Medicinal Cannabis:

Pharmacologic and Regulatory Considerations and Dispensary Requirements

Iadelisse Cruz-González PharmD, BCGP, GCG Professor

School of Pharmacy This Photo by Unknown Author is licensed under CC BY-ND University of Puerto Rico CFPR Convention- August 2021

1 Faculty Disclosure

▪ Iadelisse Cruz- Gonzalez, declares no conflict of interest

▪ This presentation has been prepared FOR EDUCATIONAL PURPOSES ONLY. It is not intended to be used for clinical decision making or patient assessment.

▪ The attendees must consult current applicable regulations, guidelines, clinical studies, expert opinions and exercise their professional judgment in order to fulfill their responsibilities and in the best interest of each patient and the profession.

2

This Photo by Unknown Author is licensed under CC BY-NC-ND 1.Describe the evolution of medicinal cannabis use Objectives 2.Explain legal implications regarding medicinal At the end of the CPE activity the cannabis at national and local level participants will be able to: 3.Describe the initial operation requirements for medical cannabis dispensaries 4.List training requirements for medical cannabis dispensaries employees 5.Identify the indications for medicinal cannabis according to regulations in Puerto Rico 6.Discuss the pharmacologic and safety considerations regarding patients using medicinal cannabis

3 Evolution of Medicinal Cannabis Use

Objective 1

4 Medicinal Cannabis BC

This Photo by Unknown Author is licensed under CC BY-SA-NC Year Country Fact / Comment 2737 B.C. China Legendary Chinese Emperor Shennong - Catalog of 365 Species of Medicinal Plants and “discover” the healing properties of marijuana. The Divine Farmer or God of Herbal Chinese Medicine Uses: malaria, constipation, rheumatic pains, and childbirth and mixed with wine as a surgical analgesic 600 B.C. India Bhang: drink of cannabis and milk, is used widely as an anesthetic. Other uses: analgesic, anticonvulsant, sedative-hypnotic, and anti- inflammatory, antibiotic, antiparasitic, antispasmodic, digestive, appetite stimulant, diuretic, aphrodisiac or anaphrodisiac, antitussive, and expectorant. 1500 B.C. Egypt Medical Papyri from Egypt mention marijuana as a cure for sore eyes and inflammation.

Encyclopedia Britannica Available online: https://www.britannica.com Accessed: April 16, 2018 Zuardi AW. History of cannabis as a medicine: a review. Braz J Psychiatry .2006;28(2):153-157. Ben Amar M. Cannabinoids in medicine: a review of their therapeutic potential. JEthnopharmacology. 2006;105(1-2):1-25. 5 Mikuriya TH. Marijuana in medicine: past, present and future. California Med.1969;110(1):34-40. Medicinal Cannabis AD

This Photo by Unknown Author is licensed under CC BY-SA Year Country Fact / Comment 79 A.D. Italy Roman naturalist, Pliny the Elder – Natural History, cites boiled cannabis roots as a treatment for gout, pain and cramped joints. 800 A.D. Islamic Islamic physicians prescribe cannabis for a variety of ailments, countries although some decry it as a “lethal poison”.

1542 A.D. Germany German physician Leonhart Fuchs names the plant Cannabis sativa.

1839-42 United British army surgeon from Irish descent, William Brooke A.D. Kingdom O’Shaughnessy introduces marijuana into medical practice as a treatment for pain, nausea and convulsions.

6 Encyclopedia Britannica Available online: https://www.britannica.com Accessed: April 16, 2018 Medicinal Cannabis

Year Country Fact / Comment This Photo by Unknown Author is licensed under CC BY-NC-ND 1850 US The United States Pharmacopeia, which issues the official handbook for dispensing medications, classifies marijuana as a legitimate medical compound. 1906 US Pure Food and Drug Act required drug labels to list dangerous drugs, Encyclopedia Britannica Available online: https://www.britannica.com cannabis was included Accessed: April 16, 2018

1925 Geneva, A League of Nations and Opium Conferences Treaty limits cannabis use Mahvan TD et al., Marijuana use in Switzerland the Elderly: Implications and to medical or scientific purposes. Aspirin and other newly developed considerations The Consultant drugs begin to replace cannabis as treatments for pain. Pharmacist 2017; 32: 341-349. Cydney Adams CBS News November US 17, 2016, 5:45 PM The man behind 1930 Harry J. Anslinger is appointed commissioner of the Federal Bureau of the marijuana ban for all the wrong Narcotics. He considers marijuana a corrupting influence and helps to reasons turn public opinion against the drug. 1937 US Marihuana Tax Act; Federal Marihuana prohibition

1942 US Removed from the United States Pharmacopeia. 7 Medicinal Cannabis

Image available: Year Country Fact / Comment https://www.unodc.org/unodc/frontpage/2015/un70.html 1961 United United Nations, New York - Single Convention on Narcotic Drugs (Print States 1962) 1964 Israel Raphael Mechoulam, the “father of cannabis research” (co-discovered THC) 1967 - 1969 United Hippie culture States 1969 United Summer of Love, Woodstock States

8 Mahvan TD et al., Marijuana use in the Elderly: Implications and considerations The Consultant Pharmacist 2017; 32: 341-349. Medicinal Cannabis

This Photo by Unknown This Photo by Unknown This Photo by Unknown Author Author is licensed under Author is licensed under CC is licensed under CC BY-SA CC BY-SA BY-SA Year Country Fact / Comment 1971 United States President Richard Nixon declares “War on Drugs”

1972 United States National Commission on Marijuana and Drug Abuse recommended decriminalization

1973 United States President Richard Nixon creates the Drug Enforcement Administration (DEA)

1986 United States President Ronald Regan - Anti Drug Abuse Act 1989 United States President George Bush - National Control Drug Policy and 1st Drug Czar - William Bennett 1996 United States California was the first state to legalize cannabis - Compassionate Use Act 1998 United States Medicinal cannabis use was approved - Alaska, Washington and Oregon

9 Mahvan TD et al., Marijuana use in the Elderly: Implications and considerations The Consultant Pharmacist 2017; 32: 341-349. Among ancient cannabis uses there is…

a. Treatment of inflammation and pain b. Rituals c. Psychedelic effects d. Alternative a and b are correct

10 Cannabaceae family (170 species,11 genera)

Cannabis Plants Cannabis (C sativa, C indica, and C Hemp ruderalis)

More than 2500 strains Cannabinoids including Terpenes Flavonoids CBD & THC

Products Dietary Drugs Foods Cosmetics supplements

This Photo by Unknown Author is licensed under CC BY-NC

FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD). Available at: https://www.fda.gov/news-events/public-health-focus/fda- 11 regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd . Accessed Jul 14, 2021 United $17.5 billion (2020)# 46% increase from 2019 States Current Cannabis Use population 332.9 M * 96 millions Dept. Hacienda de PR+

*Macro trends. U.S. Population 1950-2021Available at: https://www.macrotrends.net/countries/USA/united- states/population#:~:text=The%20current%20population%20of%20U.S.,a%200.58%25%20in Marijuana use has Blacks 4.7 to 12.7% crease%20from%202020. Accessed Jul 23, 2021. increased in 10 years ^^ #U.S. Cannabis Sales Hit Record $17.5 Billion As Americans Consume More Marijuana Than Ever Before https://www.forbes.com/sites/willyakowicz/2021/03/03/us-cannabis-sales-hit- record-175-billion-as-americans-consume-more-marijuana-than-ever-before/ . Accessed Jul (2001-2002 and 2012-2013) 23, 2021. Hispanics 3.3 to 8.4% +Noticentro Edición Estelar 4:00pm. WAPA TV. Jul 30, 2012

