Marijuana and Adolescents: Truth and Consequences Clinical Advances in Pediatrics Symposium Children s Mercy Park September 28, 2017 Disclosure Statement I have no actual or potential conflict of interest in relation to this program William P. Adelman MD, FAAP Division Director, Adolescent Medicine Children s Mercy Kansas City Associate Professor of Pediatrics wpadelman@cmh.edu 2 The Children's Mercy Hospital, 2014. 11/14 OBJECTIVES Secondary Objectives 1) Identify adolescence as uniquely vulnerable to the neurotoxic effects of marijuana 2) Recognize the current legal status of marijuana in the United States and its practical implications for adolescents 3 1. Identify the AAP evidence-based Position on marijuana including medical marijuana 2. Define terms associated with marijuana for precise discussion by pediatricians 3. Describe mechanisms of action of marijuana and cannabinoids on the brain 4. Understand some of the known harms of marijuana on the developing brain 4 State of Marijuana in US Numerous states have legalized or are considering legalization of marijuana AAP has published an evidence-based position paper and clinical report Many providers are not aware of the current state of the evidence regarding the effects of marijuana and how to discuss these issues with patients and their families 5 6 1
2015 Adolescent Substance Use (used in the last 30 days) Pediatrics 135:3 March 2015 14% 22% 7% 13%.3% 2% 7 http://pediatrics.aappublications.org/content/135/3/e769.full.pdf+html?sid=9a7cbd0abee5-464a-9c6f-02bb12f2cc92 8 Pediatrics 135:3 March 2015 Pediatrics 139:3 March 2017 9 10 AAP Marijuana Policy Statement: Recommendation #1* Adolescents Are Vulnerable 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. *There are 10 total recommendations Early substance use = high risk addiction Adolescent immaturity during critical development period = vulnerability Impulsiveness and excitement seeking Difficulty delaying gratification Poor executive function and inhibitory control Image Source: PNAS 101:8174 8179, 2004 National Academy of Scinces, U.S.A. 11 12 2
As Brain develops, there is NO safe age for marijuana THC Receptors Toddler: Cerebellum Balance, Walking, Coordination, sensory processing Preschool: Amygdala Emotional Regulation School Age: Nucleus Accumbens Motivation, Achievement Adolescent: Prefrontal Cortex Planning, organizing, Impulse Control 13 14 THC Receptors in Functional Areas of Brain Vulnerability in youth Pooled longitudinal studies. N =2537 to N=3765. Silens et al. Lancet Psychiatry, 1,: 286 293, 2014S 15 Conditional risk of use disorder in adolescents as high as 40% Daily use of MJ <age 17 associated with substantially increased risk of: Persistent MJ Dependence (OR=18) High school drop out (OR=3) Use of other drugs (OR=8) Suicide attempts (OR=7) 16 Clinical consequences of cannabis MJ use associated with depressive symptoms Significant Evidence Base Documenting Harms 18 The Children's Mercy Hospital, 2014. 11/14 3
Marijuana causes damage to corpus callosum Increased risk of psychosis 19 20 Cannabis and psychosis Prospective exposure cohort study 10 yr prospective cohort of 1923 German youth (14-24 at baseline) Examination of change over 3 time points OR = 2.2 Kuepper et al British Med J. 2011 21 OR = 1.9 Cannabis and cognitive impairment IQ measured age 13, 38; N=1037 MJ use measured age 18, 21, 26, 32, 38 IQ decline associated with regular use and dependence, dose response related to persistence None Some use 1 wave 2 waves 3+ waves Regular use +1-1 -3-2 -5 Dependence +1-1 -2-3 -6 No difference with controls for education, recent use, other substances, schizophrenia Meier et al. PNAS. 2011 Adolescent onset worse, -8 points for 3+waves 22 Measurable IQ deficits in Users MJ Use Disorders Addiction spectrum problems 23 The Children's Mercy Hospital, 2014. 11/14 4
Functional problems in youth School failure and academic problems Early pregnancy Criminal behavior Vocational problems Progression to other substance use Psychiatric symptoms 25 AAP Opposes Marijuana Use (In anyone with a brain) Known Harms outweigh any known benefit 26 Recommendation #2 The AAP opposes medical marijuana outside the regulatory process of the US Food and Drug Administration. 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. 27 Evidence for Recommendation #2 AAP-The current system of medical marijuana does not routinely include standardization of purity, dose, effects, side effects, or indications. It is outside the FDA. California Society Addiction Medicine-2010-Violates core principals of medicine 1) administering any medication via drawing hot smoke into the lungs is inherently unhealthy 2) although use of vaporizers, sprays, and tinctures solves problems inherent in smoking, treatment of illness without standardized dose or content of the medication remain a safety issue 3) if the public wants to legalize marijuana, there is no reason to force physicians to be gatekeepers in a manner that enables liberal access to marijuana but generally fails to uphold accepted standards of practice for recommending a potentially addicting medication/drug. 28 Bottom Line Definitions: Cannabinoids Cannabinoids are biologically active molecules that have a number of regulatory functions in the human body. Humans produce endocannabinoids Anandamide (N-arachidonoylethanolamine) 2-AG (2-arachidonoylglycerol) 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. 29 30 5
