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Cannabinoids: a
pediatric
perspective
Christopher Campbell
PGY2 Pediatric Pharmacy Resident
Augusta University Medical Center
University of Georgia College of Pharmacy
Disclosure
I do not have (nor does any immediate family member
have) actual or potential conflict of interest, within the
last twelve months; a vested interest in or affiliation
with any corporate organization offering financial
support or grant monies for this continuing education
activity; or any affiliation with an organization whose
philosophy could potentially bias my presentation.
Objectives
1. Describe the clinical pharmacology of medical cannabinoids in a
pediatric patient population.
2. Identify the evolving regulatory issues of cannabinoid use in the
United States.
3. Analyze current clinical data for cannabinoid use in a pediatric patient.
4. Discuss pediatric considerations regarding overuse and misuse of
cannabinoids.
Definitions
Cannabis
◦ Hemp plant from which marijuana is derived
◦ 3 species (C. sativa, C. indica, C. ruderalis)
Marijuana
◦ Dried leaves, flowers, stems, and seeds from the hemp plant
Cannabinoid
◦ Chemicals that interact with specific receptors located within
different parts of the central nervous system
http://www.drugabuse.gov/publications/drugfacts/marijuana
Types of Cannabinoids
 delta – 9 – tetrahydrocannabinol (THC)
◦ The psychoactive cannabinoid most commonly associated with marijuana
 Cannabigerols (CBG)
 Cannabichromenes (CBC)
 Cannabidiols (CBD)
 Cannbinol (CBN) and cannabinodiol (CBDL)
 Others (cannabicyclol (CBL), cannabielsoin (CBE), cannabitriol (CBT)
http://learnaboutmarijuanawa.org/factsheets/cannabinoids.htm
What’s the difference?
Cannabinoids
Psychoactive
Not Psychoactive
• Cannabinol (CBN)
• Cannabinodiol (CBDL)
• delta – 9 –
tetrahydrocannabinol (THC)
• Cannabigerols (CBG)
• Cannabichromenes (CBC)
• Cannabidiols (CBD)
http://learnaboutmarijuanawa.org/factsheets/cannabinoids.htm
Endocannabinoid System
 Anandamide
 1992: naturally occurring substance that binds to CB1 receptors was
discovered
 Shown to have inhibitory effects on serotonin type 3 receptors (antiemetic, analgesia, etc)
 2 receptors types found in early 1990s
 CB1
 Expressed on presynaptic peripheral and central nerve terminals
 Some exposure on peripheral organs
 CB2
 Concentrated in peripheral tissues and immune cells
Baron EP. Headache. June 2015
Endocannabinoid System
CB1
CB2
 One of the most abundant found in the
peripheral and central nervous system
 Primarily located on
immune cells and tissues
 Distributed throughout the brain:
 Pleasure
 Memory
 Thought
 Concentration
 Sensory and time perceptions
 Coordinated movement
 When activated, affect
inflammatory and
immunosuppressive activity
 Sparsely found in the cardiopulmonary
centers in the brainstem
Baron EP. Headache. June 2015
 Control release of cytokines
and cell migration
Cannabinoid Receptor Effects
Physiologic effects
• Tachycardia, hypertension, dry mouth and throat
Psychologic effects
• Elation, euphoria, increased appetite, heightened
perception, paranoia, anxiety, irritability, impaired short
term memory, poor coordination and balance
Baron EP. Headache. June 2015
http://www.nature.com/nrc/journal/v3/n10/images/nrc1188-i1.jpg
http://www.tokeofthetown.com/2012/01/worth_repeating_marijuana_treats_anxiety_and_depre.php
THC vs Cannabidiol
Friedman D, Devinsky O. N Engl J Med 373; 11
THC vs Cannabidiol
CANNABIDIOL
◦ Isolated in 1963
◦ Most abundant cannabinoid, contributing up to
40% of cannabis resin.
