A recent study found that professional psychotherapy combined with the administration of LSD or psilocybin was associated with significant reductions in severe depression and anxiety. These mental health improvements appeared relatively quickly and occurred within a standard hospital care program. The study results were published in the journal Psychiatry Research.
In recent years, researchers have renewed their investigation into the medical potential of classic psychedelics. Conditions such as severe depression and generalized anxiety disorder do not always respond to standard psychiatric medications. For many people, initial treatments such as selective serotonin reuptake inhibitors do not provide lasting relief from persistent sad mood or chronic worry.
People who do not respond to multiple standard treatments are often diagnosed with treatment-resistant disease. This situation leaves options in conventional medical practice limited. Psychedelic-assisted therapy has emerged as a promising alternative for these people in closely monitored experimental trials.
These therapies combine traditional talk therapy with the ingestion of mind-altering substances under professional supervision. The goal is to induce temporary changes in consciousness to help patients process difficult emotions. Trained therapists can help patients integrate these conceptual insights into their daily lives after the effects of the medication wear off.
Most of the current evidence regarding these treatments comes from randomized controlled trials. Although these trials provide rigorous baseline data, they often exclude patients with varying medical histories to isolate specific chemical variables. This strict filtering means that the results do not always fully reflect patients in general hospitals.
To understand how these treatments work outside of rigorous experiments, researchers are turning to compassionate use programs. These legal frameworks allow doctors to administer unapproved experimental drugs to patients who have exhausted all other available treatments. Switzerland operates one such framework, giving doctors limited permission to use special substances in cases of severe mental illness.
Tatiana Aboulafia-Bulaka, a researcher at Geneva University Hospital, led the effort to analyze data from one of the Swiss clinical programs. Aboulafia-Bulaka and her team wanted to evaluate outcomes for patients who received these treatments in a routine hospital setting. They sought to document changes in mental health symptoms and how well patients tolerated the experience.
The research team collected retrospective data from a cohort of adults diagnosed with treatment-resistant depression or anxiety disorders. This cohort received their first standardized treatment cycle between May 2024 and October 2025. Each individual received either 100 micrograms of LSD or 25 milligrams of psilocybin during the session.
Psilocybin is the main psychoactive compound found in certain species of hallucinogenic mushrooms. LSD is a synthetic chemical known for powerful changes in perception and thought patterns. Patients were able to select their preferred substance based on personal comfort, expected session length, and cost.
This program required extensive preparation before actually administering the drug. Patients attended a screening session where their medical history was reviewed to ensure that no underlying cardiac or neurological conditions were present. They also attended a preparatory meeting to set treatment intentions and learn coping strategies, such as breathing techniques, to deal with moments of acute fear.
On the day of treatment, patients arrived at the outpatient clinic and were settled into a quiet room under the constant supervision of a psychiatric nurse. Nurses monitored vital signs and intervened only when patients requested support or needed help dealing with difficult psychological reactions. The patient then remained in the clinic until the acute subjective effects had completely resolved.
The patient returned the next day for an integration session with the psychotherapist. During these conversations, patients discussed the images, physical sensations, and emotional revelations they experienced while administering the drug. The therapist then helped translate those abstract insights into actionable behavioral routines.
To quantify the results, the researchers administered standard psychological questionnaires at three different time points. Patients completed questionnaires at initial screening, 1 month before treatment, and 1 to 3 months after the session. These tools measured the severity of general sadness, pessimism, and habitual stress responses.
The research team observed significant reductions in both depression and anxiety scores during the treatment period. More than a third of the sample reported that their depressive symptoms were reduced by at least half. In smaller portions, modest but significant symptom relief was recorded. These benefits appear to be robust across a broader cohort, supporting previous findings from highly controlled laboratory settings.
The choice of substance does not appear to alter long-term treatment outcomes. Patients who took LSD and patients who took psilocybin experienced nearly identical improvements in their daily mental health.
Aboulafia-Bulaka and her team also looked at how patients managed their emotions before and after treatment. Some patients completed emotion regulation surveys that measured strategies such as rumination and catastrophizing. Rumination refers to thinking about negative emotions repeatedly, while catastrophizing refers to the tendency to expect the worst outcome in any situation.
After treatment, patients reported a significantly reduced tendency to ruminate, catastrophize, and blame themselves for negative events in their lives. They also demonstrated an increased ability to positively reappraise. This means it’s easier to find a constructive perspective in difficult situations. These conceptual changes are consistent with psychological theories that hold rigid thinking to be a major maintenance factor in severe depression.
Although the long-term clinical benefits were similar for both substances, the acute physical experience was markedly different. The data showed that LSD produced a longer-lasting plateau of stronger subjective effects. Psilocybin caused similar peaks in intensity, but the overall duration of the psychoactive experience was significantly shorter.
Despite these different timelines, the overall intensity of mystical experiences reported by patients was approximately comparable. Similar scores were obtained on questionnaires measuring a deep sense of belonging, distinct changes in time perception, and deep spiritual insight. These results support the concept that subjective course may be more important than specific pharmacological timelines.
Safety evaluations showed that both substances were well tolerated within the hospital environment. Although many patients reported no side effects, most of the side effects recorded were mild and temporary. The most common physical complaints included temporary blurred vision, dizziness, and mild nausea during the drug’s duration.
The research team did not record any serious medical complications or serious psychiatric emergencies during the study period. No patients discontinued treatment due to side effects. These details provide reassuring baseline evidence for medical professionals concerned about the introduction of powerful psychedelics into general outpatient clinics.
This study has several limitations due to its retrospective design and observational nature. The researchers did not include a placebo group. This means that the influence of patient expectations cannot be completely eliminated. Patients who seek rigorous medical treatment often expect to feel better, and this expectation can artificially exaggerate self-reported symptom relief.
This cohort was highly motivated given the long wait times and financial costs associated with compassionate use programs. This unique decision between participants could mean different outcomes in less motivated patient populations. Reliance on self-report questionnaires also leaves room for recall bias to influence the data.
Future studies should implement randomized designs that include active placebos to better isolate the specific physiological effects of treatment. Combining patient self-report with objective assessment from an independent clinician may ensure a more reliable assessment of long-term improvement. Until then, these findings provide an encouraging glimpse into the practical realities of psychedelic therapy in standard psychiatric settings.
The study, “Real-world efficacy and safety of psychedelic-assisted psychotherapy: Results from a large compassionate use cohort in Switzerland,” was presented by T. Aboulafia-Brakha, A. Buchard, C. Mabilais, S. Alaux, C. Amberger, L. Furtado, F. Seragnoli, JF Sabé, L. Szczesniak, and R. Iuga. , D. Zurino, and L. Penzenstadler.
