February 6, 2025 by Alex Brewer, PharmD, MBA
TL;DR
- A large survey finds natural psilocybin use linked to improved mental health but with key limitations like self-reported data.
- Psilocybin shows promise for reducing depression and anxiety in real-world use, despite study flaws.
- Natural psilocybin use may boost mental health, paving the way for future research.
Our study for review today is “Naturalistic psilocybin use is associated with persisting improvements in mental health and wellbeing: results from a prospective, longitudinal survey”, from a team of researchers across Johns Hopkins, Ohio State, and Unlimited Sciences (based in Colorado). The authors claim this is the “largest prospective survey of naturalistic psilocybin use published to date”, and I’m willing to take them at their word because whether or not it truly is the largest study of its kind to date isn’t relevant to our discussion.
What is relevant is their focus on “naturalistic psilocybin use”. In this study, people were not recruited to participate in a clinical trial. There were no researchers carefully controlling as many variables as possible in a clean, sterile environment. And no one used psilocybin made in a lab.
Instead, the research team recruited adults who planned on using psilocybin outside a clinical research environment to self-report, using surveys, on a variety of questions related to their reasons for using psilocybin and the outcomes after use. This comes with pros and cons, which we’ll dive into.
Study Design
Since this study was conducted outside a clinical trial environment, the research team used surveys to collect data.
Participants who indicated they already planned to use psilocybin were recruited to complete a total of six surveys over a total time of 3 – 4 months:
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Survey #1 was completed at the time they consented to join the study
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Survey #2 was completed two weeks before planned psilocybin use
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Survey #3 was completed the day before psilocybin use
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Survey #4 was completed 1 – 3 days after psilocybin use
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Survey #5 was completed 2 – 4 weeks after psilocybin use
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Survey #6 was completed 2 – 3 months after psilocybin use
There were 8,006 initial respondents to survey #1. This dropped to 1,182 participants who completed the 2 – 4 week post-use survey, and only 657 completed the final 2 – 3 month post-use survey.
Can you spot limitations yet? That’s a lot of paperwork.
Would you trust yourself to complete every survey, truthfully, on time? Whether you consider yourself “honest” or not, we have a plethora of data showing people tend to want to present their “best selves” on surveys – even if it involves exaggerating or fudging the truth.
Respondents were mostly college-educated White men in the U.S., with an average age of 40. Many reported past psychedelic experience, and reported using psilocybin for “self-exploration”.
The research team proposed the following hypotheses which they wanted to answer:
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“we hypothesized respondents would exhibit, on average, persisting improvements in mental health, wellbeing, and psychological functioning from before to after psilocybin use”
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“we hypothesized that aspects of individual mindset (i.e., absorption, effects of adverse childhood experiences, State of Surrender) before the experience would be significantly associated with subjective drug effects (i.e., mystical and challenging experiences) and would predict persisting effects”
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“we hypothesized that presence of a sitter during the experience would be associated with more positive persisting mental health outcomes”
Study Results
There were a variety of questions used across the surveys, and I encourage you to read the full study to learn more. I’m going to touch on highlights here.
Intent
In survey 3, participants were asked to indicate why they were interested in using psilocybin. Participants could choose more than one answer.
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81% were interested in “self-exploration”
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71% were interested in “mental health”
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Just under 44% were interested in “creativity”
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Nearly 38% were in it for “recreation”
Remember what I said above, how people often answer surveys not 100% honest but instead in a manner they think presents their “best self”, the way they want to view themselves? I suspect that respondents saw “self-exploration” as a “better” answer than “recreational” use, which still carries stigma. And isn’t “self-exploration” a type of recreation?
Food for thought.
Setting
Participants disclosed the setting of psilocybin use in survey 4.
