Cannabinoids, anxiety, and the periaqueductal gray

The use of Cannabis sativa by humans dates back several thousand years, for both its psychotomimetic and potential medicinal properties. As scientific research methods developed, the cannabinoids present in this herb were characterized, as well as their complex interface with the human central nervous system, provided by the activation of specific receptors. The subsequent description of an endogenous cannabinoid system in the mammalian brain shifted the notion of cannabis as a recreational drug to a therapeutic alternative for psychiatric disorders. However, the neuroanatomical sites mediating its effects have remained uncertain. In the present paper, we review recent data suggesting that the midbrain periaqueductal gray may be a structure involved in the anxiolytic-like effects of cannabinoids.