Marijuana as Medicine: Unintended Consequences and Concerns David - - PowerPoint PPT Presentation
Marijuana as Medicine: Unintended Consequences and Concerns David R. Reagan, MD PhD | Chief Medical Officer | September 13, 2017 Michael D. Warren, MD MPH | Deputy Commissioner for Population Health | September 13, 2017 Disclosures David
David R. Reagan, MD PhD | Chief Medical Officer | September 13, 2017 Michael D. Warren, MD MPH | Deputy Commissioner for Population Health | September 13, 2017
Image sources: 1. Cannabis plant: https://www.dea.gov/druginfo/ds.shtml 2. Cannabis and joint: NIDA, https://www.drugabuse.gov/publications/drugfacts/marijuana 3. Marijuana Cookie: By Subvertc - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18683918
Source: National Academy of Sciences. https://www.nap.edu/catalog/24625/the-health-effects-of-cannabis-and-cannabinoids-the- current-state
THC Type
CBD Type
Hybrid type
– Compound responsible for psychoactive effects – Time to onset of effect and duration of effect depends on method of ingestion
– Euphoria – Disinhibition, increased sociability – Enhanced sensory perception – Time distortion
– Typical: Impaired judgment, reduced coordination, dry mouth, anxiety, fear, distrust, panic – Others: cyclic vomiting, stress cardiomyopathy
Elation Laughing Heightened Awareness Some patients experience “high” Adverse event among 24% at anti-emetic dose and 8% at appetite stimulant dose
Source: US Food and Drug Administration. Available at: https://www.fda.gov/ohrms/dockets/dockets/05n0479/05N-0479-emc0004-04.pdf
Source for images: Drug Enforcement Administration Museum and Visitors Center. Available at: https://www.deamuseum.org/ccp/opium/history.html. Last accessed 04/13/2017.
Image sources: 1. Penicillin mold: https://commons.wikimedia.org/wiki/File:Penicillium_notatum.jpg. 2. Penicillin tablets: https://www.drugs.com/pro/penicillin-vk.html 3. Penicillin oral solution label: https://www.drugs.com/pro/penicillin-v.html
Image sources: 1. Foxglove botanical print: By Walther Otto Müller - http://caliban.mpiz-koeln.mpg.de/koehler/DIGITALIS.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=1815791 2. Dioxin label: https://www.drugs.com/pro/digox-tablets.html
– Dronabinol (Marinol)—synthetic THC
– Nabilone (Cesamet)—synthetic THC
– Epidiolex (>98% CBD) – Nabiximol (Sativex, 1:1 THC/CBD)
Source: American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA, American Psychiatric Association, 2013.
Use/Intoxication Substance Use Disorder
Reversible Self-Harm Mild: 2-3 Symptoms Moderate: 4-5 symptoms Severe: 6+ symptoms Withdrawal can occur after heavy/prolonged use
Sedatives, Marijuana, Ethanol
MAO – Monoamine oxidase (inactivates DA) VMAT2 – Vesicular monoamine transporter 2 DAT – Dopamine uptake transporter D1 – D5 – Dopamine receptors
Source: National Conference of State Legislatures. Deep Dive: Marijuana. Available at: http://www.ncsl.org/bookstore/state- legislatures-magazine/marijuana-deep-dive.aspx. Last accessed 08/13/2017.
– 22 conclusions re: therapeutic benefits, only 3 with “substantial or conclusive evidence” of benefit
nausea/vomiting
– 4 conclusions with substantial evidence of harm:
and frequent chronic bronchitis
Image source: National Academy of Sciences. https://www.nap.edu/catalog/24625/the-health-effects-of-cannabis-and-cannabinoids- the-current-state
Image source: Wake Forest School of Medicine. Available at: http://libguides.wakehealth.edu/EBP/Study. Last accessed 02/08/2017
Article: Porter J, Jick H. Addiction rare in patients treated with narcotics. New England Journal of Medicine. 1980; 302:123 Image: By Evelyn de Morgan - Secondary source: http://en.wikipedia.org/wiki/Image:Helen_of_Troy.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=160766
Helen of Troy “The Face That Launched 1,000 Ships”
Devinski O et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet
syndromes)
Average Delta-9-THC concentration of DEA Specimens by Year, 1995-2014
Source: ElSohly MA, Mehmedic Z, Foster S, Gon C, Chandra S, Church JC. Changes in Cannabis Potency over the Last Two Decades (1995-2014) - Analysis of Current Data in the United States. Biological Psychiatry. 2016. April 1; 79(7): 613–619.
Source: WA data and image: Washington State Marijuana Impact Report. Available at: https://hidtanmi.org/2016/07/01/northwest-hidta- washington-impact-report/. Last accessed 04/12/2017.
Source: Rocky Mountain High Intensity Drug Trafficking Area. The Legalization of Marijuana in Colorado: The Impact. Volume 4, September
04/20/2017.
