Abstract
Background and Aims: Legalization of cannabis (CB) for both medicinal and, in some states, recreational use, has given rise to increasing usage rates across the country. Of particular concern are indications that frequent CB use may be selectively harmful to the developing adolescent brain compared with adult-onset usage. However, the long-term effects of heavy, adolescent CB use on brain structure and cognitive performance in late-life remain unknown. A critical brain region is the hippocampus (HC), where there is a striking intersection between high concentrations of cannabinoid 1 (CB1) receptors and age-related pathology.Design: We investigated whether older adults (average age=66.6+7.2 years old) with a history of early life CB use show morphological differences in hippocampal subregions compared with older, nonusers.Methods: We performed high-resolution magnetic resonance imaging combined with computational techniques to assess cortical thickness of the medial temporal lobe, neuropsychological testing, and extensive drug use histories on 50 subjects (24 formerly heavy cannabis users [CB+ group] abstinent for an average of 28.7 years, 26 nonusers [CB− group]). We investigated group differences in hippocampal subregions, controlling for age, sex, and intelligence (as measured by the Wechsler Test of Adult Reading), years of education, and cigarette use.Results: The CB+ subjects exhibited thinner cortices in subfields cornu ammonis 1 [CA1; F(1,42)=9.96, p=0.0003], and CA2, 3, and the dentate gyrus [CA23DG; F(1,42)=23.17, p<0.0001], and in the entire HC averaged over all subregions [F(1,42)=8.49, p=0.006].Conclusions: Negative effects of chronic adolescent CB use on hippocampal structure are maintained well into late life. Because hippocampal cortical loss underlies and exacerbates age-related cognitive decline, these findings have profound implications for aging adults with a history of early life usage.Clinical Trial Registration: ClinicalTrials.gov # NCT01874886.
Highlights
Marijuana (Cannabis sativa) is the most widely used ‘‘illicit’’ drug worldwide, with an estimated 183 million past-year users worldwide,[1] over 20 million Americans reporting previous month use, and 4.6 million Americans meeting criteria for dependence in 2015.2 Adolescent cannabis (CB) use is concerning given the vulnerability of the adolescent brain.[3]
CB+ group averages were lower than CBÀ group averages across all neuropsychological measures (Fig. 4). These results provide the first evidence of an association between early life CB use and later morphology changes in the medical temporal lobe, several decades after cessation of usage
Morphological differences between groups were regionally specific to cornu ammonis (CA) and dentate gyrus (DG) regions and were not present in neocortical regions of the medial temporal lobe (MTL), including entorhinal, perirhinal, and parahippocampal cortices
Summary
Marijuana (Cannabis sativa) is the most widely used ‘‘illicit’’ drug worldwide, with an estimated 183 million past-year users worldwide,[1] over 20 million Americans reporting previous month use, and 4.6 million Americans meeting criteria for dependence in 2015.2 Adolescent cannabis (CB) use is concerning given the vulnerability of the adolescent brain.[3]. The long-term effects of heavy, adolescent CB use on brain structure and cognitive performance in late-life remain unknown. Design: We investigated whether older adults (average age = 66.6 + 7.2 years old) with a history of early life CB use show morphological differences in hippocampal subregions compared with older, nonusers. Methods: We performed high-resolution magnetic resonance imaging combined with computational techniques to assess cortical thickness of the medial temporal lobe, neuropsychological testing, and extensive drug use histories on 50 subjects (24 formerly heavy cannabis users [CB+ group] abstinent for an average of 28.7 years, 26 nonusers [CBÀ group]). Because hippocampal cortical loss underlies and exacerbates age-related cognitive decline, these findings have profound implications for aging adults with a history of early life usage.
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