Real-World Evidence · 2026

The largest study of regulated psilocybin services.

Co-authored with the University of Colorado School of Medicine. 2,752 participants. 279 facilitators. Two state programs. Submitting to a reputable peer-reviewed medical journal.

At a Glance
The study
First retrospective observational study of regulated psilocybin services in Oregon and Colorado. N = 2,752 participants documented through Althea's platform.
Mental health
Therapeutic benefit across depression, anxiety, and trauma populations. Depression scores dropped 48% with a 68% remission rate. Anxiety scores dropped 50% with a 56% response rate. Trauma and PTSD participants rated the experience as more meaningful than non-trauma participants. Effect sizes exceed published clinical trial and SSRI benchmarks.
Safety
Adverse events reported in 0.03% of cases. No triggered psychosis. No de novo suicidality. Five EMS calls across 2,752 sessions.
SSRIs
Participants on antidepressants showed equivalent therapeutic benefit. No need to taper before treatment.
Why it matters
This paper exists because Althea's platform collected the data. Participants routinely volunteer their outcomes data, and as new states come online the evidence base compounds into a structural advantage no competitor can replicate.
Section i

Real-world data across regulated psilocybin use.

2,752 documented participants across every demographic. The most complete picture of who seeks psilocybin services, why, and what happens.

2,752
Participants
Across Oregon and Colorado state programs
279
Facilitators
1 to 150 clients each
50
U.S. States
Plus international participants

This is not a clinical trial population. It is the real world. 66% reported a history of depression or anxiety. 48% reported trauma history. 30% had a diagnosis of PTSD. More than half were already seeing a mental health provider. These are people with genuine clinical need, seeking a regulated pathway.

Section ii

Who they are.

A real-world cross-section. Not a cherry-picked clinical trial population — this is who is actually seeking regulated psilocybin services.

56 / 42 / 2%
Gender
Female / Male / Non-binary
47.7
Age
Mean age · Range 21–87
68%
Prior Experience
With prior psychedelic experience
Age Distribution
Clinical history at intake

66% reported a history of depression or anxiety (1,662 of 2,533). 48% reported trauma history (1,222). 30% reported PTSD (766). 53% were currently seeing a mental health provider. These are people the FDA-approved pathway will also target — and many of them are already here.

National demand, limited supply

45% of participants traveled from outside their home state to access services. All 50 U.S. states were represented, plus 47 international participants. The demand is national. The regulated supply is not. That gap is Althea's market.

Section iii

The demand FDA labels won't absorb.

Most people in this dataset are not seeking treatment for a diagnosed condition. They are here for reasons no pharmaceutical label will ever cover. This is the spillover.

Primary Reason for Seeking Psilocybin Services
The spillover thesis

FDA approvals will be narrowly indicated — major depressive disorder, treatment-resistant depression, anxiety in terminal illness. These labels will cover roughly 28% of the people already in this dataset. The other 72% are seeking psilocybin for reasons that no pharmaceutical company will ever have a label for. FDA approval does not absorb this demand. It activates it. It breaks the stigma, educates the consumer, and sends tens of millions of newly motivated people looking for legal access. The narrow label cannot serve them. The state programs can. Althea runs the state programs.

Section iv

Efficacy that exceeds clinical trials.

Real-world outcomes that match or exceed Phase 3 benchmarks for depression, anxiety, and well-being.

