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 absorption drug. This precludes cannabis being Phytocannabinoids affect users into fat tissue and highly perfused considered for legal medical uses, and through their interactions with organs. Elimination half-life also therefore it is also not regulated,

Downloaded from www.aappublications.org/news by guest on September 27, 2021 2 DHARMAPURI et al except for dronabinol, nabilone, and other seizure disorders, including examining the co-use of tobacco and CBD. Dronabinol and nabilone are Sturge-Weber epilepsy and febrile marijuana found that marijuana use SCs. CBD is a plant-derived product infection–related epilepsy; however, was associated with greater nicotine approved for use in children as there is limited evidence for use in addiction among adolescent smokers a second-line treatment of 2 these disorders.16,17 Limitations of and that compulsion to smoke and conditions: Lennox-Gastaut syndrome these studies include the following: preference to smoke were associated and Dravet syndrome.10 use of other CBD products were not with marijuana use.20 These authors compared with use of Epidiolex, hypothesized that smoking cues for The medical conditions that CBD can treatment time was short, studies had one substance may trigger cravings be legally used for vary by state. Most small samples, and CBD was added as for the other substance and lead to studies examining CBD treatment of an adjunct rather than as a first-line increased use in adulthood.20,21 They various conditions (cachexia or treatment.15 CBD was noted to suggest that the association of wasting, AIDS, cancer pain, etc) have provide seizure-free activity in marijuana use with tobacco use been on adults. According to a small proportion of children with should be considered when a National Academy of Sciences Dravet syndrome. However, the developing prevention programs for review, cannabis and cannabinoids authors suggest that a reduction in both substances. Alcohol co-use with are effective for the treatment of seizures may be a more realistic marijuana has also been identified in chronic pain in adults, are effective as expectation with use of CBD rather several studies. Alcohol has adverse antiemetics for the treatment of than seizure-free activity.15 effects on the developing adolescent chemotherapy-induced nausea and brain similar to those for marijuana, vomiting, and are effective for Parents and providers should be such as poorer attention and improving spasticity in adults with aware that there are limited studies executive functioning, heightened multiple sclerosis.11 addressing CBD use in children or emotional reactivity, and poorer Although some benefits of marijuana adolescents and that there often is distress tolerance.22 A longitudinal for treatment of behavioral conditions cross-contamination of CBD products study examining the effect of alcohol have been reported in animal studies, with THC. Thus, CBD products may use on marijuana use found that there are few studies in humans. In 2 lead to positive urine drug test results alcohol was a significant predictor of case reports, authors noted benefits for THC. This is especially important cannabis initiation within a year. In from dronabinol in children: one for adolescents required to take drug their study, Terry-McElrath et al23 report of a 6-year-old boy with tests for sports or employment. found that co-use of marijuana and autism and the other of an adolescent Additionally, CBD products are alcohol was associated with unsafe with self-injurious behaviors.12,13 unregulated, except for those drugs driving. They suggested that co-use of that are FDA approved. alcohol and marijuana in the context The use of medical cannabis for of driving should be explored when treatment of inflammatory bowel providing preventive care. disease (IBD) has increased in recent DUAL USE OF CANNABIS AND TOBACCO years. There is some evidence that Population-based surveys from the The Bright Futures: Guidelines for cannabis may have antiinflammatory 1990s revealed that most cannabis Health Supervision of Infants, Children properties, improve IBD symptoms, users were co-users of tobacco. Until and Adolescents, Fourth Edition24 and improve quality of life. However, the recent electronic cigarette highlights health issues to be in adults, CBD did not improve IBD (e-cigarette) or JUUL epidemic, there screened for at health maintenance pathology, and use of cannabis in had been a steady decrease in self- visits. Tobacco, alcohol, and drug risk pediatric IBD is not recommended.14 report of tobacco use in youth. assessment is recommended In a systematic review of cannabis for However, youth who smoke tobacco throughout the adolescent years.24 treatment of seizures, 4 high-quality remain more likely to report The American Academy of Pediatrics randomized controlled studies found marijuana use.18,19 Co-users in this (AAP) policy statement on substance a reduction in seizures with the use of study had lower academic abuse and prevention suggests that Epidiolex, a CBD product US Food performance compared with pediatricians become familiar with Drug Administration (FDA) approved cannabis-only users and were more substance abuse screening.25 The for treatment of Dravet syndrome and likely to be male than female. In this AAP recommends using short Lennox-Gastaut syndrome. Outcomes study, the authors speculated that the validated screeners to determine using other cannabis preparations increased use of cannabis was youth at risk.25 One validated were inconclusive.15 A few small, associated with normative behavior, screener is the CRAFFT (car, relax, nonrandomized studies have whereas tobacco use was perceived alone, forget, family or friends, and suggested benefits from CBD use in as riskier behavior. Another study trouble), which screens to identify

Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 146, number 2, August 2020 3 youth aged 12 to 21 years old at risk instead of endocannabinoids, leading breastfeeding. In 1 study, the authors for alcohol or substance use, driving to various neurodevelopmental found an association between or riding risk, and substance use changes. Animal studies of prenatal marijuana detected in breast milk and disorder. CRAFFT 2.1 is an updated THC exposure provide strong decreased motor development at version of that incorporates opening evidence for these adverse effects.33 1 year; however, the authors noted questions that quantify the amount of In a review of several studies on that this result could have been use within the past 12 months, and prenatal marijuana use, investigators confounded by the use of marijuana CRAFFT 1 N includes an opening found a dose-response effect on fetal during pregnancy. In the other study, question on tobacco, including growth; increased use was associated authors compared breastfed infants smoking and/or vaping use.26 The with decreased growth.34 It was exposed to marijuana and those not tool is scored as low, medium, and unclear whether prenatal exposure exposed to marijuana; these authors high risk. CRAFFT 2.1 includes had an effect on preterm births. In noted no differences in motor or recommendations on how to discuss a meta-analysis of 31 studies on cognitive skills at 1 year.38,39 risk and how to contract for safe marijuana use during pregnancy, Human studies on maternal rides, which has been shown to investigators found that maternal marijuana use have been limited, and decrease the risk of adolescents marijuana use and concomitant most have been observational or riding in a car with someone who has tobacco exposure contributed to – retrospective, relying on patient self- been drinking or using drugs.26 adverse neonatal outcome.34 36 report. These studies have been Marijuana exposure has also been confounded by polysubstance abuse associated with NICU admissions as and had small sample sizes. At this MARIJUANA AND PREGNANCY well as with increased respiratory time, a causal relationship cannot be and neurologic infections and Marijuana is one of the most established. However, because of the hematologic morbidity.34 commonly used illicit substances in paucity of research, it is women, and the estimated prevalence Animal studies revealed that even recommended that women refrain of use among pregnant women in the low levels of exposure to marijuana from marijuana use during pregnancy United States ranges between 3% and have adverse neurologic effects.37 In and breastfeeding. The American 27 16%. From 2002 to 2014 past- a recent systematic review examining College of Obstetrics and Gynecology month marijuana use among 7 longitudinal studies on the effects and the AAP recommend that 28 pregnant women increased by 62%. of prenatal exposure on breastfeeding mothers refrain from Legalization has increased neuropsychological function in marijuana use.41,42 Standard of care accessibility and strengthened children, investigators found varied for prenatal and postnatal visits advocacy for its use, which may results between the association of should include screening for drug use, contribute to the increased use and prenatal exposure to marijuana and including marijuana use. Clinicians perceived safety for pregnant women. a child’s neuropsychological should be aware that women may Pregnant women are using marijuana development at ages 1 to 11 years. also seek information on marijuana for several reasons. In a Canadian The majority of studies demonstrated use in pregnancy and breastfeeding survey, researchers found that 77% of a negative impact of marijuana during from other sources. Clinicians should medicinal cannabis use was for pregnancy, including deficits in try to ensure that patients have treatment of nausea. Half of the neuropsychological functioning, access to current evidence-based women surveyed reported using decreased attention, memory information about marijuana use. marijuana to treat poor appetite, pain, problems, and poor impulse insomnia, or mood disorders control.37 However, there were mixed 28 ADVERSE EFFECTS FROM CANNABIS (depression and anxiety). Use of results between studies, and the USE cannabinoids during pregnancy has authors acknowledged that there may led to health concerns related to fetal be confounding biases. The adverse effects of cannabis