Medical Cannabis and its Role in Chronic Pain Management - Gregory T Carter, MD, MS - Russo CME

Medical Cannabis and its
     Role in Chronic Pain
         Management

Gregory T Carter, MD, MS
Spokane Pain Conference
November 10, 2018 2:30-3:30 PM
The Centennial Hotel
303 W North River Dr
Spokane, WA 99201

Disclosure: Educational Grant Support

 Cy Pres grant, #12-2-39485-7, awarded to the
  University of Washington Alcohol & Drug Abuse
  Institute; PI Dr. Bia Carlini; speaker is subPI
 Funding awarded to support research and education
  on the medicinal uses of cannabis in WA state
 Website for on-line physician training:

http://adai.uw.edu/mcacp/
 Speaker has no other disclosures

Learning Objectives I:
  At the conclusion of the presentation the attendee will be able to -

 Understand historical aspects of
  medicinal cannabis
 describe the major pharmacological
  effects of cannabinoids that are
  applicable to chronic pain
 Understand the current state of
  research and data base

Learning Objectives II:
  At the conclusion of the presentation the attendee will be able to -

 explain and describe the risks and benefits
  of cannabis use in this setting
 explain and describe the physiological
  changes occurring with activation of the
  endocannabinoid system through cannabis
  use
 Describe practical applications in a clinical
  setting

History

 The cannabis plant dates back approximately 35
  million years.
 Cannabis sativa among the oldest agricultural crops
  in the world, cultivated for at least 10,000 years.
 It has been used as a food, a nutraceutical, herbal
  medicine, prescription medicine and
  spiritual/recreational intoxicant for all of recorded
  human history.

History

 Pain is the most common symptom that drives
    patients to see a health care provider.
   Cannabis has long been used as an analgesic
   Its analgesic properties are noted in most, if not all,
    “materias medica” ever written. Ancient medical
    texts, both far and middle east
   Pen Ts'ao Ching -the earliest Chinese pharmacopoeia
   The Pen Ts'ao Ching was passed on by oral traditions
    established by 2700 BC

History in the USA

 Important crop: cultivated for fiber, rope, clothing,
 seeds for oil and fuel.

 Cannabis based medications were produced by Eli-
 Lilly, Parke Davis, and Sharp Dohme (now Merck
 Sharp Dohme).

 Prescribed by physicians in the United States 1890-
 1937.

Historical Use in USA

Historical Use in USA

 Medicinal cannabis products were manufactured by
  such well known pharmaceutical firms as Eli Lilly,
  Squibb, Merck, Parke-Davis, Sharp and Dohme, and
  the Smith Brothers.
 In the early 20th century cannabis was a common
  constituent of both physician’s prescriptions and an
  ingredient in patent medicines.
 In the 1920s American physicians wrote three
  million cannabis-containing prescriptions per year.

Eradication History

 1930 - Use of cannabis under increasing scrutiny by
 Federal Bureau of Narcotics (FBN).

 1937 - The Marijuana Tax Act made possession or
 transfer of cannabis illegal throughout the United
 States under federal law.

 The American Medical Association (AMA) opposed
 the act

 1942 - All use of cannabis was criminalized in the
 United States by 1942 and still remains as such
 under Federal law

Characterization History

 1964 - THC (Tetrahydrocannabinol) first isolated as
  an aromatic terpenoid in Israel by Dr. Raphael
  Mechoulam
 By comparison morphine isolated in early 19th
  century, cocoa and cocaine in middle 19th century.
  Discovered earlier because called morphine and
  cocaine are alkaloids, which will precipitate out as a
  salt – very easy to prepare.
 THC is the main psychoactive substance in cannabis
  and thought to be the primary ingredient for years

Characterization History

 By mid 1970s Elisandro Carlini studied cannabidiol
  (CBD) – shows analgesic and anti-epilipetic effects
  in animal models
 CBD originally believed to be precursor to THC. Now
  known that CBD and THC are produced
  independently
 Other cannabinoids discovered in the following years
 CBN (Cannabinol), CBV (Cannabivarin), THCV
  (Tetrahydrocannabivarin), among many others

Turning Point: Discovery of Endocannabinoid System

 Intricately involved in normal human physiology.