Depression · PHQ-9
48% reduction
N
133 pre/post pairs
Effect size
Partial η² = 0.56
Response
58% achieved ≥50% improvement
Remission
68% dropped below clinical threshold
Gender
42% improvement (F), 56% improvement (M)
Anxiety · GAD-7
50% reduction
N
211 pre/post pairs
Effect size
Partial η² = 0.59
Response
56% achieved ≥50% improvement
Remission
48% dropped below clinical threshold
Gender
48% improvement (F), 54% improvement (M)
How this compares to clinical trials and standard-of-care benchmarks
Study Population N Protocol Response Remission
Goodwin et al.
NEJM 2022		 Treatment-resistant depression (COMPASS COMP360) 233 Single 25mg dose 37% at 3 weeks —
Raison et al.
JAMA 2023		 Major depressive disorder (Usona PSIL201) 104 Single 25mg dose 42% sustained 25% sustained
Althea real-world data Depression (PHQ-9) 133 Mean 29.1mg + full service protocol 58% 68%
Kong et al.
Front. Pharmacol. 2020		 Generalized anxiety disorder (SSRI/SNRI meta-analysis) 13,338 Daily SSRI/SNRI for 8–24 weeks — 25–30%
Althea real-world data Anxiety (GAD-7) 211 Mean 29.1mg + full service protocol 56% 48%
Note: Depression trials above use MADRS, while Althea uses PHQ-9. The anxiety benchmark uses HAM-A, while Althea uses GAD-7. These instruments are not directly interchangeable, but the magnitude of improvement across measures is noteworthy — particularly given that Althea's outcomes followed a single session versus weeks of daily medication.
Pre- vs. Post-Dosing Scores · Depression & Anxiety
Why real-world results outperform trials

Clinical trials deliberately minimize psychotherapy to isolate the drug effect for FDA approval. In the real world, the medicine and the therapeutic container work together. Psilocybin services is not a pill. It is a protocol. The facilitator relationship, the set and setting, the integration session — these are features of the regulated pathway, and they appear to improve outcomes. The protocol is what Althea coordinates.

Well-being improvements beyond clinical populations

Even among participants without clinical depression or anxiety, WHO-5 well-being scores improved by 21% overall (N = 711). For those with poor baseline well-being (score ≤ 32), the improvement was dramatic: scores more than doubled, rising from 21.7 to 49.4. The therapeutic benefit extends well beyond diagnosed conditions.

Section v

Trauma & PTSD.

Nearly half of participants reported a trauma history. Their outcomes were not just comparable — they rated the experience as more meaningful.

48%
Trauma history
Of all participants
30%
Reported PTSD
766 participants
377
With 2-week outcomes
Trauma/PTSD subgroup
94%
Reported beneficial
Of trauma/PTSD participants
8.86
Meaningfulness
Out of 10 · vs. 8.45 non-trauma
7.93
Wellbeing enhancement
Out of 10
8.28
Benefits rating
Out of 10
9.53
Safety rating
Out of 10

Participants with trauma or PTSD histories rated the psilocybin experience as more meaningful than those without trauma (8.86 vs. 8.45 out of 10). Only 1.6% reported the experience as harmful. The safety rating of 9.53 out of 10 suggests that the regulated setting — with preparation, facilitation, and integration — provides a container that trauma survivors experience as safe.

Important context

No validated trauma-specific clinical instruments (such as the PCL-5) were used in this study. These findings are based on self-reported satisfaction and benefit ratings, not clinical change scores for PTSD symptoms. They indicate that trauma survivors are well-served by the current model, but formal trauma outcome measurement should be a priority for future research.

Section vi

Safety is a solved concern.

The argument against regulated psilocybin was that it would overwhelm EMS and trigger psychotic episodes. The data say otherwise.

0.03%
Adverse event rate
5
EMS calls
In 2,752 sessions
0
Triggered psychosis
Even in at-risk population
0
De novo suicidality
Pre-existing cases did not worsen
Dosing-day events
Mild and transient

The most common events were nausea (32 reports), anxiety (11), crying (8), and agitation (7) across 2,752 participants. All were noted as mild and transient by facilitators. No other event received more than two reports.

Post-dosing events
Equally minimal

At the two-week follow-up: headaches (15 reports), nausea (7), memory/attention changes (4), and insomnia (3). Again, all mild and transient. The adverse event profile in this real-world population mirrors what is seen in controlled clinical trials.