use development because exogenous are well documented. Adverse effects Another area of interest has been the cannabinoids containing THC cross include distorted perception, poor relationship between breastfeeding the fetal-placental barrier in concentration, psychosis, excessive 29–31 and maternal marijuana use. humans. vomiting, and addiction. Cannabis concentration in breast milk The endocannabinoid system plays is related to the maternal dose Endogenous cannabinoids have an a major role in fetal development, and ingested and frequency of important role in the control of neural – the concentration of CB1 receptors is ingestion.38 40 In 2 studies, authors circuits and structures in the higher in fetal brains than in adults.32 investigated outcomes for infants prefrontal cortex and the THC binds to the CB1 receptor exposed to cannabis from hippocampus. During adolescence,

Downloaded from www.aappublications.org/news by guest on September 27, 2021 4 DHARMAPURI et al these circuits mature and regulate found that individuals who used drugs associated with marijuana use attention, executive functioning, and before age 17 years old had a reduced include stimulants, cocaine, and memory. Studies have revealed that odds of high school graduation and injection drugs.51 In 2018, the the development and maturation of degree completion compared with Insurance Institute for Highway these circuits can be affected by nonusers. These individuals were Safety and the Highway Loss Data cannabis, causing impairment in more likely to have cannabis use Institute reported an increase in neurocognitive functioning.43,44 THC disorder, were more likely to use motor vehicle crashes in states that is a lipophilic substance with a long other illicit substances, and had more had legalized marijuana use. In one half-life that becomes distributed in suicide attempts.47 study comparing perceptions of various tissue, including the brain’s impaired driving after alcohol use, Animal studies of cannabis use and myelin. It is released back into the young adults felt that marijuana use psychosis have suggested bloodstream over the course of 5 to was safer than alcohol use for a remodeling of brain structure due 95 days in individuals with heavy, driving.52 However, study to effects on the endocannabinoid regular use, meaning that participants did not feel as system. These changes are similar to neurodevelopmental changes can changes seen in schizophrenia.48 In knowledgeable about the effects of continue to occur for weeks to a recent study by Di Forti et al,49 the marijuana on driving. months after consumption.45,46 Of authors found that daily marijuana note, manufactured and synthetic Toxicity from consumption of use and high-potency marijuana marijuana products may have higher marijuana has been documented in (THC content .10%) are the THC concentrations than naturally several case studies. Most individuals strongest independent predictors of occurring products, which can lead to who experience toxicity have been whether an individual will have more intense and longer-lasting exposed to high concentrations of a psychotic episode. Initiation of effects. cannabinoids. These individuals can marijuanausebyage15years experience adverse health effects, In a longitudinal study by Meier slightly increased the odds of having including sedation, respiratory et al,45 cannabis use .20 years was a psychotic episode, but this was not depression, hyperemesis, and associated with neuropsychological independent of potency and cardiotoxicity. decline, with worsening effects for frequency of use. Individuals with long-term users. In another study, daily use had a 3.2 times higher Marijuana use has also been authors explored neurocognitive likelihood of developing psychosis associated with the positive health measures in adolescents with recent compared with nonusers. Individuals effect of decreasing nausea. However, cannabis use disorder who were now who used high-potency marijuana chronic use can cause a paradoxical abstaining and also found that were 1.6 times more likely to effect, leading to hyperemesis. younger onset was associated with develop psychosis compared with Patients typically present with cyclic lower overall neurocognitive nonusers.49 Individuals who had vomiting, nausea, and epigastric pain. function. Similarly, Meier et al45 both daily use and high-potency use Interestingly, these symptoms are found persistent neurocognitive were almost 5 times as likely to often reported to be relieved by hot changes 1 year after cessation of develop psychosis compared with – showers.53 55 Capsaicin has also been cannabis use. nonusers. Further studies exploring a successful treatment of frequency and potency of use and In a recent longitudinal study on hyperemesis.55 gene expression may help elucidate marijuana use and adolescent brain the neurobiology behind the development, researchers found that A systematic review of unintentional development of psychosis due to cannabis use had adverse effects on cannabis ingestion in children and cannabis. Physicians should be IQ and executive functioning.46 This adolescents revealed rates increasing