#McVey E. Exclusive: US retail marijuana sales on pace to rise 40% in 2020, near $37 billion by 2024. Marijuana Business Daily. https://mjbizdaily.com/exclusive-us-retail-marijuana- sales-on-pace-to-rise-40-in-2020-near-37-billion-by-2023/. Published June 30, 2020.Accessed Older adults the prevalence increased from 2.4% to Jul 15, 2021. of past-year use from 2015 ^^ AHasin DS, Saha TD, Kerridge BT, et al. Prevalence of Marijuana Use Disorders in the 4.2% United States Between 2001-2002 and 2012-2013. JAMA Psychiatry. 2015;72(12):1235–1242. to 2018 ^ doi:10.1001/jamapsychiatry.2015.1858p

^ Older adults and medical marijuana: Reduced stigma and increased use (2020) Available at: https://www.health.harvard.edu/blog/older-adults-and-medical-marijuana-reduced-stigma- and-increased-use-2- th 2020040119321#:~:text=According%20to%20a%20recent%20study,4.2%25%20from%20201 2019 – Children marijuana 8 - 11.8% 5%20to%202018. Accessed Jul 23, 2021. use in the past year @ @NIDA. 2021, April 20. What is the scope of marijuana use in the United States?. Retrieved th from https://www.drugabuse.gov/publications/research-reports/marijuana/what-scope- 10 – 28.8% marijuana-use-in-united-states Accessed Jul 23, 2021. 12th - 35.7%

12 Legal Implications regarding Medicinal Cannabis at National Level Federal Regulations Objective 2

13 Federal Law: Cannabis is illegal

Schedule I substance The term ’marihuana’ means all parts of the plant Cannabis sativa L Drug Enforcement Administration (DEA) Medicare Medicaid Universities and schools' regulations Up to now, no legal charges has been presented

Image available at: https://www.campusdrugprevention.gov/content/cannabis-campus-not- 14 allowed FDA Regulation of Cannabis and Cannabis-Derived Products CBD

Federal Food, Drug and The use in human food of Not been evaluated or FDA approved Cosmetic Act hemp seed-derived food approved by FDA (FD&C Act) ingredients is LEGAL

• ONLY cannabidiol in • Other CBD products • It is ILLEGAL to market • hulled hemp seed people one year and CBD and THC as… • hemp seed protein older powder • food additive • hemp seed oil • Lennox Gastaut • use in human or animal syndrome (LGS) food • Dravet Syndrome (DS) • label these as dietary • Tuberous Sclerosis supplements Complex (TSC)

FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD)Jan 22, 2021. Available at: https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived- 15 products-including-cannabidiol-cbd . Accessed Jul 14, 2021 CBD products Quality Control and Labeling

Inaccurate labeling

69% of the products did not contain the labeled amount of CBD* Corroon J, Kight R. Regulatory status of cannabidiol in the United States: A ✓36 products (43%) having >10% of the labeled content perspective. Cannabis Cannabiboid Res. 2018;3(1):190-194. ✓22 products (26%) having <10% of the labeled content *Bonn-Miller MO, Loflin MJE, Thomas BF, et al. Labeling accuracy of cannabidiol extracts sold online. JAMA. 2017;318:1708-1709. THC not reported on label Goodman CK. Buyer beware: CBD could be this century’s snake oil. Chicago Some labels include QR codes to access certificates of analysis Tribune. July 23, 2019. Accessed at https://www.chicagotribune.com/marijuana/snscbd-oil-could-be-snake-oil- 20190724-bfd3qgsemnetbigwdmb7pxitje-story.html, Jul 22, 2019.

Contaminants Williams T. CBD is wildly popular. Disputes over its legality are a growing source of tension. New York Times. May 6. 2019. Accessed athttps://www.nytimes.com/2019/05/06/us/cbd-cannabis-marijuana- hemp.html, Jul 22, 2019.

Lack of evidence - No clinical trials S. Alcohol and Tobacco Tax and Trade Bureau. Hemp ingredients in alcohol beverage formulas. April 25, 2019. Accessed at https://www.ttb.gov/industrycirculars/ttb-industry-circulars-19-1, Jul 24, 2019.

Mull A. The CBD crackdown has begun. Atlantic. Feb 6, 2019. Accessed at Sales - States regulations differ https://www.theatlantic.com/health/archive/2019/02/new-york-city-cbd- crackdown/582193/, Jul 22, 2019.

Bridgeman MB, Abazia DT. Medicinal cannabis: history, pharmacology, and Colorado implications for the acute care setting. P T. 2017;42(3):180-188. Missouri New York – Maine Ohio – Texas - Nebraska 16 FDA Regulation of Cannabis and Cannabis-Derived Products CBD

• Precautions • Special populations • Somnolence, irritability, agitation • NO COMPREHENSIVE RESEARCH • GI distress (diarrhea - human studies) • Pregnancy - High doses • Liver injury • Reproductive toxicity of developing • Drug interactions male fetuses (animal studies) • Pets • Breast feeding • Reports of potential contaminants (e.g., • Some amount will be transferred to pesticides, heavy metals, bacteria, and babies through breast milk fungus)

FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD) Jan 22, 2021. Available at: https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol- cbd . Accessed Jul 14, 2021. 17 Epidiolex (cannabidiol) [package insert]. Carlsbad, CA: Greenwich Biosciences, Inc; 2020 FDA Regulation of Cannabis and Cannabis-Derived Products THC

• Dronabinol - synthetic versions of THC • Decreased plasma testosterone; decreased • Marijuana smoke contains many of the same sperm count, concentration, and motility* harmful components as tobacco smoke • Pregnancy • It can enter the fetal brain from the mother’s bloodstream • Research suggests increased risk for premature birth, low birth weight and potentially stillbirth • Breast feeding • Breastmilk can contain THC for up to 6d after use and may affect a newborn’s brain development (hyperactivity, poor cognitive function, others)

Dalterio SL, deRooij DG. Maternal cannabinoid exposure. Effects on spermatogenesis in male offspring. Int J Androl. 1986 Aug;9(4) FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD)Available at: https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd . Accessed Jul 14, 2021. 18 *National Academies of Science, Engineering and Medicine The health effects of cannabis and cannabinoids: committee conclusions. Published January 2017 Available online http://nationalacademies.org/hmd/~/media/Files/Report%20Files/2017/Cannabis- Health-Effects/Cannabis-conclusions.pdf . Accessed: Jul 14, 2021 DEA Continues to Prioritize Efforts to Expand Access to Marijuana for Research in the United States

Date Comment

May 14, 2021 To increase opportunities for medical and scientific research.

Review of certain marijuana grower applications, to soon register additional entities authorized to produce marijuana for research purposes.

Currently, the National Center for the Development of Natural Products at the University of Mississippi is the only approved supplier of marijuana for research purposes in the US, and that production has been exclusively for the National Institute on Drug Abuse.

