The Plant of the Future Preparing Pennsylvanian ... … · Skin/gut G. Inhibit acetylcholine...

The Plant of the Future – Preparing Pennsylvanian Pharmacists to Lead the Nation in Medical Marijuana Patient Care and Research

Lisa Yamagishi, BS, PharmD, CTTS

Clinical Pharmacist – Hospice and Palliative Care

Today’s Speaker

Lisa Yamagishi, BS, PharmD, CTTS

Originally from Long Island, New York, Dr. Yamagishi earned her Pharm.D. at University at Buffalo School of

Pharmacy and Pharmaceutical Sciences. She completed her PGY1 at Duquesne University and St.

Barnabas Health System with a focus on geriatrics and long-term care. Her PGY1 research project was on the effects of the opioid epidemic on residents in long-term care, which has been accepted for publication in The

Consultant Pharmacist. She is currently a clinical pharmacist of hospice and palliative care at Delta Care

Rx. Her areas of interest include geriatrics, palliative care, and psychiatry. She enjoys riding her fixie bike, playing board games, exploring new cuisines, playing

bass guitar, and taking pictures of her cat, Yoshimi.

Disclosures

There are no actual or potential conflict of interests to disclose in relation to this

program/presentation.

Medical Marijuana and Parkinson’s

“Ride with Larry” – 2013

http://ridewithlarrymovie.com/

https://youtu.be/zNT8Zo_sfwo

Learning Objectives

Upon completion of the activity, participants should be better able to:

• Describe features of the endocannabinoid system and cannabis pharmacology

• Discuss different medical marijuana products, dosage, and therapeutic monitoring

• Explain the Medical Marijuana Act of Pennsylvania, how it pertains to pharmacists, and how it will allow groundbreaking research opportunities for the state

Endocannabinoid System The endocannabinoid system is found in brain as well as throughout body: • Endogenous cannabinoids (endocannabinoids)

o N-arachidonoyl ethanolamide and anandamide (AEA) • Receptors that transduce the effects of endocannabinoids

o CB1 and CB2 – G-coupled receptors • Enzymes that synthesize and degrade endocannabinoids

o Biosynthesis of endocannabinoids: N-acyl-phosphatidyl-ethanolamine-selective phospholipase D (NAPE-PLD) and diacylglycerol lipases (DAGL)

o Hydrolytic inactivation: Fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL)

Handb Exp Pharmacol. 2015;231:59-93. Neurotherapeutics. 2015;12(4):692-698.

Endocannabinoids Endocannabinoid Activity Structure

Anandamide (AEA) CB1 >> CB2 agonist

2-Arachidonoyl glycerol (2-AG) CB1 ~ CB2 agonist

2-Arachidonoyl ether CB1 >> CB2 agonist

O-Arachidonoyl ethanolamine CB1 >> CB2 agonist

N-Arachidonoyl dopamine CB1 >> CB2 agonist

Pharmacol Rev. 2006;58(3):389-462.

CB1 & CB2 Receptors

https://www.fundacion-canna.es/sites/default/files/images/articles/en/articles-endocannabinoid-system_text_2.jpg

• Antinociception - CB1 receptors in the brain, spinal dorsal horn, dorsal root ganglia, and peripheral afferent neurons

• Activation linked to • Appetite stimulation • Reduction in nociceptive pain and inflammation • Treatment of central nervous system (CNS) disorders • Cardiologic regulation (vasodilation, bradycardia) • Hyperalgesia in neuropathic pain • Reduction in retinopathies • Reduction in gastro-intestinal (GI) motility due to inflammatory stimulus

CB1 Receptors

Pharmacol Rev. 2006;58(3):389-462.

CB2 Receptors • Activation linked to

o Reduction in pain and inflammation o Reduction in neurotoxicity/neurotrauma

Alzheimer’s Disease o Reduction in inflammation of atherosclerotic plaques o Reduction in GI inflammation o Reduction in age-related bone-loss

Pharmacol Rev. 2006;58(3):389-462.

Time for a Matching Activity! Endocannabinoids on CB1 and CB2 receptors

Endocannabinoids on CB1 and CB2 receptors

Structure ANSWER Endocannabinoids Action

Spinal cord A. Inhibit norepinephrine release, heartrate regulation, blood vessel constriction

Hypothalamus B. Modulates mesolimbic dopaminergic pathway involved in food reward

Parasympathetic system C. Inhibition glucoronate-induced excitotoxicity

Sympathetic system D. Inhibit glutamate and information transfer between body and brain

Neuronal cells E. Regulate level of adiponectin production

Adipose tissue F. Reduces histamine

Skin/gut G. Inhibit acetylcholine release

Pharmacol Rev. 2006;58(3):389-462.


