Marijuana 2019 FinalA

Marijuana

Laury Rosefort, MD & Deepa Camenga, MD

When I was a kid, I inhaled frequently. That was the point. Barack Obama

Learning Objectives: 1. Describe the major psychopharmacologic properties of marijuana and its effects on pediatric

health and development. 2. Learn key points in discussing marijuana use with both parents and adolescents. 3. Distinguish between legalization and decriminalization of marijuana, and the different potential

impacts of these policies on the pediatric population. 4. Understand the implications and consequences of the medical legalization of marijuana.

Primary Reference: 1. Ammerman S, Ryan S, Adelman WP. Committee on Substance Abuse, Committee on Adolescence.

AAP Technical Report on The impact of marijuana policies on youth: clinical, research, and legal update. Pediatrics. 2015;135: e769-e785.

CASE ONE:

You are seeing a 16-year-old boy, Bud, for a well child visit. His aunt, who has been his legal guardian since Bud was 9 years old, accompanies him to the visit. She tells you "I am having a hard time keeping up with Bud since the car accident last year. Now I walk with a cane and have chronic back pain." She goes on to describe new academic and behavioral difficulties that Bud is having. Bud rolls his eyes and remains silent throughout the encounter. You explain the limits of confidentiality to Bud and his aunt, and excuse her so you can speak with Bud alone.

After several minutes of probing, Bud finally opens up about the stress of watching his aunt struggle with her injuries. It reminded him of the suffering his mother went through before she died from cancer several years prior. When asked about drug use, he admits that he started experimenting with marijuana several months ago when he saw some of the relief it brought his aunt. He states that his aunt gets it from a prescriber for her "medical problems" and sometimes leaves some of the flower buds out on the kitchen counter. He tried his aunt's marijuana a few times and now obtains marijuana from friends. He currently uses marijuana about once monthly. Bud does not see what the big deal is, "It's not like I'm drinking alcohol or doing any of the `illegal' drugs, and my aunt gets it from a doctor. So, it can't be so bad."

1. What is marijuana? What are its components and routes of administration?

The term "marijuana" specifically refers to the dried leaves and flowers of the cannabis plant. Marijuana is used recreationally for its pleasurable psychoactive properties that are thought to be secondary to the psychoactive cannabinoid, tetrahydrocannabinol (THC). Marijuana also contains cannabidiol (CBD) ? a non-psychoactive cannabinoid. Cannabis sativa and Cannabis indica are the two most common species of the cannabis plant used in "medical marijuana."

The cannabis plant contains over 200 complex mixtures of cannabinoids. These cannabinoids are biologically active substances that bind to CB1 and CB2 receptors. The CB1 receptor is found widely throughout the brain (therefore facilitating the psychoactive properties of marijuana) and in certain parts of the peripheral nervous system. The function of the CB2 receptor is currently less defined, but it is found in the brain and is linked to immune function. Humans produce endogenous cannabinoids

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(endocannabinoids: anandamide and 2-arachidonoylglycerol). The endocannabinoid system has an integral role in both pre- and post-natal development, including brain and neural development, as well as regulation of energy balance and food intake (through interactions with molecules involved in weight regulation and appetite such as leptin, ghrelin, and melanocortins).

Marijuana is primarily delivered to the brain through inhalation and ingestion. The former can be achieved through smoking (i.e., combustion of marijuana) or vaporization. Users can inhale a vaporized form of marijuana by using portable devices (such as electronic cigarettes) which heat marijuana in the form of highly concentrated liquid hash oil, highly concentrated waxy forms of -9tetrahydrocannabinol, or dried cannabis buds or leaves. Inhalation via smoking or vaporization results in a rapid onset of action, whereas ingestion has a more gradual onset of action.