aware of the increasing potency of cross-sectional longitudinal study in states that had legalized legal marijuana products; for revealed differences in resting-state marijuana.56 The most common form example, the average THC content networks known to mediate executive of ingestion were cannabis resin, of marijuana sold legally in Colorado functioning (left dorsolateral followed by cookies and joints.57 is ∼18%. prefrontal cortex) and regulatory Other exposures to cannabis included control (anterior cingulate cortex). Marijuana use has also been found to passive smoke, candies, beverages, Marijuana use was associated with be linked to an increase in use of and hemp oil. The most common sign declines in neural connectivity over prescription pain medication of cannabis ingestion was lethargy. time, especially in adolescents with (opioids). Individuals who used Ataxia, mydriasis, hypotonia, and cannabis use disorder.46 In an marijuana had a 2.78 increase risk of tachycardia were also common Australian longitudinal study, authors having an opioid use disorder.50 Other presenting signs.57

Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 146, number 2, August 2020 5 NEW WAYS TO USE THC, contain higher concentrations SCS The traditional method of marijuana (compared with dried-leaf products), SCs, (eg, Spice and K2) have become and can be consumed through vape consumption has been to smoke the 60 popular recreational substances dry leaves of the plant. A joint is pens, e-cigarettes, and dabs. Dabs among young adults. These dried marijuana leaves rolled in are concentrated butane hash oil substances are plant-derived material cigarette paper. Blunts are consumed when the concentrate is adulterated with substances similar marijuana leaves rolled in heated to high temperatures and the to synthetic THC. These are readily a hollowed-out cigar. Adolescent user inhales the resulting vapor. In available for purchase online or in fl 61 users may prefer blunts to joints one study by Lo in and Earleywine, shops specializing in marijuana and because blunts hold a larger the authors examined why users tobacco paraphernalia. SCs are often quantity of marijuana and burn preferred dabs and examined marketed as safe, natural, herbal slower. However, use of blunts is whether dab use was associated with blends not intended for human a health concern because of the more problems than traditional consumption in attractive packaging. co-use of cannabis and tobacco. In cannabis use. Study participants However, these products are not astudybyFairman,58 the author reported that dabs required fewer naturally produced. They are typically found that blunt users had higher hits to achieve desired effects. Study mass produced outside of the United severity of current cannabis participants did not feel that their use States. They are typically dissolved use–related problems, reporting was associated with more problems, and mixed with dried vegetation in an more tolerance as well as spending but dab use was more likely to lead to imprecise process. The dosing of one 61 more time getting, using, and getting dependence and withdrawal. product batch can vary greatly from over the effects of cannabis. Because that of another batch. These products E-cigarettes have been advertised as of dual use of tobacco and cannabis can also be contaminated with heavy safe and healthier than traditional in blunts, there is concern that those metals, bacteria, and chemicals. For cigarettes; sales of these devices have trying to quit smoking blunts could example, in 2018, 70 individuals targeted adolescents. The 2011–2018 be at greater risk for relapse experienced serious drug overdose in National Youth Tobacco Survey and because of nicotine withdrawal Connecticut from using synthetic the Monitoring the Future survey symptoms.58 cannabis that was contaminated with both identified increases in rat poison. Unlike THC, which is e-cigarette use in middle and high Other forms of marijuana available a partial agonist at CB1 and CB2 school students compared with other for consumption include hashish (a receptors, SCs are full agonists at CB1 tobacco products.62,63 Eggers et al64 plant extract containing psychoactive and CB2 sites, increasing the potency explored use of cannabis through resins), hash oil (cannabis of SCs.66 This may account for the e-cigarette systems; cannabis use concentrate extracted from hashish), increased morbidity and mortality through e-cigarettes was higher and dabs (also cannabis concentrate). seen with the use of SCs compared among 11th-graders than ninth- 67 THC content varies but is generally with marijuana. much higher than concentrations graders and among youth with worse found in the plant. Typical THC grades. In this study, the authors also Serious adverse health effects have content of the marijuana plant ranges found that use of cannabis through been documented with the use of SCs. from 12% to 20%. Products produced e-cigarettes (versus smoking blunts) Adverse effects include cardiac by using solvents (butane hash oil had similar adverse effects on school abnormalities, coagulopathies, and and dabs) have THC