evidence·approval status checked 2026-09-29 · pipeline rows verified 2026-09-29

Psychedelic therapy FDA status: which drugs are approved, and where the rest stand

As of september 29, 2026, exactly one psychedelic-adjacent drug is FDA-approved for a psychiatric condition: esketamine (Spravato). psilocybin (COMP360) is in rolling NDA review with the final module expected in Q4 2026. MDMA-assisted therapy was rejected in august 2024; a resubmission has been reported, but no FDA record confirms one. LSD (DT120) has three positive phase 3 toplines reported in SEC filings and no NDA yet. everything else is phase 3 or earlier. the table below is the full picture, row by row, with primary sources and dates.

The short answer (checked 2026-09-29)

  • FDA-approved: esketamine (Spravato) only, for treatment-resistant depression and for depressive symptoms in MDD with acute suicidal ideation or behavior, given in certified settings under a REMS [17][18].
  • Not approved: psilocybin, MDMA, LSD, DMT and ibogaine. none is on FDA's 2026 novel drug approvals list [33]. psilocybin, MDMA, LSD and DMT remain federal Schedule I.
  • Closest to a decision: psilocybin (COMP360, rolling submission, final module expected Q4 2026) [24]. MDMA was rejected in 2024 [7]; a resubmission has been reported, but no FDA record confirms one.
  • Off-label, not approved for psychiatry: racemic ketamine, approved only as an anesthetic [4].

related trackers: what each psychiatric medication is actually FDA-approved for · FDA status of AI and digital mental health tools

The status table

last verified: september 29, 2026, including approval status against FDA's 2026 novel drug approvals list [33]. we update this page monthly, or sooner when a milestone lands — the next scheduled updates follow Compass's final NDA module and the VLS-01 phase 2b topline, both guided to Q4 2026. numbered references link to the primary sources at the bottom of the page: FDA records, ClinicalTrials.gov, SEC filings, peer-reviewed papers and government records. we do not cite press releases, trade press or news.

substanceUS regulatory status (september 2026)sponsor(s)breakthrough therapynext milestonesources
esketamine (Spravato)APPROVED — Mar 5, 2019 for treatment-resistant depression (with an oral antidepressant); Jul 31, 2020 for depressive symptoms in MDD with acute suicidal ideation or behavior (with an oral antidepressant; NDA 211243/S-004); Jan 17, 2025 first monotherapy approval for TRD (NDA 211243/S-016, Priority Review). REMS (certified setting, at least 2 hours of monitoring) still in force and in the current label; modified four times in 2025 (Mar 24, May 15, Jul 31, Oct 9) and three times in 2026, most recently Jun 24.Johnson & Johnson (Janssen)yes, TRD and MDSI — FDA lists the 2019, 2020 and 2025 approvals as breakthrough-therapy approvals (FDA does not publish the designation dates)post-marketing commitments; continued REMS[1] [2] [17] [18] [22] [3]
ketamine (racemic)approved as an anesthetic only — all psychiatric use is off-label. FDA warning on compounded ketamine (including telehealth/at-home oral) issued Oct 10, 2023.none (generic)nonenone registered for a depression indication[4]
psilocybin (COMP360)phase 3 primary endpoints met → rolling NDA underway. COMP005 (single 25 mg dose vs placebo): −3.6 MADRS points at week 6, reported Jun 2025; COMP006 (two 25 mg doses vs 1 mg): −3.8 points at week 6, reported Feb 17, 2026; 26-week COMP006 data reported Jul 7, 2026. All company-reported in SEC filings — not peer-reviewed, and no results posted to either registry record. FDA granted rolling review and, per the company, issued a National Priority Voucher in April 2026. Final NDA submission on track for Q4 2026; launch targeted H1 2027 pending approval and DEA rescheduling.Compass Pathways; Usona Institute (separate phase 3, uAspire)Compass 2018 (TRD); Usona: not verified in a primary recordfinal NDA module Q4 2026; Usona uAspire results (238 enrolled, primary completion Jan 5, 2026 per its registry record; none posted)[23] [5] [6] [24] [25]
MDMA (midomafetamine)rejected — FDA complete response letter dated Aug 8, 2024 (NDA 215455). FDA advisory committee voted against on Jun 4, 2024 (9-2 that effectiveness was not shown; 10-1 that benefits did not outweigh risks). A resubmission in Aug 2026 has been reported, but no FDA record or other primary document confirms it; Resilient has registered a phase 1 midomafetamine study with cardiac ECG assessments (started Apr 23, 2026); FDA’s letter had recommended a dedicated cardiac study. The proposed brand name Rysanso is a documented mark: a Canadian trademark registered to Resilient (Sep 7, 2026).Resilient Pharmaceuticals (formerly Lykos Therapeutics / MAPS PBC; name change effective Jul 28, 2025)Aug 15, 2017 (PTSD)an FDA-confirmed resubmission; phase 1 study NCT07584720 (primary completion estimated Jul 2026, no results posted)[7] [20] [21] [8] [19]
LSD (MM120 → DT120)phase 3, three positive toplines — company-reported in SEC filings, not yet peer-reviewed, no registry results posted. Emerge (MDD) Jun 22, 2026: −8.1 MADRS points vs placebo at week 6; Voyage (GAD) Aug 12, 2026: −5.4 HAM-A points at week 12; Panorama (GAD) Sep 14, 2026: −5.1 HAM-A points at week 12. Phase 2b published in JAMA Oct 2025. MindMed renamed Definium Therapeutics Jan 9, 2026.Definium Therapeutics (formerly MindMed)Mar 2024 (GAD); Sep 2026 (MDD)pre-NDA meeting Q4 2026; NDA filing anticipated H1 2027 (company guidance)[9] [10] [11] [26] [27] [28]
ayahuasca / DMT analogsphase 2–3 (analogs); no FDA program for ayahuasca itself — US access is via religious-use exemptions only. IV DMT SPL026 phase 2a published in Nature Medicine Feb 2026 (−7.35 MADRS points vs placebo at 2 weeks, n=34); its sponsor now lists it as a completed study supporting a deuterated-DMT successor, HLP004. BPL-003 (intranasal 5-MeO-DMT) phase 2b met its primary endpoint (registry results: 12 mg vs 0.3 mg, −5.3 MADRS points at day 29) → phase 3 initiated Q2 2026. VLS-01 (buccal DMT) phase 2b last patient dosed. Eli Lilly acquired AtaiBeckley on Sep 11, 2026.Eli Lilly (BPL-003, VLS-01, via AtaiBeckley); Cybin, trading as Helus Pharma (SPL026 → HLP004)none verified for DMT/5-MeO-DMTVLS-01 phase 2b topline Q4 2026; BPL-003 phase 3 (ReConnection-1 and -2)[12] [13] [29] [14] [30]
ibogaineno FDA efficacy trials — observational evidence only. Texas SB 2308, signed Jun 11, 2025, set up a state-matched consortium to take ibogaine through FDA trials (opioid use disorder, co-occurring substance use disorder, and other conditions where it shows efficacy); the state budget appropriated $50M for it, contingent on the bill.none active in US clinical trials; Texas consortium formingnonefirst FDA-track IND/trial under the Texas program[15] [31] [32]

