Growing up high: Neurobiological consequences of adolescent cannabis use
Canadian neuroscientists offer insights into the long-term effects of adolescent cannabis use
May 26, 2019
Science Daily/Canadian Association for Neuroscience
About one in five Canadian adolescents uses cannabis (19% of Canadians aged 15-19), and its recent legalization across the country warrants investigation into the consequence of this use on the developing brain. Adolescence is associated with the maturation of cognitive functions, such as working memory, decision-making, and impulsivity control. This is a highly vulnerable period for the development of the brain as it represents a critical period wherein regulatory connection between higher-order regions of the cortex and emotional processing circuits deeper inside the brain are established. It is a period of strong remodeling, making adolescents highly vulnerable to drug-related developmental disturbances. Research presented by Canadian neuroscientists Patricia Conrod, Steven Laviolette, Iris Balodis and Jibran Khokhar at the 2019 Canadian Neuroscience Meeting in Toronto on May 25 featured recent discoveries on the effects of cannabis on the adolescent brain.
Dr. Patricia Conrod, at Université de Montréal, studied the year-to-year changes in alcohol and cannabis use and cognitive function in a sample of adolescents consisting of 5% of all students entering high school in 2012 and 2013 in the Greater Montreal region (a total of 3,826 7th grade students). Students were assessed annually for 4 years on alcohol and cannabis use, and their cognitive function was evaluated using computarized cognitive tests. The researchers found substance use to be linked to low cognitive functioning, a finding that could be indicative of an underlying common vulnerability. Cannabis use was linked to impairments in working memory and inhibitory control, which is required for self-control. Cannabis use was also linked to deficits in memory recall and perceptual reasoning. Alcohol use was not linked to impairments in these cognitive functions, suggesting cannabis could have more long-term effects than alcohol.
More recently Dr. Conrod's team analysed the sex difference in cannabis response in the same sample of adolescents. Preliminary data indicates that cannabis use had a stronger effect on the memory functions of male students than female students. Both sexes were however, equally affected by cannabis on inhibitory control. These results help identify at-risk youth groups and target them for early intervention and information.
Dr. Steven Laviolette presented research on the effect the primary psychoactive component of cannabis, delta-9-tetrahydrocannabinol or THC, on the adolescent brain, in rodent animal models. His team demonstrated that adolescent exposure to THC induces changes in specific a region of the brain called the prefrontal cortex (PFC) and in a brain circuit, the mesolimbic pathway, that closely resemble the abnormalities observed in schizophrenia. Furthermore, adolescent THC exposure also caused affective and cognitive abnormalities including deficits in social interactions, memory processing and anxiety regulation.
Interestingly, Dr. Laviolette's team found that administration of drugs that restore normal PFC function in early adulthood could reverse the effects of adolescent THC exposure. They also demonstrated that co-administering THC with drugs that prevent the THC-induced disruption in brain signaling pathways prevented the development of schizophrenia-like effects. These results offer insights into ways to prevent or reverse THC-induced brain signaling defects in adolescents.
Dr. Iris Balodis, from McMaster University, investigates the mechanisms that motivate individuals to act and make decisions that can go against a person's best interest, as seen in people suffering from addiction. To compare decision-making in individuals suffering from cannabis addiction (also called cannabis use disorder) to healthy controls, Dr. Balodis used an effort-based decision-making test, which explores how much effort and individual is willing to make to receive a given reward. Participants are given a choice between an easy task or a hard task in which they can gain varying amounts of money (for example, pressing a lever a number within a certain time limit). During the administration of this test, Dr. Balodis and her team looked at differences in activity in different brain regions by functional magnetic resonance imaging. Initial findings suggest that there are differences in encoding the value of the reward (money received) and of the effort cost (amount of work done) in individuals addicted to cannabis relative to healthy controls. These were revealed by differences in activation of specific brain regions known to be important for motivation. This information could be key to finding cannabis addiction vulnerability factors.
Adolescent cannabis use is associated with behavioral changes related to reward and motivation in humans. Paradoxically, this use has both been suggested to increase motivation for other drug use (the gateway hypothesis) and a potential "amotivation syndrome" in which individuals are less willing to expend effort to receive a reward. It is not known whether adolescent cannabis use causes either of these responses, or if cannabis use is rather a symptom of a pre-existing state that results in these behaviours. In order to better understand the long-term effects of adolescent cannabis exposure on the brain, Dr. Jibran Khokhar, from the University of Guelph, studied the effect of THC exposure in adolescent rats on their adult behaviour. In this study, adolescent THC exposure differentially impacted instrumental (decreased lever pressing) and Pavlovian learning (increased sign-tracking). These rats also showed differences in other reward-related behaviors. These behavioural changes were accompanied by changes in the connection between different regions of the brain, including those involved in encoding reward and motivation. These results suggest adolescent cannabis exposure in rats can produce long-lasting changes in brain circuitry which might contribute to the behavioral changes observed after cannabis exposure.
