If you compare 5-MeO-DMT vs. DMT by name alone, you might think they’re pretty similar. However, these psychedelic compounds differ in potency, effects, and even how they work in the brain.

The DMT experience is powerful, short, and potentially mystical. In comparison, the 5-MeO-DMT experience is considered far more intense than what a person would encounter with DMT.

Although these psychedelics share some features, they are not interchangeable. So, why would someone choose 5-MeO-DMT or DMT? Let’s discuss these drugs, how they differ, and common questions.

What Is DMT?

DMT (N,N-Dimethyltryptamine) is also known as “the Spirit Molecule.” Canadian chemist Richard Manske first synthesized DMT in a lab in 1931.1 However, Indigenous peoples of the Amazon have used DMT-containing plants for spiritual and medicinal use for thousands of years.

How DMT works

On its own, DMT is a powerful psychedelic drug that can produce intense out-of-body experiences, altered perceptions of time and space, mystical experiences, and encounters with seemingly autonomous beings (also known as DMT entities). The DMT experience is notable for its short duration: Depending on how it’s taken, a DMT trip can last five to 30 minutes.

DMT is the primary psychoactive component in Ayahuasca, a brew traditionally prepared by Indigenous Amazonian peoples. Due to the specific combination of plants in Ayahuasca, the psychedelic trip can last as long as 10 hours.

Like psilocybin and LSD, DMT acts on 5-HT2A receptors in the brain. These receptors are like landing pads for chemical messengers called neurotransmitters. DMT changes levels of serotonin, a neurotransmitter that helps regulate emotions, mood, and cognition.2 3

We don’t yet know the extent of DMT’s therapeutic effects because there isn’t enough clinical research. However, one clinical trial, which aims to study the effects of DMT in healthy subjects, is scheduled to be completed later this year. In a separate clinical trial, investigators hypothesize that DMT will result in neuroplastic changes in healthy and depressed subjects.

What Is 5-MeO-DMT?

5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine) is a derivative of DMT. It occurs naturally in several plants and the secretions of the Sonoran Desert toad (aka the Colorado River toad, Incilius alvarius, or Bufo Alvarius toad).

How 5-MeO-DMT works

Like DMT, 5-MeO-DMT produces intense psychedelic experiences that can feature dissociation, ego death (aka ego dissolution), and hallucinations. However, people report fewer visual effects and more intense out-of-body experiences with 5-MeO-DMT. While DMT is called the Spirit Molecule, 5-MeO-DMT is also known as the God Molecule due to the profound mystical experience it can produce.

Animal models show that 5-MeO-DMT binds to serotonin receptors, specifically 5-HT2A (the same as DMT and other classical psychedelics). Although it’s not yet clear how 5-MeO-DMT works in humans, researchers theorize that it has similar effects on serotonin levels in the brain.4 5

Chemists first synthesized 5-MeO-DMT in a lab in 1936.6 However, Indigenous peoples in South America have a long history of using natural 5-MeO-DMT sources like Anadenanthera peregrina (which is used in yopo snuff) and Diplopterys cabrerana (which can be used to prepare Ayahuasca).

Small studies in humans indicate that 5-MeO-DMT is associated with improvements in depression, anxiety, and life satisfaction.7 8 However, further clinical research is needed to fully understand the therapeutic applications of this drug.

Here’s a snapshot of two notable clinical trials: King’s College London completed a clinical trial in July 2022 to study the effect of a single dose of 5-MeO-DMT in healthy subjects; results have not been published yet. In addition, GH Research Ireland Limited, a biopharmaceutical company, studied the effects of 5-MeO-DMT in patients with treatment-resistant depression (TRD) in 2021; results have not been posted yet.

The Differences Between 5-MeO-DMT and DMT

Dose

Compared to DMT, 5-MeO-DMT is approximately 10–20 times more potent in humans.9 Due to that potency, DMT is generally taken at higher doses than 5-MeO-DMT. An inhaled dose of 5-MeO-DMT is around 3–25 mg, while an inhaled dose of DMT is 30–150 mg.10 11

Experience

There is a gap in research that explicitly compares the subjective differences between 5-MeO-DMT and DMT journeys. However, surveys and online trip reports indicate that 5-MeO-DMT can produce “content-free experiences” that are defined by detachment from oneself and the environment, sensory deprivation, and the sensation of emptiness.10

In comparison, DMT experiences are generally more visual. Although ego-death and near-death experiences have been reported with high doses of DMT, users commonly report visual distortions like colorful geometric shapes and kaleidoscopic lights.12

Effects on the brain

More clinical studies are needed to understand how 5-MeO-DMT and DMT work in the brain, but current research indicates that 5-MeO-DMT has the highest affinity for the 5-HT1A and 5-HT2A receptors.13 This is significant because psychedelics’ functional and experiential effects are primarily due to the activity on these receptors, which play a role in mood and nervous system activity.