Is MDMA therapy FDA-approved?

no. FDA's advisory committee voted on june 4, 2024 — 9-2 that the data did not show effectiveness and 10-1 that benefits did not outweigh risks — with members citing functional unblinding, expectation bias and selection bias [20]. FDA's complete response letter followed, signed august 8, 2024 [7]. it found no substantial evidence of effectiveness and unestablished safety, and gave three reasons: adverse events that participants experienced as "positive" were not collected, and FDA inspections found unreported adverse events; no durability was shown beyond week 18; and about 40% of participants had taken MDMA before, which FDA said risks selection and expectation bias. it recommended a new randomized trial, an independent third-party audit of the original trial records, and a dedicated cardiac (ECG) study [7].

the sponsor — MAPS PBC, then Lykos Therapeutics (the name on FDA's letter), now Resilient Pharmaceuticals (name change effective july 28, 2025 [19]) — is reported to have resubmitted in august 2026. no FDA record, SEC filing or registry entry we can cite confirms that, so we report it as unconfirmed. two things are on the public record. Resilient registered a phase 1 study of midomafetamine with electrocardiographic cardiac-safety assessments, started april 23, 2026 [8]; FDA's letter recommended a dedicated cardiac (ECG) study, and the registry record does not say whether this is meant to be it. and the proposed brand name, Rysanso, is a Canadian trademark registered to Resilient on september 7, 2026 [19] — which documents the name and its owner, not an approval. the efficacy and durability questions FDA raised stay open until FDA acts.

When could psilocybin be approved?

psilocybin (COMP360) is the furthest along. Compass Pathways reported in SEC filings that both phase 3 trials met their primary endpoints — COMP005 in june 2025 (a single 25 mg dose beat placebo by 3.6 MADRS points at week 6) and COMP006 on february 17, 2026 (two 25 mg doses beat a 1 mg dose by 3.8 points) [23][5]. neither is peer-reviewed yet, and neither registry record has posted results. FDA granted rolling review, and the company reports that FDA issued it a National Priority Voucher in april 2026 [24]; the final NDA module is on track for Q4 2026, with launch targeted for the first half of 2027 — which depends on two things that have not happened: FDA approval and DEA rescheduling [6]. Usona Institute runs a separate phase 3 (uAspire): 238 people enrolled and its primary completion date passed on january 5, 2026, but no results have been posted [25]. worth holding onto: in the one head-to-head trial against an SSRI (escitalopram), psilocybin was not significantly better on the primary endpoint [16] — the phase 3 wins were against placebo or a 1 mg control dose, not against existing treatment.

What about LSD, DMT, and ibogaine?

LSD. Definium Therapeutics (the company formerly known as MindMed, renamed january 9, 2026 [28]) has reported three positive phase 3 toplines for its LSD tablet DT120 in SEC filings: Emerge in major depression (june 22, 2026), and Voyage (august 12, 2026) and Panorama (september 14, 2026) in generalized anxiety [10][11][26]. none is peer-reviewed yet and none of the registry records has posted results. FDA has granted breakthrough designation for anxiety (march 2024) and depression (september 2026) [28][27]; the company plans a pre-NDA meeting in Q4 2026 and an NDA filing in the first half of 2027 [26]. the published evidence base is a sponsor-funded phase 2b in JAMA [9].

DMT and analogs. the most advanced program, BPL-003, is intranasal 5-MeO-DMT — pharmacologically a different drug from ayahuasca. its phase 2b met its primary endpoint (posted registry results: 12 mg beat a 0.3 mg control by 5.3 MADRS points at day 29) [12], and phase 3 began in the second quarter of 2026 [13]. VLS-01 (buccal DMT) has dosed its last phase 2b patient, with topline expected Q4 2026 [13]. both now belong to Eli Lilly, which completed its acquisition of AtaiBeckley on september 11, 2026 [29]. the IV DMT product SPL026 was published in Nature Medicine (7.35 MADRS points better than placebo at two weeks, in 34 people) [14]; its sponsor now lists that study as groundwork for a deuterated-DMT successor, HLP004 [30]. ayahuasca itself has no US approval pathway in progress.

ibogaine. there are no FDA efficacy trials at all — the evidence is observational, self-selected, and mostly gathered abroad, and ibogaine carries documented cardiac risk (QT prolongation, fatal arrhythmias in unscreened settings). what changed recently is money: Texas SB 2308, signed june 11, 2025 [15], sets up a consortium of a drug developer, a university and a hospital to take ibogaine through FDA trials for opioid use disorder, co-occurring substance use disorder, and other conditions where it shows efficacy, with state money released only against matching outside funds [31]; the state budget appropriated $50M for it [32]. an earlier version of this paragraph said the program focused on opioid use disorder, PTSD and TBI; the statute names opioid use disorder and co-occurring substance use disorder, and TBI appears in neither the statute nor the governor's announcement. until those trials exist, ibogaine has promising signals and no efficacy evidence in the regulatory sense.

