SAHM Annual Meeting 2015 Hot Topic: The new American Academy of Pediatrics (AAP)

Position Statement (PS) on Marijuana: "The Impact of Marijuana Policies on Youth: Clinical, Research, and

Legal Update."

Seth Ammerman, M.D.Clinical Professor

Department of PediatricsDivision of Adolescent Medicine

Stanford UniversityLucile Packard Children’s Hospital Stanford

seth.ammerman@stanford.edu

Boston University School of Medicine asks all individuals involved in the development and presentation Boston University School of Medicine asks all individuals involved in the development and presentation of Continuing Medical Education (CME) activities to disclose all relationships with commercial interests. This information is disclosed to CME activity participants. Boston University School of Medicine has procedures to resolve apparent conflicts of interest. In addition, presenters are asked to disclose when any discussion of unapproved use of pharmaceuticals and devices is being discussed.

I, Seth Ammerman, MD, have no commercial relationships to disclose.I will be discussing the use of medical marijuana, which is a Schedule 1 drug federally in the US. of Continuing Medical Education (CME) activities to disclose all relationships with commercial interests. This information is disclosed to CME activity participants. Boston University School of Medicine has procedures to resolve apparent conflicts of interest. In addition, presenters are asked to disclose when any discussion of unapproved use of pharmaceuticals and devices is being discussed.

I, Seth Ammerman, MD, have no commercial relationships to disclose.I will be discussing the use of medical marijuana, which is a Schedule 1 drug federally in the US.

ObjectivesLearn key recommendations of the PS.List the differences between a Schedule 1

and Schedule 2 Drug per United States Drug Enforcement Administration (DEA) law.

Understand the misnomer of "medical marijuana" and the importance of focusing on cannabinoids.

AAP Marijuana Position Statement: Key Recommendations*

Given the data supporting the negative health and brain development effects of marijuana in children and adolescents, ages 0 through 21 years, the AAP is opposed to marijuana use in this population.

Evidence Summary (ES): numerous studies have demonstrated that regular or heavy use of marijuana, defined as using 10-19x/month, or >=20x/month respectively, can significantly impair adolescent cognitive development. Use of marijuana can also adversely affect mental health and social outcomes. Research has also shown that use during pregnancy can lead to adverse psychosocial outcomes in children.

*There are 10 total recommendations

AAP Marijuana Position Statement: Key Recommendations*

The AAP opposes “medical marijuana” outside the regulatory process of the US Food and Drug Administration (FDA). Notwithstanding this opposition to use, the AAP 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.

ES: Unlike FDA-regulated medications, the current system of medical marijuana does not routinely include standardization of purity, indications, dosing, effects, or side effects.

Key Recommendations, cont.The AAP opposes legalization of marijuana because

of the potential harms to children and adolescents. The AAP supports studying the effects of recent laws legalizing the use of marijuana to better understand the impact and define best policies to reduce adolescent marijuana use.

ES: Based on the past history and current behavior of Big Tobacco, with profit motive being primary, the targeting of adolescents by the developing marijuana industry is likely, unless truly strict and enforceable rules and regulations are in place.

Key Recommendations, cont.The AAP strongly supports research and

development of pharmaceutical cannabinoids and supports a review of policies promoting research on the medical use of these compounds. The AAP recommends changing marijuana from a Drug Enforcement Administration schedule I to a schedule II drug to facilitate this research.

ES: Limited research has shown potential therapeutic benefit of certain cannabinoids, primarily THC and CBD. The current scheduling of marijuana as Schedule 1 significantly impedes research.

Key Recommendations, cont.The AAP strongly supports the decriminalization of marijuana

use for both minors and young adults and encourages pediatricians to advocate for laws that prevent harsh criminal penalties for possession or use of marijuana. A focus on treatment for adolescents with marijuana use problems should be encouraged, and adolescents with marijuana use problems should be referred to treatment.

ES: Hundreds of thousands of youth are arrested and convicted for marijuana use and possession in the US every year, with minority youth significantly over-represented. A criminal record can have significant adverse long-term social impact on one’s education and livelihood. Additionally, taking marijuana use out of the criminal justice system, and putting it into the health care system, will put a focus on early intervention and treatment, and help prevent problem use and addiction.

Key Recommendations, cont.The AAP discourages the use of marijuana by

adults in the presence of minors because of the important influence of role modeling by adults on child and adolescent behavior.

