Long term effects of Delta-9 tetrahydrocannabinol exposure in adolescence on peripheral central cytokines

Recreational marijuana, or cannabis smoking, is widespread among adolescents. The regular use of marijuana in this age group is associated with an increased likelihood of deleterious effects. Recent extensive work in the human and experimental animal focused on the possibility that exposure to marijuana components during adolescence might have adverse health effects that persist into adulthood. Adolescent exposure to marijuana components affects neuropsychological functions in adulthood, altering brain development, cognitive function and the increasing risk of chronic psychotic disorders. Delta-9-tetrahydrocannabinol (THC), the main active principle of cannabis, modulates also peripheral immune responses, affecting both innate and acquired immunity. Both in peripheral immune system and in the central nervous system common targets for THC are pro and anti-inflammatory cytokines. The aim of this paper is to review the data available about the effect of THC exposure in adolescent experimental animals on cytokine production by peripheral immune cells as well as by brain microglia and astrocytes. Besides acute effects, that are always present, a relevant cytokine dysfunction is consistently measurable in adult animals, long time after the last administration of THC. Moreover, while acute effects are generally in the direction of blunting inflammation and neuroinflammation, interestingly the long term effects on cytokines observed in adulthood are in the opposite direction, pointing to an inflammatory and neuroinflammatory profile. We hypothesize that the presence of an inflammatory and neuroinflammatory condition consequent to THC exposure during adolescence might predispose the individual to pathological conditions characterized by an unbalanced cytokine profile.