◦ Does not appear to bind to either CB1 or CB2
◦ Interacts with ion channels, enzymes, and other
receptors
◦ Inhibits cyclooxygenase and lipoxygenase – antiinflammatory and analgesic effects
◦ May be an inverse agonist because several
studies have shown that it decreases the
psychotropic activity of THC
◦ May enhance the activity of the endogenous
cannabinoid, anandamide
◦ May have an anti-anxiety effect
http://learnaboutmarijuanawa.org/factsheets/cannabinoids.ht
m
Baron EP. Headache. June 2015
THC
◦ Isolated in 1964
◦ Partial agonist at both CB1
and CB2 receptors but also
acts at non-CB receptors
◦ Possible pro-convulsant
◦ Deleterious effects on brain
development and cognition
Pharmacokinetics
THC
• Onset: 30 minutes after inhalation
and 2 to 4 hours after ingestion
• Half-life: 7 days
• Large volume of distribution
CBD
• Onset: similar
• Half-life: 9 hours
• Bioavailability: 13 – 19%
• Metabolized by CYP3A2/4
enzymes
Borgelt LM. Pharmacotherapy 2013; 33(2):195-209
Ashton, CH. The British Journal of Psychiatry Feb 2001, 178 (2) 101-106
A brief history lesson…
Cannabinoid History
Hemp plants
used as early
as 4000 BC in
Western and
Central Asia
Use diminished
with the
introduction of
phenobarbital
(1912) and
phenytoin (1937)
1851: United States
Pharmacopeia
classified marijuana as
a legitimate medical
compound
1400 – 2000
BC: Medical
uses
documented
Baron EP. Headache. June 2015
Borgelt LM. Pharmacotherapy 2013; 33(2):195-209
Friedman D, Devinsky O. N Engl J Med 373; 11
Victorian-era
neurologists used
Indian hemp to
treat epilepsy and
reported success
Regulatory History
Marihuana Tax
Act of 1937
• Cannabis identified as a
drug of abuse by minority
and low income populations
in 1930’s
1930’s: Drug of
Abuse
Baron EP. Headache. June 2015
• Heavy tax for cannabis and
hemp use for medicinal or
industrial uses
• Failure to comply was faced
with prison and large fines
• Cannabis preparations are
removed from the United
States Pharmacopoeia and
National Formulary
1941: USP/NF
Regulatory History
Recreational
marijuana use
surges in 1960’s
and early 1970’s
1988: failed
attempt to
reschedule to
Schedule II
Controlled
Substances Act of
1970: cannabis is
labelled as a
Schedule 1
substance also
with heroin and
LSD
Baron EP. Headache. June 2015
2001 and
2006: two
more failed
attempts
2001 Department of
Health and Human
Services filed a
patent for
cannabinoids
awarded in 2003 for
“cannabinoids as
antioxidants and
neuroprotectants”
2015: federal
judges are
currently
reviewing
whether
reclassification is
warranted
http://patientsoutoftime.org/wp-content/uploads/2015/01/cannabis-states.png
http://america.aljazeera.com/.jpg
http://www.lexisnexis.com/Communities/cfsfile.ashx/__key/communityserver-blogs-components-weblogfiles/00-00-00-0022/1641.potmap.jpg
Georgia Marijuana Act
 “Haleigh’s Hope Act” signed into law in
April 2015 by Governor Nathan Deal
 Allows for possession of up to 20 ounces
of cannabis oil following a physician order if
a patient suffers from 8 serious medical
conditions
 Oil must not contain more than 5% THC
 Georgia’s medical marijuana law does not
legalize the production or sale of
marijuana, it simply decriminalizes its
possession by certain qualified individuals.
