An Introduction:

Two positive Phase 3 trials. An FDA submission on deck for Q4. And the most interesting thing about the biggest psilocybin story of the year is how quiet it was.

Compass Pathways dropped data on February 17 that, in any other therapeutic area, would’ve been front-page news. Two successful late-stage trials for treatment-resistant depression. The first classic psychedelic with a realistic shot at FDA approval. And most people I talk to had no idea it happened. 🤷

That gap between what’s actually happening in psilocybin and what most people know about it is why this newsletter exists.

I built The Magic around three running trackers that nobody else is maintaining like this:

• where it’s legal

• what’s in the clinical pipeline

• where the money is going.

You’ll be the most informed person in any room when psilocybin comes up if you read this newsletter: every two weeks, under 10 minutes.

As this is issue 01, it’s a bit longer than future issues will be.

Stay with me here…

Heroic Doses: The Main Stories

Compass Pathways now has TWO positive Phase 3 trials and is heading to the FDA

COMP360 (synthetic psilocybin) hit its primary endpoint in the second pivotal trial on Feb 17. The numbers: -3.8 point MADRS reduction vs. control, p<0.001, across 581 patients. Combined with the first trial (COMP005, -3.6 points, 258 patients), this is the strongest clinical dataset any classic psychedelic has ever produced. The company wants a rolling NDA submission by Q4 2026. If the FDA plays ball, approval could come in early 2027. The effect sizes aren’t miraculous, and the stock settled about 34% higher after an initial 50% spike, which tells you the market sees this as real but not a slam dunk. It IS real. This is the closest any psychedelic has gotten to becoming an actual prescription medicine.

Hype Check: Real deal. Not a miracle drug, but the data is solid and the regulatory path is clear.

Trump admin quietly killed the FDA fast-track for psilocybin

In October 2025, FDA Commissioner Makary put COMP360 on the shortlist for a National Priority Voucher, which would’ve sped up review significantly. HHS and White House officials vetoed it. The psilocybin candidate was the only drug removed from the final list of 10. So the same administration running the “Make America Healthy Again” playbook is blocking the fastest path to an approved psychedelic medicine. Pick a lane.

Hype Check: Bad news, but not fatal. The NDA path still exists without the voucher. It just takes longer. Watch what the FDA actually does, not what the White House says.

A short-acting psilocybin analog just got Breakthrough Therapy for postpartum depression

Reunion Neuroscience’s luvesilocin (RE104) got the FDA’s Breakthrough Therapy Designation on Feb 23 for postpartum depression. This flew under the radar but it matters. The drug is a psilocybin analog that works in 2-3 hours instead of 4-6+, which makes the monitoring and logistics way more practical. Phase 2 showed 70% remission at Day 7 AND Day 28. Postpartum depression is a new indication for the psilocybin family, and the shorter duration could be the thing that makes psychedelic-assisted therapy actually scalable.

Hype Check: Quietly huge. The short-acting angle solves one of the biggest practical barriers to psychedelic therapy. Phase 3 sometime this year.

Nearly 1 in 4 Americans now support legal psilocybin

RAND’s 2025 Psychedelics Survey (10,000+ adults) found 23% favor legal psilocybin. For context: that’s roughly where cannabis support sat in the mid-1990s, right before the first wave of state medical programs changed everything. Among current users, support jumps to 62%. Most supporters want supervised medical settings, not recreational sales. The policy translation: expect more state-level action, and expect it to be medical-model.

Hype Check: The trend line matters more than the number. This is the “early majority” signal that tells legislators they won’t lose their seats over this.

The Psilo Situation

The Psilo Situation is updated every issue. Below is the baseline. Changes from previous state are marked. If nothing moved, I’ll tell you.

A. Legalization Tracker

Running Totals (as of Mar 4, 2026)

• States with legal therapeutic/supervised access: 3 (Oregon, Colorado, New Mexico)

• States with pilot programs: 2 (New Jersey NEW, Washington)

• States with rescheduling trigger laws passed or advancing: 6 (Arizona, North Dakota, Nebraska, South Dakota

  • ADVANCING, West Virginia

  • NEW, Colorado EXPANDED)

• Cities with decriminalization: 15+

• Countries with some form of legal access: 7+ (Canada, Australia, Jamaica, Netherlands, Denmark, Germany, Czech Republic NEW)

• Active state-level bills in 2026 session: 40+ across 15+ states

What moved since the baselines were set in early Jan:

NEW: West Virginia SB 906 passed Senate 31-2 (Feb 27). Medical prescription trigger law for crystalline psilocybin upon FDA approval. Heads to House. Strong bipartisan vote in a deep red state.

ADVANCING: South Dakota HB 1099 passed Senate (Mar 2), heads to governor. Trigger law rescheduling FDA-approved psilocybin to Schedule IV. Doctor-and-counselor-supervised use. Another red state preparing infrastructure.

NEW: New Hampshire House passed therapeutic psilocybin bill (Feb 16). Regulated access under DHHS for qualifying conditions. Bipartisan. Heads to Senate.

