Does Form Affect Healing?
The argument for research into natural forms of psilocybin is captured by Roots to Thrive, a nonprofit healthcare organization in Canada that offers fully legal psychedelic therapy for those suffering from conditions like PTSD, depression, and anxiety.
Roots to Thrive is a rarity in North America, and alongside offering psychedelic mental health services, they also collect data on their work, helping to set a precedent for the future of psychedelic therapy.
This unique design not only allows them to see therapeutic results in real-time but also constantly expands the data set for psychedelic therapy, which is important to have when setting ground rules for the future of an entire mental health field.
In 2024, they published a study examining how participants experienced psilocybin in three forms during the Roots To Thrive Psilocybin-Assisted Therapy for End of Life Distress program. The study title? “‘The mushroom was more alive and vibrant’: Patient reports of synthetic versus organic forms of psilocybin.”
The three different forms were as follows:
- 25 mg of synthetic from PsyGen
- 25 mg of an ethanol mycological extract of Psilocybe cubensis
- 5 dried grams of whole Psilocybe cubensis mushrooms (not tested for purity)
In this study, two patients received three different forms of psilocybin at different times; one additional patient had experiences with the extract and whole mushrooms; and a fourth patient received the synthetic form and the mycological extract at different times during the End-of-Life Distress program, allowing for a unique within-subjects design.
It’s important to note that this study was not meant to prove that natural psilocybin is objectively better, as Avi Loren Fox at North Spore put it, the study is “designed to capture qualitative experiences in a real-world, therapeutic setting—not to mimic the blinding procedures of conventional randomized trials” (Fox, 2025).
The results?
First, all three forms proved helpful and similar for each participant; however, the real difference was seen in the felt effects of the experiences.
Roots to Thrive Study Participants described their experiences in a post-interview:
Whole mushroom: “Things were brighter, green was greener, red was redder, sort of thing. It was a brightness, a clarity, a cleanness.”
“Synthetic felt more medicine-y and less spiritual.”
“Synthetic was like I was looking through a window, looking at it. I wasn’t in it.”
“With the whole mushrooms, it felt like going on the journey together, but with the synthetic, it was like the substance was taking you for a ride.”
The natural forms of psilocybin (which contain unique compound profiles in addition to psilocybin) consistently led participants to feel more “sentient” and interactive than synthetic forms.
Having a mushroom as your shepherd sounds nice, doesn’t it?
Interestingly, all forms induced mystical or spiritual experiences; however, the form appeared to affect each participant’s view of it.
Capsule forms of both synthetic and natural psilocybin were perceived as “less spiritual,” while the whole, dried mushroom form felt more “sacred and alive.”
When asked what form was preferred, participants chose natural psilocybin.
Since social isolation and lack of connection are among the top causes of mental health conditions in the US, it makes sense that a sense of community and a trusting connection with your therapist or facilitator are both driving factors in lasting healing in intentional psychedelic use (Myers, 2003; Dorsen et al., 2025).
Because of this, it’s not surprising that feeling that psilocybin is sentient or interactive can promote healing in a unique way, not to mention the indigenous communal practices that encompass a traditional psilocybin “ceremony.”
“The synthetic… it didn’t bring the whole emotion that the whole mushroom did. The whole mushroom was more empathetic. I felt like I was in relationship with it.” — Roots to Thrive Study Participant
The downside to natural forms of psilocybin has always been the lack of standardization, but it’s only a downside when held up to scientific rigor.
Researchers in this study admittedly did not test the purity of the natural forms of psilocybin used; however, we’re reminded that they never intended this study to meet scientific rigor; instead, they wanted to mirror real-world use of psilocybin for healing.
After all, it was thousands of years of indigenous use and one westerner’s (Gordon Wasson) natural mushroom trip in a traditional ceremony with Maria Sabina that spearheaded the West’s desire to research psilocybin at all.
Ultimately, further study is required to determine how synthetic and natural forms of psilocybin interact with our brain receptors, and if there’s any difference at all.
The debate isn’t really about whether there’s a physical difference between synthetic and natural forms of psilocybin, after all, psilocybin is the same molecule whether it’s made in a mushroom or in a lab. The true difference lies in the other compounds that are found in whole mushrooms.
The nuanced differences in felt effects in this study certainly leave plenty of room for future research topics, given that natural, psilocybin-containing fungi are increasingly welcomed into research.