Structure ANSWER Endocannabinoids Action

Spinal cord D A. Inhibit norepinephrine release, heartrate regulation, blood vessel constriction

Hypothalamus B B. Modulates mesolimbic dopaminergic pathway involved in food reward

Parasympathetic system G C. Inhibition glucoronate-induced excitotoxicity

Sympathetic system A D. Inhibit glutamate and information transfer between body and brain

Neuronal cells C E. Regulate level of adiponectin production

Adipose tissue E F. Reduces histamine

Skin/gut F G. Inhibit acetylcholine release

Pharmacol Rev. 2006;58(3):389-462.


Structure Endocannabinoids Action Resultant effect

Spinal cord Inhibit glutamate and information transfer between body and brain

Decreased pain sensitivity

Hypothalamus Modulates mesolimbic dopaminergic pathway involved in food reward

Increased appetite

Parasympathetic system Inhibit acetylcholine release Bronchoconstriction, reduction in enteric contractility

Sympathetic system Inhibit norepinephrine release, heartrate regulation, blood vessel constriction

Delayed reduction in heart rate and blood pressure

Neuronal cells Inhibition glucoronate-induced excitotoxicity Neuroprotective effect – prevent cell injury

Adipose tissue Regulate level of adiponectin production Increased adiposity, insulin resistance

Skin/gut Reduces histamine Anti-pruritic effect, reduced gastric secretion

General Inhibits immune B lymphocytes, natural killer cells Anti-inflammatory activity

Pharmacol Rev. 2006;58(3):389-462.

Cannabis Cannabis genus – flowering plant consisting of sativa and indica species from Central and South Asia Fiber used for rope, clothing, bowstring, and paper for a millennia Other uses: seeds and seed oils, livestock feed, medicine, religious ceremonies, and recreation 1937 – Marijuana banned due to concern of abuse

Epilepsia. 2014;55(6):791-802. Pharmacol Rev. 2006;58(3):389-462.

http://maxpixel.freegreatpicture.com/Cannabis-Plant-Marijuana-Drug-Weed-Natural-Pot-2152604.

Chemical Constituents of Cannabis Cannabinoids (~60) – Lipophilic compounds exhibiting effects by acting on endocannabinoid receptors: • Δ9-tetrahydrocannabinol (THC) • Cannabidiol (CBD) • Cannabinol (CBN) • Δ8 THC • Cannabigerol (CBG) • Cannabichromene

Front Plant Sci. 2016;7. Pharmacol Rev. 2006;58(3):389-462.

Δ9-tetrahydrocannabinol (THC) • CB1 and CB2 partial agonist • Main psychoactive ingredient • Ajulemic acid – a ligand that is the metabolite of

THC with potent anti-inflammatory and analgesic properties without behavioral or psychoactive effect

• CB1 >> CB2 agonist • CYP3A, 2C, and P-gp substrate • Competitive CYP1A1, CYP1A2, and CYP1B1 inhibitor • Inhibits CYP2B6, CYP2A6, CYP3A7

Front Plant Sci. 2016;7.. Pharmacol Rev. 2006;58(3):389-462. Naturaldatabasetherapeuticresearchcom. 2016. http://naturaldatabase.therapeuticresearch.com/. Biochem Pharmacol 2010;79(11):1691-8.

Forensic Toxicol 2011;29:117-24. Biochem Pharmacol 1993;45(6):1323-31. Marijuana and Medicine. 1999;91-103. Drug Metab Dispos 2011;39(11):2049-56. Life Sci 2011;88(15-16):730-6.

Cannabidiol (CBD) • No activity on CB1 or CB2 • Antagonism of non-CB1 or non-CB2

• Modulator of ⍺1-adrenoreceptor • Inhibition of Anandamide (AEA) uptake and

metabolism • Antiinflammatory, neuroprotective, anxiolytic, and

antipsychotic properties • Competitive CYP2D6, CYP1A1, CYP2B6, CYP1A2,

and CYP1B1 inhibitor • Inhibits CYP3A4, CYP3A5, CYP2A6, CYP2C,

CYP3A7, CYP3A, and P-gp

Front Plant Sci. 2016;7. Pharmacol Rev. 2006;58(3):389-462. Naturaldatabasetherapeuticresearchcom. 2016. http://naturaldatabase.therapeuticresearch.com/. Biochem Pharmacol 2010;79(11):1691-8.

Forensic Toxicol 2011;29:117-24. Biochem Pharmacol 1993;45(6):1323-31. Marijuana and Medicine. 1999;91-103. Drug Metab Dispos 2011;39(11):2049-56. Life Sci 2011;88(15-16):730-6.

Other Constituents of Cannabis Terpenes/Terpenoids (>100) Phenolic Compounds (Flavonoids) (~20) Sterols Thiols “Entourage Effect”: Theory that the combination of active and ‘inactive’ synergists in cannabis modulate overall effects of the plant.

Front Plant Sci. 2016;7. Br J Pharmacol. 2011;163(7):1344-1364.

