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Is herbal medically required for pain management? Neil Craton B.Sc., M.H.K., M.D., M.C.F.P (S.E.M.), Dip. Sport and Exercise Med. Assistant Professor of Manitoba Faculty of Medicine, Adjunct Professor, Gupta School of Kinesiology and Applied Health, University of Winnipeg. Legacy Sport Medicine www.neilcraton.com

CFPC CoI Templates: Slide 1 Faculty/Presenter Disclosure

• Faculty: Neil Craton

• Relationships with commercial interests: • Grants/Research Support: None • Speakers Bureau/Honoraria: U of M Faculty of Medicine, Medical Education Resources • Consulting Fees: MPI medical consultant • Other: None CFPC CoI Templates: Slide 2 Disclosure of Commercial Support

• This program has received no financial support. • This program has received no in-kind support from. • Potential for conflict(s) of interest: • None CFPC CoI Templates: Slide 3 Mitigating Potential Bias

None to declare.

The question: Is herbal cannabis medically required for pain management of compensable injuries.

Pic of burning raft

What did The Google Machine have to say?

Is herbal cannabis medically required for this patient’s pain? What kind of evidence would you like to see to answer the question?

• Number of trials? • Number of patients studied? • Duration of trials? • Outcome measures? • Surveillance for side effects? • Interaction with other medical conditions? • Interaction with other ? I was confused by differing stances assumed by Health Canada and the Supreme Court. From Health Canada

• Dried marijuana is not an approved drug or medicine in Canada. • The Government of Canada does not endorse the use of marijuana, but the courts have required reasonable access to a legal source of marijuana when authorized by a healthcare practitioner. Canadian Medical Association.

• The CMA position has not changed: • There is insufficient scientific evidence available to support the use of marijuana for clinical purposes. • There is insufficient evidence on clinical risks and benefits, including the proper dosage of marijuana to be used and on the potential interactions between this drug and other medications.

So maybe the big shots at Health Canada are just afraid of taking a stand or not up on the literature.

I was surprised that most evidence in the Whiting paper was not smoked cannabis. • Only one trial evaluated inhaled cannabis for pain. • Most papers evaluated nabixmols spray and synthetic cannabinoid pills. JAMA.2015;313(24):2456-2473.doi:10.1001/jama.2015.6358 LastcorrectedonApril12,2016.

Some studies do show short term pain relief for smoked cannabis. I wasn’t sure if these were convincing. • Wilsey B, et al Low-dose vaporized cannabis significantly improves neuropathic pain. J.Pain 2012 39 patients, 6 hours • Abrams DI, et al Cannabis in painful HIV-associated sensory neuropathy: A randomized placebo-controlled trial. Neurology 2007; 515-21. 25 patients, 5 days • Ware et al. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ 2010. 21 patients. A total of 248 mild and six moderate adverse events (fall,2 increased pain,1 numbness,1 drowsiness1 and pneumonia1) were reported during the trial. 5 days • Cooper ZD, et al . Comparison of the analgesic effects of dronabinol and smoked marijuana in daily marijuana smokers. Neuropsychopharmacology 2013 15 patients, 6 hours Some studies show short term pain relief for smoked cannabis. • Ellis RJ, et al Smoked medicinal cannabis for neuropathic pain in HIV: A randomized, crossover clinical trial. Neuropsychopharm 2009. 34 patients, 5 days • Wilsey B, et al . A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J.Pain 2008 6):506-21. 34 patients, 6 hours • Grant I. Medicinal cannabis and painful sensory neuropathy. Virtual Mentor 2013 May 1;15(5):466-9 not available. • Andreae MH, et al. Inhaled cannabis for chronic neuropathic pain: A meta-analysis of individual patient data. J Pain 2015 178 patients, days to weeks, NNT 5.6 Man, that’s not very impressive evidence of efficacy in chronic pain… • Dozens of patients per study. • Most for a matter of hours? • One for five days. • All less than 2 weeks? • Doesn’t it make sense to have long duration studies in chronic pain patients? • Not to mention all the troubles with blinding cannabis users and the perceptual effects of the drug. National Academy of Science: Mutually exclusive statements Mutually exclusive statements