NEW: Missouri HB 1717/1643 advanced through House committee (Feb 25-26). Two tracks: veteran-focused (HB 1717) and broader adult access (HB 1643) with right-to-try provisions. Up to 150mg/year supervised use for PTSD, MDD, substance use disorders, terminal illness.

EXPANDED: Colorado SB 26-031 passed Senate 29-2 (Feb 24). Goes beyond psilocybin: auto-clears ANY Schedule I drug upon FDA+DEA approval. No separate legislation needed. They’re building the freeway before the cars show up.

NEW: Oregon HB 4040 passed House Health Committee 8-0 (Feb 17). Expands who can provide psilocybin therapy, allows out-of-state facilitator training. Cleanup bill for the nation’s first regulated program.

NEW: Hawaii Senate approved psychedelics task force bill (Feb 23). Two-year study period for psilocybin, MDMA access pathways.

NEW: Alaska task force released recommendations (Feb 27). Prepare therapist training and culturally competent care for eventual FDA approval.

NEW: Maryland task force extended through 2027 (Feb 17). Phased legalization starting with psilocybin.

NEW: Illinois SB 2772 introduces psilocybin advisory board for regulated therapeutic access.

NEW: Rhode Island H7756 permits adult home cultivation of psilocybin (contingent on FDA), referred to Judiciary Committee (Feb 12).

NEW: Czech Republic approved supervised medical psilocybin in psychiatric hospitals, effective Jan 2026. First EU-wide supervised framework.

NEW: Italy administered first psilocybin treatment for treatment-resistant depression at Chieti University Hospital (Feb 6). Authorized by AIFA.

NO MOVEMENT: Iowa HF 978 (most advanced 2026 bill, ALEC model), Connecticut HB 7065 (pending Senate), Idaho HJR 4 (restrictive ballot measure), New York (multiple active bills, no committee movement).

The pattern: Red and blue states alike are building “trigger law” infrastructure. They’re not debating whether psilocybin should be legal. They’re preparing for the moment the FDA says yes. South Dakota, West Virginia, Colorado, Arizona, North Dakota, Nebraska. That’s the story.

B. Medical Tracker

PHASE 3 (closest to potential FDA approval)

Compass Pathways, COMP360 for Treatment-Resistant Depression — UPDATED

• Two positive Phase 3 trials (COMP005 and COMP006). Both hit primary endpoints.

• COMP006 (Feb 17): -3.8 MADRS, p<0.001, n=581. 39% achieved clinically meaningful response.

• COMP005 (June 2025): -3.6 MADRS, p<0.001, n=258.

• Rolling NDA submission targeted Q4 2026. 26-week COMP006 durability data expected early Q3 2026.

• NEW: COMP202 for PTSD — FDA accepted IND (Jan 7). Phase 2b/3 trial cleared, multicenter, repeat dosing. Expanding beyond depression.

• REGULATORY HEADWIND: Trump admin removed COMP360 from FDA National Priority Voucher list (Feb 4). NDA path still intact but slower.

• Stock: surged ~50% on COMP006 data, settled ~34% higher.

• STATUS: On track for potential first-ever classic psychedelic NDA filing. This is the most important pipeline item in the space.

Helus Pharma (formerly Cybin), HLP003 for Major Depressive Disorder

• Phase 3 results expected Q4 2026.

• UPDATED: SPL026 Phase 2a data published in Nature Medicine (Feb 17). Primary endpoint met: -10.75 MADRS Week 1 (p=0.002), 35% response rate vs. 12% placebo.

• HLP004 (deuterated DMT for GAD): Phase 2 results expected Q1 2026, still pending as of Feb 13 earnings call.

NEW ENTRY: Reunion Neuroscience, RE104 (luvesilocin) for Postpartum Depression

• FDA Breakthrough Therapy Designation granted Feb 23, 2026.

• Short-acting psilocybin analog/prodrug (~2-3 hour duration vs. 4-6+).

• Phase 2 RECONNECT data: 70% remission at Day 7 and Day 28. Rapid onset from Day 1.

• Phase 3 planned for 2026.

• Also running: REKINDLE (adjustment disorder, enrolling), RECLAIM (GAD, planned Q1 2026).

• This is a new entrant to watch. The short duration could be a practical game-changer.

PHASE 2-3 / COMPETITORS

Definium Therapeutics (formerly MindMed), DT120 (LSD) for GAD/MDD — UPDATED

• Rebranded from MindMed to Definium Jan 12, 2026.

• Three Phase 3 readouts expected 2026: Voyage (GAD, Q2), Emerge (MDD, mid-year), Panorama (TRD, H2).

• NOTE: LSD-based, not psilocybin, but directly competing for the same patients.

GH Research, GH001 (5-MeO-DMT) for Treatment-Resistant Depression — UPDATED

• Clinical hold lifted Jan 5, 2026. Phase 3 cleared for global launch in 2026.

• Phase 2b results: -15.5 MADRS placebo-adjusted, 57.5% remission Day 8, 73% at 6 months.

