Can mirtazapine (TCA) be combined with magic mushrooms or truffles?

Question

It is advised against combining TCA medication such as amitriptyline, clomipramine, imipramine, mirtazapine, and nortriptyline with psychedelic drugs such as psilocybin from magic mushrooms and truffles. This is because not much research has yet been conducted into the combination of mirtazapine (a TCA) and psilocybin-containing magic mushrooms or truffles. However, research from 2022 did demonstrate that SSRIs, another group of medications with similar effects, are safe in combination with truffles. These new findings have suggested that TCAs such as mirtazapine could theoretically be safely combined with truffles and magic mushrooms. Due to the lack of rigorous research, combining TCAs with psilocybin is currently still advised against.

Some individuals who use TCAs choose to taper off in consultation with their treating physician in order to subsequently be able to have a psilocybin session. Another option is to switch to an SSRI, as SSRI use and psilocybin are considered safe.

Rai · Accepted Answer

Thank you for this important question. The subject of combining tricyclic antidepressants (TCAs) such as mirtazapine with psilocybin indeed warrants caution.

Regarding the current state of affairs: there is indeed very limited scientific research into TCAs and psilocybin. Although recent studies have shown that SSRIs appear safer in combination with psilocybin than originally thought, we cannot directly extrapolate these findings to TCAs due to fundamental differences in their mechanism of action. TCAs act much more broadly on various neurotransmitter systems than SSRIs.

Anecdotal evidence shows that many individuals who have undergone psychedelic therapy while taking antidepressants have chosen different approaches. Some have chosen to gradually taper off the medication in close collaboration with their doctor before undergoing a psilocybin session. This offers the advantage of having both the stability of professional supervision and the opportunity to experience how psychedelics can help you.

Another scenario we see regularly is that individuals have considered switching to an SSRI instead of using their TCA. This transition must, of course, take place in consultation with your practitioner, but it gives you the opportunity to explore psilocybin therapy during that transition period.

What is crucial: the neurological effects of mirtazapine on serotonergic activity can create interactions that we do not yet fully understand. Mirtazapine acts partly as a 5-HT2A antagonist, which is relevant because psilocybin binds specifically to 5-HT2A receptors. This could theoretically lead to unexpected effects, although direct cases of serious side effects are not widely reported.

Experiences:
https://tripforum.nl/recensie-truffel-therapie-marcel/stoppen-met-alcohol-slaapmedicatie-en-antidepressiva-na-mijn-eerste-truffel-ceremonie/#post-928
https://tripforum.nl/recensie-truffel-therapie-marcel/drie-jaar-na-mijn-truffelsessie/#post-1091
https://tripforum.nl/recensie-truffel-therapie-marcel/psilocybin-hohe-dosis-mit-marcel-am-2-10-2023/#post-1079

[Solved] Can mirtazapine (TCA) be combined with magic mushrooms or truffles?