DEPARTMENT OF COMMUNITY RESOURCES INTEROFFICE MEMORANDUM

TO: Board of County Commissioners VIA: Terry L. Shannon, County Administrator 115 FROM: Maureen T. Hoffman, Director DATE: July 22, 2016 SUBJECT: Dr. Mishka Terplan — Medical Presentation

Background: Dr. Mishka Terplan, Master of Public Health (MPH), Fellow of the American College of Obstetricians and Gynecologists (FACOG) Diplomat, American Board of Addiction Medicine (ABAM) certified, serves as the Medical Director for Behavioral Health System Baltimore (BHS). He joined BHS in 2014 and provides senior level medical and clinical management support, participates in quality assessment and improvement initiatives, and takes part in a variety of city-wide public health programs.

Discussion: You have requested that Dr. Terplan be placed on the agenda to present information on during a weekly BOCC meeting.

Conclusion/Recommendation: Please allot time during your September 13, 2016, BOCC meeting for Dr. Terplan to present (using the attached Power Point) information on medical cannabis.

Fiscal Impact: None

Copy: Dr. Laurence Polsky, Health Officer Medical Cannabis Maryland

Mishka Terplan MD MPH FACOG FASAM Medical Director Behavioral Health System Baltimore Cannabis is … • Probably the most • A high potential for satisfactory remedy for abuse and no accepted the treatment of medical value migraine headaches • Controlled Substance Act 1970-2016 – Dr William Osler, Textbook of Medicine 1892-1915

2 Terminology • Cannabis Plant Names • Categories of – • Refers to plant and its product – Phytocannabinoids • Oldest term • 104 cannabanoids – Marijuana • 545 total compounds • Refers to both plant and drug – Endocannabinoids • New “slang” term • 4+ cannabinoids – Cannabis – • Refers to both plant and drug • Multiple – pharmaceutical and • DSM-5 “most appropriate scientific recreational term”

3 Cannabis: A Unique Plant • Source of 3 important types of products 1. Fiber (fabric, rope) 2. Food (seed, oil) 3. Psychoactive substances (religious ritual, medicine, recreation) • Compare with: – Opium plant: psychoactive substance, food (poppy seeds) – Coca plants: psychoactive substance only

4 Cannabis Ingredients: (THC) • Primary, but not only, psychoactive ingredient of plant • Not isolated until 1964 due to technological problems – Compare to morphine (1804) and cocaine (1860)

• 1960’s to present: THC content increased from 3% to 20%

5 Cannabis Ingredients: (CBD) • First isolated in 1940 • Medical benefits: – Anticonvulsant – Anti-anxiety – Counteracts psychoactive effect of THC • Treated as Schedule 1 substance despite not being euphorogenic and is therefore illegal in US – Legal in many countries including Canada and UK

6 Cannabis Ingredients: THC/CBD Ratio • Inversely proportional • Breeding drives developments of different strains based on goal of grower – “Charlotte’s Web”: 21% CBD, <0.1% THC (= hemp)

7 One of the Oldest Known Psychoactive Substances

• Used for 12,000 years in China, India, and Central Asia • Compare with: –Alcohol 12,000 years –Opium 5,000 years –Coca 1,000 years • Introduced in Western Europe 2,500 years ago

8 Commercial Use in U.S. 1765 Post Civil War 1611 Grown by Declined due Grown by George to invention of Jamestown Washington cotton gin and settlers for at Mount competition from imported fiber Vernon hemp

1629 1800’s Major crop Grown throughout US, in New centered in England Kentucky • Cannabis slave plantations 9 History of Medicinal Use • 2700 BC. First documented – Used for centuries in India, China, Egypt, Middle East • Western medicine: mainstream use in 19th and early 20th Centuries – 1850 to 1942. Listed in U.S. Pharmacopoeia • Fluid extracts (not raw plant for inhalation) • Manufactured by major pharmaceutical companies – Prescribed for pain to Queen Victoria – Included in major medical publications • William Osler’s textbook and others 10 Context of Classification as Schedule I

"Since there is still a considerable • High potential for abuse void in our knowledge of the plant and effects of the active drug contained in it, our • No currently accepted use for recommendation is that treatment in the United States marijuana be retained within Schedule I at least until the • Lack of accepted safety for use completion of certain studies under medical supervision now underway to resolve the issue.“ Dr. Roger O. Egeberg Assistant Secretary of Health August 14, 1970