• DMT-based, not psilocybin, but targeting the same TRD indication as Compass.

AtaiBeckley (formerly atai), BPL-003 for Treatment-Resistant Depression — UPDATED

• Successful End-of-Phase 2 meeting with FDA (Mar 3, 2026). Advancing toward Phase 3.

• Also: EMP-01 (R-MDMA for social anxiety) Phase 2a topline results Feb 26. Met safety/tolerability. 49% responders vs. 15% placebo. Not psilocybin but same portfolio.

NOTABLE RESEARCH

OHSU real-world psilocybin study — NEW

• First-ever NIDA grant ($3.3M, 5 years) to study supervised psilocybin in community settings, not clinical trials. 1,600+ Oregon participants. This is the data that other states need to see before they move.

Dartmouth non-hallucinogenic receptor discovery — NEW

• Identified 5-HT1BR as a receptor that delivers psilocybin’s antidepressant effects without hallucinations. Could lead to non-psychedelic versions of the drug. Early but significant.

KEY UPCOMING DATES

• Helus HLP004 Phase 2 GAD results: Imminent (was expected Q1 2026)

• Definium DT120 Voyage Phase 3 GAD results: Q2 2026

• Compass COMP006 26-week durability data: Early Q3 2026

• Compass NDA submission target: Q4 2026

• Helus HLP003 Phase 3 MDD results: Q4 2026

C. Investment Tracker

2026 YTD Capital Activity

I’ll be honest: Q1 2026 is quiet. No major private funding rounds, no acquisitions, no IPOs in the psilocybin space so far this year.

That’s not necessarily bad news. Here’s what I think is happening: capital is sitting on the sidelines waiting for Compass to file the NDA. An FDA filing changes the entire risk calculus for investors. Until that happens, the smart money is watching, not deploying.

What DID move:

• Government research funding: $3.3M NIDA grant to OHSU (Feb), $6M New Jersey pilot allocation (Jan), $100M HHS behavioral health research fund with specific psychedelics call

• Market activity: Compass stock surged ~50% on COMP006 results (Feb 17), settled ~34% higher. That’s real institutional money reacting to real clinical data.

Context (2025 recap for the baseline):

• Total 2025 capital into psychedelic companies: ~$1.2 billion (up ~50% from 2024, 4x 2023)

• Q4 2025 saw financing activity not seen since the 2021 boom

• ~90% of 2025 dollars went to publicly traded drug developers. Private investment remains thin.

• Biggest 2025 rounds: Definium $259M, Helus $175M, AtaiBeckley $149.5M, Compass $150M, GH Research $150M

The story for Money Map this quarter: The money is waiting on the science. And the science just delivered two positive Phase 3 trials.

Microdose the News

NFL veterans are heading to Denver psilocybin clinics for brain injuries

Former players including Jim McMahon, Kyle Turley, Derek Anderson, and Brian Cushing have been doing supervised psilocybin sessions for CTE and concussion-related depression, alcohol issues, and suicidal thoughts. Conventional treatments failed. The brain-rewiring potential of psilocybin, the same neuroplasticity that makes it work for depression, might help with traumatic brain injury repair. No formal trials yet but this is going to become a much bigger story.

Whole mushrooms might work better than isolated psilocybin, and now we have the math

A computational study in Scientific Reports analyzed 15 compounds from psilocybin mushrooms and found that whole extracts interact with 44 brain proteins in ways isolated psilocybin can’t match. The “entourage effect” has been talked about anecdotally for years. Now there’s molecular docking data to back it up. This matters because every company pursuing FDA approval is using synthetic or isolated compounds. Full Spectrum for the win.

Bryan Johnson did a quantified psilocybin experiment and claims longevity benefits

The “don’t die” guy took 25mg of psilocybin and measured everything before and after. Reports a 42% cortisol drop, microbiome shifts toward reduced stress markers, and what he describes as “neural remapping.” It’s n=1 and self-reported, so take it accordingly. But when the guy who spends $2M/year optimizing his biology says psilocybin moved his metrics, people in the longevity space pay attention. [Source: Bryan Johnson/various, Jan-Feb 2026]

10 million Americans microdosed psychedelics last year

RAND’s nationally representative survey found roughly 10 million adults microdosed psilocybin, LSD, or MDMA in 2025. Among past-year psilocybin users, about two-thirds microdosed at least once. Nearly half of all reported psilocybin-use days were microdoses. The practice has gone fully mainstream, well ahead of any regulatory framework to support it. [Source: RAND Corporation, Jan 21]

An Ending

That’s issue 01 of The Magic.

I keep coming back to the same thought: the gap between what’s happening in psilocybin right now and what most people know about it is enormous. Two positive Phase 3 trials. States building trigger laws in anticipation of FDA approval. 10 million people already microdosing. The infrastructure is being built in real time and most people have no idea.

The Psilo Situation is going to grow and get sharper every issue. If I missed something LMK!

Please take a moment to respond, I want to hear from you!

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Until next time,

Sean