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Cognitive Impairment at Midlife in Long-Term Cannabis Users
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Download the PDF here
Long-term cannabis users showed significantly more informant-reported memory and attention problems at age 45 than all groups except long-term tobacco users and cannabis quitters (Table 5). Long-term cannabis users showed cognitive deficits and smaller hippocampal volume in midlife. Research is needed to ascertain whether long-term cannabis users show elevated rates of dementia in later life.
long-term cannabis users exhibited IQ decline and poorer learning and processing speed in midlife relative to their childhood IQ. People who knew them well described them as having memory and attention problems. These associations were not explained by prospectively assessed persistent tobacco, alcohol, and other illicit drug dependence or by childhood socioeconomic status, low childhood self-control, and family substance dependence history.
Participants who used cannabis more persistently had more memory and attention problems than less persistent users, according to informants, even after covariate adjustment (Table 6).
Long-term cannabis users showed significantly smaller volumes than cannabis nonusers in the left and right total hippocampus and five of 12 subfields (tail, hippocampal amygdala transition area, CA1, molecular layer, dentate gyrus), and significantly smaller volumes than midlife recreational cannabis users in the left and right hippocampus and three of 12 subfields (tail, CA1, and molecular layer) (Figure 2; see also Table S5 in the online supplement). Long-term cannabis users generally did not show significantly smaller volumes in left and right total hippocampus or hippocampal subfields than long-term tobacco users, long-term alcohol users, or cannabis quitters.
Participants who used cannabis more persistently had smaller volumes than less persistent users in the left and right hippocampus and numerous hippocampal subfields, after adjusting for sex.
cognitive functioning among midlife recreational cannabis users was similar to representative cohort norms. This suggests that infrequent, non-problem recreational cannabis use in midlife is unlikely to compromise cognitive functioning. Our results highlight the importance of not conflating long-term and recreational cannabis users in future studies.
Long-term cannabis users (N=86; 64% male) used cannabis weekly or more frequently in the past year at age 45, or were dependent on cannabis at age 45, and also used cannabis weekly or more frequently at one or more previous assessment waves. Of these, 31.4% used cannabis before age 18, 89.5% used regularly (≥4 days per week) at one or more waves (mean=3.4 waves, SD=1.4), and 72% met criteria for cannabis dependence at one or more waves. Frequency of use among long-term cannabis users at age 45 was a median of 300 days in the past year, with 64% using ≥4 days per week.
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Cognitive Impairment at Midlife in Long-Term Cannabis Users
Peter Roy-Byrne, MD, reviewing Meier MH et al. Am J Psychiatry 2022 Mar 8 NEJM Journal Watch
A prospective study documents a range of cognitive deficits in persistent cannabis users.
Is long-term cannabis use associated with cognitive deficits in midlife? To address this question, researchers in New Zealand used data from a long-term cohort study of 1037 people who were followed from childhood to midlife. Cannabis use was assessed repeatedly between ages 18 and 45, and detailed cognitive testing was performed at age 45. Long-term cannabis users (i.e., at least weekly use, both at age 45 and in at least one other period) were compared with long-term tobacco users, long-term alcohol users, recreational cannabis users (without histories of weekly use), and never users of cannabis.
Long-term cannabis users performed significantly worse on most cognitive tests than did never users; long-term cannabis users performed significantly worse on learning and memory tests than did long-term alcohol or tobacco users or recreational cannabis users.
More-persistent cannabis use over time, compared with less-persistent use, was associated with worse performance on learning, processing speed, and verbal memory. Long-term and persistent users reported significantly more subjective memory and attention problems.
Comment
Although some confounding is likely in an observational study like this, these cognitive findings could represent - at least in part - effects of long-term cannabis use, given the consistent results across multiple comparisons and the dose-response relation. Many patients think of their regular cannabis use as the same as a glass of wine with dinner, but this equivalence appears to be specious. The authors believe that these findings could be clinically consequential, given the link between midlife cognitive decline of similar magnitude and eventual risk for dementia. In my psychiatric practice, I am much less concerned about casual sporadic cannabis use and more worried about regular use, which appears to aggravate preexisting mood and anxiety disorders in some patients.
Abstract
Objective:
Cannabis use is increasing among midlife and older adults. This study tested the hypotheses that long-term cannabis use is associated with cognitive deficits and smaller hippocampal volume in midlife, which is important because midlife cognitive deficits and smaller hippocampal volume are risk factors for dementia.
Methods:
Participants are members of a representative cohort of 1,037 individuals born in Dunedin, New Zealand, in 1972-1973 and followed to age 45, with 94% retention. Cannabis use and dependence were assessed at ages 18, 21, 26, 32, 38, and 45. IQ was assessed at ages 7, 9, 11, and 45. Specific neuropsychological functions and hippocampal volume were assessed at age 45.
Results:
Long-term cannabis users showed IQ decline from childhood to midlife (mean=-5.5 IQ points), poorer learning and processing speed relative to their childhood IQ, and informant-reported memory and attention problems. These deficits were specific to long-term cannabis users because they were either not present or were smaller among long-term tobacco users, long-term alcohol users, midlife recreational cannabis users, and cannabis quitters. Cognitive deficits among long-term cannabis users could not be explained by persistent tobacco, alcohol, or other illicit drug use, childhood socioeconomic status, low childhood self-control, or family history of substance dependence. Long-term cannabis users showed smaller hippocampal volume, but smaller hippocampal volume did not statistically mediate cannabis-related cognitive deficits.
Conclusions:
Long-term cannabis users showed cognitive deficits and smaller hippocampal volume in midlife. Research is needed to ascertain whether long-term cannabis users show elevated rates of dementia in later life.
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