DEA Continues to Prioritize Efforts to Expand Access to Marijuana for Research in the United States (May 14, 2021). Available at: https://www.dea.gov/press-releases/2019/08/26/dea-announces-steps-necessary-improve-access- marijuana-research .Accessed Jul 14, 2021 19 Agriculture Improvement Act “Farm Bill” December 20, 2018

• Industrial hemp - the plant Cannabis sativa L. and any part of that plant, including the seeds thereof and all derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers, whether growing or not, with a delta-9 THC concentration of not more than 0.3% on a dry weight basis. (not controlled substance under federal Controlled Substance Act) • Products • Food or dietary supplements cannot contain CBD no matter the source (hemp or marijuana) FD&C Act / FDA • Market forces* This Photo by Unknown Author is licensed under CC BY-NC-ND

*Hemp was supposed to boost farmers. It’s turned out to be a flop. Oversupply and a lack of federal rules led to trouble for the industry. (05/ 20/2020)Available at: https://www.politico.com/news/2020/05/25/hemp- farmers-275046 Accessed Jul 2021 20 DEA on Marijuana Crops, California

• Unregulated water use from wells - Aggravates droughts problems • Waste lands • Security • Industrial growers are moving to states w/o registering with local governments and taking the product out of state, avoiding taxes • Marijuana from Mexico

DEA Los Angeles SAC Bill Bodner speaks w/ ABC7 about illegal Image available at: https://www.latimes.com/local/california/la-me-santa-barbara-pot-grows-20190612-htmlstory.html marijuana grows & counterfeit Adderall. (June 29, 2021) 21 Available at: https://www.youtube.com/watch?v=poSXdo9VViI . Accessed Jul 14, 2021. Cannabis Legal Status in United States

• Recreational use • 19 states: Colorado, Washington, Alaska, Oregon,, California, Maine, Massachusetts, Nevada, Michigan, Vermont,, Illinois, Arizona, Montana, New Jersey, South Dakota, New York, Virginia, New Mexico, Connecticut • DC, Guam • Medicinal use • 36 states, District of Columbia, Guam, Puerto Rico and U.S. Virgin Islands have approved comprehensive, publicly available medical marijuana/cannabis programs Image available at: https://www.cosmeticsdesign.com/Article/2019/01/24/Aurora-Cannabis-breaks-into- Mexico-market-with-acquisition • Some states have laws that limit THC content or allow CBD oil only Hansen Claire, Alas Horus. Where Is Marijuana Legal? A Guide to Marijuana Legalization (June 30, 2021). Available at: https://www.usnews.com/news/best-states/articles/where-is-marijuana-legal-a-guide-to-marijuana-legalization . Accessed Jul 23, 2021 22 State Medical Marijuana Laws. Available at: https://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx . Accessed Jul 23, 2021 Pharmacists and Cannabis: Most states do not specify a defined role for pharmacists

• 7 states include mandated pharmacist involvement: Connecticut, Arkansas, Louisiana, Utah, Minnesota, New York, and Pennsylvania • Connecticut - only pharmacists can obtain a medical marijuana dispensary permit (MC - Schedule II) • Louisiana- specialty marijuana pharmacy licenses and the Board of Pharmacy providing oversight (since 2018) • Minnesota, New York, and Pennsylvania - require a pharmacist on site • Arkansas - pharmacist consultant for each dispensary, but not necessarily on site • Pennsylvania - pharmacist or physician on site at the dispensary. Allows a nurse practitioner or physician assistant when a dispensary has multiple locations.

Vivian JC. Dispensing cannabis. US Pharmacist. https://www.uspharmacist.com/article/dispensing-cannabis .(April 14, 2016). Accessed Jul 11, 2021. Marijuana pharmacies: the beginning of the licensure process. Louisiana Board of Pharmacy. http://www.pharmacy.la.gov/index.cfm?md=pagebuilder&tmp=home&pid=401 . Accessed Jul 11, 2021. State of Arkansas. Arkansas Medical Marijuana Amendment of 2016. HB2190. https://www.arkleg.state.ar.us/Acts/Document?type=pdf&act=1024&ddBienniumSession=2017%2F2017R . (March 6, 2017). Accessed Jul 11, 2021. Gubb SE. Pharmacists' role under Pennsylvania's medical marijuana law. https://cdn.ymaws.com/www.papharmacists.com/resource/resmgr/Legislative/Pharmacists%27_Role_Under_Penn.pdf . Accessed Jul 11, 2021. Zheng Lili. DEA: Pharmacists dispensing marijuana would be in violation of federal law. (July 11, 2018). Available at: https://kfor.com/news/dea-pharmacists-dispensing-marijuana-would-be-in-violation-of-federal- law/#:~:text=Marijuana%2C%20a%20schedule%201%20drug,to%20work%20at%20a%20dispensary .Accessed Jul 30, 2021. Pharmacists tread carefully into the world of medical cannabis Pharmacy Today Available at: https://www.pharmlcytoday.org/article/S1042-0991(17)31966-7/fulltext .(JANUARY 2018) Accessed Jul 30, 2021. 23 Pharmacists and the future of cannabis medicine Schmitz, Natalie et al. Journal of the American Pharmacists Association, Volume 60, Issue 1, 207 - 211 Even as several states and Washington - DC, allow medical marijuana use, the federal government still strictly prohibits it a. True b. False

24 Legal Implications regarding Medicinal Cannabis at Local Level

Ley #42 (9 de julio de 2017) Ley para manejar el estudio, desarrollo e investigación del cannabis para la innovación, normas aplicables y límites Reglamento #9038 (2 julio de 2018) Reglamento para el uso, posesión, cultivo, manufactura, producción, fabricación, dispensación, distribución e investigación del cannabis medicinal. Objective 2

25 Puerto Rico and Medicinal Cannabis

• Not allowed • Smoking /exceptions Delito menos grave para aquellos • Recreational use médicos que autoricen el uso de • Driving under its effects cannabis medicinal a personas que • Bona-fide relationship no sufren de una condición • Patient’s monthly supply identificada por medio de • Product presentation reglamentación • Patient’s follow-up

Ley #42 (9 de julio de 2017) Ley para manejar el estudio, desarrollo e investigación del cannabis para la innovación, normas aplicables y límites

Reglamento #9038 (2 julio de 2018) 26 Reglamento para el uso, posesión, cultivo, manufactura, producción, fabricación, dispensación, distribución e investigación del cannabis medicinal. Initial Operation Requirements for Medical Cannabis Dispensaries in Puerto Rico

Objective 3

27 Dispensario de Cannabis Medicinal Permisología

Departamento de Salud Oficina de Sustancias Controladas y Cannabis Medicinal PO Box 70184 San Juan, PR 00936-8184

​Tel: 787-765-2929 ext.3504, 3505, 6803 y 6809​

Enlace http://www.salud.gov.pr/dept-de-salud/pages/cannabis-medicinal.aspx Correo Electrónico [email protected] [email protected]

28 Dispensarios Expedición de Licencia

Reglamento 9038 (2018) Cap. VIII Art 42, p35 La Junta Reglamentadora del Cannabis Medicinal podrá:

• Establecer la cantidad de licencias a expedirse • Recomendar cantidad de licencias a otorgar, • Regular la cantidad de solicitudes a ser aceptadas velando por el interés del paciente, su oferta y para dispensario/año natural corriente. Dicho demanda. parámetro se publicará en o antes de las primeros 15 • Evaluar las licencias de dispensarios días del año natural • capacidad económica • Basado en una proporción pacientes versus y • dispensario emitidas acceso al paciente • Considerando las limitaciones geográficas, de transportación y de acceso que enfrenta la Isla

