FDA Weighs Safety and Access Rules as Psychedelic Therapies Advance

US regulators have heard calls for clear safety and access standards for psychedelic therapies at a public meeting, part of a broader push to accelerate development of treatments such as ibogaine and psilocybin.

Nearly all psychedelic drugs remain Schedule I controlled substances in the United States, placing them in the same category as heroin or ecstasy — deemed to have no accepted medical use and a high potential for abuse. Despite that classification, several treatments derived from psychedelic compounds are under development.

What is being tested

The strongest evidence so far comes from trials in patients with severe depression or post-traumatic stress disorder who have not responded to existing treatments. Early-stage studies are also exploring psychedelic drugs for substance use disorders, borderline personality disorder, obsessive-compulsive disorder, anxiety, self-harm behaviour, chronic Lyme disease and fibromyalgia.

These treatments work mainly by activating proteins on the surface of nerve cells that govern the brain's ability to reorganise, form new connections and repair damaged circuits. Unlike conventional psychiatric drugs taken daily at home, they are typically given by medical staff in a limited number of sessions alongside intensive psychotherapy.

Where they are already authorised

Australia has approved the synthetic psychoactive drug midomafetamine (MDMA) for PTSD and psilocybin, a compound found in certain mushrooms, for treatment-resistant depression. Switzerland permits limited psilocybin psychotherapy, while Jamaica allows over-the-counter psilocybin sales in chocolates, teas and other products. Brazil and the Netherlands allow plant-based psychedelics found in ayahuasca and mushrooms.

In the US and Europe, Johnson & Johnson's esketamine nasal spray Spravato is approved for treatment-resistant depression and suicidal ideation. Esketamine is derived from one half of the ketamine molecule and, like ketamine, is technically an anaesthetic, but is regarded as a non-classical psychedelic medicine because of its mind-altering therapeutic effects. Ketamine is authorised in the US for anaesthesia and is often used off-label for depression. Mexico draws patients, including US veterans, seeking ibogaine treatment, which medical professionals can legally administer there.

Closest to approval

In the US and Europe, psilocybin is the leading candidate for authorisation, for treatment-resistant depression. In two late-stage trials, single oral doses of Compass Pathways' experimental synthetic psilocybin, COMP360, reduced depressive symptoms within days, with responses lasting up to six months. The company released one-year follow-up data in September supporting the treatment's durability and has said it expects to complete a new drug application to the FDA in late 2026.

Filament Health's naturally derived psilocybin capsule, PEX010, is being tested in the US and elsewhere for depression, PTSD and cancer-related distress. In 2025 it became the first psilocybin drug to receive a compassionate use approval in the European Union.

Definium Therapeutics' LSD-based treatment showed significant reductions in generalised anxiety disorder and depression symptoms across three trials. LSD, commonly known as acid, is a synthetic psychedelic that alters perception, mood and cognitive processes and is primarily used recreationally.

Other pipeline candidates include ibogaine, found in the roots of the African shrub iboga. Based on small studies in military veterans with traumatic brain injuries and addiction, US authorities have said they plan to accelerate research into it; companies involved in production include Psyence BioMed and Optimi Health. Also in trials are a synthetic version of 5-MeO-DMT, a substance found in frog venom, being tested as a nasal spray for refractory depression and alcohol use disorder by Beckley Psytech with Atai Life Sciences, and psilocin, the active metabolite of psilocybin, being tested intravenously by Beckley.

In two large Phase 3 trials, roughly two-thirds of patients given an MDMA capsule from Lykos Therapeutics no longer met diagnostic criteria for PTSD at follow-up, twice the rate of control groups. While effects persisted for months for many participants, the FDA declined approval in August 2024, citing problems with study methods, and requested another Phase 3 trial. Lykos has not publicly commented on plans for that study.

Known risks

Risks of psychedelic-assisted therapy include acute anxiety, panic and confusion during administration, as well as short-term worsening of mood or distress. An estimated 10% to 15% of patients experience longer-term negative effects. Psychosis or mania can also develop, particularly in people with bipolar disorder or schizophrenia or a strong family history of those conditions.

Physical risks include nausea and headache with psilocybin, fatal cardiac arrhythmias with ibogaine, and transient rises in blood pressure, heart rate and body temperature with MDMA. The likelihood of these effects is higher when the drugs are used outside clinical settings.