5-MeO-DMT for Medicinal Chemistry & Drug Development

A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine) in patients with treatment-resistant depression

This 12‑week, open‑label Phase IIa trial of a single 10 mg intranasal dose of 5‑MeO-DMT (BPL‑003) in patients (n=12) with treatment‑resistant major depressive disorder, found that the drug was generally well tolerated with mostly mild–moderate adverse events and rapid discharge readiness (median ~98 minutes). A rapid and sustained mean MADRS reduction of 12–13 points was observed from Day 2 through Day 85, with most participants meeting response criteria and several achieving remission, supporting further evaluation in larger controlled trials.

Published: February 27, 2026
Journal: Journal of Psychopharmacology
Authors: Roberts, C., Seynaeve, M., Ermakova, A. O., Dunbar, F., Wells, H., Puri, A., Bird, C., Rucker, J. J.

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Safety and tolerability of multiple sublingual microdoses of 5-MeO-DMT in adults with moderate symptoms of depression and/or anxiety: a randomized, double-blind, placebo-controlled study

This Phase I clinical trial (n=36) of sublingual 5-MeO-DMT (6-12 mg weekly doses over four weeks) in adults with moderate to high anxiety/depression demonstrated good safety and tolerability with no significant adverse events, rapid absorption with peak plasma concentrations at 20 minutes, dose-dependent neurophysiological modulation without full psychedelic effects, and maintenance of normal cognitive and behavioral function.

Published: July 15, 2025
Journal: Neuropsychopharmacology
Authors: Beatriz, M., Millón, B., Noguera, L., Bruno, D., Vita, L., Zanino, M., Kassuha, D. E., Ortiz, J. E., Feresin, G. E., Díaz-Dellavalle, P., Orosco, L., Garcés, M. A., Diez, P., Albarracín, S. G., Bruno, M. A.

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Structural pharmacology and therapeutic potential of 5-methoxytryptamines

This molecular study investigates the underpinnings of 5-MeO-DMT pharmacology and its therapeutic potential through cryogenic electron microscopy structures of 5-HT1A, medicinal chemistry, receptor mutagenesis, and mouse behaviour. The research characterizes molecular determinants of 5-HT1A signalling potency, efficacy, and selectivity, contrasting the structural interactions and pharmacology of 5-MeO-DMT with LSD and clinically used 5-HT1A agonists.

Published: May 8, 2024
Journal: Nature
Authors: Warren, A. L., Lankri, D., Cunningham, M. J., Serrano, I. C., Parise, L. F., Kruegel, A. C., Duggan, P., Zilberg, G., Capper, M. J., Havel, V., Russo, S. J., Sames, D., Wacker, D.

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Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participants

In this double-blind, placebo-controlled Phase 1 trial, intranasal BPL-003 (5‑MeO‑DMT benzoate) was well tolerated up to 12 mg and showed rapid absorption and elimination with dose‑proportional systemic exposure (Tmax ≈ 8–10 min; mean terminal half‑life <27 min) and negligible bufotenine formation. Pharmacodynamic effects scaled with plasma concentrations, producing profound, short‑lasting consciousness‑altering and mystical experiences—60% of participants had a complete mystical experience at 10–12 mg—supporting further clinical evaluation.

Published: April 14, 2024
Journal: Journal of Psychopharmacology
Authors: Rucker, J., Roberts, C. A., Seynaeve, M., Young, A. H., Suttle, B., Yamamoto, T., Ermakova, A. O., Dunbar, F., Wiegand, F.

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The potential of 5-methoxy-N,N-dimethyltryptamine in the treatment of alcohol use disorder: A first look at therapeutic mechanisms of action

This review (2024) examines the potential therapeutic mechanisms of action for alcoholism (AUD) treatment using 5-MeO-DMT. It highlights that 5-MeO-DMT can induce mystical experiences and ego-dissolution, leading to increased psychological flexibility and mindfulness, which may alleviate AUD symptoms. Additionally, preliminary evidence suggests that 5-MeO-DMT modulates neural oscillations and exhibits neuroplasticity and anti-inflammatory properties, indicating its potential clinical implications for AUD and related psychiatric comorbidities.

Published: April 10, 2024
Journal: Addiction Biology
Authors: Tap, S. C.

Open Accessindividual

Structure-activity relationships of serotonergic 5-MeO-DMT derivatives: insights into psychoactive and thermoregulatory properties

This cell & mice study explores the psychopharmacological profile of amino-substituted 5-MeO-tryptamines, focusing on their interactions with serotonin receptors and transporters, as well as their psychoactive and thermoregulatory properties. The study demonstrates selectivity for 5-HT1AR over 5-HT2AR among examined compounds using radioligand binding methodologies and computational docking analyses, and 5-MeO-pyr-T was identified as the most potent partial 5-HT releaser.

Published: March 14, 2024
Journal: Molecular Psychiatry
Authors: Puigseslloses, P., Nadal-Gratacós, N., Ketsela, G., Weiss, N., Berzosa, X., Estrada-Tejedor, R., Islam, M. N., Holy, M., Niello, M., Pubill, D., Camarasa, J., Escubedo, E., Sitte, H. H., López-Arnau, R.

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Medicinal Chemistry & Drug Development

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A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine) in patients with treatment-resistant depression

Safety and tolerability of multiple sublingual microdoses of 5-MeO-DMT in adults with moderate symptoms of depression and/or anxiety: a randomized, double-blind, placebo-controlled study

Structural pharmacology and therapeutic potential of 5-methoxytryptamines

Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participants

The potential of 5-methoxy-N,N-dimethyltryptamine in the treatment of alcohol use disorder: A first look at therapeutic mechanisms of action

Structure-activity relationships of serotonergic 5-MeO-DMT derivatives: insights into psychoactive and thermoregulatory properties

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