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43% reported using psilocybin alone
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25.7% reported using psilocybin with friends who also took psilocybin
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16.4% reported using psilocybin with a sober friend serving as a “sitter”
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1.5% reported using psilocybin with a “shaman or guide”
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Only 1.1% reported using it with a therapist
“Home” was the most common setting, with nearly 70% of respondents. Just under 16% used psilocybin outdoors in nature. Only 1.2% reported use at a concert or festival, which is lower than I expected. I’m most interested in the 0.7% who reported use in a mall, movie theatre, or similar public setting.
Dosage
Participants mostly used dried whole mushrooms (42.2%), dried ground mushrooms (19.3%), or mushroom tea (15.5%). Only 12.4% reported using more than one dose during the session.
The average reported dose was 3.1 grams. Keep in mind this is reported by the participant, and there’s no way to verify the dose. Researchers have to take them at their word.
Nearly 31% noted they used cannabis during the session. 14.8% used caffeine, and 11.5% used alcohol. 4.6% of participants noted they were on an antidepressant medication during their session.
Long-Term Measures of Wellbeing
41% of respondents met some criteria for depression prior to psilocybin use. On survey 6 (2 – 3 months post use), 14.5% of respondents answered in a manner indicating some level of depression, showing a decrease in depression scores over time. There was a similar decrease in anxiety scores over time following psilocybin use: 28.8% of survey 2 respondents met criteria for “high-risk state anxiety”, which dropped to 15.1% on survey 6.
16.3% of participants answered in a manner that met criteria for risky alcohol use on survey #1; this dropped to 10.8% of respondents on survey #6. Respondents also noted overall improvements in spiritual wellbeing and a decrease in work-related burnout.
There was no significant change in self-reported physical health.
The table below matches the hypotheses with the team’s conclusion from the data collected:
I won’t cover all the data results here – there’s a lot. Again, I encourage you to check out the full study.
Dicussion and Looking Forward
One key issue with survey-based studies is response bias. The researchers note, “individuals who experienced particularly difficult reactions or significant adverse events may not have been able or willing to respond to follow-up surveys as described in the study limitations.” There’s a non-zero chance that adverse effect rates were higher than reported here, because each post-use survey received fewer and fewer responses. There’s a tendency for people who experience negative or even neutral outcomes to drop out of surveys like this.
Speaking of drop-out – look at how many people completed survey #1, and compare to the number remaining who completed the final survey: 8,006 initial respondents to survey #1, and only 657 completed the final survey. This complicates takeaway points from the study, especially post-use surveys.
Evaluating the adverse effect data is difficult. We already touched on survivorship bias above. Further complicating matters, some respondents co-ingested other substances along with psilocybin, mainly cannabis and alcohol. This is problematic, because 1) it makes it difficult to know if side effects were due to psilocybin or another substance, and 2) side effects can be additive or synergistic across substances.
Still, there’s useful data here, and survey-based studies play an important role in the research ecosystem.
For example: this study found general improvements across answers regarding mental health and wellbeing. We can’t draw definitive conclusions such as “naturalistic psilocybin improves wellbeing”, because of the flaws noted above – other variables could have impacted the results (we can’t say for certain psilocybin caused the improvement in wellbeing – there’s no placebo or any comparator), for example. And participants self-reported their dose.
But this is useful data to move forward and conduct a controlled clinical trial using “natural” psilocybin. Finding money to conduct this sort of trial is made easier when there is data indicating promise, which is provided by cheaper but less definitive studies such as this.
“But won’t Big Pharma block those trials so they can push their own preparations?”
Where do you think they find inspiration for their preparations? The first antibiotic (penicillin) came from mold. Scientists took the natural compound – mold – and tweaked it to be something humans could safely ingest in an easy manner which could be scaled at a global level to treat infections around the globe. No one is stopping you from ingesting mold on your own today, although I do not recommend doing so.
In the same manner, I anticipate pharmaceutical psilocybin and natural psilocybin will co-exist with their own uses. Pharmaceutical preparations will likely gain favor amongst healthcare professionals for treating conditions like PTSD and severe depression, because we can reasonably assume these preparations are safe, and they’ll be available in standardized doses. But for “self-exploration”? Natural psilocybin will likely remain the preferred choice.