Astrogliosis Occurs Selectively in Amygdala of Adolescent Primate and Rodent Following Daily Δ9-Tetrahydrocannabinol
Among the advantages of this preclinical research is that there are no critical confounds (no family stress, no bad neighbourhoods, poor grades at school, no other drug use, dose and purity of THC are known, age of onset is fixed). Bear in mind: 13% of 12th graders in U.S. use marijuana daily. It's a complicated paper but here is the bottom line. In primate and rodent adolescent, daily THC caused:
- An increase in inflammatory cells (GFAP-astrogliosis) in a key region of the brain, the amygdala. This brain region is implicated in a large array of physiological functions (survival, sizing up feelings, threats, safety, generating anxiety fear, aggression, stress) and psychopathology related to marijuana use (depression, anxiety, psychosis, hyperreaction to stress, sleep problems and others).
- This response to daily THC was observed only in adolescent amygdala, not in adult amygdala treated daily with THC!
- This response to daily THC was observed only in adolescent amygdala, and not in two other brain regions examined.
- Other makers of inflammation were also elevated (complement factors). These are implicated in psychiatric disorders associated with adolescent cannabis exposure. Aberrant complement function has been linked to schizophrenia, depression, and anxiety, suggesting an overlapping contribution of this inflammatory pathway in cannabis associated psychiatric pathology.
- THC-induced increases in these inflammatory markers may drive abnormal pruning in the amygdala to the detriment of establishing appropriate connections, dysregulating its behavioural outputs.
- THC reduced two proteins that are critical for brain development and improve connections between nerve cells, but only in adolescent and not in adult amygdala.
- Cannabidiol (CBD) prevented astrogliosis but did not restore proteins implicated in connectivity.
- Increased inflammation correlated with fragmented sleep in primates. These changes may contribute to sleep disturbances observed in adolescent heavy marijuana users.
- Reduced markers for connectivity correlated with anxiety Behavior in rodents
- Same effects were found if specific brain cells (astrocytes) were isolated, cultured and exposed to THC.
- Effects required cannabinoid receptors
- THC reduced cannabinoid receptors in astrocytes in the adolescent brain, which may be the reason for these changes.
In summary: Results reveal that chronic THC exposure during a critical period of adolescent brain maturation elicited inflammatory activation of astrocytes and attenuated expression of certain proteins in the amygdala, together vital for regulation of sleep and anxiety. These mechanisms underscore the significant detrimental reorganization of the adolescent neuronal and glial landscape within the amygdala following chronic THC exposure, which does not occur in other brain regions or following comparable THC exposure in adult animals. Our results demonstrate a vital mechanism potentially underlying the increased risk of psychiatric disorders involving amygdala dysfunction following chronic cannabis use at a critical developmental stage.
(Click here for PDF Paper Source: ScienceDirect)
Bertha K Madras, PhD
Professor of Psychobiology, Department of Psychiatry
Harvard Medical School
