In brief
- A single dose of psilocybin increased sociability in mice with a baseline social deficit, and the effect lasted for at least two weeks.
- The improvement also appeared when the animals received the substance under light anesthesia, without undergoing any altered state.
- Blocking the 5-HT2A serotonin receptor beforehand completely nullified the effect.
Is it necessary to experience the “trip” for a psychedelic to leave a lasting mark? An international team led by Thomas Knöpfel has just published an experiment in Nature Communications that addresses this question in the most direct way possible: by administering psilocybin to sleeping mice. The answer, at least in this animal model and for this specific behavior, is that the lasting effect appeared regardless.
A mouse with less desire for company
The study uses mice in which the Cntnap2 gene has been inactivated, a well-established laboratory model for studying reduced sociability. Their interest in approaching another conspecific is measured using the three-chamber test, where the animal chooses between approaching another mouse or an object. After a single injection of psilocybin, these mice spent more time exploring the conspecific in tests conducted the following day, at one week, and at two weeks. A different group, evaluated for the first time at two weeks, showed the same result, which rules out the possibility that the outcome was due to the repetition of the test.
The contrast is the interesting part: in mice without a prior deficit—the wild-type mice—psilocybin did not improve anything. It did not function as a general sociability enhancer, but only where there was an underlying imbalance. It also did not modify other behaviors in the model, such as repetitive behaviors or hyperactivity.
The anesthesia experiment
To separate the biological mechanism from the subjective experience, the authors repeated the procedure with the animals under light anesthesia, so they would never pass through the altered behavioral state that, in an awake mouse, is considered the equivalent of the acute effect. The increase in sociability was maintained across all three measurements. In contrast, when they pre-treated the animals fifteen minutes earlier with a specific 5-HT2A serotonin receptor blocker, the effect disappeared. The molecular pathway proved necessary; wakefulness did not.
What it implies
It is important to keep the actual scale of the finding in perspective: this is basic research in mice, and the authors themselves warn that it does not allow us to deduce what would happen in humans, nor to present psilocybin as a treatment for autism. The Cntnap2 model is used here as a way to study altered sociability, not as a portrait of human autism, and the three-chamber test has its own limitations. The authors add another honest caveat: the anesthesia itself could potentially influence the cellular mechanisms involved.
Even so, the result touches on an open debate in psychedelic research: to what extent is the conscious experience essential for the subsequent benefit? It is the same discussion fueling the development of non-hallucinogenic analogs. Here, the data suggest that for this behavior and in this animal, the determining factor was what occurred at the receptor while the substance was active, not what the animal might have been experiencing. Whether this translates to a person, with everything the experience means for the individual undergoing it, is a different and still unanswered question.
Source
- Song C, Chang T, Buchborn T, Knöpfel T. Psilocybin enhances sociability only in altered behavioural state and does not need an awake experience to be effective. Nature Communications, 2026.
Educational content written from a harm reduction perspective and with respect for individual freedom. It is not a substitute for advice from a healthcare professional and is not intended to encourage or condemn any drug use.
