CRx MAGAZINE

Winter 2021

Arrested Development

Cannabis may have a deleterious effect on the still-developing brains of teens.

In most states where cannabis is legal for medical use, it’s only available to those 21 years of age or older. While some states allow for children of any age have access to medical cannabis for qualifying medical conditions, it’s difficult to find a qualified physician to make that recommendation.

However, because of legalization and commercialization of the cannabis industry, cannabis products have become more accessible, and in some cases, more attractive to teens. While teens often say they use cannabis to self-medicate for conditions such as stress, anxiety, and depression, there’s no science to support its effectiveness and some evidence that it may be harmful to adolescent brain development. Clinicians can play an important role in educating teens about the potential dangers of using cannabis before their brains are fully developed and helping parents have constructive conversations with their teens about cannabis.

Teens are Using Cannabis
The Substance Abuse and Mental Health Services Administration reports that cannabis use is widespread among young people. Some statistics from 2018 include the following1,2:

  • 3.1 million adolescents aged 12 to 17 have used cannabis in the past year.
  • 11.8 million young adults aged 18 to 25 have used cannabis in the past year.
  • 14% of eighth-graders have used cannabis in their lifetime.
  • 33% of 10th-graders have used cannabis in their lifetime.
  • 44% of 12th-graders have used cannabis in their lifetime.
  • 22% of 12th-graders have used cannabis in the past month.
  • 6% of 12th-graders use cannabis on a daily basis.

Why Do Teens Use Cannabis?
While there’s no one clear reason why teens (ages 12 to 17 years, also called adolescents) use cannabis, two commonly cited motives are self-medication and peer pressure.

The National Center on Addiction and Substance Abuse at Columbia University conducts a study known as “The National Survey of American Attitudes on Substance Abuse,” which has identified high stress as the No. 1 reason teens smoke, drink, or use drugs (usually cannabis).3 Other surveys often cite high stress, anxiety, and depression as reasons for teen cannabis use. However, there’s virtually no research on cannabis use among the adolescent population, so appropriate dosing, effects, and side effects are still unknown. Thus, treating stress, anxiety, or depression with cannabis in adolescents isn’t recommended.

“Because everyone else is doing it” is a common reason teen give for using cannabis (also a top reason for tobacco, alcohol, and other illegal drug use). And while peer pressure is usually considered pressure from someone of equal standing to self, with the legalization of cannabis for adults, “peer pressure” has taken on a new meaning. Now teens cite peer pressure as coming from sources other than their friends—from family members and other important adults in their lives. This is because these influential adults talk more openly about their cannabis use and express their approval of it, which leads teens to believe that cannabis use is safe for them too.

Consequences Associated With Early Cannabis Use
Because the brain is still taking shape well beyond the teen years—25 years old is the generally accepted time when the brain is believed to have reached adult development—the impact of early use of cannabis, especially THC, may be lasting. While all research in cannabis in humans is limited, research into adolescent humans is almost nonexistent as a result of ethical and scientific reasons; thus, human studies are often retrospective, and much of the direct evidence comes from animal studies.

The most significant brain development in adolescence and beyond occurs in the prefrontal cortex, the region responsible for decision making, planning, problem solving, and controlling impulses. During adolescence, the prefrontal cortex undergoes major remodeling, by which excess neuronal connections are eliminated and others are stabilized; at the same time, many neurotransmitter systems are adjusting by reducing levels of chemicals produced and changing the distribution of receptors in different brain regions. These processes help the brain transition from an immature to an adult state.4 Any outside influence on these natural processes can change the physical and chemical makeup of the brain. In an attempt to demonstrate the effects of early exposure to cannabis, a Canadian study used recall data of a large sample of seventh-graders that showed cannabis use had neurotoxic effects on inhibitory control, working memory, delayed memory recall, and perceptual reasoning—functions controlled by the prefrontal cortex.5

As a neurotransmitter system, the endocannabinoid system (ECS) is very much at risk of being altered if normal processes of development are changed by an external influence. The key components of the ECS—CB1 and CB2 receptors and their endogenous ligands, anandamide, and 2-arachidonoyl glycerol—are present and active in early brain development. Recent research has shown that the ECS plays an important role in the proliferation and differentiation of brain cells throughout brain development.6 For instance, one rat study showed that the expression of CB1 receptors gradually decreases from mid-adolescence to late adolescence. In addition, levels of anandamide increase and levels of 2-arachidonoyl glycerol are found to decline throughout adolescence.7 Given the importance of the ECS in neurodevelopment, experts postulate that externally induced changes in ECS signaling during adolescence may have profound long-term consequences on function in the adult brain. Because THC is the major psychoactive exogenous cannabinoid and acts directly through CB1 receptors, it’s thought to be the cause of some changes in neurodevelopment.

