(MIND) Program at McLean Hospital/Harvard Medical School.
During this period of neurodevelopment, the brain is thought
to be particularly sensitive to damage from drug exposure. And
the frontal cortex — the region critical to planning, judgment,
decision-making and personality — is one of the last areas to
fully develop, Gruber says.
Also immature in teens is the endocannabinoid system.
As its name implies, this system comprises the physiological
mechanisms that respond to THC. That system is important for
cognition, neurodevelopment, stress response and emotional
control, and it helps to modulate other major neurotransmitter
systems, says Krista Lisdahl, PhD, director of the Brain
Imaging and Neuropsychology Laboratory at the University of
Repeated exposure to marijuana can dial down cellular
activity in the endocannabinoid system. Such interference
might be a bigger problem for immature brains, says Lisdahl.
“That sets the stage for why adolescents may be more
sensitive to the effects of repeated marijuana exposure, from a
Indeed, a number of studies have found evidence of brain
changes in teens and young adults who smoke marijuana.
In 2013, Rocío Martín-Santos, MD, PhD, at the University
of Barcelona, and colleagues reviewed 43 studies of chronic
cannabis use and the brain. They found consistent evidence of
both structural brain abnormalities and altered neural activity
in marijuana users. Only eight of those studies focused on
adolescents, but the findings from those studies suggested that
both structural and functional brain changes emerge soon
after adolescents start using the drug. Those changes may
still be evident after a month of abstaining from the drug, the
researchers reported (PLOS ONE, 2013).
Some of those brain abnormalities have been linked
to cognitive differences. Gruber found that regular, heavy
marijuana users — those who reported smoking five of
the last seven days, and more than 2,500 times in their lives
— had damage to their brains’ white matter, which helps
enable communication among neurons. Those white matter
changes were correlated with higher impulsivity, she found,
particularly in people who began smoking before age 16
Much of Gruber’s work compares heavy, regular marijuana
users who began before and after age 16. Her results suggest
there’s greater risk in starting young. Compared with users
who began after 16, early-onset smokers made twice as many
mistakes on tests of executive function, which included planning,
flexibility, abstract thinking and inhibition of inappropriate
responses. As adults, those who started using before 16 reported
smoking nearly 25 times per week, while those who started later
smoked half as often, about 12 times per week. The early-onset
smokers also reported smoking an average of nearly 15 grams
each week, versus about 6 grams for their late-onset counterparts
(Psychology of Addictive Behaviors, 2012).
Gruber’s participants had reported using marijuana at least
five times in the past week. But other labs have found structural
differences in the brains of less frequent users. Jodi Gilman,
PhD, at Massachusetts General Hospital/Harvard Center for
Addiction Medicine, and colleagues used MRI to look for brain
changes in 18- to 25-year-olds who smoked marijuana at least
once per week, but were not dependent on the drug.
Compared with nonusers, the smokers had changes in the
shape, volume and gray matter density of two brain regions
associated with addiction: the nucleus accumbens (which plays
a role in motivation, pleasure and reward processing) and the
amygdala (a region involved in memory, emotion and decision-
making). Participants who smoked more often had more
significant differences (Journal of Neuroscience, 2014).
But the case against marijuana isn’t closed. Other studies
have failed to turn up evidence that marijuana use results in
brain abnormalities. In one recent example, Barbara Weiland,
PhD, at the University of Colorado at Boulder, and colleagues
attempted to replicate Gilman’s study in adolescents and adults
who smoked marijuana daily. But Weiland’s team argued that
previous studies, including Gilman’s, failed to adequately
control for alcohol use by the participants. After carefully
matching for alcohol intake in the control and experimental
subjects, the researchers failed to find physical differences in the
nucleus acumbens or the amygdala of daily marijuana smokers
(Journal of Neuroscience, 2015).
On the other hand, says Lisdahl, Weiland’s subjects were
primarily male — and some research suggests females might be
more sensitive to marijuana’s effects during adolescence.
In other cases, too, the evidence against marijuana is
frustratingly mixed. While some studies have found increased
risk for mood disorders and psychotic symptoms among
marijuana users, for instance, a new study by Jordan Bechtold,
PhD, at the University of Pittsburgh Medical Center, and
colleagues found that chronic use among teenage boys did
not raise the risk of later depression, lung cancer, asthma or
psychotic symptoms (Psychology of Addictive Behaviors, 2015).
In hopes of painting a clearer picture of marijuana’s
potential risks to youth, NIDA plans to launch the Adolescent
Brain and Cognitive Development (ABCD) study later this
year. The prospective longitudinal study will follow 10,000
individuals across the United States over a decade, starting
when they’re 9 or 10. “The idea is to look at what these kids are
like before they start using substances, and then follow over
time what happens to their brains,” Weiss says.
Other important questions remain to be answered. Much of
the research on the long-term cognitive effects of cannabis has
focused on heavy users. It’s not clear whether there’s a safe level
of use, Lisdahl says. Nor is it known whether the brain changes