Medical Cannabis in Maryland A Presentation to the Nurse Practitioner Association of Maryland Howard Community College, Columbia Maryland October 22, 2016 Deborah Miran,

Former Maryland Medical Cannabis Commissioner Debra Kimless, MD,

Medical Director, ForwardGro Focus on Pharmacology

• Defined as the study of drug (synthetic, natural, or endogenous) action which exerts a biochemical or physiological effect

• Pharmacodynamics studies the effect of the drug on biological systems ( interaction of the drug with biological receptors)

• Pharmcokinetics studies the effect of biological systems on the drug (absorption, distribution, metabolism, and excretion

ENDOCANNABINOID SYSTEM FUNCTION

ENDOCANNABINOID SYSTEM

• ENDOGENOUS LIGANDS= AEA/ 2-AG ENDOCANNABINOIDS

• RECEPTORS= CB1/CB2 • ENZYMES= SYNTHESIS/ HYDROLYSIS

1988 CB1 RECEPTOR WAS DISCOVERED 1993 CB2 RECEPTOR WAS DISCOVERED

LD50

• IBUPROFEN: 636mg/kg • CAFFEINE :192mg/kg • NICOTINE: 50 mg/kg • HEROIN: 22 mg/kg • It would take a 70kg man to smoke 1,500 lbs in a 15 minutes time period to die

Therapeutic Index=Toxic Dose÷Effective Dose

• Over the counter drugs- 1:20 • Prescription drugs- 1:10 • Cannabis- 1:20,000-1:40,000

Proceed with Warning

PATIENTS OPERATING HEAVY MACHINERY

HISTORY OF SEVERE HEART DISEASE

HISTORY OF SEVERE HTN

HISTORY OF MI

1992 DISCOVERED ANANDAMIDE N-arachindonoylethanolamine AEA

1995 2 AG WAS IDENTIFIED 2-ARACHIDONOYLGLYEROL

SYNTHETIC single molecule FAAH INHIBITOR by BIAL Pharma Fri Jan 15, 2016 French drug trial disaster leaves one brain dead, five injured Experimental painkiller that has left one person brain-dead and five seriously ill has been given to NINETY people, warns French health minister – and there is NO antidote

CANNABIS-THE PLANT

LATIN NAME: Cannabis Inflorentia • Chemical manufacturing factory • Over 100 phytocannabinoids-cannabinoids found in plants • Over 50 terpenes-reason for the particular scent • psychoactivity found in only a few of the 100+ cannabinoids

24

THCA THC

CBDA CBD

DECARBOXYLATION

THCA

• Anti-Spasmotic/Muscle Relaxant • Anti-Proliferative • Anti-Inflammatory • Anti-Emetic • Anti-Epileptic • Insomnia • Pain Relief

THC

• Psychoactive and Energetic • Analgesic/Pain relief • Anti-Bacterial • Anti-Emetic • Bronchodilator

• Appetite Stimulant • Neuro-protective

CBD

• Non-Psychoactive • Analgesic • Anti-Anxiety • Anti-Bacterial • Anti-Convulsive • Neuro-protective • Antidote for THC toxicity

CBGA

• Anti-Bacterial • Pain Relief • Anti-Inflammatory • Anti-Proliferative

THC Absorption Route of administration and drug formulation determines rate of absorption Inhalation – Rapid and efficient delivery from lungs to brain Bioavailability ranges from 2-56% Tmax is approximately 10 minutes Oral – Slower, lower, delayed Cmax Bioavailability ranges from 10-20% Tmax is approximately 4-6 hours Rectal – Higher absorption rate than oral and lower first pass effect Bioavailability approximately twice oral Tmax is 2-8 hours Sublingual/Buccal – Avoids first pass effect. Kinetic data for Cmax and Tmax is not well established Dermal – Avoids first pass effect. Many cannabinoid receptors in dermis and epidermis. Kinetic data for Cmax and Tmax is not well established. THC Distribution

• Distribution is rapid into tissue • Rapid metabolism by the liver • THC is highly lipophilic • Highly perfused in lung, liver, heart, and brain tissue

