A systematic review of randomized trials of psychedelics in humans found that most studies use inert placebos rather than active comparators, and very few assess whether blinding was successful. Of 86 unique studies, 61.2% used an inert placebo, 20.0% used active comparators, and only 17.3% included any assessment of blinding; when assessed, blinding success was generally poor. Only 3 of 21 therapeutic trials compared psychological support to a minimally supportive condition. The review concludes that randomized psychedelic trials underutilize blind assessment, active drug controls, and adequate control conditions for psychological support, and recommends improvements to trial methods.
A review sponsored by a public-private partnership addresses clinical trial design for new opioid use disorder (OUD) treatments that target systems other than the μ-opioid receptor. The authors present consensus recommendations for evaluating novel therapies such as cannabinoids, psychedelics, sedative-hypnotics, and immunotherapeutics. Key design elements include specifying the treatment stage (e.g., early abstinence, long-term recovery), defining the treatment's role (adjunctive or independent), selecting patient-informed primary outcomes that assess opioid use patterns, retention, and quality of life, and monitoring adverse events like relapse or overdose, especially when patients are not on maintenance opioid agonist or antagonist medications. Incorporating input from people with lived experience is urged to accelerate development and uptake of effective therapeutics.
Ketamine causes less cognitive impairment than triazolam at doses that produce greater subjective effects, and unlike triazolam, it does not lead to an underestimation of impairment. In a double-blind study with 20 healthy volunteers, ketamine impaired balance only when assessed early, while triazolam impaired psychomotor coordination and divided attention regardless of task order. Triazolam also tended to impair working memory and episodic memory more than ketamine at doses that produced lower subjective effects and higher performance estimates.