Pharmacokinetics and Pharmacodynamics of an Innovative Psychedelic N,N-Dimethyltryptamine/Harmine Formulation in Healthy Participants: A Randomized Controlled Trial
Aicher, H. D., Caflisch, L., Dornbierer, D. A., Elsner, C., Hempe, A., Kost, J., Landolt, H-P., Marten, L., Meling, D., Mueller, J., Mueller, M. J., Poetzsch, S. N., Puchkov, M., Quednow, B. B., Scheidegger, M., Seifritz, E., Steinhart, C., Suay, D., Wicki, I.
This secondary analysis of an RCT (n=31) evaluates a novel pharmaceutical formulation of DMT and harmine in healthy male volunteers. The study finds that intranasal DMT and buccal harmine (pharmahuasca) produce consistent pharmacokinetic profiles and safe, well-tolerated effects resembling ayahuasca, with subjective experiences lasting 2-3 hours. This formulation is proposed as a safer, standardised alternative for potential therapeutic use in mental health disorders.
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 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.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.