Functional Correlates of Verbal Memory Deficits Emerging During Nicotine Withdrawal in Abstinent Adolescent Cannabis Users

Background Cannabis remains the most widely used illicit substance by adolescents and is typically consumed by this population in the context of ongoing tobacco use. Human studies have shown that both cannabis and tobacco exert effects on cognitive function; however, little is known about possible interacting effects of these drugs on brain function and cognition during adolescent development. Methods Verbal learning and memory were assessed in 20 adolescent users of tobacco and cannabis and 25 adolescent tobacco users with minimal history of cannabis use. Functional magnetic resonance imaging was used to examine brain function and functional connectivity while a subset of these subjects performed a verbal working memory task. Results Delayed recall of verbal stimuli deteriorated during nicotine withdrawal among cannabis users but not among comparison subjects. During high verbal working memory load, nicotine withdrawal selectively increased task-related activation of posterior cortical regions and was associated with disruption of frontoparietal connectivity in adolescent cannabis users relative to comparison subjects. Conclusions These observations suggest that cannabis use during adolescent development may disrupt neurocircuitry supporting verbal memory formation and that deficits associated with disruption of these neurocircuits are unmasked during nicotine withdrawal.