• 1. CONCLUSION 4-1 There is substantial evidence that cannabis is an effective treatment for chronic pain in adults. Mutually exclusive statements

• 1. CONCLUSION 4-1 There is substantial evidence that cannabis is an effective treatment for chronic pain in adults. • 2. very little is known about the efficacy, dose, routes of administration, or side effects of commonly used and commercially available cannabis products in the United States….more research is needed on the various forms, routes of administration, and combination of cannabinoids.

Shouldn’t the statement be: There is incomplete and very limited evidence of very short term relief of chronic pain with cannabinoids, (not cannabis)? Surely Canadian Family Docs will have a more cogent statement. Help from the CFPC: 2013

• In light of conflicting and, in some cases, absent evidence on the effectiveness and safety of marijuana used for medical purposes, the CFPC requests the development of recommendations on the risks and benefits of the use of marijuana for specific medical conditions • Recommendations should be developed by clinicians who do not have a conflict of interest with regard to the promotion of medical marijuana. Prescribing smoked cannabis for chronic non-cancer pain. Kahan, M. et al Canadian Family 2014; 60:183-190. Kahan, CFP 2014

1. The evidence supporting smoked cannabis for pain is limited and weak. The longest duration trial as of 2014 was for 15 days. Mutually exclusive statements?

1. The evidence supporting smoked cannabis for pain is limited and weak. The longest duration trial as of 2014 was for 15 days. 2. Smoked cannabis, is indicated for severe neuropathic pain that has failed to respond to standard treatments. • Wouldn’t a scientist say there is insufficient evidence to use smoked herbal cannabis for pain? CFPC dosage makes patients heavy users and after two weeks…so your patient is in entirely uncharted territory. • Subjects in one trial experienced relief of pain with one inhalation of 9.4% THC cannabis smoked three times per day. We don’t need to worry about this uncharted territory, after all its “medicinal”? Cannabis in medicine: a national educational needs assessment among Canadian .

BMC Med Educ. 2015 Mar 19;15:52. • Ziemianski D1 • RESULTS: • Four hundred and twenty six responses were received and the most desired knowledge concerned "potential risks of using cannabis for therapeutic purposes" and "safety, warning signs and precautions for patients using CTP". • The largest gap between perceived current and desired knowledge levels was "dosing" and "the development of treatment plans".

Harm: Psychotic illness and the development of schizophrenia.

There is substantial evidence of a statistical association between cannabis use and: •The development of schizophrenia or other psychoses, with the highest risk among in the most frequent users (12-1) • Schizophr Bull. 2016 Feb 15. Meta-analysis of the Association Between the Level of Cannabis Use and Risk of Psychosis. • Marconi A1,

• High levels of cannabis use increase the risk of psychotic outcomes and confirms a dose-response relationship. • Although a causal link cannot be unequivocally established, there is sufficient evidence to justify harm reduction prevention programs. I thought reefer madness was a puritanical joke? Harm: Other significant psychiatric manifestations: There is moderate evidence of a statistical association between cannabis use and: • Increased symptoms of mania and hypomania in bipolar patients (regular cannabis use) (12-4) • A small increased risk for the development of depressive disorders (12-5) • Increased incidence of suicidal ideation and suicide attempts with a higher incidence among heavier users (12-7a) • Increased incidence of suicide completion (12-7b) • The development of any type of anxiety disorder, (Mod evidence) (12-8a) • Increased severity of posttraumatic stress disorder symptoms among individuals with PTSD Canadian Family Physician February 2018

• Simplified guideline for prescribing medical cannabinoids in primary care • G. Michael Allan MD CCFP et al. CFP, February 2018

• Strong recommendation against using cannabis for acute pain • Recommendation against using cannabinoids for chronic neuropathic pain. Health Canada 2018

