A single dose of psilocybin given to rats 4–24 hours before a relapse test reduced cue-induced heroin seeking, though it did not alter actual heroin taking. Blocking the serotonin 2A receptor with antagonists worsened relapse. Psilocybin regulated about twice as many genes in the prefrontal cortex at a higher dose, with ketanserin blocking over 90% of these gene changes, including the IL-17a cytokine receptor. Psilocybin also regulated four chemokine/cytokine genes, and selectively inhibiting IL-17a in the prefrontal cortex was enough to reduce heroin relapse. The findings suggest psilocybin reduces heroin relapse and point to IL-17a signaling as a possible downstream pathway.
A review of preclinical and clinical data examines whether cannabinoids and ketamine can modulate the reconsolidation of maladaptive memories, a process that may underlie their potential therapeutic use in post-traumatic stress disorder and substance use disorders. The authors propose that memory reconsolidation modulation is a hypothetical process explaining the efficacy of these substances, and they report findings that support or do not support this working hypothesis. Metaplasticity is suggested as a common process mediating the effects of cannabinoids and ketamine on maladaptive memories.