The Psychedelic Medicine Pipeline 2026

The psychedelic drug development landscape has reached an inflection point in early 2026, with Compass Pathways achieving the first positive Phase 3 psilocybin trial results in June 2025, while Lykos Therapeutics' MDMA rejection has reshaped industry expectations for regulatory rigor. Six compounds now hold FDA Breakthrough Therapy Designation, and a potential FDA policy shift toward single-trial approvals could accelerate the path to market. This report provides a comprehensive status update on all major Phase 2/3 programs as of January 2026.

1. Regulatory Landscape​

1.1 The FDA's MDMA Decision and Its Impact​

The FDA's August 2024 rejection of Lykos Therapeutics' MDMA-assisted therapy for PTSD—following a 9-2 negative advisory committee vote—sent shockwaves through the industry. The Complete Response Letter, publicly released in September 2025 under FDA's new transparency initiative, cited three critical failures: inadequate adverse event collection during dosing sessions, insufficient durability data, and high rates of prior MDMA use creating expectancy bias. The rejection forced Lykos to rebrand as Resilient Pharmaceuticals and reduce staff by 75%.

However, December 2025 brought potentially transformative news: FDA Commissioner Marty Makary indicated the agency plans to allow just one pivotal trial for NDAs rather than the traditional two—a policy change expected within 3-6 months that could benefit companies like Usona Institute and Compass Pathways.

1.2 Spravato Monotherapy Approval​

Spravato received expanded approval as a monotherapy for treatment-resistant depression in January 2025, marking a significant milestone for ketamine-based therapeutics.

1.3 Current Breakthrough Therapy Designations​

Current Breakthrough Therapy Designations in the psychedelic space include:
• MDMA for PTSD (Lykos/Resilient, August 2017)
• COMP360 psilocybin for TRD (Compass Pathways, October 2018)
• Psilocybin for MDD (Usona Institute, November 2019)
• MM-120 LSD for GAD (MindMed, March 2024)
• CYB003 for MDD (Cybin/Helus, March 2024)
• BPL-003 5-MeO-DMT for TRD (AtaiBeckley, October 2025)
• TSND-201 methylone for PTSD (Transcend, July 2025)

2. Psilocybin Programs​

2.1 Compass Pathways COMP360​

Compass Pathways' COMP360 achieved the first positive pivotal trial results for any classic psychedelic in June 2025. The COMP005 trial enrolled 258 patients with treatment-resistant depression across 32 U.S. sites, demonstrating a statistically significant 3.6-point MADRS reduction versus placebo at Week 6 (p<0.001). A second pivotal trial, COMP006, is enrolling 568 patients evaluating two 25mg doses administered three weeks apart.

Following a positive September 2025 FDA meeting, Compass is exploring a rolling NDA submission with a potential FDA decision in late 2026 or early 2027—commercial launch plans have been accelerated by 9-12 months.
Compass has also expanded into PTSD, with FDA accepting a new IND in January 2026 for a Phase 2b/3 trial. Open-label Phase 2 data showed a remarkable 29.9-point CAPS-5 reduction and 81.8% response rate with a single 25mg dose.

2.2 Cybin/Helus Pharma CYB003​

Cybin, rebranded as Helus Pharma in January 2026, is advancing CYB003 (deuterated psilocin) through two Phase 3 trials for major depressive disorder. The APPROACH study is actively dosing approximately 220 patients, with topline data expected Q4 2026. Phase 2 durability data showed exceptional results: 75% remission at 4 months and 71% remission sustained through 12 months.

2.3 Usona Institute Phase 3​

Usona Institute's non-profit Phase 3 uAspire trial launched in March 2024 and is currently recruiting at academic centers and VA medical centers. Their Phase 2 data, published in JAMA, showed sustained response rates of 42% versus 11% for placebo (p=0.002).

2.4 Psilocybin Programs Summary Table​

Program	Sponsor	Phase	Indication	Key Results	BTD
COMP360	Compass	3	TRD	-3.6 MADRS vs placebo (p<0.001)	Yes
CYB003	Cybin/Helus	3	MDD	71% 12-month remission (Ph2)	Yes
Psilocybin	Usona	3	MDD	42% sustained response	Yes
PSX-001	Incannex	2→2b/3	GAD	-12.8 HAM-A vs placebo	No
SYNP-101	B.More	2b	AUD	Ongoing	No

3. LSD Programs​

3.1 MindMed MM-120 Overview​

MindMed has emerged as the clear leader in LSD clinical development, with four Phase 3 trials underway or planned for MM-120 (lysergide D-tartrate). The company received BTD in March 2024 for generalized anxiety disorder based on exceptional Phase 2b results: a single 100μg dose produced a 7.6-point HAM-A reduction versus placebo (Cohen's d = 0.88), with 65% achieving clinical response and 48% remission at Week 12—all from a single administration without psychotherapy.