ES: Adults, and parents in particular, are role models for children and adolescents. Actions speak louder than words, and if a parent uses a substance regularly in front of their child, the child is more likely to use it as well.

Drug Enforcement Agency (DEA) Scheduling

Started with congressional passage of the Controlled Substances Act (CSA) in 1970, signed into law by President Nixon.

Congress has the ultimate authority to decide a drug’s schedule.

The DEA is essentially the gatekeeper and enforcer of the CSA, although changes to scheduling can also be requested by Health and Human Services (HHS), the FDA (Food and Drug Administration), or private citizens/groups.

The U.S. Attorney General can unilaterally change the scheduling of a drug, though Congress can override that decision.

Drug Enforcement Agency (DEA) Scheduling

There are 5 categories of DEA Drug Schedules: 1-5.

Schedule 1 by definition includes drugs that are considered by the DEA to have no currently accepted medical use and a high potential for abuse.

Schedule 2 is slightly less restrictive than Schedule 1, etc.

Not all drugs are scheduled, e.g., antibiotics.

DEA Drug Schedule 1Schedule I drugs, substances, or chemicals

are defined as drugs with no currently accepted medical use and a high potential for abuse. Schedule I drugs are the most dangerous drugs of all the drug schedules with potentially severe psychological or physical dependence.

Some examples of Schedule I drugs are: heroin, lysergic acid diethylamide (LSD), marijuana (cannabis), 3,4methylenedioxymethamphetamine (ecstasy), methaqualone, and peyote.

DEA Drug Schedule 2Schedule II drugs, substances, or chemicals

are defined as drugs with a high potential for abuse, less abuse potential than Schedule I drugs, with use potentially leading to severe psychological or physical dependence. These drugs are also considered dangerous.

Some examples of Schedule II drugs are: cocaine, methamphetamine, methadone, hydromorphone (Dilaudid), meperidine (Demerol), oxycodone (OxyContin), fentanyl, Dexedrine, Adderall, and Ritalin.

DEA Drug Schedule 3Schedule III drugs, substances, or chemicals

are defined as drugs with a moderate to low potential for physical and psychological dependence. Schedule III drugs abuse potential is less than Schedule I and Schedule II drugs but more than Schedule IV.

Some examples of Schedule III drugs are: Combination products with less than 15 milligrams of hydrocodone per dosage unit (Vicodin), Products containing less than 90 milligrams of codeine per dosage unit (Tylenol with codeine), ketamine, anabolic steroids, testosterone.

DEA Drug Schedule 4Schedule IV drugs, substances, or chemicals

are defined as drugs with a low potential for abuse and low risk of dependence.

Some examples of Schedule IV drugs are: Xanax, Soma, Darvon, Darvocet, Valium, Ativan, Talwin, Ambien.

DEA Drug Schedule 5Schedule V drugs, substances, or chemicals

are defined as drugs with lower potential for abuse than Schedule IV and consist of preparations containing limited quantities of certain narcotics. Schedule V drugs are generally used for antidiarrheal, antitussive, and analgesic purposes.

Some examples of Schedule V drugs are: cough preparations with less than 200 milligrams of codeine or per 100 milliliters (Robitussin AC), Lomotil, Motofen, Lyrica, Parepectolin.

Definitions: MarijuanaThe cannabis plant , which contains a large

number of biologically active cannabinoids.  There are numerous species and subspecies of

cannabis; Cannabis sativa and indica are the two most commonly utilized plants.

Psychotropically, Cannabis sativa typically causes an alert and energetic high, whereas Cannabis indica causes a relaxed and lethargic high.

Both species have been hybridized repeatedly, and a typical medical marijuana plant will have varying amounts of both sativa and indica.

 

Marijuana, cont.Marijuana is a complex mixture of cannabinoids (over

200 have been identified) and other molecules, and the risk: benefit ratio of this mixture has not generally been well-defined. 

Over the past several decades, selective breeding of marijuana species has resulted in higher concentrations of cannabinoids such as THC in the plant oil, resulting in a more potent psychotropic effect as well as possible increased risk of adverse effects.  Any product that requires smoking to release the desired

effects generally cannot be recommended by physicians, because smoke contains tar and other harmful chemicals.

Vaporization would be a preferred harm reduction method.

Definitions: THCTHC: Tetrahydrocannabinol, also know as delta-9-

tetrahydrocannibinol, is the primary psychoactive cannabinoid in the marijuana plant.

