Ayahuasca Tramadol Red Discussion: Ayahuasca and Tramadol

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Ayahuasca and Tramadol​

Ayahuasca is a psychoactive brew traditionally used in Amazonian shamanic practices, made from a combination of the Banisteriopsis caapi vine and the leaves of the Psychotria viridis plant, or other plants containing similar active compounds. The two key psychoactive components in ayahuasca are DMT (dimethyltryptamine) and MAOIs (monoamine oxidase inhibitors) from the B. caapi vine.

DMT is a potent hallucinogen that naturally occurs in various plants and animals, including the human body. When consumed orally, DMT alone is usually broken down in the gut by the enzyme monoamine oxidase (MAO) and thus becomes inactive. However, in the ayahuasca brew, the B. caapi vine provides MAO inhibitors, which block the action of this enzyme, allowing DMT to be absorbed and remain active in the body for an extended period.

Once DMT enters the bloodstream and crosses the blood-brain barrier, it binds to serotonin receptors, particularly the 5-HT2A receptor, which is heavily involved in the regulation of mood, perception, and cognition. This activation leads to a range of powerful psychological and sensory experiences, often described as visions or hallucinations, which can include visual patterns, altered sense of time, intensified emotions, and profound spiritual insights.

The B. caapi vine, in addition to providing MAOIs, contains harmala alkaloids such as harmine and harmaline, which are believed to contribute to the overall psychoactive experience by enhancing the mental clarity and focus during the journey. These alkaloids also have their own psychoactive effects, including mild antidepressant properties and modulation of the central nervous system, which can contribute to feelings of euphoria and well-being.


Tramadol is a centrally acting analgesic used to treat moderate to moderately severe pain. Firstly, tramadol acts as a weak agonist of the mu-opioid receptors in the brain and spinal cord. Mu-opioid receptors are part of the endogenous opioid system, which regulates pain perception. By binding to these receptors, tramadol mimics the action of naturally occurring pain-relieving compounds like endorphins, thereby reducing the sensation of pain. However, compared to stronger opioids like morphine, tramadol has a relatively low affinity for these receptors, which is why it is often considered a milder opioid.

In addition to its opioid activity, tramadol inhibits the reuptake of two key neurotransmitters: serotonin and norepinephrine. These neurotransmitters play important roles in modulating pain through descending inhibitory pathways in the brain and spinal cord. By preventing their reabsorption into nerve cells, tramadol increases the levels of both serotonin and norepinephrine in the synaptic cleft, enhancing their ability to suppress pain signals. This non-opioid component of tramadol’s action is similar to the mechanisms seen in some antidepressants, contributing to its analgesic effects.

Once ingested, tramadol is metabolized in the liver by the enzyme CYP2D6 into an active metabolite called O-desmethyltramadol, which has a much stronger affinity for mu-opioid receptors than the parent compound. This metabolite plays a significant role in tramadol’s overall pain-relieving effects. Individuals who metabolize tramadol quickly (ultra-rapid metabolizers) may experience stronger opioid effects, while poor metabolizers may not experience as much pain relief due to lower levels of this metabolite.

Tramadol also lowers the seizure threshold, meaning it can increase the risk of seizures, particularly in individuals with a history of epilepsy or when taken in combination with other medications that lower the seizure threshold, such as antidepressants or antipsychotics.


Combining ayahuasca with tramadol presents significant risks due to their overlapping effects on serotonin and other neurotransmitter systems.

• The main concern with combining these substances is the risk of serotonin syndrome, a potentially life-threatening condition. Both ayahuasca’s MAOIs and tramadol can drastically increase serotonin levels. When taken together, this can lead to dangerous symptoms like agitation, confusion, rapid heart rate, high blood pressure, sweating, and even seizures.
• Tramadol also lowers the seizure threshold, further increasing the risk of convulsions when combined with the stimulant effects of ayahuasca.
• Additionally, the opioid effects of tramadol may interact with the psychotropic effects of DMT, amplifying dissociation, anxiety, or paranoia, potentially leading to a dangerous or overwhelming psychological experience.
• Ayahuasca’s effects on cardiovascular health, including increased heart rate and blood pressure, can be compounded by tramadol, which has similar side effects. This could increase the risk of severe cardiovascular events, especially in individuals with pre-existing conditions. Moreover, tramadol’s opioid-like properties may worsen the nausea and vomiting often associated with ayahuasca, potentially leading to dehydration or other physical complications.
• Ayahuasca contains MAO inhibitors, which can affect how other drugs are metabolized. Tramadol's metabolism may be altered, leading to either increased or prolonged effects, which can elevate the risk of toxicity or prolonged adverse effects such as sedation or respiratory depression

Given these potential risks, combining ayahuasca and tramadol is highly dangerous and should be avoided due to the significant chance of serotonin syndrome, seizures, and cardiovascular stress.

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