Discussion: Ayahuasca & Methoxetamine

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Ayahuasca & Methoxetamine​

Ayahuasca is a psychoactive brew traditionally used in spiritual ceremonies, primarily in the Amazon basin. It contains two key components:

• DMT (N,N-Dimethyltryptamine): A potent serotonergic psychedelic, DMT primarily acts as an agonist at the serotonin 5-HT2A receptor. It induces intense visual and auditory hallucinations, altered states of consciousness, and mystical experiences.
• MAOIs (Monoamine Oxidase Inhibitors): Ayahuasca includes beta-carbolines like harmine, harmaline, and tetrahydroharmine, which act as reversible inhibitors of the enzyme monoamine oxidase (MAO). This enzyme normally degrades monoamines (e.g., serotonin, dopamine, and norepinephrine), and its inhibition results in increased levels of these neurotransmitters.

Methoxetamine (MXE) is a dissociative anesthetic, chemically related to ketamine and PCP, with a unique pharmacological profile:
NMDA Receptor Antagonist: MXE primarily exerts its effects by blocking the NMDA (N-methyl-D-aspartate) receptor, which is involved in pain perception, memory, and mood. This blockade leads to dissociative effects, including detachment from reality and altered sensory perception.
Serotonin and Dopamine Reuptake Inhibitor: MXE has secondary actions, including the inhibition of the reuptake of serotonin and dopamine, which can contribute to mood elevation and psychoactive effects.

Combining Ayahuasca and MXE potentially leads to complex interactions:

• Serotonergic System Overload: Both Ayahuasca (through DMT's direct agonism and MAOIs' indirect effects) and MXE (through serotonin reuptake inhibition) elevate serotonin levels. This synergy could lead to serotonin syndrome, a potentially life-threatening condition characterized by confusion, agitation, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and in severe cases, seizures.
• Cognitive and Perceptual Overload: The combination of intense hallucinations induced by DMT and the dissociative, reality-altering effects of MXE may lead to overwhelming experiences, potentially exacerbating psychological distress or precipitating psychotic episodes in susceptible individuals.
• Unpredictable Pharmacokinetics: MAOIs in Ayahuasca could alter the metabolism of MXE, affecting its potency, duration, and side effects, making the experience unpredictable and potentially more hazardous.
• Side effects also could include nausea, vomiting (common with Ayahuasca alone), increased heart rate, blood pressure fluctuations, and severe anxiety or panic attacks.

The combination of Ayahuasca and MXE is fraught with risks due to their synergistic effects on serotonin levels and their individual actions on perception and cognition. The unpredictability of the interaction, compounded by the potential for severe physiological and psychological effects, suggests that such a combination should be approached with extreme caution, if at all.

This lack of information likely reflects the relatively obscure nature of this combination and the inherent risks of combining powerful psychoactive substances without a clear understanding of their interactions.

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