An Introduction

The most interesting thing about psilocybin right now isn’t the depression story. Everyone’s watching Compass walk toward the FDA. That’s the obvious play…

The real story is that psilocybin keeps showing up in places nobody expected it. OCD. Smoking cessation. Lyme disease. Three new studies dropped in the last two weeks targeting three completely unrelated conditions, and all three worked. Not “showed promise in a petri dish” worked. Worked in actual humans with actual treatment-resistant conditions.

Read the stories below to learn about how

• one dose fixed OCD symptoms 20 years of meds couldn’t

• one session allowed smokers to quit at 6x the rate of nicotine patches

• two doses cut lime disease symptom burden by 40%

Plus the latest tracking for legalization/decriminalization, medical, and investments into the space.

This is issue 02 of The Magic.

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Heroic Doses: The Main Stories

One dose of psilocybin basically fixed treatment-resistant OCD

Yale ran the first real placebo-controlled trial of psilocybin for OCD, and the results are absurd. 28 adults who’d been living with OCD for an average of 20 years and failed at least two prior treatments got a single dose.

Symptom scores dropped 9.76 points within 48 hours (placebo group didn’t move). By one week, about 70% hit clinically meaningful improvement. The effects held at 12 weeks.

The lead researcher called the speed and durability “remarkable” and “better and faster than other medications for OCD.” One participant had temporary suicidal ideation that resolved under monitoring, so it’s not without risk. But for a condition this stubborn, these numbers are wild. (JAMA)

Hype Check: If this replicates, it’s a game-changer for the 2-3 million Americans with OCD. One dose, 12 weeks of relief. Nothing else does that, nothing.

Psilocybin crushed nicotine patches in a head-to-head trial

Johns Hopkins put 82 smokers through a randomized trial: psilocybin plus cognitive behavioral therapy versus nicotine patches. Six months later, 17 psilocybin participants had quit versus 4 on patches. That’s more than six times the odds of staying cigarette-free.

Published in JAMA Network Open on March 10, researchers point to neuroplasticity and what they describe as a “new sense of agency” in participants. It’s been 20 years since a genuinely new smoking cessation mechanism emerged. This might be it. (NPR)

Hype Check: JAMA-published, head-to-head against the standard of care, and the effect size is genuinely enormous. Hard to ignore this one.

Decriminalization actually increased psilocybin use, and now we have the math

A new JAMA study used causal-inference methods to measure whether decriminalization in Oregon and Colorado actually changed behavior.

It did.

Oregon’s 2020 measure led to a 2.1 percentage-point jump in 12-month use, roughly 70,000 to 90,000 additional users per year.

Colorado’s 2022 measure: 1.8 points, roughly 85,000 to 110,000 extra users.

Most of the increase happened outside regulated programs. This is the first study to move past correlation and establish an actual causal link between policy change and usage rates. (JAMA)

Hype Check: Important data for both sides of the debate. Legalization advocates get proof that policy works. Critics get ammunition that unregulated use is growing faster than the clinical infrastructure. Both are right.

The Psilo Situation

The Psilo Situation is updated every issue. Changes from issue 01 are marked. If nothing moved, I’ll tell you.

A. Legalization Tracker

Running Totals (as of Mar 19, 2026)

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

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

• States with trigger laws enacted: 2 (South Dakota SIGNED, Arizona)

• States with trigger laws advancing: 6 (West Virginia, Colorado, North Dakota, Nebraska, Minnesota NEW, Utah NEW)

• Cities with decriminalization: 15+

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

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

What moved since issue 01:

SIGNED INTO LAW: South Dakota HB 1099 (Mar 10). Governor Rhoden signed the trigger law. Crystalline polymorph psilocybin becomes legal for mental health therapy the moment the FDA approves it and the DEA reschedules. House vote was 58-7, Senate 21-12. Veterans’ groups pushed hard for this one. Another deep red state with infrastructure ready to go on day one of federal approval. (SDPB)

NEW: Minnesota HF2906 cleared two House committees on bipartisan voice votes (Mar 9-14) and is headed to the floor. This one’s different from the trigger law model. It would directly launch a supervised therapeutic pilot capped at 1,000 patients in the first three years, reclassify psilocybin from Schedule I to IV, and license 20-50 facilitators. Qualifying conditions: depression, PTSD, anxiety, substance use disorder, chronic pain. Adults 21+, three-phase sessions (prep, dosing, integration), oversight under the Office of Cannabis Management. No recreational access. A US Army veteran testified it was “life-saving.” Directly implements the state’s 2025 Psychedelic Medicine Task Force recommendations. (Marijuana Moment)

ADVANCING: Iowa HF 978 moved through Senate subcommittee (Mar 18-19). Still the most advanced 2026 bill with the ALEC model framework. It was listed as “no movement” in issue 01. It’s moving now. (Iowa Capital Dispatch)

ADVANCING: Hawaii SB 3199 cleared Senate Ways & Means 12-0 (Mar 17). The task force we tracked in issue 01 is now a specific bill creating a two-year Mental Health Emerging Therapies Task Force with DOH, the AG’s office, and UH med school. Focused on veterans, first responders, and suicide prevention.

