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Marijuana and the Pediatric Population Sadhana Dharmapuri, MD,A,B Kathleen Miller, MD, FAAP,C Jonathan D

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Marijuana and the Pediatric Population Sadhana Dharmapuri, MD,A,B Kathleen Miller, MD, FAAP,C Jonathan D Marijuana and the Pediatric Population Sadhana Dharmapuri, MD,a,b Kathleen Miller, MD, FAAP,c Jonathan D. Klein, MD, MPHa Cannabinoids, the psychoactive compounds in marijuana, are one of the most abstract commonly used substances in the United States. In this review, we summarize the impact of marijuana on child and adolescent health and discuss the implications of marijuana use for pediatric practice. We review the changing epidemiology of cannabis use and provide an update on medical use, routes of administration, synthetic marijuana and other novel products, the effect of cannabis on the developing brain, other health and social consequences of use, and issues related to marijuana legalization. EPIDEMIOLOGY sure” (18.9%) students. Older students Cannabis is one of the most commonly had a higher prevalence of current used psychoactive substances in the marijuana use, with 13.1% of ninth- United States. grade students, 18.7% of 10th-grade students, 22.6% of 11th-grade aDepartment of Pediatrics, University of Illinois at Chicago, In recent years, the increase in potency students, and 25.7% of 12th-grade Chicago, Illinois; bDepartment of Pediatrics, Cook County of cannabis (which includes a sixfold to students reporting current use. With Health and Hospitals System, Chicago, Illinois; and sevenfold increase in cAdolescent Medicine Fellowship Program, Division of legalization, marijuana use during General Pediatrics and Adolescent Health, Department of tetrahydrocannabinol [THC] content), pregnancy has become more common, Pediatrics, University of Minnesota, Minneapolis, Minnesota the proliferation of alternative forms of with 7.1% of pregnant women cannabis for consumption, and Drs Dharmapuri and Klein drafted the initial reporting marijuana use in the manuscript and reviewed and revised the electronic vapor device use pose past month and 3.1% reporting manuscript; Dr Miller reviewed and revised the challenges to both public health and daily use.3 manuscript; and all authors approved the final clinical practice.1 In 2017, the Centers manuscript as submitted and agree to be for Disease Control and Prevention Only one recent study has examined the accountable for all aspects of the work. Youth Risk Behavior Survey found that relationship between the availability of DOI: https://doi.org/10.1542/peds.2019-2629 19.8% of youth of high school age legal medical marijuana and use in Accepted for publication Feb 27, 2020 reported past-month marijuana use, adolescents. This cross-sectional survey Address correspondence to Jonathan D. Klein, MD, 2 and 35.6% had ever tried marijuana, of students whose school was within MPH, Department of Pediatrics, University of Illinois down from a peak rate of 47.1% in a 5-mile radius from a medical at Chicago, 840 S Wood St, MC 856, Chicago, IL 60612. 1997. Synthetic marijuana use also dispensary did not find increased use of E-mail: [email protected] declined, from 9% in 2015 to 6% in marijuana among these youth.4 More PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 2017. Although use has declined, youth studies are needed to determine the 1098-4275). who use marijuana often engage in effect of proximity to medical Copyright © 2020 by the American Academy of other risk-taking behaviors that impact dispensaries on marijuana use. Pediatrics their overall well-being; for example, FINANCIAL DISCLOSURE: The authors have indicated 13% of youth reported driving after National surveys have found that youth they have no financial relationships relevant to this using marijuana.2 In 2017, ever use of who engaged in marijuana use in later article to disclose. marijuana among Black or African teen-aged years (.17) were less likely FUNDING: No external funding. American (42.8%) and Hispanic to develop substance use disorders POTENTIAL CONFLICT OF INTEREST: The authors have (42.2%) students was higher than compared with those who started indicated they have no potential conflicts of interest among white (32.0%) students. The earlier. Positive attitudes toward to disclose. prevalence of current marijuana use school, parental monitoring, and strong was also higher among gay, lesbian, and disapproval of peer’s substance abuse To cite: Dharmapuri S, Miller K, Klein JD. Marijuana bisexual (30.6%) students compared were found to be protective factors and the Pediatric Population. Pediatrics. 