SSRIs with psilocybin, magic mushrooms, or truffles: what are the options for each substance?

Fluoxetine, Prozac and Sarafem

Fluoxetine is the SSRI where time requires the most attention. The half-life of fluoxetine itself is approximately 4 to 6 days with chronic use. In addition, the active metabolite norfluoxetine remains present for much longer, with a half-life that is around 9.3 days in older label information and is described as even longer in other official information. As a result, fluoxetine can continue to affect the serotonergic system for weeks, even after a person has stopped taking it.

With option 1, i.e., continued use, the fastest route is usually that preparation can start within about 1 to 2 weeks and the session can be scheduled relatively quickly thereafter. The advantage is that you do not induce a withdrawal phase. The disadvantage is that fluoxetine can flatten the intensity of the psilocybin experience and that, due to its long duration of action, this drug is also difficult to “just” bypass.

With option 2, i.e., tapering off faster and then waiting, fluoxetine is the slowest SSRI of them all. Five times the half-life of fluoxetine alone amounts to approximately 20 to 30 days. If you also take norfluoxetine into account, that waiting period can practically run towards 47 days. Including an accelerated tapering, a ceremony plan therefore often ends up taking about 4 to 8 weeks, and sometimes longer. 

With option 3, i.e., tapering off gradually and then stabilizing, it is more realistic to think in terms of several months. For some people, 2 to 4 months can already be tight, especially after long-term use. Particularly with fluoxetine, it makes more sense not only to look at the half-life but also at how long the nervous system needs to feel stable again. That is also the reason why this route often offers the best chance of a psilocybin experience with as little reduction as possible.

Sertraline, Zoloft and Lustral

Sertraline has an average terminal half-life of approximately 26 hours. Pharmacologically, therefore, it is cleared from the body much faster than fluoxetine. This makes planning more straightforward, but it still does not mean that someone is immediately clinically ready for a session as soon as the drug has largely disappeared from the blood.

With option 1, continued use, preparation can usually take place within 1 to 2 weeks. This route is practically the fastest, but there remains a chance that the psilocybin experience will be less deep or less pronounced. For some people, this is actually workable, especially if anxiety or restlessness is a major part of their symptoms.

With option 2, tapering off more rapidly and then waiting five times the half-life, purely pharmacologically this results in a waiting period of approximately 5 to 6 days after the last dose. In practice, the tapering itself must be added to this, meaning the total planning often comes to about 2 to 4 weeks. This is a realistic middle ground if the patient does not experience too severe dysregulation upon dose reduction.

With option 3, gradually tapering off and stabilizing, a process of approximately 1 to 3 months is often more realistic. With long-term use or previous withdrawal problems, this may take longer. The advantage of this route is that you run less risk of the session being disrupted by insomnia, anxiety, irritability, or other withdrawal symptoms.

Paroxetine, Paxil and Seroxat

Paroxetine has an average half-life of approximately 21 hours. On paper, this appears to be a drug that is quickly cleared from the body, but in practice, paroxetine is notorious for withdrawal symptoms if you stop too soon. The official product information also explicitly warns against discontinuation syndrome and advises tapering off gradually.

With option 1, continued use, preparation can often start again within 1 to 2 weeks. That is the fastest and sometimes also the least disruptive route. The downside is that the psilocybin effect may be diminished, causing someone to sink less deeply into the material than hoped.

With option 2, tapering off faster and then waiting, based purely on half-life, you arrive at approximately 4 to 5 days after the last dose. However, paroxetine is precisely a medication where that pharmacological calculation tells only part of the story. In practical planning, it is therefore often more realistic to think in terms of about 3 to 6 weeks rather than just a few days plus a mini-tapering.

With option 3, gradually tapering off and stabilizing, a course of approximately 2 to 4 months is often more logical, and sometimes longer. Especially for people who have been using paroxetine for months or years, this is frequently the safest and most comfortable route. It is also often the route with the best chance of performing the ceremony without withdrawal symptoms clouding the experience.

Citalopram, Celexa and Cipramil

Citalopram has an average terminal half-life of approximately 35 hours. This places the drug in the middle category in terms of timing. It is not as slow-acting as fluoxetine, but also not as short-acting as fluvoxamine. Abrupt discontinuation is advised against in the official information, because citalopram can also cause significant withdrawal symptoms.

