Now What? THC Exposure and the Adolescent Brain
By Mark Gold, MD
As more states move to decriminalize or legalize marijuana and THC-related products, researching potential harms associated with cannabis use is an even more important field of study. In certain cases, such as marijuana-related medications, there is sound evidence. Usually, the manufacturer of a drug has to do clinical trials, called FDA trials, to demonstrate dose, safety, and efficacy for a particular problem or illness. The FDA did approve the first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy. This was a well-conceived and logical trial and process. It resulted in the approval of Epidiolex (cannabidiol, or CBD) oral solution for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome, in patients two years of age and older. This was the first FDA-approved drug that contains a purified drug substance derived from marijuana. It was also the first FDA approval of a drug for the treatment of patients with Dravet syndrome. Notably, however, the FDA did not approve a crude plant or marijuana, but CBD. CBD does not cause intoxication or euphoria, the “high” that comes from marijuana’s tetrahydrocannabinol (THC). In this case, we know that the medication is safe, we know its formulation and composition, and we know the dose. We also know that before this treatment, there were no good alternatives.
According to pediatricians and research scientists, there’s no scientific evidence supporting the acceptability of adolescent marijuana use, and products sold in dispensaries pose considerable risks to children and teens.1 The situation with cannabis, vaping THC, and other preparations is considerably different from that of an FDA-approved medication. In these cases, sadly, we are doing the research after the fact. We know that laws are meant to prevent children from using and smoking marijuana, but the public appears confused about safety warnings when children and adolescents seem like they are safely given cannabis for seizures. Recent data shows that use is increasing among young people. A SAMHSA report found that marijuana is teens’ most widely used illicit drug.2 Frequent marijuana use, in both youth (aged 12-17 years) and young adults, appears to be associated with risk for opioid use, heavy alcohol use, and major depressive episodes. Youth have access to the legal cannabis and related product markets, as well as the thriving illicit marketplace for drugs. Health problems linked to vaping may be in the headlines, as many of those with reported lung damage have vaped THC, but it is not the only problem facing teen users.3
What does the latest research tell us about the effects of cannabis on the adolescent brain, and do we know enough to make recommendations?
Science has not shown that cannabis is performance-enhancing like amphetamines, psychostimulants, or medications like methylphenidate given to people with learning problems. Research has clearly shown that adult cannabis use can affect a person’s memory, performance and ability to learn. Recently, Gorey et. al. conducted a systematic review of 21 human and animal studies to investigate whether age influenced the effects of cannabis on the brain, and found preliminary evidence that suggested it does. Further understanding the differences between how cannabis affects the adult brain versus the adolescent one could help us create better messaging and education for youth about how cannabis could affect them.
What did this review find about marijuana and the adolescent brain?
This systematic review aimed to understand the role of age in the association between cannabis use and cognition. It looked at human and animal studies, testing whether age altered the relationship between cannabis exposure and cognitive outcomes.
Though the review did not render a conclusive answer to this question, it did help us make sense out of the data and develop new approaches and hypotheses:
General executive functioning was found to be more impaired in adolescents than in adults who used cannabis.
Age-effects of cannabis use may be more profound in heavy and dependent users.
Craving and compromised inhibitory control after cannabis use do not diminish as quickly in adolescents as they do in adults.
After sustained abstinence from cannabis use, adolescents no longer experience symptoms of impaired learning, and their brain function normalizes. Animal studies investigating the specific effects of synthetic cannabinoids did not find behavioral alterations. Studies exploring neural effects, however, did find variations between adolescent and adult rodents in impairment levels, with young rats experiencing higher levels of impairment.
Adolescence and exposure to cannabis - a broader look
Consistent with previous research, this combination of impaired inhibition control and greater cravings after cannabis use may lead to binge-like tendencies in adolescents, making them more vulnerable to using larger amounts of cannabis during a short duration. Adolescents did display lower control than adults 3 hours or more after using cannabis, and their cravings were higher. When scientists debate marijuana’s effects, they do not wonder if it improves attention, concentration, or memory, as they do with psychostimulants. Instead, they wonder how profoundly marijuana interferes with development, learning, math skills, and memory. Little evidence was found to support the hypothesis that repeated cannabis exposure can lead to larger impairments in executive functioning and IQ in adolescents than in adults.
