Discussion: Ayahuasca & SSRIs

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Ayahuasca & SSRIs​

Ayahuasca, a traditional Amazonian brew known for its psychoactive properties. Ayahuasca is a brew made from the Banisteriopsis caapi vine and the leaves of the Psychotria viridis plant. The primary active ingredients in Ayahuasca are:

1. DMT (N,N-Dimethyltryptamine): A powerful psychedelic compound found in the Psychotria viridis leaves. DMT is structurally similar to serotonin and can bind to serotonin receptors in the brain, leading to altered perceptions and intense visual and auditory experiences.
2. Harmine, Harmaline, and Tetrahydroharmine: These are β-carboline alkaloids found in the Banisteriopsis caapi vine. They act as monoamine oxidase inhibitors (MAOIs), preventing the breakdown of DMT in the digestive system, allowing it to enter the bloodstream and cross the blood-brain barrier.

Selective Serotonin Reuptake Inhibitors (SSRIs), such as fluoxetine (Prozac), sertraline (Zoloft), and citalopram (Celexa), are a class of drugs used to treat depression, anxiety, and other mood disorders. They work by inhibiting the reuptake of serotonin. SSRIs block the reabsorption of serotonin into neurons, increasing the level of serotonin available in the synaptic cleft and enhancing neurotransmission.


The primary concern with combining Ayahuasca and SSRIs is the serotonin syndrome, a potentially life-threatening condition caused by excessive serotonin activity in the brain. The interaction mechanisms include:

• Serotonin Receptor Agonism: Both Ayahuasca (through DMT) and SSRIs increase serotonin levels in the brain. DMT acts as a serotonin receptor agonist, directly stimulating serotonin receptors, while SSRIs increase the availability of serotonin in the synaptic cleft.
• Inhibition of Serotonin Metabolism: The β-carbolines in Ayahuasca inhibit monoamine oxidase (MAO), an enzyme that breaks down serotonin. This inhibition can lead to elevated serotonin levels when combined with SSRIs, which already increase serotonin levels by preventing its reuptake.

Side Effects and Dangers:

• Serotonin syndrome is the most significant risk when combining Ayahuasca with SSRIs. Symptoms include:
  • Mild: Agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, and muscle twitching.
  • Severe: High fever, seizures, irregular heartbeat, and unconsciousness. Severe serotonin syndrome can be fatal if not treated promptly.

• Hypertensive Crisis. The combination of MAOIs (from Ayahuasca) and certain substances, including SSRIs, can lead to hypertensive crisis, characterized by:
  • Severe Headache: Often described as the worst headache ever experienced.
  • Nausea and Vomiting: Accompanied by a sudden spike in blood pressure.
  • Chest Pain: Which may indicate cardiac complications.

The combination of Ayahuasca and SSRIs poses significant risks due to their synergistic effects on serotonin levels. Both substances increase serotonin activity through different mechanisms, leading to an increased risk of serotonin syndrome and hypertensive crisis.

All things considered, we recommend avoiding this combination under any conditions.