Discussion: SSRIs & DMT

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SSRIs & DMT​

Selective Serotonin Reuptake Inhibitors (SSRIs) primarily function by inhibiting the reuptake of serotonin (5-HT) into the presynaptic neuron. This increases the availability of serotonin in the synaptic cleft, enhancing serotonergic neurotransmission. Over time, SSRIs may lead to changes in the sensitivity and density of various serotonin receptors (e.g., 5-HT1A, 5-HT2A), which contributes to their therapeutic effects and side effects.

Common SSRIs:
- Fluoxetine (Prozac)
- Sertraline (Zoloft)
- Escitalopram (Lexapro)
- Paroxetine (Paxil)
- Citalopram (Celexa)


N,N-Dimethyltryptamine (DMT) is a potent agonist at several serotonin receptors, particularly the 5-HT2A receptor. This receptor activation is believed to be responsible for the DMT profound psychedelic effects. DMT is rapidly metabolized by monoamine oxidase (MAO), primarily MAO-A, leading to a very short duration of action when administered without MAO inhibitors.


Interaction Mechanisms

• Serotonin Receptor Modulation: Since SSRIs increase serotonin levels and DMT acts on serotonin receptors, there can be an enhanced agonistic effect, particularly at the 5-HT2A receptor.
• Altered Pharmacokinetics: SSRIs might affect the metabolism of DMT. For instance, fluoxetine is a potent inhibitor of CYP2D6, an enzyme involved in DMT metabolism, which could alter the intensity and duration of DMT's effects.

Potential Dangers of Combining SSRIs and DMT

• Serotonin Syndrome: Combining SSRIs and DMT significantly raises the risk of serotonin syndrome, a potentially life-threatening condition caused by excessive serotonin activity. Symptoms include confusion, agitation, rapid heart rate, and high blood pressure, dilated pupils, loss of muscle coordination, and muscle rigidity.
• Intense Psychedelic Experiences: The combination might intensify the psychedelic effects of DMT, potentially leading to overwhelming experiences or psychological distress or trauma in some individuals.
• Mild to Moderate Side Effects: In studies, some participants reported mild to moderate adverse events, such as nausea and transient increases in blood pressure, which typically resolved during the dosing visit. No serious drug-related adverse events were reported in these trials
• Unpredictable Interactions: The pharmacodynamic and pharmacokinetic interactions are not well-understood, leading to unpredictable effects and potential harm.

While both substances have therapeutic potential individually, their combination carries significant risks, particularly the potential for serotonin syndrome and intense psychological reactions. Current research does not support the safe or effective use of this combination outside of controlled clinical settings.

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