29 Dispensarios Expedición de Licencia Reglamento 9038 (2018) Cap. VIII Art 42, p35 • Recomendar cantidad de licencias a otorgar La Junta Reglamentadora del Cannabis • Interés del paciente Medicinal (Junta) podrá: • Oferta y demanda • Establecer la cantidad de licencias a expedirse • Evaluar las licencias de dispensarios • Regular la cantidad de solicitudes a ser • Capacidad económica aceptadas para dispensario/año natural • Acceso al paciente corriente • Publicado en o antes de las primeros 15 días del año natural • Proporción pacientes versus licencias de dispensario emitidas • Limitaciones geográficas, de transportación y de acceso que enfrenta la Isla

30 Dispensario Licencia/Autorización

Ley #42 (2017) - Cap. I Art 2, p7 Reglamento #9038 (2018) - Cap. XII, Art 58, p72 Reglamento #9038 (2018) - Cap. I Art 5, p8 • Vigencia de la licencia - 1 año • Licencia o autorización • emitida por la Junta Reglamento #9038 (2018) - Cap. I Art 5, p5 • Dispensario autorizado • toda propiedad comercial donde se vende cannabis al detal a los pacientes o a sus acompañantes autorizados e incluyendo el servicio de entrega a los pacientes autorizados

31 Dispensario Pago de Derechos

Reglamento #9038 Cap. XXV Art 129, p 148-150 • Los pagos de derechos se realizarán en sellos de rentas internas • Solicitud de Licencia $5,000.00 • Licencia y Renovación $20,000.00

This Photo by Unknown Author is licensed under CC BY-NC-ND 32 Dispensario Documentación

Reglamento #9038 (2018) Cap. XII, Art 59, p75 • Tener visibles las licencias, permisos y certificaciones expedidas para propósitos de su operación • Mantener copia de los procedimientos operacionales estandarizados internos y un programa de control de calidad y garantía de calidad • Protocolos y Procedimientos de Estándares Operacionales (Standard Operation Procedures (SOP’s) • Procedimiento sobre las medidas para evitar la contaminación y mantener la seguridad del producto

33 Dispensarios Seguridad

Reglamento #9038 (2018) - Cap. XII Art Ley # 42 (2017) - Cap. V Art 17, p 18 60, p 75-76; Cap. XII Art 58, p73 •Iluminación y Limpieza •Herramientas digitales de •“No entre -Área de Acceso información del paciente Restringido - Acceso limitado SOLO al •Facilitar la adquisición del cannabis paciente de Cannabis Medicinal” medicinal en cualquier dispensario, •Letreros de Entrada y Salida 12“ x pero garantizando que no se exceda 12” mínimo y letras ½”de altura de la cantidad dispuesta por dicho mínimo reglamento •Registro de Inventario •Nombre del empleado que remueve el producto, el día y hora, la descripción del producto, nombre y número de paciente o acompañante autorizado •Contrato del Sistema de Rastreo de Inventario del Departamento de This Photo by Unknown Author is licensed under CC BY-SA Salud 34 Dispensarios Seguridad

Ley #42 (2017) - Cap. V Art 17, p18 o Sistemas de vigilancia electrónica ✓ Monitoreado y funcionando 24/7 ✓ Transmitiendo video y fotos en vivo o Centro de comando certificado

Reglamento #9038 (2018) - Cap. IX Art 50, p48; Cap. XII Art 58, p72 o Al menos 1 guardia de seguridad durante el horario de operaciones y abierto al público ✓ Expediente delictivo ✓ Controlar/Autoriza el acceso al establecimiento This Photo by Unknown Author is licensed under CC BY-NC-ND ✓ Verificar la tarjeta de identificación del patrocinador 35 Dispensarios Seguridad - Sistema de vigilancia

Mensajes de voz Grabación de El centro de comando Capacidad de Monitoreo Alarmas pregrabados videos/fotos 24/7 debe poder recibir… continuar funcionando • Perímetro • Alarmas de pánico • Sistema programado • Incluyendo los • Transmisión con Pese a interrupción del con activación para enviar estos a puntos de venta fecha y hora correcta servicio eléctrico • Sensores de manual agencias de orden de los eventos (sin movimiento público • Las grabaciones se que se obscurezca la • "duress alarms” retendrán por un imagen) • "holdup alarms" mínimo de 90 días luego del suceso • Mensajes para alertar sobre fallas del sistema, dentro de un máxima de 5 minutos (sistema de notificación de fallas)

Reglamento #9038 (2018)- Cap. XII Art 58, p72 -73 36 Dispensario Localización y Áreas

Ley #42 (2017) - Cap. V Art 17, p16 Reglamento #9038 - Cap. XII, Art 58, p72 -73

• Localización o la presentación, promoción, • El dispensario debe tener al menos 2 accesos rotulación o cualquier anuncio de un ÁREAS SEPARADAS CON CONTROLES DE dispensario - no podrá estar a menos de cien ACCESO (100) metros de una escuela pública o privada 1.acceso general y/o centro de cuido 2.área de administración - todos los registros del establecimiento incluyendo aquellos que exige este reglamento y se almacenará la bóveda con el dinero producto de las ventas 3.área de bóveda para almacenamiento de cannabis medicinal y/o productos derivados 4.acceso restringido de dispensación 5.área de carga

37 Dispensario Acceso

Reglamento #9038 (2018) • Paciente o acompañante - registro para el uso del Cannabis Medicinal válido y vigente (Cap. II Art 8 p14)

Ley #42 (2017) • Paciente residente en PR o acompañante autorizado - identificación emitida por la Junta (Cap. I Art 1, p6; Cap. III Art 13, p14) • Pacientes no residentes en PR - identificación de su jurisdicción (Cap. V Art 17, p16) • No se admiten menores de 21 años (Cap. III Art 10, p13)

• No se permite consumir cannabis en el dispensario (MARCO LEGAL QUE This Photo by Unknown Author is licensed under CC BY-SA-NC PROVEE ESTA LEY, p6 y Cap. III Art 10, p13) 38 Medicinal cannabis dispensary requirements in Puerto Rico include… a. Tracking system b. Vaults for money and cannabis c. Security mechanisms d. All alternatives are correct

39 Training Requirements for Employees of Medical Cannabis Dispensaries in Puerto Rico

Objective 4

40 Documento en WORD Reglamento #9038- Cap. XII Art 59, p75 ; Cap. XXV Art 129, p150 Todo propietario de un dispensario de Cannabis Medicinal debe obtener y retener copia de la documentación que evidencie que Requisitos de cada dispensador posee Capacitación de • Adiestramiento de Licencia Ocupacional Técnico de • 6 hrs. Educación (3 hrs. /año) • Curso sobre dispensación de Cannabis Medicinal (Curso de Dispensario Técnico de Dispensario ) • 6 hrs. Educación (3 hrs. /año) • Licencia ocupacional vigente (2 años)

41 Reglamento #9038- Cap. XXV Art 129, p150 • Solicitud para Licencias Ocupacionales de Individuos • Pago de derechos • Gerencial $500.00 Requisitos de • Empleado $150.00 Capacitación de Técnico de Dispensario

42 In Puerto Rico, budtenders or dispensary technicians must have a minimum academic preparation of (check all that apply):

a. Fourth year of high school b. Two years of post-secondary studies c. Bachelor of Science degree d. One year in some health-related job

43 Indications for Medicinal Cannabis in Puerto Rico

Ley #42 (9 de julio de 2017) Ley para manejar el estudio, desarrollo e investigación del cannabis para la innovación, normas aplicables y límites

Reglamento #9038 (2 de julio de 2018) Reglamento para el uso, posesión, cultivo, manufactura, producción, fabricación, dispensación, distribución e investigación del cannabis medicinal.

