What to do when cannabis gets admitted I have nothing to disclose and no conflicts of interest or funding sources I will be discussing unapproved drugs and unapproved uses for drugs Kari L. Franson, PharmD, PhD, BCPP Associate Dean and Associate Professor Department of Clinical Pharmacy University of Colorado Skaggs School of Pharmacy & Pharmaceutical Sciences Objectives At the completion of this activity, the participant will be able to: 1. Guide patients & clinicians regarding the issues of if, when, where, and how to use cannabis safely and, in regard to therapeutic uses, effectively 2. Describe the legal issues that arise when hospital patients are using cannabis lawfully under state laws
A provider asks What can you tell me about the diseases that medical marijuana has been approved for? Number of states with various approved medical conditions Alzheimer s disease (11) Epilepsy/seizures (29) Nausea (21) ALS (18) Glaucoma (27) Pain (25) Arthritis (3) Hepatitis C (12) Parkinson s disease (10) Cachexia (24) HIV/AIDS (28) Peripheral neuropathy (5) Cancer (28) Multiple sclerosis (15) PTSD (24) Crohn s disease (19) Muscle spasticity (22) Tourette s syndrome (4) Wong FH, Borgelt LA, Franson KL. Int Med Rev 2018 Tell me what you think I believe that patients gain the most benefit using medical cannabis for: A. Nausea and vomiting control B. Appetite stimulation C. Pain control D. Seizure control E. Feeling of euphoria
National Academies: Health Effects of Cannabis Conclusive or substantial evidence that cannabis or cannabinoids are effective: as anti-emetics in the treatment of chemotherapy-induced nausea and vomiting (oral cannabinoids) for treatment of chronic pain in adults (cannabis) for improving patient-reported multiple sclerosis (MS) spasticity symptoms, but limited evidence for clinicianmeasured spasticity (oral cannabinoids) National Academies of Sciences, Engineering, and Medicine. 2017. The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. Washington, DC: The National Academies Press. doi: 10.17226/24625. National Academies: Health Effects of Cannabis Moderate evidence that cannabinoids, primarily nabiximols, are effective: to improve short-term sleep outcomes in patients with sleep disturbance associated with obstructive sleep apnea, fibromyalgia, chronic pain, and MS. National Academies of Sciences, Engineering, and Medicine. 2017. The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. Washington, DC: The National Academies Press. doi: 10.17226/24625.
National Academies: Health Effects of Cannabis Limited evidence that cannabis or oral cannabinoids are effective for: increasing appetite and decreasing weight loss associated with HIV/AIDS (cannabis and oral cannabinoids) improving symptoms of Tourette syndrome (THC capsules) improving anxiety symptoms in individuals with social anxiety (cannabidiol) improving symptoms of post-traumatic stress disorder (nabilone) better outcomes (i.e., mortality, disability) after a traumatic brain injury or intracranial hemorrhage statistical association National Academies of Sciences, Engineering, and Medicine. 2017. The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. Washington, DC: The National Academies Press. doi: 10.17226/24625. National Academies: Health Effects of Cannabis Limited evidence that cannabis or oral cannabinoids are ineffective for: improving symptoms of dementia (cannabinoids) improving intraocular pressure associated with glaucoma (cannabinoids) reducing depressive symptoms in individuals with chronic pain or MS (nabiximols, dronabinol, and nabilone) National Academies of Sciences, Engineering, and Medicine. 2017. The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. Washington, DC: The National Academies Press. doi: 10.17226/24625.
