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