Objective 5

44 Indicaciones para uso de Cannabis Medicinal Condiciones Médicas Debilitantes

Reglamento #9038 - Cap. I Art 5, p 3

Alzhéimer • Desórdenes de Ansiedad (Diagnostic and Statistical Manual of Mental Disorders) • Anorexia • Desórdenes relacionados al Virus de la • Artritis Inmunodeficiencia Humana (VIH) • Autismo • Enfermedades degenerativas (Esclerosis Lateral Amiotrófica, Esclerosis Múltiple, • Cáncer y el tratamiento de quimioterapia para Enfermedad Inflamatoria Intestinal) el Cáncer • Enfermedades incurables y avanzadas que • Depresión requieran un cuidado paliativo • Epilepsia • Fibromialgia

45 Indicaciones para uso de Cannabis Medicinal, continuación…

• Glaucoma • Síndrome de Inmunodeficiencia Adquirida • Hepatitis C (SIDA) • Trastorno Bipolar • Insomnio • • Lesiones en el Cordón Espinal Cualquier otra condición que cause caquexia • • Migraña Dolor crónico • Náuseas severas o espasmos musculares • Neuropatías Periferales persistentes • Parkinson • otra que el Cuerpo Asesor Médico • Síndrome de Estrés Postraumático recomiende y la Junta así lo exprese mediante Determinación Administrativa.

46 The following are heath conditions included in the #9038 bylaws, except:

a. Anxiety b.Hepatitis C c. Chronic pain d.Attention deficit/hyperactivity disorder

47 Medicinal Cannabis Pharmacologic and Safety Considerations

Objective 6

48 Cannabinoids Pharmacology

Endogenous cannabinoid > 100 cannabinoid Endocannabinoid system Therapeutic effects substances compounds* • Anandamide Active cannabinoids: • Common to all vertebrates • G – Protein coupled ✓1964 - delta-9 and many invertebrates cannabinoid receptors • 2-arachidonoyl-glycerol (2- tetrahydrocannabinol • CB1 – Central Nervous AG) (THC) – partial agonist • Present in living organisms System (CNS), most since 600 million years abundant • Others: Noladin ether, ✓Cannabidiol ago • CB2 – Immune Cells, Virodhamine, N- (CBD) – negative immune function, arachidonyldopamine(NA allosteric modulator inflammation, CNS DA), Oleamide • Other mechanisms of action

Mahvan TD et al., Marijuana use in the Elderly: Implications and considerations The Consultant Pharmacist 2017; 32: 341-349. *National Institutes of Health - National Institute on Drug Abuse. ¿Es la marihuana un medicamento? (July 2015): pages. 1-5. Melton ST. Stirring the Pot: Potential drug Interactions with Marijuana Published: June 8, 2017. Available online: https://www.medscape.com/viewarticle/881059 Accessed: February 12, 2018. 49 Bianca Calderon, T. J. Sayre,. Cannabidiol Use in Older Adults. Published: March 19, 2020. US Pharmacist https://www.uspharmacist.com/article/cannabidiol-use-in-older-adults . Accessed September 11, 2020. Cannabinoids Receptors: CB1

o THC Central and o Pain modulation (CNS) peripheral o Antiemetic neurons o Appetite stimulant GI system Liver o Psychoactivity o CBD Connective o Pain modulation (CNS) tissues, Adipocytes o Anticonvulsant muscles

CV system Gonads

Mahvan TD et al., Marijuana use in the Elderly: Implications and considerations The Consultant Pharmacist 2017; 32: 341-349. National Institutes of Health - National Institute on Drug Abuse. ¿Es la marihuana un medicamento? (July 2015): pages. 1-5. Levinsohn EA, Hill KP. Clinical uses of cannabis and cannabinoids in the United States. J Neurol Sci. 2020 Apr 15;411:116717. doi: 10.1016/j.jns.2020.116717. Epub 2020 Jan 30. PMID: 32044684. 50 Int J Mol Sci. 2018;(19):833. doi:10.3390/ijms19030833. Cannabinoids Receptors: CB2

o THC o Process of inflammation (Inflammatory bowel disease, Crohn’s disease) o Pain pathways (e.g., neuropathic pain) Immune o CBD cells o Process of inflammation o Pain pathways (e.g., neuropathic pain) o Mechanism not fully understood Brain o Multiple Sclerosis - spasticity and central pain (RCTs)

Mahvan TD et al., Marijuana use in the Elderly: Implications and considerations The Consultant Pharmacist 2017; 32: 341-349. National Institutes of Health - National Institute on Drug Abuse. ¿Es la marihuana un medicamento? (July 2015): pages. 1-5. Levinsohn EA, Hill KP. Clinical uses of cannabis and cannabinoids in the United States. J Neurol Sci. 2020 Apr 15;411:116717. doi: 10.1016/j.jns.2020.116717. Epub 2020 Jan 30. PMID: 32044684. Int J Mol Sci. 2018;(19):833. doi:10.3390/ijms19030833. 51 Epilepsy - CBD

Non-Cannabinoid MOAs 1. Decreasing synaptic release of glutamate 2. Stimulating alpha-3 and alpha-1 glycine receptors 3. Activating 5-HT receptors 4. Altering GABA, adenosine and norepinephrine signaling 5. Modulation of intra-cellular calcium through GPR-55, TRPV, and VDAC

Image available a: https://www.frontiersin.org/files/Articles/345007/fphar-09-00482-HTML/image_m/fphar-09-00482-g001.jpg. Accessed Jul 24, 2021 52 Which of the following substances is an endogenous ligand for the cannabinoid receptor? a. 2-arachidonoyl-glycerol (2-AG) b. Anandamide c. Prostaglandin d. There is no known endogenous ligand

53 What to High quality evidence of cannabis consider as a Patient’s history of adequate trials with FDA pharmacist approved drugs Medical and psychiatric evaluation to identify risk when taking factors care of a patient Discuss legal and logistical concerns with using using Cannabis? cannabis Challenges during hospitalization

“Start low – go slow – stay low” approach*

*MacCallum CA, Russo EB. Practical considerations in medical cannabis administration and dosing. Eur J Int Med. 2018;49:12-18 54 Medicinal Cannabis: Formulations

Administration Labeling Strength Purity form Differences

• Inhalation •Different degrees of •Cryptococcus, Mucor, and • THC : CBD ratio might • Oral strength depending on Aspergillus fungi, and not be specified • Oromucosal (spray) product and Escherichia coli, Klebsiella pneumoniae, and • Topical - creams, environmental factors Acinetobacter baumannii ointments, patches, bacteria. vaginal sprays, and rectal (e.g., bacteria and fungi in suppositories marijuana samples from • Food/drinks Northern California dispensaries)