content ranging performance. Both e-cigarette neurologic and psychiatric 68 from 39% to 80%.59 Nonsolvent- delivery of cannabis and blunt use abnormalities. Cardiac effects produced concentrates have THC were associated with greater tobacco include tachycardia and acute 64 69,70 concentrations between 39% use. Physicians should consider myocardial infarction. A cardiac and 60%. methods of delivery when discussing fatality was reported in a young adult cannabis use because e-cigarettes are after smoking SCs.71 Hematologic Marijuana is also available as a novel route of administration and abnormalities due to long-acting vaporizable cannabis concentrates, as appeal to youth who are not vitamin K–dependent antagonist edibles, or as liquids. Vaporizable otherwise susceptible to cannabis via contamination of SCs have been concentrates include "shatter" (a blunts or joints. The AAP 2015 policy reported.71 In a review of SC use, brittle, translucent material made statement on electronic nicotine reports of acute kidney injury were from marijuana plant materials and delivery systems strongly noted. All individuals required solvents), "oil," wax," and "butane recommends that pediatricians hospitalization, and one individual hash." Vaporizable cannabis screen for and discourage vaping required dialysis.72 Neurologic concentrates contain 60% to 85% device use.65 abnormalities are also well

Downloaded from www.aappublications.org/news by guest on September 27, 2021 6 DHARMAPURI et al documented. SCs have been linked to not pay for medicinal marijuana intoxication.76 It is important to strokes, seizures, and psychiatric because the federal government counsel patients and parents about effects, including anxiety, agitation, prohibits the sale of schedule I drugs. the THC content in CBD products and suicidal ideation, and psychosis. The to note that they lack regulation by neuropsychologic effects of SCs, In general, consumers aged 21 years the FDA. Pediatricians should also compared with marijuana, are or older can purchase marijuana refer to individual state laws for enhanced because of the difference in legally from recreational dispensaries. further information concerning SC action at CB1 and CB2 sites. Although many cannabis purchases purchasing, use, and possession of occur through traditional illegal face- marijuana. There can be significant variation in to-face sales, cannabis products can SC potency, which can lead to serious also be purchased online, both adverse health events. These through legal recreational use sales CANNABIS USE DISORDER compounds can be mixed with other and illegal drug markets on the dark Monitoring the Future survey data psychoactive substances, (eg, ecstasy, Web. Recreational sales are cash only suggest that most adolescents do not bath salts, and others). SC detection is in most states. Prices vary by product perceive marijuana use as harmful, fi often dif cult in medical settings, and type, weight, and location of the sale. addictive, or associated with typical drug screening is often not For example, a sativa-hybrid dried withdrawal.77,78 However, 8% to 12% helpful. Providers should be aware of plant bought online costs $60 per 3.5 of marijuana users will develop possible adverse side effects of SC g, and indica dried leaf bought from moderate to severe cannabis use and should have a high index of a recreational dispensary costs $18 disorders. Additionally, animal suspicion when patients present with per gram. studies reveal that marijuana can symptoms that could be due to prime the brain to the effects of other consumption of SCs. A variety of marijuana products are available in recreational and medical illicit substances. Although less dispensaries. Retail shops may clearly delineated in humans, according to the Substance Abuse and MARIJUANA AND THE MEDIA display menus listing THC content, cannabis strain, and the mood or Mental Health Services In 2019, marijuana was legal in 33 symptom relief it may provide. For Administration, 4.2 million people in states for medical use and in 11 states example, Afgooey (indica strain), has the United States had cannabis use for recreational use by adults. As 22.9% THC and is advertised as disorder in 2017. The Diagnostic and legalization has increased, more and "manageable psychoactivity and Statistical Manual of Mental Disorders, fi more information has appeared in a wide range of applications, Fifth Edition de nes cannabis use mainstream press and social media including pain relief and sedation."73 disorder as use of cannabis for at fi discussing the bene ts and risks of Although different strains may be least 1 year with the presence of 1 or fi marijuana. Reports include discussion advertised as sedating or 2 other ndings consistent with fi of different strains of marijuana invigorating, there is no scientific addiction and signi cant impairment fi 79 plants, health bene t claims, adverse evidence to support these claims. of functioning and distress. effects, where to purchase marijuana, These aspects of a product may be Although cannabis use can negatively fi ’ how to obtain medical certi cation, due to other components