Combining psychedelic science, contemplative practices, and Indigenous and other traditional knowledge systems in integrative, community-based models of care could transform global health. Both contemplative practices and certain psychedelic substances reliably induce self-transcendent experiences that positively affect health, well-being, and prosocial behavior, and combining them appears synergistic. Traditional knowledge systems offer ethnobotanical expertise and time-tested practices. A decolonized agenda for psychedelic research requires collaborative engagement with traditional knowledge stewards to co-develop evidence-based integrative care accessible to their communities. Health systems could include Indigenous and traditional healers as stakeholders in designing, implementing, and evaluating community-based approaches for safely scaling psychedelic treatments.
Repeated or high-dose subanesthetic ketamine causes excitotoxic neuronal damage and lasting cognitive deficits in animals, especially perinates. Infrequent low-to-moderate doses (<1 mg/kg human intravenous equivalent) do not produce overt brain damage in rats and nonhuman primates. In humans, frequent high-dose (>1 g/day) recreational users show memory and executive function impairments. However, a large clinical trial found that intranasal esketamine at up to 84 mg weekly or every other week for several years is associated with maintained or slightly improved cognition in adults with major depression, though some elderly patients showed potential worsening in attention and processing speed. Direct comparisons of esketamine and off-label racemic ketamine at higher doses are lacking.