European Neuropsychopharmacology
August 7, 2023
Natacha Perez, Florent Langlest, Luc Mallet et al.
85 citations
A systematic review and dose-response meta-analysis of seven double-blind randomized placebo-controlled trials involving 489 adults with depression found that the optimal daily dose of psilocybin to reduce depression scores varies by population. The 95% effective dose (ED95) was 8.92 mg/70 kg for secondary depression, 24.68 mg/70 kg for primary depression, and 36.08 mg/70 kg when combining both subgroups. Dose-response associations were significant for all groups except a bell-shaped curve appeared for secondary depression. Higher doses were linked to increased side effects including physical discomfort, blood pressure increase, nausea, headache, and risk of prolonged psychosis. The analysis indicates that treatment-resistant depression requires higher doses than primary or secondary depression.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
November 1, 2022
Marco Solmi, Chaomei Chen, Charles Daure et al.
55 citations
Over the past century, clinical research on psychedelics has evolved from an early focus on safety into a 'psychedelic renaissance' after the 1990s. A scientometric analysis of 31,687 documents from the Web of Science identified major research themes: hallucinogens/entheogens, entactogens, novel psychoactive substances (NPS), and dissociative substances. The field has shifted from basic science to clinical applications, including phase 2 and 3 trials and evidence synthesis. Recent trends include NPS, ketamine-associated brain changes, and ayahuasca-assisted psychotherapy. The USA and Canada lead in productivity, reflecting legislative influences. This translational evolution has already led to esketamine approval for depression and may lead to further approvals across mental and physical conditions. Toxicology screening tools for NPS are urgently needed and may follow a similar path.
Molecular psychiatry
March 1, 2025
Michel Sabé, Adi Sulstarova, Alban Glangetas et al.
39 citations
A systematic review and meta-analysis assessed the risk of psychedelic-induced psychosis in people with schizophrenia. Among population studies, the incidence was 0.002%; in uncontrolled trials, 0.2%; and in randomized controlled trials, 0.6%. In uncontrolled trials that included individuals with schizophrenia, 3.8% developed long-lasting psychotic symptoms. Of those who experienced psychedelic-induced psychosis, 13.1% later developed schizophrenia. The evidence suggests schizophrenia might not be an absolute exclusion for clinical trials on psychedelics for treatment-resistant depression and negative symptoms, but low study quality and limited data warrant a conservative approach until more research is done.
Annales Médico-psychologiques revue psychiatrique
July 10, 2024
Federico Seragnoli, Gabriel Thorens, Louise Penzenstadler et al.
8 citations
A team at Geneva University Hospitals developed an interdisciplinary model for psychedelic-assisted psychotherapy (PAP) that combines the altered state of consciousness induced by LSD or psilocybin with traditional dialogue-based psychotherapy. Since 2014, Swiss law has allowed exceptional medical authorizations for these substances. From September 2020 to February 2024, the team received 224 personal authorizations (114 for LSD, 110 for psilocybin) and conducted 396 individual sessions. The protocol includes patient selection, preparatory psychoeducation, controlled substance administration, and integration sessions. The authors argue that psychedelic-induced consciousness alteration can act as a catalyst to revive stalled psychotherapeutic processes and call for continued research and broader clinical integration of PAP.
Cognitive Therapy and Research
March 29, 2025
Federico Seragnoli, Fabienne Picard, Gabriel Thorens et al.
4 citations
The noetic (insightful) quality of mystical-type experiences in psychedelic-assisted therapy may arise from changes in metacognition—the ability to monitor and evaluate one's own thoughts. Drawing on existing metacognition models, the authors propose that psychedelics activate procedural, performance-based metacognitive feelings, producing an 'Aha!' experience interpreted as a feeling of epistemic gain. This framework could help explain therapeutic mechanisms such as intention setting, music's role, traumatic memory recall, and spiritual bypassing. The paper reviews theoretical links between metacognition and altered states like meditation and lucid dreaming, then outlines future research directions.
Molecular psychiatry
May 29, 2026
Mickael Eskinazi, Rayan Nasserdine, Romane M Cusin et al.
