Cannabinoids, working memory, and schizophrenia

摘要

In this issue, Bossong ef al. (1) report that delta-9-tetrahydrocan-nabinol (THC), the primary psychoactive constituent in canna-bis, can induce both abnormal working memory (WM) performance and altered brain activity. Based on these findings, they suggest a role for endocannabinoids in both prefrontal cortical function and the pathophysiology of schizophrenia. Deficits in neurocognition, particularly processes related to WM, have been known to be core features of schizophrenia for nearly 2 decades (2). Existing antipsychotic drugs, all of which block dopa-mine (DA) D_2 receptors, have limited efficacy against neurocogni-tive deficits. Treatments based on alternate hypotheses involving the neurotransmitters gamma-aminobutyric acid (GABA) and glu-tamate (GLU) are of considerable interest. Of note, in numerous brain regions relevant to working memory processes, both GABA and GLU release are modulated by the activation of central canna-binoid receptors (CB1 Rs), which are among the most abundant G protein-coupled receptors in the nervous system (3), and the principal target of THC.