National Academies: Health Effects of Cannabis No or insufficient evidence to support or refute that cannabinoids are effective for: cancer-associated anorexia cachexia syndrome and anorexia nervosa cancers, including glioma irritable bowel syndrome epilepsy spasticity in patients with paralysis due to spinal cord injury chorea and certain neuropsychiatric symptoms associated with Huntington s disease symptoms associated with amyotrophic lateral sclerosis (ALS) Parkinson s disease or levodopa-induced dyskinesia dystonia treatment for mental health outcomes in individuals with schizophrenia or schizophreniform psychosis achieving abstinence in the use of addictive substances National Academies of Sciences, Engineering, and Medicine. 2017. The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. Washington, DC: The National Academies Press. doi: 10.17226/24625. Chemotherapy induced nausea and vomiting Small studies compared THC (dronabinol, nabilone) to dopamine antagonists Dronabinol showed anti-emetic efficacy over neuroleptics (but high risk of bias) NNT = 3.4 Depression (13%), hallucinations (6%), paranoid delusions (5%), occurred, but patients preferred cannabis over control (RR 0.33; 95% CI 0.24-0.44) Smoking relief 70-100% vs. capsule relief 76-88% The standard of care for prevention of CINV for highly and moderately emetogenic chemotherapy is: 5-HT3 receptor antagonist, dexamethasone, aprepitant/fosaprepitant Tramer MR, Carroll D, Campbell FA, et. al. BMJ 2001; Musty RE, Rossi R J Cannabis Ther 2001; Todaro B. J Natl Compr Canc Netw. 2012 Machado Rocha FC, Stefano SC, De Cassia Haiek R, et. al. Eur J Cancer Care 2008
Chronic (neuropathic and cancer) pain Review of trials with >30% reduction in pain 2 cancer pain trials 6 neuropathic pain trials Concluded moderate quality of evidence to support the use of cannabis for chronic pain Common analgesics for neuropathic pain *to achieve 30% reduction in pain Whiting PF, Wolff RF, Deshpande S, et al. JAMA 2015 Grant I. Report to the State of California 2010 Multiple sclerosis-associated spasticity American Academy of Neurology (AAN) evidence-based guideline recommendations Oral cannabis extract, synthetic THC, Sativex Several double-blinded RCTs > 1,000 patients Subjectively improved spasticity and pain Sativex also helped with urinary frequency Objective measures not significant Smoked cannabis Data inadequate to determine safety/efficacy Yadav V, Bever C, Bowen J, Bowling A, et. Al. Neurology 2014
Cachexia and appetite stimulation 8 controlled studies in AIDS- or cancer-related cachexia 3 studies of smoked marijuana (up to 67 patients) Others used dronabinol Non-statistically significant weight gain, increase appetite, and improve functional status Megestrol 750 mg weight gain > dronabinol 5 mg Combo did not lead to additional weight gain Cancer patient results were less consistent Abramovici H. Health Canada 2013 Timpone JG, Wright DJ, Li N, et. al. AIDS Res Hum Retro 1997 Post-Traumatic Stress Disorder A few RTC show improved symptoms Observational study >2200 Veterans from 1992-2011 Never users, stoppers, continuing users and starters Adjusted for covariates of baseline symptoms, drug & alcohol use, violent behavior and employment Marijuana use associated with worsening of PTSD symptom severity, violent behavior, and alcohol & drug use Wilkinson ST, J Clin Psychiatry 2015
Seizures Uncontrolled case series in intractable childhoodonset epilepsy CBD : THC ratio 20 : 1 Median monthly seizure frequency Baseline 30.0 (interquartile range [IQR] 11.0 96.0) After 12 week treatment 15.8 (IQR 5.6 57.6) Some weaned patient from another AED after starting CBD Adults case reports and patient surveys Seizure exacerbation with discontinuation German study no effect Friedman D, Devinsky D, NEJM 2015 Gloss D, Vickery B. Cochrane Database Syst rev 2014 Glaucoma Systemic administration of cannabis IOP by 30% Pilot study of 6 patients IOP for 2 hours Uncontrolled study 9 patients with open-angle glaucoma THC qid IOP Patients appeared to develop tolerance, and all discontinued the study Flach AJ. Trans-American Ophthalmological Society 2012
Tell me what you think How would you respond to a 40 yo patient who asks you to help them use cannabis for cancer pain? The patient asks Are you worried I am going to get addicted? NIDA (http://drugabuse.gov/sciencefair/)
