both are short-acting, 5-MeO-DMT primarily targets the 5-HT1A receptor with less affinity for 5-HT2A compared to classic psychedelics. Subjectively, it often produces experiences described as a "whiteout" with less complex visuals than DMT.
Psilocybin: Found in certain mushrooms, psilocybin is converted to the active compound psilocin in the body. Psilocin is structurally similar to serotonin and primarily activates 5-HT2A receptors, similar to DMT. A major distinction is the duration; smoked DMT lasts 5-20 minutes, while psilocybin effects last 4-6 hours. Oral DMT, such as in ayahuasca which includes an MAOI, has a longer duration comparable to a psilocybin trip.

Chemical and Pharmacological Comparison

A comparison highlights the similarities and differences. These substances are indolealkylamines, a subgroup of tryptamines, and their psychoactive effects relate to their action on 5-HT2A serotonin receptors.


Feature	N,N-DMT	5-MeO-DMT	Psilocybin (Psilocin)
Chemical Class	Tryptamine	Tryptamine	Tryptamine
Primary Receptor	5-HT2A, 5-HT1A	5-HT1A, with lower affinity for 5-HT2A	5-HT2A
Potency	Standard tryptamine potency	4-20x more potent than DMT	Less potent than DMT
Duration (Smoked)	5–20 minutes	15-30 minutes	N/A (typically ingested)
Duration (Oral)	Inactive without MAOI	Inactive without MAOI	4–6 hours
Visuals	Intense, complex, geometric, entity encounters	Often described as a "whiteout" or lack of complex visuals	Moderate to strong, often geometric and colorful
Subjective Feel	Immersive, otherworldly, information-rich	Ego dissolution, non-dual awareness, sometimes overwhelming	Introspective, emotional, connected to nature

Other Related Tryptamines

Besides 5-MeO-DMT and psilocybin, numerous synthetic tryptamine analogues of DMT exist, such as DPT and 4-AcO-DMT. 4-AcO-DMT is thought to be a prodrug for psilocin, yielding effects similar to psilocybin. These demonstrate how slight structural changes can create a variety of effects and potencies.

Legal and Safety Considerations

DMT, 5-MeO-DMT, and psilocybin are Schedule I controlled substances in the U.S. and many other countries, making them illegal outside of specific research settings. The DEA has proposed increased production quotas for research into FDA-approved treatments in 2025. Combining tryptamines, especially with MAOIs or other serotonergic drugs, poses serious risks like serotonin syndrome.

Visit the National Institute on Drug Abuse (NIDA) for more information on hallucinogens.

Conclusion

The closest drug to DMT depends on the comparison criteria. Chemically, 5-MeO-DMT is a direct analogue. Pharmacologically, psilocin (from psilocybin) has a similar 5-HT2A receptor mechanism, leading to comparable hallucinogenic experiences, but lasting much longer. Subjectively, oral DMT (ayahuasca) is often compared to psilocybin, while smoked DMT is unique in its intensity and brevity. 5-MeO-DMT, despite chemical similarity, offers a distinct, less visual experience. While related, no drug perfectly mimics DMT's singular effects.

Frequently Asked Questions

No. While they are structurally very similar, 5-MeO-DMT is significantly more potent than N,N-DMT and engages serotonin receptors differently, leading to subjectively distinct experiences that are often less visual.

Psilocybin is converted to psilocin in the body, which, like DMT, acts on 5-HT2A receptors. The main difference is duration; psilocybin trips last 4-6 hours, while smoked DMT effects last only 5-20 minutes. Orally active DMT (ayahuasca) has a duration more comparable to psilocybin.

Tryptamines are a class of compounds that share a core chemical structure (indolealkylamine). They are structurally similar to the neurotransmitter serotonin. This class includes natural psychedelics like DMT, psilocybin, and 5-MeO-DMT.

DMT's primary psychedelic effects are mediated by its action as an agonist at the serotonin 5-HT2A receptor. It also shows affinity for other serotonin receptors like 5-HT1A and 5-HT2C.

No. In the United States, DMT, psilocybin, and 5-MeO-DMT are Schedule I controlled substances, making their possession, sale, and use illegal outside of federally approved research. Some local jurisdictions have moved to decriminalize them, but they remain illegal under federal law.

DMT is rapidly metabolized in the body by an enzyme called monoamine oxidase (MAO). This rapid breakdown is why the effects are so brief when it is smoked or injected. When taken orally as part of an ayahuasca brew, it is combined with an MAO inhibitor, which allows it to be active for a much longer period.

Unlike other classic psychedelics such as LSD and psilocybin, research suggests there is very little development of tolerance (tachyphylaxis) with repeated use of DMT.