Wherefore the magic? The evolutionary role of psilocybin in nature
Kirsty J. Matthews Nicholass, Ilona Flis, Me Hanley, M.e Knight, S.m Lane, G Littlejohn, M.d.f Thom, R.a Billington, R Boden, R Cummins, B.j Green, C Griffin, S Jones, D Salmon, I Sleep, N Smirnoff, J.s Ellis
bioRxiv (Cold Spring Harbor Laboratory) December 19, 2025 preprint DOI: 10.64898/2025.12.17.694186 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | Drosophila larvae and adults |
| Topics | Psilocybin |
| Keywords | Invertebrate Evolutionary biology Ecology Zoology Natural selection |
| Key findings | Psilocybe mushroom extracts reduce survival, development, and locomotion in fruit flies, supporting a defensive evolutionary role for psilocybin, but this effect does not depend on the 5HT2A receptor. |
Abstract
Abstract Research into psychedelic compounds is in resurgence due to the exciting potential for their use in the treatment of psychiatric and mental health disorders. Despite this revival, remarkably little is known about their evolution. One of the most intriguing psychedelic compounds is psilocybin, the compound found in ‘magic’ mushrooms and used in ritual ceremonies in Central America for generations. Associated with agaricomycete fungi of the genus Psilocybe , psilocybin acts in a similar way to the neurotransmitter serotonin, yet how and why natural selection favoured its biosynthesis remains unclear. Given the resemblance to serotonin, modulation of invertebrate behaviour for defence is a likely explanation, but neither this nor alternative hypotheses have ever been formally tested. Here, we show that Drosophila larvae exposed to extracts from Psilocybe mushrooms exhibit reduced survival, pupation rates, and inhibited locomotion. Adults exposed during development show reduced thorax and wing size, along with increased fluctuating asymmetry, indicating developmental stress. Conversely, mutants lacking 5HT2A receptors showed the same response to Psilocybe extracts as wild-type flies. Furthermore, DNA metabarcoding revealed that while Psilocybe semilanceata demonstrates a distinct invertebrate community compared to most other grassland fungi, it overlapped with the non-psychedelic species Mycena epipterygia . This study provides a crucial first step toward understanding the evolutionary role of psilocybin-producing fungi and provides a grounding for future research into the molecular mechanisms, ecological interactions and evolutionary origins of psychedelic compounds in nature.
Comparable studies
Other experimental studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Healthy human volunteers | 1998 | Experimental study | |
| Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin Participants in controlled laboratory experiments receiving a moderate to high oral... | 2015 | Validation study using pooled data from five laboratory experiments | n = 184 |
| Broadband Cortical Desynchronization Underlies the Human Psychedelic State Healthy human participants | 2013 | Experimental study | |
| Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer Participants with cancer-related psychiatric distress who completed a parent randomized... | 2020 | Long-term within-subjects follow-up analysis | n = 15 |
| Enzymatic Synthesis of Psilocybin | 2017 | Laboratory study |
Citations in the library
Cites 20
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- The pharmacology of psilocybin Addiction Biology October 1, 2002
- Emotions and brain function are altered up to one month after a single high dose of psilocybin. Scientific Reports February 10, 2020
- Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder. Translational Psychiatry November 8, 2021
and 15 more in the library