Image sources: https://www.childrenscolorado.org/conditions-and-advice/marijuana-what-parents-need-to-know/resources/
Sources: 1. Wang GS, Le Lait MC, Deakyne SJ, Bronstein AC, Bajaja L, Roosevelt G. Unintentional Pediatric Exposures to Marijuana in Colorado, 2009-2015. JAMA Pediatrics. 2016;170(9):e160971. 2. Wang GS, Roosevelt G, Heard K. Pediatric Marijuana Exposures in a Medical Marijuana State. JAMA Pediatrics. 2013;167(7):630-633.
Last-month use of marijuana, ages 12-17 (as of 2015)
Adapted from: Smart Approaches to Marijuana. SAM Educational Briefs & Data on Marijuana Policy. February 2017. Available at: https://learnaboutsam.org/wp-content/uploads/2017/02/06Feb2017-SAM-educational-briefs.pdf. Last accessed 04/12/2017. 5.9% 0.0% 2.0% 4.0% 6.0% 8.0% 10.0% 12.0% Utah Nebraska Iowa Oklahoma Tennessee Ohio Hawaii Minnesota South Dakota Arkansas Illinois South Carolina Florida Texas Pennsylvania Delaware Wisconsin Michigan California New Mexico District of Columbia Maryland Oregon Maine Alaska Colorado 50 States and District of Columbia
“Recreational” use legalized as of 2015 “Medical” use legalized as of 2015 Neither “medical” nor “recreational” use legalized as of 2015
Source: Jessica B. Hancock-Allen JB, Barker L, VanDyke M, Holmes DB. Notes from the Field: Death Following Ingestion of an Edible Marijuana Product — Colorado, March 2014. Morbidity and Mortality Weekly Report. July 24, 2015 / 64(28);771-772. Available at: https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6428a6.htm. Last accessed 04/12/2017.
…death of a man aged 19 years after consuming an edible marijuana product… initially the decedent ate only a single piece of his cookie, as directed by the sales clerk. Approximately 30–60 minutes later, not feeling any effects, he consumed the remainder of the cookie. During the next 2 hours, he reportedly exhibited erratic speech and hostile behaviors. Approximately 3.5 hours after initial ingestion, and 2.5 hours after consuming the remainder of the cookie, he jumped off a fourth floor balcony and died from trauma. The autopsy, performed 29 hours after time of death, found marijuana intoxication as a chief contributing factor.…only confirmed findings were cannabinoids (7.2 ng/mL delta-9 tetrahydrocannabinol [THC] and 49 ng/mL delta-9 carboxy-THC, an inactive marijuana metabolite). The legal whole blood limit of delta-9 THC for driving a vehicle in Colorado is 5.0 ng/mL
Sources: 1. Bradford AC, Bradford WD. Medical marijuana laws reduce prescription medication use in Medicare Part D. Health
analgesic overdose mortality in the United States, 1999-2010. JAMA Internal Medicine. 2014; 174(10): 1668-1673.
“For nervous prostration, brain exhaustion, depression of spirits, mental and physical debility, neurasthenia, sick headache, neuralgia, cases of the opium, tobacco, alcohol or chloral habit, weak status of the voice…..”
Image source: https://www.washingtonpost.com/news/wonk/wp/2017/04/11/doctors-once-treated-alcoholism-with-heroin-now-they- want-to-treat-heroin-addiction-with-marijuana
The AAN does not advocate for the legalization of marijuana-based products for use in neurologic disorders at this time, as further research is needed to determine the benefits and safety of such products. This is of paramount importance when marijuana-based products are used in patients with underlying neurologic disorders, or in children whose developing brains may be more vulnerable to the toxic effects
The AAP opposes “medical marijuana”
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…The AAP
because of the potential harms to children and adolescents.
Our AMA calls for further adequate and well-controlled studies of marijuana and related cannabinoids in patients who have serious conditions for which preclinical, anecdotal, or controlled evidence suggests possible efficacy and the application of such results to the understanding and treatment of disease…Our AMA urges that marijuana's status as a federal schedule I controlled substance be reviewed with the goal of facilitating the conduct of clinical research and development of cannabinoid-based medicines, and alternate delivery methods. This should not be viewed as an endorsement of state-based medical cannabis programs, the legalization of marijuana, or that scientific evidence on the therapeutic use of cannabis meets the current standards for a prescription drug product.
There is no current scientific evidence that marijuana is in any way beneficial for the treatment of any psychiatric disorder. In contrast, current evidence supports, at minimum, a strong association of cannabis use with the onset of psychiatric disorders. Adolescents are particularly vulnerable to harm, given the effects of cannabis on neurological development. The National Council on Alcoholism and Drug Dependence, Inc. (NCADD) is
for legal medical use should be scheduled and monitored under FDA oversight, and should be held to the same FDA standards imposed on other dangerous prescription drugs including those regarding warnings, labeling, and the ordering and filling of prescriptions.
ASAM does not support the legalization of marijuana and recommends that jurisdictions that have not acted to legalize marijuana be most cautious and not adopt a policy of legalization until more can be learned from the “natural experiments” now underway in jurisdictions that have legalized marijuana. ASAM supports the use of cannabinoids and cannabis for medicinal purposes
those established by the FDA research and post-marketing surveillance processes.