Lifetime cannabis use is associated with several aspects of brain structure and function in later life but cannabis use may not be the cause of these changes, according to a new study by researchers at Oxford Population Health and the Department of Psychiatry. This is the largest observational study of relationships between cannabis use and brain structure and function to date and the first to use genetic data to determine whether cannabis causes brain changes. The study is published in BMJ Mental Health.
Cannabis use has increased worldwide following its legalisation for medical and recreational purposes in many countries but the potential long term effects on the brain remain unclear. Previous studies have found that regular cannabis use is associated with a decline in neurocognitive abilities and has had a damaging effect on brain structure and function.
However, these studies have also not been able to pinpoint whether cannabis can actually cause neurocognitive decline or damage to the brain. It is also not currently known whether there is a safe threshold for cannabis use.
In this study, researchers looked at data from 15,896 participants in the UK Biobank study who had undergone a brain imaging (MRI) scan. 3,641 of the participants reported ever using cannabis and 12,225 participants had never used cannabis.
The level of cannabis use among the participants who had reported ever using it varied from once to twice to more than 100 times. These participants were further divided into low frequency users, defined as lifetime cannabis use of up to ten times, and high frequency users defined as lifetime use of 11–100+ times.
The researchers also looked at associations between the participants’ genetic data and likelihood of lifetime cannabis use to more accurately determine whether cannabis use had caused changes in the brain.
Key findings:
- In the observational analysis, cannabis use was associated with multiple measures of changes in brain structure and function;
- Participants who had ever used cannabis had poorer white matter integrity, a part of the brain that is important for cognitive function;
- Neither the duration of cannabis abstinence nor the frequency of cannabis use were associated with any of the observed findings in brain structure and function. There were also no differences between the low and high frequency of consumption groups;
- Most associations were observed in functional connectivity among the men; in women, associations were primarily seen in white matter integrity, suggesting that cannabis use affects men and women differently;
- In the genetic analyses, there were no significant associations between genetically predicted cannabis dependence/abuse or lifetime cannabis use with neurocognitive decline and brain structure and function.
Saba Ishrat, DPhil candidate at the Department of Psychiatry’ said ‘Cannabis users had significant differences in brain structure and function, most markedly for markers of lower white matter microstructure integrity. However, our results need to be interpreted with careful consideration and further 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.’
Dr Anya Topiwala, Senior Clinical Researcher at Oxford Population Health and Honorary Consultant psychiatrist at Oxford Health NHS Foundation Trust, said ‘Genetic analyses found no support for causal relationships underlying these observed associations.
There are several possible explanations for the discrepancies between the observational and Mendelian randomisation findings. For example, an unmeasured variable, such as diet, or use of certain medications, might have influenced the observational findings. The genetic analyses may also have had less statistical power to detect small effects.’
The researchers also acknowledge the limitations of using the UK Biobank, which includes predominantly healthy White participants, and few participants with heavy or dependent cannabis use.
They were also unable to look at the time points during life that might be especially vulnerable to cannabis effects, and the study relied on participants’ recall concerning the amount or frequency of cannabis use during their lifetime.