cmhn/mmap regional meeting cannabinoids in chronic pain · cmhn/mmap regional meeting cannabinoids...
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CMHN/MMAP Regional MeetingCannabinoids in Chronic Pain
Windsor – Friday June 10, 2016
Michael Verbora, MBA, MD, CCFP
Focused Practice in Chronic Pain
Physician Champion, Cannabinoid Medical Clinic
Faculty/Presenter Disclosure
• Faculty: Pending University of Toronto Appointment
• Program: CMHN/MMAP Windsor Regional Meeting
• Relationships with Commercial Interests:o Grants/Research Support: noneo Speakers Bureau/Honoraria: noneo Consulting Fees: noneo Other: Physician Champion at Cannabinoid Medical Clinic
Disclosure of Commercial Support
• This program has received financial support OCFP from in the form of Honoraria for presentation and an educational grant from MOH.
• This program has received in-kind support from OCFP/CEP in the form of logistical support.
• Potential for conflict(s) of interest:– Dr. Verbora has received honoraria from the OCFP
Mitigating Potential Bias
• The OCFP is a not-for profit organization that does not benefit from the mention of any products mentioned within the presentation.
• All information presented and recommendations involving clinical medicine are based on evidence found in medical literature and conforms to commonly accepted accepted standards.
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Learning Objectives
• Become aware of the endocannabinoid system, its receptors, ligands and therapeutic benefits
• Understand the role of cannabinoids in chronic pain patients and review evidence
• Apply cannabinoids to a case study
• Confirmation Bias
• Research Bias – 94% of funded studies on marijuana had a primary outcome that was attempting to prove cannabis was harmful
The Case – Ashleigh Potter
32 yo F
PMH – sexual abuse, substance use disorder (cocaine, resolved x 10 years), disc herniation (L3,4,5) + bilateral facet joint arthritis, opiate dependence (concerning behaviors)
Meds – hydromorphContin 30mg q8H + hydromorphone 8mg, q4h, PRNPast Meds Trialed – Oxycontin
Social – Windsor, single mother, tried cannabis and was helpful for pain and opiate reduction
FH – alcoholism, ADHD
Endocannabinoid System
The endocannabinoid system is:
A) Found in virtually every organ in the body
B) Limited to Central and Peripheral Nervous System
C) Well represented in the brainstem
D) Responsible for a “fight or flight” response
E) Clearly defined in it’s function
Definitions
• Cannabinoids are a class of compounds that act on cannabinoid receptors in the human body
• Endocannabinoids are cannabinoids that are naturally produced in the body (endogenous)
• Phytocannabinoids are cannabinoids produced by the cannabis plan
• Synthetic cannabinoids are laboratory-synthesized compounds that bind to cannabinoid receptors
• Some are used as pharmaceuticals (e.g. Nabilone)
• Some are used as street drugs (e.g “Spice” and “K2”)
Endocannabinoid System
• Immune Function
• Appetite
• Sleep
• Pain
• Inflammation
• Metabolism/Energy Homeostasis
• Reproduction
• Mental Health
• Cardiovascular Function
• Bone Development
• Psychomotor Behavior
• Memory
• Regulation of stress/emotional state
• Learning
• Digestion
Lipid signaling system that science has shown to be involved in:
CannabinoidsClass of chemicals that interact with cannabinoid receptors repression of neurotransmitter release
• ENDOCANNABINOIDS
(<10 known to date)
• PHYTOCANNABINOIDS
(Over 70 known to date)
CannabinoidsClass of chemicals that interact with cannabinoid receptors repression of neurotransmitter release
• Synthetic Cannabinoids
• Nabilone
• Sativex (Nabiximol)
• Modulate nociceptive thresholds• Inhibit release of pro-inflammatory molecules• Display synergistic effects with other systems that influence analgesia, especially the
endogenous opioid system.
The Major Cannabinoids
• Δ9-THC
• Partial CB1 and CB2 agonist
• Responsible for the psychoactive effects of cannabis
• Effective for relief of acute pain, muscle spasms, controlling nausea and stimulating appetite
• CBD
• Partial antagonist of CB1 and CB2 agonists, blocks enzyme breakdown of endogenous cannabinoids
• Activates: serotonin, adenosine
• Blocks: PPAR
• Not psychoactive
• Possible anti-inflammatory, analgesic, anti-nausea, anti-emetic, anti-psychotic, anti-ischemic, anxiolytic and anti-epileptic effects
Entourage effect: A theory that all of the various compounds present in the plant work together in a cooperative manner yielding the best results
Nabilone
- Single molecule
- Standardized dosing
- Longer onset of action
- Longer duration of action
Herbal Cannabis
- Over 80 cannabinoids
- Over 350 terpenes/flavonoids
- Shorter onset of action (inhaled)
- Shorter duration of action (inhaled)
- Easily titrated
What are the differences between synthetic and natural?