 Cannabinoid receptors are found in the brain and
  peripheral tissues – nerves, gut, immune cells.
 Dense receptor concentration in the cerebellum, basal
  ganglia, and hippocampus.
 Few cannabinoid receptors in the respiratory areas in
  brainstem.
 The cannabinoid receptors CB1 and CB2, two G protein-
  coupled receptors that are located in the central and
  peripheral nervous systems, and ubiquitously throughout
  human physiological systems.

The Endocannabinoid System

 Endocannabinoids are both neuromodulators and
  immunomodulators.

 Controls pain, appetite, mood, sleep, gut motility, muscle
  coordination, short term memory.

 Inflammatory levels – endocannabinoids suppress inflammation.

 Activation of cannabinoid receptors leads to activation of
  GTPases in macrophages, neutrophils, and B/T cells.

 CB2 receptors regulate migration of B cells and maintain healthy
  IgM levels.

Physiological Effects of Endocannabinoids

 Endocannabinoids are often produced as an adaptive
 response to cellular stress, aimed at reestablishing cell
 homeostatis. “Runner’s high”

 Endocannabinoids affect a large number of physiological
 processes including:

  •   Feeding behavior                 •   Learning, memory emotions
  •   Energy balance, metabolism, GI   •   Immune and inflammatory
                                           responses
      function
                                       •   Cardiovascular function
  •   Pain perception
                                       •   Reproduction
  •   Motor control and posture
                                       •   Bone formation

Cannabinoid Receptors

 G-protein-coupled receptors
 CB1 receptors highly expressed in the brain
   --CB1 receptors also found in adipose tissue, liver, muscle, the GI tract,
    pancreas, and reproductive and cardiovascular tissue.
 CB2 receptors are expressed primarily in immune cells
   CB2 receptor expression in neurons is being studied.

The CB1 Receptor

    The CB1 receptor consists of 7 transmembrane helices.
Courtesy of Patricia Reggio, PhD

Key ECS Elements

Cannabinoid receptors are G-protein-coupled receptors         • Central nervous system
                                                               - Hippocampus
                                                               - Basal ganglia
                                                               - Cortex
                                                               - Cerebellum
                                                               - Hypothalamus
                                                               - Limbic structures
                                                               - Brainstem
                                                              • GI tract (myenteric neurons
                                                                 and epithelial cells)
   *360 *472
                                                              • Liver (hepatocytes)
                                          CB1 receptor        • Adipose tissue
Endocannabinoids
                                                              • Muscle
                                                              • Pancreas (α-cells)

                                    2-Arachidonoyl-glycerol   • Immune cells and tissues
      Anandamide                                               - T cells, B cells
                                                               - Macrophages
Endogenous, phospholipid-derived metabolites that bind         - Dendritic cells
to and activate cannabinoid receptors.                         - Spleen, tonsils
                                          CB2 receptor         - Adipose tissue

Difference Between Classical & Retrograde Neurotransmission

         Classical neurotransmitter   Retrograde neurotransmitter
Presynaptic                                                   Presynaptic

Postsynaptic                                                 Postsynaptic

Cannabis plant: cannabinoids, terpenoids and more

Major Cannabinoids
 Tetrahydroncannabinol (THC) – mind altering properties

 Cannabidiol (CBD): analgesia; moderates effects of THC.

 Cannabinol (CBN): anticonvulsant.

 Tetrahydrocannabivarin (THCV): anti-inflammatory.

 Cannabichromene (CBC): mixed effects.

 Cannabicyclol (CBL)

Types of Cannabis Plants

 Type 1: High THC, Low or No CBD*
 Type 2: Equal amounts of THC and CBD**
 Type 3: Low THC, High CBD/CBN**

 *generally preferred for recreational use
 **generally preferred for medical use

Indica vs Sativa

 Indica: short dense plants, darker green; higher
  amounts of THC and lesser CBD/CBN or equal
  amounts THC/CBD produced (type 1&2 plants).
 Sativa: tall, thin plants, light green, reach heights of
  20 feet. Sativa plants typically have lower overall
  THC content than Indica plants. May produce higher
  amounts of CBD. Type 3 plants. Hemp is a
  subspecies of Sativa plants

Research: what is the data base?