3.2 Active Phase 3 Studies​

Three Phase 3 studies are actively enrolling:

• VOYAGE (GAD): ~200 patients, first dosed December 2024, readout expected H1 2026
• PANORAMA (GAD): ~250 patients including a 50μg control arm to address blinding concerns, readout expected H2 2026
• EMERGE (MDD): ~140 patients, first dosed April 2025, readout expected mid-2026

A fourth trial, ASCEND, is planned for mid-2026 initiation. MindMed raised $258.9 million in October 2025 to fund the programs, with CEO Rob Barrow calling 2026 "the most significant year in our history."

4. MDMA and Methylone Programs​

4.1 Transcend Therapeutics TSND-201 (Methylone)​

The Lykos MDMA rejection has created an opening for Transcend Therapeutics' methylone program. TSND-201 received BTD in July 2025 following impressive Phase 2 IMPACT-1 results: a 9.64-point placebo-adjusted CAPS-5 reduction at Day 64 (p=0.011), 57.1% response rate (vs 19.2% placebo), and 60.7% loss of PTSD diagnosis.
Critically, methylone is non-hallucinogenic and requires no wrap-around psychotherapy—addressing two major concerns that plagued the MDMA program. Phase 3 trials are planned for 2026.

4.2 Lykos/Resilient MDMA Status​

Lykos (now Resilient Pharmaceuticals) continues negotiations with FDA regarding resubmission, but faces a multi-year timeline for any additional Phase 3 trial. The company hired Dr. David Hough, former leader of J&J's Spravato program, to guide FDA engagement. Some insiders suggest potential approval within 12 months given the current political climate, though most estimates extend to 2028 or beyond.

5. Ketamine Programs​

5.1 Spravato (Janssen)​

Spravato's January 2025 monotherapy approval strengthens Janssen's position in the ketamine space. The TRD4005 trial demonstrated -6.8 MADRS point reduction versus placebo for the 84mg dose (p<0.001) with 22.5% remission at Week 4 versus 7.6% for placebo. Over 140,000 patients have now received Spravato worldwide.

5.2 Tasman Therapeutics R-107​

Tasman Therapeutics' R-107 represents a potential paradigm shift with its oral extended-release formulation designed for at-home self-administration. Phase 2 BEDROC data published in Nature Medicine (June 2024) showed 73% response rate with 75% achieving remission within one week. The 180mg twice-weekly dose demonstrated a -6.1 MADRS reduction versus placebo with excellent tolerability and minimal dissociation. Phase 3 enrollment began H2 2025, targeting FDA submission in 2027.

5.3 Solvonis Therapeutics Programs​

Solvonis Therapeutics' SVN-001 combines IV ketamine with manualized CBT for severe alcohol use disorder. Phase 2 showed 86% sustained abstinence at 6 months versus 2% at baseline. The Phase 3 MORE KARE trial across 8-9 UK NHS sites expects results in late 2027.

SVN-002, a sublingual esketamine film, received positive FDA pre-IND feedback in December 2024 for a 505(b)(2) pathway.

5.4 NRx Pharmaceuticals NRX-100​

NRx Pharmaceuticals' NRX-100 has filed an NDA for suicidal ideation in depression, with FDA decision expected by end of 2025. The program received Fast Track designation in August 2025 and a $4.3 million PDUFA fee waiver.

6. DMT and 5-MeO-DMT Programs​

6.1 GH Research GH001 (Inhaled 5-MeO-DMT)​

The short-acting tryptamine space has seen major advances, with GH Research's GH001 (inhaled 5-MeO-DMT) emerging as a frontrunner. Phase 2b results (February 2025) demonstrated a -15.5 point placebo-adjusted MADRS reduction at Day 8 (p<0.0001) with 57.5% remission versus 0% for placebo. The FDA clinical hold that delayed development was lifted January 5, 2026, clearing the path for U.S. Phase 3 initiation. The median psychoactive experience lasts just 11 minutes, with 97.4% of patients discharge-ready within one hour.