Natural sources

Sustainability is a particular issue with 5-MeO-DMT sourced from Sonoran Desert toad venom. Unfortunately, this toad is a threatened species, and the venom harvesting process can endanger both the toad and its natural habitat. Synthetic 5-MeO-DMT is a more sustainable option than toad secretion.

What 5-MeO-DMT and DMT Have in Common

Interactions with MAOIs and RIMAs

The monoamine oxidase enzyme quickly breaks down 5-MeO-DMT and DMT, which means you won’t feel a psychoactive effect if you consume these psychedelics orally. However, 5-MeO-DMT and DMT’s psychedelic effects are prolonged when they’re paired with a monoamine oxidase inhibitor (MAOI) or reversible inhibitor of monoamine oxidase A (RIMA).

An Ayahuasca experience can last as long as 10 hours because recipes for this psychoactive brew tend to combine plants that contain DMT and MAOIs or RIMAs. However, this interaction also explains the danger of certain drug interactions.

Don’t combine 5-MeO-DMT, DMT, and other substances or drugs that contain MAOIs or RIMAs, such as certain antipsychotic drugs. For example, SSRIs (a type of antidepressant medication) should not be combined with 5-MeO-DMT.14

Tolerability

5-MeO-DMT and DMT are not considered to be addictive. Neither drug induces tolerance or physical withdrawal symptoms in dose-finding studies.10 15 However, it’s possible to become psychologically dependent on any substance, particularly with repeat use.

If you or someone you know are struggling with substance use or addiction, reach out to the Substance Abuse and Mental Health Services Administration (SAMHSA) National Helpline at 1-800-662-4357 for information about support and treatment facilities in your area.

Duration

Both psychedelics work quickly, although the DMT experience is slightly shorter. DMT generally lasts up to 30 minutes, while 5-MeO-DMT lasts up to 45 minutes.3 10 If these drugs are paired with a MAO inhibitor, as in Ayahuasca, the psychedelic experience can last four hours or more.

Frequently Asked Questions

Is toad venom and DMT the same?

Toad venom is not the same thing as DMT. Toad venom refers to the secretions of the Sonoran Desert toad, which contains 5-MeO-DMT. On the other hand, DMT is a psychedelic compound found in plants and animals or produced in a lab.

What plant does DMT come from?

DMT comes from many plants, including Banisteriopsis caapi and Psychotria viridis, which Indigenous peoples use to prepare Ayahuasca. DMT is also found in some plants in the Phalaris, Delosperma, Acacia, Desmodium, Mimosa, Virola, and Psychotria genera.16

What is a tryptamine drug?

A tryptamine drug is a hallucinogen that primarily acts on the 5-HT2A receptor.17 Examples of tryptamine derivatives include 5-MeO-DMT, DMT, and psilocybin.

Is 5-MeO-DMT legal?

5-MeO-DMT is illegal in the United States, as is DMT. Per the Drug Enforcement Administration, both drugs are classified as Schedule I controlled substances, which means unlawful possession is illegal at the federal level. Some parts of the country have decriminalized the possession of naturally occurring hallucinogens like 5-MeO-DMT, but decriminalization doesn’t mean legalization.

5-MeO-DMT vs. DMT: Which Is Better?

It’s easy to focus on the similarities when considering 5-MeO-DMT or DMT: Both drugs produce short trips and profound mystical experiences. However, according to anecdotal reports, people new to psychedelics should not start with 5-MeO-DMT. This drug’s intense experiences and high potency shouldn’t be taken lightly.