Psychosis risk — data over fear

Despite efforts to discourage at-risk individuals, a considerable number of participants with psychosis-related personal or family histories received psilocybin. Of 69 people reporting a history of psychosis, 42 were administered psilocybin. There were only two reported events — a headache and a difficult emotional experience — neither involving psychosis. This does not mean the risk is zero, but the data provide no evidence that regulated psilocybin services triggers psychotic episodes.

Suicidality — pre-existing, not triggered

Eleven participants endorsed suicidal thoughts or self-harm at two weeks post-dosing. Seven had pre-dosing data: their mean PHQ-9 was 19.6 before treatment (severe depression) and 16.0 after. These were severely depressed individuals who did not respond to treatment. The data suggest their suicidality predated the psilocybin experience, not that psilocybin caused it. This is the same pattern seen in clinical trials for any antidepressant intervention.

Serotonin syndrome — not observed

A common concern when combining psilocybin with SSRIs or SNRIs is the risk of serotonin syndrome — a potentially dangerous condition caused by excess serotonergic activity. Of the 153 participants taking SSRIs or SNRIs who received psilocybin, there were zero reported cases of serotonin syndrome. Notably, SSRI/SNRI users received a significantly higher mean dose of psilocybin than non-users (34.2 mg vs. 24.1 mg) — meaning the serotonergic load was elevated on both sides of the equation, and still no events were observed. No participants required emergency medical intervention related to serotonergic complications. While this does not eliminate the theoretical risk, the complete absence of events across 153 concurrent-use cases at elevated doses is a meaningful real-world safety signal.

Section vii

Antidepressants don't block the benefit.

One of the most consequential findings for the addressable market. Participants taking SSRIs or SNRIs achieved equivalent therapeutic outcomes.

With antidepressants
153
SSRI/SNRI users
Mean dose
34.2 mg
MEQ-30
94.7
PHQ-9 diff
p = 0.63 (n.s.)
GAD-7 diff
p = 0.72 (n.s.)
Response rate
p = 0.82 (n.s.)
Without antidepressants
785
Non-SSRI/SNRI users
Mean dose
24.1 mg
MEQ-30
104.4
PHQ-9
Equivalent improvement
GAD-7
Equivalent improvement
Response rate
Equivalent
Lower Subjective Experience on Antidepressants · MEQ-30
Undifferentiated Therapeutic Outcomes · PHQ-9 & GAD-7

There was a pharmacological signal: SSRI/SNRI users required a significantly higher mean dose (34.2 mg vs. 24.1 mg) and reported lower subjective experience scores (MEQ-30: 94.7 vs. 104.4). This is consistent with the hypothesized down-regulation of serotonin 5-HT2A receptors from chronic antidepressant use.

But here is what matters for the business: despite the attenuated subjective experience, the therapeutic outcomes were statistically equivalent. PHQ-9 scores dropped 46% for SSRI users vs. 48% for non-users (p = 0.63). GAD-7 scores dropped 47% vs. 51% (p = 0.72). Response rates were indistinguishable (p = 0.82). The chart above makes this visible — the MEQ-30 gap disappears when you look at what actually matters: clinical improvement.

What this means for the addressable market

Roughly one in eight American adults is currently taking an antidepressant. Most clinical trial protocols require participants to taper off — a process that is time-consuming, potentially dangerous, and a major barrier to access. This data shows that tapering may not be necessary for therapeutic benefit. That dramatically expands who can benefit from psilocybin services and lowers the barrier to participation.

Section viii

More is not better.

Therapeutic benefits appear to operate on a threshold, not a dose-dependent continuum. Lower doses work just as well.

Therapeutic Outcome by Dose · PHQ-9 & GAD-7

Improvements in both depression and anxiety scores were not significantly different for participants receiving less than 30 mg versus 30 mg or more of psilocybin. The mean dose administered was 29.1 mg — comparable to the standard 25 mg clinical trial dose.