http://www.georgiacannabis.org/obtain-medical-marijuana/
http://www.cnn.com/2015/04/16/us/georgia-medical-marijuana-bill-signing-haleigh-cox/
http://www.ajc.com/news/news/medical-marijuana-bill-georgia-facts/nkwWM/
Cancer
Crohn’s disease
Lou Gehrig’s disease
Mitochondrial disease
Multiple sclerosis
Parkinson’s disease
Seizure disorders
Sickle cell disease
Legal Marijuana*
*According to the Federal government
 Investigational New Drug Program – closed in 1992
 12 patients allowed to continue; two patients remain in the program
 Federally approved source of research-grade cannabis at a farm at the
University of Mississippi
 Cannabis-derived pharmaceuticals
◦ Dronabinol (schedule III) and Nabilone (schedule II)
 Treatment of nausea and vomiting associated with cancer
 Treatment of anorexia associated with weight loss in patients with acquired
immune deficiency syndrome (dronabinol)
 Nabiximols (not FDA approved)
 Symptomatic relief of spasticity in adults with multiple sclerosis
 Symptomatic relief of neuropathic pain in patients with MS
 Intractable cancer pain
Baron EP. Headache. June 2015
Lexicomp. “Dronabinol”. Accessed October 13, 2015.
Lexicomp. “Nabilone”. Accessed October 13, 2015
American Academy of Pediatrics
The federal and state governments should
establish robust health surveillance
regarding the impact of marijuana,
particularly on children and adolescents.
In states that have legalized marijuana for
recreational use, the AAP strongly
recommends strict enforcement of rules and
regulations that limit access, marketing and
advertising to youth.
Research and development should be
conducted of pharmaceutical cannabinoids.
The AAP recommends changing marijuana
from a DEA Schedule 1 to a DEA Schedule 2
to facilitate this research.
Where marijuana is sold legally, either for
medicinal or recreational purposes, it should
be contained in child-proof packaging to
prevent accidental ingestion.
https://www.aap.org/en-us/about-the-aap/aap-press-room/pages/American-Academy-ofPediatrics-Reaffirms-Opposition-to-Legalizing-Marijuana-for-Recreational-or-MedicalUse.aspx
The AAP discourages adults from using
marijuana in the presence of children
because of the influence of role modeling by
adults on child and adolescent behavior.
End of the history
lesson…
Baron EP. Headache. June 2015
Pediatric Cannabinoid
(Possible) Indications
 Epilepsy
 Attention-deficit hyperactivity disorder
 Autism spectrum disorder
 Perinatal Brain Injury
 Neuroblastoma
Why cannabinoids in
epilepsy?
1) Endocannabinoid system
◦ Anandamide can affect excitability in the neuronal networks by
activating the transient receptor potential (TRP) cation channel
2) Epilepsy patients have defects in endocannabinoid
◦ Patients with newly diagnosed temporal-lobe epilepsy had significantly lower
levels of anandamide in CSF than healthy controls
◦ Tissue from patients undergoing surgery for epilepsy had lower levels of CB1
receptor messenger RNA vs. cadavers without epilepsy
3) Found that mice, anandamide levels rise after seizures
suggesting a role in anti-seizure activity
Friedman D, Devinsky O. N Engl J Med 373; 11
CBD and Antiepileptic Effects
At high concentrations, activates the
nuclear peroxisome proliferatoractivated receptor-gamma
Inhibits the cellular uptake
and degradation of the
endocannabinoid anandamide
Modulates intracellular calcium
concentration and inhibits Ttype calcium channels
Cilio MR et al. Epilepsia. 2014. 55 (6): 787-790
Cannabinoids for epilepsy: Cochrane
Review
Objective
• Assess the efficacy of marijuana, or one of marijuana’s constituents in the
treatment of people with epilepsy
Inclusion
• 4 randomized reports including a total of 48 patients, each of which used
cannabidiol as the treatment agent
Results
• No reliable conclusions on efficacy but 200 – 300 mg daily of cannabidiol
was safely administered to a small number of patients for a short period
of time
Gloss D, Vickrey B. Cochrane Database of Systematic Reviews 2012, Issue 6
American Academy of
Neurology
Conclude that “for patients with epilepsy, data are
insufficient to support or refute the efficacy of
cannabinoids for reducing seizure frequency”
There is NOT sufficient evidence to prescribe CBD or
recommend self-treatment with smoked marijuana
Koppel BS et al. Neurology 2014; 82:1556-1563
Why are parents using
cannabis?
