Long-Term Cannabis Use, Cognitive Decline, and the Hippocampus

Timmen L. Cermak MD

New data shows the negative impact of long-term cannabis use on cognition and hippocampal volume at age 45. IQ declines by a mean of 5.5 points and hippocampal volume decline by 12 percent after decades of persistent cannabis use. Changes caused by long-term cannabis use resemble risk factors for dementia later in life.

Our hippocampus is a complex brain structure deep in the temporal lobe that plays a major role in learning and memory. It is very plastic and very vulnerable. Hippocampal plasticity is demonstrated by studies of London taxi drivers: The more they memorize the warren of streets and allies in their ancient city, the larger their hippocampus grows.[1] Its vulnerability is demonstrated by studies showing that both the amount and duration of cannabis use contribute to hippocampal volumes being an average of 12 percent smaller[2]. Animal studies show this is caused by a 44 percent reduction in synapses and shorter dendritic length.[3] Multiple studies have shown that decreased hippocampal volume is associated with cognitive decrements.

Cognitive impact on long-term cannabis users at age 45

With this introduction, I want to turn attention to Madeline Meier’s important new article, “Long-term Cannabis Users Show Lower Cognitive Reserves and Smaller Hippocampal Volume in Midlife.”[4] Meier’s article offers a critical sequel to previous descriptions of the Dunedin, NZ, cohort of over a thousand people born in 1972-1973 who have now been studied into their fifth decade. After measuring baseline cognitive abilities at age 13 (before any drug use), each was interviewed about their substance use at 18, 21, 26, 32, 38, and now 45. Thorough neurocognitive testing at 38 revealed that individuals who started cannabis use during adolescence and persisted through adulthood experienced an average eight-point IQ decline since age 13.

Meier now reports the results of interviews and neurocognitive testing at age 45. Control groups include people who have never used cannabis, those with long-term tobacco use, those with long-term alcohol use, those who use cannabis recreationally (less than weekly), and those who have quit cannabis use. MRIs of hippocampal volumes and standardized reports of memory and attention by significant others were also obtained. Following are the results and conclusions:

  1. At 45 years old, long-term cannabis users (typically 1-4 times weekly) exhibited a mean 5.5-point childhood-to-adulthood IQ decline, with poorer learning and processing speed. The impact of cannabis is dose-dependent, with those who used cannabis more persistently showing greater IQ decline on tests of learning, processing speed, and verbal memory. This decline was significantly larger than for those who never used cannabis. People identified as knowing members of the cohort well described long-term users as having more memory and attention problems than non-users.
  2. Long-term cannabis users showed significantly larger IQ decline, poorer learning and memory, and poorer processing speed than long-term tobacco or alcohol users. This finding conflicts with the popular claim that cannabis use is safer in all ways than alcohol.
  3. Non-problematic recreational cannabis use (less than weekly) in midlife is unlikely to compromise cognitive functioning. Their mean IQ decline was 3.5 points.
  4. Long-term cannabis users who quit still showed subtle cognitive deficits. Long-term cannabis users did not perform significantly worse than cannabis quitters on any test.
  5. Long-term cannabis users showed smaller hippocampus volume, and persistence of cannabis use showed dose-response associations with both smaller hippocampal volume and cognitive deficits. Meier takes pains to point out that smaller hippocampal volume is likely not the sole cause of cognitive deficits. Multiple other brain areas with dense concentrations of cannabinoid receptors likely also contribute to the decline in cognitive function.

It should be quickly noted that while a mean decline of 5.5 IQ points means half of the long-term cannabis users experienced more than a 5.5-point loss, they still were not diagnosable as being cognitively impaired. Their cognitive decline may have altered employment opportunities for which they were qualified, but they were in no way demented. Yet.

The trajectory of cannabis-induced cognitive decline in midlife

Here is the unknown: Studies of the general population show that mild cognitive deficits and greater hippocampal atrophy in midlife are risk factors for later dementia after age 70.[5] Meier is concerned that cognitive child-to-adult changes associated with long-term cannabis use observed in the Dunedin study are like those that predict steeper cognitive decline later in life. At this point, it is unknown, and unknowable, whether cannabis-induced changes in midlife have the same trajectory as those occurring for other non-cannabis-related reasons.

We will have to wait at least 30 more years for the fate of participants in the Dunedin study to be revealed when they enter their eighth decade. At 77 years old, I will not live to see the answer to the question of whether changes seen at 45 years old are harbingers of later dementia, or not.

But it is something to consider if you are a long-term regular cannabis user. We know that multiple sclerosis patients who use cannabis to control painful muscle spasms have earlier cognitive decline. Does this have any relationship to the fate of cannabis users without the overlay of multiple sclerosis? No one can say one way or the other, and it is important not to allow today’s uncertainties to feed into scare tactics. Nor is it wise to ignore what data we do have. Each person must evaluate their own tolerance for risk. Awareness of the limited facts we have is necessary for each one of us to make reasonable personal decisions for ourselves.

References

1. K. Woollett and E. A. Maguire. Acquiring “the Knowledge” of London’s Layout Drives Structural Brain

Changes. Curr Biol, 2011; 21(24–2): 2109–14.

2. M. Yucel, et al. Regional Brain Abnormalities Associated With Long-term Heavy Cannabis Use. Arch Gen

Psychiatry, 2008; 65(6): 694–701.

3. Scallet, et al. Morphometric Studies of the Rat Hippocampus Following Chronic

Delta-9-Tetrahydrocannabinol (THC). Brain Res, 1987; 436(1): 193–8.

4. M. Meier, et al, Long-term Cannabis Users Show Lower Cognitive Reserves and Smaller Hippocampal Volume in Midlife, Am J Psychiatry. 2022 May; 179(5): 362–374

5. Knopman, D. et al. Midlife vascular risk factors and midlife cognitive status in relation to prevalence of mild cognitive impairment and dementia in later life: The Atherosclerosis Risk In Communities Study. Alzheimer’s & Dementia 2018; 14(11):1406–15.

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