A review of seven trials involving 464 adults with major depressive disorder found that psilocybin significantly reduces depression symptoms and is generally safe and tolerable. Higher doses (35–50 mg per 70 kg of body weight) and a double-dosing schedule were associated with better outcomes. The overall quality of the trials was moderate, and the authors note that the results are limited by small sample sizes and short follow-up periods, indicating a need for further research.
A novel formulation combining deuterated dextromethorphan (SAL0114) with bupropion showed twice the metabolic stability of standard dextromethorphan in both laboratory and mouse tests, and bupropion further increased its exposure by 2.4 times. The combination demonstrated superior antidepressant and synergistic effects in mouse and rat models compared with the non-deuterated dextromethorphan-bupropion combination, while maintaining the same in vitro activity. Deuteration did not alter the compound's activity but improved its stability, potentially reducing neurologic side effects from metabolites and allowing lower bupropion doses. Clinical studies are needed to confirm these preclinical findings.
A bibliometric analysis of 30 years of research on MDMA-assisted therapy for PTSD, anxiety, and depression shows a substantial increase in publications over the past decade. The United States leads in output, the Multidisciplinary Association for Psychedelic Studies (MAPS) is the most productive institution, and Rick Doblin is a highly influential researcher. The research focus has shifted from studying MDMA's neurotoxicity to exploring its therapeutic mechanisms, safety, and clinical applications. The analysis identifies key research trajectories and challenges, including the need for improved trial design, greater sample diversity, and evaluation of long-term effects to support clinical integration.