Transcript SAHM Annual Meeting 2015 Hot Topic: The new American

Seth Ammerman, M.D.
Clinical Professor
Department of Pediatrics
Division of Adolescent Medicine
Stanford University
Lucile Packard Children’s Hospital Stanford
[email protected]
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.
Objectives
 Learn 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 1
 Schedule 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 2
 Schedule 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 3
 Schedule 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 4
 Schedule 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 5
 Schedule 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: Marijuana
 The 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 welldefined.
 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: THC
 THC: 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: Hemp
 Hemp: 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: Basics
 Cannabinoids 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 system
 CB2 is found in certain immune system cells.
 Humans produce “endocannabinoids” including
anandamide (N-arachidonoylethanolamine) and 2-AG (2arachidonoylglycerol).
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 chemotherapyinduced 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.
Resources
 American 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.com
 Substance 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-andpublications/publications/substance-abuse.html