What "breakthrough therapy" does and doesn't mean

most of the drugs in this table hold FDA breakthrough therapy designation, and it is routinely misread as near-approval. it isn't. the designation speeds up FDA meetings and review logistics for drugs showing preliminary promise on serious conditions — that's all. it says nothing final about efficacy, and it guarantees nothing: MDMA-assisted therapy held breakthrough designation from august 15, 2017 [21] and was rejected in 2024. when a press release leads with "FDA breakthrough therapy," read it as "FDA agreed to talk faster," not "FDA agreed."

What the psilocybin trials actually show

the phase 3 results in the table above are company-reported. the peer-reviewed record is smaller and more mixed than the headlines. the largest published trial is phase 2b: in 233 adults with treatment-resistant depression, a single 25 mg dose of COMP360 cut MADRS scores at week 3 by 12.0 points against 5.4 with a 1 mg control, a 6.6-point difference; the 10 mg dose was not significantly better than control; adverse events occurred in 77% of the 25 mg group; and suicidal ideation or self-injurious behavior was seen in all dose groups [34]. in 104 adults with major depression, a single 25 mg dose against niacin as an active placebo produced a significantly greater MADRS reduction through week 6, with sustained response but not higher remission [35]. in the one head-to-head against an SSRI, 59 adults with moderate-to-severe depression, two doses of psilocybin were not significantly better than six weeks of daily escitalopram on the primary depression score at week 6; secondary outcomes appeared to favour psilocybin but were not corrected for multiple comparisons, so no superiority claim is supported [16].

the earlier, smaller trials are the ones most often quoted. 27 adults were randomised to immediate or delayed psilocybin-assisted therapy; 71% showed a clinically significant response at weeks 1 and 4 and 54 to 58% met remission criteria, against a waitlist control that cannot separate drug effects from expectancy [36]. in 51 people with life-threatening cancer and depression or anxiety, a high dose against a very low dose produced large decreases that about 80% still showed at six months [37]. outside depression, 95 adults with alcohol use disorder randomised to psilocybin or diphenhydramine alongside 12 weeks of psychotherapy had a significantly lower percentage of heavy-drinking days over 32 weeks, with no serious adverse events in psilocybin recipients [38].

the caveat that sits over all of them: a review of psychedelic randomised trials from 1990 to 2020 found they have generally not reported pre-trial expectancy or whether blinding held, and argued that effect sizes are likely over-estimated because participants can tell what they got [39]. the authors do not say the drugs do nothing; they say the size is uncertain. that is also FDA's own objection in the MDMA letter above [7].

Microdosing: where placebo control is enforced, the benefit disappears

microdosing is a different intervention from the supervised single doses above: roughly a tenth of a recreational dose, taken repeatedly, usually unsupervised. the randomised evidence points the other way from the surveys. the most recent synthesis, 24 studies and 3,681 participants searched to february 2026, found no clear reduction in depressive symptoms (SMD −0.19, 95% CI −0.56 to 0.19), anxiety or stress in randomised trials, with adverse-event rates similar to control, and attributed the improvements seen in observational studies to expectancy and lifestyle [40]. in the largest placebo-controlled study, 191 people built their own placebo control into their routine: every psychological outcome improved over four weeks in the microdose group, and improved just as much on placebo, with the few acute differences explained by participants correctly guessing their capsules [41]. in 34 people under double-blind conditions, subjective effects were stronger on the active dose only among those who guessed correctly, and wellbeing, creativity, cognition and perception showed no benefit, with small changes in the direction of impairment [42]. the full record, including the app surveys that point the other way, is on the microdosing page.

Psilocybin with an antidepressant or lithium: what has been measured

two findings in opposite directions, for people already on a psychiatric medication. in a double-blind crossover in healthy volunteers, two weeks of escitalopram left psilocybin's positive mood effects intact and reduced its bad effects, anxiety and cardiovascular effects [43]. in an online survey of 611 reports, about half of people on an SSRI (0.47) or SNRI (0.55) reported weaker-than-expected mushroom effects, a blunting that persisted for up to three months after stopping the antidepressant [44]. the two are not in conflict; they measured different things over different durations. with lithium the signal is danger, from the weakest kind of evidence: of 62 online reports of a classic psychedelic taken with lithium, 47% involved seizures and 39% medical attention, against none of 34 reports on lamotrigine [45]. trip reports are self-selected and 47% is not a rate, but the contrast is hard to explain away, and the clinical trials excluded people with bipolar disorder for a reason. none of this is guidance on combining anything; it is what the record holds. the lithium page carries the same signal beside its label.

The legal status, stated plainly

psilocybin and psilocyn are listed in schedule I of the controlled substances act, 21 CFR 1308.11(d), the schedule for substances with no currently accepted medical use and a high potential for abuse [46]. no FDA-approved psilocybin product exists, and nothing sold or shared as psilocybin today is one. Compass's breakthrough therapy designation (2018) [24] speeds FDA meetings; it is not an approval, and the launch its filings target depends on both FDA approval and DEA rescheduling, neither of which has happened [6]. a small number of state programmes operate outside the FDA process; state law changes quickly, and a primary legal source beats a listicle.