   PubMed search done one 9/2/2018
   Opioid = 150,323
   marijuana = 28,241
   Opiate = 20,615
   Cannabis = 18,506
   Methadone = 15, 744
   Cannabinoids = 15,566
   Oxycodone = 3339
   Hydrocodone = 1070

Research on Cannabis

 Due to restrictions on research the animal
  model/basic science data base is far more
  extensive than human studies
 Primarily done in rodent models
 Some work done in primates
 Variable delivery systems and outcome
  measures

Conducting clinical research using cannabis:

 Drug Enforcement Admin (DEA) - Schedule I
 DEA provides researchers with a special registration
  and has certain requirements at the site cannabis
  will be studied.
 Funding from National Institute on Drug Abuse
  (NIDA) within the National Institutes of Health
 NIDA provides cannabis from the University of
  Mississippi

Human Research - Evaluation of medicinal cannabis in
humans is still evolving – but remains significantly restricted
                   due to Federal laws in US

 COMPARED TO PHARMA - Studies are small, imperfectly
  controlled, use smoked cannabis, limited by regulations (NIDA
  budgets of $500,000 versus millions in industry trials). trials are
  small – typically single centered, short duration

 Feds require using Mississippi cannabis -poor composition and
  irregular bioavailability. Historically delivered as cigarettes -
  delivery system suboptimal – smoking

 The discovery of the endocannabinoid system has stirred
  research interest from industry – still laws make research
  difficult since cannabis is schedule 1. Won’t have
  industry/pharma funding until that changes.

Patient reports of efficacy and the Internet

 Internet = new source of patient reported data.
  Widely available to both clinicians and the public
 This has led to melding of peer-reviewed data and
  anecdotal reporting. This creates challenges in terms
  of improving the quality and safety of medical care.
 There is scientific evidence and “real-world
  evidence”—that is, evidence derived from data
  gathered from actual patient experiences, in all their
  diversity
 How we may adapt “real-world evidence” into
  scientific evidence is a daunting task

Cannabis and Evidence-based medicine (EBM)

 Historically recorded use of cannabis as medicine
  dates back thousands of years
 EBM is a relatively new concept, coming of age only
  in the last quarter century and partly driven by
  technological developments (modern computers and
  the internet)
 Today most nationally funded health care systems in
  the United States are basing practice guidelines on
  EBM.
 Goal is standardizing practice through EBM clinical
  practice guidelines (CPG).

Example of a well done EBM Class 1 Study on
     smoked cannabis for neuropathic pain

Abrams DI, Rowbotham MC, Petersen KL, et al. Cannabis in painful HIV-
associated sensory neuropathy: a randomized placebo-controlled trial.
Neurology 2007; 68(7):515-21.

Metanalysis of Human Data for pain

 Phillips TJ, Cherry CL, Cox S, Marshall SJ, Rice AS.
  Pharmacological treatment of painful HIV-associated sensory
  neuropathy: a systematic review and meta-analysis of
  randomised controlled trials. PLoS One 2010; 28;5(12):e14433.
 Martín-Sánchez E, Furukawa TA, Taylor J, Martin JL. Systematic
  review and meta-analysis of cannabis treatment for chronic pain.
  Pain Med 2009; 10(8):1353-68.
 Campbell FA, Tramèr MR, Carroll D, Reynolds DJ, Moore RA,
  McQuay HJ. Are cannabinoids an effective and safe treatment
  option in the management of pain? A qualitative systematic
  review. BMJ 2001; 323(7303):13-6.
 Machado Rocha FC, Stéfano SC, De Cássia Haiek R, Rosa
  Oliveira LM, Da Silveira DX. Therapeutic use of Cannabis sativa
  on chemotherapy-induced nausea and vomiting among cancer
  patients: systematic review and meta-analysis. Eur J Cancer
  Care 2008;17(5):431-43.