Learning Objectives





Socrative Response Question Which of the following formulations of medical cannabis is illegal in Pennsylvania? A. Oral tinctures B. Oils for vaporization C. Topical creams D. Dry leaf E. None. They are all legal

Dosage Forms In Pennsylvania, under Act 16 of 2016, it is unlawful to smoke medical marijuana. It is dispensed in the following forms: • Pill • Oil • Topical forms, including gel, creams, or ointments • A form medically appropriate for administration by

vaporization or nebulization, excluding dry leaf or plant form • (until dry leaf of plant form become acceptable)

• Tincture • Liquid

Pennsylvania Medical Marijuana Program. 2018. https://www.pa.gov/guides/pennsylvania-medical-marijuana-program/#Dispensaries

Phase-In of Dry Leaf Dry leaf (”flower”) medical marijuana phased in at dispensaries August 1, 2018 Per PA Secretary of Health: " The dry leaf form of medical marijuana provides a cost-effective option for patients” You can inhale it, but you cannot smoke it!

Pennsylvania Pressroom. 2018. https://www.media.pa.gov/Pages/Health-Details.aspx?newsid=518 saries

https://www.gannett-cdn.com/-mm-/e1d78d18d18c0e71d5c7c4a0350b598687f50fe1/c=0-50-534-352/local/-/media/2018/02/14/PAGroup/YorkDailyRecord/636541977096557883-medical-marijuana-cannabis-bottle-getty-

large.jpg?width=3200&height=1680&fit=crop

Vaporization Pre-filled cartridges with vaporization devices Onset: <15 minutes Duration: ~2 hours Bioavailability: 2- 56% • Varied by number, duration, and spacing of puffs,

hold time, and inhalation volume, or how a person smokes

Highest peak concentrations, fastest onset, and shortest duration compared to other methods/preparations.

Chemistry & biodiversity. 2007;4(8):1770-1804.

https://inhalemd.com/wp-content/uploads/2015/05/Vaporizer-Marijuana-Smoking-1-1080x675.jpg

Pill Capsules, tablets Onset: <2 hours Peak plasma concentration: • 2 – 6 hours • Lower than inhalation

o Peak concentration of 5ng/mL from 15mg oral THC or 10mg vaporized THC

Extended-release formulations available

Epilepsy & Behavior. Cannabinoids and Epilepsy. 70 (Part B): 313–318. Columbia Care NY. 2018. https://col-careny.com/columbia-care-launches-nations-first-dose-metered-extended-release-pharmaceutical-quality-medical-marijuana-tablets/.

Colorado Department of Public Health. 2018. http://idpc.net/publications/2017/02/monitoring-health-concerns-related-to-marijuana-in-colorado-2016.

Oral Liquids Oils, tinctures, suspensions, syrups Administration: Oral or sublingual Onset: • Sublingual: <30 minutes • Oral: <1 hour Peak plasma concentration: • 2 – 6 hours • Lower than vaporization

o Peak concentration of 5ng/mL from 15mg oral THC or 10mg vaporized THC

http://col-careny.com/wp-content/uploads/2016/05/CCNY_VAPE_MOCK_UP_r3.jpg Chemistry & biodiversity. 2007;4(8):1770-1804.


Topicals Creams, balms, salves, lotions, transdermal patches, and oils Permeability: may be dependent on topical base Topical preparations • Local anti-inflammatory effects • Pharmacokinetics - ?? Transdermal patches • Systemic controlled-release of drug • Half-life ~1 hour, duration ~48 hours

Further clinical trials needed for safety and clinical application

Int J Pharm. 2002;241(2):329-339. Chemistry & biodiversity. 2007;4(8):1770-1804.

J Pain Res. 2010:11.

https://c1.staticflickr.com/5/4535/38575222632_dcb509b959_b.jpg

Dosing

CBD:THC ratio or percentage strength Examples: 20T:1C; 1T:1C; 1T:20C

Psychopharmacology (Berl). 2011;219(1):247-249. Epilepsia. 2014;55(6):791-802.

https://col-careny.com/columbia-care-launches-nations-first-dose-metered-extended-release-pharmaceutical-quality-medical-marijuana-tablets/

Dosing THC Dosing: • Low (2.5 – 5mg) – appetite stimulation, improved movement, neuropsychiatric

improvement • Medium (5 - 10mg) – decreased spasticity, neuropathic pain relief • High (10 – 20mg) – strong pain relief (cancer, AIDS)

CBD Dosing: • >20C:1T shown to have anti-seizure activity • Doses up to 1500mg/day have no significant central nervous system side effects • More studies needed

Drug Alcohol Depend. 2013;128(1-2):64-70. Pharmacol Rev. 2006;58(3):389-462.

Clin J Pain. 2014;30(6):472-478. Epilepsia. 2014;55(6):791-802.

