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.
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.
J Psychopharmacol
February 28, 2023
Polina Ponomarenko, Federico Seragnoli, Abigail Calder et al.
22 citations
Combining psychedelic substances with group psychotherapy may enhance group connectedness and interpersonal learning, potentially improving prosocial behavior by providing direct opportunities to practice new behavioral patterns. Challenges include a more rigid therapy structure and possible loss of patient openness, which can be mitigated by adequate therapeutic training. The article analyzes existing clinical and neurobiological literature using Yalom's 11 therapeutic factors as a framework, aiming to support clinical research on this approach.
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.
Asian journal of psychiatry
June 26, 2025
Adi Sulstarova, Luise Scheuerlein, Silvia Monari et al.
4 citations
Psychedelic-induced psychosis is rare, occurring in less than 1% of users in controlled trials, but evidence on its treatment is limited. A systematic review of 93 cases from 1955 to 2024 found that LSD (47.3%) and MDMA (38.7%) were the most common substances involved, with an average patient age of 23.7 years and 88% male. Psychosis lasted about 1.8 weeks on average. Second-generation antipsychotics had a response rate of 91.3%, significantly higher than first-generation antipsychotics at 27%. Electroconvulsive therapy also showed a 91% response rate. Follow-up revealed 34% of patients later developed schizophrenia spectrum disorders and 20.4% bipolar disorder, though limited follow-up data constrain these findings.
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.
J Psychiatry Neurosci
July 25, 2025
Michel Sabé, Federico Seragnoli, Gabriel Thorens et al.
2 citations
A case report describes the use of serotoninergic psychedelics to treat depressive and negative symptoms in a person with schizoaffective disorder. The treatment was associated with improvements in these symptoms, suggesting a potential therapeutic benefit. The report highlights the need for further research into psychedelic-assisted therapy for this population.
Philosophical Psychology
July 7, 2025
Florián Cova, Federico Seragnoli
2 citations
Psychedelic experiences share key features with the emotions of awe and being moved. Awe involves a reduced sense of self, a need to adjust one's understanding, and altered time perception; being moved involves feelings of insight, meaningfulness, and connectedness. These emotions may play an important role in psychedelic-assisted psychotherapy. A two-process model is proposed to explain how emotions contribute to therapeutic outcomes, and several testable hypotheses derived from the model are presented.
Schizophrenia Research
March 13, 2026
Michel Sabé, Paul Grof, Nathan B. Sackett et al.
1 citation
Serotonergic psychedelics, which are being explored for treatment-resistant depression, might also help with depressive and negative symptoms in schizophrenia spectrum disorders (SSDs). Schizophrenia and depression share some underlying brain disturbances, including problems with dopamine, glutamate, and neuroplasticity, as well as abnormal brain network connectivity. Depressive symptoms in SSDs may combine features of both disorders, and psychedelics could potentially recalibrate maladaptive brain networks. Preclinical studies show psychedelics increase dendritic spines and BDNF and restore reward sensitivity. Clinical evidence is limited: uncontrolled psychedelic use is linked to increased psychosis, but controlled administration may be tolerated in stable individuals. Only one early-phase trial with MDMA in schizophrenia is ongoing; no randomized trials have tested psilocybin or LSD in SSDs. The authors conclude that psychedelics are biologically plausible but unproven for these symptoms.
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.
Therapeutic advances in psychopharmacology
January 1, 2026
Kristian Beichmann, Polina Catzeflis, Helena D Aicher et al.
In Switzerland, physicians provide psychedelic-assisted therapy (PAT) with psilocybin, LSD, or MDMA under case-by-case exemptions from the Federal Office of Public Health. An anonymous survey of 41 physicians found that PAT is used mainly for depression, anxiety, PTSD, and chronic pain. Most physicians work in private practices (82%) and use body-oriented (61%), psychodynamic (59%), and eclectic (54%) approaches. Psilocybin is the most used substance (85%), followed by MDMA (71%) and LSD (65.9%). Substance choice is linked to diagnosis: psilocybin for depression (54%) and substance use disorder (46%), MDMA for PTSD (86%) and anxiety (54%). Music is played in 90% of sessions. Group therapy is common; 42% provide both individual and group settings. Challenges include legal constraints, high patient expectations, and financial barriers.
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.
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.