6.2 AtaiBeckley BPL-003 (Intranasal 5-MeO-DMT)​

AtaiBeckley's BPL-003 (intranasal 5-MeO-DMT) received BTD in October 2025 following Phase 2b results showing 12.1-point MADRS reduction versus control (p=0.003) in the largest controlled 5-MeO-DMT study ever conducted (196 patients). The November 2025 merger of atai Life Sciences and Beckley Psytech created a combined pipeline with Phase 3-ready programs in both TRD and alcohol use disorder.

6.3 Cybin CYB004 (Deuterated DMT)​

Cybin's CYB004 (deuterated DMT) completed Phase 2 enrollment for generalized anxiety disorder in September 2025, with topline data expected Q1 2026. The intramuscular formulation offers a 55-120 minute experience—substantially longer than inhaled 5-MeO-DMT but shorter than psilocybin sessions.

6.4 AtaiBeckley VLS-01 (Buccal DMT Film)​

AtaiBeckley's VLS-01 (buccal DMT film) is conducting a Phase 2 trial (Elumina) in TRD with topline data expected H2 2026, though enrollment has been slower than anticipated.

7. Novel Compounds and Psychoplastogens​

7.1 AbbVie/Gilgamesh Bretisilocin​

The $1.2 billion AbbVie acquisition of Gilgamesh Pharma's bretisilocin in August 2025 represents landmark validation of psychedelic therapeutics. Phase 2a results showed a 28-point MADRS reduction and 94% remission rate with a short-acting tryptamine designed for 2-hour in-clinic administration. AbbVie will advance the program to late-stage development.

7.2 Delix Therapeutics DLX-001 (Zalsupindole)​

Delix Therapeutics' DLX-001 (zalsupindole) leads the non-hallucinogenic psychoplastogen space. Phase 1b data (October 2025) demonstrated a 12-point MADRS drop in MDD patients with once-daily or twice-weekly dosing—without any psychedelic effects or cardiovascular safety signals. FDA has cleared a Phase 2 design featuring at-home administration.

7.3 Ibogaine Development​

Ibogaine development received significant state funding, with Texas appropriating $50 million (Senate Bill 2308) and Arizona adding $5 million for clinical trials targeting PTSD, addiction, and traumatic brain injury. The UTHealth Houston IMPACT consortium is initiating Phase 2 trials across 12 Texas institutions in 2026.

7.4 Reunion Neuroscience RE104​

Reunion Neuroscience's RE104 (prodrug of 4-OH-DiPT) delivered positive Phase 2 results for postpartum depression: 23.0-point MADRS reduction versus 17.2 points for control (p=0.0094), with 92.7% of patients discharge-ready within 4 hours. Phase 3 is planned for 2026.

8. Critical Milestones Expected in 2026​

The coming year will be decisive for the psychedelic therapeutics sector. Key data readouts include:

Timeline	Program	Company	Event
Q1 2026	CYB004	Cybin	Phase 2 GAD topline
Q1 2026	COMP005/006	Compass	26-week/9-week TRD data
H1 2026	VOYAGE	MindMed	Phase 3 GAD readout
Mid-2026	EMERGE	MindMed	Phase 3 MDD readout
Q3 2026	COMP006	Compass	26-week TRD data
H2 2026	VLS-01	AtaiBeckley	Phase 2 TRD topline
H2 2026	PANORAMA	MindMed	Phase 3 GAD readout
Q4 2026	APPROACH	Cybin/Helus	Phase 3 MDD topline

9. Conclusion​

The psychedelic therapeutics pipeline has matured substantially since Q3 2025, with Compass Pathways' positive Phase 3 results establishing proof-of-concept for psilocybin in treatment-resistant depression and positioning the company for a potential late-2026 NDA submission. The Lykos MDMA rejection has paradoxically strengthened the sector by forcing sponsors to design more rigorous trials with better blinding, comprehensive adverse event collection, and clearer separation of drug versus therapy effects.

Several programs could reach FDA approval within the next 18-24 months: COMP360 psilocybin remains the frontrunner, followed by MindMed's MM-120 LSD and Cybin's CYB003. The potential shift to single-trial approval standards could accelerate multiple programs. Meanwhile, major pharmaceutical validation through AbbVie's bretisilocin acquisition signals growing confidence in the therapeutic potential of psychedelics.

Key uncertainties remain around regulatory requirements for psychotherapy-assisted models, insurance reimbursement pathways, and infrastructure needs for specialized treatment settings. However, the breadth of programs in Phase 2/3 development—spanning psilocybin, LSD, MDMA, ketamine, DMT, 5-MeO-DMT, and novel psychoplastogens—suggests that at least some psychedelic therapeutics will reach patients within the next few years.

 

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