Phytocannabinoids on Diseases Disease Treatment/Effect THC CBD

Appetite Promotion X

Nociceptive Pain/Inflammation X

Neurotoxicity and Neurotrauma* X X

Epilepsy X X

Nausea X

Glaucoma and Retinopathy X

IBD X

Arthritis X

Anxiety/Depression +/- X

*Acute injury (traumatic brain injury [TBI], stroke, epilepsy); Chronic neurodegenerative disorders (multiple sclerosis (MS), Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis (ALS), Tourette’s syndrome, tardive dyskinesia, dystonia, and Alzheimer’s

Pharmacol Rev. 2006;58(3):389-462.

Socrative Response Question JH is a 4 year old girl who has epilepsy that has not been managed with traditional medications. Cannabis products containing which of the following cannabinoids appear to reduce seizures in children? A. Cannabinol (CBN) B. Cannabidiol (CBD) C. Cannabichromene (CBC) D. Tetrahydrocannabinol (THC)

Charlotte’s Web

Dr. Sanjay Gupta – “Weed”

CNN 2013

https://youtu.be/CiShwotFJR8?t=10m54s

Therapeutic Effects • In adults with chemotherapy induced nausea/vomiting, oral cannabis are

effective anti-emetics • In adults with chronic pain, patients treated with cannabis or cannabinoids

are more likely to experience clinically significant reduction in pain • In patients with multiple-sclerosis spasticity, short-term use of oral

cannabinoids improves spasticity symptoms • For these conditions the effects of cannabinoids are modest; for all other

conditions there is inadequate information to assess their effects

The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. https://doi.org/10.17226/24625.

Adverse Effects Respiratory: • Smoking cannabis on a regular basis is associated with chronic cough and phlegm production Psychosocial: • Recent cannabis use (< 24 hours) impairs the performance in cognitive domains of learning,

memory, and attention • Cannabis use during adolescence is related to impairments in subsequent academic achievement

and education, employment and income, and social relationships and social roles


Adverse Effects Problem Cannabis or Other Substance Abuse • Greater frequency of cannabis use increases the likelihood of developing problem cannabis use • Initiating cannabis use at a younger age increases the likelihood of developing problem

cannabis use • Cannabis use is likely to increase the risk for developing substance dependence (other than

cannabis use disorder) Pregnancy: • Smoking cannabis during pregnancy is linked to lower birth weight in the offspring


Adverse Effects Injury and Death: • Cannabis use prior to driving increases the risk of being involved in a motor vehicle accident

Mental Health: • Heavy cannabis users are more likely to report thoughts of suicide than non-users • Cannabis use is likely to increase the risk of developing schizophrenia and other psychoses; the

higher the use the greater the risk • For individuals diagnosed with bipolar disorders, near daily cannabis use may be linked to

greater symptoms of bipolar disorder than non-users • Regular cannabis use is likely to increase the risk for developing social anxiety disorder


Adverse Effects Cancer • There is modest evidence that cannabis use is associated with one subtype of testicular cancer • There is minimal evidence that parental cannabis use during pregnancy is associated with

greater cancer risk in offspring • The evidence suggests that smoking cannabis does not increase the risk for certain cancers

(i.e., lung, head, and neck) in adults


Cannabis Drug-drug Interactions • Chlorpromazine • Clobazam • Clozapine • CNS depressants (e.g.

barbiturates, benzodiazepines)

• Disulfiram • Hexobarbital • Hydrocortisone

• Ketoconazole • MAO inhibitors • Phenytoin • Protease inhibitors

(indinavir, nelfinavir) • Theophylline • Tricyclic antidepressants • Warfarin

Patient counseling: Use caution when taking medications and marijuana at the same time. Some medications have known interactions with marijuana, and others may have interactions that have not yet been identified


Marijuana and Opiates • Limited evidence - Rates of overdose death from opioid pain relievers may be reduced in states

with legal medical marijuana compared to states without • Insufficient evidence - There is conflicting research on whether or not marijuana use is

associated with a decrease in opioid use by individuals with a history of opioid addiction treatment or injection drug use

• Mixed evidence - There is conflicting research on whether or not marijuana use is associated with a decrease in opioid use by chronic pain patients


Learning Objectives





1996 - California passed Proposition 215, making it the first state in the United States of America to legalize medical marijuana As of January, 2019: • 33 states, the District of Columbia, Guam, and

Puerto Rico have medical marijuana programs. • All but 3 states allow “low THC, high CBD”

products

State Medical Marijuana Laws

National Conference of State Legislatures. 2018. http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx

https://upload.wikimedia.org/wikipedia/commons/0/0c/Medical-cannabis-card-california.jpg

Socrative Response Question Active Learning: Socrative Response System In the United States of America, use of medical marijuana is: A. Legal. B. Illegal. C. Possibly legal. It seems like it anyway… D. Possibly illegal. Sounds risky!

Federally, marijuana is a Schedule I substance under the Controlled Substance Act. • 2013 – ”Cole Memorandum” - Update to Marijuana Enforcement Policy

o While marijuana remains illegal federally, states where medical marijuana is legal shall have "strong, state-based enforcement efforts.... and will defer the right to challenge their legalization laws at this time.”