Lynch ME et al., 2011 review

Lynch ME, Campbell F. Cannabinoids for Treatment of Chronic
Non-Cancer Pain; a Systematic Review of Randomized Trials. Br J
Clin Pharmacol 2011 2(5):735-44 PMID: 21426373

 Systematic review of RCTs for cannabis treating chronic non-cancer
  pain: neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed
  chronic pain.
 Quality of trials = excellent.
 15 of the 18 trials showed significant analgesic effect of cannabis.
 No serious adverse effects; only a few withdrawals from the studies.

 Overall evidence indicates that cannabinoids are
  safe and effective.

Lynch ME et al., 2015 f/u review

 Lynch ME, Ware MA. Cannabinoids for the Treatment of Chronic Non-
    Cancer Pain: An Updated Systematic Review of Randomized Controlled
    Trials. J Neuroimmune Pharmacol. 2015; 10(2):293-301
 Eleven new trials
 Quality of trials excellent.
 Seven trials showed significant analgesic effect.
 Several trials also showed improvement in sleep, muscle stiffness and
  spasticity
 Adverse effects most frequently reported such as fatigue and dizziness were
  mild to moderate in severity and generally well tolerated.
 This review adds further support that currently
    available cannabinoids are safe, moderately effective
    analgesics that provide a reasonable therapeutic
    option in the management of chronic non-cancer pain.

Hill KP. Medical Marijuana for Treatment of Chronic Pain and Other
    Medical and Psychiatric Problems: A Clinical Review. JAMA 2015; 23-
                            30;313(24):2474-83

 Use of marijuana for chronic pain, neuropathic pain,
    and spasticity due to multiple sclerosis is supported
    by high-quality evidence.
   Six trials that included 325 patients examined
    chronic pain
   6 trials that included 396 patients investigated
    neuropathic pain
   12 trials that included 1600 patients focused on
    multiple sclerosis
   “Several of these trials had positive results,
    suggesting that marijuana or cannabinoids
    may be efficacious for these indications”

Cohen NL, Heinz AJ, Ilgen M, Bonn-Miller MO. Pain, Cannabis Species,
 and Cannabis Use Disorders. J Stud Alcohol Drugs. 2016 77(3):515-20.

 163 medical cannabis users completed assessments
  of medical cannabis use motives, history, preferences
  (species type), and problems, as well as current pain
  level.
 Individuals who used cannabis to manage chronic
  pain experienced fewer cannabis use problems than
  those who did not use it for pain; among those who
  used it for pain, the average pain level in the past
  week was not associated with cannabis use problems.
 individuals who used cannabis for chronic
  pain were more likely to use indica over
  sativa.

Mücke M, Phillips T, Radbruch L, Petzke F, Häuser W. Cannabis-based
medicines for chronic neuropathic pain in adults. Cochrane Database Syst
                   Rev. 2018 2018 Mar 7;3:CD012182

 included 16 studies, 1750 participants.
 studies ranged from 2 to 26 weeks long
 Study quality: low in 2 studies, moderate in 12
  studies and high in 2 studies.
 9 studies were at high risk of bias for study size.
 Cannabis-based medicines increased
  number of people achieving 50% or greater
  pain relief compared with placebo (21%
  versus 17%; - 95% confidence interval)

Baron EP, et al Patterns of medicinal cannabis use, strain analysis, and substitution effect
among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis

                        cohort. J Headache Pain. 2018 24;19(1):37

 Chronic pain was the most common reason for cannabis
  use, consistent with most registries. The majority of headache
  patients treating with cannabis were positive for migraine.
 Hybrid strains were preferred: high THC (Δ9-
  tetrahydrocannabinol)/THCA (tetrahydrocannabinolic acid), low
  CBD (cannabidiol)/CBDA (cannabidiolic acid), strain with
  predominant terpenes β-caryophyllene and β-myrcene, most
  preferred in the headache
 May reflect the potent analgesic, anti-inflammatory, and anti-
  emetic properties of THC, with anti-inflammatory and analgesic
  properties of other cannabinoids and terpenoids
 Prospective studies are needed, but results may provide early
  insight into optimizing crossbred cannabis strains

Societal Benefit

 overall reductions in Medicare spending when states
  implemented medical marijuana laws were estimated to
  be $165.2 million per year in 2013.
 Bradford AC, Bradford WD. Medical Marijuana Laws
 Reduce Prescription Medication Use In Medicare Part D.
 Health Aff (Millwood). 2016 1;35(7):1230-6.