11 Possible Medical Uses • FDA approved for – Chemotherapy-induced nausea and vomiting – Appetite stimulation • High quality evidence for – Chronic pain, neuropathic (especially HIV/AIDS) • Approved in Canada – Spasticity of multiple sclerosis, spinal cord injury – Anticonvulsant (CBD for Dravet Syndrome) – Glaucoma • Poor quality evidence for – PTSD, anxiety, sleep

12 Are there any confirmed studies that show the medical benefits of medical cannabis? • Yes – but depends upon indication • Indications from MMC: – A chronic or debilitating disease or medical condition that results in a patient being admitted into hospice or receiving palliative care; – Or a chronic or debilitating disease or medical condition or the treatment of a chronic or debilitating disease or medical condition that produces: cachexia, anorexia, wasting syndrome, severe or chronic pain, severe nausea, seizures or persistent muscle spasms. – PTSD

13 Cannabinoids and Pain • Analgesic properties extensively documented and widely accepted in Western medical practice in 19th and early 20th Centuries • Cannabinoids act centrally and peripherally • CB1 receptors : 10 x more in CNS than mu-opioid receptors, especially in pain areas – Modulate neuronal excitability and inflammation – None present in brainstem • No overdose from respiratory depression

14 15 Cannabis and Pain • Appears effective for different types of pain – Neuropathic, Fibromyalgia, rheumatoid arthritis – HIV neuropathy – no reduction in viral load or CD4 cell count • Minimal tolerance • No toxic overdoses or end organ failure • Enhances analgesic effect of opioids

16 Spasticity

17 Cachexia, anorexia, wasting syndrome

• Results – overall benefit – (Rocha et al 2008) Systematic review – Dose-related adverse sedating and psychotropic effects • Limitations – most placebo controlled – fewer studies compare cannabis to newer anti-emetics

18 PTSD, anxiety, sleep

• Studies mixed – at best • Poor study design • More likely that cannabis worsens rather than improves PTSD

19 Addiction & Side Effects

20 32 23 17 15 11 9 9 5 4

21 Use of cannabis for at least a one year period, with the presence of at least two of the following symptoms, accompanied by significant impairment of functioning and distress: • Difficulty containing use of cannabis- the drug is used in larger amounts and over a longer period than intended. • Repeated failed efforts to discontinue or reduce the amount of cannabis that is used • An inordinate amount of time is occupied acquiring, using, or recovering from the . • Cravings or desires to use cannabis. This can include intrusive thoughts and images, and dreams about cannabis, or olfactory perceptions of the smell of cannabis, due to preoccupation with cannabis. • Continued use of cannabis despite adverse consequences from its use, such as criminal charges, ultimatums of abandonment from spouse/partner/friends, and poor productivity.

22 Cannabis Use Disorder (Continued) • Other important activities in life, such as work, school, hygiene, and responsibility to family and friends are superseded by the desire to use cannabis. • Cannabis is used in contexts that are potentially dangerous, such as operating a motor vehicle. • Use of cannabis continues despite awareness of physical or psychological problems attributed to use- e.g., anergia, amotivation, chronic cough. • Tolerance to Cannabis, as defined by progressively larger amounts of cannabis are needed to obtain the psychoactive effect experienced when use first commenced, or, noticeably reduced effect of use of the same amount of cannabis • Withdrawal, defined as the typical withdrawal syndrome associate with cannabis, or cannabis or a similar substance is used to prevent withdrawal symptoms.

Mild – Two or Three Symptoms Moderate- Four or five symptoms Severe- Six or more symptoms

23 Cannabis Withdrawal Syndrome • New diagnostic category in DSM-5 • Symptoms usually mild – Irritability, anxiety, insomnia, disturbing dreams, decreased appetite, restlessness, depressed mood • Cravings can be clinically significant • Time course – Onset 24 to 72 hours, peak within first week, duration 1 to 2 weeks • Sleep difficulties may last more than 30 days • Usually manageable with mild medication – Research: positive response to dronabinol 24 Negative Effects of Heavy Cannabis Use • Prospective study of 1,000 from birth to 38 found cognitive deficits if heavy use began before age 18 in: – IQ (8 points, no recovery) – Attention (poor recovery) – Memory – Processing speed – Reasoning skill • Insomnia: short term improvement but possible long term exacerbation 25 Interaction With Psychiatric Disorders

