Legalized Marijuana: Uses, Misuses & Abuses Kennon Heard University of Colorado SOM Dept Of Emergency Medicine Disclosures Research grants McNeil Consumer Healthcare (Acetaminophen) Rare Disease Therapeutics (Black Widow Spider) Royalties Up To Date (Acetaminophen Poisoning) Off label use of APM for vomiting Objectives At the end of this lecture you will be able to Describe the basic pharmacology of cannabis Recognize how route of exposure affects symptoms from exposure Identify marijuana products Treat common complications of marijuana use Interpret urine drugs screens for marijuana
Pharmacology Marijuana contains multiple active constituents Cannabinoid acids (THC) inactive Decarboxylated to the active phenols Decarboxylation occurs with heating Smoking Cooking Pharmacology Cannabinoids bind to CBD receptors CDB1 (CNS) and CBD 2 (Immune) Endocannabinoids are derived from arachadonic acid Effects vary with the specific cannabinoid concentrations present in each product Tetrahydrocannabinol ( )-trans-δ9-tetrahydrocannabinol (THC) Major psychoactive component of cannabis However > 30 substances in cannabis are active THC is a low affinity, partial agonist Doesn t bind tightly /does not fully activate vs. synthetic cannabinoids (Spice)
Cannabidiol (CBD) Up to 40% of cannabinoids in MJ May antagonize THC effects Popularized for treatment of pediatric epilepsy Charlotte s Web/Realm Oil FDA approved orphan drug Possibly used for MS Approved in Canada Medical MJ Per the Colorado constitution, recommended for : Cancer Glaucoma HIV or AIDS Chronic pain Seizures Chronic nausea Cachexia Persistent muscle spasms Emerging evidence for MS, Inflam BD, PTSD Routes of Exposure Smoked Inhaled (vaping) Vaporize without combustion Ingestion Dermal, rectal, injection
Dose 10mg of THC is roughly equivalent to the amount in a medium-sized joint 10 mg is the unit dose for edibles in Colorado Smoking Combust the plant product to volatilize the cannabinoids Joints Water pipe (bong) Inhalation - peak concentrations within minutes Easy to titrate Higher addiction potential? Carcinogens Smells like burning Vaping Heat marijuana until the THC is vaporized Lower temperature Does not combust (unlike smoking) Less THC destruction What to vape? Plant product THC fluids Hash oil
Vaporizing Temperature Cannabinoids volatilize at different temperature THC - 157 C. CBD - 160-180 C. Delta-8-THC - 175 178 C. CBN - 185 C. CBC - 220 C. THCV - 220 C. Plant product Vape fluids Soda Edibles Hashish Dronabinol What is out there Plant Products Most THC is in the flowers and leaves Less in stems 3% to 33% THC Hash resin made from trichomes Cannabinoid-rich glandular hairs Mechanical separation and pressed together THC content ranges from almost none to 70%
Ingestion More traditional medication profile may not peak for 6 hours Difficult to titrate Easier to overdose Edibles Colorado limits THC in edible pot products 10mg per serving Maximum of 10 servings per package Edibles must be sold in opaque, childproof containers that explicitly warn the product contains marijuana Cannot put it in commercial products Making Edibles
Organic extraction of cannabinoids from cannabis Plant products soaked in butane Heated to evaporate off solvent Hash Oil Hash Oil 30 to 95% cannabinoid Legal status of home cooking unclear until recently Now outlawed in Colorado Our burn unit has treated approximately 30 patients in the past 5 years for burns related to hash oil manufacturing Hash Oil
Dronabinol Synthetic THC Used for loss of appetite associated with weight loss in patients with AIDS and chemo nausea and vomiting 2.5, 5 and 10 mg tablets Not commonly abused Can be vaped Euphoria Dizziness Red eyes and dilated pupils Dry mouth Increased appetite Slowed reaction time A distorted sense of time Random thinking Effects Complications Intoxication medical complications occur rarely, if at all Now we see a few cases a week Too stoned to fly Anxiety Psychosis reported very rarely Not clear if it is an effect or unmasking underlying disease
Marijuana Hyperemesis 2004 Frequent (daily) use for months to years profusely vomit, sweating, colicky abdominal pain, and polydipsia..... take multiple hot baths or showers attempted to cope at home unless they exhausted their hot water supply or became debilitated by severe vomiting. At this point they would present to hospital Vomiting..refractory to the spectrum of antiemetic medication. Allen Gut 2004 Diagnostic Criteria Simonetto Mayo Clin Proc 2012 > 2 visits for vomiting without anatomic cause within 1 year 2 hospitals, 1 year pre and 1 post Rate of visits doubled after legalization Rate of having documented use tripled We did not find showering documented frequently
Management Initially most managed as usual abdominal pain IV fluids Opioid pain medications 5HT 3 antiemetics This led to frustration and admissions Our treatment of choice 5-10 mg iv with diphenhydramine Reviewing our outcomes Avoid opioids and benzodiazepines Sublingual olanzapine for outpt treatment? Promethazine may also work Withdrawal Previously dismissed as non-entity New designation in DSM 5 Estimated 10% of users become dependent (severe withdrawal syndrome) Most have only mild symptoms (except craving) Symptoms peak 1-3 days
DSM Criteria Cessation of cannabis use that has been heavy and prolonged (i.e., usually daily or almost daily use over a period of at least a few months). > 2 of the following Irritability, anger or aggression Nervousness or anxiety Sleep difficulty (i.e., insomnia, disturbing dreams) Decreased appetite or weight loss Restlessness Depressed mood At least one of the following physical symptoms causing significant discomfort: abdominal pain, shakiness/tremors, sweating, fever, chills, or headache Synthetic Cannabinoids Developed for medicinal use Now produced in China, Eastern Europe Specific compounds vary Compounds sprayed on plant products Sold as incense not for human consumption Initially legal due to definitions Many states have passed class regulation Synthetic Cannabinoids Bind to CBD receptors High affinity/high potency Clinical effects are not known until someone smokes it Not detected by routine urine drug screens Most exposures are unremarkable
General Effects Symptoms N=1,353 (%) Tachycardia 541 (40%) Agitation/irritability 317 (23.4%) Vomiting 207 (15.3%) Drowsiness/lethargy 183 (13.5%) Confusion 164 (12%) Nausea 139 (10%) Hallucination/delusion 127 (9.4%) Hypertension 110 (8.1%) Dizziness/vertigo 99 (7.3%) Chest pain 64 (4.7) Mamba 76 cases in 3 weeks to 2 ED s ADB-PINACA Altered mental status (67.6%) Agitation (42.1%), Seizures (14.4%). Intubation (12.7%) Bradycardia- 10% <50 BPM
Urine Drug Screen 11-nor-Δ 9 -THC-9-COOH Standard cutoff 50 ng/ml Specific for marijuana False positives are near impossible Assay specific Efavirenz, pantoprazole Cannot be positive from passive smoke If you are positive, you were high Summary Cannabis has complex pharmacology Eating delays onset and peak of symptoms New products and delivery more potent Intoxication rarely results in medical care Treat hyperemesis with APM Synthetics are unpredictable + is + on urine drug screen