NEW: Utah advanced a bill funding psychedelic clinical trials for veterans’ mental health. Psilocybin, MDMA, and DMT for PTSD. Trials targeted to start by 2027.

NEW: Massachusetts has multiple bills advancing: H.4050 (adult-use framework), S.1400/H.4200 (pilot program), and veteran-specific measures. Worth watching.

DIED: New Hampshire HB 1796 (Mar 13). The House Health committee declared it “inexpedient to legislate,” citing DHHS staffing costs and early-stage evidence. A minority report pushed back, calling it “evidence-based” harm reduction. Note: a separate bipartisan psilocybin therapy bill did advance and heads to Finance this month. New Hampshire isn’t done. (Marijuana Moment)

FEDERAL: DEA finalized increased 2026 production quotas for psilocybin research (up to 40,000-50,000 grams, plus 80,000 grams psilocin). A big jump from 2025 levels. More raw material for more clinical trials. (Marijuana Moment)

NO MOVEMENT: West Virginia SB 906 (still needs House action), Colorado SB 26-031 (passed Senate, awaiting House), Connecticut HB 7065, Oregon HB 4040, Illinois SB 2772, Rhode Island H7756, New York (multiple bills, no committee movement), Idaho HJR 4, Alaska task force, Maryland task force.

The pattern: Issue 01 was about states building trigger laws. Issue 02 is about those trigger laws getting signed and direct therapeutic programs advancing. South Dakota went from “heading to the governor” to law in eight days. Minnesota is building a full therapeutic program from scratch. The infrastructure buildout is accelerating.

B. Medical Tracker

PHASE 3 (closest to potential FDA approval)

Compass Pathways, COMP360 for Treatment-Resistant Depression

• No new data since issue 01. Two positive Phase 3 trials stand. Rolling NDA submission targeted Q4 2026.

• 26-week COMP006 durability data still expected early Q3 2026.

• COMP202 for PTSD: Phase 2b/3 trial underway.

• Regulatory headwind from Trump admin voucher veto remains.

• STATUS: Unchanged. Still the most important pipeline item in the space.

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

• Phase 3 results still expected Q4 2026.

• NEW: HLP004 Phase 2 GAD results released (Mar 5). The 20mg dose hit: -10.4 point HAM-A reduction, 59% response rate, 32% remission at 6 weeks. On paper, not bad for generalized anxiety disorder. The market disagreed. Stock crashed 33% on the day. The read: investors wanted remission numbers closer to the psilocybin benchmarks being set by Compass, and 32% didn’t clear that bar. HLP004 is a deuterated DMT compound, not psilocybin, so the comparison isn’t perfectly clean. But the market reaction tells you where expectations sit right now. (GlobeNewsWire)

Reunion Neuroscience, RE104 (luvesilocin) for Postpartum Depression

• No movement since issue 01. Breakthrough Therapy Designation stands. Phase 3 planned for 2026.

• Also running: REKINDLE (adjustment disorder), RECLAIM (GAD).

PHASE 2-3 / COMPETITORS

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

• Timeline shift: Voyage (GAD) Phase 3 data now expected early Q3 2026 (was Q2). Pushed back slightly.

• Emerge (MDD) and Panorama (TRD) readouts still expected mid-year and H2 respectively.

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

• No change since issue 01. Phase 3 prep continues after Jan clinical hold lift.

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

• Phase 2a data published in Journal of Psychopharmacology (Mar 17). Full peer-reviewed results now public. (GlobeNewsWire)

• Phase 3 on track for Q2 2026 initiation. Moving from FDA meeting to trial launch.

NOTABLE RESEARCH (new this issue)

Yale OCD trial — First placebo-controlled RCT for psilocybin in OCD. Single dose, rapid response, 12-week durability. This opens an entirely new indication. (See Heroic Doses for full details.)

JHU smoking cessation trial — Psilocybin 6x more effective than patches. JAMA Network Open. First major new cessation mechanism in 20 years. (See Heroic Doses.)

JHU Lyme disease pilot — Two psilocybin doses reduced post-treatment Lyme symptoms by ~40%. Improvements in pain, fatigue, sleep, and mood lasting six months. Preliminary but could extend to long COVID and chronic fatigue. (See Microdose the News.)

