WHAT TO KNOW ABOUT PSYCHEDELICS
Drugs are being tested to treat disorders and several other ailments
U.S. President Donald Trump signs an executive order encouraging more research into ibogaine April 18 in the Oval Office of the White House in Washington.
HEALTH CARE
President Donald Trump signed an executive order this month directing health regulators to speed reviews of psychedelic treatments and increase federal funding for research into their use in response to advocates for the drug ibogaine.
Presently almost all psychedelic drugs in the United States are considered Schedule I controlled substances, in the same class as heroin or ecstasy, meaning they are deemed to have no medical use and high risk for abuse.
Drugmakers are testing several treatments derived from psychedelic compounds.
The strongest evidence for use of the drugs so far came from trials in patients with severe depression or post-traumatic stress disorder who didn't respond to existing treatments.
Early stage trials also are test psychedelic drugs for substance abuse disorders, borderline personality disorder, obsessive-compulsive disorders, anxiety, selfharm behavior, chronic Lyme disease and fibromyalgia.
How do they work?
Psychedelic treatments work primarily by activating proteins on the surface of nerve cells that regulate the brain's ability to reorganize, form new connections, and repair damaged circuits. Unlike traditional psychiatric drugs that may be taken at home on a daily basis, these treatments are usually administered by medical personnel in a limited number of sessions to supplement intensive psychotherapy.
Which ones are authorized for use?
In Australia, the synthetic psychoactive drug midomafetamine, or MDMA, is approved for PTSD, and psilocybin — a naturally occurring psychedelic compound in certain mushrooms — is authorized for treatment-resistant depression.
Switzerland allows limited use of psilocybin psychotherapy, while Jamaica allows psilocybin sales over the counter in chocolates, teas and other products. Brazil and the Netherlands allow plant-based psychedelics found in ayahuasca and mushrooms.
In the U.S. 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. Like ketamine, esketamine is technically an anesthetic but has been considered a nonclassical psychedelic medicine because it produces mind-altering eff ects that can be therapeutic. Ketamine is authorized in the U.S. for anesthesia but is often used off -label for depression.
Mexico attracts patients, including U.S. veterans, seeking treatment with legally administered ibogaine there.
Which are in trials?
In the U.S. and Europe, the leading candidate for authorization is psilocybin 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 6 months.Compass said it expects to complete a new drug application submission to the FDA this year.
Filament Health's naturally derived psilocybin capsule, PEX010, is being tested in the U.S. and elsewhere for depression, PTSD and cancer-related distress. In 2025, PEX010 became the first psilocybin drug to receive a compassionate use approval in the European Union.
Psychedelic drugs in the pipeline also include ibogaine, a compound found in the roots of the African shrub iboga. Based on small studies in military veterans with traumatic brain injuries and addiction, U.S. authorities said they plan to accelerate research into ibogaine.Companies involved in production include Psyence BioMed and Optimi Health.
Also in clinical 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 in partnership with Atai Life Sciences, and psilocin, the active metabolite of psilocybin, is being tested in intravenous form by Beckley.
In two large Phase 3 trials, about two-thirds of patients receiving an MDMA capsule from Lykos Therapeutics no longer met diagnostic criteria for PTSD at follow-up, twice that of patients in the control groups. The FDA declined approval in August 2024, citing problems with study methods, and requested another Phase 3 trial.
What are the risks?
Risks of psychedelic-assisted therapy include acute anxiety, panic and confusion during administration of the medicine, as well as short-term worsening of mood or distress. An estimated 10% to 15% of patients experience longer-term negative eff ects.
Psychosis or mania also can develop, especially in people with bipolar disorder or schizophrenia or a strong family history of those disorders.
Physical risks include nausea and headache with psilocybin, fatal cardiac arrhythmias with ibogaine, and transient increases in blood pressure, heart rate and body temperature with MDMA.
The risks of any of these eff ects are higher when the drugs are used outside of clinical settings.
