Synthesizing 5-MeO-DMT to Meet Clinical Needs

The magical and mighty molecule called 5-methoxydimethyltryptamine (5-MeO-DMT) mesmerizes us with its potent, visionary properties. Those who explore its mystical healing dexterity report wanting to “connect with all that is, transcendence, downloading universal knowledge, and understanding of self.” [1] These intentions have led to the moniker of “god molecule.” In fact, The Church of the Tree of Life considered 5-MeO-DMT a sacrament.

In addition to transcendent, otherworldly properties, psychedelic molecules like 5-MeO-DMT have been of resurgent interest for their ability to quickly reverse mental illnesses like post-traumatic stress disorder, depression, anxiety, and for the role they can play during end-of-life treatments. [2-4]

5-MeO-DMT is most commonly associated with the Sonoran Desert toad. Secretions of its parotid gland are obtained via squeezing the gland and catching the milky white product against something like a glass sheet. Once depleted, the toad requires 4-6 weeks to replenish its stock.

Just a single inhalation of the toad secretion has been linked to decreased depression and anxiety as well as a concomitant increase in mindfulness and the quality of and satisfaction with life. [5] The trouble is that with the soaring interest in faster options for controlling and changing one’s mindset, coupled with the medicinal prowess that 5-MeO-DMT offers, a sizeable stockpile of the toad secretion is needed.

A 2020 study evaluated the chemical synthesis of 5-MeO-DMT such that a product with known purity and strength could be obtained. [5] In addition, freebasing 5-MeO-DMT isn’t considered to be a “pharmaceutically acceptable approach.” Although inhaling a dry powder, applying a transdermal, or using intravenously injected 5-MeO-DMT are possibilities, these researchers sought an intramuscular injection. Previous studies have demonstrated the “advantageous duration of action compared to the intense rapid-onset produced by other intraperitoneal routes.”

A precise 20 mg/mL solution containing saline, excipients, and between 2-15 mg of 5-MeO-DMT provided a stable preparation, unlike the freebase form which has limited water solubility and can degrade when exposed to oxygen. To mitigate water solubility issues, the researchers explored 5-MeO-DMT salts, including hydrochloride, sulfate, fumarate, and succinate forms. The sulfate form produced an undesirable gum. The hydrochloride salt produced a crystalline solid, but it readily absorbed moisture from the environment, becoming a liquid under higher humidity.

The fumarate and succinate forms were adequate, however, due to the possible reactivity of fumaric acid when sterilizing by autoclave, the researchers nominated the succinate salt. Their synthesis and subsequent processing steps led to >98% purity but there was a noticeable color variation due to varied lots of a reagent, so, much like in cannabis processing, the researchers turned to activated charcoal to clean up the color. This process produced a 49% yield of 5-MeO-DMT (136 g), therefore, augmenting the yield is a future goal of the research team.

A 2004 survey by the International Union for Conservation of Nature didn’t place the Sonoran Desert toad on the endangered list, but interest in harvesting 5-MeO-DMT have exploited toad populations. Other studies have pointed to chemically synthesized 5-MeO-DMT as having significant ecological importance. [1]



[1] Uthaug MV, Lancelotta R, van Oorsouw K, 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;236(9):2653-2666. [journal impact factor = 3.130; times cited = 17 (Semantic Scholar)] [2] Garcia-Romeu A, Kersgaard B, Addy PH. Clinical applications of hallucinogens: A review. Exp Clin Psychopharmacol. 2016;24(4):229-268. [journal impact factor = 3.157; times cited = 84 (Semantic Scholar)] [3] Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016;30(12):1181-1197. [journal impact factor = 4.153; times cited = 564 (Semantic Scholar)] [4] Ot’alora G M, Grigsby J, Poulter B, et al. 3,4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: A randomized phase 2 controlled trial. J Psychopharmacol. 2018;32(12):1295-1307. [journal impact factor = 4.153; times cited = 62 (Semantic Scholar)] [5] Sherwood AM, Claveau R, Lancelotta R, Kaylo KW, and Lenoch K. Synthesis and characterization of 5-MeO-DMT succinate for clinical use. ACS Omega. 2020;5:32067-32075. [journal impact factor = 3.512; times cited = 1 (Semantic Scholar)]


Image Credit: Sherwood AM, Claveau R, Lancelotta R, Kaylo KW, and Lenoch K. Synthesis and characterization of 5-MeO-DMT succinate for clinical use. ACS Omega. 2020;5:32067-32075.

About the author

Jason S. Lupoi, Ph.D.

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