• Evidence from epidemiological studies also suggests: • a dose-dependent effect between cannabis use and suicidality, especially in men. • dose-dependent, acute and transient behavioural and cognitive effects mimicking acute psychosis. • early, chronic, and heavy use and psychosis and schizophrenia. • Cannabis use is also associated with earlier onset of schizophrenia in vulnerable individuals and exacerbation of existing schizophrenic symptoms and worse clinical outcomes. Health Canada 2018. Harm

• high doses of THC can produce anxiety and lower mood. • chronic, heavy use of THC and the onset of anxiety, depressive and bipolar disorders, and the persistence of symptoms related to PTSD, panic disorder, depressive disorder, and bipolar disorder.

• Our patients will probably be lifelong heavy users… Harm: Cognitive impairment

• There is moderate evidence of a statistical association between cannabis use and:

The impairment in the cognitive domains of learning, memory, and attention (acute cannabis use) (11-1a) Harm: Car crashes. Can my patient drive if they use cannabis for pain management? There is substantial evidence of a statistical association between cannabis use and: • Increased risk of motor vehicle crashes (9-3) Harm: Academic and occupational underachievement There is limited evidence of a statistical association between cannabis use and: • Impaired academic achievement and educational outcomes (11-2) • Increased rates of unemployment and/or low income (11-3) • Impaired social functioning or engagement in developmentally appropriate social roles (11-4) If patients can’t drive on a t.i.d dose regimen, can they work? How can this be part of a rehab program?

•Jimenez XF. Cannabis for chronic pain: Not a simple solution. Cleve Clin J Med. 2018. Jimenez. Cleveland Clinic

• The true danger of cannabis lies in what we already know with certainty. Herbal cannabis undisputedly results in dose dependent cognitive and motivational problems. • If we are encouraging physical therapy and home exercise to counter deconditioning, socialization to reverse depression, cognitive- behavioral therapy to increase coping, returning to work to prevent prolonged disability and other active measures to prevent pain from becoming chronic, then why would we suggest treatments known to blunt motivation, energy, concentration, and overall mood? • As a general central nervous system suppressant, cannabis works broadly against our best efforts to rehabilitate patients and restore their overall function. Harm: Underachievement What causes this pervasive underachievement and even cognitive decline?

• Chronic cannabis use in adolescence may cause persistent disruptions in these developing prefrontal and reward pathways, impacting important intellectual functions like working memory, sustained attention, verbal memory, and general intellectual functioning. • Dev Cogn Neurosci. 2015 Jul 23. • Impact of cannabis use on prefrontal and parietal cortex gyrification and surface area in adolescents and emerging adults. • Shollenbarger SG1, • CONCLUSIONS: • Cannabis use was associated with reduced gyrification in PFC regions implicated in self-referential thought and social cognition. Results suggest that these gyrification characteristics may have cognitive implications. Neuropsychological studies. Meier et al Proc Natl Acad Sci U S A. 2012 Oct 2;109(40)

• 1,037 subjects from birth until age 38 years, performing neuropsychological assessments at ages 13 and 38 years, as well as ascertaining cannabis use at ages 18, 21, 26, 32, and 38 years. • Persistent cannabis use was associated with a decline in neuropsychological performance across many domains. • Adolescent-onset cannabis use was correlated with a 10-point decrease in measured IQ. Behavioral consequences