THC Metabolism Hepatic • Primary metabolites are 11-OH-THC (active) and THCCOOH (inactive) • Hydroxylation of THC by liver enzyme cytochrome P450 • More than 100 metabolites have been identified Extra Hepatic • Brain, lung, intestine • Hydrolyzing enzymes including cytochrome P450 • Some are pharmacologically active, but relative activity is unknown

THC Elimination • Within 5 days, 80-90% THC dose is excreted in the form of hydroxylated and carboxylated

metabolites • Approximately 65% excreted in feces • Approximately 20% excreted in urine

Kinetics of CBD and CBN

• CBD absorption and distribution similar to THC • Bioavailability via inhalation ranges from 11-45% • Bioavailability via sublingual is same as inhalation

• CBD metabolism subject to similar first pass effect upon oral administration • CBD elimination is largely excreted unchanged in feces • CBN has approximately 10% of activity of THC • CBN metabolism is similar to THC, but less extensive

Maryland’s Program • In 2013, Maryland General Assembly created Natalie M. LaPrade Medical Cannabis Commission

to carry out program to dispense cannabis to Maryland patients based on “Academic Medical Centers

Background

• Revised in 2014: • Created current model with growers/dispensaries

• Revised again in 2015 and 2016 • Added additional practitioners including NPs

Commission

• 16 Commissioners • Secretary of Health and Mental Hygiene • Representative of Comptroller • 14 Appointees of Governor

• Staggered terms • Chairman appointed by Governor • Includes a nurse and 2 patient advocates

Regulations

• Commission started developing regulations in fall of 2013 • Many drafts and public comment • Final Regulations became effective September 14, 2015

Code of Maryland Regulations

• COMAR Title 10: Department of Health and Mental Hygiene • Subtitle 62: Natalie LaPrade Medical Cannabis Commission Regulations • Chapters 1 to 35 • Link to regulations on Commission website: mmcc.maryland.gov

Program Principles

• Principles of Maryland’s Medical Cannabis Program: • Ensure proper security and protection of public safety • Assure the highest quality medicine is produced and distributed • Expedite patient access

Grower/Processor/Dispensary licenses

• For Growers, Dispensaries and Processors, there are two stages in applying: First stage – Pre-approval:

• Complete a detailed application and submit by deadline • Application reviewed, scored and ranked by independent third party reviewer

Second stage – Issue License: • Pre-approved applicant completes financing, construction, hiring, training, etc. and prepares to

open • Commission investigates financial background • Applicant tells Commission that it is ready for inspection of premises and operation • Commission inspects premises, reviews S.O.P.s, training • If inspection passed , Commission awards license to start operating

Current Status of Program

• Commission received 1081 applications: • 146 grower applications • 124 processor applications • 811 dispensary applications • 15 growers and 15 processors were selected on August 5, 2016

Physician Registration

• Visit mmcc.maryland.dhmh.gov • Click physician registry and register as a certifying physician • Form requires name, address, BOP license, CDS license • Select medical conditions • Sign attestations

Qualifying Conditions

• Cachexia • Anorexia • Wasting Syndrome • Severe and/or chronic pain • Severe nausea • Seizures • Severe or persistent muscle spasm • Glaucoma • PTSD

An Important Regulation

• A physician may be registered to treat a patient who has a condition that is: • Severe • For which other medical treatments have been ineffective

• If the symptoms can reasonably be expected to be relieved by the medical use of cannabis

Other Registries

• Patient- Will include basic identification and demographics, ID card optional • Caregiver- Same as patient, must be over 21, ID card required • Minor patients- Same as patient, parent/guardian declaration required and notarized • Written certification form

Qualifying Patients

• Patient must register with Commission before physician can issue written certification • Patient must

• Live in Maryland; or • Be physically present in Maryland for the purpose of receiving medical care from a

medical facility in Maryland • If younger than 18 years old, parent or guardian must be caregiver • No fee for patient unless patient desires ID card

