| Reference code: | PT/FB/BL-2020-333.08 |
| Location: | BF-GMS
|
Title:
| Pharmacokinetics and pharmacodynamics of an innovative psychedelic N,N-Dimethyltryptamine/Harmine formulation in healthy participants: A randomized controlled trial
|
| Publication year: | 2025
|
URL:
| https://doi.org/10.1093/ijnp/pyaf001
|
| Abstract/Results: | ABSTRACT:
Background: Recent interest in the clinical use of psychedelics has highlighted plant-derived medicines like ayahuasca showing rapid-acting and sustainable therapeutic effects in various psychiatric conditions. This traditional Amazonian plant decoction contains N,N-dimethyltryptamine (DMT) and ß-carboline alkaloids such as harmine. However, its use is often accompanied by distressing effects like nausea, vomiting, and intense hallucinations, possibly due to complex pharmacokinetic/pharmacodynamic (PK-PD) interactions and lack of dose standardization.
Methods: This study addresses these limitations by testing a novel pharmaceutical formulation containing pure forms of DMT and harmine in a double-blind, randomized, placebo-controlled trial with 31 healthy male volunteers. We evaluated PK-PD by monitoring drug and metabolite plasma levels, subjective effects, adverse events, and cardiovascular parameters. Each participant received three randomized treatments: 1) 100 mg buccal harmine with 100 mg intranasal DMT, 2) 100 mg buccal harmine with intranasal placebo, and 3) full placebo; using a repeated-intermittent dosing scheme, such that 10 mg of DMT (or placebo) was administered every 15 minutes.
Results: DMT produced consistent PK profiles with Cmax values of 22.1 ng/ml and acute drug effects resembling the psychological effects of ayahuasca with a duration of 2-3 hours. Likewise, buccal harmine produced sustained-release PK profiles with Cmax values of 32.5 ng/ml, but lacked distinguishable subjective effects compared to placebo. All drug conditions were safe and well tolerated, indicating the formulation's suitability for clinical applications.
Conclusion: This study underscores the potential of a patient-oriented pharmaceutical formulation of DMT and harmine to reduce risks and improve therapeutic outcomes in treating mental health disorders.
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| Accessibility: | Document exists in file
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Language:
| eng
|
Author:
| Mueller, M. J.
|
Secondary author(s):
| Aicher, H. D., Dornbierer, D. A., Marten, L., Suay, D., Meling, D., Elsner, C., Wicki, I. A., Müller, J., Poetzsch, S. N., Caflisch, L., Hempe, A., Steinhart, C. P., Puchkov, M., Kost, J., Landolt, H. P., Seifritz, E., Quednow, B. B., Scheidegger, M.
|
Document type:
| Article
|
Number of reproductions:
| 3
|
Reference:
| Mueller, M. J., Aicher, H. D., Dornbierer, D. A., Marten, L., Suay, D., Meling, D., Elsner, C., Wicki, I. A., Müller, J., Poetzsch, S. N., Caflisch, L., Hempe, A., Steinhart, C. P., Puchkov, M., Kost, J., Landolt, H. P., Seifritz, E., Quednow, B. B., & Scheidegger, M. (2025). Pharmacokinetics and pharmacodynamics of an innovative psychedelic N,N-Dimethyltryptamine/Harmine formulation in healthy participants: A randomized controlled trial. The International Journal of Neuropsychopharmacology, 28(1), pyaf001. https://doi.org/10.1093/ijnp/pyaf001
|
| 2-year Impact Factor: | 3.7|2024
|
| Impact factor notes: | Impact factor not available yet for 2025
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| Times cited: | 4|2025-09-27
|
| Indexed document: | Yes
|
| Quartile: | Q1
|
| Keywords: | N / N-dimethyltryptamine / Harmine / Pharmacodynamics / Pharmacokinetics / Psychedelics
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Pharmacokinetics and pharmacodynamics of an innovative Psychedelic N,N-Dimethyltryptamine/Harmine formulation in healthy participants: A randomized controlled trial |