2. How prevalent is marijuana use in the US? Worldwide?

According to the World Health Organization, approximately 2.5 percent of the world's population ? 147 million people ? use marijuana. Adolescents and young adults have relatively higher prevalence rates of marijuana use globally. In the United States, marijuana is the most commonly used illicit drug. The prevalence of cannabis use has increased more rapidly than that of other drugs, such as opiates or cocaine in the past decade. According to the National Survey on Drug Use and Health the prevalence of past-month marijuana use in the US more than doubled between 2001-2002 and 2014-2015. The percentage of past-month users continued to climb in 2017 to 9.6 percent of the population aged 12 or older. According to the National Institutes of Health's Monitoring the Future Survey, in 2018 35.9% of 12th graders in the US reported past-year use of marijuana. This 2018 survey continues to demonstrate that daily marijuana use exceeds daily tobacco cigarette use among 12th graders, which occurred for the first time in 2015 since the study's inception (in the 1970s; 6% vs. 5.5%). Additionally, a large proportion of adolescents continue to perceive marijuana to be a harmless substance; 73.3% of 12th graders did NOT view regular marijuana use as harmful. Furthermore, in 2018, vaping of marijuana (as well as other ilicit substances) increased substantially as this modality of drug use has become more mainstream.

3. What are some of the psychological and physical effects of marijuana?

Because of the varying amounts of THC and CBD in any given plant, the psychoactive properties differ from one plant to another, but include impaired attention, concentration, and executive functioning, as well as the "high" for which recreational users search. Tachycardia and systolic hypertension are two of the most consistent objective physical effects of marijuana use. Other short-term effects include drowsiness, ataxia, increased appetite/thirst, conjunctival injection, dry mouth, anxiety, insomnia, hallucinations and short-term memory loss. Long-term effects, discussed further below, include impairments in cognitive functioning and psychomotor slowing. In the population of young children who are at risk for ingestion, physical manifestations of toxicity can include behavioral changes, sleepiness, hyperkinesis, respiratory depression, and coma. Death solely from marijuana intoxication/overdose has never been reported.

4. What is known about the effects marijuana can have on the growth and development of the adolescent brain?

The adverse effects of marijuana, particularly as it pertains to motor function, cognitive functioning and learning, have been well documented and include impairments in memory, attention span, concentration and problem solving, and psychomotor slowing. Studies analyzing functional MRIs of abstinent marijuana users have shown abnormalities in brain function during cognitive tasks suggesting marijuana-related changes to the brain that are not yet fully understood. Additionally, data supporting increased risk of psychosis in heavy marijuana users predisposed to developing schizophrenia is now starting to emerge.

Recent neurodevelopmental studies have shown that brain maturation extends into the mid-20s. Among the last areas to mature is the prefrontal cortex, which is the area of the brain responsible for facilitation of communication between the higher order areas of the brain and the lower sensorimotor areas. There is concern that heavy marijuana use in the adolescent period interferes with synaptic pruning and myelination, resulting in changes in the hippocampal region, prefrontal cortex and white

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matter volume, and correlating with poorer neurocognitive functioning. It has been postulated that the earlier illicit substances, including marijuana, are initiated, the more likely substance use disorders are to occur. According to a national study looking specifically at individuals who began using marijuana prior to any other drug, lifetime cumulative probability estimates indicated that 44.7% of individuals progressed to other illicit drug use at some time in their lives, adding evidence to the "gateway effect" of drug use.

5. What is the difference between legalization and decriminalization of marijuana?

Legalization refers to allowing the legal cultivation, sale, use, and/or possession of marijuana. Decriminalization refers to the elimination of criminal penalties for the possession or use of small amounts of marijuana. Both concepts have been at the center of global debate in reference to marijuana, particularly as it pertains to the adolescent population.

The US Federal government has maintained the illegal status of marijuana and its possession, use, cultivation and sale, in accordance with international treaties. Marijuana shares the Schedule I federal classification with other illicit drugs such as cocaine and heroin. As such, penalties for its use or possession have been linked to high criminal consequences often leading to incarceration. Despite this federal classification, many states have moved in the direction of lessening the legal impact of marijuana possession through legalization and decriminalization laws.

Through legalization and/or decriminalization laws, states have been able to lessen criminal offense charges to help circumvent the long-term consequences and stigmatization of federal charges. In fact, one of the biggest arguments for decriminalization is shifting from a law enforcement approach to that of a public health approach, minimizing punitive consequences for minor offenses and instead emphasizing the importance of medical treatment for drug dependence or addiction.

Incarceration of marijuana users disproportionally affects minority youth leading to the long-term consequences of felony charges such as inability to vote and discrimination for future employment. Studies on decriminalization laws in the US have not only shown that marijuana use among adolescents did not increase after those laws were put into place but also demonstrated significant savings in cost and resources within the criminal justice system.