Lifetime dependency risk with use 100 % 75 50 25 32% MJ addiction risk in teens 23% 17% 15% 9% 0 Hall and Degenhardt. Lancet. 2009 Strahny A. CBHSQ Report. 2013 A mother asks Is cannabis going to fry my son s brain? Brain development in adolescence Limbic region Immediate rewards Impulsive behavior Cortex Long term gain Thoughtful behavior http://erichengelhardt.net/neuro-facts.html accessed 5/28/2013
Effect on neuropsychological functioning Persistent cannabis users show neuropsychological decline from childhood to midlife Prospective study of 1,037 individuals followed from birth (1972/1973) to 38 years of age Within-person IQs : Never used 100.64 Used, never regularly 101.24 Used regularly 90.77 Impairment of learning, memory, and executive functions Meier MH, et al. Proc Natl Acad Sci. 2012 Chronic cognitive effects of cannabis (A) Relation between amount of marijuana smoked 2 and Repetition of Numbers Task, number correct for the high Shipley IQ group (squares) and the low Shipley IQ group (circles). (B) Relation between amount of marijuana smoked 2 and performance on the Stroop task for the high Shipley IQ group (squares) and the low Shipley IQ group (circles) Bolla KI, et al. Neurology, 2002
Cannabis and psychosis Multiple studies have demonstrated an increased risk of psychosis in THC users 3 meta-analyses have shown an odds ratio of 1.4 to 2.9 Risk with cannabis use is up to 3 fold higher compared to those who did not use cannabis After control for a variety of confounding factors including other drug use and socioeconomic variables Pierre JM. Current Psychiatry. 2011 The patient asks Are there other effects of cannabis besides in the brain? Potential AEs from chronic cannabis use Respiratory Increased sputum production, wheezing, bronchitis Potential increase in chronic bronchitis, emphysema, and airway inflammation Gastrointestinal Cannabinoid hyperemesis syndrome Genitourinary Increased risk of failing a drug test Reproductive Menstrual cycle disruption Decreased sperm count Impotence and decreased libido May decrease lactation Hematology/ Potential increased risk of nasopharyngeal carcinoma Oncology Potential for increased risk of lung cancer, however, data is inconclusive. Many products may contain other carcinogens. Cannabis smoke contains known carcinogens. Metabolic/Endocrine Potential to increase insulin resistance in adipose tissue 24
Acute cardiovascular effects of THC Heart rate HRV The variation in the time interval between heartbeats (RR-interval) HRV is a predictor of mortality after MI L Zuurman, et al. Br J Clinical Pharmacology. 2008 Cannabis use and long-term mortality among survivors of AMI Kaplan-Meier estimates of post-mi survival among 87 cannabis users and 174 propensity-matched nonusers. Frost L, et al. American Heart Journal. 2013
Tell me what you think How would you respond to the patient who says no one has ever died from using cannabis? The patient asks I still want to try it How much should I take? THC dosing is known; but not known for other CBs Typical effective dosing of inhaled THC Low dose < 7 mg Medium dose = 7 18 mg High dose > 18 mg There is a known tolerance to THC down regulation of CB1 receptors, and G-protein activation High probability of tolerance with chronic use, and low with intermittent Chronic = daily for a week, intermittent = weekly L Zuurman, et al. Br J Clinical Pharmacology. 2008
A patient asks How often should I take it? PK profile of smoked THC Smoking cannabis turns ~50% of the THC content into smoke Up to 50% of inhaled smoke is exhaled again, and some undergoes localized metabolism in the lung Bioavailability of a inhaled dose of THC is between 10-25% Effects are perceptible within seconds and fully apparent in a few minutes Effects last about 3 hours Strougo A, et al. J Psychopharmacology. 2008 PK profile of oral THC Onset of effect is delayed: 1-3 hours due to slow absorption from the gut Bioavailability of THC after oral ingestion ranges from 5-20% in the controlled environment of clinical studies Weight, metabolism, gender and eating habits play a role in absorption Effects last about 6 12 hours Agurell S, Halldin M, Lindgren JE, et al. Pharmacological reviews. 1986
