Abstract
Cannabidiol (CBD) is a non-intoxicating phytocannabinoid whose purported therapeutic benefits and impression of a high safety profile has promoted its increasing popularity. CBD’s popularity is also increasing among children and adolescents who are being administered CBD, off label, for the treatment of numerous symptoms associated with autism spectrum disorder, attention deficit hyperactivity disorder, anxiety, and depression. The relative recency of its use in the adolescent population has precluded investigation of its impact on the developing brain and the potential consequences that may present in adulthood. Therefore, there’s an urgency to identify whether prolonged adolescent CBD exposure has substantive impacts on the developing brain that impact behavioral and cognitive processes in adulthood. Here, we tested the effect of twice-daily intraperitoneal administrations of CBD (20 mg/kg) in male and female C57BL/6J mice during the adolescent period of 25–45 days on weight gain, and assays for locomotor behavior, anxiety, and spatial memory. Prolonged adolescent CBD exposure had no detrimental effects on locomotor activity in the open field, anxiety behavior on the elevated plus maze, or spatial memory in the Barnes Maze compared to vehicle-treated mice. Interestingly, CBD-treated mice had a faster rate of learning in the Barnes Maze. However, CBD-treated females had reduced weight gain during the exposure period. We conclude that prolonged adolescent CBD exposure in mice does not have substantive negative impacts on a range of behaviors in adulthood, may improve the rate of learning under certain conditions, and impacts weight gain in a sex-specific manner.
Highlights
Cannabidiol (CBD) is one of the most abundant cannabinoids naturally produced by the plant, Cannabis sativa, and the dominant phytocannabinoid produced by the hemp variety (Citti et al, 2019)
There were no differences in time spent in the center quadrant, P = 0.51 (Figure 1Biv). This result confirmed the psychoactive efficacy of our CBD compound and supported the investigation of a suprathreshold dose (20 mg/kg) for reducing anxiety in healthy C57BL/6J mice that is either at or above the effective dose detected in previous studies in rats (Guimarães et al, 1990; Resstel et al, 2009) and mice (Schiavon et al, 2016; Zieba et al, 2019)
Its unapproved uses for the treatment of pain, anti-emesis, anxiety, sleep, and stress reduction has led to an increase in CBD exposure during infancy, childhood, and adolescence (Aran et al, 2018; Bertrand et al, 2018; Sarrafpour et al, 2020; Moss et al, 2021)
Summary
Cannabidiol (CBD) is one of the most abundant cannabinoids naturally produced by the plant, Cannabis sativa, and the dominant phytocannabinoid produced by the hemp variety (Citti et al, 2019). The perception of CBD’s therapeutic benefits and high safety profile have led to off-label CBD administration in children for treating symptoms of numerous conditions including anxiety, hyperactivity, and autism spectrum disorder. Somnolence is often reported as one of the more common acute centrally mediated adverse events of CBD use in children and adults (Devinsky et al, 2017; Szaflarski et al, 2018; Barchel et al, 2019), but the frequency of overall adverse effects seems to increase with dose and additional pharmacotherapies (Devinsky et al, 2017). One notable study found that cognitive performance was unaltered after one year of CBD treatment (Epidolex) in a cohort of children with treatmentresistant epilepsy (Thompson et al, 2020), little is known about long-term consequences that may persist or present in adulthood
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