Medical Marijuana and Pain...
Transcript of Medical Marijuana and Pain...
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Medical Marijuana and Pain
Management.
Dilip Kapur
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Recreational Gardening
Hydroponic Retailers per Million Population
3.55 3.618.19
33
65
0
10
20
30
40
50
60
70
Sydney Melbourne Auckland Cairns/FNQ Adelaide
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Effects of Cannabinoids
• Sedation
• Anxiolysis
• Euphoria
• Appetite stimulation
• Analgesia
• Antiemesis
• Ataxia
• Dysphoria
• Tachycardia
• Hyperacusis
• Temporal distortion
• Slowed reaction time
• Executive dysfunction
• Visual impairment
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Cannabinoids and Analgesia
• Cannabinoids are analgesic (but many
confounders).
– Central CB1 mechanisms
– Peripheral CB2 mechanisms
– ? Central vanilloid mechanisms
• There are NO adequately powered RCT’s
examining cannabinoid analgesia in chronic
pain.
were
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CB1 Receptor(All areas of brain and dorsal spinal cord).
Anandamide
2AG
Noladine Ether
Virodhamine
N-Arachidonyl D
CB1
G
Exogenous
Cannabinoids
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The Evidence
• Campbell et al. BMJ. (323) July 7 2001
– CONCLUSIONS
– No evidence of any useful effect in
postoperative pain
– No evidence of superiority of any cannabinoid
over codeine
– Troublesome psychotropic effects
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In Acute Pain
Anaesthesiology 2006; 104: 1040 - 1046
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Adverse Events
0
2
4
6
8
10
12
14
5mg 10mg 15mg
Mild
Moderate
Severe
Serious
n = 11 n = 30 n = 24
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Campaign for the Legalisation of
Cannabis
• “.. evidence has arisen to indicate that
cannabis successfully, and in a positive way
effects treatment of many medical
conditions such as Multiple Sclerosis,
nausea, chronic pain, and asthma. The body
of evidence supporting this claim exists and
is growing”.
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Making Myths
• Put something beyond the law
• Leave a host of questions unanswered
• Handball the debate to the activist lobby.
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The Myths.
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Cannabis infusion devices
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Other Banned Miracle Drugs
http://prohibition.osu.edu
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Finding Evidence
Observation Conclusion
Observation Conclusion
Scientific Experiment
Validity?
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The Observation
• HERBAL CANNABIS (MARIJUANA)
– (…and no other substance)
• Provides dramatic pain relief when nothing
else will help.
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Problems in Trials
• Svendsen et al.
– MS Patients
– 3 weeks on either Dronabinol 10 mg or placebo
followed by 3 week washout prior to crossover.
– Modest clinical response favouring Dronabinol
– 23 adverse events in Dronabinol group v 11 in
placebo group.
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Copyright ©2004 BMJ Publishing Group Ltd.
Svendsen, K. B et al. BMJ 2004;329:253
Spontaneous pain intensity during one week baseline, last week of active treatment, and last week of placebo treatment. Each line represents one patient. Active-placebo group=patients
randomised to active medication in first treatment period (n=12); placebo-active group=patients randomised to placebo in first treatment period (n=12); NRS=numerical rating
scale
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Recent Trials
Dronabinol - Placebo
Base Dronabinol Placebo
V2
0
2
4
6
8
10
V1
Svendsen, K. B et al. BMJ 2004;329:253
Blinding in Trial
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Recent Trials
Placebo - Dronabinol
Base Placebo QDronab
V2
0
2
4
6
8
10
V1
Svendsen, K. B et al. BMJ 2004;329:253
Blinding in Trial
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Recent Trials
Pooled Data
Base Placebo Dronabinol
V2.1
0
2
4
6
8
10
V1.1
Svendsen, K. B et al. BMJ 2004;329:253
Blinding in Trial
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Blinding
16
6
2
0
2
4
6
8
10
12
14
16
18
Correct Identification Wrong Identification Unable to Determine
Svendsen, K. B et al. BMJ 2004;329:253
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State of the Evidence
Finnerup et al. Lancet Neurology.
January 7, 2015 http://dx.doi.org/10.1016/S1474-4422(14)70251-0
CANNABINOIDS COMBINED ns 12.1(8.8-20)
Conclusion – Weak Evidence Against use of cannabinoids in Neuropathic pain
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Spasticity
SMD = -0.12(-0.24 – 0.01)
Whiting, PF et al. JAMA June 23/30, 2015 Volume 313, Number 24
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Pain
OR = 1.41(0.99 – 2.00)
Whiting, PF et al. JAMA June 23/30, 2015 Volume 313, Number 24
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A Randomised double-blind
comparison of the effects of
Nabilone and Dihydrocodeine in
the treatment of chronic
neuropathic pain
D. Kapur, B. Frank RVI Newcastle
M.G. Serpell WIG Glasgow
J.H. Hughes SCH
Middlesboro’
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Final Recruitment
• 96 patients enrolled
• 80 patients completed crossover study
• 2 major subgroups
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Overall Summary
1234567
Week
52
57
62
67
Nab
DHC
P = 0.03 (Summary measures ANOVA)
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Other Findings
• No difference in:
– Depression
– Anxiety
– SF 36 Role Physical
– SF 36 Vitality
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Alternative Commentary on the
Evidence
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Be careful what you ask for!
• US Experience, THC Potency %:
– MML state = 9.08 (6.15)
– Non-MML State = 5.60 (4.01)
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Ghosh, TS et al. NEJM, 2015; 372(11):991-3
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Fig. 2. Proportion of drivers in a fatal motor vehicle crash who were marijuana-positive in Colorado and 34 states without medical
marijuana laws from 1994 to 2011.
Stacy Salomonsen-Sautel, Sung-Joon Min, Joseph T. Sakai, Christian Thurstone, Christian Hopfer
Trends in fatal motor vehicle crashes before and after marijuana commercialization in Colorado ☆
Drug and Alcohol Dependence, Volume 140, 2014, 137–144
http://dx.doi.org/10.1016/j.drugalcdep.2014.04.008
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We Need to Talk About Your
Work.
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Effects of Cannabinoids
• Sedation
• Anxiolysis
• Euphoria
• Appetite stimulation
• Analgesia
• Antiemesis
• Ataxia
• Dysphoria
• Tachycardia
• Hyperacusis
• Temporal distortion
• Slowed reaction time
• Executive dysfunction
• Visual impairment
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Conclusions:
• Cannabinoids are miraculous drugs;
– so are opioids, antidepressants, anticonvulsants
etc
• Their effect in chronic, peripheral
neuropathic pain appears limited
• The debate is political rather than clinical
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A Final Word
• Falsehood flies, and truth comes limping
after it, so that when men come to be
undeceived, it is too late.
– Jonathan Swift (1667 – 1745).