Marijuana and the Pediatric Population
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
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 a
Department 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
c
sevenfold increase in Adolescent 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 Drs Dharmapuri and Klein drafted the initial
cannabis for consumption, and 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,
and 35.6% had ever tried marijuana,2 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: jonklein@uic.edu
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
article to disclose.
using marijuana.2 In 2017, ever use of who engaged in marijuana use in later
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
to disclose.
among white (32.0%) students. The earlier. Positive attitudes toward
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
and the Pediatric Population. Pediatrics. 2020;
bisexual (30.6%) students compared were found to be protective factors
146(2):e20192629
with heterosexual (19.1%) and “not against substance use disorder.3
Downloaded from www.aappublications.org/news at Childrens Mercy Hosp on February 22, 2021
PEDIATRICS Volume 146, number 2, August 2020:e20192629 STATE-OF-THE-ART REVIEW ARTICLE 279PHARMACOLOGY 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.
better understand the effects of found in smooth muscle,
Metabolism of THC occurs mainly in
various forms of cannabis on youth. myocardium, adipocytes, and
the liver by the cytochrome P450
preganglionic sympathetic neurons.
Cannabis occurs naturally as a plant, system. CBD inhibits cytochrome
The CB2 receptor is expressed in
leading to production of cannabis oxidases; thus, it may interfere with
peripheral blood mononuclear cells
products made of dried leaves, oils, other commonly used medications.
as well as in the smooth muscle,
and concentrates. Many cannabis CBD has a regulatory effect on THC,
myocardium, and vascular
products contain numerous with the potential to decrease some
endothelium.
substances, including terpenes, adverse effects (ie, tachycardia,
flavonoids, alkaloids, and .100 THC acts as an agonist at CB1 and anxiety, and sedation).5
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
and antiinflammatory effects.7 CBD risperidone.9 Drug interactions noted
The endocannabinoid system, has weak affinity for CB1 receptors,
composed of endocannabinoids and for CBD included increases in serum
does not interact directly with CB2 levels of antiepileptic drugs, resulting
cannabinoid receptors, is widely receptors, and does not produce the
distributed in the brain and spinal in sedation.8
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
including inflammation, appetite pharmacokinetic profiles 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 and 1-mg tablets, is prescribed up to
Phytocannabinoids, plant-derived
absorption has more variability and 3 times a day, and is approved for
cannabinoids, can be categorized into
lower bioavailability. The acute chemotherapy associated nausea and
several classes; d-9
effects of ingested cannabis may last vomiting.8
tetrahydrocannabinol (generally
for several hours, depending on
known as THC) and cannabidiol
concentration, formulation of the
(generally known as CBD) are the
product, and gastrointestinal motility, MEDICAL USES OF CANNABIS
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 at Childrens Mercy Hosp on February 22, 2021
280 DHARMAPURI et alexcept 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 at Childrens Mercy Hosp on February 22, 2021
PEDIATRICS Volume 146, number 2, August 2020 281youth 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
Marijuana is one of the most and neurologic infections and
established. However, because of the
commonly used illicit substances in hematologic morbidity.34
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
16%.27 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
pregnant women increased by 62%.28 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
(depression and anxiety).28 Use of results between studies, and the ADVERSE EFFECTS FROM CANNABIS
cannabinoids during pregnancy has authors acknowledged that there may USE
led to health concerns related to fetal be confounding biases. The adverse effects of cannabis use
development because exogenous are well documented. Adverse effects
cannabinoids containing THC cross Another area of interest has been the
include distorted perception, poor
the fetal-placental barrier in relationship between breastfeeding
concentration, psychosis, excessive
humans.29–31 and maternal marijuana use.
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 at Childrens Mercy Hosp on February 22, 2021
282 DHARMAPURI et althese 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 knowledgeable about the effects of
changes seen in schizophrenia.48 In
continue to occur for weeks to marijuana on driving.