• 2014 - Rohrabacher–Farr Amendment o Part of omnibus spending bill, where the Justice department cannot appropriate funds

to interfere with the implementation of state medical cannabis laws



Federally, marijuana is a Schedule I substance under the Controlled Substance Act. • 2018 - Marijuana Enforcement Memorandum

o Rescinded 2013 announcement o ”Marijuana is a dangerous drug… activity is a serious crime” o Allows Federal prosecutors to prosecute “marijuana activities”

• March 2018 – FY2018 Omnibus Spending Bill o Extends 2014 Rohrabacher–Farr Amendment until September 2018


National Conference of State Legislatures. 2018. http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx Forbescom. 2018 https://www.forbes.com/sites/tomangell/2018/03/21/congress-protects-medical-marijuana-from-jeff-sessions-in-new-federal-spending-bill/#7cf816753575.

http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx







PA 2016 Act 16 Pennsylvania’s Medical Marijuana Act • Signed into law April 17, 2016 • “Temporary measure pending Federal approval of and access to medical

marijuana through traditional medical and pharmaceutical avenues” o Until 3 years after Congress removes marijuana from Schedule I from the

Federal Controlled Substances Act • Administered by the Pennsylvania Department of Health (DOH) • Provides patients with a serious medical condition access to medical marijuana • Chapter 19 - Allows the use of medical marijuana in order to conduct research

The official website for the Pennsylvania General Assembly. 2018. : http://www.legis.state.pa.us/cfdocs/legis/li/uconsCheck.cfm?yr=2016&sessInd=0&act=16. Medical Marijuana - Act 16 of 2016. Pennsylania Pharmacists Association. 2018.

http://c.ymcdn.com/sites/www.papharmacists.com/resource/resmgr/Legislative/Act16_MedMarijuana_PPASummar.pdf.

http://www.legis.state.pa.us/cfdocs/legis/li/uconsCheck.cfm?yr=2016&sessInd=0&act=16

“Serious Medical Conditions” 1. Cancer 2. Positive status for human immunodeficiency

virus or acquired immune deficiency syndrome 3. Amyotrophic lateral sclerosis 4. Parkinson's disease 5. Multiple sclerosis 6. Damage to the nervous tissue of the spinal cord

with objective neurological indication of intractable spasticity

7. Epilepsy 8. Inflammatory bowel disease 9. Neuropathies

10. Huntington's disease 11. Crohn's disease 12. Post-traumatic stress disorder 13. Intractable seizures 14. Glaucoma 15. Sickle cell anemia 16. Severe chronic or intractable pain of

neuropathic origin or severe chronic or intractable pain in which conventional therapeutic intervention and opiate therapy is contraindicated or ineffective

17. Autism

The official website for the Pennsylvania General Assembly. 2018. : http://www.legis.state.pa.us/cfdocs/legis/li/uconsCheck.cfm?yr=2016&sessInd=0&act=16.


Medical Marijuana Advisory Board Oversee program and examine/analyze law and events relating to the program Fifteen members: 7 permanent, 8 appointed by Governor and legislative leaders of House/Senate

Permanent members: • Secretary of Health • Commissioner of the Pennsylvania State Police (PSP) • Chairman of the State Board of Pharmacy • Commissioner of the Bureau of the Professional and Occupational Affairs • Physician General • President of the PA Chiefs of Police Association • President of the PA District Attorneys Association, or a designee from each department



Identification Cards Patient/Caregivers: • Register for the Medical Marijuana Program at

medicalmarijuana.pa.gov • Pay $50 fee • Expires 1 year after issuance

Pennsylvania Medical Marijuana Program. Commonwealth of Pennsylvania. 2018. https://www.pa.gov/guides/pennsylvania-medical-marijuana-program/#PatientsandCaregivers.



Identification Cards Patient Identification Cards: • Must have one of 17 “serious medical conditions” • Obtain certification from practitioner who is registered through PA

DOH Medical Marijuana Program • If <18 years old, must have caregiver register on their behalf • Patient is prohibited from the following while under the influence

(>10ng/mL THC in blood): o Work with chemicals requiring a permit o Use high-voltage electricity o Perform tasks in confined spaces or heights (i.e. working in

mines) o Work that may result in public health or safety risk




Identification Cards Caregiver Identification Cards: • Must be >21 years old • Be appointed by the patient • Provide fingerprints and a full background check

• Caregivers may provide care for up to 5 patients • Patient may designate up to 2 caregivers




Growers/Processors

"A person… which holds a permit from the department under this act to grow and process medical marijuana” • No more than 25 growers/processors in PA • No more than 5 growers/processors may

issued permits as dispensaries

The official website for the Pennsylvania General Assembly. 2018. : http://www.legis.state.pa.us/cfdocs/legis/li/uconsCheck.cfm?yr=2016&sessInd=0&act=16. Commonwealth of Pennsylvania. 2018. https://www.pa.gov/guides/pennsylvania-medical-marijuana-program/#PatientsandCaregivers.