How we verify

how we verify this page. every source cited here is a primary record: an FDA document (approval and complete response letters, labels, advisory committee minutes and briefing documents, FDA's breakthrough-approvals list), a ClinicalTrials.gov registry record, an SEC filing, a peer-reviewed paper checked against PubMed, or a government record — each with its URL and access date. we do not cite press releases, company investor pages, trade press, news or advocacy groups; they can point us to a primary record, and the primary record is what we cite. where the only record of a phase 3 result is a company's SEC filing, we say "the company reported" and treat it as unconfirmed until peer review or posted registry results. retracted papers are excluded (three MAPS phase 2 MDMA papers were retracted in august 2024; none is relied on here). we publish nothing we could not verify, and we mark what we don't know rather than inferring it. we are not clinicians, and this page reports regulatory status — it is not medical advice.

the rule we apply to approval dates: when a sponsor's announcement and an FDA action document disagree, the FDA document wins. an announcement is dated when the company chose to announce; the approval is dated when FDA signed. those are usually different days, and the gap is where most published errors come from.

correction, september 29, 2026. we replaced every press-release, investor-relations, trade-press and advocacy citation on this page with a primary record, and that changed several facts. an earlier version of this page said esketamine's suicidal-ideation indication was approved august 3, 2020 — the date of the company's announcement; FDA's approval letter is signed july 31, 2020 [2]. it said FDA's complete response letter on MDMA was issued august 9, 2024; the letter is signed august 8, 2024 [7]. it said MDMA was resubmitted in august 2026 "without a new Phase 3 study", citing a MAPS statement, with contents and a review clock drawn from trade reporting; no primary record confirms the resubmission, so we now report it as unconfirmed. it gave Resilient's rename as august 2025; the name change was effective july 28, 2025 [19]. it gave esketamine's breakthrough designations as 2013 and 2016, Compass's as october 2018 and Usona's as november 2019; FDA does not publish designation dates, Compass's filings say only 2018, and we found no primary record for Usona's, so those dates are removed. it said Usona's uAspire finished enrolling in november 2025; the registry shows 238 enrolled and a primary completion date of january 5, 2026, and we cannot confirm the november date. it said the REMS was modified on march 24 and october 9, 2025; FDA approved four REMS modifications that year [1]. it said the IV DMT product SPL026 "is not advancing as-is"; its sponsor's filing says it supports the HLP004 program [30]. and it described the Texas ibogaine program as focused on PTSD and TBI; see the ibogaine paragraph above. the same pass brought the table up to date: Panorama read out on september 14, 2026, BPL-003 entered phase 3, Eli Lilly acquired AtaiBeckley, and COMP006's 26-week data were released on july 7, 2026.

correction, august 18, 2026. this page previously gave january 21, 2025 as the date esketamine was approved as monotherapy. that is the date of J&J's press release. the FDA action was january 17, 2025 — NDA 211243 supplement S-016, an efficacy supplement reviewed under priority review, approved in a letter signed by Tiffany R. Farchione, MD, director of FDA's division of psychiatry [17]. the Drugs@FDA record for the application lists the same date independently. the table, the FAQ and the source list now cite the approval letter as the primary source and the press release as secondary. the indication itself was never wrong, only the date.

every classic psychedelic in this table (psilocybin, MDMA, LSD, DMT) is investigational and remains federally Schedule I. the two exceptions run the other way: esketamine is FDA-approved, and racemic ketamine is Schedule III — an approved anesthetic since 1970, used off-label in psychiatry. nothing here is a recommendation to seek or use any of them — talk to a licensed professional about your options. if you're in crisis, call or text 988 (u.s.), 24/7, free.

Questions

Which psychedelics are FDA-approved in 2026?

one: esketamine (Spravato), a ketamine-derived nasal spray approved for treatment-resistant depression (2019, with monotherapy added January 17, 2025) and for depressive symptoms in MDD with acute suicidal ideation or behavior (2020). it is only administered in certified settings under a REMS safety program. no classic psychedelic — psilocybin, MDMA, LSD, DMT, ibogaine — is FDA-approved for anything as of september 29, 2026: none appears on FDA’s list of 2026 novel drug approvals, checked that day [33].

Is MDMA-assisted therapy FDA-approved?

no. FDA issued a complete response letter dated August 8, 2024, two months after its advisory committee voted 9-2 that effectiveness was not shown and 10-1 that benefits did not outweigh risks. the letter recommended a new randomized trial, an independent audit of the original trial data, and a dedicated cardiac study. a resubmission by Resilient Pharmaceuticals (formerly Lykos) in August 2026 has been reported, but no FDA record confirms it, so we do not state it as fact. what is on the public record: Resilient registered a phase 1 midomafetamine study with cardiac ECG assessments that started in April 2026. (an earlier version of this answer gave August 9, 2024 as the letter date and stated the resubmission and its contents as fact, citing a MAPS statement and trade reporting; the letter is signed August 8, and neither source meets our citation rules.)

What is Rysanso?

Rysanso is the brand name Resilient Pharmaceuticals (formerly Lykos, the MAPS spin-out) holds for its MDMA (midomafetamine) product — the PTSD treatment FDA rejected in 2024, and for which a resubmission has been reported but not confirmed by any FDA record. the name itself is documented: it is a registered Canadian trademark of Resilient (filed February 29, 2024; registered September 7, 2026; class 5, pharmaceutical preparations for psychedelic and psychotropic treatments, PTSD among the listed conditions). that it will be the US trade name is trade reporting, not an FDA or sponsor document. Rysanso is not approved anywhere; there is no product to prescribe or buy, and anything sold under that name today is not it.

When could psilocybin be approved?