Mahvan TD et al., Marijuana use in the Elderly: Implications and considerations The Consultant Pharmacist 2017; 32: 341-349. Barrett J, Assistant Editor. Fungal, Bacterial Contaminants Found in Some Medical Marijuana. Pharmacy Times. (February 15, 2017). Available at: 55 http://www.pharmacytimes.com/news/fungal-bacterial-contaminants-found-in-some-medical-marijuana . Accessed: February 5, 2018 Dosage form Onset Duration Comments Inhaled Rapid (5-10 min.) 2-4 hrs. Toxicity -rare Absorption Rapid time to peak and self titration* Oral Slow (30 min. to 2 hrs.) 4-12 hrs. Toxicity - Time to peak 1-2 hrs. that increased can be delayed 6 hrs. due accidental to digestion* overdose* *Mahvan TD et al., Marijuana use in the Elderly: Implications and considerations The Consultant Pharmacist 2017; 32: 341-349. (children and N. Schmitz, L. Richert / Journal of the American Pharmacists Association 60 (2020) 207e211 adolescents)

Parmar JR, Forrest BD, Freeman RA. Medical marijuana patient counseling Oromucosal 15 to 40 min. 2 to 4 hrs. points for health care professionals based on trends in the medical uses, efficacy, and adverse effects of cannabis-based pharmaceutical drugs. Res (CBD) Social Adm Pharm. 2016 Jul-Aug;12(4):638-54. doi: 10.1016/j.sapharm.2015.09.002. Epub 2015 Sep 16. PMID: 2644347 Tincture 30 min. 4-6 hrs. **National Academy of Sciences (Health and Medicine Division): The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and (THC:CBD) Recommendations for Research. January 12, 2017. Accessed at https://www.nap.edu/catalog/24625/the-health-effects-of-cannabis-and- cannabinoids-the-current-state Rectal use 1-2 hrs. 4-8 hrs. Suppositories Topical use 15-30 min.** 2 hrs. CBD • Patch accumulates in • Cream adipose tissue • Spray 56 EFFECT OF CANNABINOIDS ON DRUG-METABOLIZING ENZYME CYTOCHROME P450 Cannabinoid Substrate Inhibit Induce

THC 2C9 2B6 1A2 Distribution 2C19 2C9 3A4 2D6 95-99% protein bound 3A4 CBD 2C9 1A1 3A4 1A2 1B1 Metabolism 2B6 st Liver 1 pass: 11-OH-THC and CBD 2C9 Interactions 2C19 2D6 3A4 Parmar JR, Forrest BD, Freeman RA. Medical marijuana patient counseling points for health care professionals based on trends in the medical uses, efficacy, and adverse effects of cannabis-based pharmaceutical drugs. Res Social Adm Pharm. 2016 Jul- Aug;12(4):638-54. doi: 10.1016/j.sapharm.2015.09.002. Epub 2015 Sep 16. PMID: 2644347 Cannabis 1A2

Bianca Calderon, T. J. Sayre. Cannabidiol Use in Older Adults. Published: March 19, 2020. US Pharmacist (smoked) 3A4 https://www.uspharmacist.com/article/cannabidiol-use-in-older-adults . Accessed September 11, 2020 57 Elimination • THC - Occurs over several days • THC 20% to 35% in urine 65% to 80% in feces

• CBD - most unchanged in feces

58

Lemberger L, Axelrod J, Kopin IJ. Metabolism and disposition of delta-9-tetrahydrocannabinol in man. Pharmacol Rev. 1971;23:371–380. Goulle JP, Saussereau E, Lacroix C. Delta-9-tetrahydrocannabinol pharmacokinetics] Ann Pharm Fr. 2008;66:232–244. Adverse effects to consider if a patient using Cannabis

CNS anxiety, panic attacks, CARDIOVASCULAR psychosis, dysphoria, EYES tachycardia, bradycardia, Cannabis hyperemesis drowsiness, dizziness, vertigo, Dry mouth reddened eyes, changes in increased blood pressure, syndrome ataxia, difficulty in visual perception orthostasis concentration, euphoria, impaired motor skills

LOW RISK OF OVERDOSE AND DEATH REPORTS: RESPIRATORY SYSTEM Immunosuppression Changes in blood glucose Increased risk of bleeding increased risk of heart failure, cough and bronchitis (smoked) stroke, coronary artery disease, sudden cardiac death, and hypertension

Parmar JR, Forrest BD, Freeman RA. Medical marijuana patient counseling points for health care professionals based on trends in the medical uses, efficacy, and adverse effects of cannabis-based pharmaceutical drugs. Res Social Adm Pharm. 2016 Jul-Aug;12(4):638- 54. doi: 10.1016/j.sapharm.2015.09.002. Epub 2015 Sep 16. PMID: 2644347. National Academies of Science, Engineering and Medicine The health effects of cannabis and cannabinoids: committee conclusions. Published January 2017 Available online http://nationalacademies.org/hmd/~/media/Files/Report%20Files/2017/Cannabis-Health- 59 Effects/Cannabis-conclusions.pdf . Accessed: Jul 14, 2021 Medicinal Cannabis: Contraindications

Absolute contraindications Relative contraindications

• Allergies • Severe cardiovascular, • Acute psychosis and immunological, liver, or other unstable psychiatric kidney disease, especially conditions in acute illness • Cannabis may exacerbate arrhythmia or a history of arrhythmias

This Photo by Unknown Author is licensed under CC BY-ND 60 Perwee R. Handbook of Cannabis (Handbooks in Psychopharmacology) Reprint Edition 2015 Government of the District of Columbia, Department of Health. Medical Cannabis Adverse Effects & Drug Interactions. (Dec 22, 2015). Available at: https://doh.dc.gov/sites/default/files/dc/sites/doh/publication/attachments/Medical%20Cannabis%20Adverse%20Effects%20and%20Drug%20Interactions_0.pdf Accessed Jul. 30, 2021 FDA approved Cannabinoid Products Cannabinoid Dosage Form Schedule Dose Indication Synthetic delta-9-THC tablets /capsules III 2.5–10 mg oral chemotherapy induced nausea and vomiting - liquified dronabinol II l5 mg/mL oral cachexia related to HIV (AIDS) or solution cancer

Nabilone capsules II 1 – 2 mg twice chemotherapy-induced nausea and synthetic cannabinoid daily for adults vomiting (similar to THC) 0.5 –1 mg twice cachexia related to HIV or cancer daily for pediatric antiemetic and analgesic for patients neuropathic pain

Cannabidiol pure plant derived 100 V weight-based childhood seizures (1yr. and older) mg/mL of pure CBD dosing from Patient Medication Guide extract (sesame oil) 5mg/kg/day to of 20 mg/kg/day max.