PA MEDICAL MARIJUANA WATCH. 2018. https://pammjwatch.wordpress.com/2017/06/12/breaking-pa-dept-of-health-expects-phase-2-medical-mj-permits-to-be-issued-in-early-2018/.


https://www.pa.gov/guides/pennsylvania-medical-marijuana-program/#PatientsandCaregivers







“Seed-to-Sale” Grower/processors and dispensaries are required to have a tracking system • PA requires the use of MJ Freeway’s real-time electronic tracking system

• Provides “seed-to-sale” tracking system for growers/processors to dispensaries • Records sales to patients as well as patient data for dispensaries

• Tracking system information must be reported to DOH within 1 year of issuance of permit, and every 3 months thereafter

Pennsylvania Department of Health. 2018. Available at: http://www.health.pa.gov/My%20Health/Diseases%20and%20Conditions/M-P/MedicalMarijuana/Documents/1-16-18%20MM%20Guidance%20for%20Laboratory%20Testing%20and%20Sampling%20FINAL.pdf.

Pabulletincom. 2018. Available at: https://www.pabulletin.com/secure/data/vol47/47-19/827.html.PA MEDICAL MARIJUANA WATCH. 2018. https://pammjwatch.wordpress.com/2017/06/12/breaking-pa-dept-of-health-expects-phase-2-medical-mj-permits-to-be-issued-in-early-2018/.

https://mjfreeway.com/images/logo.png

http://www.health.pa.gov/My Health/Diseases and Conditions/M-P/MedicalMarijuana/Documents/1-16-18 MM Guidance for Laboratory Testing and Sampling FINAL.pdf







Testing • Testing is performed twice: during harvest and during processing • Testing done according to the American Herbal Pharmacopeia’s ”Cannabis Inflorescence

Standards of Identity, Analysis, and Quality Control”:

• Cannabinoid content • Terpenes • Pesticide analysis • Residual solvents • Heavy metal • Microbiological testing • Moisture content

Pennsylvania Department of Health. 2018. http://www.health.pa.gov/My%20Health/Diseases%20and%20Conditions/M-P/MedicalMarijuana/Documents/1-16-18%20MM%20Guidance%20for%20Laboratory%20Testing%20and%20Sampling%20FINAL.pdf.

https://www.midwestcompassion.org/wp-content/uploads/2016/11/Lab-650x265.jpg








Dispensary “A person… which holds a permit issued by the department to dispense medical marijuana" • No more than 50 dispensaries in PA • Each dispensary may not have more than 3 separate locations • May not operate on the same site as a grower/processor • May not be located within 1,000 feet of the property line of a public, private or parochial school or a

day-care center

Those who are awarded permits are required to take a 2 hour training course


PA MEDICAL MARIJUANA WATCH. 2018. https://pammjwatch.wordpress.com/2017/06/12/breaking-pa-dept-of-health-expects-phase-2-medical-mj-permits-to-be-issued-in-early-2018/.









Packaged Product Label Must include: • Name of grower/processor • Name of the dispensary • The form/species of medical marijuana • Percentage of THC/CBD • Any other labeling required by DOH

https://natureswaymedicine.com/wp-content/uploads/2018/02/image4-e1519137552682.jpeg The official website for the Pennsylvania General Assembly. 2018. : http://www.legis.state.pa.us/cfdocs/legis/li/uconsCheck.cfm?yr=2016&sessInd=0&act=16.


Dispensing to Patients/Caregivers • No more than 30-day supply may be dispensed during one time • Product must be kept in original package after dispensing • Safety insert:

• Methods of administering doses • Potential dangers of medical marijuana • How to recognize problematic use/services for treatment of problematic use • How to prevent/deter misuse by minors or others










Dispensing to Patients/Caregivers Sealed package labeling: • The packaging date/Expiration date • “This product is for medicinal use only. Women should not consume during pregnancy or while

breastfeeding except on the advice of the practitioner who issued the certification and, in the case of breastfeeding, the infant's pediatrician. This product might impair the ability to drive or operate heavy machinery. Keep out of reach of children.”

• Number of doses, species, and % of CBD/THC • A warning that the medical marijuana must be kept in the original container in which it was

dispensed • A warning that unauthorized use is unlawful and will subject the person to criminal penalties










Dispensary Requirements • Must have a physician or pharmacist onsite at all times during hours of operation • If a dispensary has more than 1 location, a physician assistant or a certified registered nurse

practitioner may be onsite at each of the other locations in lieu of the physician or pharmacist

• Physicians, pharmacists, physician assistants, and certified registered nurse practitioners must take a 4 hour training course