• Problems with finances • Conflict in relationships • Diminished life satisfaction and achievement • Increased risk of abusing other addictive substances. • Increased risk of unemployment, welfare use and worklessness. • Decreased motivation to work. • Adverse educational outcomes with increased likelihood of dropping out of school. My, at least cannabis doesn’t have any other medical consequences…. Harm: Cardiovascular problems. Using marijuana raises the risk of stroke and heart failure even after accounting for demographic factors, other health conditions and lifestyle risk factors such as smoking and alcohol use. Marijuana and Coronary Heart Disease Sep 22, 2016 | Expert Analysis • Aust N Z J Public Health. 2016 Jun;40(3):226-30. Heavy cannabis users at elevated risk of stroke: evidence from a general population survey. • Hemachandra et al. • Australians aged 20-24 years (n=2,383), 40-44 years (n=2,525) and 60- 64 years (n=2,547) RESULTS: • Cannabis users (n=1,043) had 3.3 times the rate of stroke/TIA • Elevated stroke/TIA was specific to participants who used cannabis weekly or more often with no elevation among participants who used cannabis less often. • CONCLUSIONS: • Heavy cannabis users in the general community have a higher rate of non-fatal stroke or transient ischemic attack than non-cannabis users. Conclusion

Increased duration of marijuana use is associated with increased risk of death from hypertension.

Recreational marijuana use potentially has cardiovascular adverse effects which needs further investigation. Yikes, there seem to be a lot of evidence of Risks of Cannabis that I had not heard about. • Increased risk of chronic psychotic disorders including schizophrenia • Respiratory cancers. • Increase risk of depression. • Two to four-fold risk of suicide in regular users. • Three to four fold risk for myocardial infarction and stroke. • Two to three fold risk for testicular cancers. • Increased risk of abusing other addictive substances. • Increased risk of unemployment, welfare use and worklessness. • Decreased motivation to work. Risks of Cannabis

• Impaired short-term memory making it difficult to learn and retain information • Impaired motor coordination interfering with driving skills and increasing the risk of injuries. • An increase in road traffic accidents including fatal crashes. • Altered judgment • Sympathomimetic toxicity (high BP, fast heart rate, agitation, MI, stroke) • Intractable vomiting • Paranoia and psychosis. Risks of Cannabis

• Addiction. (Generally around 10% of users, 17% of those who begin use in adolescence and up to 50% of those who are daily users will become addicted) • Altered brain development. • Lower verbal memory, processing speed, as well as deficits in attention. • Adverse educational outcomes with increased likelihood of dropping out of school. • Cognitive impairment with lower IQ among those who are frequent users during adolescence. • Problems with finances • Conflict in relationships • Diminished life satisfaction and achievement • Chronic bronchitis/sputum production/wheezing.

Guess how many papers I found on CBD in pain management? No clinical trials on pub med for CBD oil in human pain management. So where is all the information coming from?

Influences?

• Health Care • Legal weed is everywhere — unless you’re a scientist • The push to legalize marijuana may overtake research on medical benefits. • Politico 2018 Déjà vu?

•Marijuana is the new Oxycontin’: Should we be concerned with how docs are learning about pot?

• Global News, March 24, 2019

A medical history lesson: Lessons from the opioid crisis ABINGDON, Va., May 10 — The company that makes OxyContin plead guilty today in federal court to criminal charges:

- that they misled regulators, doctors and patients about the drug’s risk of addiction and its potential to be abused.

Purdue Pharma heavily promoted OxyContin to doctors who had often had little training in the treatment of serious pain or in recognizing signs of drug abuse in patients. Bloomberg.com

• Sackler Family Sued by New York Over Opioid ‘Catastrophe’ • March 28, 2019 • Opioid lawsuit targets rich family behind drug that fueled US crisis • Sackler family, which owns Purdue Pharma, the maker of OxyContin, accused of fueling addiction while boosting profits… The guardian.com Lessons from the opioid crisis.

• Short term studies show efficacy of opioids for pain (2-6 weeks). • No long term studies conducted. • Short term data used to justify long term use. • Drug companies lie about dosing, safety and efficacy. • Naïve or conflicted physicians and advocacy groups encourage prescribing. • Long term data shows many adverse effects. • Drug diversion, addiction, opioid induced hyperalgesia, tolerance and epidemic of deaths occur, mostly in people living in poverty. • Medical doctors were a big part of the problem. What would you conclude? Is herbal cannabis medically required for pain management. References

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