Psychosis ADHD • Association is • Self-medication clear, but cause for anxiety, and effect not insomnia, and determined distractibility

26 Other consequences • Smoking cannabis – similar cancer and respiratory risks of tobacco – but less common

27 Drunk and Drugged Driving • Alcohol effects have greater impact on complex tasks that require conscious control • Cannabis effects have greater impact on automatic driving functions • Cannabis users are more aware of being impaired and tend to use various behavioral strategies to compensate for impairments  Adding alcohol eliminates the ability to use these strategies effectively  Result: impairments at doses that would be insignificant if either substances were used alone

28 Maryland MMC

29 Current Local Legal Status • DC – Legal for medical use – Recreational use legalized by ballot initiative (65%) • Approved in all but one precinct • Home use only. Commercial sales not legal • Unsuccessful attempt by U.S. Congress to block • Maryland – Legal for medical use (not yet implemented) – Recreational use decriminalized

30 Medical Cannabis in Maryland • Law enacted 2013 and 2014, amended 2015 • Regulated by Maryland Medical Cannabis Commission – January, 2015: first full-time paid director – October, 2015: final regulations issued • Process – Physicians must register – Producers and dispensaries must be licensed – Physician writes recommendation for patient – Patient obtains medication from dispensary 31 Current Status of Program • September, 2015: Applications for licenses for producers and dispensaries were released • November, 2015: Deadline for submission of applications • End of January, 2016: Commission to award pre- approvals • Commission is not yet registering physicians or patients • Updates and answers to FAQs at mmcc.maryland.gov

32 Prescriptions? Indicating type of cannabis? • No prescriptions – recommendations • Patients – legal card holders if – 1) legal resident MD and 2) possess a “document-driven” condition as outlined by DHMH and MMC • Physicians – in order to recommend – must register via MMC and renew every 2 yrs. As “certifying physicians” they can issue written certificates for their patients to obtain and use medical cannabis. • CME-like resources available for physicians, but not required

33 Will there be a pharmacist onsite at the dispensary responsible for dispensing? • No • Max 2 dispensaries per senatorial district (47) • Licenses to grow will be awarded in summer – no sales until 2017 • Cannabis will be dispensed in dried flower or processed form including extracts, oils, tinctures, but not as “food” • Edible cannabis not permitted

34 Will there be warning labels included on the package or container of the medical marijuana? • Yes – sort of • Each batch of usable cannabis will state the THC quantity (as expressed as a percentage) • 30 day supply = 120 grams of usable cannabis, 36 grams THC max • Patients will sign a statement (at the dispensary) attesting to risks and uncertainty of medical science – Pregnant Women - Before a patient can receive medical cannabis at a dispensary, the patient has to sign a statement (“attest”) that the patient understands, among other things, that “scientific research has not established the safety of the use of medical cannabis by pregnant women,” and that the use of medical cannabis is not approved by the U.S. Food and Drug Administration.

35 Questions

36 Synthetic Cannabinoids: History • 1970s-80s. Synthesized for scientific research – Trying to identify the molecular structure that activates the endocannabinoid receptors • Results became publicly available as research papers and patents • Information appropriated by drug dealers • 2004. Appeared in Europe as “Spice,” “K2” • Subsequent chemical alterations to evade illegality and detection – Broad array of non- molecules

37 Synthetic Cannabinoids: Clinical • Motivation to use: initially promoted as a safer and legal alternative to cannabis • Routes of administration – Smoked after being sprayed on herbal material or as vaporized liquid – Drunk as a tea • Full agonists: 100 times more potent than THC (a partial agonist) • Acute effects – Tachycardia, increased BP, nausea and vomiting – Anxiety, agitation, paranoia, hallucinations, violence

38 Synthetic Cannabinoids: Treatment

• No specific treatment for toxicity or withdrawal

• Management problem in acute care settings

39 Synthetic Cannabinoids: Good News

• 2012. Synthetic Drug Abuse Prevention Act • 2013-15. Increased enforcement of laws • 2013-15. Significant decrease in use by 8th, 10th, 12th graders. See “Monitoring the Future” (www.monitoringthefuture.org) – Appears to be due to both increased perception of risk and decreased availability

40 Synthetic Cannabinoids Trends in Annual Use: Grades 8, 10 , 12

41