90mg psilocybin from truffles and no effect or trip?

It sometimes happens that people hardly react to psilocybin. Today I supervised a session where the client in question took approximately 90 mg of psilocybin. The first dose was 30 grams of truffles. An hour later, he felt less depressed, but there were no hallucinations or trip. So, after this hour, the dose was doubled to see what effect it would have. Unfortunately, after half an hour there was no additional effect, and time was running out for a possible third dose. So, another 30 mg of psilocybin was added. In this way, 90 mg of psilocybin was ingested.

The pupils are only slightly dilated and the depressive feelings are gone. This shows that something is happening. Otherwise, there isn't really a trip. We hope that it is doing something good in the background after all, and that psilocybin is making the cells healthier on a chemical level through its antioxidant properties and BDNF-increasing neuroplastic effects. After all, there is no real tripping experience.

How can you to have little effect from such a high dose of psychedelicsThis client has used antidepressants for a long time, and this may have resulted in serotonergic downregulation. This means that the receptors for serotonin and various psychedelics function less effectively or are present in lower numbers (in certain brain regions).

In addition, there are several other possible explanations. Long-term use of SSRIs or SNRIs can not only reduce the number of 5-HT2A receptors but also permanently alter their sensitivity. Even after tapering off, it can take months for the receptor response to fully recover. In some cases, there appears to be a prolonged attenuation of the psychedelic effect.

Genetic differences may also play a role. Variations in liver enzymes (such as CYP enzymes) influence how quickly psilocin is broken down. In very rapid metabolizers, the active substance can disappear from the system more quickly, preventing the peak from occurring. However, this usually does not fully explain the absence of virtually all subjective effects at such a high dose.

Furthermore, we sometimes see that people do indeed respond pharmacologically. Think of pupil dilation and mood improvement. However, they do not have a clear visual or mystical experience. This suggests that the substance reaches the brain and has an effect, but that the cortical networks responsible for the typical “trip experience” are less responsive.

Finally, psychological control also plays a role. Some people unconsciously hold strongly to cognitive control mechanisms. Even at high doses, consciousness can then remain remarkably stable, with little subjective distortion.

Although a deep trip often acts as a catalyst, its absence does not automatically mean there is no therapeutic effect. The observed improvement in mood suggests that something neurochemical did indeed happen. Time will tell whether that is sufficient for long-lasting change.

We might make another attempt in the future, but first we need to work on higher receptor sensitivity. Fortunately, this is possible with certain supplements and time for receptor recovery. Or sometimes a different psychedelic might do the trick.