WEDNESDAY, Dec. 23 (HealthDay News) -- Marijuana use among teens may
trigger neurological changes in the developing brain that lead to increased
anxiety and stress levels that could persist into adulthood, new animal
Although the finding stems solely from work conducted with adolescent and
adult lab rats -- not yet replicated among humans -- the work suggests that
certain troublesome changes in levels of the key brain chemicals serotonin
and norepinephrine may linger long after marijuana use ceases.
"Here, the goal was simply to understand the neurological mechanism that
could be underlying the specific phenomenon of depression and anxiety
observed in previous studies among adolescents chronically exposed to
cannabis," explained study author Dr. Gabriella Gobbi, a psychiatric
researcher at the Research Institute of the McGill University Health Centre
"And what we found with the animals we worked with is that when those that
were exposed to cannabis as adolescents became adults they had low serotonin
activity, which is related to depressive behavior, and high norepinephrine
levels, which is related to an increase in anxiety and stress," Gobbi
"This means," she cautioned, "that cannabis exposure when young seems to
cause changes in the adult brain. And these changes could perhaps be
irreversible, even if you stop consuming cannabis."
The study findings were released online Dec. 5 in advance of publication in
an upcoming print issue of Neurobiology of Disease.
The authors note that the main ingredient in marijuana --
delta-9-tetrahydrocannabinol (THC) -- has previously been identified as
having an impact on receptors in the brain that regulate cognition and
In addition, they point out that the adolescent brain is perhaps
particularly sensitive to both drug use and related stress, given that this
is the pre-adult period during which the brain and its neurochemical
composition undergoes extensive reshaping and reorganizing.
To assess the role cannabis may play on adolescent brain development, for 20
days -- a period characterized as "prolonged exposure" -- adolescent rats
were given daily injections of either a low-dose (0.2 milligrams/kilograms)
or high-dose (1.0 milligrams/kilograms) of cannabis. For comparison, a group
of adult rats underwent a similar regimen.
Following cannabis exposure, both the adolescent and adult groups went 20
days drug-free to allow the effects of drug withdrawal to dissipate, as well
as to allow for a wide range of cognitive testing to gauge the long-term
effects of cannabis exposure on task execution and mood.
The authors noted that by the conclusion of the 20-day waiting period, the
previously adolescent rats were effectively adults.
The team found that chronic exposure to cannabis during adolescence does
appear to provoke abnormal emotional activity into adulthood, typified by
the onset of depression, poorer social interaction, heightened anxiety and
What's more, Gobbi and her colleagues also found a drop in serotonin levels
in the adult brain following either low- or high-dose adolescent ingestion
and an increase in norepinephrine levels following high-dose exposure.
Rats who had already reached adulthood when chronically exposed to cannabis,
however, appeared to experience far less of the detrimental emotional
reactions found among adolescent rats. Indeed, adult rats, they observed,
seemed to be able to readily cope with, and even overcome, most of the
neurological impairments that arose as a result of cannabis exposure.
"We were a little bit surprised by our findings because we didn't expect to
see such a strong effect on the adult brain from adolescent usage. It was a
very significant effect," said Gobbi.
"So, in general, I think that what people should take away from this work,"
she advised, "is that just because it's a plant it doesn't mean that
marijuana is harmless. It's a pharmacologically active drug, and it must be
used with awareness."
For his part, however, Dr. Adam Bisaga, an addiction psychiatrist at New
York State Psychiatric Institute, minimized the relevance of the findings.
"I think the translational value of this research is very limited insofar as
what the clinical relevance to humans might be," Bisaga cautioned. "It's
always very difficult to translate from animal models to humans. Yes, there
is some indication that this may be of importance to humans. But most of the
data with patients that I am familiar with suggests that most of these
cannabis-exposure deficits are reversible. So, for the time being I'm not
that impressed, although it's certainly something to further study in
humans," he added.
"This is not new," he noted. "Clinicians know well that exposure to large
amounts of cannabis in adolescence may produce enduring changes in emotional
functioning and reactivity in vulnerable individuals, such as
difficult-to-treat anxiety and depressive symptoms. What this paper does is
to try to characterize more precisely the components of this syndrome using
animal models of emotional reactivity."