The question of whether cannabis use causes cognitive deficits or structural changes in the brain is still an open one, and has mostly been tested in adolescents and young adults. There is good reason for this emphasis: the brain is vulnerable and continues to develop throughout the teen years and into the twenties, and those are typical ages when cannabis use is experimented with and can become chronic.

Several studies comparing cannabis use among young people with matched individuals who have not used cannabis have found evidence of subtle cognitive deficits and structural brain differences among the cannabis users. Various uncertainties remain controversial, including the potential importance of how frequently and for how many years cannabis is used, the potency of the cannabis used (in terms of THC content, the psychoactive component of cannabis), and the possible inclusion in such studies of individuals who may be at unrecognized high risk for mental illness, especially psychotic disorders.

In general, the medical and mental health significance of observed differences between young, ostensibly healthy users and non-users of cannabis remains a subject of debate, and long-term effects still have not been rigorously tested.

The question of potential longer-term impact of chronic cannabis use was central to a team of investigators led by Madeline H. Meier, Ph.D., of Arizona State University, and Terrie E. Moffitt, Ph.D., of Duke University. They have published results of a preliminary study on the question in the American Journal of Psychiatry. Dr. Moffitt is a 2010 BBRF Ruane Prize winner, as is another team member, Avshalom Caspi, Ph.D.; Ahmad R. Hariri, Ph.D., a 2003 BBRF Young Investigator, was also a member of the team.

The researchers said the effects of long-term cannabis use upon brain function and structure in midlife and older users are especially pertinent with legalization of cannabis in many states, and increasing use of the drug among baby boomers (b. 1946-64), “a group that used cannabis at historically high rates as young adults and who now use cannabis at historically high rates as midlife and older adults.”

Are all midlife and older adult cannabis users at risk? The team estimates that perhaps 10%-15% of users in this age range are dependent upon the drug. “Distinguishing problem and non-problem users is important,” the researchers stressed, since those who use cannabis relatively infrequently in midlife without the problems associated with long-term use may not differ in risk from non-users. Another question the team asked: how do cognitive and other brain differences among chronic cannabis users, if they exist, compare with those seen in chronic alcohol or tobacco users in the same age group? Do differences, if any, persist after cessation of cannabis use? And finally: do structural brain differences among chronic cannabis users, if any, underlie cognitive deficits and do they predict higher risk for dementia later in life?

To study these questions, the team utilized a well-documented cohort of 1,037 individuals representative of people born in Dunedin, New Zealand in 1972 and 1973. 938 members of the group, followed through age 45, formed the basis for the analysis in the cannabis study. Among a host of factors, cannabis use and dependence were assessed in members of the cohort at ages 18, 21, 26, 32, 38, and 45. The group was also tested for IQ at three points in childhood—ages 7, 9, and 11—and again at age 45. Specific neuropsychological functions and volume of the brain’s hippocampus were assessed at age 45. There has been some evidence, not conclusive, that the hippocampus, critical in learning and memory, can be adversely impacted in chronic cannabis users—its size and functional effectiveness reduced.

Analysis of the New Zealand data revealed that long-term cannabis users showed a decline in IQ from childhood to midlife (typically by about 5.5 points), as well as deficits in their midlife learning ability and brain processing speed. Study participants’ friends and relatives also supplied information in response to questionnaires which indicated that chronic users were more likely to experience memory and attention problems.

“These deficits were specific to long-term cannabis users,” the team made clear. “They either were not present or were smaller among long-term tobacco users, long-term alcohol users, as well as those who used cannabis recreationally in midlife and those who stopped using cannabis altogether by midlife.” The team defined recreational users as those who used cannabis between 6 and 51 days a year (i.e., less than weekly) in midlife (ages 32, 38, or 45); “quitters” were defined as those who no longer used at age 45 but at one of the earlier time-points in the study had been diagnosed with cannabis dependence or used regularly, i.e., 4 or more times per week.

“Cognitive functioning among midlife recreational cannabis users was similar” to norms in the overall cohort of 938 people. “Quitters showed subtle cognitive deficits” of uncertain significance. Long-term chronic users of cannabis showed smaller hippocampal volume in 5 of 12 subregions of the hippocampus. However, the evidence did not support connecting smaller hippocampal volume with observed cognitive deficits. Such a connection may or may not exist. The team speculates that additional, more complex factors or processes may be involved in causing cognitive deficits among chronic life-long cannabis users; the nature of such mechanisms remains unclear.

A number of potential “confounding” factors was noted in the team’s paper. One is the fact that many long-term cannabis users also use tobacco, alcohol, and other drugs. “Disentangling cannabis effects is challenging,” they said. Still, their findings did show that the use of other substances cannot account fully for the cognitive effects seen in long-term cannabis users. Another concern was the lack of data on the potency of THC in cannabis used by participants in the study and how this may have changed over time; the cannabis that study participants use today is many times more potent, on average, than cannabis that they used prior to the 2000s.

The key question raised by the study, which merits continued exploration in this cohort and others, the team said, was whether midlife cognitive deficits in long-term cannabis users, to the extent they exist, raise risk or even predict dementia later in life.