Anecdotal cases of
children
successfully
treated with
medical marijuana
(CBD enriched
preparations)
Cilio MR et al. Epilepsia. 2014. 55 (6): 787-790
Prominent
internet and
national media
attention
Belief that
treatments
derived from
natural products
are safer or more
effective is
common and
potentially
dangerous
Charlotte
 Charlotte is a little girl from Colorado
with Dravet syndrome
 Frequent bouts of febrile and afebrile
status epilepticus
 Failed multiple medications:
◦ Levetiracetam, oxcarbazepine, topiramate,
zonisamide, valproate, clobazam, clonazepam,
and diazepam
 At 5 years of age, had significant
cognitive and motor delays, required a
feeding tube, and needed full assistance
with activities of daily living
 50 generalized tonic-clonic seizures per
day
http://www.cnn.com/2013/08/07/health/charlotte-child-medical-marijuana/
Charlotte’s Web
A high concentration CBD/THC strain of
cannabis produced by a medical
marijuana group in Colorado
Charlotte’s Web, supplied by Realm of
Caring, is based out of Colorado and
parents and families are moving there to
attempt treatment
Parents began
giving Charlotte
low doses of
plant extract and
slowly increased
the dose over
time
Month 3: >90%
reduction in
generalized tonicclonic seizures and
weaned from other
AEDs
http://www.cnn.com/2013/08/07/health/charlotte-child-medical-marijuana/
Month 20: 2-3
nocturnal generalized
tonic-clonic seizures per
month, feeds and drinks
by mouth by herself and
autistic behaviors have
improvement, walking
and talking
Parental reporting of response to oral
cannabis extracts for treatment of
refractory epilepsy
Methods:
• Retrospective chart review of children and adolescents who were given oral cannabis extracts
(OCE) for treatment of their epilepsy
• Seizure response was based on parental report of total seizure frequency prior to initiating OCE
treatment
• Deemed a responder if parental report of >50% reduction in seizure frequency
Patients:
• 75 patients (45.3% male)
• Mean age 7.33; range 0.5 – 18.25
Results
• 43/75 (57%) of parents reported some improvement
• 25/75 (33%) reported to have >50% reduction in seizures
• 2/75 (0.3%) reported to be seizure free by their last follow up
• No difference in response rate between different types of oral cannabis extract (CBD,
CBD+other OCE, THC only, other)
Press CA et al. Epilepsy and Behavior 45 (2015) 49-52
Parental reporting of response to oral
cannabis extracts for treatment of
refractory epilepsy
Other Improvements
Adverse Effects
• Improved behavior/alertness in
25/75 (33%)
• Improved language 8/75 (11%)
• Improved motor skills 8/75 (11%)
• Increased seizures 10/75 (13%)
• Somnolence/fatigue 9/75 (12%)
• GI symptoms 8/75 (11%)
Press CA et al. Epilepsy and Behavior 45 (2015) 49-52
Parent survey of cannabidiolenriched cannabis use
 Stanford University
 Survey of 24 questions
 Diagnosis and seizure types
 Parental-reported effect of cannabidiol-enriched cannabis
on the child’s seizure frequency and side effects
 Administered to Facebook group of 150 parents
supporting the use of cannabidiol-enriched cannabis
to treat children with treatment-resistant epilepsy
Porter BE et al. Epilepsy Behav. 2013; 29(3):574-577
Parent survey of cannabidiolenriched cannabis use
Population Demographics
Results
• Age range: 2 – 16 years old
• Seizure Types:
• Dravet syndrome = 13
• Doose = 4
• Lennox-Gastaut syndrome = 1
• Idiopathic early-onset epilepsy = 1
• 18/19 patients experienced treatment resistant
epilepsy for more than 3 years before trying
CBD