Why is this important?
While this review did not present a new, conclusive answer, the authors provided ample evidence to support the idea that cannabis affects young minds in different and often more severe ways than it does adult ones. This observation is consistent with other research showing vastly different effects of drugs of abuse on the very young relative to the old. With this in mind, instead of being dismayed or surprised by the academic or memory problems of an adolescent using THC or cannabis-related products, it may be better to suggest abstinence, or a period of abstinence. A 2018 study indicates the potential effectiveness of this approach. It recruited and randomly assigned 88 adolescents and young adults who used cannabis regularly to 4 weeks of cannabis abstinence, verified by decreasing 11-nor-9-carboxy-∆9-tetrahydrocannabinol urine concentration, or a monitoring control condition with no abstinence requirement. This study assessed memory and attention at baseline and every week, over 4 weeks, with the Cambridge Neuropsychological Test Automated Battery. It found an effect of abstinence on verbal memory across the entire 4 weeks of abstinence.
Over time, researchers will gain more expertise in adolescent brain development and substance use. Recently highlighted in JAMA, a first-of-its-kind National Institutes of Health-funded study is underway.4 It will test 12,000 healthy 9 and 10-year-old children at 21 sites around the country, measuring their mental and physical health and cognition while tracking their brain changes, substance use, digital media habits, and more. These findings should help us understand what a healthy brain is and what normal cognitive development looks like. They will include the effects of marijuana. This study will be very important and unique in part because of its neuroimaging and neuropsychological tests on memory and performance over a long period of time. Neuroimaging is a major focus of the Adolescent Brain Cognitive Development (ABCD) study. Gaya Dowling, PhD, a neuroscientist at the National Institute on Drug Abuse, is the ABCD study Director. She was interviewed for the JAMA article, and her comments highlight the growing importance of the field’s focus on adolescent brain development and substance use:
Dr Dowling: "One of the reasons that the study was initiated was because there were so many changes that were going on in the environment that these kids are growing up in. For example, we had a lot of policy changes with respect to marijuana and we had new delivery devices for nicotine. There was little known about what that impact was going to be on adolescents.
But even more specifically, one of the main drivers for the study was to understand the impact of substance use on brain development. Most studies that have tried to answer that question have compared people who have used drugs to those who haven’t used drugs. What that doesn’t allow you to do is see what a person’s brain may have looked like before they started using drugs. By enrolling kids before there’s any substance use, we can see what those changes might be. And that’s really a unique contribution.”
We are likely to know if, when, and how marijuana disrupts memory and interferes with performance, cognition, and development. In the meantime, no use is the best advice for young people. This advice is consistent with our Surgeon General's recent advisory on marijuana and, he would add, it is also best to refrain from use during pregnancy.5
Digitale, E. (2018) Teens shouldn't use medical marijuana, but the plant's active compounds have select uses, debaters agree. Scope, Stanford Medicine
National Survey on Drug Use and Health. (2018) Reports and Detailed Tables, Types of Illicit Drug Use. SAMHSA
Carman, A. (August 22, 2019) More than 100 vapers have contracted a severe lung disease, per CDC. The Verge
Abbasi, J. (August 14, 2019) With Neuroimaging, Large NIH Study Could Shine a Light on the Adolescent Brain. JAMA
Kaplan, S. (August 29, 2019) Surgeon General Warns Pregnant Women and Teenagers Not to Smoke or Vape Marijuana. New York Times
Gorey, C., Kuhns, L., Smaragdi, E., Kroon, E., & Cousijn, J. (2019). Age-related differences in the impact of cannabis use on the brain and cognition: a systematic review. European archives of psychiatry and clinical neuroscience
Schuster, R.M., Gilman, J., Schoenfeld, D., Evenden, J., Hareli, M., Ulysse, C., Nip, E., Hanly, A., Zhang, H., Evins, A.E. (2018) One Month of Cannabis Abstinence in Adolescents and Young Adults Is Associated With Improved Memory. Journal of Clinical Psychiatry
Dr. Mark S. Gold is a teacher of the year, translational researcher, author, mentor and inventor best known for his work on the brain systems underlying the effects of opiate drugs, cocaine and food. Read more by Dr. Gold here.