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CANNABIS
Fact & Fiction
DISCLOSURE
Medical Director and 1/3rd ownerThe Aurora Clinic(An OMMP Clinic)
OBJECTIVES
1. List reported uses for medical cannabis
2. Oregon Medical Marijuana Program (OMMP) qualifying conditions
3. Demonstrate how this is interpreted
4. Common cannabis formulations
5.How raw cannabis is utilized medicinally
6. Recommended dosing for some conditions
7. Current evidence regarding medical cannabinoids
8. Legal issues
REPORTED USES
•Anti-Emetic•Sleep Aide•Anti-Spasmotic•Anti-Seizure•Appetite Stimulant
Anxiolytic PTSD
Analgesic NeuropathicNociceptive
QUALIFYING CONDITIONS DEFINED BY THE OMMP [1]
Diagnoses:
Cancer
Glaucoma
Agitation due to Alzheimer’s
HIV/AIDS
Post-Traumatic Stress Disorder
Symptoms Cachexia
Severe Pain
Severe Nausea
Seizures – not limited to epilepsy
Persistent Muscle Spasms
HOW THESE QUALIFIERS GET INTERPRETED
SEVERE PAIN
Severe pain• Any condition causing severe pain • Complex regional pain syndrome• Chronic pain syndrome• Chondromalacia patella• Colitis – ulcerative • Costochondritis• Chronic back pain• Degenerative joint disease (DJD)• Degenerative disc disease (DDD)• Dyspareunia• Fibromyalgia• Fallen arches with severe foot pain• Gout• GERD (reflux)• Hallux rigidus
• Herniated disc• Hip labral tear• IBS (irritable bowel syndrome)• Lumbar stenosis• Lumbago• Lupus with joint involvement• Metatarsalgia• Migraine headaches• Meniscal tear• Neuropathy • Non-allopathic lesions• Osteoarthritis
SEVERE PAIN
• Osteochondritis dissecans • Osteochondrodysplasias• Psoriatic arthritis• Poorly healed fractures • Polychondritis
• Plantar fasciitits• Pes planus (flat feet)• Ruptured disc• Radiculopathy• Rheumatoid arthritis
• Reflex sympothetic dystrophy• Spinal stenosis• Spondylosis• Spina bifida• Scoliosis• Severe peptic ulcers• Severe joint pain• Synovitis• TMJ• Trigeminal neuralgia
SEVERE NAUSEA
• Any condition causing nausea • BPV - benign positional vertigo• Chemotherapy• Chronic nonspecific nausea• Chronic nonspecific vomiting• Diverticulosis• IBS• Medication associated nausea• Menier's disease
• Medication associated nausea• Menier's disease• Nephropathy• Other GI disorders• Peptic ulcers• Radiation therapy• Sprue• Vertigo
MUSCLE SPASMS
• Any condition causing muscle spasms • Chronic back pain• Charcot-Marie-Tooth disease• Limb trauma• Muscular disorders• Multiple Sclerosis
• Movement disorders• Nocturnal leg cramps• Parkinson’s disease • Restless leg syndrome• Tourette’s syndrome• Spasticity conditions
OTHER
PTSD
Cancer
Seizure/Epilepsy
Glaucoma
HIV/AIDS
Cachexia
COMMON AVAILABLE FORMULATIONS
DRONABINOL (MARINOL)
Dronabinol (Marinol) Nausea & Vomiting Anorexia/Weight loss AIDS – Associated Cost: $110 to $931 [2]
NABIXIMOLS (SATIVA)
Nabiximols (Sativa) Neuroptahic Canada only
NABILONE (CESAMET)
Nabilone (Cesamet) Nausea & VomitingCost: $8210 [2]
RAW CANNABIS
Raw Cannabis Cost: ~$145/oz [3]
SMOKING IS PASSÉ
EDIBLES (MEDIBLES)
TINCTURES
TOPICALS
VAPORIZING
MAYO DOSING INFORMATION [4]
STRENGTH OF EVIDENCE SLIDE [5]
KEY TO GRADES [5]
A Strong scientific evidence for this use
B Good scientific evidence for this use
C Unclear scientific evidence for this use
D Fair scientific evidence against this use (it may not work)
F Strong scientific evidence against this use (it likely does not work)
CHRONIC PAIN – B [5]
Marijuana has been studied for the treatment of chronic pain. It has been used in people whose pain did not respond to other drugs such as narcotics. Cannabis-based products like Sativex® are used to treat different types of pain, such as pain from cancer or multiple sclerosis. It is approved in Canada and many parts of Europe. In the United States, it is being studied in people who have cancer-related pain. Other cannabis-based products, such as the U.S. Food and Drug Administration (FDA) -approved dronabinol (Marinol®), are also being studied
MULTIPLE SCLEROSIS – B [5]
Marijuana has been studied for the relief of multiple sclerosis symptoms, such as nerve pain, muscle spasms, and urinary disorders. The active ingredients have effects on the central nervous system and immune cells.
