medical marijuana and pain...

Medical Marijuana and Pain

Management.

Dilip Kapur

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

Effects of Cannabinoids

• Sedation

• Anxiolysis

• Euphoria

• Appetite stimulation

• Analgesia

• Antiemesis

• Ataxia

• Dysphoria

• Tachycardia

• Hyperacusis

• Temporal distortion

• Slowed reaction time

• Executive dysfunction

• Visual impairment

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

CB1 Receptor(All areas of brain and dorsal spinal cord).

Anandamide

2AG

Noladine Ether

Virodhamine

N-Arachidonyl D

CB1

G

Exogenous

Cannabinoids

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

In Acute Pain

Anaesthesiology 2006; 104: 1040 - 1046

Adverse Events

0

2

4

6

8

10

12

14

5mg 10mg 15mg

Mild

Moderate

Severe

Serious

n = 11 n = 30 n = 24

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”.

Making Myths

• Put something beyond the law

• Leave a host of questions unanswered

• Handball the debate to the activist lobby.

The Myths.

Cannabis infusion devices

Other Banned Miracle Drugs

http://prohibition.osu.edu

Finding Evidence

Observation Conclusion

Observation Conclusion

Scientific Experiment

Validity?

The Observation

• HERBAL CANNABIS (MARIJUANA)

– (…and no other substance)

• Provides dramatic pain relief when nothing

else will help.

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.

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

Recent Trials

Dronabinol - Placebo

Base Dronabinol Placebo

V2

0

2

4

6

8

10

V1


Blinding in Trial

Recent Trials

Placebo - Dronabinol

Base Placebo QDronab

V2

0

2

4

6

8

10

V1


Blinding in Trial

Recent Trials

Pooled Data

Base Placebo Dronabinol

V2.1

0

2

4

6

8

10

V1.1


Blinding in Trial

Blinding

16

6

2

0

2

4

6

8

10

12

14

16

18

Correct Identification Wrong Identification Unable to Determine


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

Spasticity

SMD = -0.12(-0.24 – 0.01)

Whiting, PF et al. JAMA June 23/30, 2015 Volume 313, Number 24

Pain

OR = 1.41(0.99 – 2.00)

Whiting, PF et al. JAMA June 23/30, 2015 Volume 313, Number 24

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’

Final Recruitment

• 96 patients enrolled

• 80 patients completed crossover study

• 2 major subgroups

Overall Summary

1234567

Week

52

57

62

67

Nab

DHC

P = 0.03 (Summary measures ANOVA)

Other Findings

• No difference in:

– Depression

– Anxiety

– SF 36 Role Physical

– SF 36 Vitality

Alternative Commentary on the

Evidence

Be careful what you ask for!

• US Experience, THC Potency %:

– MML state = 9.08 (6.15)

– Non-MML State = 5.60 (4.01)

Ghosh, TS et al. NEJM, 2015; 372(11):991-3

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

We Need to Talk About Your

Work.

Effects of Cannabinoids

• Sedation

• Anxiolysis

• Euphoria

• Appetite stimulation

• Analgesia

• Antiemesis

• Ataxia

• Dysphoria

• Tachycardia

• Hyperacusis

• Temporal distortion

• Slowed reaction time

• Executive dysfunction

• Visual impairment

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

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).

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