What serotonin syndrome is
Serotonin is a brain chemical involved in mood, sleep, and other functions. Serotonin syndrome happens when there is too much serotonin activity — most often when 'two or more medicines or drugs that affect the body's level of serotonin are taken together,' according to MedlinePlus [1]. It ranges from mild to a medical emergency.
Warning signs
MedlinePlus lists symptoms that can appear within minutes to hours, including agitation or restlessness, a fast heartbeat and raised blood pressure, a high body temperature, heavy sweating, loss of coordination, overactive reflexes, and, in severe cases, confusion [1]. Severe serotonin syndrome is an emergency — call 911.
Supplements that raise serotonin
Several popular supplements increase serotonin activity, which is exactly why combining them with serotonergic medications is risky:
- St. John's wort. NCCIH warns that 'taking St. John's wort with certain antidepressants or other drugs that affect serotonin...may lead to increased serotonin-related side effects, which can be serious' [2].
- 5-HTP and L-tryptophan — direct precursors the body converts toward serotonin.
- SAMe — also affects serotonin activity.
The risky combinations
The concern is combining these supplements with other things that raise serotonin, such as antidepressants (SSRIs, SNRIs, MAOIs), migraine triptans, tramadol, and certain other medications. NCCIH also notes St. John's wort can weaken many medicines by lowering their blood levels [2].
Practical guidance
- Don't combine serotonin-raising supplements with antidepressants, triptans, or other serotonergic drugs without a clinician's guidance.
- Tell your prescriber about any of these supplements — including before starting a new medication (see [when to talk to a doctor](/learn/when-to-talk-to-a-doctor-about-supplements)).
- Act on symptoms: if agitation, a racing heart, high temperature, or confusion develop after combining serotonergic products, seek urgent care.
- These supplements are sometimes used for mood or sleep (see [supplements for anxiety](/learn/supplements-for-anxiety)); the safety issue is specifically about combinations.