of the plant, impact the user s health, to date it has where to use marijuana, and other 74,75 not been linked to fatal such as terpene content. Further 80–82 topics. Thus, pediatricians should be research is needed to accurately overdoses. In addition, aware of the information about describe the effects of specific individuals can experience cannabis marijuana use being disseminated products. withdrawal. The Diagnostic and through the media. Marijuana can be Statistical Manual of Mental Disorders, obtained through dispensaries for Many people purchase medical and Fifth Edition describes cannabis medicinal purposes with appropriate recreational marijuana online. In withdrawal as having $3 of the certification. Generally, patients need a 2017 JAMA study, authors found following signs and symptoms within to consult with a physician and need that nearly 70% of CBD products sold the 1 week of discontinuing use: (1) to have a qualifying condition (which online contained higher or lower irritability, anger, or aggression; (2) varies in different states). Depending concentrations of the drug than was nervousness or anxiety; (3) sleep on the state, they may be given an on their label. Some CBD products difficulty or insomnia; (4) decreased identification card, which allows them contained significant amounts of THC. appetite or weight loss; (5) to purchase marijuana at a medical CBD products sold for vaping were restlessness; (6) depressed mood; dispensary. The amount an individual mislabeled 88% of the time, and THC and (7) at least 1 of the following: may possess or purchase also varies was detected in 18 of 84 samples, abdominal pain, shakiness or tremors, by state. Medicaid and Medicare will some with enough to produce sweating, fever, chills, or headache.79

Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 146, number 2, August 2020 7 Being young, having a lower recommendations and to counsel 7. Ebbert JO, Scharf EL, Hurt RT. Medical socioeconomic status, male sex, and appropriately to prevent exposure cannabis. Mayo Clin Proc. 2018;93(12): being a minority increases the risk of and thus harm to developing brains. 1842–1847 developing cannabis use disorder.83 The health and well-being of children 8. Manrique-Garcia E, Zammit S, Dalman C, and adolescents should be prioritized Hemmingsson T, Andreasson S, Allebeck Several treatments have been when providing this information. P. Prognosis of schizophrenia in investigated for treatment of cannabis More research is needed on the long- persons with and without a history of use disorder. In a review by Brezing term effects of marijuana and should cannabis use. Psychol Med. 2014;44(12): 84 – and Levin, the authors found also be focused on prevention of use 2513 2521 several medication treatments that in adolescents. 9. Brzozowska NI, de Tonnerre EJ, Li KM, may be of benefit. Only one study was et al. The differential binding of focused on treating adolescents: antipsychotic drugs to the ABC topiramate reduced marijuana use in ABBREVIATIONS transporter P-glycoprotein predicts adolescents but was not well cannabinoid-antipsychotic drug tolerated.85 In adult studies, AAP: American Academy of interactions. gabapentin has been found to reduce Pediatrics Neuropsychopharmacology. 2017; – withdrawal, reduce cravings, and CBD: cannabidoil 42(11):2222 2231 improve cognitive functioning. e-cigarette: electronic cigarette 10. Neale M. Efficacy and safety of cannabis Dronabinol and nabilone were also FDA: US Food and Drug for treating children with refractory found to improve withdrawal Administration epilepsy. Nurs Child Young People. 2017; fl symptoms and reduce cannabis IBD: in ammatory bowel disease 29(7):32–37 86,87 use. Nabilone plus zolpidem also SC: synthetic cannabinoid 11. National Academies of Sciences, improved withdrawal symptoms and THC: tetrahydrocannabinol Engineering, and Medicine; Health and reduced cannabis use.88 Limitations Medicine Division; Board on Population to the current studies include Health and Public Health Practice; inclusion of individuals with severe Committee on the Health Effects of cannabis use disorder and high Marijuana. The Health Effects of Cannabis and Cannabinoids: The attrition rates. Brezing and Levin84 REFERENCES Current State of Evidence and note that reduction in use, rather than Recommendations for Research. abstinence, may be an appropriate 1. ElSohly MA, Mehmedic Z, Foster S, Gon C, Chandra S, Church JC. Changes in Washington, DC: National Academies goal for treatment of cannabis use Press; 2017 disorder. 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Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/early/2020/07/09/peds.2 019-2629 References This article cites 78 articles, 4 of which you can access for free at: http://pediatrics.aappublications.org/content/early/2020/07/09/peds.2 019-2629#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Substance Use http://www.aappublications.org/cgi/collection/substance_abuse_sub Addiction http://www.aappublications.org/cgi/collection/addiction_sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml

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