Cannabinoids, including marijuana and its primary pharmacologically-active alkaloid, delta-9-tetrahydrocannabinol (THC), exert their psychoactive effects on multiple brain regions in concert with multiple neurotransmitter systems, including dopaminergic, GABAergic, glutaminergic, and cholinergic systems106. Like other drugs of abuse, including cocaine, amphetamines, opiates, nicotine and alcohol, the cannabinoids produce their rewarding effects primarily by increasing dopamine release in the nucleus accumbens, a major terminal field of the mesolimbic dopamine system106. Proposed mechanisms include both direct effects of cannabinoids on dopaminergic neurotransmission in the nucleus accumbens, and indirect effects of cannabinoids on brain CB1 cannabinoid receptors causing the release of endogenous opioids, which then act on opioid receptors in the VTA causing release of dopamine in the nucleus accumbens107. In addition to these mechanisms, however, there has been increasing recognition of the role that exogenous and endogenous cannabinoids may play in CB1 receptor-mediated synaptic transmission and synaptogenesis in the adult CNS108, and, more important to this review, in the regulation of multiple aspects (e.g., neuronal proliferation, migration, differentiation, survival, and synaptogenesis) of prenatal CNS development109. The early and widespread distribution of cannabinoid receptors in
