If you’re asking about psilocybin long-term effects, the human studies give you a real but limited answer: the longest follow-up runs 365 days after a single supervised dose. In the 2026 JAMA Network Open trial, the primary end point (day 8) was met, but the between-group difference on the secondary MADRS measure was no longer significant at day 365 (mean difference -3.68, P = .20). Daily use and multi-year use have not been tested in the human trials covered here, so that part of your question is still open.
Why the psilocybin news is confusing you
The 2026 JAMA Network Open trial gave 35 adults with moderate to severe recurrent major depressive disorder either a single 25 mg dose of psilocybin or niacin 100 mg as an active placebo, plus five psychotherapy support sessions over 17 days. The primary end point, the between-group difference in change in MADRS score at day 8, was met. The MADRS differences on days 15 and 42 were also significant. On day 365, the secondary end point was no longer significant (mean difference -3.68, P = .20). Self-reported symptoms stayed different between the groups through day 102, with isolated differences on days 283 and 343.
Read together, these are small randomized trials. Randomizing means people are assigned to groups by chance, which is what lets a study compare psilocybin with a control. With 24 to 36 people per study, they can show a pattern but cannot rule out less common effects, and none followed people for years.
What the human studies found, study by study
The table lists the four human studies in this review, from oldest to newest.
| Study | Who took part | What was given | How long followed | What it found |
|---|---|---|---|---|
| 2006 study in Psychopharmacology (2006 study) | 36 adults new to hallucinogens who took part regularly in religious or spiritual activity | 30 mg/70 kg psilocybin or methylphenidate, in a counterbalanced, double-blind design; six others received methylphenidate, then psilocybin | Two months after sessions | Volunteers rated the experience as having substantial personal meaning. Community observers rated sustained positive changes in attitudes and behavior. |
| 2022 12-month follow-up (2022 12-month follow-up) | 27 adults aged 21 to 75 with moderate to severe depression; 24 completed both sessions | Two psilocybin sessions with supportive psychotherapy; randomized to immediate or 8-week-delayed treatment | 12 months after the second dose | Large decreases in depression scores at 1, 3, 6 and 12 months. Response was 75% and remission 58% at 12 months. No serious adverse events were judged related to psilocybin in the long-term period. |
| 2022 microdosing study (2022 microdosing study) | 34 people starting to microdose | 0.5 g of dried Psilocybe cubensis or placebo, double-blind | Acute and short-term effects | No evidence to support enhanced well-being, creativity or cognitive function. Lower EEG theta-band power. A few small changes toward cognitive impairment. |
| 2026 JAMA Network Open trial (2026 JAMA trial) | 35 adults with moderate to severe recurrent major depressive disorder, Northern Stockholm Psychiatric Clinic | Single 25 mg psilocybin or niacin 100 mg, plus five psychotherapy sessions over 17 days | 365 days | Primary end point (day 8) met. MADRS differences significant on days 15 and 42; not significant on day 365 (secondary end point). Two psilocybin participants had persistent, severe anxiety that required medical attention. |
Is psilocybin bad for your brain?
In people, the studies here report short-term changes in brain activity and mood, and few serious side effects. The clearest brain signal in people comes from the microdosing study, which recorded lower theta-band EEG power after low doses. A 2022 mouse study found that a single high dose changed more than 1,500 transcripts in the prefrontal cortex three hours after dosing, but that a single administration did not produce any long-lasting transcriptional changes there. Mice are early context, not a prediction for people. For more on the research, see our psilocybin brain effects research guide.
What happens when you take psilocybin every day, or microdose for a long time?
No human study covered here followed daily use. The daily-dosing research is in mice: in a seven-day test, daily psilocybin at 0.3 mg/kg had no significant effect on body weight or food intake.
For microdosing in people, the closest data is the 2022 microdosing trial. It looked at acute and short-term effects, and it found no evidence to support enhanced well-being, creativity or cognitive function. Its authors conclude that expectation underlies at least some of the anecdotal benefits attributed to microdosing. why trials need a placebo group (our research library) explains why that design matters when you read online reports. So the long-term question for microdosing is still open.
Is psilocybin the safest drug?
The trials don’t rank psilocybin against other drugs, so they can’t tell you whether it is the safest. What they do report is that, in the 2026 trial, most treatment-emergent adverse events were transient and of mild to moderate severity, and no drug-related serious adverse events were reported. The same trial found that psilocybin was generally well tolerated, but that some individuals required additional support after dosing due to anxiety.
