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

Abstract 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. The review aimed to synthesize the existing literature on the neurocognitive, structural, and functional outcomes associated with cannabis and NTP co-use. A systematic search of peer-reviewed articles resulted in a pool of 1,107 articles. Inclusion criteria were: 1) data-based, 2) age range of 13-35 or, for preclinical studies, non-adult subjects, 3) cannabis and NTP group jointly considered, and 4) neurocognitive, structural neuroimaging, or functional neuroimaging as an outcome measure. A total of 12 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. Of the 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.