Experimental mice have been telling us this for years, but pot-smoking humans didn’t want to believe it could happen to them: Compared with a person who never smoked marijuana, someone who uses marijuana regularly has, on average, less gray matter in his orbital frontal cortex, a region that is a key node in the brain’s reward, motivation, decision-making and addictive behaviors network.

More ambiguously, in regular pot smokers, that region is better connected than it is in non-users:The flow of signal traffic is speedier to other parts of that motivation and decision-making network, including across the superhighway of “white matter” that connects the brain’s hemispheres.

The researchers who conducted the study speculate that the orbital frontal cortex’s greater level of “connectedness” – which is especially pronounced in people who started smoking pot early in life – may be the brain’s way of compensating for the region’s underperforming gray matter. Whether these “complex neuroadaptive processes” reverse themselves when marijuana use stops is an important unanswered question, they added.

The new findings, reported Monday in the journal PNAS, confirm findings about chronic marijuana use from rodents. But scientific evidence in humans has been more mixed.

Even now, however, the authors of the study acknowledge that they cannot discern whether a pot smoker’s smaller orbital frontal cortex is the cause or the result of chronic marijuana use. A 2012 study found that subjects with a smaller orbital frontal cortex at age 12 were more likely to start using marijuana by age 16, suggesting that deficits in this crucial region may predispose one to substance-abuse behaviors.

This study, conducted by researchers from the University of Texas’ Center for Brain Health and the Albuquerque-based Mind Research Network, did not follow subjects over time, so it is at a disadvantage in showing cause and effect. Instead, it compared 48 “chronic” marijuana users (at least four times a week over the past six months) with 62 non-using control subjects who were matched for age and gender with the using group. Subjects were an average age of 28 to 30 years old.

Researchers noted that the IQ of the marijuana-using group was significantly lower than that of the non-using group – not a finding of the study, but an incidental factor that might be indirectly linked to marijuana use.