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
No evidence tougher policies deter adolescent cannabis use
February 19, 2019
Science Daily/University of Kent
A new study has found no evidence that teenage cannabis use is lower in countries with tougher
The study, by Alex Stevens, Professor in Criminal Justice in Kent's School for Social Policy, Sociology and Social Research, used data from the World Health Organisation's Health Behaviour in School-aged Children survey. This survey asked over 100,000 teenagers in 38 countries, including the UK, USA, Russia, France, Germany and Canada, about their cannabis use.
Professor Stevens's analysis of the data found no association between a country having a more liberal policy on cannabis use and higher rates of teenage cannabis use. The analysis controlled for differences between the countries, including their national income, and between the teenagers, including their gender, their affluence and psychological problems.
The new study was undertaken in response to a 2015 study that had concluded there was an association between policy liberalisation and a higher likelihood of adolescent cannabis use. This study has been used in the past to justify calls for tougher policies for cannabis use.
However, Professor Stevens found this was based on a misinterpretation of that study's own numerical results. When taking into account the differences in cannabis use between boys and girls in different countries, and using more of the available data, a statistically significant association between policy liberalisation and adolescent cannabis use cannot be found.
Professor Stevens said: 'My new study joins several others which show no evidence of a link between tougher penalties and lower cannabis use. This is useful information for governments as they consider the best way to deal with cannabis. As it is, the harms and costs of imposing criminal convictions on people who use cannabis do not seem to be justified by an effect in reducing cannabis use.'
https://www.sciencedaily.com/releases/2019/02/190219111730.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
Cannabis linked to bipolar symptoms in young adults
Cannabis use in youth is linked to bipolar symptoms in young adults, finds new research
November 30, 2017
Science Daily/University of Warwick
Cannabis use in youth is linked to bipolar symptoms in young adults, finds new research by the University of Warwick.
Researchers from Warwick Medical School found that adolescent cannabis use is an independent risk factor for future hypomania -- periods of elated mood, over-active and excited behaviour, and reduced need for sleep that are often experienced as part of bipolar disorder, and have a significant impact on day-to-day life.
Led by Dr Steven Marwaha, a clinical academic Psychiatrist, the research analysed data from the Avon Longitudinal Study of Parents and Children and found that teenage cannabis use at least 2-3 times weekly is directly associated with suffering from symptoms of hypomania in later years.
There was a dose response relationship such that any use still increased the risk but less powerfully.
The Warwick research is the first to test the prospective association between adolescent cannabis use and hypomania in early adulthood, whilst controlling for important other factors that might explain this connection (e.g psychotic symptoms).
Cannabis use was also found to mediate the association of both childhood sexual abuse and hypomania, and male gender and hypomania.
The findings suggest frequent adolescent cannabis use is likely to be a suitable target for interventions that may allay the risk of young people developing bipolar disorder.
Commenting on the research, Dr Marwaha said: "Cannabis use in young people is common and associated with psychiatric disorders. However, the prospective link between cannabis use and bipolar disorder symptoms has rarely been investigated.
"Adolescent cannabis use may be an independent risk factor for future hypomania, and the nature of the association suggests a potential causal link. As such it might be a useful target for indicated prevention of hypomania."
Cannabis is one of the most commonly used illegal substances of abuse in western countries. Problematic use in the general population is as high as 9.5% in the United States, while 2.6% of the UK population report having been cannabis dependent in the last year.
https://www.sciencedaily.com/releases/2017/11/171130214932.htm