The effect of THC on memory is well documented and is the basis for the use of medical cannabis in posttraumatic stress disorder patients. However, evidence in rats shows that early exposure to THC may change the formation of the hippocampus and lead to problems with learning and memory tasks later in life. In addition, chronic THC exposure may speed the loss of neurons in the hippocampus, which may mimic age-related memory loss and decrease a teen’s ability to learn new information.8

It’s important to note that most studies examining the association between adolescent cannabis use and changes in brain development and cognition were initiated to support assertions of cannabis’ harmful effects. To date, there are no published studies intended to suggest benefit or contradict studies demonstrating harmful effects. However, a 2018 review of systematic reviews and meta-analyses of studies that investigated correlations between changes in brain function and cognition and cannabis use in adolescents concluded that adolescent cannabis use is inconsistently associated with alterations in brain development and cognitive performance.9 And while the authors recommend that their findings be used as a warning against adolescent cannabis use, the message compounds the confusion over the risks of early cannabis use. Furthermore, studies demonstrating that abstinence from cannabis for longer than 72 hours may diminish the cognitive deficits associated with adolescent cannabis use provide a reason to question the conclusions of previous work. Cannabis advocates propose that research intended to demonstrate the harmful effects of cannabis use may overstate the magnitude and persistence of cognitive deficits associated with use and fail to offer an impartial view of the science.

Other Considerations
In today’s more cannabis-positive environment, some researchers have turned to closely controlled drug experiments in animals to examine whether THC exposure can cause irrevocable neurologic harm. For instance, in one study, rats were given a THC-like synthetic cannabinoid drug in early and mid-adolescence, which interfered with gamma aminobutyric acid (GABA), a major inhibitory neurotransmitter in the adult rat. As a result, the brains of adult rats given THC as adolescents were considered underdeveloped.10

Similarly, in a more advanced trial, a group of Canadian researchers who exposed adolescent rats to THC also found that it impairs GABA signaling when the animals become adults. In addition, they found that this impairment leads to overactivity of the dopamine system in the brain region involved in motivation and reward processing.11 To the extent to which these findings may translate to humans, this could help explain the noted increased vulnerability for addiction later in life that some epidemiological studies have reported for people who begin using cannabis early in life.12

Unfortunately, in line with the nature of young science, even the same research group may yield conflicting results. A 2012 study showed declines in IQ between childhood and adulthood in cannabis users, whereas a matched group of nonusers didn’t see a decline.13 Then, in 2018, the same research group concluded that the IQ declines weren’t attributable to cannabis; instead, it found that “family background factors” likely explained why the adolescent cannabis users performed worse on IQ test as adults.14

Nonetheless, the New England Journal of Medicine published a paper in 2014 with the following “Adverse Health Effects of Marijuana Use” and backs them up with survey data15:

  • difficulty learning;
  • injury;
  • car accidents;
  • risky sexual behavior; and
  • bronchitis.

One thing is clear: The risk of cannabis use disorder increases in those who use cannabis before age 18. In fact, cannabis use disorder accounts for 50% of admissions for substance use disorder treatment among those aged 12 to 17.16

The National Institutes of Health is funding the Adolescent Brain Cognitive Development study, a major longitudinal investigation that will track a large sample of Americans from late childhood (before statistical age at first use of drug) to early adulthood. The study will use neuroimaging and other advanced tools to clarify precisely how and to what extent cannabis and other substances, alone and in combination, affect adolescent brain development.

Conclusion
With the expanded legalization of cannabis for medical and adult use, clinicians and parents alike need to understand the potential effects of cannabis use in adolescents. But thus far, definitive answers about cannabis’ effect on young brains are based on biased research questions and sometimes contradictory findings. However, experts in the medical cannabis space recommend that adolescents wait until their brains have matured—at least into their 20s—before they start using cannabis medically or recreationally. In a news feature published in the Proceedings of the National Academy of Sciences of the USA, Harvard Medical School neuroscientist Jodi Gilman, PhD, says, “We still don’t have a handle on how THC affects the adolescent brain. There’s a lot of evidence pointing toward negative outcomes, but more research needs to be done.”17 This suggests that teens should give their brains a chance to be more fully developed before exposure to something that could change its trajectory.