a recent study by Di Forti et al,49 the
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
marijuana use by age 15 years
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 at Childrens Mercy Hosp on February 22, 2021
PEDIATRICS Volume 146, number 2, August 2020 283NEW 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
consumption has been to smoke the and can be consumed through vape popular recreational substances
dry leaves of the plant. A joint is pens, e-cigarettes, and dabs.60 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
users may prefer blunts to joints one study by Loflin and Earleywine,61 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
a study by Fairman,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
more time getting, using, and getting dependence and withdrawal.61 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
Other forms of marijuana available e-cigarette use in middle and high
a partial agonist at CB1 and CB2
for consumption include hashish (a school students compared with other
receptors, SCs are full agonists at CB1
plant extract containing psychoactive tobacco products.62,63 Eggers et al64
and CB2 sites, increasing the potency
resins), hash oil (cannabis explored use of cannabis through
of SCs.66 This may account for the
concentrate extracted from hashish), e-cigarette systems; cannabis use
increased morbidity and mortality
and dabs (also cannabis concentrate). through e-cigarettes was higher
seen with the use of SCs compared
THC content varies but is generally among 11th-graders than ninth-
with marijuana.67
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
from 39% to 80%.59 Nonsolvent- delivery of cannabis and blunt use abnormalities.68 Cardiac effects
produced concentrates have THC were associated with greater tobacco include tachycardia and acute
concentrations between 39% use.64 Physicians should consider myocardial infarction.69,70 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 at Childrens Mercy Hosp on February 22, 2021
284 DHARMAPURI et aldocumented. 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,
often difficult 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,
display menus listing THC content, according to the Substance Abuse and
MARIJUANA AND THE MEDIA Mental Health Services
cannabis strain, and the mood or
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,
more information has appeared in a wide range of applications, Fifth Edition defines cannabis use
mainstream press and social media including pain relief and sedation."73 disorder as use of cannabis for at
discussing the benefits and risks of Although different strains may be least 1 year with the presence of 1 or
marijuana. Reports include discussion advertised as sedating or 2 other findings consistent with
of different strains of marijuana invigorating, there is no scientific addiction and significant impairment
plants, health benefit claims, adverse evidence to support these claims. of functioning and distress.79
effects, where to purchase marijuana, These aspects of a product may be Although cannabis use can negatively
how to obtain medical certification, due to other components of the plant, impact the user’s health, to date it has
where to use marijuana, and other such as terpene content.74,75 Further not been linked to fatal
topics. Thus, pediatricians should be research is needed to accurately overdoses.80–82 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 at Childrens Mercy Hosp on February 22, 2021
PEDIATRICS Volume 146, number 2, August 2020 285Being 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):
and Levin,84 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: cannabidiol 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;
symptoms and reduce cannabis IBD: inflammatory bowel disease 29(7):32–37
use.86,87 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
attrition rates. Brezing and Levin84 Cannabis and Cannabinoids: The
REFERENCES Current State of Evidence and
note that reduction in use, rather than
1. ElSohly MA, Mehmedic Z, Foster S, Gon Recommendations for Research.
abstinence, may be an appropriate Washington, DC: National Academies
goal for treatment of cannabis use C, Chandra S, Church JC. Changes in
cannabis potency over the last 2 Press; 2017
disorder. However, there is no
decades (1995–2014): analysis of 12. Kurz R, Blaas K. Use of dronabinol
consensus in the literature defining
current data in the United States. Biol (delta-9-THC) in autism: a prospective
a meaningful reduction in use. Psychiatry. 2016;79(7):613–619 single-case-study with an early infantile
Although research on medications for autistic child. Cannabinoids. 2010;5(4):
cannabis use disorder continues; 2. Kann L, McManus T, Harris WA, et al.
Youth risk behavior surveillance - 4–6
motivational and cognitive behavioral
United States, 2017. MMWR Surveill 13. Budney AJ, Hughes JR, Moore BA,
therapies continue to be the Summ. 2018;67(8):1–114 Vandrey R. Review of the validity and
mainstays of treatment at this time.
3. Han B, Compton WM, Blanco C, DuPont significance of cannabis withdrawal
RL. National trends in substance use syndrome. Am J Psychiatry. 2004;
and use disorders among youth. J Am 161(11):1967–1977
CONCLUSIONS Acad Child Adolesc Psychiatry. 2017; 14. Phatak UP, Rojas-Velasquez D, Porto A,
Marijuana is one of the most 56(9):747–754.e3 Pashankar DS. Prevalence and patterns
commonly used psychoactive 4. Shi Y, Cummins SE, Zhu SH. Medical of marijuana use in young adults with
substances. The literature reveals marijuana availability, price, and inflammatory bowel disease. J Pediatr
a number of health concerns product variety, and adolescents’ Gastroenterol Nutr. 2017;64(2):261–264
associated with marijuana use, from marijuana use. J Adolesc Health. 2018; 15. Elliott J, DeJean D, Clifford T, et al.
