Dos(e)Age: Role of Dose and Age in the Long-Term Effect of Cannabinoids on Cognition

Cannabis is still the most widely used illicit drug around the world. While its use has always been prevalent among adolescents, recent evidence suggests that its consumption is also increasing among other population groups, such as pregnant women and aged people. Given the known impact of cannabis on brain development and behavior, it is important to dissect the possible long-term impact of its use across different age groups, especially on measures of cognitive performance. Animal models of cannabinoid exposure have represented a fundamental tool to characterize the long-lasting consequences of cannabinoids on cognitive performance and helped to identify possible factors that could modulate cannabinoids effects in the long term, such as the age of exposure and doses administered. This scoping review was systematically conducted using PubMed and includes papers published from 2015 to December 2021 that examined the effects of cannabinoids, either natural or synthetic, on cognitive performance in animal models where exposure occurred in the prenatal period, during adolescence, or in older animals. Overall, available data clearly point to a crucial role of age in determining the long-term effect of cannabinoid on cognition, highlighting possible detrimental consequences during brain development (prenatal and adolescent exposure) and beneficial outcomes in old age. In contrast, despite the recent advances in the field, it appears difficult to clearly establish a possible role of dosage in the effects of cannabinoids on cognition, especially when the adolescent period is taken into account.

Automated summary

Cannabis remains the most widely used illicit drug globally and its use is increasing among various population groups, including pregnant women and older individuals. The impact of cannabis on brain development and behavior is well-known, making it crucial to examine the long-term effects of cannabis use on cognitive performance across different age groups. Animal models have been instrumental in studying the lasting consequences of cannabinoids on cognition and identifying factors such as age of exposure and administered doses that can modulate these effects. This scoping review highlights the significant role of age in determining the long-term impact of cannabinoids on cognition, with potential detrimental consequences during brain development (prenatal and adolescent exposure) and beneficial outcomes in old age. However, establishing a clear role of dosage in the cognitive effects of cannabinoids, especially during adolescence, remains challenging.