Harm reduction: the things worth knowing first
Psycology does not tell anyone to take anything. This exists because people do, and because the difference between a rough night and a hospital visit is usually information somebody did not have. None of this is medical advice.
Psilocybin and medication: the interactions
Lithium (Mood stabiliser · Do not combine)
The most serious interaction on this page. There are repeated, credible reports of seizures and of severely disordered states when psilocybin is taken by someone on lithium, including in people with no seizure history.
What to do: Do not combine. Do not stop lithium to make room for it either: stopping a mood stabiliser carries its own major risk and is a conversation for your prescriber, not a plan you make yourself.
MAOIs (Antidepressant · Do not combine)
Monoamine oxidase inhibitors change how the body clears serotonergic drugs, and can potentiate psilocybin unpredictably and enormously. The result is not a stronger version of the same experience, it is a different and much less controllable one.
What to do: Do not combine. This includes the "reversible" MAOIs like moclobemide, and it includes syrian rue and other harmala-containing preparations people take deliberately for exactly this potentiation.
Tramadol (Painkiller · Do not combine)
Tramadol lowers the seizure threshold on its own and is serotonergic as well. Combining it with a serotonergic psychedelic raises both the seizure risk and the serotonin toxicity risk.
What to do: Do not combine.
Amphetamines and cocaine (Stimulant · Do not combine)
Stimulants raise heart rate and blood pressure, sharpen anxiety, and make a difficult headspace much harder to settle. With MDMA there is additional serotonergic load on top.
What to do: Avoid. Prescribed stimulants for ADHD are a conversation for your prescriber; do not simply skip doses without advice.
SSRIs (Antidepressant · Reduces or blocks)
Long-term SSRI use usually reduces the effects of psilocybin, sometimes to almost nothing, because the receptors involved adapt. The genuine danger is not the blunting, it is people redosing repeatedly to push through it.
What to do: Expect a much weaker effect and do not chase it with more. Serotonin syndrome from this combination is rare but not impossible, especially at high doses or alongside other serotonergic drugs. Never taper or stop an antidepressant without your prescriber.
SNRIs (Antidepressant · Serious caution)
Like SSRIs, usually blunting, but with a more serotonergic and noradrenergic profile and a worse discontinuation picture. Reports of adverse combinations are more common than with SSRIs.
What to do: Serious caution, and the same rule: never stop or skip doses to compensate. Venlafaxine in particular has a harsh discontinuation syndrome.
Tricyclics (Antidepressant · Serious caution)
Tricyclics can potentiate psychedelics rather than blunt them, and several carry cardiac effects of their own.
What to do: Serious caution. Assume the effect will be stronger and less predictable than expected.
Antipsychotics (Antipsychotic · Reduces or blocks)
Most antipsychotics block the receptor psilocybin acts on, which reduces or ends the effects. Some are used in emergency settings for exactly that reason. They are not a casual off-switch and can produce their own unpleasant effects.
What to do: Do not use one recreationally to end an experience. If someone is in crisis, that is a medical decision for medical people.
Benzodiazepines (Sedative · Serious caution)
Benzodiazepines reduce anxiety and will cut an experience short or flatten it. They are genuinely useful as a planned safety measure in supervised settings, and genuinely habit-forming.
What to do: Not something to take casually alongside. If a benzodiazepine is your plan for a difficult moment, that plan should be made with a doctor, not on the night.
St John's Wort (Supplement · Serious caution)
Serotonergic, and a powerful inducer of liver enzymes that changes how other drugs are cleared. People often forget it counts because it is sold in supermarkets.
What to do: Serious caution. Treat it like a real antidepressant, because pharmacologically it is one.
Triptans (Migraine · Serious caution)
Serotonergic migraine drugs. Combined serotonergic load is the concern.
What to do: Caution, and space them apart. Speak to a pharmacist.
5-HTP and tryptophan (Supplement · Serious caution)
Direct serotonin precursors. Adding them to a serotonergic drug adds risk for no benefit.
What to do: Avoid on the day. Popular in "stacks", which is exactly why it is worth naming.
Dextromethorphan (Cough medicine · Serious caution)
Serotonergic at the doses found in cough medicine, and dissociative above them. An easy accidental combination during a cold.
What to do: Avoid. Check the label of any cough or cold remedy.
Cannabis (Recreational · Serious caution)
Strongly potentiates and destabilises the experience, and is one of the most common factors in people describing a night that turned frightening. Edibles are worse because of the delay.
What to do: The most common avoidable mistake. If a difficult moment arrives, cannabis will usually deepen it rather than settle it.
Alcohol (Recreational · Low risk, still care)
Mostly dulls the experience while adding nausea, dehydration and worse judgement. Not a dangerous combination in the pharmacological sense, at moderate amounts, and still a bad one.
What to do: Not recommended. Judgement is the thing you least want to spend.
Blood pressure and heart medication (Cardiac · Serious caution)
Psilocybin modestly raises heart rate and blood pressure. For someone with a heart condition, uncontrolled hypertension or a history of arrhythmia, that matters more than it does for most people.
What to do: Talk to a doctor first. Heart conditions are a genuine contraindication, not a footnote.
The full page also covers who should not take psilocybin, how to sit for someone, what to do in a hard moment, the day after, and support lines by country.