Non-hallucinogenic psilocin derivatives — Fluorinated carbamate analogs of psilocin that retain antidepressant activity but minimize psychedelic effects. Lead compound “4e” showed stable brain penetration with significantly reduced hallucinogenic markers in mice. Journal of Medicinal Chemistry, Mar 8. (See Microdose the News.)

Myelin repair from psychedelics — Psilocybin and MDMA shown to promote myelin remodeling in PTSD brains, potentially connecting short-term psychedelic effects with long-term structural recovery. Biological Psychiatry, Mar 4. (See Microdose the News.)

RMPDS real-world research grant — Rocky Mountain Poison & Drug Safety awarded a NIDA grant to expand the National Survey Investigating Hallucinogenic Trends. Large-scale safety and risk data as states roll out programs. (Denver Health)

KEY UPCOMING DATES

• Definium DT120 Voyage Phase 3 GAD results: Early Q3 2026 (pushed from Q2)

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

• AtaiBeckley BPL-003 Phase 3 initiation: Q2 2026

• Compass NDA submission target: Q4 2026

• Helus HLP003 Phase 3 MDD results: Q4 2026

C. Investment Tracker

2026 YTD Capital Activity

Still quiet. Q1 2026 continues with no major private funding rounds, acquisitions, or IPOs in the psilocybin space. The pattern from issue 01 holds: capital is waiting for Compass to file the NDA.

What DID move:

The biggest money story this cycle isn’t a deal, but a crash. Helus Pharma stock dropped 33% on March 5 after releasing HLP004 Phase 2 results. The data wasn’t terrible (59% response, 32% remission) but the market wanted more. That single-day move tells you two things: investor expectations in this space have been set by Compass’s Phase 3 numbers, and anything that doesn’t match that bar gets punished. Hard.

Government research funding continues to be the main capital flow:

• RMPDS awarded NIDA grant for large-scale real-world psychedelic safety research (Mar 17)

• DEA production quota increases signal more federal research dollars coming

• OHSU $3.3M and New Jersey $6M from issue 01 still active

Stock Watch:

• Compass (CMPS): ~$6.06 (Mar 17). Settled from post-Phase 3 highs. 52-week range: $2.27-$8.89.

• Helus (HELP): ~$7.86. Down 33% on HLP004 data, partially recovered.

• Definium (DFTX): ~$18.66. 52-week range: $4.70-$19.62. Holding up best in the space.

• AtaiBeckley (ATAI): ~$3.69. 52-week range: $1.15-$6.75.

• GH Research (GHRS): ~$15.50. Stable after clinical hold lift recovery.

The story for the Investment Tracker this quarter: The market is separating winners from also-rans. Compass data lifts the whole sector temporarily, but individual catalysts (like Helus’s HLP004 miss) get judged against that benchmark. Capital is still on the sidelines for private deals. The NDA filing, probably Q4, is the next big unlock.

Microdose the News

Scientists built psilocybin that works without the trip

Researchers created five modified versions of psilocin (psilocybin’s active form in the body) that keep the antidepressant effects but drastically reduce the psychedelic experience. The lead compound, boringly named “4e,” penetrated the brain efficiently and showed significantly fewer hallucinogenic markers in mouse studies. Published in the Journal of Medicinal Chemistry on March 8.

Think about what that means: separate the therapeutic benefit from the 6-hour trip and you remove the biggest practical barrier to scaling psychedelic medicine. No trip sitters. No special clinics. Maybe just a prescription and a normal Tuesday watching Bob’s Burgers reruns after work. (ScienceDaily)

Psychedelics might actually repair brain wiring damaged by trauma

New research in Biological Psychiatry found that psilocybin and MDMA promote myelin remodeling in the brain. Myelin is the insulation around your nerve fibers. Trauma degrades it.

The finding suggests psychedelics aren’t just giving people a temporary reset. They might be fixing structural damage. If this holds up, it bridges the gap between “I felt better after the session” and “my brain is literally rewired.”

Early, but the kind of early that matters. (EurekAlert)

Two psilocybin sessions cut Lyme disease symptoms by 40%

A Johns Hopkins pilot study gave two psilocybin doses to patients with post-treatment Lyme disease, the kind where the infection is gone but the fatigue, pain, brain fog, and depression stick around. Symptom burden dropped about 40%, with improvements lasting six months. There are currently zero approved treatments for this condition, and millions of people have it.

Researchers think the same approach could work for long COVID and chronic fatigue syndrome. Small study, but it’s targeting a massive unmet need. (Johns Hopkins)

An Ending

Issue 02 of The Magic is in the books. Two weeks, and the landscape already looks different.

Thanks for subscribing to this little newsletter full of gigantic stories. Amazing things keep being discover. Tune in and I’ll keep you in the loop. Next issue drops in two weeks.

Until next time,

Sean