Taken together, the research results presented in this symposium help decipher the links between cannabis use and long-lasting changes in the brain, which underlie changes in behaviour in adolescent humans, and in studies reverse-translating these findings to animal models. Research in humans shows that adolescent cannabis use is widespread, and associated with defects in working memory, self-control and motivation. Similar results were obtained in animal studies, through which researchers were also able to test therapies that can reverse the effects of adolescent cannabis use in adulthood. These findings provide keys to prevent and treat the long term effect of adolescent cannabis use.
https://www.sciencedaily.com/releases/2019/05/190526135747.htm
Cannabis use in teens linked to risk of depression in young adults
Cannabis use among adolescents is found to be associated with increased risk of depression and anxiety in adulthood
February 13, 2019
Science Daily/University of Oxford
Cannabis is the most commonly used recreational drug by teenagers worldwide. In Canada, among youth aged 15 to 19 years, the rate of past-year cannabis use is 20.6 percent, while in England, 4 percent of adolescents aged 11 to 15 years used cannabis in the last month.
While there has been a lot of focus on the role of cannabis use in psychosis, there has been less attention on whether cannabis use is associated with an increased risk of common mental health disorders, such as depression and anxiety.
Researchers from McGill University and the University of Oxford carried out a systematic review and meta-analysis of the best existing evidence and analysed 23,317 individuals (from 11 international studies) to see whether use of cannabis in young people is associated with depression, anxiety and suicidality in early adulthood.
They found that cannabis use among adolescents is associated with a significant increased risk of depression and suicidality in adulthood (not anxiety). While the individual-level risk was found to be modest, the widespread use of the drug by young people makes the scale of the risk much more serious.
The population attributable risk was found to be around 7%, which translates to more than 400,000 adolescent cases of depression potentially attributable to cannabis exposure in the US, 25,000 in Canada and about 60,000 in the UK.
Dr. Gabriella Gobbi, Professor, Department of Psychiatry, McGill University and a scientist at the Research Institute of the McGill University Health Centre, states: "While the link between cannabis and mood regulation has been largely studied in preclinical studies, there was still a gap in clinical studies regarding the systematic evaluation of the link between adolescent cannabis consumption and the risk of depression and suicidal behaviour in young adulthood. This study aimed to fill this gap, helping mental health professionals and parents to better address this problem."
Professor Andrea Cipriani, NIHR Research Professor of Psychiatry at the University of Oxford, said: 'We looked at the effects of cannabis because its use among young people is so common, but the long-term effects are still poorly understood. We carefully selected the best studies carried out since 1993 and included only the methodologically sound ones to rule out important confounding factors, such us premorbid depression.'
'Our findings about depression and suicidality are very relevant for clinical practice and public health. Although the size of the negative effects of cannabis can vary between individual adolescents and it is not possible to predict the exact risk for each teenager, the widespread use of cannabis among the young generations makes it an important public health issue.
'Regular use during adolescence is associated with lower achievement at school, addiction, psychosis and neuropsychological decline, increased risk of motor vehicle crashes, as well as the respiratory problems that are associated with smoking.'
The active ingredient in cannabis,THC, mediates most of psychoactive and mood-related effects of cannabis and also has addictive properties. Preclinical studies in laboratory animals reported an association between pubertal exposure to cannabinoids and adult-onset depressive symptoms. It is thought that cannabis may alter the physiological neurodevelopment (frontal cortex and limbic system) of adolescent brains.
While the review of observational studies was the first to look at the effects of cannabis use in adolescents only, it was not possible to predict the risk at the individual level, nor was it possible to discern information about the dose-dependent risk of cannabis use.
https://www.sciencedaily.com/releases/2019/02/190213172307.htm
Adolescent cannabis use alters development of planning, self-control brain areas
November 6, 2018
Science Daily/University of Illinois at Chicago
Adolescent marijuana use may alter how neurons function in brain areas engaged in decision-making, planning and self-control, according to researchers at the University of Illinois at Chicago.
The findings, which were presented at Neuroscience 2018, the annual meeting of the Society for Neuroscience, are the result of an animal model study focused on the structural development of the prefrontal cortex, or PFC, which controls high-level cognitive functions.
Within the PFC, a support structure called the perineuronal net forms a lattice of proteins around inhibitory cells, helping to secure their connections with excitatory neurons and regulate PFC activity. Perineuronal net formation is sensitive to drug use, but the effects of marijuana are not known.
To investigate how adolescent marijuana use affects perineuronal nets in the PFC, the UIC researchers gave adolescent rats a synthetic cannabinoid which was similar to THC, the main psychoactive compound in marijuana, for one day, 10 days, or 10 days followed by a period of abstinence. They then compared perineuronal net structure in these rats to those in drug-free animals.
Animals exposed to the cannabinoid showed a reduction in net development around inhibitory cells during adolescence, and this reduction was more common in male animals.
"Our evidence suggests that exposure to cannabinoids during adolescence alters brain maturation in the prefrontal cortex," said Eliza Jacobs-Brichford, study lead author and UIC Ph.D. candidate in psychology. "These results may offer a mechanistic explanation for functional and behavioral changes caused by adolescent cannabinoid exposure."