• All other employees of medical marijuana organizations must take 2 hour course










Medical Professional 4-hour Course Must be approved for continuing education credits by: • The State Board of Medicine and the State Board of Osteopathic Medicine • The State Board of Pharmacy • The State Board of Nursing Current Approved Training Providers: • TheAnswerPage Inc • Extra Step Assurance LLC • The Lambert Center for the Study of Medicinal Cannabis and Hemp at Thomas Jefferson University • University of the Sciences • Philadelphia College of Osteopathic Medicine (PCOM) • Pennsylvania State Nurses Association



Practitioners • Must take 4 hour course and apply through the

registry • Must be trained to treat serious medical condition • May not work in a dispensary • May not hold economic interest in medical marijuana • May not advertise that they certify patients for the

program • May not offer certification to self, family, or household

member

Practitioner must review Prescription Drug Monitoring Program


https://thefreshtoast.com/wp-content/uploads/2017/05/NY-publishes-list-of-doctors-who-will-recommend-medical-marijuana-1.jpg


Research Program DOH program to study medical marijuana on treatment/symptom management of serious medical conditions • Once a serious medical condition has >25 patients, DOH will petition FDA and US DEA for approval to

study medical marijuana on that condition • Vertically integrated health system and a university may submit request to participate • Approval of a vertically integrated health system to participate allows it to:

o Dispense medical marijuana o Grow medical marijuana



Academic Clinical Research Centers Allows for accredited medical schools that operates/partners with acute care hospitals to conduct research with medical marijuana. • Must partner with grower/processor that

holds a permit (clinical registrants)

Academic research centers to report findings within 1 year of publication/conclusion of study to DOH


https://www.medicalmarijuanablog.com/wp-content/uploads/2015/08/The-Obama-Administration-Made-Medical-Marijuana-Research-Easier.png


Academic Clinical Research Centers Clinical Registrants • Only 8 may exist in PA • May operate up to 6 dispensaries • For each research study, must disclose to DOH

• Reason for research project • Strain of medical marijuana to be used • Anticipated duration of study • Evidence of approval of institutional review board



Certified Medical Marijuana Academic Clinical Research Centers

• Drexel University College of Medicine, Philadelphia; • Lewis Katz School of Medicine at Temple University, Philadelphia; • Penn State College of Medicine, Hershey; • Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia; • The Perelman School of Medicine at the University of Pennsylvania, Philadelphia; • University of Pittsburgh School of Medicine, Pittsburgh; • Lake Erie College of Osteopathic Medicine-Erie (LECOM); and • Philadelphia College of Osteopathic Medicine, Philadelphia.



The Road to Research • April 5th – November 8th, 2018: Application window for clinical registrants • October 4th, 2018: Announcement of 8 clinical registrant applications paired with

Academic Clinical Research Centers

Pennsylvania Pressroom. 2018: https://www.media.pa.gov/Pages/Health-Details.aspx?newsid=533

https://www.media.pa.gov/Pages/Health-Details.aspx?newsid=533



The Road to Research • November 27th, 2018: Lawsuit filed by a group of

medical marijuana cultivation and dispensary operators against the Department of Health o Clinical registrants have “super permits” that

have not met rigorous standards of commercial dispensaries/growers

o Academic Research Clinical Research Centers already partnered with clinical registrants prior to application – process vulnerable to ”pay to play”

Mjbizdaily.com. 2018: https://mjbizdaily.com/wp-content/uploads/2018/12/lawsuit-filed-in-the-Commonwealth-Court-of-Pennsylvania.pdf

The Road to Research • December 5th, 2018: Pennsylvania rejects all 8 clinical registrant applicants

o None met rigorous requirements o Administration to open second round of applications

• December 26th, 2018: Pennsylvania Department of Health issued temporary regulations to allow health organizations to pair with more than one clinical registration

Pennsylvania Pressroom. 2018: https://www.media.pa.gov/Pages/Health-Details.aspx?newsid=546 The Columbian. 2018: https://www.columbian.com/news/2018/dec/26/pennsylvania-expands-partnerships-for-marijuana-research




Prospective Research Requirements for Schedule I controlled substance: • Approval from the Food and Drug Administration for

Investigational New Drug • Registration with the Drug Enforcement

Administration • Approval from the National Institute of Drug Abuse

o Only 1 federally approved cultivation site: University of Mississippi School of Pharmacy

• Local Investigational Review Board approval

NIDA Drug Supply Program. 2017: https://www.drugabuse.gov/researchers/research-resources/nida-drug-supply-program.

https://pharmacy.olemiss.edu/marijuana/wp-content/uploads/sites/30/2017/08/royal-slider-1-1024x577.jpg

Future of Pennsylvania Research Investigational Studies? • Will need DEA to approve more research grow sites OR • Will need DEA to re-schedule marijuana from Schedule I controlled substance Probably will be observational studies • Cannot use medical marijuana from our dispensaries for randomized/controlled trials!

Questions?

References

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References

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15. Russo E. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011;163(7):1344-1364.

16. Commonwealth of Pennsylvania. Pennsylvania Medical Marijuana Program. 2018. https://www.pa.gov/guides/pennsylvania-medical-marijuana-program/#Dispensaries. Accessed March 9, 2018.