 Medical cannabis laws are associated with significantly
 lower state-level opioid overdose mortality rates.
 Bachhuber MA, Saloner B, Cunningham CO, Barry
 CL.Medical cannabis laws and opioid analgesic overdose
 mortality in the United States, 1999-2010. JAMA Intern Med.
 2014 ;174(10):1668-73.

Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A
    Systematic Review and Meta-analysis. JAMA 2015; 23-30;313(24):2456-73.

 79 trials (6462 participants) were included
 Most trials showed improvement in
    symptoms associated with use of
    cannabinoids
   nausea and vomiting
   reduction in pain
   reduction in spasticity
   Common AEs included dizziness, dry mouth, nausea,
    fatigue, somnolence, euphoria, vomiting,
    disorientation, drowsiness, confusion, loss of
    balance, and hallucination

Use discretion in reading literature

 Walitt B, Klose P, Fitzcharles MA, Phillips T, Häuser W. Cannabinoids
  for fibromyalgia. Cochrane Database Syst Rev. 2016 Jul
  18;7:CD011694
 This study actually only looks at nabilone.
  Nabilone is 100% THC, not the same thing as
  “cannabinoids”
 Authors found no convincing, unbiased, high quality
  evidence suggesting that nabilone is of value in
  treating people with fibromyalgia.
 The tolerability of nabilone was low in people with
  fibromyalgia.

Stockings E, et al Cannabis and cannabinoids for the treatment of people with
    chronic non-cancer pain conditions: a systematic review and meta-analysis of
              controlled and observational studies. Pain 2018 May 25.

 no significant impacts upon physical or emotional
    functioning
   low-quality evidence of improved sleep and patient
    global impression of change.
   Evidence for effectiveness of cannabinoids in CNCP
    is limited.
   Effects suggest NNTB are high, and NNTH low, with
    limited impact on other domains.
   It appears unlikely that cannabinoids are highly
    effective medicines for CNCP.
   From NIDA; limited bibliography (40 references)

Nielsen S, Sabioni P, Trigo JM, Ware MA et al. Opioid-Sparing Effect of
            Cannabinoids: A Systematic Review and Meta-Analysis.
               Neuropsychopharmacology 2017. 42(9):1752-1765

 included pre-clinical and clinical studies
 19 pre-clinical and 9 clinical studies met the search criteria.
 17 of 19 pre-clinical studies provided evidence of synergistic
  effects from opioid and cannabinoid co-administration.
 pre-clinical studies indicate that the median effective dose
  (ED50) of morphine administered in combination with delta-
  9-tetrahydrocannabinol (delta-9-THC) is 3.6 times lower
  (95% confidence interval (CI) 1.95, 6.76; n=6) than the ED50
  of morphine alone. Thus pre-clinical studies provide robust
  evidence of the opioid-sparing effect of cannabinoids,
 Only 1 of 9 clinical studies identified provided very-
  low-quality evidence of such an effect.
 Prospective high-quality-controlled clinical trials
  are required to determine the opioid-sparing effect
  of cannabinoids.

Abuhasira R, Schleider LB, Mechoulam R, Novack V. Epidemiological
characteristics, safety and efficacy of medical cannabis in the elderly. Eur J Intern
                                 Med. 2018;49:44-50.

 prospective study- included 2736 patients above 65 years of age who
    received medical cannabis from January 2015 to October 2017 in clinic
   Outcomes were pain intensity, quality of life and adverse events at six
    months.
   mean age was 74.5 ± 7.5 years.
   The most common indications for cannabis treatment were pain (66.6%)
    and cancer (60.8%).
   After six months of treatment, 93.7% of the respondents reported
    improvement in their condition and the reported pain level was reduced
    from a median of 8 on a scale of 0-10 to a median of 4. Most common
    adverse events were: dizziness (9.7%) and dry mouth (7.1%).
   After six months, 18.1% stopped using opioid analgesics or reduced their
    dose.
   cannabis is safe and efficacious in the elderly population.
   Cannabis use may decrease the use of other prescription medicines,
    including opioids. Gathering more evidence-based data, including data
    from double-blind randomized-controlled trials, in this special population
    is imperative.