Compass Pathways is in a rolling NDA review after two phase 3 trials met their primary endpoints (COMP005, June 2025; COMP006, February 17, 2026 — both company-reported in SEC filings, neither yet peer-reviewed), with the final module expected in Q4 2026 and a launch targeted for H1 2027 — contingent on FDA approval and DEA rescheduling, neither of which is guaranteed. the company also reports that FDA issued it a National Priority Voucher in April 2026; per the company’s filing, FDA has said voucher holders get a decision within 1–2 months of a complete application, though that can be extended.

Is psilocybin legal in my state?

psilocybin remains a federal Schedule I substance everywhere in the US — FDA approval has not happened. state laws differ and change quickly, so check your state’s current statutes or a primary legal source rather than a listicle. legal state programs, where they exist, operate outside the FDA process.

Is ketamine the same as esketamine?

no. esketamine (Spravato) is one mirror-image half of the ketamine molecule, FDA-approved for specific depression indications and given in certified clinics. racemic ketamine — the generic drug used in infusion and telehealth clinics — is approved only as an anesthetic; every psychiatric use of it is off-label, and FDA warned about compounded at-home ketamine in October 2023.

What does "breakthrough therapy designation" actually mean?

it speeds up FDA communication and review logistics for a drug that shows preliminary promise on a serious condition. it is not an approval, not an endorsement of efficacy, and not a guarantee — MDMA-assisted therapy held breakthrough designation from August 2017 and was still rejected in 2024.

Does psilocybin work for depression? What the trials show

in the peer-reviewed trials: a single 25 mg dose beat a 1 mg control by 6.6 madrs points at week 3 in 233 adults with treatment-resistant depression, with adverse events in 77% of the 25 mg group and suicidal ideation or self-injury seen in every dose group [34]; a single 25 mg dose beat niacin through week 6 in 104 adults, with sustained response but not higher remission [35]; and in the one head-to-head against an ssri, two psilocybin doses were not significantly better than six weeks of escitalopram on the primary outcome in 59 adults [16]. the smaller, earlier trials (27 adults against a waitlist; 51 people with cancer) report large effects that their designs cannot separate from expectancy [36][37]. a review of psychedelic trials argues effect sizes are likely over-estimated because participants can tell what they got [39]. the phase 3 results are so far company-reported only [23][5].

Does microdosing psilocybin work?

not in randomised trials. the most recent synthesis (24 studies, 3,681 participants, searched to february 2026) found no clear reduction in depressive symptoms, anxiety or stress in randomised trials, with adverse-event rates similar to control, and attributed the improvements seen in surveys to expectancy and lifestyle [40]. in the largest placebo-controlled study, 191 people improved as much on placebo capsules as on microdoses over four weeks [41]; in 34 people under double-blind conditions the only reliable difference was in those who guessed correctly, and cognition showed small changes toward impairment [42]. the full microdosing record is on its own page.

What do the studies show about psilocybin with an antidepressant or lithium?

two findings in opposite directions, and one danger signal. in a double-blind crossover in healthy volunteers, two weeks of escitalopram left psilocybin’s positive effects intact and reduced its bad effects, anxiety and cardiovascular effects [43]; in a survey of 611 reports, about half of people on an ssri or snri reported weaker mushroom effects, lasting up to three months after stopping [44]. with lithium, 47% of 62 online reports of a psychedelic taken alongside it involved seizures and 39% medical attention, against none of 34 reports on lamotrigine [45]; trip reports are self-selected and 47% is not a rate, but the contrast is hard to explain away, and the clinical trials excluded people with bipolar disorder. none of this is guidance on combining anything; psilocybin remains schedule i [46].

Can I join a psychedelic therapy trial?

active trials are listed on clinicaltrials.gov — search the drug name plus your condition. trials screen carefully (psychosis-spectrum conditions, cardiac risk, and some medications are common exclusions), and being in one may mean receiving a placebo.