The amount of THC in a given plant varies widely (~15% is common), depending on the species and subspecies of marijuana utilized in breeding the plant.

Cannabadiol (CBD)CBD is a non-psychoactive cannabinoid.CBD is currently being studied for:

Improved control of certain chronic neurological conditions, including intractable seizures.

immune enhancement.Cancer treatment.

Little is known about dose-response relationships of use of CBD; too little may be ineffective and too much may cause adverse effects.

Definitions: HempHemp: a low-THC (<0.3%) strain of

Cannabis sativa. Hemp is not utilized for psychoactive

effects; rather, hemp is used to make a variety of consumer products including paper, textiles, clothing, health food, and bio-fuel.

Hemp is legally grown in a number of countries including Spain, China, Japan, Korea, France, and Ireland.

Cannabinoids: BasicsCannabinoids are biologically active molecules

that have a number of regulatory functions in the human body. 

Currently cannabinoid biology is poorly understood. 

Humans have endocannabinoid receptors known as CB1 and CB2.

CB1 is found in the brain and nervous systemCB2 is found in certain immune system cells.

Humans produce “endocannabinoids” including anandamide (N-arachidonoylethanolamine) and 2-AG (2-arachidonoylglycerol).

Cannabinoids, cont.Anandamide is an endogenous ligand that

is involved in binding THC and CBD to endocannabinoid receptors .

2-AG is also an endogenous ligand and is involved with neuromodulation in CB1 receptors.

Both naturally occurring cannabinoids, e.g., THC and CBD, and synthetic cannabinoid molecules, can bind the human endocannabinoid receptors and have biologic activity. 

Medical Marijuana“Medical Marijuana” is a misnomer; the compounds

that may have therapeutic benefit are the cannabinoids.Regardless of the species, the main active ingredients

currently utilized for the desired medicinal effects are delta-9 tetra-hydro-cannabinol (THC), a psychoactive

cannabinoid.cannabidiol (CBD), a non-psychoactive cannabinoid.

Buds and leaves of the plant are smoked, vaporized, and/or cooked (and drunk or eaten) for their effects. 

Cannabinoid extractions may also produce therapeutic benefits; e.g., % of THC or CBD can be assessed and manipulated.“Charlotte’s Web” is a CBD-based product with low

(<0.3%) THC.

Legal synthetic forms of medical marijuana

Two legal synthetic forms of marijuana are available in the United States and approved by the Food and Drug Administration.Dronabinol (marinol), is a Schedule III oral medication

approved by the Food and Drug Administration for the treatment of AIDS-related wasting, and chemotherapy-induced nausea and vomiting. Dronabinol is a capsule which must be taken whole orally; this

may prove problematic in the face of nausea or vomiting. Additionally, the onset to symptom relief with dronabinol is

significantly longer versus smoked marijuana. Nabilone (cesamet), is an oral capsule with properties

similar to dronabinol but is a Schedule II medication due to a possible higher abuse potential.

Legal synthetic forms of medical marijuana, cont.

The third form of legal medical marijuana is known as Sativex, a cannabinoid-based oral-mucosal spray.

Sativex is currently approved in Canada and the United Kingdom for symptomatic relief of neuropathic pain in multiple sclerosis.

Sativex is also approved in Canada as an adjunctive analgesic treatment in patients with cancer pain. Sativex is currently undergoing late stage clinical testing in

Europe and the United States for similar indications. Sativex contains equal amounts of THC and CBD. Sativex is rapidly absorbed and easy to titrate, which may

make it a more effective and easy-to-use medication that dronabinol.

Onset of desired effects typically occurs within minutes.

Evidence-based Medical Indications for Marijuana

There have been no published clinical trials on the use of medical marijuana/cannabinoids in the pediatric and adolescent populations

Research has identified areas of therapeutic potential for these molecules, including analgesia in chronic neuropathic pain.appetite stimulation in debilitating disease.spasticity in multiple sclerosis.cachexia.

THC and CBD have been utilized either alone or together.

ResourcesAmerican Academy of Pediatrics:

www.aap.org/marijuana National Institute on Drug Abuse: www.drugabuse.gov Office of National Drug Control Policy:

www.whitehouse.gov/ondcp Smart Approaches to Marijuana:

http://learnaboutsam.comSubstance Abuse and Mental Health Services

Administration: www.samhsa.gov US Department of Health & Human Services, Office of

Adolescent Health: www.hhs.gov/ash/oah/resources-and-publications/publications/substance-abuse.html