Mari Carmen Torres-Moreno, Esther Papaseit, Marta Torrens, et al. Assessment of Efficacy
and Tolerability of Medicinal Cannabinoids in Patients With Multiple Sclerosis. A Systematic
           Review and Meta-analysis. JAMA Network Open. 2018;1(6):e183485.

 Cannabis safe for use in this population
 Oral compounding only - results suggest a limited
  efficacy of cannabinoids for the treatment of
  spasticity, pain, and bladder dysfunction in patients
  with MS.

Using in clinical medicine

 Clinical Pharmacology
 Methods of use
 Dosing paradigms
 Side effects
 Patient instructions
 Risk/Benefits

CLINICAL PHARMACOLOGY OF CANNABIS

 95-99% plasma protein bound -hydroxylation,
    oxidation, and conjugation for rapidly clearance
    from plasma
   First-pass metabolism through liver (after PO
    admin) to 11-OH-THC
   Elimination is slow: days to weeks 20-35% found in
    urine; 65-80% found in feces; stored in adipose;
   Pregnancy Category C: in breast milk
   Works through a known receptor based system

Routes of delivery

   •       Smoking: fastest acting but irritates the bronchial tree.
   •       Vaporizing: 70% fewer irritants than smoking and preserves more cannabinoids
    than smoking
   •       Water Pipe (Bong): Removes irritants and THC in equal proportions, cools
    smoke but still smoking.
   •       Sublingual: Tincture applied under the tongue. Acts in about 15 minutes.
   •       Tea: Traditional form consumed for millennia in India. Can be made from leaves,
    roots, or flowering tops. Usually made with milk or cream to absorb fat soluble
    cannabinoids.
   •       Oral/Edibles: Take minimum of 45 to 75 minutes to act. l.
   •       Topical: Used for over a century by curanderos in Southern Mexico and Central
    America to treat arthritis in hands and wrists.
   •       Prescription: Dronabinol (Marinol) (THC), Nabiximol (Sativex) (Canada, UK
    and EU)
   •       Rectal: RSO suppositories.
   •       Juicing: The raw, newly picked plant (undried) has all its cannabinoids in the
    acid form including THCa (the non-psychotropic precursor to THC,) CBDa, etc. There are
    apparently no psychotropic effects from juicing the newly picked plant.


Methods of Use

 DO NOT SMOKE – Use vaporizer for fast effect.

 Oral or sublingual tincture ingestion for longer effect.

 Topical for local effect.

 Use low doses of cannabis that has high CBD/CBN
 and low THC.

 Do not need to be high to get pain relief.

Vaporization of Cannabis

 Safe alternative to smoking

How Do Vaporizers Work?

 When cannabinoids are heated to between 285 °F
 (140 °C) and 392 °F (200 °C) they boil and vaporize
 – “e-cigarette.”

 Studies show that vaporization is most effective at
 around 338 °F (170 °C).

 A vaporization temperature over 392 °F (200 °C) will
 burn the cannabis, creating unwanted smoke.

Dosing Paradigms

         Self titration - START
          LOW; GO SLOW.

         Vapor: 2-3 inhalations,
          stop, wait ten minutes.

         Do not need to be high to
          get pain relief.

Side Effects

 Disinhibition, relaxation, drowsiness

 Feeling of well being, exhilaration, euphoria

 Sensory - perceptual changes

 Recent memory impairment

 Balance/stability impaired

 Decreased muscle strength, small tremor

 Poor on complex motor tasks (e.g., driving)

Effects on Behavior

 Can impair judgment.
 Slowed reaction time.
 Motor impairment.
 Disorganized thoughts, confusion.
 May get paranoia, agitation.

  Do Not Drive!

