Psilocybin together with Mirtazapine

Psilocybin + Mirtazapine provides:

1. Neurochemical interactions: Psilocybin (truffles or magic mushrooms), like LSD, acts primarily through agonism of 5-HT₂A receptors. Mirtazapine is a strong antagonist of 5-HT₂A. As a result, mirtazapine will exert the same opposing effect on psilocybin as it does on LSD. Additionally, mirtazapine blocks 5-HT₃ and 5-HT₂C, which can reduce nausea and some hallucinatory effects of psilocybin. Overall, therefore, mirtazapine limits the neurochemical effects of psilocybin.

2. Therapeutic effect: Mirtazapine significantly reduces the psychedelic effects of psilocybin. As with LSD, the primary therapeutic effect—the psychoactive effect via 5-HT₂A—will be attenuated. Patients on mirtazapine will experience less intense insights or visions during a psilocybin session. This can negate the effectiveness of psilocybin therapy. Mirtazapine's sedative effect can further dampen the trip (more drowsiness, less energy).

3. Danger or risks: There are no safety issues with this combination. Risks are comparable to LSD + mirtazapine: possible additional sedation and a theoretical chance of serotonin syndrome, although this is very small. No specific dangers are reported in the literature beyond the standard considerations for each substance individually. The combination can, however, lead to increased drowsiness and cognitive confusion during the psychedelic experience. Risks of overdose or complications are not substantially greater.