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N,N-dimethyltryptamine + harmala
- Development stage
- Phase 1
- Lead developer
- Psychae Institute
- Modality
- Metabolically Activated Prodrugs → Prodrugs/Conditional Activator Small Molecules → Small Molecules, Classical Binding Small Molecules → Small Molecules
- Administration
- Buccal, Intranasal, Oral
01
Overview
N,N-dimethyltryptamine + harmala is a combination of the serotonergic psychedelic N,N-dimethyltryptamine (DMT) and harmala alkaloids (such as harmine, harmaline, and tetrahydroharmine), which act as reversible inhibitors of monoamine oxidase A (RIMAs). In traditional settings, this combination is known as ayahuasca, a plant-based brew used for spiritual and medicinal purposes. In modern clinical development, standardized pharmaceutical formulations (often referred to as pharmahuasca) are being investigated for the treatment of major depressive disorder, alcohol use disorder, and other treatment-resistant psychiatric conditions. The harmala alkaloids inhibit the gastrointestinal and hepatic metabolism of DMT by monoamine oxidase A, thereby rendering DMT orally active and prolonging its psychedelic and therapeutic effects. The combination promotes neuroplasticity, emotional processing, and cognitive flexibility.
- Other names
- ayahuascadimethyltryptamine/beta-carbolinesdimethyltryptamine/harmine/harmaline/tetrahydroharmineDMT/beta-carbolinesDMT/harmine/harmaline/THHpharmahuasca
02
Targets
HTR1A (Serotonin receptor 1A (5-hydroxytryptamine receptor 1A))HTR2A (Serotonin receptor 5-HT2A)5-HT2C (5-hydroxytryptamine receptor 2C)MAOA (Monoamine oxidase A)SERT (Sodium-dependent serotonin transporter)SIGMAR1 (Sigma non-opioid intracellular receptor 1)
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