Side effects: what the studies report
| Side effect | What the study reported | Study |
|---|---|---|
| Anxiety needing extra support | Some individuals needed additional support after dosing. Two psilocybin participants had persistent, severe anxiety that required medical attention. | 2026 JAMA trial |
| Mild to moderate, short-lived effects | Most treatment-emergent adverse events were transient and of mild to moderate severity. | 2026 JAMA trial |
| Anxiety and mood changes during sessions | Acute perceptual changes, subjective experiences and labile moods including anxiety. | 2006 study |
| Stronger effects at low doses | Acute effects were significantly more intense for the active dose than placebo, but only for participants who correctly identified their condition. | 2022 microdosing study |
Who should avoid psilocybin?
Who should skip psilocybin is a decision to make with a clinician who knows your health history. The 2022 12-month and 2026 trials enrolled adults with moderate to severe depression, while the 2006 study enrolled hallucinogen-naïve adults active in religious or spiritual practice and the microdosing study enrolled people starting to microdose. The 2026 trial’s anxiety cases show that a session can be hard. If a mushroom product is sold as a dietary supplement, the NCCIH guidance on dietary supplements notes that many have not been tested in pregnant women, nursing mothers or children, and that some may harm you if you have a medical condition or take certain prescription medications.
Gummies and “legal psychedelics”: a different risk
Gummies and edibles sold as “legal psychedelics” are a separate category. As of November 2026, the FDA’s December 18, 2024 update says that Amanita muscaria and its constituents muscimol, ibotenic acid and muscarine “do not meet the safety standard for use in food and that their use as food ingredients may be harmful,” and it recommends that people avoid eating foods with these ingredients. Our amanita muscaria gummies legality guide covers the UK position. The NCCIH guidance also notes that “what’s on the label may not be what’s in the product.”
Are psychedelics bad for your body?
In the 2022 mouse study, a single 3 mg/kg dose had no effect on body temperature, blood glucose, corticosterone, cholesterol, triglycerides or insulin, and sub-chronic microdosing had no metabolic effects in obese mice. Mice are early context, and they do not show how people’s bodies respond.
What is still not known
- Years of use. The longest human follow-up here is 365 days.
- Daily use. The daily-dosing research here is in mice.
- Repeated dosing. The 2026 trial’s authors call for “further investigation into repeated dosing or adjunctive treatment strategies.”
- Whether benefits last past one year. On the 2026 trial’s secondary MADRS measure, the between-group difference was no longer significant on day 365.
- Who is suited to it outside the conditions studied.
Your options side by side
| Option | What it is | What the studies show | Who it suits and limits |
|---|---|---|---|
| Psilocybin in a clinical trial | Studied in the trials above, given with supportive psychotherapy sessions | In the 2022 study, large decreases in depression scores at 12 months; in the 2026 trial, the day 8 primary end point was met and the day 365 secondary MADRS difference was not significant | People a study enrolls. Small numbers and anxiety cases are the limits. Ask the study team about eligibility and cost. |
| Psilocybin outside a trial | Legal status depends on where you live and can change | No human study covered here followed daily or multi-year use | Talk with a clinician first, and check the current rule where you live |
| Microdosing mushrooms | Small, repeated doses taken on a schedule | The 2022 placebo-controlled trial found no evidence of enhanced well-being, creativity or cognitive function | Studied for acute and short-term effects only |
| Reishi mushroom supplements | Dried and taken as an extract in liquid, capsule or powder form | MSK lists nausea, insomnia and liver injury as side effects | MSK notes reishi can increase bleeding risk if you take blood thinners such as warfarin. Discuss with a clinician first. |
| Amanita muscaria gummies | Sold as “legal psychedelics” or “psychedelic edibles” | FDA says these ingredients do not meet the safety standard for use in food | FDA recommends people avoid eating foods with these ingredients |
The Compass Pathways psilocybin phase 3 and FDA status page covers one company’s development program. Whether any psilocybin-based treatment is approved where you live is the first thing to ask your clinician, who can also compare it with other depression treatments available to you.
Cost, legal status and where to check
Prices change, so check today’s price directly with the company or your clinic. If you are considering a trial, ask the study team what it costs you, if anything. Psilocybin’s legal status varies by country and state and can change, so check your national or state health agency for the current rule before you make any decision. This is information, not legal advice.
Questions to take to your clinician
- Is any psilocybin-based treatment approved where I live, and for what?
- Are there trials I could join, and what are their eligibility rules?
- How would my health history and current medicines affect this decision?
- What follow-up would you recommend after a session?
By MushroomHealthBenefits.com Research & Editorial Team
This article is for general information purposes only and does not constitute medical advice. Consult your doctor or qualified healthcare provider before making changes to your health routine.