Serotonin syndrome

Serotonin syndrome is what happens when there is too much serotonin activity in the body. It usually comes from combining two things that each raise serotonin: MDMA with an antidepressant, tramadol or DXM with an SSRI, or almost anything serotonergic with an MAOI. Most cases start within 6 to 24 hours of the combination, and the most severe cases involve MAOIs.

Signs it is happening
  1. Tremor, shivering, or muscles twitching and jerking on their ownEspecially in the legs. Muscles that go rigid are a sign it is severe.
  2. Rising temperature with heavy sweating
  3. Agitation, confusion, or being unable to keep still
  4. Fast heartbeat, dilated pupils, diarrhoea
What to do
  1. 01Stop. No more of anything, and no stimulants to counteract it.
  2. 02Treat a climbing temperature as the emergency.Get them somewhere cool, take layers off, cool them with water and moving air.
  3. 03Call 911 for fever, rigid or twitching muscles, or confusion.Tell them exactly what was taken. Hospitals treat it with sedation, cooling and a serotonin blocker, but only once staff know to look for it.
01 / Before

If you are going to combine anyway

  1. Do not combine anything serotonergic with an MAOI.That includes ayahuasca and Syrian rue. MAOIs need roughly two weeks to clear, so stopping the day before is not enough.
  2. On an SSRI? Do not redose MDMA to chase an effect that feels blunted.SSRIs can dull how MDMA feels, which tempts people to take more of the part that causes the problem.
  3. Count cold medicine and painkillers too.DXM (in cough syrup) and tramadol both raise serotonin, and both are easy to forget about.
02 / Why

How it happens

Serotonin is a signalling chemical in the brain and the body. It is involved in mood, but also in muscle control, body temperature and the gut, which is why an excess shows up as twitching, heat and diarrhoea rather than just a strange mood.

Different drugs raise it in different ways. MDMA releases it, SSRIs stop it being cleared away, and MAOIs stop it being broken down. Combining two of them attacks the same system from two directions, and the effects stack.

The danger is heat. Muscles that are constantly contracting produce heat, and a body temperature of 41 °C or higher needs intensive care.

03 / On MixSafe

Substances that carry this risk

MixSafe raises a whole-mix warning when two or more of these are in the same mix. The list is kept narrow on purpose, so it is not every drug that can contribute. Each pair still has its own rating.