[176]. Levels of 2-AG are 50–1,000 times higher than those of anandamide. Its proposed role is as an autocrine messenger in axonal guidance [86] and as a retrograde messenger in the adult brain [134]. CB1Rs are predominantly presynaptic [61] and are mainly localized to axons and nerve terminals. CB1Rs are particularly abundant in the hippocampus on the terminals of a cholecystokinin (CCK) GABAergic basket cell interneurons [111] as well as in the dentate gyrus [57] and, at a lower level, in glutamatergic pyramidal cells. The primary effect of cannabinoids is the modulation of neurotransmitter release via activation of presynaptic CB1Rs (reviewed in [67]). There are several possible mechanisms by which cannabinoids induce positive, negative, and cognitive symptoms of schizophrenia.