Sources

  1. PRIMARY — FDA approval letters and REMS history for Spravato, NDA 211243 (Drugs@FDA): original approval Mar 5, 2019; REMS modifications approved Mar 24 (S-018), May 15 (S-021), Jul 31 (S-024) and Oct 9, 2025 (S-025), and Jan 23 (S-027, the linked letter), Apr 13 (S-028) and Jun 24, 2026 (S-029). Re-checked 2026-09-29. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/211243Orig1s027ltr.pdf
  2. PRIMARY — FDA supplement approval letter, NDA 211243/S-004: new indication for depressive symptoms in adults with MDD with acute suicidal ideation or behavior, plus REMS modifications. "Approved, effective on the date of this letter"; electronic signature Tiffany R. Farchione, MD, Acting Director, Division of Psychiatry, 07/31/2020. The approved label states that an effect in preventing suicide or reducing suicidal ideation or behavior has not been demonstrated. Accessed 2026-09-29. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2020/211243Orig1s004ltr.pdf
  3. Janik A, et al. Esketamine Monotherapy in Adults With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry 2025;82(9):877-887. PMID 40601310; NCT04599855 (TRD4005, "Study 3" in the label). n=378; esketamine minus placebo at day 28: −5.1 MADRS points (56 mg) and −6.8 (84 mg). Funded by Janssen Research & Development. Accessed 2026-09-29. https://doi.org/10.1001/jamapsychiatry.2025.1317
  4. FDA — warning to patients and providers about compounded ketamine, including at-home use, Oct 10, 2023. FDA removed the live page; its own Compounding Risk Alerts index now links this Internet Archive capture, cited here for that reason. Re-verified 2026-09-01. https://web.archive.org/web/20260530025451/https://www.fda.gov/drugs/human-drug-compounding/fda-warns-patients-and-health-care-providers-about-potential-risks-associated-compounded-ketamine
  5. SEC filing — Compass Pathways plc, Form 8-K filed Feb 17, 2026: the company reported that COMP006 met its primary endpoint (two doses of COMP360 25 mg vs 1 mg, −3.8 MADRS points at week 6, 95% CI −5.8 to −1.8, p<0.001) and that it had requested an FDA meeting on a rolling submission. Accessed 2026-09-29. https://www.sec.gov/Archives/edgar/data/1816590/000181659026000007/cmps-20260217.htm
  6. SEC filing — Compass Pathways plc, Form 8-K filed Jul 7, 2026: the company reported COMP006 26-week (Part B) results and that a rolling NDA submission is underway, with final submission on track for Q4 2026 and launch anticipated in H1 2027 subject to FDA approval and DEA rescheduling. Accessed 2026-09-29. https://www.sec.gov/Archives/edgar/data/1816590/000181659026000047/cmps-20260707.htm
  7. PRIMARY — FDA complete response letter, NDA 215455 (midomafetamine capsules, Lykos Therapeutics), electronically signed 08/08/2024, as published in FDA’s complete response letter database (openFDA). FDA found the application did not provide substantial evidence of effectiveness or establish safety; cited unreported and uncollected adverse-event data, no demonstrated durability beyond week 18, and selection and expectation bias (about 40% of participants reported prior MDMA use); recommended a new randomized trial, an independent third-party data audit, and a dedicated cardiac (ECG) study. Accessed 2026-09-29. https://download.open.fda.gov/crl/CRL_NDA215455_20240808.pdf
  8. PRIMARY — ClinicalTrials.gov NCT07584720, Resilient Pharmaceuticals: phase 1, open-label study of midomafetamine at therapeutic and supratherapeutic doses in healthy adults, including electrocardiographic cardiac-safety assessments; start Apr 23, 2026; primary completion estimated Jul 23, 2026; no results posted. Accessed 2026-09-29. https://clinicaltrials.gov/study/NCT07584720
  9. MM120 phase 2b in generalized anxiety disorder, JAMA 2025 (PMID 40906494). Accessed 2026-08-17. https://pubmed.ncbi.nlm.nih.gov/40906494/
  10. SEC filing — Definium Therapeutics, Form 8-K filed Jun 22, 2026, exhibit 99.1: the company reported positive topline results from the phase 3 Emerge study of DT120 in MDD (n=75 DT120, 74 placebo; MADRS −13.3 vs −5.2 at week 6, difference −8.1, p<0.0001). Registry record NCT06941844 (149 enrolled; no results posted). Accessed 2026-09-29. https://www.sec.gov/Archives/edgar/data/1813814/000110465926076091/tm2618434d1_ex99-1.htm
  11. SEC filing — Definium Therapeutics, Form 8-K filed Aug 12, 2026, exhibit 99.1: the company reported positive topline results from the phase 3 Voyage study of DT120 in GAD (n=107 per arm; HAM-A −11.6 vs −6.2 at week 12, difference −5.4, p<0.0001, d=0.81). Registry record NCT06741228 (214 enrolled; no results posted). Accessed 2026-09-29. https://www.sec.gov/Archives/edgar/data/1813814/000110465926094528/tm2622948d1_ex99-1.htm
  12. SEC filing — atai Life Sciences N.V., Form 8-K filed Jul 1, 2025, exhibit 99.1: the company reported positive topline results from the BPL-003 phase 2b study in treatment-resistant depression (n=193). Registry record NCT05870540, with posted results: 12 mg vs 0.3 mg, least-squares mean difference −5.3 MADRS points at day 29, p=0.0033. Accessed 2026-09-29. https://www.sec.gov/Archives/edgar/data/1840904/000114036125024290/ef20051402_ex99-1.htm
  13. SEC filing — AtaiBeckley Inc., Form 10-Q for the quarter ended Jun 30, 2026 (filed Aug 11, 2026): BPL-003 phase 3 activities in TRD initiated (ReConnection-1, ~350 patients; ReConnection-2, ~230; primary endpoint MADRS at week 4); VLS-01 Elumina phase 2b last patient dosed, topline anticipated Q4 2026. Accessed 2026-09-29. https://www.sec.gov/Archives/edgar/data/2081043/000119312526344720/atai-20260630.htm
  14. Erritzoe D, et al. A short-acting psychedelic intervention for major depressive disorder: a phase IIa randomized placebo-controlled trial. Nat Med 2026;32(2):591-598. PMID 41699126; NCT04673383. IV DMT (SPL026), n=34; MADRS difference −7.35 vs placebo at 2 weeks (95% CI −13.62 to −1.08). Accessed 2026-09-29. https://doi.org/10.1038/s41591-025-04154-z read our summary of this study →
  15. Office of the Texas Governor — Governor Abbott signs SB 2308 (ibogaine clinical-trial law), Jun 11, 2025: state matching funds for an FDA drug trial run by a public university with a drug company and hospital. Re-checked 2026-09-29. https://gov.texas.gov/news/post/governor-abbott-signs-ibogaine-treatment-research-law-at-texas-capitol
  16. Carhart-Harris R, et al. Trial of Psilocybin versus Escitalopram for Depression. NEJM 2021 (PMID 33852780) — null primary endpoint in the head-to-head against an SSRI. Accessed 2026-08-17. https://doi.org/10.1056/NEJMoa2032994 read our summary of this study →
  17. PRIMARY — FDA approval letter, NDA 211243/S-016 (Spravato monotherapy for treatment-resistant depression). "Approved, effective on the date of this letter"; electronic signature Tiffany R. Farchione, MD, Director, Division of Psychiatry, 01/17/2025. Also records fulfilment of postmarketing commitment 3577-3 from the Mar 5, 2019 approval letter. Accessed 2026-08-18. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/211243Orig1s016ltr.pdf
  18. PRIMARY — Spravato prescribing information as approved under S-016 (rev. 01/2025): monotherapy indication, and Study 3 (NCT04599855) results. The current label on DailyMed (Medication Guide revised 09/2026) carries the same indications and the at-least-2-hour monitoring requirement. The Drugs@FDA record for NDA 211243 independently lists SUPPL-16 as approved 2025-01-17 under Priority Review (efficacy supplement). Accessed 2026-08-18, re-checked 2026-09-29. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/211243s016lbl.pdf
  19. PRIMARY — Canadian Intellectual Property Office trademark record RYSANSO, application 2313121, registration TMA1443089: owner Resilient Pharmaceuticals, Inc. (name change from Lykos Therapeutics recorded Feb 13, 2026, effective Jul 28, 2025); filed Feb 29, 2024; registered Sep 7, 2026; Nice class 5, pharmaceutical preparations for psychedelic and psychotropic treatments incl. PTSD. Establishes the name and its owner, not its use as the US brand. Accessed 2026-09-10. https://ised-isde.canada.ca/cipo/trademark-search/2313121