Qualifying Patients

• Physician and patient must have a “bona fide” relationship: • Treatment or counseling relationship • Physician has

• Reviewed patient’s relevant medical records • Completed an in-person assessment of the patient’s medical history and current

medical condition • Created and maintained records of patient condition in accord with medically accepted

standards • Reasonable expectation physician will

– Monitor patient progress while using medical cannabis – Take medically indicated action

• To provide follow-up care • Regarding efficacy of medical cannabis as treatment • Report any adverse event associated with use of medical cannabis

Costs to Physicians and Patients

• No fees to be paid by physicians • No fees to be paid by patients to register or to obtain a written certification • If patient wishes to obtain an identification card from the Commission, fee $50

Current Status of Program

• Commission now registering physicians • Over 180 physicians registered • Registry for patients should be released in November

Written Certifications ”The Prescription”

• Issue by logging onto commission website – Physician’s name, license number, telephone number – Patient’s name, DoB, address, county

– Condition(s) requiring medical cannabis – Date patient is qualified – (Optional) Print out certification for patient use

• Basic quantity limit of 30-day supply • 30-day supply defined as:

– 120 grams of usable cannabis or – 36 grams of Delta9-THC in a medical cannabis infused product

• Physician may authorize greater quantity on determination that those amounts inadequate to meet patient’s medical needs

• Physician shall terminate certification if – Patient meets exclusion criteria – Treatment no longer medically necessary – Adverse effects outweigh medical benefits – Evidence patient is diverting cannabis

• May terminate for abuse of any substance • Notify Commission of termination in one (1) business day • Patient may seek renewal not less than 30 calendar days after issuance • Physician may renew if

– Patient is still registered – Bona fide physician-patient relationship still exists – Patient meets inclusion criteria – Patient does not meet exclusion criteria – Medical benefits likely outweigh health risks

• Cannot renew without full in-person patient assessment within 365 days before renewal

Quality Cannabis as Medicine • Goal to produce medicine that is consistent, batch to batch, lot to lot • Growers and processors encouraged to produce cannabis in a range of means and routes of

administration • Growers and processors to produce plant varieties and products containing high CBD levels, in

addition to other plants & products Quality-Testing Requirements • Producers must test all products for potency and purity • Producers must perform stability testing to assure shelf life • Producers must retain samples sufficient for follow-up testing in the event of a complaint Quality-Reporting • Complaints, adverse events and recalls

– All licensees and registered physicians must be prepared to receive, organize, record and respond to complaints and reports of adverse events

– All substantive complaints and reports of serious adverse events must be investigated – If re-analysis reveals that the retention sample does not meet specification, producers must

order a recall Dispensaries ”The Pharmacy”

• Dispensaries to be located throughout the state: – Up to two per each of 47 state senatorial districts

– Up to 15 associated with licensed growers (not counted in senatorial district allocation) Dispensaries-Training

• Extensive training of dispensary agents in: – Pharmacology of cannabis – Potential therapeutic and adverse effects of cannabis – Dosage forms and pharmacodynamics – Potential drug interactions – Recognition of symptoms of substance use disorders and acute intoxication

At Dispensary

• Patient or caregiver goes to the dispensary, or contacts dispensary for delivery by dispensary • Patient or caregiver presents proof of identity • Dispensary logs onto Commission database to confirm validity of written certification and

amount of Cannabis that can be dispensed • Patient consults trained dispensary agent on appropriate medication • Every time cannabis is dispensed, the patient must acknowledge that the patient is not immune

from liability or prosecution for: – Operating a vehicle under the influence of medical cannabis – Smoking in a public place – Smoking in a motor vehicle – Acting under the influence in a manner that would constitute negligence or professional

malpractice. – Smoking cannabis on private property where not allowed

• Patient also must acknowledge: – It is illegal to transfer the cannabis to any person – Obtaining medical cannabis does not exempt patient from prosecution under federal

law – Scientific research has not established the safety of the use of medical cannabis by

pregnant women – Use of medical cannabis to treat a medical condition is not approved by the U.S. FDA