MEDICAL MARIJUANA AND PAIN THE SCIENCE, REGULATIONS AND ETHICAL DILEMMAS

CHRONIC PAIN

ACKNOWLEDGEMENT CONTRIBUTORS •  •  •  • 

Dr. Michael Negraeff,Pain Specialist Dr Pam Squire,Pain Physician Dr. Pippa Hawley,Internist/Cancer Pain Subspecialist Julie Singer BSc(Kin),Medical Rep-Tilray

DISCLOSURE DAVID G. HUNT, M.D., FRCP(C) • 

Honoraria for Presentations and Preceptorships – Janssen Ortho, Purdue Pharma, Valeant

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Honoraria for Consulting and Presentations - Pfizer

OBJECTIVES • 

To Summarize the Current Understanding of the Science of Cannabinoids at a Level which can be Understood by this Diverse Audience

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To Review the Recent Federal Legislation on Medicinal Marijuana and Discuss How it Impacts on M.D./RN Prac.,Patients,and Producers

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To Define the Ethical Dilemmas Health Providers are Encountering in Prescribing Medicinal Marijuana.

AUDIENCE PARTICIPATION Do you ever feel uncomfortable or

1.  2. 

uneasy when a patient or family member with chronic pain requests treatment with marijuana? Yes… No..

AUDIENCE PARTICIPATION

CAN YOU EXPLAIN WHY YOU FEEL UNCOMFORTABLE?

AUDIENCE PARTICIPATION I AM UNCOMFORTABLE BECAUSE : 1.  2.  3.  4.  5. 

I don’t know the risks versus benefits,or drug interaction I have little experience, knowledge and few guidelines to safely prescribe marijuana I’m unsure if the Marijuana is actually relieving the pain. Marijuana is a “Gateway” drug which may lead to abuse,misuse more addictive drugs or diversion Major National Medical Organizations advise against prescribing Marijuana and/or I’m worried about a College Review.

MARIJUANA- THE SCIENCE

DO WE HAVE ALL THE ANSWERS?

CANNABINOIDS

SITES OF ACTION Location of CB 1receptors

Brain

PAG RVM

Brainstem

dorsal root ganglion

Spinal Cord

primary afferent receptor

ENDOGENOUS CANNABINOIDS Several identified : Anandamide, 2AG, PEA Anandamide • 

Produced by the body- act at the cannabinoid receptors

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Similar effect to THC, but less potent

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Has both, central (CB1) and peripheral(CB2) effects

RECEPTORS The CB1 receptors are mainly located in the brain: •  Basal ganglia, hippocampus •  Cerebral cortex & cerebellum •  Also spinal cord & primary afferent nociceptors The CB2 receptors are exclusively located in periphery: •  Spleen & tonsil •  Mast cells Mack 2001

ABUNDANCE OF RECEPTORS CB1 extraordinarily abundant in the brain...

Joy 1999

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10 times more abundant than mu opioid receptors

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Few CB1 receptors are present in the cardiorespiratory area of the brain stem, which makes maijuana and cannabinoid drugs safe in overdose

ENDOCANNABINOID SYSTEM WIDESPREAD FUNCTIONS

Joy 1999

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Memory and Sleep

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Appetite and Metabolism

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Pain Perception and Modulation

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Stress Response and Balance of Excitatory / Calming Effects

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Intestinal motility

DEFINITION Cannabinoids are the main active components of the plant Cannabis Sativa (Marijuana)

CANNABINOIDS Cannabis Sativa More than 400 chemical compounds hundreds of compounds

Marijuana (dried leaves and flowering heads)

Non-cannabinoids The most potent psychoactive ingredient

Psychoactive •  Δ9-THC •  Δ8-THC •  cannabinol (weak)

Kalant 2001

More than 60 types of cannabinoids

Isolated pure compounds Cannabinoids

Active but not psychoactive •  cannabidiol

Inactive •  more than 60 compounds

MEDICAL BENEFIT • 

THC--delta9-tetrahydrocannabinol •  Psychoactive,analgesic,antiemetic, relaxes muscles, anticonvulsant, can decrease and increase anxiety, decrease depression •  Precipate psychosis in vulnerable

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CBD—cannabidiol •  Non-psychotropic,analgesic,antiemetic, antianxiety, anti-psychotic, inhibits metabolism of THC, may reduce psychoactive effects of THC

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RATIO—THC/CBD

ACTION ON SYSTEMS Pain pathway

Cannabinoids

Serotoninergic

Stimulation suppresses GABA

Norepinephrine

Stimulation suppresses GABA

Glutamate/NMDA

Blocks NMDA in dorsal horn

Inflammatory Response

Blocks inflammatory action of Prostaglandins and substance P

Opiate System

Act on opioid receptors: kappa, delta and mu

POTENTIAL BENEFITS** IN CHRONIC PAIN

•  Neuropathic Pain** •  Arthritis-RA,OA •  Fibromyalgia •  Musculoskeletal •  Palliative Care •  Muscle spasm/Spasticity •  PTSD and Anxiety