• Unsuccessfully tried median 12 other
antiepileptics
• Seizure Frequency pre-CBD: 2 per week to 250
per day
• 16/19 (84%) reported a reduction in their
child’s seizure frequency
• 2/16 reported to be seizure free
• 8/16 reported a greater than 80%
reduction in seizure frequency
• 3/16 reported a greater than 50%
reduction in seizure frequency
• 12/19 patients weaned their child from
another AED
• Other effects:
• Better mood (15/19, 79%)
• Increased alertness (14/19, 74%)
• Better sleep (13/19, 68%)
• Drowsiness (7/19, 37%)
• Fatigue (3/19, 16%)
Intervention
• Dose Ranges: 0.5 mg/kg/day to 28.6 mg/kg/day
• THC: 0 to 0.8mg/kg/day
Porter BE et al. Epilepsy Behav. 2013; 29(3):574-577
Parent survey of cannabidiolenriched cannabis use
 Cannot verify:
 Dose
 Response
 Parents have an interest in using CBD for their children’s
seizures which may select for positive outcomes
 Conclusions:
 Parents report reduced seizures in a refractory group of childhood
epilepsies which warrants further study
 Favorable side effect profile with potential benefits in cognition and mood
Porter BE et al. Epilepsy Behav. 2013; 29(3):574-577
Perceived efficacy of
cannabidiol enriched cannabis
extracts
Population Demographics
• 117 respondents, median age 6 (3-10)
• Number of failed medications, median 8 (4-12)
• Failed ketogenic diet therapy before CBD exposure, n =
53 (45.3%)
• Epilepsy Conditions, n (%)
• Infantile spasms, 45 (38.5)
• Lennox-Gastaut syndrome, 24 (20.5)
• Infantile spasms and/or Lennox-Gastaut syndrome, 53
(45.2)
• Dravet syndrome, 15 (12.8)
• Other/unknown, 44 (37.6)
CBD Exposure
• Duration, months, median 6.8 (3.8-9.8)
• Continued CBD treatment at time of survey, 93%
• CBD product with at least 15:1 ratio of CBD to THC, 83.5%
• CBD dosage, mg/kg/day, n = 46 median 4.3 (2.9 – 7.5)
• Number of concomitant medications 2 (0 – 3)
Hussain SA. Epilepsy and Behavior 47 (2015) 138-141
Results
• Efficacy
• N = 100 (85%) reported a
reduction in seizure
frequency
• N = 16 (14%) reported
complete seizure
freedom
• 86% reported changes in
frequency within 14 days
Clinicaltrials.gov
 88 studies found related to “cannabidiol”
 30 studies related to epilepsy
 6 studies related to dementia/delirium
 14 studies related to autoimmune diseases
 4 studies found related to “cannabidiol AND
pediatrics”
 Many more for Dravet’s syndrome, Lennox—Gastaut
syndrome, and cannabidiol
Clinicaltrials.gov
Cannabidiol Use at Augusta
University
http://www.gru.edu/research/studies/cannabidiol/images/doctor.png
http://www.gru.edu/research/studies/cannabidiol/release1214.php
Epidiolex® (cannabidiol) in
Treatment Resistant Epilepsy
Objective:
• Ten centers have independent FDA approved open-label Expanded Access
Programs and have treated children and young adults with treatment-resistant
epilepsies with pure CBD
Intervention:
• Open-label cannabidiol given as a liquid and titrated to a daily dose of 25mg/kg
Results:
• 123 patients with 12 weeks of continuous exposure
• Median reduction of -46% at week 12
• Dravet patients: reduction of -50% by week 12
• LGS: reduction of -52% by week 12
• Adverse reactions: somnolence (21%), diarrhea (17%), fatigue (17%), and
decreased appetite (16%)
Devinsky O. AAN 67th Annual Meeting Abstract. April 13, 2015
Clinicaltrials.gov
A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in
Children and Young Adults With Dravet Syndrome
• Randomized, double blind, placebo controlled trial
• Primary Outcome Measures:
• Mean percentage change from baseline in convulsive seizure frequency
