New research shows that the effects of chronic cannabis abuse on the cerebellum and people's sleep patterns vary by sex, with female users reporting lower quality of sleep than men — particularly if they started using cannabis during adolescence. 

The study, published May 13 in Frontiers in Psychiatry, adds to a growing body of knowledge about how women are more adversely affected by long-term substance abuse than men, shining light specifically on how chronic cannabis use and sex interact to affect brain structure, Peter Manza, a research fellow at the National Institute on Alcohol Abuse and Alcoholism Laboratory of Neuroimaging and corresponding author of the study, told The Academic Times. 

"We've been interested for a while now in sex differences in the outcomes for people with substance use disorders more generally," he said. "Until recently, this was an unappreciated or understudied area. We're realizing that, even though the overall prevalence of substance abuse and use disorders is higher among men, when women do have substance use disorders, their outcomes are generally worse than men's."

The cerebellum is an area of the hindbrain that is classically associated with balance, movement and coordination, but has turned into a popular research target for neuroscientists and psychologists as it becomes more apparent that the cerebellum influences many forms of behavior, and could have even played an important role in the evolution of the human brain. 

"It really does seem to play a role in not just movement, but in cognition and motivation, and seems to come up over and over again in studies looking at the pathophysiology of substance use disorders," Manza said. "I suppose it's not so surprising, given the massive number of neurons packed into that region relative to the rest of the brain." 

Drawing data from the Human Connectome Project — a map of neural pathways charted by a consortium led by Washington University in St. Louis — Manza and his colleagues looked at interactions between 10 different regions of the brain and self-reported sleep quality in 170 chronic cannabis users, matching them with an equal number of carefully selected control subjects who were similar in age, sex, race, body mass index and both tobacco and alcohol use. In other words, the researchers tried to control as many variables as possible to make it very likely that differences in the groups were due to cannabis use — not other, possibly co-occurring, factors. 

"One of the major issues with early substance abuse studies was that people just kind of did their best to get a control group that was maybe related on a couple of factors to the substance use group," he said. "But we know there are many complex social and demographic factors that are inextricably linked with substance use. So, it's really important for us to find healthy controls who look pretty similar to the substance use group on these background demographic factors." 

Chronic use was defined in the study as either a lifetime diagnosis of cannabis dependence or more than 100 total uses throughout their lives. Alongside brain volume and cannabis use, the researchers also examined sleep quality. "We thought that it's a really important behavioral outcome for people with cannabis use disorder," Manza said. Though cannabis helps people sleep in the short term, chronic users generally experience worse sleep over time. 

On average, the cannabis-using group had smaller cerebellums than their controls — an effect driven by the women in the study, who showed significantly lower cerebellum volumes, while men did not. The cannabis-using group also had more self-reported sleep issues than the control group; again, this effect was more prominent among the female cannabis users. 

What's more, women who said that they began using cannabis during adolescence reported the highest levels of disturbed sleep, which tracks with a large body of evidence showing that cannabis' long-term effects are particularly deleterious when people start consuming it at an early age. Among subjects who started using cannabis after the age of 18, the difference in sleep quality between men and women was negligible, Manza said. 

"The effect really seemed to be driven by women who started using cannabis at a young age," he explained. "That gave us more confidence that this may be truly related to the use of cannabis, as opposed to maybe some condition that predisposes people to both have sleep problems and to use cannabis. In this study, we could not demonstrate a true causal effect because you can't put people into two different groups and give one cannabis chronically; that would not be ethical. The best we could do here is report after the fact what people's experiences are." 

With the cerebellum representing the likeliest brain structure behind the effect observed in the study, Manza believes the research could inform future preclinical research in rodents focused on establishing causality between using cannabis and volume loss in the cerebellum. 

"Going forward, we need to always be really mindful of the impact of sex on these effects," he said. "We need to address these health disparities, and we also need to see what this means for the pathophysiology of addiction." 

The study, "Cannabis affects cerebellar volume and sleep differently in men and women," published May 13 in Frontiers in Psychiatry, was authored by Katherine L. McPherson, Dardo G. Tomasi, Gene-Jack Wang and Peter Manza, National Institute on Alcohol Abuse and Alcoholism; and Nora D. Volkow, National Institute on Drug Abuse.