Federal Law: Marijuana Marijuana is a Schedule I drug under Federal Controlled Substances Act Makes possession, usage, purchase, sale, and/or cultivation of marijuana illegal at the federal level May not by prescribed, administered, or dispensed Other Schedule I drugs include: Lysergic acid diethylamide (LSD) Diacetylmorphone (Heroin) Gamma Hydroxybutyric Acid (GHB) MDMA (AKA Ecstasy ) Mescaline 1
More than half of new illicit drug users begin with Marijuana Next most common are prescription pain relievers, followed by inhalants (which are most common among younger teenagers) National Institutes of Health: NIDA DrugFacts Nationwide Trends 2012. Available at: http://www.drugabuse.gov/publications/drugfacts/nationwide-trends 2
Adverse Effects of Marijuana Use -Volkow, Nora et al. N Engl J med. Volume 370, Issue 23, pages 2219-27. June 2014. 3
Increasing Potency of THC Volkow, Nora et al. N Engl J Med. Volume 370, Issue 23, Pages 2219-29. June 2014. 4
Marijuana s Effects Strains of Marijuana contain mixture of cannabinoids that have different effects on the user Two important cannabinoids THC: Δ 9 -tetrahydrocannabinol (THC) Psychoactive component; creates high CBD: cannabidiol Non-psychoactive component; anti-seizure effects Ratios of THC/CBD in medical marijuana are often compared in medical marijuana discussions 5
Cannabis Pharmacology THC was isolated in 1964 Cannabis has two specific G protein-coupled cannabinoid-binding receptors: CB1 (or Cnr1) CB2 (orcnr2) CB1 receptors Found in the brain High densities in the basal ganglia, substantia nigra, cerebellum, hippocampus, and cerebral cortex Located presynaptically and their activation inhibits the release of acetylcholine, L-glutamate, Aminobutyric acid, noradrenaline, dopamine, and 5-hydroxytryptamine CB2 receptors Located peripherally in immune system tissues (splenic macrophages), B lymphocytes, peripheral nerve terminals, and the vas deferens Believed to participate in the regulation of immune responses and inflammatory reactions Goldfrank s Toxicologic Emergencies - Chapter 83: Cannabinoids 6
Cannabis Mechanism of Action Mechanism producing psychoactive effects of cannabinoids not fully elucidated Activity at CB1 receptors is believed to be responsible for the clinical effects of cannabinoids Involves regulation of cognition, memory, motor activities, nociception, nausea & vomiting Cannabinoid receptors are normally activated by endocannabinoids that are naturally occurring chemicals in the body that regulate brain development and function Anandamide is an endocannabinoid Goldfrank s Toxicologic Emergencies - Chapter 83: Cannabinoids 7
Charlotte s Web (medical marijuana oil) Named after Charlotte Figi, a 5 year old child with epilepsy (Dravet syndrome) who used the marijuana oil to reduce her seizures She was in hospice and began using the oil in 2012 for end of life comfort measures and her seizures decreased dramatically (previously 50 seizures a day; after the oil 1 seizure a month) The oil contains a high amount of cannabidiol which proponents claim contain the medicinal properties and low levels of THC, the ingredient that produces the high Strain of cannabis with high CBD/THC ratio More CBD (anti-seizure cannabinoid) than THC (psychoactive cannabinoid) CBD>10% THC<0.8% Regular cannabis generally has THC 12-21% and CBD 0.1-0.3% Oil made by a non profit organization called the Realm of Caring in Colorado run by 5 brothers (The Stanley brothers) Another oil Epidiolex has been granted Orphan Status and is currently in Phase II clinical trials for use in Lennox-Gastaut syndrome (LGS) and Dravet syndrome in children Her story triggered state legislatures to push for legalization of the medical marijuana oil for treatment of children with epilepsy http://www.msnbc.com/hardball/the-new-faces-marijuana; http://www.gwpharm.com/lgs%20orphan%20designation.aspx 8
Common Terms Associated with Marijuana Cannabinoids Term for the over 60 bioactive substances in Cannabis sativa The major cannabinoids are cannabinol (CBD), and tetrahydrocannabinol (THC) The principal psychoactive cannabinoid is Δ 9 -tetrahydrocannabinol (THC) Marijuana Common name for a mixture of dried leaves and flowers of the C. sativa plant; Schedule I Hashish Hashish and hashish oil are the pressed resin and the oil expressed from the pressed resin, respectively (Both Schedule I); very potent Hemp Distinct variety of the plant species cannabis sativa that contains minimal amounts of THC Various parts of the plant can be utilized as a fiber in the making of textiles, paper, paints, clothing, plastics, cosmetics, foodstuffs, insulation, animal feed and other products Marinol & Cesamet Marinol (dronabinol) Synthetic THC available by prescription (Schedule III) Cesamet (nabilone) Synthetic cannabinoid available by prescription (Schedule IIII) Goldfrank s Toxicologic Emergencies - Chapter 83: Cannabinoids; Hemp: http://norml.org/marijuana/industrial/item/introduction-5; DEA Scheduling: http://www.justice.gov/dea/pr/multimedia-library/publications/drug_of_abuse.pdf#page=68 9