On the other hand, legalization and/or decriminalization laws pose some safety concerns for children and youth populations. Some studies have shown increases in accidental ingestion of marijuana by young children who live in states where medical marijuana is legal and/or legalization/decriminalization laws are in place. Additionally, with growing data on the negative physical, mental and behavioral effects of marijuana, there is concern that legalization in particular minimizes these harms and may lead to higher use among adolescents.

As such, the AAP strongly supports decriminalization, but opposes legalization of marijuana recommending a focus on treatment of youth with marijuana use issues.

Other professional organizations such as the American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) support reclassification of marijuana at the federal level, as more rigorous research efforts on the efficacy, safety and long-term effects of medical marijuana use can be pursued.

See Resources for sites with state-specific information regarding marijuana laws.

6. What is known about the medicinal benefits of marijuana?

There has been growing popularity of cannabis derived medicinal products contributing to the changing landscape of marijuana use in the US. According to a 2017 report from the National Academies of Sciences, Engineering, and Medicine, there is "conclusive or substantial evidence" supporting the effectiveness of cannabis and cannabinoids for the treatment of the following conditions in adults: chronic pain, multiple sclerosis, and nausea and vomiting associated with chemotherapy. However, there are few published studies evaluating the use of medical marijuana in children or adolescents. Studies of medical cannabis use in adolescence have been limited to severe refractory seizures/epilepsy. Case reports have documented success of cannabis to treat children with epilepsy,

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anxiety, depression, ADHD, and autism. However, the strength of evidence and generalizability need to be further explored in well-designed trials. As such, the AAP opposes the use of medical marijuana outside of the regulatory process of the FDA but "recognizes that marijuana may currently be an option for cannabinoid administration for children with life-limiting or severely debilitating conditions and for whom current therapies are inadequate."

7. How would you approach the discussion of marijuana with Bud? His aunt?

It is important to counsel Bud about the physical and cognitive harm marijuana may have on him, both in the short- and long-term, and to screen for other substance use with a validated screening tool. Moderators can refer to the chapter on Substance Use Disorders for a more detailed discussion about screening. Given his aunt's history of chronic pain, it is particularly important to screen for prescription opioid use. Other health risks include driving under the influence of marijuana (especially in combination with alcohol or other drugs) or riding with an intoxicated driver. Understanding Bud's underlying psychological reasoning for marijuana use will also help providers address life stressors, identify alternate coping strategies, and make timely referrals for psychiatric/psychological care and/or specialized substance use treatment if warranted. Given that Bud uses marijuana monthly, a brief motivational intervention is warranted with close follow up to determine if Bud needs more intensive care.

A conversation with Bud's aunt will also be paramount to the success of getting Bud to quit using marijuana. Determining the aunt's perceptions of marijuana use, both recreational and medicinal, will help inform your approach to your discussion.

In this case, access to marijuana through legal medical channels has resulted in experimentation and use behaviors in Bud. His aunt's marijuana use, particularly in Bud's presence, should be discouraged, given the impact adult role modeling has on child and adolescent behavior. Bud's aunt should be cautioned to store her medications securely, and she should receive guidance about additional resources that are available to Bud for counseling and/or substance use treatment.

CASE TWO:

You are seeing a 5-day-old infant, Mary, for her first newborn visit. Jane, her mother reports that breastfeeding has been going remarkably well despite it being her first time. While Jane denies any overwhelming sadness or depressive symptoms, and has a negative depression screen, she admits that it has been a very stressful transition to motherhood. When asked about how she copes with the stress, she states "Cigarettes used to do the trick but I quit when I found out I was pregnant since I know it's bad for the baby." You probe about smoking exposure and find out that both parents will occasionally smoke marijuana when the baby is asleep. Jane states "We obviously don't smoke weed in front of the baby... besides, marijuana is just a plant. It shouldn't hurt my baby right?"

8. What is the effect of prenatal exposure to marijuana? How does marijuana affect breast milk?

Marijuana is one of the most commonly reported recreational drug used among pregnant and lactating women, with higher reported usage among urban, young, and socioeconomically disadvantaged pregnant women. Prenatal use of marijuana has been linked to preterm delivery, fetal growth retardation and subtle deficits in learning, memory, and executive function.