17. Wolf Administration: Phase-in of Dry Leaf Medical Marijuana Starts Aug. 1 at Dispensaries. Pennsylvania Pressroom. https://www.media.pa.gov/Pages/Health-Details.aspx?newsid=518. Published 2019. Accessed January 1, 2019.

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20. Columbia Care Launches Nation’s First Dose-Metered, Extended-Release, Pharmaceutical-Quality Medical Marijuana Tablets. Columbia Care NY. 2018. https://col-careny.com/columbia-care-launches-nations-first-dose-metered-extended-release-pharmaceutical-quality-medical-marijuana-tablets/. Accessed March 9, 2018.

21. Monitoring health concerns related to marijuana in Colorado: 2016. Colorado Department of Public Health. 2018. http://idpc.net/publications/2017/02/monitoring-health-concerns-related-to-marijuana-in-colorado-2016. Accessed March 19, 2018.

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26. Gaston, Tyler E.; Friedman, Daniel (2017-05-01). "Pharmacology of cannabinoids in the treatment of epilepsy". Epilepsy & Behavior. Cannabinoids and Epilepsy. 70 (Part B): 313–318.

27. Columbia Care Launches Nation’s First Dose-Metered, Extended-Release, Pharmaceutical-Quality Medical Marijuana Tablets. Columbia Care NY. 2018. https://col-careny.com/columbia-care-launches-nations-first-dose-metered-extended-release-pharmaceutical-quality-medical-marijuana-tablets/. Accessed March 9, 2018.


29. Challapalli P, Stinchcomb A. In vitro experiment optimization for measuring tetrahydrocannabinol skin permeation. Int J Pharm. 2002;241(2):329-339.

30. Lourenco Jorge L, Campelo Feres C, Telles-Dias P. Topical preparations for pain relief: efficacy and patient adherence. J Pain Res. 2010:11.

31. Zuardi A, Hallak J, Crippa J. Interaction between cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC): influence of administration interval and dose ratio between the cannabinoids. Psychopharmacology (Berl). 2011;219(1):247-249.

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36. State Medical Marijuana Laws. National Conference of State Legislatures. 2018. http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx. Accessed March 17, 2018.

37. 2016 Act 16. The official website for the Pennsylvania General Assembly. 2018. Available at: http://www.legis.state.pa.us/cfdocs/legis/li/uconsCheck.cfm?yr=2016&sessInd=0&act=16. Accessed March 16, 2018.

https://doi.org/10.17226/24625

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Depend. 2013;128(1-2):64-70.

39. Issa M, Narang S, Jamison R et al. The Subjective Psychoactive Effects of Oral Dronabinol Studied in a Randomized, Controlled Crossover Clinical Trial for Pain. Clin J Pain. 2014;30(6):472-478.

40. 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. https://doi.org/10.17226/24625.


42. State Medical Marijuana Laws. National Conference of State Legislatures. 2018. http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx. Accessed March 17, 2018.

43. 2016 Act 16. The official website for the Pennsylvania General Assembly. 2018. Available at: http://www.legis.state.pa.us/cfdocs/legis/li/uconsCheck.cfm?yr=2016&sessInd=0&act=16. Accessed March 16, 2018.

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47. Guidance of Quality Testing and Sampling By Approved Laboratories. Pennsylvania Department of Health. 2018. http://www.health.pa.gov/My%20Health/Diseases%20and%20Conditions/M-P/MedicalMarijuana/Documents/1-16-18%20MM%20Guidance%20for%20Laboratory%20Testing%20and%20Sampling%20FINAL.pdf. Accessed March 17, 2018.

48. PA Bulletin, Doc. No. 17-827. Pabulletincom. 2018. https://www.pabulletin.com/secure/data/vol47/47-19/827.html. Accessed March 18, 2018.

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Accessed March 16, 2018.





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59. Congress Protects Medical Marijuana From Jeff Sessions In New Federal Spending Bill. Forbescom. 2018 https://www.forbes.com/sites/tomangell/2018/03/21/congress-protects-medical-marijuana-from-jeff-sessions-in-new-federal-spending-bill/#7cf816753575. Accessed March 28, 2018.

60. Mjbizdaily.com. https://mjbizdaily.com/wp-content/uploads/2018/12/lawsuit-filed-in-the-Commonwealth-Court-of-Pennsylvania.pdf. Published 2019. Accessed January 2, 2019.

61. Wire Services. Pennsylvania expands partnerships for marijuana research. The Columbian. https://www.columbian.com/news/2018/dec/26/pennsylvania-expands-partnerships-for-marijuana-research/. Published 2019. Accessed January 2, 2019.

62. NIDA Drug Supply Program. Drugabuse.gov. https://www.drugabuse.gov/researchers/research-resources/nida-drug-supply-program. Published 2019. Accessed January 3, 2019.

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