A review of adult neurogenesis
Neurogenesis is the process by which new brain cells (called neurons) are produced. Once thought to be restricted to the developmental phase of life, it is now (mostly accepted) that neurogenesis also occurs in the adult brain–but in only two regions: the olfactory bulbs and the hippocampus.
Olfaction involves the perception and identification of odors we pick up in the environment, which is carried out by the olfactory bulbs and other parts of the cortex. The hippocampus is the seahorse-shaped structure that supports episodic memory (like remembering what you ate for breakfast) located deep in the brain.
Levels of neurogenesis in the hippocampus are associated with memory function and may be associated with Alzheimer’s disease, as people with Alzheimer’s may have lower levels of neurogenesis. Therefore, the majority of research has focused on the hippocampus, where memories are made. However, neuroscientists remain a bit perplexed about why neurogenesis occurs in adults and how it contributes to normal brain function.
But one thing they’ve discovered is that endocannabinoids play an important role in this process.
Through activation of cannabinoid receptors 1 and 2 (CB1 and CB2), endocannabinoids trigger a molecular cascade of events regulated by two pathways, CREB and mTORC.1 And these signaling pathways affect the creation of new neurons in the brain. CB1, in particular, activates a growth factor called brain-derived neurotrophic factor (or BDNF), which boosts neurogenesis.
Studies from pre-clinical models have shown that chronic, but not acute, administration of CB1 and CB2 agonists (chemicals that activate receptors) increases the number of new cells produced in a region of the hippocampus called the dentate gyrus.2 Additionally, there are less new cells in models which have had their CB2 receptors genetically removed.1
Other studies have found that both tetrahydrocannabinol and cannabidiol treatment increases levels of neurogenesis in the hippocampus.3,4 In fact, preliminary evidence suggests that cannabichromene may increase levels of neurogenesis by stimulating the production of adult neural stem cells.5
Despite these positive findings, the overall literature on neurogenesis is quite mixed, to say the least. Both experiments carried out in cells (in vitro) and in live models (in vivo) have produced a dizzying spectrum of results–either significant enhancements, reductions, or no effect at all. Why is that?
Studying neurogenesis is quite tricky. When new cells are born, it takes time for them to migrate and integrate into pre-existing networks in the brain. Researchers try to measure the number of new cells after they’ve settled into their new homes. To do this, they use a drug that labels newly dividing cells and then count these cells–but this method is not fool proof. To complicate matters further, it’s also difficult to manipulate the amount of neurogenesis taking place, although some methods work a bit better than others.6
Despite adult neurogenesis being an interesting and quirky feature of the brain, why are neuroscientists and cannabinoid scientists so eager to study it?
Changes in levels of both neurogenesis and endocannabinoid activity have been associated with memory and mood disorders.7 And it’s possible that a better understanding of how cannabinoids impact neurogenesis could provide a novel target for treatment, or help us figure out which cannabinoids might be most beneficial.
So will using cannabis increase the numbers of new cells in your brain? Well, it’s too soon to say yes with certainty. But it is far less likely that cannabis will kill your brain cells, as these studies and others have demonstrated the potent neuroprotective properties that cannabinoids hold.
- Prenderville, J.A., et al. “The Role of Cannabinoids in Adult Neurogenesis.” Br J Pharmacol. vol.172, no.16, 2015, pp. 3950-3963. (impact factor: 6.81; cited by: 40)
- Wolf, S.A., et al. “Cannabinoid Receptor CB1 Mediates Baseline and Activity-induced Survival of New Neurons in Adult Hippocampal Neurogenesis.” Cell Communication and Signaling. vol.8, no.12, 2010, pp.1-14. (impact factor: 5.324; cited by: 131)
- Suliman, N.A., et al. “Delta-9-Tetrahydrocannabinol (Δ9-THC) Induce Neurogenesis and Improve Cognitive Performances of Male Sprague Dawley Rats.” Neurotox Res. vol.33, 2018, pp. 402-411. (impact factor: 3.538; cited by: 7)
- Campos, A.C., et al. “The Anxiolytic Effect of Cannabidiol on Chronically Stressed Mice Depends on Hippocampal Neurogenesis: Involvement of the Endocannabinoid System.” International Journal of Neuropsychopharmacology. vol.16, no.6, 2013,
pp. 1407-1419. (impact factor: 4.009; cited by: 128)
- Shinjyo., N., & Di Marzo, V. “The Effect of Cannabichromene on Adult Neural Stem/Progenitor Cells.” Neurochem Int. vol.63, no.5, 2013, pp. 432-437. (impact factor: 3.994; cited by: 38)
- Kempermann, G., et al. “Human Adult Neurogenesis: Evidence and Remaining Questions.” Cell Stem Cell. vol.23, 2018, pp. 25-30. (impact factor: 21.464; cited by: 133)
- Scarante, F.F. “Cannabinoid Modulation of the Stressed Hippocampus.” Front Mol Neurosci. vol.411, no.10, 2017, pp. 1-17. (impact factor: 3.720; cited by: 8)