References

  1. Manske RHF. A SYNTHESIS OF THE METHYLTRYPTAMINES AND SOME DERIVATIVES. Can J Res. 1931 Nov 1;5(5):592–600. https://cdnsciencepub.com/doi/abs/10.1139/cjr31-097
  2. Strassman RJ. Human psychopharmacology of N,N-dimethyltryptamine. Behav Brain Res. 1996;73(1–2):121–4. https://pubmed.ncbi.nlm.nih.gov/8788488/
  3. Barker SA. N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function. Front Neurosci. 2018 Aug 6;12:536. https://www.frontiersin.org/articles/10.3389/fnins.2018.00536/full
  4. Shen H-W, Jiang X-L, Yu A-M. Nonlinear pharmacokinetics of 5-methoxy-N,N-dimethyltryptamine in mice. Drug Metab Dispos. 2011 Jul;39(7):1227–34. https://pubmed.ncbi.nlm.nih.gov/26977821/
  5. Nagai F, Nonaka R, Satoh Hisashi Kamimura K. The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain. Eur J Pharmacol. 2007 Mar 22;559(2–3):132–7. https://pubmed.ncbi.nlm.nih.gov/17223101/
  6. Erspamer V, Vitali T, Roseghini M, Cei JM. 5-Methoxy- and 5-hydroxyindoles in the skin of Bufo alvarius. Biochem Pharmacol. 1967 Jul 7;16(7):1149–64. https://pubmed.ncbi.nlm.nih.gov/6053590/
  7. Davis AK, So S, Lancelotta R, Barsuglia JP, Griffiths RR. 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. Am J Drug Alcohol Abuse. 2019 Mar 1;45(2):161–9. https://pubmed.ncbi.nlm.nih.gov/30822141/
  8. Uthaug MV, Lancelotta R, van Oorsouw K, Kuypers KPC, Mason N, Rak J, et al. A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms. Psychopharmacology (Berl). 2019 Sep;236(9):2653–66. https://pubmed.ncbi.nlm.nih.gov/30982127/
  9. McKenna DJ, Towers GH, Abbott FS. Monoamine oxidase inhibitors in South American hallucinogenic plants Part 2: Constituents of orally-active Myristicaceous hallucinogens. J Ethnopharmacol. 1984 Nov;12(2):179–211. https://pubmed.ncbi.nlm.nih.gov/6521493/
  10. Ermakova AO, Dunbar F, Rucker J, Johnson MW. A narrative synthesis of research with 5-MeO-DMT. J Psychopharmacol (Oxford). 2022 Mar;36(3):273–94. https://journals.sagepub.com/doi/full/10.1177/02698811211050543
  11. Barker SA. Administration of N,N-dimethyltryptamine (DMT) in psychedelic therapeutics and research and the study of endogenous DMT. Psychopharmacology (Berl). 2022 Jan 22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8782705/
  12. Luke D. Discarnate entities and dimethyltryptamine (DMT): Psychopharmacology, phenomenology and ontology. J Am Soc Psych Res. 2011 Jan 1;75.1(902):26–42. https://psycnet.apa.org/record/2011-04822-003
  13. Reckweg JT, Uthaug MV, Szabo A, Davis AK, Lancelotta R, Mason NL, et al. The clinical pharmacology and potential therapeutic applications of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). J Neurochem. 2022 Feb 11. https://onlinelibrary.wiley.com/doi/full/10.1111/jnc.15587
  14. Yu A-M. Indolealkylamines: biotransformations and potential drug-drug interactions. AAPS J. 2008 Jun;10(2):242–53. https://link.springer.com/article/10.1208/s12248-008-9028-5
  15. Winstock AR, Kaar S, Borschmann R. Dimethyltryptamine (DMT): prevalence, user characteristics and abuse liability in a large global sample. J Psychopharmacol (Oxford). 2014 Jan;28(1):49–54. https://journals.sagepub.com/doi/10.1177/0269881113513852
  16. Carbonaro TM, Gatch MB. Neuropharmacology of N,N-dimethyltryptamine. Brain Res Bull. 2016 Sep;126(Pt 1):74–88. https://pubmed.ncbi.nlm.nih.gov/27126737/
  17. Araújo AM, Carvalho F, Bastos M de L, Guedes de Pinho P, Carvalho M. The hallucinogenic world of tryptamines: an updated review. Arch Toxicol. 2015 Aug;89(8):1151–73. https://pubmed.ncbi.nlm.nih.gov/25877327/