Selective serotonin reuptake inhibitor · Antidepressant
2 dangerous interactions — combining SSRIs with certain substances may be life-threatening.
Updated
Mar 16, 2026
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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.
Last updated
Mar 16, 2026
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If someone is in crisis, call 911 or Poison Control: 1-800-222-1222
No dosage data available.
Full dosage guideNo duration data available.
| Substance | Status | Note |
|---|---|---|
| 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. |
| DXM | Unsafe | DXM has significant serotonergic activity. Combined with SSRIs, there is meaningful risk of serotonin syndrome. Several cases have been reported, some serious. This combination should be avoided. |
| 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. |
No toxicity data available.
The combinations listed below may be life-threatening. Independent research should always be conducted to ensure safety when combining substances.
DXM has significant serotonergic activity. Combined with SSRIs, there is meaningful risk of serotonin syndrome. Several cases have been reported, some serious. This combination should be avoided.
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.
| Full | Unknown |
| Half | Unknown |
| Zero | Unknown |
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