physical health effects to mental 63(1):88–93 Cannabis-based products for pediatric
health effects, that can occur over the 5. Foster BC, Abramovici H, Harris CS. epilepsy: a systematic review. Epilepsia.
course of development and social Cannabis and cannabinoids: kinetics 2019;60(1):6–19
consequences associated with use. It and interactions. Am J Med. 2019; 16. Kaplan EH, Offermann EA, Sievers JW,
is important for providers to be 132(11):1266–1270 Comi AM. Cannabidiol treatment for
aware of policies and laws around 6. Lu HC, Mackie K. An introduction to the refractory seizures in Sturge-Weber
marijuana in their states to provide endogenous cannabinoid system. Biol syndrome. Pediatr Neurol. 2017;71:
appropriate and evidenced-based Psychiatry. 2016;79(7):516–525 18–23.e2
Downloaded from www.aappublications.org/news at Childrens Mercy Hosp on February 22, 2021
286 DHARMAPURI et al17. Gofshteyn JS, Wilfong A, Devinsky O, Quality, Substance Abuse and Mental review. Paediatr Perinat Epidemiol.
et al. Cannabidiol as a potential Health Services Administration; 2016 2018;32(6):512–532
treatment for febrile infection-related 28. Brown QL, Sarvet AL, Shmulewitz D, 38. Baker T, Datta P, Rewers-Felkins K,
epilepsy syndrome (FIRES) in the acute Martins SS, Wall MM, Hasin DS. Trends Thompson H, Kallem RR, Hale TW.
and chronic phases. J Child Neurol. in marijuana use among pregnant and Transfer of inhaled cannabis into
2017;32(1):35–40 nonpregnant reproductive-aged human breast milk. Obstet Gynecol.
18. Agrawal A, Budney AJ, Lynskey MT. The women, 2002–2014. JAMA. 2017;317(2): 2018;131(5):783–788
co-occurring use and misuse of 207–209
39. Astley SJ, Little RE. Maternal marijuana
cannabis and tobacco: a review. 29. Young-Wolff KC, Tucker LY, Alexeeff S, use during lactation and infant
Addiction. 2012;107(7):1221–1233 et al. Trends in self-reported and development at one year. Neurotoxicol
19. Webster L, Chaiton M, Kirst M. The co- biochemically tested marijuana use Teratol. 1990;12(2):161–168
use of tobacco and cannabis among among pregnant females in California
adolescents over a 30-year period. from 2009–2016. JAMA. 2017;318(24): 40. Tennes K, Avitable N, Blackard C, et al.
J Sch Health. 2014;84(3):151–159 2490–2491 Marijuana: prenatal and postnatal
exposure in the human. NIDA Res
20. Rubinstein ML, Rait MA, Prochaska JJ. 30. Colorado Department of Public Health
Monogr. 1985;59:48–60
Frequent marijuana use is associated & Environment. Monitoring health
with greater nicotine addiction in concerns related to marijuana in 41. Committee on Obstetric Practice.
adolescent smokers. Drug Alcohol Colorado: 2018 summary. Available at: Committee opinion No. 722: marijuana
Depend. 2014;141:159–162 https://drive.google.com/file/d/1cyaRNi use during pregnancy and lactation.
T7fUVD2VMb91ma5bLMuvtc9jZy/view. Obstet Gynecol. 2017;130(4):e205–e209
21. Brook JS, Lee JY, Brook DW. Trajectories Accessed June 12, 2020
of marijuana use beginning in 42. Section on Breastfeeding.
adolescence predict tobacco 31. Gunn JK, Rosales CB, Center KE, et al. Breastfeeding and the use of human
dependence in adulthood. Subst Abus. Prenatal exposure to cannabis and milk. Pediatrics. 2012;129(3). Available
2015;36(4):470–477 maternal and child health outcomes: at: www.pediatrics.org/cgi/content/full/
a systematic review and meta-analysis. 129/3/e827
22. Meruelo AD, Castro N, Cota CI, Tapert SF. BMJ Open. 2016;6(4):e009986
Cannabis and alcohol use, and the 43. Rubino T, Realini N, Braida D, et al.
