Men With History of Cannabis Use Have Less Cognitive Decline From Early Adulthood to Late Midlife

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Cannabis is the most widely used drug listed on the Drug Enforcement Administration’s Schedule I, which includes drugs that have a high potential for abuse. Prior evidence shows of some short-term negative effects of cannabis use on cognition, but there are only few studies that explore long-term effects, such as age-related cognitive decline. Authors of research published in Brain and Behavior aimed to investigate potential associations between cannabis use and age-related cognitive decline from early adulthood to late midlife within a male population, and whether these associations depended on age of initiation of cannabis use or the number of years of frequent use.

For this study, the investigators utilized data from the Danish Aging and Cognition (DanACo) cohort, which was designed to study predictors of age-related cognitive decline from young adulthood to late midlife. Additionally, the cohort was based on a pooling of 2 follow-up studies, both of which were identical in their designs. According to the investigators, the studies were based on reassessments of cognitive abilities in late midlife using the conscription board intelligence test, with a mean retest interval of about 44 years (p1 and p99: 35 and 53 years). In the follow-up studies, examinations at conscription were conducted in 1967 through 1989, when the men had a mean age of about 20 years (p1 and p99: 18 and 26 years). The follow-up examinations were conducted again in 2015 through 2017 and 2019 through 2022, when the men had a mean age of about 64 years (p1 and p99: 55 and 72 years).

Further, cannabis use was defined as a current or former use at the time of follow-up, and those who never used or almost never used cannabis were referred to as nonusers. Additionally, self-reported information on the age of cannabis initiation was categorized into the following age groups: younger than 18 years (<18); 18 through 25 years; and older than 25 years (>25). Information on frequency of cannabis use was only available in 1 follow-up study, which included a question on how often (never/almost never, less than once a month, approximately once a month, a couple of times a month, approximately once a week, a couple of times a week, and every day/almost every day) the men had used different types of illicit drugs during different age periods (<15, 15–18, 19–25, 26–30, 31–40, 41–50, 51–60, and >60 years) as well as within the last 12 months.

In addition, frequent cannabis use was operationalized as using cannabis a couple of times a week or more, and no frequent use indicated that they had never used cannabis twice a week or more often, regardless of how long they had been using it. The years of frequent cannabis use were calculated by adding the number of years for each age category (eg, 7 years for the category “19–25 years”) in which the men indicated a frequent use by the definitions specified above, thus assuming a consistent use within each age period. Years of frequent cannabis use included any combination of age periods between initiation and the present, regardless of how recent or how long ago the usage occurred. The years of frequent cannabis use were then categorized into 3 groups: no frequent use, 10 or fewer years of frequent cannabis use, and over 10 years of frequent cannabis use.

For cognitive decline, ability was assessed using Børge Priens Prøve, which demonstrates high reliability and validity. The assessment is a timed group-administered intelligence test that consists of 78 items distributed on 4 subsets: letter matrices (19 items); verbal analogies (24 items); number series (17 items); and geometric figures (19 items). Total scores ranged from 0 to 78, which were based on the number of correct answers.

According to the findings, the mean cognitive decline among the 5162 enrolled men was about 6.2 IQ points over an average of 44 years. Among this population, approximately 39.3% had used cannabis at least once. Those who used cannabis had a slightly higher average IQ at conscription, whereas the mean IQ difference between cannabis users and nonusers was somewhat larger at the follow-up. For nonusers, the mean cognitive decline was about 6.8 IQ points. Results of both unadjusted and adjusted models showed significantly less cognitive decline among cannabis users compared with nonusers (unadjusted model: 1.5 IQ points less cognitive decline; fully adjusted model: 1.3 IQ points less cognitive decline).

Further, among cannabis users, approximately 51.1% had their cannabis use initiation before the age of 18 years whereas initiation between 18 and 25 years was about 43.5% and after 25 was 5.4%. Those who initiated use after the age of 25 years had an unadjusted mean cognitive decline of about 5.8 IQ points, with both the unadjusted and adjusted models showing a nonsignificant association between the age of initiating cannabis use and cognitive decline.

Among cannabis users, approximately 78.3% had never had a frequent—at least twice a week—use of cannabis, whereas 10.1% had been frequent cannabis users for less than 10 years and 11.7% had been frequent cannabis users for 10 years or more. Those without frequent cannabis use experienced an unadjusted mean cognitive decline of 4.5, and both the unadjusted and adjusted models showed no significant differences in cognitive decline between men with and without frequent cannabis use.

The main limitation of the study, according to the authors, was the low participation rate in the DanACo cohort. Approximately 14.3% of the invited men had participated in the follow-up examinations, which may influence the generalizability of the results and potentially increase the risk of selection bias. There is a possibility that men with heavy cannabis use—whether it is current or previous use—were less likely to participate in the follow-up studies; however, it is not obvious that their willingness to participate would be dependent on their cognitive decline. Further, the study only enrolled men, therefore, these findings may not be applicable to women.

REFERENCE

Høeg KM, Frodegaard RL, Grønkjær M, et al. Cannabis use and age-related changes in cognitive function from early adulthood to late midlife in 5162 Danish men. Brain Behav, 2024;14:e70136. doi:10.1002/brb3.70136