How does cannabis use affect brain structure?

A recent observational study suggests that lifetime cannabis use is linked to various changes in brain structure and function in later life. 

However, when researchers conducted a genetic analysis on the same data, they found that these associations might not be causal, indicating that other unidentified factors could be at play. 

The experts highlight the need for further investigation to fully understand how the frequency and potency of cannabis use may impact the brain, particularly given the global increase in cannabis use following its legalization in many areas for medical and recreational purposes.

Concerns over long-term brain health

The scientists underscore the importance of a deeper understanding of cannabis’s long-term effects, especially since its use has been linked to deleterious effects on neurocognitive performance, brain structure, and function. 

Moreover, the precise threshold of safe cannabis consumption, if any exists, is currently unknown. 

While past observational studies have suggested changes in brain structure among regular users, these studies could not confirm causation, and few have focused on older populations, where the effects of lifelong cannabis use are especially relevant.

Genetic links to risk factors

To strengthen the evidence base, the researchers used Mendelian randomization, a genetic method that employs genetic variants as stand-ins for particular risk factors. 

In this study, the method was used to identify any potential causal links between cannabis use or dependence and changes in brain structure. 

Data was drawn from a large group of UK Biobank participants (15,896 people), which included both genetic profiles collected from 2012-13 and MRI brain imaging data collected from 2014-19.

Brain structure and frequent cannabis use 

Participants were asked if they had “ever taken cannabis,” with response options ranging from occasional use to over 100 times. 

Based on responses, 3,641 participants who answered “yes” were categorized as lifetime cannabis users, averaging 61 years in age, while the 12,225 “no” responders formed a comparison group, with an average age of 64. 

Cannabis users were further categorized into low-frequency users (lifetime use of up to 10 times) and high-frequency users (lifetime use of 11 to 100+ times). The participants also reported the age at which they last used cannabis.

Cannabis and brain structure changes

The research team accounted for multiple influential factors, including age at first scan, sex, socioeconomic status, mental health, BMI, blood pressure, and various lifestyle factors, ensuring a more accurate assessment of cannabis-related brain differences. 

After adjusting for these factors, the results showed that cannabis use was associated with changes in multiple brain structures and functions.

Participants who had used cannabis at any point in their life displayed lower integrity in their white matter – a part of the brain critical to cognitive function. This was especially prominent in the corpus callosum, the major pathway connecting the left and right sides of the brain. 

Gender differences in brain changes 

Additionally, cannabis users had weaker neuronal connectivity in the default mode network, which is generally active during periods of mind-wandering and self-reflection. The researchers noted that these areas are densely packed with cannabinoid receptors, suggesting a possible direct impact of cannabis.

Despite these associations, the study found no significant link between either the length of time since last cannabis use or the frequency of use and changes in brain structure and function. 

However, they observed gender differences: significant associations were found across six specific brain regions in men, while associations in women spanned 24 brain structures and regions, primarily affecting white matter integrity in women and functional connectivity in men. 

According to the researchers, these results indicate that cannabis may impact male and female brains differently.

Lifelong cannabis use and brain structure 

Applying Mendelian randomization to the findings, the researchers found no significant associations between genetically predicted cannabis dependence or lifetime use and changes in brain structure. 

“To the best of our knowledge, this is the largest observational study of relationships between cannabis use and brain structure and function to date, and the first Mendelian randomisation investigation,” the authors wrote. 

“Cannabis users had significant differences in brain structure and function, most markedly for markers of lower white matter microstructure integrity. Genetic analyses found no support for causal relationships underlying these observed associations.”

Limitations of the study

There are several possible reasons for the disparity between the observational and Mendelian randomization findings. The researchers propose that other variables, such as family history, diet, or specific medications, may have influenced the observational findings. 

Additionally, they note that the Mendelian randomization analyses may have had limited statistical power to detect subtle effects.

Further, Mendelian randomization looks at the lifelong impact of cannabis use, while the changes in brain structure noted in observational studies may be due to factors arising at various points in an individual’s life, rather than a cumulative lifelong effect. 

The researchers also point to the limitations of the UK Biobank data, which includes predominantly healthy white participants with few reporting cannabis use disorders. Due to this demographic limitation, the findings may not fully represent the diversity of cannabis users worldwide.

Furthermore, the study faced limitations in assessing critical time points during life that could reveal when cannabis use most impacts brain structure. 

Future research directions

“Our results need to be interpreted with careful consideration. Additional research is needed to understand the effects of heavy cannabis use in this population, including considerations of potency and related information to inform public policy,” the authors wrote.

Further research may be crucial in clarifying the long-term impacts of heavy and frequent cannabis use on brain health, with implications for both public health policy and individual health awareness.

The study is published in the journal BMJ Mental Health.

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