Mahvan TD et al., Marijuana use in the Elderly: Implications and considerations The Consultant Pharmacist 2017; 32: 341-349. Levinsohn EA et al. Clinical uses of cannabis and cannabinoids in the United States. Journal of the Neurological Sciences 411 (2020) 116717 Rubin R. The path to the first FDA-approved cannabis-derived treatment and what comes next. JAMA. 2018;320(12):1227-1229. Cannabidiol [package insert]. Carlsbad, CA: Greenwich Biosciences, Inc; 2020 61 England and Canada approved Cannabinoid Product

Cannabinoid Dosage Form Dose Indication Nabiximols oromucosal spray 4-8 sprays daily neuropathic pain*, spasticity* and standardized extract of 27mg/mL THC+ 25mg/mL CBD Most patients require 12 overactive bladder, among others tetrahydrocannabinol sprays or less; dosage (THC), cannabidiol should be adjusted as (CBD), other minor needed and tolerated. cannabinoids

Mahvan TD et al., Marijuana use in the Elderly: Implications and considerations The Consultant Pharmacist 2017; 32: 341-349. GW Pharma LTD. PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION. (Rev. Dec 11, 2019) Available at: https://omr.bayer.ca/omr/online/sativex-pm- en.pdf. Acceded Aug 3, 2021 62 Evidence Based Medicine and Cannabis

Indication Evidence Comments

Chronic pain in adults (cannabis)* Conclusive/ Risk vs Benefit Substantial Opiates vs Cannabis * ** 64% reduction in use of opioids*** Medicare D Depressive symptoms Ineffective in patients with chronic pain* (nabiximols, dronabinol, nabilone)

*National Academies of Science, Engineering and Medicine The health effects of cannabis and cannabinoids: committee conclusions. Published January 2017 Available online http://nationalacademies.org/hmd/~/media/Files/Report%20Files/2017/Cannabis-Health-Effects/Cannabis-conclusions.pdf Accessed: February 14, 2018 **National Institutes of Health - Marijuana and Cannabinoids: A Neuroscience Research Summit. 2016 NIH Campus, Bethesda, Maryland Available online: https://www.drugabuse.gov/sites/default/files/briefmjsummitmeetingsummary.pdf Accessed: April 16, 2018. 63 ***Boehnke KF, Litinas E, Clauw, DJ. Medical cannabis use is associated with decreased opiate medication use in a retrospective cross-sectional survey of patients with chronic pain. J Pain. 2016;17(6):739–44 Evidence Based Medicine and Cannabis

HIV related to Neuropathic pain Diabetic neuropathy neuropathic pain • Vaporized cannabis • Inhaled cannabis • Smoked cannabis (1ry therapy) • Central neuropathic pain • Spontaneous patient pain rating • Reduced central, peripheral and (spinal cord injury and disease) • Dose-dependent reduction in HIV-associated neuropathic • Reduced pain - rating scale pain pain • No evidence of a dose- • RTCs • RTCs dependent effect • UNKNOWN effective analgesic combination THC:CBD • NO RTCs

WHO Expert Committee on Drug Dependence Pre-Review. Cannabis plant and cannabis resin Section 4: Therapeutic use (2018). Available at: https://www.who.int/medicines/access/controlled-substances/Section4.CannabisPlant.TherapeuticUse.pdf . Accessed Jul 30, 2021. 64 Evidence Based Medicine and Cannabis

This Photo by Unknown Author is licensed under CC BY-NC

Indication Evidence Comments Nausea/Vomiting Limited THC (dronabinol tablets, nabilone) in HIV and cancer patients Nausea/Vomiting due to Moderate Oral cannabinoids effective as anti-emetics * chemotherapy Ondansetron vs Cannabis (survey: both effective) **

*National Academies of Science, Engineering and Medicine The health effects of cannabis and cannabinoids: committee conclusions. Published January 2017. Available online http://nationalacademies.org/hmd/~/media/Files/Report%20Files/2017/Cannabis-Health- Effects/Cannabis-conclusions.pdf Accessed: February 14, 2018 65 *Olivier Beauchet. Medical cannabis use in older patients: Update on medical knowledge. Maturitas 118 (2018) 56–59 **Zikos, T.A., Nguyen, L., Kamal, A. et al. Marijuana, Ondansetron, and Promethazine Are Perceived as Most Effective Treatments for Gastrointestinal Nausea. Dig Dis Sci 65, 3280–3286 (2020). https://doi.org/10.1007/s10620-020-06195-5 Evidence Based Medicine and Cannabis - Multiple Sclerosis

https://www.webconsultas.com/esclerosis-multiple/sintomas-de-la-esclerosis-multiple-317

Painful spasms / Spasticity Symptoms Central pain Bladder frequency** Neuropathic pain**

Oral cannabis extract Conclusive evidence Limited evidence (nabiximols) and patient reported* clinician measured* orally administered, THC appear to be the most effective cannabinoid

*National Academies of Science, Engineering and Medicine The health effects of cannabis and cannabinoids: committee conclusions. Published January 2017 Available online http://nationalacademies.org/hmd/~/media/Files/Report%20Files/2017/Cannabis-Health-Effects/Cannabis-conclusions.pdf Accessed: February 14, 2018 National Institutes of Health - Marijuana and Cannabinoids: A Neuroscience Research Summit. 2016 NIH Campus, Bethesda, Maryland Available online: https://www.drugabuse.gov/sites/default/files/briefmjsummitmeetingsummary.pdf Accessed: April 16, 2018. 66 **Schrot RJ, Hubbard JR. Cannabinoids: Medical implications. Ann Med. 2016;48(3):128-141. Evidence Based Medicine and Cannabis - Epilepsy

Useful for 30% of Limited evidence refractory patients

Adults (-) Children (+)

Dravet Syndrome, Lennox- CB1 activity Gastaut Syndrome, Doose Side effects: cognitive & Syndrome behavioral

National Institutes of Health - Marijuana and Cannabinoids: A Neuroscience Research Summit. 2016 NIH Campus, Bethesda, Maryland Available online: https://www.drugabuse.gov/sites/default/files/briefmjsummitmeetingsummary.pdf Accessed: April 16, 2018. 67 Evidence Based Medicine and Cannabis

Image available at: http://seniorcarecorner.com/good-night-sleep- seniors

Indication Evidence Comments Improving short-term sleep Moderate Cannabinoids, primarily nabiximols outcomes in individuals with sleep disturbance associated with… The quality of sleep achieved with cannabis may be • obstructive sleep apnea syndrome poor *** • fibromyalgia • chronic pain • multiple sclerosis

Image available at: http://seniorcarecorner.com/good-night-sleep-seniors

National Academies of Science, Engineering and Medicine The health effects of cannabis and cannabinoids: committee conclusions. Published January 2017 Available online http://nationalacademies.org/hmd/~/media/Files/Report%20Files/2017/Cannabis-Health-Effects/Cannabis-conclusions.pdf Accessed: February 14, 2018 *** WHO Expert Committee on Drug Dependence Pre-Review .Cannabis plant and cannabis resin. Section 4: Therapeutic use 2018 68 Evidence Based Medicine and Cannabis – Anorexia and Weight Loss

This Photo by Unknown Author is licensed under CC BY

Indication Study type Evidence Comments

AIDS associated RTC w Limited* ** Dronabinol and smoked cannabis anorexia and placebo significantly greater weight gain than weight loss (THC) n=67 ** administration of a placebo**

*National Institutes of Health - Marijuana and Cannabinoids: A Neuroscience Research Summit. 2016 NIH Campus, Bethesda, Maryland Available online: https://www.drugabuse.gov/sites/default/files/briefmjsummitmeetingsummary.pdfF Accessed: April 16, 2018. ** WHO Expert Committee on Drug Dependence Pre-Review. Cannabis plant and cannabis resin 69 Section 4: Therapeutic use (2018). Available at: https://www.who.int/medicines/access/controlled-substances/Section4.CannabisPlant.TherapeuticUse.pdf . Accessed Jul 30, 2021. Evidence Based Medicine and Cannabis - Opioids

