Cannabinoid (THC specifically) and neurogenesis and its effects on working memory

Cannabis usage and working memory function have a complicated relationship. Working memory is the ability of an individual to mentally store and manipulate happenings of stimuli over a short duration and respond to the situation. Marijuana smoking is assumed to contribute to the working memory deficits in humans that is within a few hours of drug administration, there are acute effects on the working memory. Smoking cannabis causes a reversible disruption of the short-term memory that the primary psychoactive cannabis component is known as delta‐9‐tetrahydrocannabinol (THC) induces. A single dose of THC affects the multiple cellulars and signaling pathways, thus changing the neuronal, microglial, and astrocytic signaling. People use THC for medical uses, hemp, and as a recreational drug. Adolescence is a critical period where the brain is developing, but also most cannabis addicts are youths, THC in cannabis disrupts the eCB brain system, and effects are likely to persist into adulthood. The administering of the Δ9-THC disrupts the episodic and working memory in humans. The high concentration of Δ9-THC in the brain affects memory functioning in that it decreases the performance of an individual in tasks involving short-term memory. For example, the addict suffers from impaired verbal recall for the next few hours after the oral administration of Δ9-THC. However, one should note that the effects depend on the type of cannabis that the individual uses; for example, individuals taking a higher dosage of Δ9-THC have greater memory impairment.

Neurogenesis gets influenced by various external factors and contributes to hippocampal learning and memory (Suliman, Taib, Moklas, & Basir, 2018). The hippocampus brain structure is a site of adult neurogenesis that is neural progenitor cells are found in the dentate gyrus of the hippocampus. It is vulnerable to the impairing effects of exposure to THC, especially on adolescents. The adult brain is more resistant to developing the psychopathologies resulting from acute THC. A dosage of THC challenges the eCB system as it causes changes in gene expression. It causes a decline in neurogenesis, for example, the CB1 downregulation (Leishman, Murphy, Mackie, & Bradshaw, 2018). For young people regularly using cannabis, this caused an increased risk of psychopathology. Chronic exposure to THC during adolescence period may cause deficits in memory and spatial learning (Calabrese & Rubio‐Casillas, 2018). If continued in adulthood, exposure to cannabis causes a stronger decrease in dorsal hippocampal neurogenesis. Suliman, Taib, Moklas, & Basir (2018) claim that THC alters the hippocampus morphology, for example, causes a decrease in the number of neurons and synapse. It also reduces the amount of newly generated cells. Acute THC may not affect the number of neural progenitor cells present in the dentate gyrus, but through cell survival or proliferation, it affects neurogenesis. Vascular endothelial growth factor (VEGF) is known to stimulate the survival of immature neurons and induce cell survival (Leishman, Murphy, Mackie, & Bradshaw, 2018). Thus, the administering of THC reduces mRNA, which reduces the Kdr and survival of the new neurons. Some of the genes that acute THC alters have restricted expression to neurogenesis sites. For instance, the cyclin-dependent kinase inhibitor 1A (Cdkn 1 a) expression is limited to the adult neurogenesis site, hippocampal neurons in the subgranular zone of the dentate gyrus (Leishman, Murphy, Mackie, & Bradshaw, 2018). Therefore, acute THC helps in the decrease in neurogenesis. Continued use of THC supports decreases in neurogenesis, which contributes to psychopathologies.


Calabrese, E. J., & Rubio‐Casillas, A. (2018). Biphasic effects of THC in memory and cognition. European journal of clinical investigation48(5), e12920.

Leishman, E., Murphy, M., Mackie, K., & Bradshaw, H. B. (2018). Δ9-Tetrahydrocannabinol changes the brain lipidome and transcriptome differentially in the adolescent and the adult. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids1863(5), 479-492.

Suliman, N. A., Taib, C. N. M., Moklas, M. A. M., & Basir, R. (2018). Delta-9-Tetrahydrocannabinol (∆ 9-THC) Induce Neurogenesis and Improve Cognitive Performances of Male Sprague Dawley Rats. Neurotoxicity Research33(2), 402-411.

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