CONTRAINDICATIONS • 

Known Sensitivity/Allergy to Marijuana

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Uncontrolled Hypertension/Arrhythmias

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Active Ischemic Heart Disease

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Chronic Hepatitis C

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Schizophrenia,Paranoia

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Pregnancy/Breast Feeding

•  Under 18**

RELATIVE CONTRAINDICATIONS • 

History of psychosis

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History of Drug or Alcohol Addiction

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Severe liver dysfunction

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Use with other psychoactive drugs,sedativehypnotics or benzodiazepines Careful monitoring with comorbid depression or other psychiatric disorders

ACUTE SIDE EFFECTS Symptom / Effect CNS

Cardiovascular

Others

Sedation Dizziness Somnolence Euphoria / high Blurred vision Anxiety Panic Paranoia Psychosis Depression Ataxia Asthenia Cognitive effects

Most common √ √ √

Rare

√ √ √ √ √ √ √ √ √ √

Postural Hypotension Vasodilation (red eyes) Tachycardia Palpitations Dry mouth Headache

Common

√ √ √ √ √

*If smoked - Respiratory effect such as bronchitis, COPD, lung infection.

√

OVERDOSE THE OVERALL ACUTE TOXICITY OF THC IS LOW Acute studies show that it is virtually impossible to die from acute administration of THC alone Low concentration of CB1 receptors in the brainstem cardiopulmonary centres, probably accounts for the high margin of safety with marijuana

LONG TERM EFFECTS Dependency Cognitive Psychosis & schizophrenia

- Lower risk than alcohol and tobacco - Rare with therapeutic use only (unlike opioids) - Withdrawal symptoms in heavy chronic users - Impaired in heavy chronic users (resolve after 30 days of abstinence) - Higher risk to develop symptoms in young people - May precipitate in predisposed people

Immunity Pregnancy

- Unknown - low birth rate, prematurity and intrauterine growth retardation

CANNIBIS USE DISORDER SUBSTANCE ABUSE DISORDER Indications •  Heavy Daily Smoking •  Excess Time and Money Spent on Using •  Impaired Work or School Performance •  Dysfunctional Social Relationships •  Repeated Attempts to Quit or Reduce Use

MEDICAL MARIJUANA

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DOSING GUIDELINES FOR SMOKED MARIJUANA Dosing is uncertain-1 gram=2 joints Start Low and Go Slow eg 1inhalation of 25mgms tid with 9% THC** Average Dose 1-3 grams/24hours Many Factors can Alter Dose

MEDICAL MARIJUANA

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GUIDELINES FOR VAPORIZING Heat Ground Marijuana to a Temp.that Vaporizes Cannabinoids but does Not Burn Cannibis Vaporizes @ 180-195 degrees Higher the Temp the More Cannabinoids Released Avoids Most of the Carcinogens Health Canada only recommends the Volcano Medic

MEDICAL MARIJUANA

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DOSING GUIDELINES FOR INGESTED MARIJUANA An Alternative to Respiratory System Slower Onset Time-30-60 min. Don’t take 2nd Dose before Effects of First Dose Fully Realzed Can Last up to 12hours Eaten Cannibis Requires a Higher Dose approx. 2.5 times Inhaled Dose to Reach Comparable Blood Conc,

MARIJUANA- THE REGULATIONS

DO WE HAVE ALL THE ANSWERS?

MEDICAL MARIJUANA REGULATIONS BEFORE MARCH 31,2014 • 

•  •  •  •  •  • 

Gov’t Issued Individual Licences to Patients with Designated Dx to Allow Possession of a Specific Amount. M.D. Had to Set Limits on Grams/Day Licensed Patients Could Obtain Marijuana by: -Buying from Gov’t -Grow Own -Nominate Someone to Grow for Them All these Licenses Have Expired

CHRONIC PAIN SYNDROME AND THE LAW

PREJUDICIAL LABLE OR VALID DIAGNOSIS?

MARIJUANA FOR MEDICAL PURPOSES R. AFTER MARCH 31,2014-MMPR •  •  •  •  •  •  • 

No One Can Grow Any M.D. or Nurse Practioner** May Prescribe by Completing a ‘ Medical Document’ Daily Allowable is 1-5 Grams Authorized Patients Must Buy from a Licensed Producer Once Registered to a Producer,the Patient Can’t Switch Producer Couriers it toPatient or his/her M.D Maximum Possession is 30 Days Supply

MEDICAL MARIJUANAREGULATIONS BODIES ADVISING AGAINST Rx MARIJUANA -Canadian Medical Association -College of Family Physicians of Canada -Federation of Medical Regulatory Authorities -College of Physicians and Surgeons of B.C.

