Óleo full spectrum de Cannabis sativa: efeitos terapêuticos e sexodependentes nas alterações comportamentais e salivares após a exposição pré-natal ao crack em ratos Wistar

Abstract

The use of psychoactive drugs, such as crack cocaine, represents a serious public health issue in Brazil, affecting approximately 2 million people. Its highly addictive effect occurs due to rapid absorption in the lungs, leading to user dependence. The impact of the drug becomes even more concerning when considering pregnant users, as crack metabolites cross the placental barrier and cause harm to fetal development. These damages include cognitive deficits, behavioral changes, increased risk of epilepsy, and lesions in the central nervous system, frequently associated with neurotoxicity and oxidative stress. Although there are psychosocial interventions for treatment, there are still no effective pharmacological therapies to minimize the damage, making the search for new approaches urgent. This study investigated the therapeutic potential of full-spectrum Cannabis sativa oil rich in cannabidiol (FS-CBD) to reduce the damage caused by prenatal crack cocaine exposure (PN-Crack). Pregnant rats were exposed to crack (200 mg) daily from days 5 to 21 of gestation, and their offspring, in adulthood, were divided into four experimental groups and treated with FSCBD (30 mg/kg, orally) or saline solution (0.9%) for 7 days. Behavioral tests were conducted to assess anxiety, depression, locomotor activity, and long-term memory. Additionally, samples of saliva, salivary glands, thymus, and spleen were collected for analysis of relative weight and cellularity. The results revealed, for the first time, that exposure to PN-Crack induces sex-dependent changes in behavior, physiology, and glandular functions in adult F1 rats. Females exposed to PN-Crack showed reduced weight gain, suggesting metabolic and hormonal changes, while males showed greater resistance to these changes, indicating a differential response between sexes. Exposure to PN-Crack resulted in anxiety-like and depression-like behavior in both sexes, with FS-CBD treatment being effective in partially mitigating these effects. Regarding salivary function, PN-Crack exposure affected salivary flow and glandular weight in a sex-dependent manner, with FS-CBD showing a protective effect, also varying between sexes. No significant statistical differences were observed in the lymphoid organs. This study suggests that FS-CBD may be a promising therapeutic approach, especially considering the sex differences, with potential to improve the quality of life for children exposed to crack during gestation and offer innovative therapeutic alternatives.