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.
BMC psychiatry
January 26, 2024
Laetitia Vanderijst, Felix Hever, Anne Buot et al.
11 citations
A proposed clinical trial will test whether adding psilocybin-assisted therapy to inpatient rehabilitation for severe alcohol use disorder is feasible and effective. In a double-blind, randomized, placebo-controlled phase II trial, 62 participants aged 21–64 will receive either a high dose (30 mg) or an active placebo dose (5 mg) of psilocybin alongside a brief psychotherapy based on acceptance and commitment therapy. The main outcome is the difference in heavy drinking days from baseline to four weeks after hospital discharge. Secondary outcomes include drinking behavior up to six months, mental health symptoms, neuroplasticity, and cognitive mechanisms. The trial is registered as EudraCT 2022-002369-14 and NCT06160232.
Pharmaceutics
June 11, 2025
Bernard Do, Luc Mallet, Maxime Annereau et al.
D-lysergic acid diethylamide (D-LSD), being investigated for alcohol use disorder, is extremely sensitive to light, which complicates formulation for clinical trials. A liquid-filled capsule formulation was developed to protect D-LSD from photodegradation while providing accurate dosing. Using liquid chromatography with ion mobility spectrometry and mass spectrometry, along with quantum chemical calculations, researchers characterized degradation products. Photostress studies showed that D-LSD in solution rapidly degrades into photoisomers and photooxidative byproducts, but the capsule formulation markedly reduced these transformations under ICH-compliant conditions. Orthogonal stability profiling is essential for guiding formulation development, and this capsule approach may offer a viable, photostable platform for future clinical investigation of D-LSD.
Research Square (Research Square)
January 4, 2024
Laetitia Vanderijst, Felix Hever, Anne Buot et al.
A proposed double-blind, randomized, placebo-controlled phase II trial will test whether adding psilocybin-assisted therapy to a 4-week inpatient rehabilitation program for severe alcohol use disorder is feasible and clinically effective. Sixty-two participants aged 21–64 years will receive either a high dose (30 mg) or an active placebo dose (5 mg) of psilocybin, both paired with a brief acceptance and commitment therapy intervention. The primary clinical outcome is the change in percentage of heavy drinking days from baseline to four weeks after hospital discharge. Secondary outcomes include drinking behavior up to six months, symptoms of depression and anxiety, neuroplasticity, and changes in neurocognitive systems linked to addiction.