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 research suggests.
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 in Montreal.
"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 continued.
"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 emotion.
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 increased stress.
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."
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 in Montreal.
"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 continued.
"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 emotion.
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 increased stress.
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."
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