Selective serotonin reuptake inhibitors (SSRIs) include fluoxetine, sertraline, citalopram, escitalopram, paroxetine, and fluvoxamine. They are the most commonly prescribed antidepressants. SSRIs significantly interact with many recreational substances — they block or diminish the effects of psychedelics and MDMA, and can cause serotonin syndrome when combined with serotonergic drugs.
Evidence Snapshot
Last updated
Mar 16, 2026
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Safety at a Glance
High Risk- Dangerous with: Fenfluramine, Tramadol
- Start with a low dose and wait for onset before redosing
- Test your substance with reagent kits when possible
- Never use alone — have a sober person present
If someone is in crisis, call 911 or Poison Control: 1-800-222-1222
Duration
No duration data available.
Interactions
| Substance | Status | Note |
|---|---|---|
| Fenfluramine | Dangerous | Serotonin syndrome risk. CYP2D6 inhibition by fluoxetine/paroxetine also causes dangerous fenfluramine accumulation. |
| Tramadol | Dangerous | Tramadol is an SNRI in addition to being an opioid. Combined with SSRIs, the serotonergic effects stack, creating a high risk of serotonin syndrome. Tramadol also lowers the seizure threshold, which SSRIs can further reduce. |
| MDMA | Caution | SSRIs significantly diminish or block the effects of MDMA by competing for the serotonin transporter. While not typically life-threatening, there is some risk of serotonin syndrome, and users often dangerously increase MDMA doses trying to overcome the blockade. |
| LSD | Low Risk & Decrease | SSRIs tend to diminish the effects of LSD. The serotonergic interaction is generally not dangerous, but the trip will likely be significantly weaker. Some users report unpredictable or altered effects. |
| Psilocybin Mushrooms | Low Risk & Decrease | SSRIs diminish psilocybin effects by competing at serotonin receptors. Generally not dangerous but the experience will be significantly reduced. Abruptly stopping SSRIs to trip is more dangerous than the combination itself. |
Toxicity & Safety
No toxicity data available.
Dangerous Interactions
The combinations listed below may be life-threatening. Independent research should always be conducted to ensure safety when combining substances.
Serotonin syndrome risk. CYP2D6 inhibition by fluoxetine/paroxetine also causes dangerous fenfluramine accumulation.
Tramadol is an SNRI in addition to being an opioid. Combined with SSRIs, the serotonergic effects stack, creating a high risk of serotonin syndrome. Tramadol also lowers the seizure threshold, which SSRIs can further reduce.
Tolerance
| Full | Unknown |
| Half | Unknown |
| Zero | Unknown |
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