Endocannabinoid Actions Endocannabinoid Actions The neuron s volume control dials down neuron activity when too strong Endocannabinoids travel from postsynaptic to pre-synaptic CB receptors to decrease presynaptic release of neurotransmitters across the synapse 31 32 Cannabinoids: Biology Definitions: Marijuana Currently cannabinoid biology is incompletely understood. 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 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 most commonly utilized Cannabis sativa typically causes an alert and energetic high, Cannabis indica causes a relaxed and lethargic high. Both species have been hybridized repeatedly. A typical medical marijuana plant will have varying amounts of both sativa and indica. 33 34 Definitions: THC Medical Marijuana THC: Tetrahydrocannabinol, also know as delta-9- tetrahydrocannibinol, the primary psychoactive cannabinoid in the marijuana plant. The amount of THC in a given plant varies widely THC has 2-4x the binding affinity to CB receptors as compared to endocannabinoids 35 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. Percentage of THC or CBD can be assessed and manipulated. 36 6
Pharmaceutical Cannabinoids Two marijuana-based medications are available in the United States and approved by the Food and Drug Administration. Dronabinol (marinol) Schedule III oral medication approved for the treatment of AIDS-related wasting, and chemotherapy-induced nausea and vomiting. capsule taken whole orally Onset of symptom relief longer than smoked marijuana. Nabilone (cesamet) oral capsule with properties similar to dronabinol Schedule II medication due to a possible higher abuse potential. 37 38 Pharmaceutical Cannabinoids THC Receptors Nabiximols (Sativex) cannabinoid-based oral-mucosal spray. approved in Canada, United Kingdom, Spain, New Zealand for relief of neuropathic pain / spasticity in multiple sclerosis. approved in Canada as an adjunctive analgesic treatment in patients with cancer pain. undergoing late stage clinical testing in the United States similar indications. contains equal amounts of THC and CBD. 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. 39 40 Recommendation #3 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. Evidence for Recommendation #3 Based on the past history and current behavior of the tobacco industry, with profit motive being primary, the likelihood of adolescents being targeted by the developing marijuana industry is likely, unless truly strict and enforceable rules and regulations are in place. 41 42 7
Status of Adolescents and Marijuana Based on current prevalence of marijuana use among adolescents, the added market pressures and access issues that are likely to occur with further legalization may be problematic. 2015 Adolescent Substance Use 8th 10th 12th 10% 22% 35% 12% 25% 35% 8th 10th 12th 8th 10th 12th * * ** ** 10% 4% 1%.5% 14% 6% 3%.8% 16% 11% 4%.6% *Used in the last 30 days **Used in the last year Monitoring the Future Survey 2015 http://www.monitoringthefuture.org. 43 44 Percent of US 12th Graders Reporting Using Substances in Lifetime, 2000-2015 Percent Who Use Daily Monitoring the Future Survey 2015 Monitoring the Future Survey 2015 45 46 2017 Legalization Status US Enthusiasm for Marijuana US 47 48 8
Perceived Risk of Harm and Marijuana Use - US 12th Graders: 1975-2015 Use and Perceived Risk Monitoring the Future Survey 2015 49 50 Marijuana acceptance has outpaced scientific support Summary Increasing acceptance among adults of the potential medical benefits of marijuana, despite limited evidence and known harms The majority of Americans live in a state where marijuana is legal for adults Adolescent marijuana use is increasing Pediatricians are likely to be asked questions about indications for medical marijuana for adolescents Pediatricians may be asked to prescribe (recommend) marijuana by their adolescent patients, or by parents for their children who are not responding to usual medications for a variety of chronic conditions. 51 1) Adolescents are uniquely vulnerable to the neurotoxic effects of marijuana 2) Marijuana is legal for medical or recreational purposes in MOST of the United States with an associated presumption of low risk of harm 3) Adolescents should NOT use marijuana 52 Practice Change Resources As a result of attending this session, I encourage you to incorporate these changes: Recognize adolescence as uniquely vulnerable to the neurotoxic effects of marijuana Clearly and unequivocally recommend to your pediatric and adolescent patients to NEVER use marijuana, or to stop current use 53 American Academy of Pediatrics: www.aap.org/marijuana Substance Abuse and Mental Health Services Administration: www.samhsa.gov 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 Marijuana Policy Project: www.mpp.org Drug Policy Alliance: www.drugpolicy.org 54 9