  20. PRIMARY — FDA, minutes of the Jun 4, 2024 Psychopharmacologic Drugs Advisory Committee meeting (midomafetamine for PTSD). Vote on effectiveness: yes 2, no 9; vote on benefit-risk with FDA’s proposed REMS: yes 1, no 10. Members cited functional unblinding, expectation bias and selection bias. Accessed 2026-09-29. https://www.fda.gov/media/180463/download
  21. PRIMARY — FDA briefing document for the Jun 4, 2024 advisory committee meeting: breakthrough therapy designation for midomafetamine for PTSD was granted on August 15, 2017. Accessed 2026-09-29. https://www.fda.gov/media/178984/download
  22. PRIMARY — FDA CDER, Breakthrough Therapy Designation Approvals (data as of Dec 31, 2025): lists Spravato NDA 211243 original (05-Mar-2019), supplement 4 (31-Jul-2020, MDD with acute suicidal ideation or behavior) and supplement 16 (17-Jan-2025). Accessed 2026-09-29. https://www.fda.gov/media/95302/download
  23. SEC filing — Compass Pathways plc, Form 8-K filed Jun 23, 2025: the company reported that COMP005 met its primary endpoint (single dose of COMP360 25 mg vs placebo, −3.6 MADRS points at week 6, 95% CI −5.7 to −1.5, p<0.001; 258 participants dosed), noting FDA had not yet reviewed the data. Registry record NCT05624268 (completed; no results posted). Accessed 2026-09-29. https://www.sec.gov/Archives/edgar/data/1816590/000181659025000085/cmps-20250623.htm
  24. SEC filing — Compass Pathways plc, Form 10-Q for the quarter ended Jun 30, 2026 (filed Aug 5, 2026): breakthrough therapy designation for COMP360 in TRD received in 2018; FDA granted the request for rolling review of the NDA; in April 2026 FDA issued a National Priority Voucher for COMP360 in TRD. COMP006 registry record NCT05711940 (572 enrolled; no results posted). Accessed 2026-09-29. https://www.sec.gov/Archives/edgar/data/1816590/000181659026000058/cmps-20260630.htm
  25. PRIMARY — ClinicalTrials.gov NCT06308653 (uAspire), Usona Institute: phase 3 psilocybin in MDD; 238 enrolled (actual); primary completion Jan 5, 2026 (actual); status active, not recruiting; no results posted. Accessed 2026-09-29. https://clinicaltrials.gov/study/NCT06308653
  26. SEC filing — Definium Therapeutics, Form 8-K filed Sep 14, 2026, exhibit 99.1: the company reported positive topline results from the phase 3 Panorama study of DT120 in GAD (n=96 DT120, 97 placebo; HAM-A −9.8 vs −4.7 at week 12, difference −5.1, p<0.0001, d=0.64), a pre-NDA meeting scheduled for Q4 2026 and NDA filing anticipated in H1 2027. Registry record NCT06809595 (245 enrolled; no results posted). Accessed 2026-09-29. https://www.sec.gov/Archives/edgar/data/1813814/000110465926107275/tm2625365d1_ex99-1.htm
  27. SEC filing — Definium Therapeutics, Form 8-K filed Sep 8, 2026, exhibit 99.1: the company reported that FDA granted breakthrough therapy designation for DT120 in MDD, its second after GAD. Accessed 2026-09-29. https://www.sec.gov/Archives/edgar/data/1813814/000119312526384403/dftx-ex99_1.htm
  28. SEC filing — Definium Therapeutics, Form 10-K for 2025 (filed Feb 26, 2026): FDA breakthrough designation for DT120 in GAD announced March 2024; name changed from Mind Medicine (MindMed) Inc. to Definium Therapeutics, Inc. on January 9, 2026. Accessed 2026-09-29. https://www.sec.gov/Archives/edgar/data/1813814/000119312526076742/dftx-20251231.htm
  29. SEC filing — AtaiBeckley Inc., Form 8-K filed Sep 11, 2026: merger with a subsidiary of Eli Lilly and Company completed on September 11, 2026; AtaiBeckley is now a wholly owned subsidiary of Lilly. Accessed 2026-09-29. https://www.sec.gov/Archives/edgar/data/2081043/000114036126036283/ef20081247_8k.htm
  30. SEC filing — Cybin Inc. (trading as Helus Pharma), annual information form filed with Form 40-F, Jun 29, 2026: lists the SPL026 phase 2a among completed studies supporting its HLP004 (deuterated DMT, formerly CYB004) program. Accessed 2026-09-29. https://www.sec.gov/Archives/edgar/data/1833141/000183314126000046/cybin-annualinformationfor.htm
  31. PRIMARY — Texas Legislature, SB 2308 (89th Legislature, Regular Session), enrolled text: a consortium of a drug developer, a university and a hospital to run FDA drug-development trials of ibogaine for opioid use disorder, co-occurring substance use disorder, and other neurological or mental health conditions where it shows efficacy; state funds released only against matching non-state funds. Accessed 2026-09-29. https://capitol.texas.gov/tlodocs/89R/billtext/html/SB02308F.htm
  32. PRIMARY — Texas General Appropriations Act for 2026–27 (SB 1, 89th Legislature, enrolled), Article IX, Sec. 18.74: contingent on SB 2308, the Health and Human Services Commission is appropriated $50,000,000 from the General Revenue Fund in fiscal year 2026 to implement it. Accessed 2026-09-29. https://capitol.texas.gov/tlodocs/89R/billtext/pdf/SB00001F.pdf#page=1013
  33. PRIMARY — FDA, Novel Drug Approvals for 2026 (45 approvals, the latest dated Sep 28, 2026; none is psilocybin, MDMA, LSD, DMT, 5-MeO-DMT or ibogaine). Accessed 2026-09-29. https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2026
  34. Goodwin GM, et al. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. NEJM 2022 (phase 2b, n=233; industry funded). Accessed 2026-10-05. https://doi.org/10.1056/NEJMoa2206443 read our summary of this study →
  35. Raison CL, et al. Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. JAMA 2023 (n=104, niacin active placebo; industry funded). Accessed 2026-10-05. https://doi.org/10.1001/jama.2023.14530 read our summary of this study →
  36. Davis AK, et al. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry 2021 (n=27, waitlist control). Accessed 2026-10-05. https://doi.org/10.1001/jamapsychiatry.2020.3285 read our summary of this study →
  37. Griffiths RR, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol 2016 (n=51, crossover). Accessed 2026-10-05. https://doi.org/10.1177/0269881116675513 read our summary of this study →
  38. Bogenschutz MP, et al. Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder. JAMA Psychiatry 2022 (n=95). Accessed 2026-10-05. https://doi.org/10.1001/jamapsychiatry.2022.2096 read our summary of this study →
  39. Muthukumaraswamy SD, Forsyth A, Lumley T. Blinding and expectancy confounds in psychedelic randomized controlled trials. Expert Rev Clin Pharmacol 2021 (systematic review). Accessed 2026-10-05. https://doi.org/10.1080/17512433.2021.1933434 read our summary of this study →
  40. Meshkat S, et al. Efficacy and Safety of Psychedelic Microdosing on Psychological Outcomes in Healthy Adults: A Systematic Review and Meta-Analysis. CNS Drugs 2026 (24 studies, 3,681 participants, searched to Feb 2026). Accessed 2026-10-05. https://doi.org/10.1007/s40263-026-01325-5 read our summary of this study →
  41. Szigeti B, et al. Self-blinding citizen science to explore psychedelic microdosing. eLife 2021 (n=191, self-blinded placebo control). Accessed 2026-10-05. https://doi.org/10.7554/eLife.62878 read our summary of this study →
  42. Cavanna F, et al. Microdosing with psilocybin mushrooms: a double-blind placebo-controlled study. Transl Psychiatry 2022 (n=34). Accessed 2026-10-05. https://doi.org/10.1038/s41398-022-02039-0 read our summary of this study →
  43. Becker AM, et al. Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Subjects. Clin Pharmacol Ther 2022 (supported in part by Mind Medicine). Accessed 2026-10-05. https://doi.org/10.1002/cpt.2487 read our summary of this study →
  44. Gukasyan N, et al. Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use. J Psychopharmacol 2023 (retrospective survey, 611 and 1,542 reports). Accessed 2026-10-05. https://doi.org/10.1177/02698811231179910 read our summary of this study →
  45. Nayak SM, et al. Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports. Pharmacopsychiatry 2021 (case series; 62 lithium and 34 lamotrigine reports). Accessed 2026-10-05. https://doi.org/10.1055/a-1524-2794 read our summary of this study →
  46. PRIMARY — 21 CFR 1308.11(d), Schedule I hallucinogenic substances, listing psilocybin and psilocyn (eCFR, current). Content confirmed via the eCFR renderer API 2026-10-05; the eCFR site itself blocks automated reads. https://www.ecfr.gov/current/title-21/chapter-II/part-1308/section-1308.11