Chris Halsor, a Colorado-based cannabis law expert and founder of Understanding Legal Marijuana, who often gives presentations to parents and clinicians on how to identify when people have been using cannabis and how to address cannabis use with teens, gives the following tips for starting conversations with teens about cannabis use:

  • Know the different cannabis administration methods. Teens aren’t simply smoking cannabis. They may have access to edibles, vape pens, inhalers, and concentrates that don’t have any odor or flavor and are easy to conceal. Understand that it’s not the same as what “we” (parents and clinicians) grew up with. Be alert to high stress levels and boredom, which may lead to cannabis use, and recognize changes in behavior, which may be a sign of cannabis use.
  • Familiarize yourself with the potential risks of cannabis by individuals at a young age and try to discuss it in terms teens understand. Halsor suggests it’s like the signal bars on your smartphone; if you start using at a young age, you’ll be stuck at one or two bars and never get full service.
  • Hold judgment if you discover a teen has been using cannabis. Condemning use will likely lead the teen to deny future use and disregard any other message you try to convey. Talk to teens with respect, understanding, and curiosity.

Bonnie Johnson, MS, RDN, HCP, is a registered dietitian nutritionist, food industry consultant, speaker, and certified cannabis consultant. She spends much of her volunteer time educating a variety of audiences about the benefits and potential risks of using cannabis to treat chronic pain, anxiety, insomnia, and other ailments. As a consultant, she works with the food and cannabis industries to bring science-based education to health care professionals and category-changing products to market.

References

1. Substance Abuse and Mental Health Services Administration. Key substance use and mental health indicators in the United States: results from the 2018 National Survey on Drug Use and Health. https://www.samhsa.gov/data/sites/default/files/cbhsq-reports/NSDUHNationalFindingsReport2018/NSDUHNationalFindingsReport2018.pdf. Published August 2019. Accessed October 14, 2020.

2. Monitoring the Future Study: trends in prevalence of various drugs. National Institute on Drug Abuse website.  https://www.drugabuse.gov/drug-topics/trends-statistics/monitoring-future/monitoring-future-study-trends-in-prevalence-various-drugs. Updated December 17, 2020.

3. Survey of American Attitudes on Substance Abuse 2012. Partnership to End Addiction website. https://drugfree.org/reports/national-survey-on-american-attitudes-on-substance-abuse-xvii-teens/. Published August 2012. Accessed October 14, 2020.

4. Gogtay N, Giedd J, Lusk L, et al. Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci U S A. 2004;101(21):8174-8179.

5. Lorenzetti V, Hoch E, Hall W. Adolescent cannabis use, cognition, brain health and educational outcomes: a review of the evidence. Euro Neuropsychopharmacol. 2020;36:169-180.

6. Harkany T, Guzmán M, Galve-Roperh I, Berghuis P, Devi L, Mackie K. The emerging functions of endocannabinoid signaling during CNS development. Trends Pharmacol Sci. 2007;28(2):83-92.

7. Ellgren M, Artmann A, Tkalych O, et al. Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects. Eur Neuropsychopharmacol. 2008;18(11):826-834.

8. Rubino T, Realini N, Braida D, et al. Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood. Hippocampus. 2009;19(8):763-772.

9. Scott J, Slomiak S, Jones J, Rosen A, Moore T, Gur R. Association of cannabis with cognitive functioning in adolescents and young adults: a systematic review and meta-analysis. JAMA Psychiatry. 2018;75(6):585-595.

10. Cass D, Flores-Barrera E, Thomases D, Vital W, Caballero A, Tseng K. CB1 cannabinoid receptor stimulation during adolescence impairs the maturation of GABA function in the adult rat prefrontal cortex. Mol Psychiatry. 2014;19(5):536-543.

11. Renard J, Szkudlarek H, Kramar C, et al. Adolescent THC exposure causes enduring prefrontal cortical disruption of GABAergic inhibition and dysregulation of sub-cortical dopamine function. Sci Rep. 2017;7(1):11420.

12. Agrawal A, Neale M, Prescott C, Kendler K. A twin study of early cannabis use and subsequent use and abuse/dependence of other illicit drugs. Psychol Med. 2004;34(7):1227-1237.

13. Meier M, Caspi A, Ambler A, et al. Persistent cannabis users show neuropsychological decline from childhood to midlife. Proc Natl Acad Sci U S A. 2012;109(40):E2657-E2664.

14. Meier M, Caspi A, Danese A, et al. Associations between adolescent cannabis use and neuropsychological decline: a longitudinal co-twin control study. Addiction. 2018;113(2):257-265.

15. Volkow ND, Baler RD, Compton WM, Weiss SR. Adverse health effects of marijuana use. N Engl J Med. 2014;370(23):2219-2227.

16. Winters K, Lee C. Likelihood of developing an alcohol and cannabis use disorder during youth: association with recent use and age. Drug Alcohol Depend. 2008;92(1-3):239-247.

17. Shen H. News feature: cannabis and the adolescent brain. Proc Natl Acad Sci U S A. 2020;117(1):7-11.

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