during the maintenance period (Day 15 to the end of the evaluable period)
• Secondary Outcome Measures:
• Convulsive seizure free
• Adverse effects
• Caregiver Global Impression of Change (CGIC)
• GW Pharmaceuticals
A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P; CBD)
as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome
in Children and Adults
Clinicaltrials.gov
ADHD and Autism
 Sparse data
 Gaining popularity particularly on social media sites
 Mice models have demonstrated altered endocannabinoid signaling in the
CNS and reported as a promising role for cannabis as treatment by the
mainstream media
https://www.facebook.com/Moms4MJ?fref=nf
Dronabinol in Autism Case
Report
 Six year old boy with early infant
autism
 Intervention: dronabinol drops, one
drop (0.62mg) in the morning which
was gradually increased day to day
 Symptom severity was determined by
using the ABC (Aberrant Behavior
Checklist)
 Results:
 Maximum tolerated dose effect reached
(2 drops in the AM, 1 midday, 3 drops in
the evening = 3.62 mg/day)
 ABC subscales significant decreased over
6 months
Kurz R et al. Cannabinoids 2010; 5(4):4-6
Dronabinol Self-Injurious
Behavior (SIB) Case Series
Patients:
• 10 mentally handicapped adolescent patients exhibiting treatmentresistant self-injurious behavior
• Failed previous medications (range 4 -17)
Intervention:
• dronabinol 2.5 mg BID – 5 mg QID
Results:
• 7/10 had a significant improvement in their SIB and overall
mood/well being as reported by caregivers
• 2/10 experienced agitation and drug was discontinued
• Follow up 6 months later, patients still had benefit
Kruger T. J Dev Behav Pediatr. 2006; 27:433
Perinatal Brain Injury
 Can be induced by:
 Neonatal asphyxia
 Neonatal hypoxia-ischemic encephalopathy (HIE)
 Stroke-induced focal ischemia
 Results in:






Glutamate excitoxicity
Neuroinflammation
Oxidative stress
Apoptotic-necrotic cell death
Brain lesions
Long-lasting functional impairment
Current therapies for HIE
 Hypothermia – only clinical intervention
that has shown some effectiveness in
reducing brain damage
 Magnesium sulfate – inhibits glutamate
excitotoxicity
 N-acetylcysteine allopurinol – reduce
oxidative stress
 Minocycline – modulates the
neuroinflammatory response
 Endocannabinoid system responds early to neuronal injury
 Prevents glutamate excitotoxicity, activation of cell death pathways,
infiltration of circulating leukocytes across the blood brain barrier
Fernandez-Lopez D. et al. Brain Sci 2013, 3, 1043-1059
Experimental Models
Newborn hypoxic-ischemic
brain damage in piglets
Newborn hypoxic-ischemic
brain damage in mice
Pazos MR. et al. Neuropharmacology 71 (2013) 282-291
Castillo A. et al. Neurobiology of Desease4 37 (2010) 434 - 440
• CBD reduced the density of
necrotic neurons
• Modulation of inflammation
and oxidative stress
• CBD reduced cell death in immature mouse
brain
• Modulation of glutamine release, cytokine
production, and COX-2 expression
Neuroblastoma
 Proposed
antitumor activity of cannabis preparations
 Vanilloid receptors/peroxisome proliferator activated receptors
 In vitro Testing
 CBD and THC reduced viability of neuroblastoma cells in a dose- and timedependent way
 CBD treatment had a significantly better response vs. THC treated cells in a
single cell line (p = 0.0004)
 In vivo Testing
 Mice were treated with daily intraperitoneal injections of THC, cannabadiol,
ethanol, or untreated
 Results:
 THC and CBD groups has significantly reduced tumor growth
Fisher T. Current Oncology. 2016. 23: S15-S22
What is the harm?