Can cannabis treat opioid withdrawal and reduce opioids related deaths?**

Opioids or cannabis for pain control * ***

Approximately 9% of those who use cannabis will develop dependence****

Among those who use cannabis regularly, up to 30% percent would have cannabis use disorder. (DSM-V) ****

* Olfson M. et al., Cannabis Use and Risk of Prescription Opioid Use Disorder in the United States. American Journal of Psychiatry January 2018, Vol. 175, No. 1, pp. 47 – 53 ** Shover CL, Davis CS, Sanford C, et al. Association between medical cannabis laws and opioid overdose mortality has reversed over time. Proc Natl Acad Sci U S A. 2019;116(26):12624–6. *** WHO Expert Committee on Drug Dependence Pre-Review .Cannabis plant and cannabis resin. Section 4: Therapeutic use 2018 ****Hasin DS, Saha TD, Kerridge BT, et al. Prevalence of marijuana use disorders in the United States between 2001–2002 and 2012– 2013. JAMA Psychiatry. 2015;72(12):1235–42. 70 Other Indications Indication Study type Administration Form Evidence Comment with Limited PTSD RCT w placebo2 Smoked cannabis Poor No significant difference Evidence Systematic review6 Various Very scant evidence Prospective study Various Poor Insufficient evidence Cannabis users vs non users3 A Review of Clinical Nabilone Limited 72% reported total 1 National Academies of Science, Engineering and Medicine The health effects of cannabis and cannabinoids: committee conclusions. Published Effectiveness and cessations or lessening of January 2017 Available online http://nationalacademies.org/hmd/~/media/Files/Report%20Files/2017/Can Guidelines4 severity of recurrent nabis-Health-Effects/Cannabis-conclusions.pdf Accessed: February 14, 2018 nightmares 2 Bonn-Miller MO, Sisley S, Riggs P, Yazar-Klosinski B, Wang JB, Loflin MJE, et al. (2021) The short-term impact of 3 smoked cannabis preparations versus 1 placebo on PTSD symptoms: A randomized cross-over clinical trial. PLoS ONE Tourette’s Small trials THC 10mg max., Limited therapeutic effects of 16(3): e0246990. https://doi.org/10.1371/journal.pone.0246990 syndrome THC capsules THC capsules on tic 3 Marcel O. Bonn-Miller, Megan Brunstetter, Alex Simonian, Mallory J. Loflin, Ryan Vandrey, Kimberly A. Babson, and Hal Wortzel. Cannabis and capsules/placebo severity and global Cannabinoid Research.ahead of print http://doi.org/10.1089/can.2020.0056 clinical outcomes 4 Cowling T, MacDougall D. Nabilone for the Treatment of Post-Traumatic Stress Disorder: A Review of Clinical Effectiveness and Guidelines [Internet]. Anxiety Systematic review 5 CBD capsule or Limited General anxiety disorder, Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Feb 20. PMID: 31553551. and sublingual spray as social anxiety disorder, 5 Skelley, Jessica W. et al. Use of cannabidiol in anxiety and anxiety-related anxiety- either monotherapy anxiety related to PTSD disorders (2019) Journal of the American Pharmacists Association, Volume 60, Issue 1, 253 – 261 DOI: https://doi.org/10.1016/j.japh.2019.11.008 related or adjunctive 6 O'Neil ME, Nugent SM, Morasco BJ, Freeman M, Low A, Kondo K, Zakher B, disorders therapy 400mg max Elven C, Motu'apuaka M, Paynter R, Kansagara D. Benefits and Harms of Plant-Based Cannabis for Posttraumatic Stress Disorder: A Systematic Review. Ann Intern Med. 2017 Sep 5;167(5):332-340. doi: 10.7326/M17-0477. Epub 2017 Aug 15. PMID: 28806794. 71 Potential for Drug Diversion Marijuana Effects in Children and Adolescents

https://www.drugabuse.gov/video s/reward-circuit-how-brain- Addiction responds-to-marijuana https://youtu.be/s27f7Jzy2k0 • Cannabis has addictive potential and may lead Cognitive to other drug use Impairment ** disorders*** Mental Illness* • Greater cognitive impairment if cannabis • Decreased memory use is frequent and Potentially • Decreased attention early in life detrimental to • Lower IQ • Impaired decision fetus making • THC – mice

*National Institutes of Health - The Adolescent Brain Cognitive Development (ABCD) Study. Available online: https://www.drugabuse.gov/news-events/nida-notes/2017/06/researchers-speak-abcd-study Accessed: April 16, 2018. **Poulton, R., Moffitt, T. E., & Silva, P. A. (2015). The Dunedin Multidisciplinary Health and Development Study: overview of the first 40 years, with an eye to the future. Social Psychiatry and Psychiatric Epidemiology, 50(5), 679–693. http://doi.org/10.1007/s00127-015- 1048-8 *** National Institutes of Health - Marijuana and Cannabinoids: A Neuroscience Research Summit. 2016 NIH Campus, Bethesda, Maryland Available online: https://www.drugabuse.gov/sites/default/files/briefmjsummitmeetingsummary.pdf Accessed: April 16, 2018.72 ***Levinsohn EA, Hill KP. Clinical uses of cannabis and cannabinoids in the United States. J Neurol Sci. 2020 Apr 15;411:116717. doi: 10.1016/j.jns.2020.116717. Epub 2020 Jan 30. PMID: 32044684. Marijuana and ethanol

Binge drinking

Substance use disorder (especially alcoholism) Major depressive disorder This Photo by Unknown Author is licensed under CC BY-NC-ND

National Institutes of Health - Marijuana and Cannabinoids: A Neuroscience Research Summit. 2016 NIH Campus, Bethesda, Maryland Available online: 73 https://www.drugabuse.gov/sites/default/files/briefmjsummitmeetingsummary.pdf Accessed: April 16, 2018. Motor Vehicle Accidents and Marijuana Use

WHO 8,700 traffic deaths worldwide (JAMA April 2018)

Cannabis is the most common illicit Blood level as low as 1-2 mcg/L drug identified in motor vehicle crashes and fatalities in US* Cannabis 1.5 -2,5 x motor vehicle crashes or deaths**

Cannabis + Alcohol The THC threshold is under study

*National Highway Traffic Safety Administration, National Forensic Laboratory Information System- Marijuana –Impaired Driving: A Report to the Congress. Published: July 2017. Available online: https://www.nhtsa.gov/sites/nhtsa.dot.gov/files/documents/812440-marijuana-impaired-driving-report-to- congress.pdf .Accessed: April 16, 2018. National Institutes of Health - Marijuana and Cannabinoids: A Neuroscience Research Summit. 2016 NIH Campus, Bethesda, Maryland Available online: https://www.drugabuse.gov/sites/default/files/briefmjsummitmeetingsummary.pdf . Accessed: April 16, 2018. Brady, J. E., & Li, G. (2014). Trends in Alcohol and Other Drugs Detected in Fatally Injured Drivers in the United States, 1999–2010. American Journal of Epidemiology, 179(6), 692–699. http://doi.org/10.1093/aje/kwt327 74 **Schrot RJ, Hubbard JR. Cannabinoids: Medical implications. Ann Med. 2016;48(3):128-141. Medicinal cannabis use concerns regarding patient safety include (check all the ones that apply):

a.Onset of action and efficacy/toxicity b.Potential for addiction c.Car accidents d.All alternatives are correct

75 References

• Please see the footnote in each slide