The Science of Ayahuasca: DMT, the Harmala Alkaloids & the Brain

A note on this article. This is educational science writing, not medical advice, and nothing here is a promise of benefit or cure. Much of the research below is early-stage. Read our health & safety guidelines before considering a retreat.

At Ayaselva we prepare the medicine ourselves — cutting and pounding the vine, cooking it with the chacruna leaves over two days, and involving our guests in the process. Because we work with it so directly, we care about understanding why it does what it does. Here is the chemistry, told plainly.

A partnership of two plants

Ayahuasca’s power comes not from one plant but from a remarkable partnership. The leaves of Psychotria viridis (chacruna) contain DMT, a potent visionary compound. The Banisteriopsis caapi vine contains a group of compounds called harmala alkaloids — chiefly harmine and tetrahydroharmine (THH) — that act as monoamine oxidase inhibitors (MAOIs).

Why does that matter? Taken by mouth on its own, DMT is broken down almost instantly by the enzyme MAO in the digestive system, and nothing happens. The vine’s MAOIs block that breakdown, allowing the DMT to become orally active. This is the elegant chemistry behind the brew — and why the tradition pairs these two specific plants.

DMT: the visionary molecule

DMT (dimethyltryptamine) occurs naturally in many plants and animals, including humans, where it has been detected in cerebrospinal fluid, blood, and urine. Structurally it resembles serotonin, which lets it interact with serotonin receptors — particularly the 5-HT2A receptor implicated in the effects of many psychedelics.

Its acute effects can include vivid visual and emotional experiences and a felt sense of transcending ordinary time and space. Researchers such as Dr. Rick Strassman (whose work produced DMT: The Spirit Molecule) reignited modern interest in the compound. Much about its role in the body — including the long-speculated link to the pineal gland — remains genuinely unresolved, and honest writers should say so.

Harmine and THH: the quiet partners

The vine’s alkaloids do more than enable the DMT.

• Harmine is a β-carboline that, in preclinical studies, has shown neuroprotective and antioxidant effects. In animal models it improved memory performance and raised levels of BDNF (brain-derived neurotrophic factor), a protein important to brain plasticity. These results are promising but come mostly from cell and animal studies — not yet conclusive human trials.
• Tetrahydroharmine (THH) is a reversible MAO-A inhibitor that may also act as a mild serotonin agonist. Early research explores its potential for mood and cognition, and possible neuroprotective and anti-inflammatory properties — again, mostly preliminary.

What happens in the brain

Ayahuasca’s combined chemistry interacts with several systems — serotonin receptors (5-HT1A, 5-HT2A), sigma-1 receptors, and others. Two threads of research stand out:

• Neuroplasticity and neurogenesis. Studies suggest ayahuasca compounds can promote the brain’s capacity to reorganise — forming new connections, and in some research stimulating the growth of new neurons and the release of neurotrophic factors like BDNF.
• The default mode network (DMN). Ayahuasca appears to quiet the DMN, the network tied to self-referential thinking and rumination. Loosening rigid, repetitive thought patterns may be part of why people report relief from stuck states — a thread that connects to the therapeutic research.

What long-term studies suggest — and the caveats

Studies of regular, ceremonial ayahuasca users generally do not find cognitive deficits or increased psychopathology; many report improved mood, greater wellbeing, and reduced impulsivity. But there is an essential caveat: people with a history of psychiatric conditions, or who use certain medications or substances, can be at real risk. This is precisely why careful screening and a supervised, supportive setting are not optional.

The honest summary is this: the science is fascinating, the early findings are encouraging, and the work is far from finished. Understanding the molecules deepens our respect for the medicine — but it is the tradition, the setting, and the care around it that make working with ayahuasca safe and meaningful. If you would like to talk it through, we are here.