2020; 146(2):e20192629 with heterosexual (19.1%) and “not against substance use disorder.3 Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 146, number 2, August 2020:e20192629 STATE-OF-THE-ART REVIEW ARTICLE PHARMACOLOGY endocannabinoid receptors CB1 and varies. THC has a fast initial half-life Although a comprehensive review of CB2 and related binding proteins in (6 minutes) and a longer terminal pharmacokinetics and the nervous system. CB1 receptors half-life (22 hours). Chronic users pharmacodynamics is beyond the are found in the central nervous have longer elimination times, with . scope of this review, it is helpful to system on neurons in the prefrontal THC present for 24 hours. CBD has summarize the kinetics of cannabis cortex, basal ganglia, hippocampus, a long terminal half-life, from and common cannabis extracts and amygdala, hypothalamus, and 33 hours to 5 days, depending on the concentrates to aid clinicians in cerebellum. CB1 receptors are also amount used. found in smooth muscle, better understand the effects of Metabolism of THC occurs mainly in myocardium, adipocytes, and various forms of cannabis on youth. the liver by the cytochrome P450 preganglionic sympathetic neurons. system. CBD inhibits cytochrome Cannabis occurs naturally as a plant, The CB2 receptor is expressed in oxidases; thus, it may interfere with leading to production of cannabis peripheral blood mononuclear cells other commonly used medications. products made of dried leaves, oils, as well as in the smooth muscle, CBD has a regulatory effect on THC, and concentrates. Many cannabis myocardium, and vascular with the potential to decrease some products contain numerous endothelium. adverse effects (ie, tachycardia, substances, including terpenes, 5 flavonoids, alkaloids, and .100 THC acts as an agonist at CB1 and anxiety, and sedation). cannabinoids. There is no CB2 receptor sites. Binding the Drug interactions have been noted standardized form of cannabis; the receptor site reduces with the use of cannabis. For example, presence and relative amount of neurotransmission, producing effects cannabis containing THC has been various substances may differ such as impairments in learning, associated with increased rates of between cannabis extracts as well as memory, spatial orientation, and psychotic relapse and treatment between products designed to be attention and physiologic effects such failure.8 In an animal study, THC had smoked or vaporized.5 as tachycardia. THC also has analgesic a negative effect on the efficacy of fl 7 and antiin ammatory effects. CBD risperidone.9 Drug interactions noted The endocannabinoid system, fi has weak af nity for CB1 receptors, for CBD included increases in serum composed of endocannabinoids and does not interact directly with CB2 cannabinoid receptors, is widely levels of antiepileptic drugs, resulting receptors, and does not produce the in sedation.8 distributed in the brain and spinal intoxicating effects of THC ingestion. cord. This system has a regulatory Synthetic cannabinoids (SCs) are role in many physiologic processes, There is considerable variation in the biochemically similar to THC and are fi including inflammation, appetite pharmacokinetic pro les of THC and used for both medicinal purposes and regulation, immune function, CBD between users, by cannabis recreational purposes. Dronabinol is cardiovascular function, neural dosages and forms, with acute and a schedule III drug and is approved development, pain, the sleep and chronic use, and by route of for the treatment of nausea and wake cycle, psychiatric disease, and administration. Smoked and/or vomiting associated with others. Endocannabinoids, vaporized cannabis has a rapid onset chemotherapy and for the treatment endogenous lipids with precursors of action, with peak levels achieved of anorexia and weight loss due to that are present in lipid membranes, within 10 minutes and greater AIDS. Dronabinol typically comes in interact with endocannabinoid bioavailability compared with oral 2.5-, 5-, and 10-mg tablets and is receptors CB1 and CB2.6 Being ingestion. Bioavailability of THC taken 1 or 2 times a day in doses of lipophilic, cannabinoids are rapidly ranges from 2% to 56% with smoked up to 40 mg/day. Nabilone, absorbed. or vaporized cannabis and from 11% a schedule II SC, comes in 0.25-, 0.5-, to 45% with smoked CBD. Oral Phytocannabinoids, plant-derived and 1-mg tablets, is prescribed up to absorption has more variability and cannabinoids, can be categorized into 3 times a day, and is approved for lower bioavailability. The acute several classes; d-9 chemotherapy associated nausea and effects of ingested cannabis may last 8 tetrahydrocannabinol (generally vomiting. for several hours, depending on known as THC) and cannabidiol concentration, formulation of the (generally known as CBD) are the MEDICAL USES OF CANNABIS product, and gastrointestinal motility, most abundant and studied forms. vascularity, and blood flow.5 The Drug Enforcement Agency has THC is considered the main Distribution of THC is time dependent classified cannabis as a schedule I psychoactive component of the plant. and is immediate with
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