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Brain Differences Seen With Combined Cannabis, Tobacco Use

The use of cannabis and tobacco in combination may have unique effects on the brain and memory that in some ways contradict established neural responses, a new study suggests.

Imaging showed smaller hippocampal volumes, and testing showed worse memory among participants who used cannabis alone or with tobacco in comparison with nonusers, but smaller volumes were associated with better memory among users of marijuana plus tobacco.

The findings underscore the need to include the likelihood of comorbid tobacco use in cannabis research.

“Approximately 70% of individuals who use marijuana also use tobacco,” said principal investigator Francesca Filbey, PhD, director of cognitive neuroscience of addictive behaviors at the Center for Brain Health, in New York City, in a press statement.

“Our findings exemplify why the effects of marijuana on the brain may not generalize to the vast majority of the marijuana-using population, because most studies do not account for tobacco use.”

Their report was published this month in the journal Behavioural Brain Research.

Total Hippocampal Volumes

The study involved four groups of adults from two larger studies conducted at the University of New Mexico, in Albuquerque, which included cannabis-only users (n = 36), tobacco-only users (n = 19), combined cannabis and tobacco users (n = 19), and non–using healthy control participants (n = 16).

Criteria for cannabis users’ inclusion was reported use of cannabis at least four times per week during the past 6 months, verified by urinalysis. Tobacco users’ criteria included having used tobacco 10 or more times daily, verified by carbon monoxide breath monitor, and having had fewer than 3 months of abstinence in the past year.

After controlling for brain size and recent alcohol use, MRI showed smaller total hippocampal volumes among participants who used cannabis and tobacco, compared with the tobacco-only users and the control participants.

Interestingly, the reductions in hippocampus size in the combination group of cannabis and tobacco users were not significantly different from those of users of cannabis alone.

“It was surprising that this was not significantly different,” Dr Filbey told Medscape Medical News. “It is possible that with a large sample size, we may be able to detect a difference.”

Even more unexpected were findings showing that although in the nonuser control individuals, there was a trend linking larger hippocampal volume with improvements on memory scores, the users of cannabis and tobacco in combination showed worse memory and delayed recall scores that were associated with larger, not smaller, hippocampal volumes (P = .05 and P = .04, respectively), with scores improving with smaller hippocampal size.

“Taken together, the [cannabis and tobacco] users exhibited abnormal links between hippocampal volume and memory scores, and these relationships significantly deviated from the same patterns among control subjects,” the authors write.

The cannabis and tobacco users nevertheless had the smallest hippocampal volumes of the four groups, and they also had the lowest memory performance.

Dr Filbey speculated that the abnormal findings on hippocampal size and memory in cannabis and tobacco users could stem from an effect seen before with nicotine.

“It is possible that we may be seeing cognitive-enhancing effects of nicotine on memory function that is greater in those with smaller hippocampal volumes,” she said.

“Studies have found that this enhancing effect from nicotine is greater in those with greater impairment.”

Unusual Neuronal Effect

The findings suggest that a highly unusual neuronal effect can take place with the combination of cannabis and tobacco use, said Frank J. Vocci, PhD, coeditor of the American Society of Addiction Medicine’s Journal of Addiction Medicine and president of Friends Research Institute, Inc, in Baltimore, Maryland.

“This is certainly counterintuitive,” he told Medscape Medical News. “It strikes me as odd that you would get essentially a good response in the combination users group [in terms of memory], so there clearly is something going on that isn’t quite understood between nicotine and marijuana users and memory that has to be worked out,” he said.

“Small hippocampal volume is not considered to have a beneficial effect, so it certainly is an intriguing finding and needs replication in a larger study.”

The study’s authors have disclosed no relevant financial relationships. Dr Vocci has been a consultant for Reckitt-Benckiser Pharmaceuticals and for generic manufacturers of buprenorphine products. He has also been an investigator and consultant for buprenorphine studies funded by Braeburn Pharmaceuticals and Titan Pharmaceuticals. All of Dr Vocci’s consulting fees go to his employer, Friends Research Institute, Inc.

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