Subjective experience scores (MEQ-30) plateaued around 25 mg and did not significantly increase with larger doses. The correlation between an individual's MEQ-30 score and their symptom improvement was weak (R² = 0.09–0.10), suggesting that the intensity of the psychedelic experience is not the primary driver of therapeutic benefit.

Why this matters commercially

If therapeutic benefit does not require heroic doses, the implications ripple across the economics of the model. Lower product cost per session. Less intimidating for first-time participants, which improves conversion. Facilitators need not recommend aggressive dosing. The finding also supports the viability of more accessible session formats — potentially shorter administration windows, broader facilitator training, and lower barriers to entry for new participants.

Section ix

The data layer that makes this possible.

This paper does not exist without Althea. The compliance platform that earned us 75% provider share is the same platform that generated the largest real-world evidence dataset in the category.

Althea created the app-based tools that facilitators use to document their compliance with state law. Embedded in that workflow — at the preparatory session, the dosing session, and the integration session — are the validated clinical instruments (PHQ-9, GAD-7, WHO-5, MEQ-30) that produced this dataset.

Participants routinely volunteer their outcomes data to advance the research mission. The 2,752 participants in this paper represent a snapshot. As more participants opt in and new states come online, the evidence base compounds.

Real-time outcomes dashboard

Alongside the paper, Althea will publish a real-time outcomes dashboard — referenced within the paper itself — giving researchers, regulators, and the public live access to anonymized outcome trends. This dashboard will be cited across press coverage of the paper, positioning Althea as the authoritative data source for the category.

The compounding moat
Real-world evidence is a structural advantage, not a one-time asset.

Pharmaceutical companies pursuing FDA-approved psychedelic medicines will need real-world evidence to expand their labels and run post-approval studies. Regulators writing rules for new state programs will need outcome data to justify policy. Insurers evaluating coverage decisions will need evidence of cost-effectiveness. Althea is becoming the default data partner for the category because we run the workflow that generates the evidence.

The through-line

Compliance software earned us the provider network. The provider network gave us the dataset. The dataset produced a paper that validates the category. The paper strengthens the case for regulatory expansion, which grows the market Althea already dominates. This is not a research project. It is a flywheel.

withalthea.com →

Section x

The research team.

Co-authored with faculty at the University of Colorado School of Medicine — the academic institution leading psychedelic policy research.

Scott Thompson, PhD
Scott Thompson, PhD
Professor of Psychiatry
University of Colorado School of Medicine
Director of the Psychedelic Public Policy Partnership. Lead author of the study.
C. Neill Epperson, MD
C. Neill Epperson, MD
Professor of Psychiatry & Chair
University of Colorado School of Medicine
Chair of the Department of Psychiatry, CU School of Medicine. Board certified in Psychiatry. Senior author of the study.
Section xi

Limitations.

Honest accounting of what this study can and cannot tell us. These are typical of early real-world evidence — and the scale of the dataset partially compensates for several of them.

  • Open-label, unblinded design with no placebo control group
  • Self-report outcome measures (PHQ-9, GAD-7, WHO-5) rather than clinician-administered assessments
  • Two-week follow-up endpoint — no long-term durability data
  • Potential dropout and response bias: participants who had positive experiences may be more likely to complete follow-up assessments
  • Limited racial diversity (76% White), limiting generalizability to broader populations
  • Retrospective observational design — cannot establish causation, only association
  • No trauma-specific validated instruments (e.g., PCL-5) for the trauma/PTSD subgroup analysis
Why these limitations don't diminish the signal

Every limitation listed above is standard in early real-world evidence studies. Randomized controlled trials for psilocybin (Goodwin, Raison) also face limitations — including small sample sizes and highly selected populations. What this study offers that trials cannot is ecological validity at scale: 2,752 real people, in real clinical settings, with real comorbidities, making real decisions about their care. Future studies — including longer follow-up and clinician-rated assessments — will build on this foundation.