Clinical Effects

 no overdose, overall well tolerated if used as advised

 No constipation

 No respiratory suppression

 Relieves pain, improves sleep

 Improves appetite

 Works synergistically with opioids – potential to lower
  opioid dose -Decrease needs for opioids?

Advising the Patient

 Adverse effects: mainly seen in new users.

 Start low, go slow and easy.

 These are reversible, short lived effects (3-4 hours max).

 Serious adverse effects NOT seen in chronic users.

Authorizing a patient:

 Risk Evaluation and Mitigation Strategy
 Screen the patient – use standard the risk screening
  tools.
 Stratify treatment: If the patient is legit, try the
  standard non-opioid drugs first: AEDs, SSRIs, SNRIs,
  TCAs, etc. If the standard first line meds do not work then
  –consider CANNABIS before OPIOIDS.
 Start low go slow, Monitor for abberrant behavior and
  dependency
 If patient already on opioids, then use cannabis to lower
  their dose of opioids (and other meds).

Who may authorize in WA state?

 Physicians (MD/DO)
 Advanced Care Practitioners: Physician Assistants
  (PA-Cs) and Advanced Registered Nurse
  Practitioners (ARNP)
 Naturopathic Physicians (ND)

 Having authorization saves your patient money (less
 taxation) and allows them to possess more cannabis

For what conditions?

 Cancer, human immunodeficiency virus (HIV), multiple
    sclerosis, epilepsy or spasticity disorders.
   Intractable pain (pain unrelieved by standard medical
    treatments
   Glaucoma
   Crohn's disease
   Hepatitis C with debilitating nausea or intractable pain
   Diseases which result in nausea, vomiting, wasting,
    appetite loss, cramping, seizures, muscle spasms, or
    spasticity
   chronic renal failure requiring hemodialysis.
   Posttraumatic stress disorder.
   Traumatic brain injury.
   Mental health conditions don't qualify

Drug interactions

 drug-drug interactions not well documented -
    there is a need for more study
   May decreases bioavailability of methadone
   May enhance some anti-cholinergic side
    effects: dry mouth, tachycardia
   CBD may inhibit benzodiazepine
    metabolism
   Forms of cannabis with higher THC concentration
    may enhance cognitive and psychomotor
    effects of other medications and intoxicants –
    this is particularly important when counseling the
    patient regarding driving

Other effects

 Medical cannabis also has similar adverse effects as
  the FDA-approved cannabis-based medications
  mainly consisting of:
 CNS related adverse effects
 Cardiovascular –tachycardia, possible hypotension
 respiratory related adverse effects not common
  unless smoked. Cannabinoids are bronchodilators
  and may improve some forms of reactive airway
  disease

Final comments

 Patient should use high quality cannabis to
    improve efficacy: high CBD, CBN, lower
    THC –
   do not need to be high to get pain relief
   use a delivery route that maximizes benefits and
    minimizes side effects.
   Cannabis is not for everyone - Some people cannot
    tolerate it or it does not work for them.
   There is a risk for psychological addiction.
   Tolerance may develop in heavy, long term users -
    may need higher doses.
   Patient/family will have to purchase or grow it still
    some social stigma.

What About Marinol?

 100% THC in pure form is a schedule 3 drug (Marinol).

 Natural cannabis at 3 - 15% THC is schedule I, dangerous,
  no medical use.
 Purification and concentration is NOT always a good thing.

 Effective medical cannabis = low THC, high in other
  cannabinoids.
 Marinol is a powerful sedative hypnotic, prescribe with
  caution

Newer Products – Sativex

 1:1 combination from two clonal
  cannabis cultivars yielding a high
  THC extract and a high CBD extract

 THC and CBD comprise some 70%
  (w/w) of the total BDS

 Each 100 μL pump-action spray
  provides 2.7mg of THC and 2.5mg of
  CBD

 Intermediate onset: 15-40 minutes

 Allows dose titration; Reduces first
  pass metabolism
 Not avail in USA now

Epidiolex

 is a formulation of CBD. Like Sativex, it is derived
  from cannabis
 contains no THC
 Approved here for Lennox-Gastaut Syndrome
  (refractory seizures).
 No data on chronic pain

Thank you

 Questions/Discussion