MEDICAL MARIJUANAREGULATIONS GUIDELINES of BC College of Physicians and Surgeons for Rx Medical Marijuana -Document -Conventional Therapies NOT Helpful -Failed Trial Pharamceutical Cannabinoid -Assess Addiction Risk -Discuss Risks and Obtain Written Consent -Reassess for Misuse/Abuse/Diversion

MEDICAL MARIJUANAMEDICAL LIABILITY GUIDELINES of Canadian Medical Protective Association -Know and Comply with Regulations and Policies of Provincial College -If Decide to Prescribe have a MEANINGFUL Consent Discussion and DOCUMENT. -Physicians are NOT Obliged to Complete a Medical Document if: 1)  Unfamiliar with Treatment 2)  Feel it is Medically Inappropriate

PRESCRIBING MEDICAL MARIJUANA

ARE THERE ETHICAL DILEMMAS? IF SO…WHAT ARE THEY?

PLACEHOLDER

PATIENTS’ PERSPECTIVE**

•  Provide Relief from poorly managed Health problems as an

Aternative or Adjunctive Rx

•  Can increase Compliance with Meds by Controlling Nausea •  A Natural means of Self Management •  Benign side effect Profile •  Harm Reduction by Using it as a Substitute for more

Addictive Rx

•  WORRIES Include:-excessive use,social stigma,safe

access,lack of consistent safe product

PATIENT BENEFITS WITH NEW SYSTEM

•  Time from M.D. authorization to Patient receiving

drug is dramatically reduced.

•  Producers must Undergo Quality Control

Inspections for Contaminants

•  Producers must list the Level of Active

Cannabinoids in their products

•  Reduce the Risk of Fire from Home Growing

MEDICINAL MARIJUANA

IN PAIN MEDICINE… MOST OF OUR THERAPEUTIC AGENTS ARE OFF LABLE

CHRONIC PAIN – DRUG ARMAMENTARIUM •  •  •  • 

Non Opiate Analgesics NSAIDS Opiates Adjuvants •  Anticonvulsants •  Antidepressants •  Muscle Relaxants •  Neuroleptics •  Cannabinoids •  NMDA Receptor Blocker •  Local Anesthetic

SOMETIMES MORE HARM THAN GOOD NSAID / COXIBS •  All Roughly Same Efficacy •  Side Effects usually DOSE DEPENDENT •  16,500 US Deaths / Year – As dangerous as FIREARMS!

SOMETIMES MORE HARM THAN GOOD OPIATES •  Can be Lethal •  Many Side Effects are usually Dose Dependent •  Greater Potential for misuse,abuse,diversion and addiction •  May develop tolerance or Opiod Induced Hyperalgesia at high doses

PHYSICIANS’ PERSPECTIVE FOR • 

I have many patients with Chronic Pain who I have observed to be more functional ,with improved mood and sleep which they attribute to using street Marijuana

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In resistant Chronic Pain Sufferers poorly responsive to a wide variety of therapeutic agents, I will trial a synthetic cannabinoid eg Nabilone/Cesamet.If this is not tolerated and there are no contraindications, I may then support a trial of Marijuana.

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I treat the prescibing of Marijuana the exact same way I educate, prescribe,monitor, manage and document all my other pain patients on opiates or psychoactive agents.

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Pharmacological agents are only ONE arm of effective Chronic Pain Management- we must treat the whole patient.

PHYSICIANS’ PERSPECTIVE AGAINST

•  Marijuana is NOT a prescription Medicine •  Insufficient scientific evidence •  I am unwilling to prescibe Marijuana without knowing: •  •  •  • 

Risks Benefits Potential Complications Drug Interactions

•  I am warned by my Licencing Body that I may be subject to

Negligence Claims if unforseen complication

•  I have no time to properly assess, prescribe, monitor, and

document these patients

PHYSICIANS’ PERSPECTIVE AGAINST

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HOW TO SAY NO TO YOUR PATIENT’S REQUEST FOR MARIJUANA

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There are few reliable published studies on the benefits of marijuana in its smoked form

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There are many uncertainties about the effects,both benificial and harmful of smoked marijuana

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As a result, I am not comfortable prescribing a drug without knowing the risks,benefits, potential complications and drug interactions

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If you still feel it may help,I will try to assist you to find a physician who is more knowledgeable with the issues related to medicinal maijuana.

COMPLEX PAIN CENTRE - ST. PAULS HOSPITAL 15 YEARS EXPERIENCE WITH CANNABINOIDS USEFUL IN CHRONIC PAIN WHEN: •  Not Responsive to Reasonable Dose of Opiate and Adjuvants •  Intolerant to Side Effects of Opiates •  •  • 

Opiate Requirement Continue to Escalate Allergic to Opiates Associated Marked Anxiety

COMPLEX PAIN CENTRE - ST. PAULS HOSPITAL 15 YEARS EXPERIENCE WITH CANNABINOIDS USEFUL IN CHRONIC PAIN WHEN: cont’d •  Associated Unresponsive Sleep Disorder •  Neuropathic Pain Intolerant to Anti-Convulsants •  Centralization of Neuropathic Pain

QUESTIONS? [email protected]

POTENTIAL BENEFITS** IN CHRONIC PAIN

•  Neuropathic Pain** •  Arthritis-RA,OA •  Fibromyalgia •  Musculoskeletal •  Palliative Care •  Muscle spasm •  PTSD ,Anxiety,and Migraine