Substance Spotlight — Psychedelics & Empathogens: ibogaine, noribogaine, and the question the field has not answered yet

Psychedelic-assisted therapy is having the strangest year in its modern history — by which I mean the modern history that runs from MAPS’ first IND through Lykos’ 2024 complete-response letter through the Trump administration’s April 18 executive order “Accelerating Medical Treatments for Serious Mental Illness.” Two weeks ago, DemeRx announced an FDA-accepted IND for noribogaine in alcohol use disorder — the first US clinical trial of an ibogaine derivative. Yesterday, a STAT op-ed by a researcher in the field argued that the EO is broadly the right direction but that the field is not as ready as the political moment suggests.

Both things are true.

Where the science actually is

Compass Pathways cleared its second Phase 3 primary endpoint for COMP360 (psilocybin) in treatment-resistant depression — mean MADRS difference of -3.8 (25 mg vs 1 mg, p<0.001). Combined with the rolling NDA review and the Commissioner’s National Priority Voucher granted in late April, Compass now expects a regulatory decision in late 2026 or early 2027 — roughly 9–12 months ahead of the initial timeline. That is the strongest position any psychedelic developer has held vis-à-vis FDA approval to date.

DemeRx’s noribogaine program (DMX-1001) is at a much earlier stage but is conceptually significant. Phase 1 multiple-ascending-dose data showed noribogaine safe and well-tolerated up to 80 mg daily, with QT effects observed but not clinically relevant — directly addressing the cardiac-safety concern that has historically been the largest barrier to ibogaine reaching FDA-supervised study. A Phase 2 alcohol-use-disorder study is targeted for 2027.

Lykos Therapeutics, by contrast, reorganized last fall after FDA’s complete-response letter on its MDMA-assisted therapy application for PTSD, with workforce reduced by roughly 75%. The unresolved issues identified in that decision — functional unblinding, unstandardized therapeutic protocols, and durability of effect — have not gone away. They are the same questions noribogaine’s Phase 2 design will have to answer if it advances.

What the executive order actually does

The April 18 EO did three concrete things: it directed FDA to fast-track psychedelic candidates for serious mental illness; it committed approximately $50 million for ibogaine studies (largely earmarked for veterans); and it preceded the issuance of three Commissioner’s National Priority Vouchers, including the one Compass received. The EO did not change scheduling, did not change reimbursement, and did not change the therapeutic protocols that determine whether any of these treatments can actually be delivered in a safe and equitable way at scale.

The STAT op-ed’s caution lands here. A regulatory pathway that fast-tracks approval without parallel investment in supervised-dosing infrastructure, therapist training, post-approval surveillance, and equitable access creates exactly the kind of gap that drives unsupervised “underground” use — the population most at risk for the cardiac and psychological adverse events that Lykos and DemeRx have spent years trying to characterize.

Where the field disagrees

There is a meaningful split between researchers who believe the political tailwind is being used responsibly (Compass-style: rolling submission, Phase 3 evidence, REMS in place) and those who worry that the same tailwind is encouraging right-to-try expansions and therapy-tourism flows that will outpace the safety infrastructure. The STAT op-ed names this directly. Both camps want regulated, evidence-based access; they disagree on the speed and the sequencing.

The other split is on indication strategy. Psilocybin for TRD is the most mature program and the most likely to be the first FDA-approved psychedelic-assisted therapy. Methylone for PTSD is moving. Noribogaine for AUD is conceptually exciting but Phase 1. MDMA for PTSD is, for now, on hold. Anyone reading this in early recovery from alcohol use disorder should know: the noribogaine pathway is real, but it is at least three years from any regulated availability, and the cardiac-safety bar remains substantial.

Psilocybin for TRD is the most mature program and the most likely to be the first FDA-approved psychedelic-assisted therapy.

Why this matters for people in recovery

For families and individuals reading about Compass, DemeRx, or the executive order in the news, the practical answer in May 2026 is: there is no FDA-approved psychedelic-assisted therapy for any addiction indication today. Spravato (esketamine, a dissociative — different mechanism) remains the only FDA-approved psychiatric medication in this broad pharmacological neighborhood, and it is approved for treatment-resistant depression rather than for substance-use disorders. Ketamine clinics offer off-label care of varying quality. If you are reading this from inside a substance-use disorder, the most evidence-based treatments remain the ones already on the shelf — buprenorphine, methadone, naltrexone, acamprosate, contingency management, cognitive behavioral therapy — and they are accessible now.

What the field is doing right now is building a credible pathway for a future generation of treatments. That work matters. It is not a substitute for treatment that exists today.

If you or someone you love is struggling, please call 988 (Suicide & Crisis Lifeline) or SAMHSA’s National Helpline at 1-800-662-HELP. Both are free and confidential.