Psilocybin, LSD, and 2C-B produce distinct short- and long-term brain energy patterns in rats, study finds

A rat study suggests that psilocybin, LSD, and 2C-B produce distinct patterns of brain energy use both shortly after dosing and one week later, challenging the practice of treating serotonergic psychedelics as interchangeable. PET scans found drug-specific metabolic signatures: psilocybin increased relative activity in the dorsal striatum and insula, LSD reduced cortical metabolism while increasing activity in midbrain and emotional regions, and 2C-B showed reduced frontal activity with a pronounced midbrain dopamine-related hotspot. One week later, psilocybin retained the clearest network effect, including stronger insula-prefrontal coordination, while 2C-B effects remained concentrated in dopamine-producing midbrain regions. The authors suggest, speculatively, that distinct neural effects could eventually inform treatment matching, but the study involved only healthy rats, measured no behavior, used relative metabolic comparisons, and did not directly establish therapeutic relevance in humans.