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Psilocybin and mirtazapine

Reduces effects

Antidepressant, NaSSA · also: remeron, zispin, avanza

Mirtazapine is expected to blunt or block a mushroom experience and add sedation, but this combination has not been studied directly.

Blocks the experience almost entirely, more completely than an SSRI does. Taken during an experience it will substantially reduce it, along with heavy sedation.

Claims re-checked against the cited sources:

Why it happens

Mirtazapine is an antagonist at 5-HT2 and 5-HT3 receptors as well as alpha-2 adrenergic receptors, and it also blocks histamine H1 receptors, which accounts for its sedation. Because psilocybin's effects depend on 5-HT2A activation, a 5-HT2 antagonist would be expected to reduce them, as other 5-HT2A blockers do in human studies.

What is known

Its 5-HT2A antagonism is well characterised. The blocking effect is consistently reported.

2025
The Remeron label describes mirtazapine as an antagonist at 5-HT2 and 5-HT3 receptors, alpha-2 adrenergic receptors and histamine H1 receptors. REMERON (mirtazapine) US prescribing information, DailyMed
2001
Mirtazapine blocks 5-HT2 and 5-HT3 receptors; sedation is among its most common adverse effects. Anttila & Leinonen, CNS Drug Reviews 2001
1998
In healthy volunteers, psilocybin's psychotomimetic effects were blocked dose-dependently by the 5-HT2A antagonist ketanserin and by risperidone. Vollenweider et al., NeuroReport 1998

Safety guidance

  • If you take mirtazapine, expect a much weaker or absent effect and heavy drowsiness.
  • Do not redose to push through the block.
  • Do not stop mirtazapine to take mushrooms without your prescriber.
  • For a difficult experience, a benzodiazepine is the better-studied rescue option in research settings than mirtazapine.
Do not stop a prescribed medication on your own. Stopping or skipping a prescribed drug to take mushrooms can be more dangerous than either alone. Talk to whoever prescribes it.

When to seek help

Seek help for excessive sedation, difficulty staying awake, confusion, or any breathing problem, especially if alcohol or other sedatives were also taken. Emergency red flags.

Common questions

Will mushrooms work on mirtazapine?

Probably much less than usual, because mirtazapine blocks 5-HT2 receptors, though no study has tested it directly.

Can I use mirtazapine to end a trip?

It might blunt it, but it has not been studied for this and causes heavy sedation; in research settings a benzodiazepine is the standard rescue medication.

Is the combination dangerous?

No specific danger is documented. The main issues are a wasted dose, redosing and sedation.

Sources

  1. [1]Anttila & Leinonen, 'A review of the pharmacological and clinical profile of mirtazapine' (2001)

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