Cannabinoids as a class…• Cannabinoids should be considered a Therapeutic Class
• Cannabinoids are considered a third line agent for chronic neuropathic pain (CPS 2014 guidelines)
Cannabis Drug Safety - LD50/ED50/TD50
• LD50 – “the dose at which 50% of laboratory animals die from the drug”
• ED50 – “the median effective dose that produces a quantal effect in 50% of the population”
• TD50 – “median toxic dose of a drug at which toxicity occurs in 50% of the cases (type of toxicity important)”
• Therapeutic Index – LD50/ED50 – “safety window for achieving benefit compared to toxicity”
Cannabis Safety
• LD50 – 1:20,000 to 1:40,000• In order to induce death someone who have to smoke 20,000 to 40,000 times
as much cannabis as found in a single marijuana cigarette
• Therapeutic Index of Various Drugs
• Cannabis 1000:1
• Diazepam 100:1
• Morphine 70:1
• Cocaine 15:1
• Alcohol 10:1
• Digoxin 2:1
A smoker would theoretically have to consume nearly 1 500 pounds of marijuana within fifteen minutes to induce a lethal response.
Experimental and Clinical Psychopharmacology 1994. Vol. 2, No. 3, 244-268 Comparative Epidemiology of Dependence on Tobacco, Alcohol, Controlled Substances, and Inhalants: Basic Findings From the National Comorbidity Survey
Neuropathic Pain
• Neuropathic pain of at least three months in duration caused by trauma or surgery, with allodynia or hyperalgesia
• 23 cannabis naïve subjects• Randomized, Double Blind, Placebo Cross-Over Design• 2.5%, 6%, 9.4% THC or placebo• Delivered as a single smoked inhalation 3 times daily
• 4 – 14 day period – 5 days active, 9 days washout
Ware et al – Results
Pre-specified Secondary Outcomes
• Improvement in anxiety, sleep
Primary Outcome 11 item numeric rating scale
Design• Chronic pain – MSK, post traumatic, arthritic, cancer, fibromyalgia, MS,
sickle cell• Cannabis non-naïve subjects on sustained release morphine or oxycodone• Randomized, Double Blind, Placebo Cross-Over Design• Inhaled vaporized cannabis• Delivered 3 x / day for 5 days
Abrams DI et al. Clin.Pharmacol.Ther. 90: 844-851.
• Statistically significant 27% [95% CI 9 – 46] reduction in pain score• No significant effect on opiate metabolism• Limited by:
• Small sample size• Short duration
• Conclusion: vaporized cannabis augments analgesic effects of opiates without altering plasma opiate levels may be able to use cannabinoids to lower opiate treatment
Abrams DI et al. Clin.Pharmacol.Ther. 90: 844-851.
Abrams et al - Results
Baseline Post Cannabis
Systematic Review of 11 RCT trials (1185 patients)- Labelled as high quality trials (oxford scale), all assessed non-cancer pain based on formal
pain scale- 7 of the trials indicated positive benefits of cannabinoids (nabixmols, nabilone, herbal
cannabis) on pain (primary outcome)- Some of the trials used gabapentinoids or TCAs as control group- Several trials indicated improvements in secondary outcomes
- Sleep, muscle stiffness and spasticity
The Case – Ashleigh Potter
32 yo F
PMH – sexual abuse, substance use disorder (cocaine, resolved x 10 years), disc herniations (L3,4,5) + bilateral facet joint arthritis, opiate dependence (concerning behaviors)
Meds – hydromorphContin 30mg q8H + hydromorphone 8mg, q4h, PRNPast Meds Trialed – Oxycontin
Social – Windsor, single mother
FH – alcoholism, ADHD
Cannabinoid Prescription
Cannabis History – has tried friends cannabis and found this therapeutic and allowed patient to spare opiate use, not using regularly, no other past information provided re: use of cannabis
Rx:
Step 1 – trial of longacting synthetic cannabinoids – Nabilone 0.5-1mg TID (titrate to effect, max 2mg TID), encourage/monitor opiate decrease (start with PRN then longacting dose)
Step 2 – add fast acting vaporized herbal cannabis – start with CBD strains and titrate up THC to effect
Case for Cannabinoids
Cannabinoids are proven to be effective in decreasing neuropathic pain
Cannabinoids can have opiate sparing properties and hence allow us to titrate down the opiate (harm reduction/safety)
Cannabinoids are well tolerated and may have side benefits (improved sleep, mood, anxiety)
Cannabinoids are safe and have a much higher TI compared to opiates/other medications and lower dependence/addiction rate
Patient has tried cannabinoids and states benefits (“cannabinoid responder”)
Summary
• Cannabinoids are it’s own therapeutic class and should be consider for chronic pain management
• The endocannabinoid system regulates numerous cellular processes and is involved in a wide array of symptom management
• Cannabinoids are non toxic and have a much higher therapeutic index than available medications to date
• Cannabinoids have been proven to be effective for neuropathic pain in high quality RCTs and Meta-analysis
• The only legal way to obtain cannabis in Canada is through the MMPR mail order system, through Licensed Producers once authorized by a physician
What is in Marijuana? Cannabis (Sativa, Indica, or Ruderalis)
Marijuana (dried leaves and flowering heads)
Isolated pure compounds
Non-cannabinoids:
Terpenes & FlavonoidsCannabinoids
Psychoactive• Δ9-THC
• Δ8-THC
• cannabinol (weak)
Active but not
psychoactive• cannabidiol (CBD)
Inactive• more than 60
compounds
More than 450
chemical
compoundsMore than 80
types of
cannabinoids