A systematic review of neuroimaging studies on psychedelics for major depressive disorder found that psilocybin, ayahuasca, and LSD alter brain activity and connectivity in ways linked to antidepressant response. Key changes include amygdala activity and functional connectivity alterations, shifts in medial and ventromedial prefrontal cortex connectivity, and decreased global brain network modularity. One ayahuasca study reported increased limbic activity. The evidence, based on only four datasets, suggests the default mode and limbic networks may be important targets for future research, but more data are needed to confirm these preliminary findings.
All participants reported decreased pain with ketamine infusions, though pain experiences varied. To improve ketamine's benefit for chronic neuropathic pain, it is important to address stigma, research ways to extend the duration of its effects, and provide a safe treatment environment. Understanding barriers and facilitators, along with implementing participant suggestions, can inform ketamine programs, improve access to pain management, and guide future research.
Most patients with chronic pain at a Toronto pain clinic were willing to join a clinical trial testing MDMA-assisted therapy for pain relief. Among 42 patients surveyed, 76% expressed willingness to participate in the EASE-Pain trial, which compares MDMA with an active placebo. White/European participants were more likely to be willing than nonwilling. The main motivators were pain relief (62%) and seeking alternatives to ineffective treatments (26%). Common concerns included side effects (43%), impacts on comorbidities (19%), and stigma associated with MDMA (19%). The findings suggest that protocol modifications, such as better patient education on drug effects, may improve trial enrollment and acceptability.