Cannabis is widely used by adolescents, and animal studies have shown long-term harm from its main psychoactive component, THC, but often ignore other cannabinoids like CBD. In female rats, giving THC and CBD together in a 3:1 ratio—based on illegal cannabis samples—reduced some behavioral changes and alterations in CB1 receptors and microglia in the prefrontal cortex caused by THC alone. However, a combination resembling 'light cannabis' (CBD:THC at 33:1, total THC 0.3%) caused lasting cognitive problems and anhedonia, along with increased GAD67 levels in the prefrontal cortex, indicating possible long-term effects on GABA signaling.
Adolescent exposure to THC in female rats leads to long-lasting behavioral changes in adulthood, including memory deficits, social withdrawal, altered emotional reactivity, and heightened sensitivity to the effects of PCP. These changes are accompanied by reduced levels of the enzyme GAD67 and the neurotransmitter GABA in the prefrontal cortex, as well as increased glutamate and cFos activity in the prefrontal cortex and dorsal striatum. The findings suggest that adolescent THC exposure may contribute to the development of psychotic-like behaviors later in life.