32. Mato S, Del Olmo E, Pazos A. Ontogenetic Changes in hippocampal morphology
developing brain. Behav Brain Res.
development of cannabinoid receptor and neuroplasticity induced by
2017;325(pt A):44–50
expression and signal transduction adolescent THC treatment are
23. Terry-McElrath YM, O’Malley PM, functionality in the human brain. Eur associated with cognitive impairment
Johnston LD. Alcohol and marijuana J Neurosci. 2003;17(9):1747–1754 in adulthood. Hippocampus. 2009;19(8):
use patterns associated with unsafe 33. Benevenuto SG, Domenico MD, Martins 763–772
driving among US high school seniors: MA, et al. Recreational use of marijuana
high use frequency, concurrent use, 44. Crews F, He J, Hodge C. Adolescent
during pregnancy and negative
and simultaneous use. J Stud Alcohol cortical development: a critical period
gestational and fetal outcomes: an
Drugs. 2014;75(3):378–389 of vulnerability for addiction.
experimental study in mice. Toxicology.
Pharmacol Biochem Behav. 2007;86(2):
24. Hagan JF Jr., Shaw JS, Duncan PM, eds. 2017;376:94–101
189–199
Bright Futures: Guidelines for Health 34. Metz TD, Borgelt LM. Marijuana use in
Supervision of Infants, Children, and 45. Meier MH, Caspi A, Ambler A, et al.
pregnancy and while breastfeeding.
Adolescents, 4th ed. Elk Grove Village, IL: Persistent cannabis users show
Obstet Gynecol. 2018;132(5):1198–1210
American Academy of Pediatrics; 2017 neuropsychological decline from
35. Conner SN, Bedell V, Lipsey K, Macones childhood to midlife. Proc Natl Acad Sci
25. Committee on Substance Use and GA, Cahill AG, Tuuli MG. Maternal U S A. 2012;109(40):E2657–E2664
Prevention. Substance use screening, marijuana use and adverse neonatal
brief intervention, and referral to outcomes: a systematic review and 46. Camchong J, Lim KO, Kumra S. Adverse
treatment. Pediatrics. 2016;138(1): meta-analysis. Obstet Gynecol. 2016; effects of cannabis on adolescent brain
e20161210 128(4):713–723 development: a longitudinal study.
Cereb Cortex. 2017;27(3):1922–1930
26. Boston Children’s Hospital. About the 36. Carter RC, Wainwright H, Molteno CD,
CRAFFT. Available at: https://crafft.org/ et al. Alcohol, methamphetamine, and 47. Silins E, Horwood LJ, Patton GC, et al;
about-the-crafft/. Accessed August 6, marijuana exposure have distinct Cannabis Cohorts Research
2019 effects on the human placenta. Alcohol Consortium. Young adult sequelae of
Clin Exp Res. 2016;40(4):753–764 adolescent cannabis use: an integrative
27. Bose J, Hedden SL, Lipari RN, et al. Key
analysis. Lancet Psychiatry. 2014;1(4):
Substance Use and Mental Health 37. Sharapova SR, Phillips E, Sirocco K,
286–293
Indicators in the United States: Results Kaminski JW, Leeb RT, Rolle I. Effects of
From the 2015 National Survey on Drug prenatal marijuana exposure on 48. Rubino T, Parolaro D. Cannabis abuse in
Use and Health. Rockville, MD: Center neuropsychological outcomes in adolescence and the risk of psychosis:
for Behavioral Health Statistics and children aged 1–11 years: a systematic a brief review of the preclinical
Downloaded from www.aappublications.org/news at Childrens Mercy Hosp on February 22, 2021
PEDIATRICS Volume 146, number 2, August 2020 287evidence. Prog Neuropsychopharmacol 59. Meier MH, Docherty M, Leischow SJ, marijuana abuse in an adolescent.
Biol Psychiatry. 2014;52:41–44 Grimm KJ, Pardini D. Cannabis Anatol J Cardiol. 2016;16(7):542–543
49. Di Forti M, Quattrone D, Freeman TP, concentrate use in adolescents.
70. Shanks KG, Clark W, Behonick G. Death
et al. The contribution of cannabis use Pediatrics. 2019;144(3):e20190338
associated with the use of the synthetic
to variation in the incidence of 60. Carlini BH, Garrett SB, Harwick RM. cannabinoid ADB-FUBINACA. J Anal
psychotic disorder across Europe (EU- Beyond joints and brownies: marijuana Toxicol. 2016;40(3):236–239
GEI): a multicentre case-control study. concentrates in the legal landscape of
Lancet Psychiatry. 2019;6(5):427–436 WA State. Int J Drug Policy. 2017;42: 71. Moritz E, Austin C, Wahl M, et al. Notes
26–29 from the field: outbreak of severe
50. Olfson M, Wall MM, Liu SM, Blanco C. illness linked to the vitamin K
Cannabis use and risk of prescription 61. Loflin M, Earleywine M. A new method of antagonist brodifacoum and use of
opioid use disorder in the United cannabis ingestion: the dangers of synthetic cannabinoids - Illinois,
States. Am J Psychiatry. 2018;175(1): dabs? Addict Behav. 2014;39(10): March–April 2018. MMWR Morb Mortal
47–53 1430–1433 Wkly Rep. 2018;67(21):607–608
51. Mack KA, Jones CM, Ballesteros MF. 62. Arrazola RA, Singh T, Corey CG, et al; 72. Buser GL, Gerona RR, Horowitz BZ, et al.