Harm to Marijuana
 50-70% more carcinogenic ingredients than cigarette smoke
that can lead to lung cancer
 Cardiac adverse effects
 tachycardia, hypertension, syncope, palpitations, transient ischemic
attacks
 Central nervous system adverse effects
 psychological dysfunction, memory formation, depersonalization,
paranoia, anxiety, changes in mood
 Gateway drug
Seamon MJ. Am J Health-Syst Pharm 2007 (64): 1037-1044
Emergency Department
Visits
Three groups of patients:
1) exacerbation of chronic issues (asthma) because of
smoking marijuana
2) acute effects from eating too many edibles
◦ tachycardia, hallucinations, or cyclic vomiting
3) children admitted to the ED
Berger E. Annals of Emergency Medicine. 2014 (64) 4
Pediatric Marijuana Exposures
in a Medical Marijuana State
Methods and Objective
• Retrospective cohort study from January 1, 2005 through December 31, 2011.
• To compare the proportion of marijuana ingestions by young children who sought
care at a children’s hospital in Colorado before and after modification of drug
enforcement laws in October 2009 regarding medical marijuana possession
Patients Population
• 1378 patients younger than 12 years old evaluated for unintentional ingestions:
• 790 patients before September 30, 2009 and 588 patients after October 1, 2009
• Median age was 2.6 years (IQ range, 1.6 – 3.0)
• 56.8% male
Wang GS. et al. JAMA Pediatrics 2013 (167) 7
Colorado Case
In 2009, the
state
modified
enforcement
efforts
Medical
Marijuana
passes in 2000
No ED visits
by children in
Colorado for
marijuana
exposure
Berger E. Annals of Emergency Medicine. 2014 (64) 4
Mid 2009 –
2011 – 14
pediatric
marijuana
exposure visits
Pediatric Marijuana Exposures
in a Medical Marijuana State
Results:
• Annual ED census of 65,000 visits:
• 0 of 790 (0%) to 14 of 588 (2.4%) (p<0.001)
• Those exposed: range 8mo to 12 years, 64.2% males
• Symptoms included: lethargy (9), ataxia (1),
respiratory insufficiency (1)
• 8 admissions
• 2 admissions to the ICU
• 8 of 14 cases involved medical marijuana and 7
were from food products
Wang GS. et al. JAMA Pediatrics 2013 (167) 7
Poison Control Centers
 Pediatric marijuana exposures call volume increased by
30.3% between 2005 and 2011 in the states where laws
decriminalizing marijuana has been passed
 Most parents and grandparents say the child got into an
edible
Colorado State of the State address in early January
 “Just as we must implement the voters’ wishes on marijuana, we are
obligated to make sure that children and parents understand brain
development and the risks of underage use” – Governor John
Hickenlooper
Berger E. Annals of Emergency Medicine. 2014 (64) 4
Packaging and Labeling
 Products have labels and packaging that can be easily mistaken for
conventional food products by young children
 Most products lack regulatory and safety packaging
http://cdn.shopify.com/s/files/1/0754/5733/products/bottle_large.gif?v=1422330668
http://www.drugfree.org/wp-content/uploads/2011/07/Pill-bottles-7-8-11-2.jpg
https://upload.wikimedia.org/wikipedia/commons/4/43/Surgeon_General's_warning_cigarettes.jpg
Medical Marijuana and the
Role of the Pharmacist
 Patient and Family Counseling
 Many of the detrimental neurocognitive effects of acute marijuana
intoxication have a hangover effect with effects lasting at least 1 day after
last use and with subtle effects even measurable 1 month later among
adolescents
 Doubling of the odds of fatal motor vehicle accident for adolescents and
adults driving under the influence of cannabis
 Adolescent use may be associated with a decline in intelligence quotient
 Adverse psychiatric issues with heavy use
 Medical Professional Education
 Educate on the differences between cannabinoids and help remove the
stigma around appropriate and legal use of cannabidiol products
 CBD potent inhibitor of CYP 2B6, 2C8, 2C9, 2C19, and 3A4
