Over the past few years, psychedelics have captured growing attention in mental health research. From psilocybin (the active compound in “magic mushrooms”) to LSD and DMT, these substances are being studied in clinical settings to better understand their potential to relieve symptoms of depression, especially in cases where traditional treatments have not worked.
But a common and important question remains: how safe are these studies?
Recent research has shown that psychedelic-assisted therapy may offer meaningful improvements for individuals living with major depressive disorder (MDD) and treatment-resistant depression (TRD).
In a 2022 study published in JAMA Psychiatry, participants receiving psilocybin-assisted sessions experienced clinically significant reductions in depressive symptoms that were sustained for several weeks after treatment. Likewise, a Johns Hopkins University trial found that 71% of participants showed improvement four weeks after psilocybin-assisted therapy, with nearly half maintaining the benefit three months later.
These findings have encouraged ongoing research efforts worldwide and prompted the U.S. Food and Drug Administration (FDA) to grant Breakthrough Therapy Designation to psilocybin-based approaches for depression, reflecting both their potential and the need for continued evaluation through safe, structured studies.
Despite the enthusiasm, psychedelic studies are not casual experiences. They take place in highly controlled, medical environments, designed to ensure safety and data integrity.
Before enrollment, participants undergo comprehensive health screenings to rule out any risks, such as psychosis, mania, or unstable medical conditions. During dosing sessions, trained clinical staff remain present at all times to monitor psychological and physiological responses.
According to a 2023 JAMA Psychiatry review, across hundreds of participants in psychedelic trials, no serious drug-related adverse events have been reported when conducted under proper supervision. Common temporary effects, such as mild anxiety or nausea, typically resolve within hours.
Another layer of safety in psychedelic studies involves psychological preparation and integration.
Participants meet with trained therapists before the dosing session to discuss expectations and emotional readiness (“set”), and the sessions take place in calm, supportive environments (“setting”). Afterward, integration sessions help participants process their experiences in a healthy, structured way.
This approach, often described as “therapy-assisted dosing” is considered essential to both the safety and potential benefit of psychedelic research.
In 2023, the FDA issued its first draft guidance for psychedelic drug trials, reinforcing that these studies must follow the same scientific and ethical standards as any other investigational drug research. The guidance also highlights unique considerations for psychedelics, such as managing altered states of consciousness and ensuring patient support during and after sessions.
This regulatory involvement reflects a growing recognition of the field’s potential — and a commitment to protecting participants every step of the way.
While psychedelics for depression are not yet approved treatments, the science is advancing quickly and safely.
Clinical research shows encouraging signs that these substances, when used responsibly and within medical settings, may offer new hope for people living with depression.
At Segal Trials, our role is to support the advancement of this science through ethical, participant-centered research that prioritizes safety, transparency, and compassion.
JAMA Psychiatry (2023): Safety and Efficacy of Psilocybin-Assisted Therapy
Johns Hopkins Center for Psychedelic and Consciousness Research (2022)
U.S. Food & Drug Administration (2023): Draft Guidance for Clinical Trials with Psychedelic Drugs
National Institutes of Health (2024): Review on Psychedelics and Depression