The Influence of Cannabis and Nicotine Co-use on Neuromaturation: A Systematic Review of Adolescent and Young Adult Studies

Accumulating evidence suggests that the use of cannabis and nicotine and tobacco-related products (NTPs) during the adolescent years has harmful effects on the developing brain. Yet, few studies have focused on the developing brain as it relates to the co-administration of cannabis and NTPs, despite the high prevalence rates of co-use in adolescence. This review aims to synthesize the existing literature on neurocognitive, structural neuroimaging, and functional neuroimaging outcomes associated with cannabis and NTP co-use. A systematic search of peer-reviewed articles resulted in a pool of 1107 articles. Inclusion criteria were 1) data-based study; 2) age range of 13 to 35 years or, for preclinical studies, nonadult subjects; 3) cannabis and NTP group jointly considered; and 4) neurocognitive, structural neuroimaging, or functional neuroimaging as an outcome measure. Twelve studies met inclusion criteria. Consistent with the literature, cannabis and nicotine were found to have independent effects on cognition. The available research on the co-use of cannabis and NTPs demonstrates a potential nicotine-related masking effect on cognitive deficits associated with cannabis use, yet there is little research on co-use and associations with neuroimaging indices. In neuroimaging studies, there is preliminary evidence for hippocampal volume differences in co-users and a lack of evidence for co-use differences related to nucleus accumbens activity during reward processing. Notably, no structural neuroimaging studies were found to examine the combined effects of nicotine and cannabis in adolescent-only populations. Further research, including longitudinal studies, is warranted to investigate the influence of cannabis and NTP co-use on maturation.