Illicit drug use, illicit drug use Centers for Disease Control and Acute kidney injury associated with
disorders, and drug overdose deaths in Prevention (CDC). Tobacco use among smoking synthetic cannabinoid. Clin
metropolitan and nonmetropolitan middle and high school students - Toxicol (Phila). 2014;52(7):664–673
areas - United States. [published United States, 2011–2014. MMWR Morb
correction appears in MMWR Surveill Mortal Wkly Rep. 2015;64(14):381–385 73. The Apothecarium Dispensary. SOMA
Summ. 2017;66(45):1262]. MMWR delivery and pickup menu. Available at:
63. Cullen KA, Ambrose BK, Gentzke AS, https://apothecarium.com/soma-menu-
Surveill Summ. 2017;66(19):1–12 Apelberg BJ, Jamal A, King BA. Notes heartjane. Accessed June 12, 2020
52. Keyes KM, Wall M, Cerdá M, et al. How from the field: use of electronic
does state marijuana policy affect US cigarettes and any tobacco product 74. Russo EB. Taming THC: potential
youth? Medical marijuana laws, among middle and high school cannabis synergy and
marijuana use and perceived students - United States, 2011-2018. phytocannabinoid-terpenoid entourage
harmfulness: 1991–2014. Addiction. MMWR Morb Mortal Wkly Rep. 2018; effects. Br J Pharmacol. 2011;163(7):
2016;111(12):2187–2195 67(45):1276–1277 1344–1364
53. Blohm E, Sell P, Neavyn M. Cannabinoid 64. Eggers ME, Lee YO, Jackson K, Wiley JL, 75. Komori T, Fujiwara R, Tanida M, Nomura
toxicity in pediatrics. Curr Opin Pediatr. Porter L, Nonnemaker JM. Youth use of J, Yokoyama MM. Effects of citrus
2019;31(2):256–261 electronic vapor products and blunts fragrance on immune function and
54. Sorensen CJ, DeSanto K, Borgelt L, for administering cannabis. Addict depressive states.
Phillips KT, Monte AA. Cannabinoid Behav. 2017;70:79–82 Neuroimmunomodulation. 1995;2(3):
hyperemesis syndrome: diagnosis, 65. Walley SC, Jenssen BP; Section on 174–180
pathophysiology, and treatment- Tobacco Control. Electronic nicotine 76. Bonn-Miller MO, Loflin MJE, Thomas BF,
a systematic review. J Med Toxicol. delivery systems. Pediatrics. 2015; Marcu JP, Hyke T, Vandrey R. Labeling
2017;13(1):71–87 136(5):1018–1026 accuracy of cannabidiol extracts sold
55. Dezieck L, Hafez Z, Conicella A, et al. 66. Aung MM, Griffin G, Huffman JW, et al. online. JAMA. 2017;318(17):1708–1709
Resolution of cannabis hyperemesis Influence of the N-1 alkyl chain length of 77. The Monitoring the Future Study;
syndrome with topical capsaicin in the cannabimimetic indoles upon CB(1) and University of Michigan. Figure 3:
emergency department: a case series. CB(2) receptor binding. Drug Alcohol marijuana: trends in annual use, risk,
Clin Toxicol (Phila). 2017;55(8):908–913 Depend. 2000;60(2):133–140 disapproval, and availability: grades 8,
56. Wang GS, Le Lait MC, Deakyne SJ, 67. Tait RJ, Caldicott D, Mountain D, Hill SL, 10, and 12. 2016. Available at: http://
Bronstein AC, Bajaj L, Roosevelt G. Lenton S. A systematic review of www.monitoringthefuture.org/data/
Unintentional pediatric exposures to adverse events arising from the use of 16data/16drfig3.pdf. Accessed March
marijuana in Colorado, 2009–2015. synthetic cannabinoids and their 22, 2017
JAMA Pediatr. 2016;170(9):e160971 associated treatment. Clin Toxicol 78. The Monitoring the Future Study;
57. Tai S, Fantegrossi WE. Pharmacological (Phila). 2016;54(1):1–13 University of Michigan. Figure 4:
and toxicological effects of synthetic 68. Davidson C, Opacka-Juffry J, Arevalo- marijuana: trends in daily use, risk,
cannabinoids and their metabolites. Martin A, Garcia-Ovejero D, Molina- disapproval, and availability: grades 8,
Curr Top Behav Neurosci. 2017;32: Holgado E, Molina-Holgado F. Spicing up 10, and 12. 2016. Available at: http://
249–262 pharmacology: a review of synthetic www.monitoringthefuture.org/data/
cannabinoids from structure to adverse 16data/16drfig3.pdf. Accessed March
58. Fairman BJ. Cannabis problem
events. Adv Pharmacol. 2017;80:135–168 22, 2017
experiences among users of the
tobacco-cannabis combination known 69. Keskin M, Hayıroglu M_I, Keskin Ü, Eren 79. American Psychiatric Association.