With option 1, continued use, preparation for a psilocybin, truffle, or mushroom session is often possible within 1 to 2 weeks. This is practically attractive and prevents disruption caused by sudden tapering. However, the chance remains that the experience will feel less powerful or less complete.

With option 2, tapering off faster and then waiting, you end up with approximately 7 to 8 days for citalopram at five times the half-life. If you add an accelerated tapering process to that, the total schedule usually comes to around 2 to 4 weeks. For many people, this is the route that feels most feasible, provided they are not too sensitive to withdrawal.

For option 3, gradually tapering off and stabilizing, a window of approximately 1 to 3 months is often a more realistic one. With long-term use, this can increase. This route generally offers the lowest chance that restlessness, insomnia, or dysregulation resulting from the tapering process will carry over into the ceremony itself.

Escitalopram, Lexapro and Cipralex

Escitalopram has an average half-life of approximately 27 to 32 hours. This is also the SSRI for which we have the most direct experimental information in combination with psilocybin. In the controlled study of escitalopram and psilocybin, the positive mood effects of psilocybin largely persisted, while anxiety and adverse effects actually decreased. This makes escitalopram the SSRI where option 1 is relatively defensible in some cases, provided the rest of the situation is stable.

With option 1, continued use, a preparation of about 1 to 2 weeks is often sufficient. For some people, this is actually the best route, because the risk of withdrawal symptoms is eliminated and the combination does not automatically block the entire experience. However, it remains an individual decision, as not everyone reacts the same way.

With option 2, tapering off more quickly and then waiting, five times the half-life results in approximately 6 to 7 days. Including the tapering itself, this usually means about 2 to 4 weeks in practical planning. This is often feasible with shorter use or when previous dose reductions were well tolerated.

For option 3, gradually tapering off and stabilizing, approximately 1 to 3 months is often more logical. With longer use or sensitivity to dysregulation, this may increase further. This route is usually most suitable if someone wants both as full an experience as possible and a sustainable transition to less or no medication.

Fluvoxamine, Luvox and Faverin

Fluvoxamine has an average half-life of approximately 15.6 hours in young, healthy adults. In the elderly, this half-life can be significantly longer, up to approximately 17.4 to 25.9 hours depending on the dose and situation. This means that fluvoxamine can be eliminated pharmacologically quite quickly, but also that age is an additional factor to consider in planning.

With option 1, continued use, it still holds true that preparation is often possible within 1 to 2 weeks. The advantage is rest and continuity. The disadvantage is once again that the psilocybin effect may be less pronounced.

With option 2, tapering off more quickly followed by a wait, based purely on half-life, you arrive at approximately 3 to 4 days for younger adults. In practical planning, however, you usually still end up with about 2 to 4 weeks, especially if you want to taper off cautiously or if the person is somewhat older. For the elderly, it is advisable to build in extra margin, as fluvoxamine is demonstrably cleared more slowly in this age group. 

For option 3, gradually tapering off and stabilizing, approximately 1 to 3 months is often a workable starting point, and sometimes longer for older users or long-term use. This makes this route particularly interesting when someone is sensitive to anxiety or when the session really only needs to be scheduled once the system feels calm and predictable again.

Substances such as LSD, MDMA, ayahuasca, psilohuasca, and psiloflora

With LSD, similar interactions are generally assumed as with psilocybin, truffles, and magic mushrooms. Here too, SSRIs can dampen or alter the effects. Therefore, broadly speaking, the same considerations apply regarding continued use, tapering, and stabilization, although the direct modern research literature on LSD is more limited than on psilocybin.

Substances such as MDMA, ayahuasca, psilohuasca, and psiloflora require extra caution when using an SSRI. The information in this article regarding tapering off SSRIs can broadly serve as a starting point for MDMA, ayahuasca, psilohuasca, and psiloflora as well, but with an important difference. Option 1 is not a suitable route in this case. In the case of ayahuasca and psilohuasca (including Chocbliss or Cacao Bliss), this is primarily because these combinations rely on MAO-A inhibition, meaning that concomitant use with SSRIs is considered a significant contraindication due to the risk of serotonergic toxicity and other undesirable interactions. The same applies, to a lesser extent, to psiloflora. We exercise the same caution, as it also contains an MAO-inhibiting component.

Option 2 That could be a possibility, provided that after tapering, not only is approximately five times the half-life taken into account, but also an extra safety margin to account for the fact that degradation and recovery may differ per person. Option 3, So, tapering off gradually, then stabilizing, and only then doing the session is generally the safest option.