Making Mental Health Drugs: Promising Therapies And Manufacturing Challenges
By Katie Anderson, Chief Editor, Pharmaceutical Online
More psychedelic therapies for mental health may soon be on the market, with an Executive Order being issued on Apr. 18, 2026 by President Trump directing the U.S. Department of Health and Human Services (DHHS), U.S. Food and Drug Administration (FDA), Drug Enforcement Administration (DEA) and The Department of Veterans Affairs (VA) to collaborate on fast-tracking these important therapies to patients.
The order notes the prevalence of mental health disorders such as depression, substance abuse, and post-traumatic stress disorder (PTSD). It also references rising suicide rates, especially the disproportionate statistics of veteran suicides.
Psychedelic therapies have shown promise in treating mental health disorders, but it will take close collaboration and cooperation of all related agencies and manufacturers to make this promise a reality.
FDA Approval Roadblocks
Currently, there are no classic psychedelics approved by the FDA. Psychedelic-adjacent ketamine was approved by the FDA as an anesthetic in 1970, and esketamine was approved for depression in 2019.
The FDA has granted Breakthough Therapy designation for a handful of psychedelic compounds in the past decade, including: Lykos’ MDMA-assisted therapy (2017), Compass Pathway’s COMP360 (2018), Ursona’s psilocybin (2019), Cybin’s CYB003 (2024), and MindMed’s MM120. However, none have been approved, and the closest to reaching the finish line was Lykos, which was found to have bias, side effect/risk concerns, and missing data. One major hurdle many psychedelics will face during clinical trails is blinding the clinician and patient, when it is pretty obvious who got the drug and who didn’t.
Under the new order, FDA will grant Commissioner’s National Priority Vouchers to Breakthrough Therapy drugs that show promise over current mental illness therapies. The FDA announced it had issued three NPVs to companies for psilocybin (treatment resistant depression and major depression disorder) and methylone (PTSD); however, it did not note which companies received these NPVs. It is also allowing an early phase clinical study of noribogaine hydrochloride to move forward following an Investigational New Drug (IND) submission.
Final guidance documents for sponsors developing these drugs is also expected, including recommendations for study design, data collection, patient monitoring and clinical trial design.
Legal Compliance
Beyond FDA approval, the production of psychedelic therapeutics requires registration with both the Drug Enforcement Administration (DEA) and the individual state. Psychedelics are schedule 1 substances with the DEA, and facilities must be registered to handle these substances. As you can imagine, the application is detailed, with strict guidelines on the security of the materials, safe handling of the chemicals, and personnel disclosures. As such, there are not many manufacturers that carry this registration.
These facilities must have vaults to store the materials, constant documentation throughout the process to account for the materials, and staff must be specially trained and verified. The facilities must also be registered with their individual state for the handling of controlled substances.
Promising Psychedelics and Adjacent Therapies
Compass Pathway and Helus Pharma (formerly Cybin) are both in phase III for their psychedelic therapies. Compass’ COMP360 is a psilocybin for treatment-resistant depression, and it is considered a frontrunner in the space.
Helus Pharma’s HLP003 is a psilocin for major depressive disorder in phase III clinical trials. The company also has a DMT therapy in phase II trails for generalized anxiety disorder.
Definium (formerly MindMed) is in phase III clinical trails for its LSD derivative DT120 for both major depressive disorder and generalized anxiety disorder. It also has a MDMA in phase II for autism treatment.
Large pharma manufacturers are starting to enter the market. In fall 2025, AbbVie acquired bretisilocin (GM-2505) from Gilgamesh Pharmaceuticals Inc. for $1.2 billion. GM-2505 is targeted to major depressive disorder.
Notably, there are biotechs taking a different route by developing neuroplastogens without hallucinogenic effects. These drugs are able to treat mental health disorders without the controlled substance restrictions.
Delix Therapeutics’ zalsupindole (DLX-001) is currently moving to phase II clinical trials for major depressive disorder. EB-003 from Enveric is moving to phase I clinical trails for the treatment of depression, PTSD and generalized anxiety.
Better Mental Health On The Way
The Executive Order to speed up the advancement of psychedelics for mental health treatment certainly is a step in the right direction, but there are still challenges that need to be resolved. Designing these clinical trails without bias and providing the right documentation and data are just two of these challenges. As most of the manufacturers are biotechs without manufacturing capabilities, commercial quantities may put capacity constraints on the handful of facilities approved to make these drugs.
Once approved and produced, these therapies also face the challenge of needed supervision in dosing. And with the breadth of patients suffering from severe depression, anxiety, and PTSD, this challenge may prove larger than expected.
One thing is for sure—better mental health treatments are on the way. Whether through psychedelics or psychedelic-inspired treatments, the industry is taking positive steps toward better mental health for patients.