as blunts. Drug Alcohol Depend. 2015; M. Acute myocardial infarction and Diagnostic and Statistical Manual of
150:77–84 ischemic stroke coexistence due to Mental Disorders, 5th ed. Washington,
Downloaded from www.aappublications.org/news at Childrens Mercy Hosp on February 22, 2021
288 DHARMAPURI et alDC: American Psychiatric Association; cannabis use disorder, 2012–2013: Dronabinol for the treatment of
2013 findings from the National cannabis dependence: a randomized,
80. Calabria B, Degenhardt L, Hall W, Epidemiologic Survey on Alcohol and double-blind, placebo-controlled trial.
Lynskey M. Does cannabis use increase Related Conditions-III. Am J Psychiatry. Drug Alcohol Depend. 2011;116(1–3):
the risk of death? Systematic review of 2016;173(6):588–599 142–150
epidemiological evidence on adverse 84. Brezing CA, Levin FR. The current state 87. Haney M, Cooper ZD, Bedi G, Vosburg
effects of cannabis use. Drug Alcohol of pharmacological treatments for SK, Comer SD, Foltin RW. Nabilone
Rev. 2010;29(3):318–330 cannabis use disorder and withdrawal. decreases marijuana withdrawal and
81. Budney AJ, Vandrey RG, Hughes JR, Neuropsychopharmacology. 2018;43(1): a laboratory measure of marijuana
Thostenson JD, Bursac Z. Comparison 173–194 relapse. Neuropsychopharmacology.
of cannabis and tobacco withdrawal: 85. Haney M, Ramesh D, Glass A, Pavlicova 2013;38(8):1557–1565
severity and contribution to relapse. M, Bedi G, Cooper ZD. Naltrexone 88. Herrmann ES, Cooper ZD, Bedi G,
J Subst Abuse Treat. 2008;35(4):362–368 maintenance decreases cannabis self- et al. Effects of zolpidem alone and
82. Hall W. Alcohol and cannabis: administration and subjective effects in in combination with nabilone on
comparing their adverse health effects daily cannabis smokers. cannabis withdrawal and
and regulatory regimes. Int J Drug Neuropsychopharmacology. 2015;
a laboratory model of relapse
Policy. 2017;42:57–62 40(11):2489–2498
in cannabis users.
83. Hasin DS, Kerridge BT, Saha TD, et al. 86. Levin FR, Mariani JJ, Brooks DJ, Psychopharmacology (Berl). 2016;
Prevalence and correlates of DSM-5 Pavlicova M, Cheng W, Nunes EV. 233(13):2469–2478
Downloaded from www.aappublications.org/news at Childrens Mercy Hosp on February 22, 2021
PEDIATRICS Volume 146, number 2, August 2020 289Marijuana and the Pediatric Population
Sadhana Dharmapuri, Kathleen Miller and Jonathan D. Klein
Pediatrics 2020;146;
DOI: 10.1542/peds.2019-2629 originally published online July 13, 2020;
Updated Information & including high resolution figures, can be found at:
Services http://pediatrics.aappublications.org/content/146/2/e20192629
References This article cites 78 articles, 4 of which you can access for free at:
http://pediatrics.aappublications.org/content/146/2/e20192629#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
Downloaded from www.aappublications.org/news at Childrens Mercy Hosp on February 22, 2021You can also read