A systematic review of 23 studies examined whether serotonergic psychedelics (psilocybin, LSD, mescaline, DMT/ayahuasca) or MDMA can trigger manic or hypomanic symptoms. Rates of such symptoms ranged from 5.8% in controlled trials of psilocybin-assisted therapy for depression to 30% in naturalistic studies of people with bipolar disorder. When manic symptoms occurred, they were typically acute and self-limited. Higher risks were seen in individuals with bipolar I disorder, family vulnerability, polysubstance use, or unsupervised use. Registry data showed a 4% prevalence of later transition to bipolar disorder, with little evidence for a hallucinogen-specific signal. The authors conclude that these substances pose a low but clinically meaningful relative risk of transient mood symptoms in susceptible individuals while remaining relatively safe in controlled settings.
Psychology International
December 19, 2025
M Cheng, Tatiana Aboulafia Brakha, Albert Buchard et al.
LSD and psilocybin produce different patterns of heart rate change over time in patients with treatment-resistant depression or anxiety disorders. In a small retrospective study of 30 patients receiving either substance during supervised sessions, LSD caused a delayed but sustained heart rate increase peaking at 3–4 hours, while psilocybin led to an earlier decline. Anxiety levels did not explain these differences, and no serious cardiovascular events occurred. The distinct temporal profiles suggest the two psychedelics may activate the cardiovascular system differently in clinical populations, though the findings are preliminary due to the small sample and retrospective design.
medRxiv
December 1, 2025
Tatiana Aboulafia Brakha, Albert Buchard, Cédric Mabilais et al.
preprint
In a real-world clinical setting, a single dose of LSD (100 µg) or psilocybin (25 mg) combined with psychotherapy significantly reduced depression and anxiety symptoms in 115 adults with treatment-resistant disorders. Symptoms were measured one to three months after treatment, with no serious adverse events. Patients also showed reduced rumination, self-blame, and catastrophizing, along with increased positive refocusing and reappraisal. Both substances produced comparable clinical benefits despite different subjective effect profiles. The findings suggest that psychedelic-assisted psychotherapy is feasible and effective in routine specialized care.
Research Square
December 1, 2025
Albert Buchard, Federico Seragnoli, Michel Sabé et al.
Early maladaptive schemas (EMS) are common in people seeking psychedelic-assisted psychotherapy and are strongly linked to baseline depression and anxiety. In 192 adults assessed for EMS and 74 patients followed through psilocybin- or LSD-assisted therapy, baseline schema burden—especially around failure and defectiveness—was tied to cognitive-depressive symptoms. However, schema burden did not predict the quality of the acute psychedelic experience or moderate overall symptom improvement. Patients experienced significant reductions in depression and anxiety with each session, but these changes depended on initial symptom severity, not their schema profile. Treatment effects were similar for psilocybin and LSD. The findings indicate that EMS are useful for identifying cognitive-emotional themes, such as core beliefs about failure, to address during psychotherapeutic integration, rather than for patient selection or outcome prediction.
Psychoactives
September 1, 2025
M Mercier, Cédric Mabilais, Vasileios Chytas et al.
A patient with persistent somatoform pain disorder and recurrent depressive disorder underwent four sessions of psilocybin-assisted psychotherapy. The intervention was associated with reduced negative impact of pain on daily life, increased pain acceptance, improved quality of life, and fewer depressive symptoms. The case suggests that psychedelics combined with psychotherapy may offer a novel approach to chronic pain treatment, though controlled studies are needed.
Psychoactives
August 1, 2025
L. Cazorla, S. Alaux, C. Amberger et al.
Salivary oxytocin levels changed significantly over time during a single LSD-assisted psychotherapy session in people with treatment-resistant major depressive disorder. Perceived psychedelic intensity also varied significantly. These findings suggest oxytocin may serve as a biomarker for the therapy's effects. The study was a small observational pilot; larger controlled trials are needed to confirm the results and clarify how oxytocin dynamics relate to changes in depressive symptoms and mental flexibility.
Research Square (Research Square)
May 12, 2023
Gabriel Thorens, Louise Penzenstadler, Leonice Furtado et al.
A patient with generalized anxiety disorder and claustrophobia who had not improved with conventional therapy underwent three sessions of psilocybin-assisted psychotherapy that included both imaginary and real exposure to an elevator. After treatment, anxiety and fear of closed spaces, elevators, and planes decreased. Scores on the Beck Depression Inventory-II, State-Trait Anxiety Inventory, and Fear Questionnaire showed significant improvement. The patient reported feeling more relaxed, more willing to face fearful situations, and a shift in perception of fearful stimuli, possibly reflecting new memory representations and a disconfirmatory experience.