PK profile of oromucosal THC/CBD - Sativex One study did not find difference between oral THC capsules and oromucosal spray PK Peak concentration THC 1.5 hours Peak concentration CBD 1.3 hours 2-fold inter-patient variability in peak THC and CBD levels Karschner EL, Clin Chem 2011 Further dosing considerations THC substrate of CYP3A4 & 2C9 CBD substrate of CYP3A4 & 2C19 Possible drug interactions sedation, ataxia: CNS depressants, anticholinergics heart rate: sympathomimetics effects of: hexobarbital, hydrocortisone, clozapine, phenytoin, warfarin effects of: propofol, indinavir, theophylline Horn JR, Pharmacy Times 2014
Vaporizing cannabis plant or concentrate Same immediate effects and benefits as smoking Heats 285-392 F vaporizing CBs Conductive vs. convective heating Images from: www.cannastick.com; https://spendabit.co/go?q=vape&offset=0 ; www.procon.org Dabbing cannabis concentrates CBs are extracted by solvents Butane hash oil (BHO), dabs, earwax, butter or shatter >90% of CBs Superheat nail (with blow torch) and add dab Users quickly develop tolerance Images from: https://www.zamnesia.nl/dabbing/2365-glazen-olie-bong-blaze-swirl.html
Edible baked goods, candies, tinctures Edibles have CBs added, or are infused with CB butter, oil or alcohol Colorado 10mg serving size and 100mg maximum/package Doesn t release toxins Discreetly consumed Must exit dispensary in child resistant packaging Now also prohibit edibles that resemble animals, people or fruit Images from: http://www.leafscience.com/2015/10/27/beginners-guide-marijuana-edibles/ Cannabis infused creams, lotions and oils THC not charged, but lipophilic properties limit it getting to site of action Most products claim no psychoactive effects, so THC not getting absorbed Patch with occlusion and vehicle to enhance absorption Images from: http://www.vaildaily.com/news/14759677-113/soaking-in-the-cannabis-what-topical-thc-products-can-do http://www.americanpharmaceuticalreview.com/featured-articles/170872-lipids-in-transdermal-and-topical-drug-delivery/
So how can I help? https://teens.drugabuse.gov/drug-facts/marijuana C.R.S. 12-42.5-123. Unprofessional conduct - grounds for discipline 1) The board may suspend, revoke, refuse to renew, or otherwise discipline any license or registration. (c) Has violated: (III) Any state or federal law pertaining to drugs; https://www.colorado.gov/pacific/dora/pharmacy_laws
Institutions carry risk for allowing cannabis use Because they are accredited through the Center for Medicare & Medicaid Services, hospitals could be found to be in violation, lose federal funding, and face penalties The Joint Commission Standard MM.03.01.05 policy states: The hospital safely controls medications brought into the hospital by patients, their families, or licensed independent practitioners. Borgelt LM & Franson KL. Hosp Pharm 2017,582(2):89-90. http://www.jointcommission.org/assets/1/6/sample-medications_hap.pdf Accessed Dec 2016. Institutions carry risk for allowing cannabis use Joint Commission Standard MM.03.01.05 includes the following elements of performance: The hospital defines when medications brought into the hospital can be administered Before use, the hospital identifies the medication and visually evaluates the medication s integrity The hospital informs the prescriber and patient if the medication brought into the hospital is not permitted http://www.jointcommission.org/assets/1/6/sample-medications_hap.pdf Accessed Dec 2016.
Institutions carry risk for allowing cannabis use The Washington Health Care Association template http://www.whca.org/files/2013/04/sample-medical-marijuana-policy.pdf (Accessed Aug 2016) Institutions carry risk for allowing cannabis use The institution may choose to access the cannabis product through the FDA s expanded access (compassionate use) program This program allows access for an individual patient or more widespread use when the disease state is serious and a sponsor is actively developing the product http://www.fda.gov/newsevents/publichealthfocus/expandedaccesscompassionateuse/default.htm Accessed Aug 2016.
Tell me what you think I believe that patients are most likely to access cannabis at my institution by: A. Compassionate use processes B. Following Joint Commission Standard MM.03.01.05 processes C. Changing law Review today s session Provided information for you to guide patients & clinicians regarding the issues of if, when, where, and how to use cannabis safely and, in regard to therapeutic uses, effectively Described the legal issues that arise when hospital patients are using cannabis lawfully under state laws