Hadland SE et al. J Dev Behav Pediatr 36:115-123, 2015
Conclusions
 Medical cannabinoids may have a place in pediatric care
especially in refractory epileptic states
 Current regulation of cannabinoid use is changing allowing for
better access to medications and increased research in these
areas
 The legalization and widespread availability also increases the
risk of unintentional and intentional administration in children
leading to an increase in emergency room visits
 Pharmacists should support continued research in this area
and offer counseling and assistance with medication
management
Toward Drugs Derived from
Cannabis
Methods
• Controlled trial of 9 patients with uncontrolled temporal lobe
epilepsy who had failed treatment with multiple medications
Intervention
• Four patients in cannabidiol arm: 200 mg daily for 3 months
• Five patients in placebo arm: placebo daily for 3 months
Results
• Group 1: two patients seizure-free for the entire three months,
one patient with partial improvement
• Group 2: no patient showed improvement
Mechoulam R. Carlini EA. Naturwissenschaften 65, 174-179 (1978)
Chronic Administration of Cannabidiol
to Healthy Volunteers and Epileptic
Patients
Population:
• 16 subjects aged 22 – 35
• 11 men and 5 women
• Average weight of 65 kg
Intervention
• Group 1: Cannabidiol 3 mg/kg daily for 30 days
• Group 2: Placebo daily for 30 days
Results
• Group 1: somnolence (2)
• Group 2: withdrew (1), palpitations (1)
• Neurological and clinical examinations, EEG and ECG tracings, blood and urine
analyses were within normal limits
Cunha JM et al. Pharmacology 21: 175-185 (1980)
Chronic Administration of Cannabidiol
to Healthy Volunteers and Epileptic
Patients
Population
• 15 epileptic patients, 11 women and 4 men, aged 14-49 (average 24)
• Patients with frequent convulsions for at least 1 year who were not reacting
satisfactorily to the prescribed antiepileptic drugs they were receiving
Intervention
• Group 1: cannabidiol 200mg – 300mg daily
• Group 2: placebo
• Scored 0-3 : 0 = complete improvement, 1 = partial improvement, 2 = small
improvement, 3 = without improvement
Results
• Group 1: 50% (4 of 8 patients) showed complete improvement (median = 0), 1 patient
with partial improvement, 2 patients showed small improvement, 1 patient without
improvement
• Group 2: 7/8 patients reported no improvement (median 3); 1 patient showed
complete improvement (median 0)
Cunha JM et al. Pharmacology 21: 175-185 (1980)
Anticonvulsant effect of
cannabidiol
Methods
• Controlled trial of 12 institutionalized, mentally handicapped patients with
frequent seizures uncontrolled with conventional anticonvulsant therapy
Intervention
• Group 1: cannabidiol 300 mg daily for the first week then 200 mg daily for
the next three weeks
• Group 2: placebo
Results
• No statistically significant different in seizure frequency between the two
groups
• Mild drowsiness reported
Ames, FR et al. South African Medical Journal 1985; 69:14
Double-blind clinical study of
cannabidiol as a secondary
anticonvulsant
Methods
• Randomized, controlled, cross-over trial of 12 patients with incompletely
controlled epilepsy
Intervention
• Patients received:
• Conventional antiepileptics for 3 months
• Placebo for 6 months
• Randomized to:
• Cannabidiol 100 mg three times a day for 6 months then placebo for 6 months
• Placebo for 6 months then cannabidiol 100 mg three times a day for 6 months
Results
• “no discernable effect”
• “no effects on seizure pattern, character or frequency”
Trembly. Marijuana ‘90 Internation Conference on Cannabis and Cannabinoids 1990.
Christopher Campbell
PGY2 Pediatric Pharmacy Resident
Augusta University Medical Center
University of Georgia College of Pharmacy
[email protected]
[email protected]
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