Serotonin Syndrome Warning Signs: What to Watch For

Quick answer — when to call 911

Call 911 for any of these: temperature over 104°F, seizure, muscle rigidity that will not release, or the person cannot be roused. Call poison control (1-800-222-1222 in the US) for suspected serotonin syndrome with a temperature under 101°F and mild symptoms.

Serotonin syndrome can go from mild to life-threatening in hours. When in doubt, go to the ER.

What serotonin syndrome is

Serotonin syndrome is a drug reaction caused by too much serotonin activity in the nervous system. It almost always involves two or more serotonergic drugs, or one drug at a very high dose.²

Doctors also call it "serotonin toxicity." The severity depends on how much serotonin activity is present. Mild cases resolve when the drugs clear. Severe cases can cause seizure, kidney failure, or death.

Onset is fast — usually within 6 to 24 hours of the trigger dose. That timing is why the risk is highest during and just after a psychedelic session.

Early signs (mild)

If two or more of these are present, stop and take the person's temperature. Any fever plus any of the above raises the concern.

Moderate signs

Moderate signs need an ER, not a wait-and-see approach. Do not drive the person yourself if temperature is climbing.

Life-threatening signs

Hunter Serotonin Toxicity Criteria

The Hunter Criteria are the clinical checklist doctors use. They are more accurate than older criteria.¹

A person is diagnosed with serotonin toxicity if they took a serotonergic drug AND meet any one of the following:

1. Spontaneous clonus.
2. Inducible clonus PLUS agitation or sweating.
3. Ocular clonus (twitching eye movements) PLUS agitation or sweating.
4. Tremor PLUS hyperreflexia.
5. Muscle rigidity PLUS temperature over 100.4°F PLUS ocular or inducible clonus.

Clonus is the key finding. It is the single most specific sign. Ankle clonus is easiest to check: dorsiflex the foot quickly and see if it twitches repeatedly.

Which psychedelics carry the risk

All classic psychedelics act on serotonin receptors. The risk of serotonin syndrome from a psychedelic alone is low. The risk from a psychedelic plus another serotonergic drug is much higher.

• Ayahuasca — the highest risk. The brew is itself an MAOI.
• MDMA — potentially fatal with MAOIs. Also risky with tramadol.
• Psilocybin — low direct risk. Watch for lithium.
• LSD, DMT, 5-MeO-DMT — similar to psilocybin. MAOI combinations raise the risk.
• Ketamine — the lowest serotonergic risk of any psychedelic-adjacent drug.

The most dangerous non-psychedelic drugs on the list: MAOIs, SSRIs, SNRIs, tramadol, dextromethorphan (DXM), St. John's Wort, and methylene blue.³

Full washout windows are in our psychedelic medication safety guide. Screen every drug and supplement using our medication safety checker before a session.

What to do if you spot signs

1. Stop the drug. No more doses of anything serotonergic.
2. Take a temperature. A real thermometer, not a hand on the forehead.
3. Cool the person if temperature is climbing. Remove layers, apply cool wet cloths, move to a cooler room.
4. Call poison control (1-800-222-1222 in the US) for guidance if symptoms are mild.
5. Go to the ER for any temperature over 100.4°F plus any neuromuscular sign.
6. Call 911 for temperature over 104°F, seizure, or altered consciousness.
7. Tell the ER what was taken. Honesty saves lives. Good Samaritan laws protect most drug-related calls.

At the hospital, treatment is supportive: IV fluids, cooling, benzodiazepines for agitation, and cyproheptadine as a serotonin antagonist in severe cases. Do not try to treat this at home with any over-the-counter drug.

Frequently asked questions