“The recent discovery that the hippocampus is able to generate new neurons throughout a human’s lifespan has changed the way we think about the mechanisms of psychiatric disorders and drug addiction,” says Wen Jian and colleagues in a study published in the Journal of Clinical Investigation in 2005.

It appears that cannabinoids are able to modulate pain, nausea, vomiting, epilepsy, ischemic stroke, cerebral trauma, multiple sclerosis, tumors, and many other disorders. Cannabinoids act on two types of receptors, the CB1 receptors (found mainly in the brain) and the CB2 receptors (found mainly in the immune system). The CB1 receptor is one of the most abundant G protein coupled receptors in the mammalian brain and it accounts for most, if not all,
of the centrally mediated effects of cannabinoids.

Cannabionoid receptors are evolutionarily conserved amoung various vertebrates and invertebrates which have been separate for 500 million years.

Hippocampal neurogenesis is suppressed following chronic administration of the major drugs of abuse (including opiates, alcohol, nicotine, and cocaine). However, CB1-knockout mice display
significantly decreased hippocampal neurogenesis, suggesting that CB1 receptors activated by endogenous, plant-derived, or synthetic cannabinoids may promote hippocampal neurogenesis.

Wen Jiang and colleagues have given the first evidence suggesting that both embryonic and adult hippocampal neural stem/progenitor cells (NS/PCs) express CB1 receptors. Cannabinoids can regulate the proliferation of hippocampal NS/PCs by acting on CB1 receptors. They found that both the synthetic cannabinoid HU210 and the endocannabinoid anandamide profoundly promote embryonic hippocampal NS/PC proliferation. Chronic, but not acute, HU210 significantly increases the number of newborn hippocampal neurons in adult rats by promoting NS/PC proliferation.

These promoting effects are not the outcome of hippocampal neuronal death, as no neuronal loss or dying hippocampal neurons were detected following chronic HU210 injection. A significant increase was observed in the hipoppocampal newborn neurons of mice following twice-daily
HU210 injection for 10 days.

It has been shown that acute, high doses of cannabinoids produce anxiety-like effects in rats and depression-like effects in mice. But chronic administration of high, but not low, doses of HU210 exerts anxiolytic- and antidepressant-like effects. This suggests that cannabinoids are the only illicit drug that can promote adult hippocampal neurogenesis following chronic  administration. “This increase in hippocampal neurogenesis underlies the mechanism of
anxiolytic- and andtidepressant-like effects produced by a high dose chronic HU210 treatment.”

Source: Jiang W, Zhang Y, Xiao L, Cleemput JV, Ji S-P, Bai G,&Zhang X (2005). Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. Journal of Clinical Investigation, 115, 3104-3116