Marinol (dronabinol) Synthetic THC Indications Chemotherapy-associated nausea and vomiting refractory to other antiemetics AIDS-related anorexia Dosage Antiemetic: 5ng/m² PO 1-3 hours before chemotherapy, then every 2-4 hours afterwards for a total of 4-6 doses/day (Max 15ng/m²/does up to 6 doses/day Appetite stimulant (AIDS-related): 2.5mg PO before lunch and dinner; titrate up to a maximum of 20mg/day Schedule III Store in the refrigerator 10
Cesamet (nabilone) Synthetic cannabinoid similar to THC Indications Treatment and prophylaxis chemotherapy-induced nausea/vomiting Dosage 1-2mg PO twice daily (Max: 6mg/day) May administer 2 or 3times per day during the entire chemotherapy course; continue up to 48 hours after the last chemotherapy dose Initial does should be given 1-3 hours before chemotherapy A dose of 1-2mg the night before chemotherapy may also be of benefit Not detected as THC on urine testing; avoids problems with drug screening The most commonly encountered adverse were drowsiness, vertigo, dry mouth, euphoria (feeling high ), ataxia, headache, and concentration difficulties Lexicomp; http://www.regencerx.com/docs/physicianrx/gastrointestinal-anti-nausea-cesamet-0207.pdf 11
Why Are These Not Abused? Marinol & Cesamet Onset of action is slow and gradual Effects as dysphoric, unappealing, and undesirable; reported negative psychoactive effects; too strong Patient cannot regulate or control effect as with smoking More expensive than smoked cannabis Doesn t contain a mix of cannabinoids Potential reduction in therapeutic benefits from combination User preference for natural cannabis NORML Website. Marinol vs. Natural Plant. Available at: http://norml.org/component/zoo/category/marinol-vs-natural-cannabis Calhoun SR, et al. Abuse potnetial of dronabinol (Marinol). J Psychoactive Drugs. 1998 Apr-Jun;30(2):187-96. Ware MA, et al. The abuse potential of the synthetic cannabinoid nabilone. Addiction. 2010 Mar;105(3):494-503. 12
Other Cannabinoid Medications in Development Sativex General Information Oromucosal spray; close to 1:1 ration of THC/CBD Indicated for muscle spasms in muscular sclerosis patients who to not respond to other treatments Available in 25 countries; mostly in Europe Undergoing Phase III trials in the US Product Information Not for patients under 18 Stored in refrigerator prior to use; after open, may keep at room temperature; good for 28 days Common side effect is dizziness Dose is titrated up; usually sprayed twice a day; max of 12 sprays GW Pharmaceuticals is the company attempting to gain FDA approval for Sativex Epidiolex (also from GW Pharma) Orphan drug for pediatric epilepsy Dravet & Lennox-Gastaut Syndromes Still an investigational drug; does not have FDA approval yet; Phase 3 trials in 2015 98% CBD and no THC Liquid form like Charlotte s Web 13
Pharmacists Attitudes Some in Support Seek a more active role in clinical applications for cannabis-based medicines Believe pharmacists should be involved as the drug experts and need to seize the opportunity Pharmacists are already experienced at dispensing controlled substances to the public Some opposed Unresolved legal and regulatory issues Marijuana scheduling and threat of federal prosecution Potential to lose DEA license for dispensing marijuana Request more trials showing clinical safety & efficacy Desire federally approved dosage forms and reclassification to enable legal sales No standard guidelines for dosing currently exist 14
Medical Marijuana State Legislation & Pharmacists Connecticut First state to require a pharmacist to work in a dispensary to dispense medical cannabis Minnesota Second state with a similar program only a pharmacist may dispense cannabis Michigan Public Act 268 enacted, but will only be implemented if the federal government changed marijuana to Schedule II Allows for state certification of pharmaceutical-grade cannabis The state would regulate growers, and cannabis would be sold in pharmacies 15