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 Dauré 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.
Current neuropharmacology
January 1, 2024
Michel Sabé, Chaomei Chen, Wissam El-Hage et al.
25 citations
A scientometric analysis of 42,170 publications on posttraumatic stress disorder (PTSD) from 1945 to 2022 identified four major research trends: war veterans and refugees, treatment of PTSD/neuroimaging, evidence syntheses, and somatic symptoms of PTSD. The largest cluster focused on evidence synthesis for genetic predisposition and environmental exposures leading to PTSD. War-related trauma research has shifted from battlefield in-person exposure to drone operator trauma and is being outpaced by civilian trauma research, including the COVID-19 pandemic, postpartum, and grief disorder. Recent trends show a burst in PTSD treatment research involving Mhealth, virtual reality, and psychedelic drugs. The USA dominates collaboration networks, with a recent surge of publications from China. Compared to other psychiatric disorders, there is a lack of high-quality randomized controlled trials for pharmacological and nonpharmacological treatments.
Eur Neuropsychopharmacol
November 7, 2025
Mikkel Højlund, Helin Y. Kafali, Begüm Kırmızı et al.
12 citations
A living systematic review with meta-analysis examined the efficacy, safety, and all-cause discontinuation of serotonergic psychedelics and MDMA for treating mental disorders. The review found that these substances show promise in reducing symptoms of conditions such as depression, anxiety, and post-traumatic stress disorder, with some evidence supporting their therapeutic potential. However, the authors note that the overall quality of evidence is limited by small sample sizes, short follow-up periods, and methodological concerns. Safety profiles varied, with most adverse events being mild to moderate, though serious adverse events were reported in some studies. The review emphasizes the need for larger, more rigorous trials to confirm these findings.
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.
International journal of molecular sciences
September 14, 2025
Jacopo Sapienza, Marco Spangaro, Stefano Comai et al.
2 citations
Schizophrenia involves excessive loss of brain connections, partly due to overactive microglia that prune synapses. A genetic variant in complement component 4 (C4) is strongly linked to the disease and drives this pruning. Brain scans using a new tracer for synaptic vesicle glycoprotein 2A (SV2A) confirm lower synaptic density in the prefrontal cortex of people with schizophrenia, supporting the synaptic hypothesis. Psychedelics like LSD and psilocybin promote neuroplasticity and synaptogenesis in animal and lab studies, potentially counteracting synaptic loss and improving negative and cognitive symptoms. The authors suggest starting with microdoses in deficit schizophrenia patients, then escalating if results are positive.
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.
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.
Psychedelics
May 14, 2026
Joseph la Torre, Jade Gallo, Matteo Buonaroti et al.
People with histories of psychotic symptoms who used psychedelics in naturalistic settings reported both benefits and harms. Benefits included personal growth, insight, increased spirituality, and symptom reappraisal. Challenging experiences and adverse effects also occurred, especially when set and setting were unfavorable. The findings question the categorical exclusion of this population from psychedelic research and therapy, and call for more holistic, ethically guided study of psychedelic-assisted therapy for this underserved group.
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.