Ayahuasca is a psychoactive brew that produces intense visual hallucinations, deep emotional experiences, and significant physical effects like vomiting, all lasting roughly four to six hours. It works by combining two plants whose chemicals depend on each other: one provides the hallucinogenic compound DMT, and the other prevents your gut from breaking that compound down before it reaches your brain.
How the Brew Works in Your Body
Ayahuasca is traditionally made from two Amazonian plants: Banisteriopsis caapi and Psychotria viridis. The second plant contains DMT, a powerful psychedelic compound. Here’s the catch: if you swallowed DMT on its own, an enzyme in your stomach called monoamine oxidase would destroy it before it ever reached your bloodstream. You’d feel nothing.
The first plant solves that problem. It contains compounds called harmala alkaloids (harmine, harmaline, and THH) that temporarily block that stomach enzyme. With the enzyme shut down, DMT passes intact through your digestive system and into your brain. Researcher Jonathan Ott confirmed this by giving people DMT tablets with and without the enzyme-blocking compound. Without it, the DMT had no psychoactive effect at all.
The harmala alkaloids may also contribute their own mild psychoactive effects, separate from DMT. Their combined action with DMT appears to be additive rather than synergistic, meaning each compound contributes its own effects rather than amplifying the other.
What the Experience Feels Like
Effects typically begin within 30 to 60 minutes of drinking the brew. DMT levels in the blood peak around 75 to 110 minutes after ingestion, and the full experience lasts four to six hours. The intensity builds gradually, hits a sustained peak in the middle hours, then tapers off.
During that window, the psychological effects can be profound. People commonly report intense visual and auditory hallucinations, a feeling of being transported to an entirely different reality, dramatic shifts in mood and thought patterns, and altered perception of time and space. One of the most characteristic experiences is “ego dissolution,” a sense that the boundary between yourself and the world around you has dissolved, replaced by a feeling of deep unity with everything. Some users report experiences that feel like confronting their own death, which many later describe as transformative rather than traumatic.
The emotional range is wide. A single session can move between terror, grief, euphoria, and profound peace. This is not a recreational high. Most people describe it as one of the most intense psychological experiences of their lives.
The Purge
Vomiting and diarrhea are so common during ayahuasca ceremonies that practitioners call them “the purge” and consider them a central part of the experience rather than an unwanted side effect. Both the DMT and the harmala alkaloids contribute to these emetic and purging effects, and they are considered among the brew’s major pharmacological activities alongside its hallucinogenic properties.
In traditional Amazonian use, the purge carries spiritual significance. It’s framed as the body releasing emotional or spiritual toxins. From a pharmacological standpoint, the brew is simply triggering nausea through its interaction with serotonin receptors in the gut and the enzyme-blocking effects of the harmala alkaloids. Either way, most people who drink ayahuasca should expect to vomit.
What Happens in the Brain
DMT activates serotonin receptors (specifically the 5-HT2A type) in the brain’s outer layer, the cortex. This triggers a cascade: increased serotonin release, heightened excitability of key brain cells, and a flood of the neurotransmitter glutamate. The net result is that normal patterns of brain activity become desynchronized. Neurons that usually fire together in orderly rhythms start firing more independently.
One of the most studied effects involves the brain’s “default mode network,” a set of interconnected regions that are active when you’re daydreaming, thinking about yourself, or mentally time-traveling to the past or future. This network is closely tied to your sense of identity and your internal narrative about who you are. Ayahuasca disrupts it. Brain imaging studies show reduced blood flow and connectivity within this network during the experience, while connections between brain regions that don’t normally communicate increase.
The result is a brain that is, temporarily, less constrained, more flexible, and less anchored to your usual self-referential thinking patterns. This is likely the neurological basis of ego dissolution. Alpha brainwave power, which correlates strongly with default mode network activity, drops measurably, sometimes specifically in the brain region most central to the network.
Long-term ayahuasca users show structural brain changes on imaging scans: thickening in the anterior cingulate cortex (involved in emotional regulation and decision-making) and thinning in several regions associated with the default mode network. Whether these changes are beneficial or simply reflect adaptation remains an active question.
Neuroplasticity and Lasting Brain Changes
DMT and related psychedelics are sometimes called “psychoplastogens,” compounds that rapidly stimulate a period of enhanced neuroplasticity, meaning the brain’s ability to form new connections and reorganize itself. Animal studies using DMT have shown increased neurogenesis (the growth of new brain cells) in mice, and DMT has increased the frequency and strength of excitatory signals between neurons in rat brain tissue even at doses that wouldn’t produce hallucinations.
In humans, one study found that ayahuasca increased levels of BDNF, a protein that supports the growth and survival of neurons, in both healthy volunteers and people with depression. A second study, however, found no change. The picture is still incomplete, but the leading theory is that ayahuasca opens a window of heightened brain plasticity that may explain why a single session can produce psychological effects lasting weeks or months.
Effects on Depression
The most rigorous clinical evidence comes from a randomized, double-blind, placebo-controlled trial involving 29 patients with treatment-resistant depression, meaning their depression hadn’t responded to conventional antidepressants. After a single dose of ayahuasca, depression scores were significantly lower than placebo within one day, and the difference grew larger over the following week.
By day seven, 64% of people in the ayahuasca group met the criteria for a treatment response, compared to 27% in the placebo group. The effect size at day seven was large (Cohen’s d of 1.49 on one depression scale and 0.98 on another). About 36% of the ayahuasca group were in full remission at one week versus 7% with placebo. These are striking numbers for people whose depression had resisted standard treatment, though the trial was small and larger studies are needed to confirm the findings.
Physical Effects on the Body
Beyond the purge, ayahuasca causes modest cardiovascular changes. In controlled dosing studies, diastolic blood pressure (the bottom number) increased by about 9 mmHg at higher doses, peaking around 75 minutes in. Systolic blood pressure and heart rate showed small, nonsignificant increases. For a healthy person, these changes are minor. For someone with cardiovascular conditions or on blood pressure medication, they could be more concerning.
Serious Safety Risks
The most dangerous risk associated with ayahuasca involves drug interactions. Because the brew contains potent enzyme inhibitors (MAOIs), combining it with substances that increase serotonin levels can trigger serotonin syndrome, a potentially life-threatening condition involving dangerously high body temperature, seizures, and organ failure.
The highest-risk combinations include:
- SSRIs and other antidepressants: The interaction between ayahuasca’s MAOI compounds and SSRIs (like sertraline, fluoxetine, or escitalopram) is the most well-documented danger. These medications need to be discontinued weeks before a ceremony, not days.
- Stimulants: Amphetamines, MDMA, and cocaine all pose serious risks when combined with MAOIs.
- Opioids: Heroin, morphine, codeine, and related drugs.
- Over-the-counter cold medicines: Anything containing dextromethorphan (often labeled DXM, DM, or “Tuss”) is dangerous with ayahuasca. This includes many common cough syrups and cold medications.
- CNS depressants: Benzodiazepines and barbiturates.
Reputable retreat centers require medical screening and typically ask participants to stop contraindicated medications at least four weeks before a ceremony. Ayahuasca is also not recommended for people with bipolar disorder, as it can trigger episodes that persist well beyond the ceremony itself. Honesty during screening isn’t a formality. It’s the primary safety mechanism.