Pharmacokinetics and pharmacodynamics of an innovative psychedelic N,N-dimethyltryptamine/harmine formulation in healthy participants: a randomized controlled trial.
Michael J Mueller, Helena Aicher, Dario Dornbierer, Laurenz Marten, Dila Suay, Daniel Meling, Claudius Elsner, Ilhui A Wicki, Jovin Müller, Sandra N. Poetzsch, Luzia Caflisch, Alexandra Hempe, Camilla P Steinhart, Maxim Puchkov, Jonas Kost, Hans-Peter Landolt, Erich Seifritz, Boris B. Quednow, Milan Scheidegger
The International Journal of Neuropsychopharmacology December 28, 2024 DOI: 10.1093/ijnp/pyaf001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, randomized, placebo-controlled trial Peer reviewed |
|---|---|
| Sample size | 31 |
| Population | Healthy male volunteers |
| Interventions | 100 mg buccal harmine with 100 mg intranasal DMT 100 mg buccal harmine with intranasal placebo full placebo |
| Topics | 5-MeO-DMT DMT |
| Keywords | Harmine Pharmacodynamics Pharmacokinetics Psychedelics hallucinogens Entheogens DMT N Psychoactive substances Pharmacology drug interactions Drug metabolism |
| Citations | 10 |
| Registration | NCT04716335 |
| Key findings | A novel formulation of buccal harmine and intranasal DMT produced safe, ayahuasca-like psychological effects with consistent pharmacokinetic profiles in healthy volunteers. |
Abstract
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 β-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. 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 3 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. N,N-dimethyltryptamine 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. 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. Neurodynamics of prosocial emotional processing following serotonergic stimulation with N,N-dimethyltryptamine (DMT) and harmine in healthy subjects (NCT04716335) https://clinicaltrials.gov/ct2/show/NCT04716335.