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  • confirmedis compass pathways' psilocybin therapy close to fda approval?said on Huberman Lab, 2026-09-28; the speaker is right: compass pathways' psilocybin program for treatment-resistant depression is the closest any classic psychedelic has come to a u.s. approval decision. two phase 3 trials met their primary endpoints, the fda allowed a rolling new drug application and gave the program a national priority voucher, and the company expects to finish its submission in q4 2026.
  • overstateddoes one executive order fast-track both ibogaine and other psychedelics?said on Huberman Lab, 2026-09-28; the speaker is right. a single executive order, EO 14401 of april 18, 2026, names ibogaine and also directs federal agencies to speed up psychedelic drugs more broadly, so "the same order" covers both.
  • falseis ibogaine on track for fda approval before mdma or psilocybin?said on Huberman Lab, 2026-09-28; ibogaine does have real federal momentum. an april 2026 executive order names "ibogaine compounds" twice, and on october 5, 2026 the fda put out a formal request for input on how ibogaine trials should be run, alongside early-phase trials funded by arpa-h and nida.
  • overstatedhas ibogaine never been tested in university drug trials?said on Huberman Lab, 2026-09-28; the most prominent university work on ibogaine, the stanford veterans study, is not a drug trial: stanford measured veterans before and after treatment, but the ibogaine itself was given at a private clinic near tijuana, and the paper says "stanford played no role in ibogaine administration." no randomized, placebo-controlled trial run by a university has shown that ibogaine itself works, and a 2026 review of thirty years of research says the evidence is not yet enough to support clinical use.

every check quotes one sentence, links the original at the timestamp, and takes each assertion to the primary record. the full list: /checked.