Recreational use of marijuana is among the risky choices often made by adolescents, and likely to become more prevalent with greater availability due to its shifting legal status in some states and Canada.
These impulsive choices are taking place during a key period of brain development and could have costs later in life, according to the researchers.
"Adolescence is a crucial time for fine-tuning the balance of excitatory and inhibitory neurons in the brain, which combine to control precise patterns of brain activity," said Jamie Roitman, UIC associate professor of psychology and study co-author. "Substance use as a teenager thus has the potential to disrupt the normal developmental trajectory of the PFC, with potentially long-term consequences for decision-making."
Hu Chen, UIC research assistant professor of psychiatry, and Amy Lasek, UIC associate professor of psychiatry, are co-authors on the paper.
The study was supported with funds from the National Institute on Drug Abuse, one of the National Institutes of Health, and a UIC Provost Award for Graduate Research.
https://www.sciencedaily.com/releases/2018/11/181106150439.htm
Children whose mothers use marijuana are more likely to try it at younger age
September 24, 2018
Science Daily/Elsevier
When mothers use marijuana during the first 12 years of their child's life, their cannabis-using children are more likely to start at an earlier age than children of non-using mothers, according to a new study from the Harvard T.H. Chan School of Public Health published in the American Journal of Preventive Medicine. This study is the first to establish a relationship between maternal cannabis use during a child's lifetime and earlier initiation in a nationally-representative, longitudinal cohort, and examine the role of race, gender, and other social environmental factors.
"Early initiation is one of the strongest predictors of the likelihood of experiencing health consequences from marijuana use. In a shifting regulatory environment in which we expect adult marijuana use to become more normative, developing a deeper and more nuanced understanding of social risk factors for early initiation is a critical step in intervention design and delivery. Incorporating maternal cannabis use into our understanding of the important risk factors for early initiation may help us better identify at-risk youth for more tailored or intensive prevention strategies," explained lead investigator Natasha A. Sokol, ScD, currently of the Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University School of Public Health, Providence, RI, USA.
The investigators analyzed two linked cohorts of The National Longitudinal Survey of Youth 1979 (1980-1998 waves) and Child and Young Adults (1988-2014 waves) to assess the timing and extent of maternal and child marijuana use and initiation. They evaluated the data for 4,440 children and 2,586 mothers for the effect of maternal marijuana use between a child's birth and age 12 on that child's subsequent marijuana initiation, controlling for potentially important factors related to the child's early life behavior and cognition and the family's socioeconomic position and social environment. Overall, 2,983 children (67.2 percent) and 1,053 mothers (35.3 percent) self-identified as cannabis users. The investigators found that the children whose mothers used marijuana were at increased risk for marijuana initiation prior to age 17 and began at a median age of 16, compared to age 18 among children of non-users, noting that this effect was slightly stronger among non-Hispanic non-black children.
Although marijuana is generally thought to be less harmful compared with other drugs of abuse, the likelihood of experiencing health consequences associated with marijuana use is strongly linked to age at initiation, such that those who initiate earlier are at much greater risk. Negative consequences may be particularly marked for children and adolescents during these developmentally critical ages. Child and adolescent cannabis use is associated with impairments in attention, concentration, decision-making and working memory, and increased impulsivity, which may persist for weeks after use, with evidence that some cognitive effects, including reductions in IQ, may linger into adulthood. Among cannabis users, earlier initiation is associated with increased risk of anxiety and depressive disorders.
The United States is currently experiencing a sea change surrounding marijuana. This cultural shift is expected to result in increases in the prevalence, frequency, visibility, and/or acceptability of adult marijuana use. Understanding the impact of parent use on early marijuana initiation is an important step in anticipating the ways in which social environmental changes may alter the disease burden associated with marijuana in the US.cognitive effects
The findings indicate that children of marijuana-using parents may be an important subgroup for identification and early, evidence-based intervention by pediatricians and adolescent healthcare providers. Although future research on the mechanisms underpinning this relationship is necessary before more specific recommendations can be made, marijuana prescribers and other physicians may consider educating marijuana-using parents about early marijuana initiation and equipping them with evidence-based preventive strategies to delay marijuana use in their children. Further research may seek to understand best practices for preventing early initiation, such as decreasing or pausing use, reducing the visibility of use until children are older, and providing training, tools, and resources to help address these issues.
"Cannabis has recognized therapeutic benefits for treating a number of different medical conditions. There is also evidence that the availability of legal medical and recreational cannabis may reduce population opioid overdose deaths. Cannabis arrests account for more than half of all drug arrests in the US, and cannabis possession is a major driver of racial disparities in arrest and incarceration. For these reasons, total cannabis prohibition may not be consistent with public health objectives. Instead, given the neurocognitive, health, and social consequences associated with early use, delaying initiation may be an important, but undervalued, public health goal," commented Dr. Sokol.
https://www.sciencedaily.com/releases/2018/09/180924084340.htm