While empiric evidence surrounding the effect of THC in breast milk is still emerging, it is already known that the levels of THC in breast milk could be up to 8 times as concentrated as the serum levels of chronic users, concentrations of THC are measurable in breast milk up to 6 days post exposure, and that THC is readily absorbed and metabolized by infants. Other studies suggest some association with sedation, low tone, poor suckling, and delayed motor development in infants breastfed by chronic marijuana users.

Less is known about CBD which is gaining increasing popularity as an over-the-counter anti-emetic in pregnancy. However, data are sparse for this emerging trend, and there is lack of product regulation and standardization.

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Given the lack of safety data in humans, and animal studies that suggest disruption of normal brain development, the AAP, American College of Obstetricians and Gynecologists (ACOG), and Academy of Breastfeeding Medicine recommend avoidance of all cannabis products (either recreational or medicinal) during pregnancy and breastfeeding.

9. How would you counsel this mother and father on the use of marijuana?

It would be important to stress that even though marijuana is "just a plant," it contains compounds that may affect their child's growth and development. Additionally, marijuana's known cognitive effects will compromise Mary's parents' ability to effectively care for the baby. In some states, marijuana possession is a criminal offense that may result in incarceration. Therefore, parental use of marijuana may also affect their ability to remain consistently present in children's lives.

As outlined above, as Mary grows, unintentional ingestion of marijuana becomes a growing concern given the presence of marijuana in the home. States that have legalized marijuana use for recreation and/or medical purposes, have shown an increase in unintentional pediatric exposures and toxicities. Furthermore, while secondhand marijuana smoke has been linked to infants admitted for respiratory compromise, the long-term effects of secondary exposure to marijuana are not well understood.

Additional References:

1. American Academy of Family Physicians. Marijuana: Policy Statement. 2014. Retrieved May 1, 2016,

from

2. American College of Obstetricians and Gynecologists. Committee on Obstetric Practice. Marijuana

use during pregnancy and lactation. Committee Opinion No. 722. Obstet Gynecol. 2017;130(4):

e205?e209.

3. American College of Physicians. Supporting Research into the Therapeutic Role of Marijuana:

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4. Astley SJ, Little RE. Maternal marijuana use during lactation and infant development at one year.

Neurotoxicol Teratol. 1990;12(2): 161-8.

5. Bertrand KA, et al. Marijuana Use by Breastfeeding Mothers and Cannabinoid Concentrations in

Breast Milk. Pediatrics.2018;142(3): e20181076.

6. Campbell CT, Phillips MS, Manasco K. Cannabinoids in Pediatrics. J Pediatr Pharmacol Ther

2017;22(3): 176?185.

7. Center for Behavioral Health Statistics and Quality. Key substance use and mental health indicators

in the United States: results from the 2016 National Survey on Drug Use and Health (HHS

Publication No. SMA 17-5044). 2017. Retrieved March 16, 2018, from .

8. Committee on Substance Abuse and Committee on Adolescence. AAP Policy Statement on The

impact of marijuana policies on youth: clinical, research, and legal update. Pediatrics.

2015;135(3): 584-7.

9. Fried PA, Watkinson B, Gray R. Growth from birth to early adolescence in offspring prenatally

exposed to cigarettes and marijuana. Neurotoxicol Teratol. 1999;21(5): 513-25.

10. Garry A, et al. Cannabis and breastfeeding. Journal of Toxicology. 2009;596149.

11. Lu HC, Mackie K. An Introduction to the Endogenous Cannabinoid System. Biol Psychiatry.

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12. Meier MH, et al. Persistent cannabis users show neuropsychological decline from childhood to

midlife. Proc Natl Acad Sci USA. 2012;109: E2657-2664.

13. National Academies of Sciences, Engineering, and Medicine. The health effects of cannabis and

cannabinoids: Current state of evidence and recommendations for research. 2017. Washington, DC:

The National Academies Press. Retrieved March 30, 2018, from



cannabinoids.aspx.

14. National Institutes of Health, National Institute of Drug Abuse. Monitoring the Future 2018 Survey

Results. Retrieved March 13, 2019, from

statistics/infographics/monitoring-future-2018-survey-results.

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