A systematic review of 21 studies found that mindfulness meditation relieves pain through multiple mechanisms, including modulation of brain activity in regions such as the anterior cingulate cortex and anterior insula, and enhancement of structural and functional connectivity. The analgesic effects persist even when opioid receptors are blocked, indicating a nonopioidergic pathway. Pain acceptance and altered pain control beliefs serve as key mediators. Long-term practice increases pain threshold and reduces unpleasantness via heightened activity in salience and attentional control regions. Most studies involved healthy subjects with experimental pain, so findings require careful interpretation for chronic pain populations.
Psychedelics may help treat neuropsychiatric disorders by disrupting entrenched associations and promoting new learning. In rats performing a Pavlovian task where sequential cues predict rewards, the psychedelic DOI (a 5-HT2A/2C agonist) increased dopamine signaling in the nucleus accumbens core to rewards and to cues immediately preceding them, but not to more distal predictive cues. This elevated dopamine occurred independently of changes in reward value and supports increased prediction error signaling. The findings suggest psychedelics could engage error-driven learning mechanisms to disrupt or form new associations.