ALS – C [5]
Current studies show that THC may lack benefit in people who have amyotrophic lateral sclerosis. More research is needed.
APPETITE STIMULANT – C [5]
Current studies show that cannabis-based therapy may lack benefit on weight loss and anorexia related to cancer. Early studies suggested that marijuana may improve appetite in people who have cystic fibrosis (mucus buildup in the organs) and AIDS. More research is needed.
CHEMOTHERAPY SIDE EFFECTS - C [5]
Studies suggest that marijuana may help reduce nausea and vomiting in people undergoing chemotherapy. However, it may cause side effects such as sleepiness and changes in mood. One review suggests that marijuana may cause more side effects in children undergoing chemotherapy than other therapies. However, the effect of cannabis alone is unclear, and further research is needed.
EATING DISORDERS – C [5]
In patients with eating disorders THC had a lack of effect on weight, caloric intake, and psychiatric assessment. Further research is required.
EPILEPSY – C [5]
Early studies suggest that marijuana taken with antiseizure drugs may lower seizure risk in people with epilepsy. However, the evidence is limited. More research is needed on whether marijuana may be effective in treating epilepsy.
NEUROMUSCULAR DISORDERS – C [5]
Marijuana has been studied in the treatment of symptoms of nerve and muscle disorders. Researchers looked for possible benefits on appetite, saliva production, mood, muscle health, and sleep. More research is needed before conclusions can be made.
GLAUCOMA – C [5]
People who have glaucoma have high pressure in the eye, which may lead to optic nerve damage and vision loss. Some studies suggest that THC may lower eye pressure, while CBD may lack benefit or actually increase pressure. More research is needed to understand the possible role of marijuana in glaucoma treatment.
QUALITY OF LIFE – C [5]
There is some controversy over the use of marijuana in people who have cancer or other long-term illnesses. It has been studied for increasing appetite, treating stomach problems, improving mood and sleep, and reducing pain. More research is needed before conclusions can be made.
PERCEPTION VS. REALITY
Perception
The way one thinks about or understands
something or someone
Reality
The true situation that exists
Merriam-Webster Dictionary
[6]
[6]
URBAN MYTHS
[7]
NAUSEA & VOMITING
FINDINGS
Dronabinol > Neuroleptics but not actually demonstrated in studies
Dronabinol = Placebo But preferred over placebo
No clinically significant difference between Cannabinoids and neuroleptics in treatment of chemotherapy induced N&V
Clinically Significant difference in favoring cannabinoids over neuroleptics in the treatment of chemotherapy induced N&V [8]
HYPEREMESIS SYNDROME
Weekly marijuana use
Usually <50
Cyclic Nausea & Vomiting
Compulsive hot shower/baths
~use greater than a year Althougth 32% used <1 year
Diaphoresis
Bloating
Abdominal pain
Flushing
Weight loss
Morning predominance [9]
FINDINGS
Cochrane Review group RCT
Any intervention Any form Any route Compared with Placebo or Standard of Care In patient, clinic, home based setting
Total: 7 studies – only 3 adequately concealed control from intervention
Weight change Body Fat Caloric intake N&V Overall performance
“…the evidence for positive effects in patients with HIV/AIDS is limited, and some of that which exists may be subject to the effects of bias…”
Limitations:
Small numbers
Short duration [10]
SEIZURE
FINDINGS
4 studies (RCT blinded or not) N: 48 Primary Outcome:
Seizure free x 1 year 3x interseizure interval
Secondary Outcome: 6 month responder rate Objective Quality of Life Adverse Events
Epileptic treatment continued in all studies
No details of randomization process No indication if control & treatment groups were the same or different
All 4 reports only answered the secondary outcome: adverse effects No significant side effects noted [11]
GLAUCOMA
ALL BASED ON THIS STUDY
Invest Ophthalmol. 1975 Jan;14(1):52-5.
Marijuana smoking and reduced pressure in human eyes: drug action or epiphenomenon?
Flom MC, Adams AJ, Jones RT.
Abstract
Normal pressure within the human eye was reduced after smoking a socially relevant dose of marijuana (12 mg. delta9-9-tetrahydrocannabinol), but only for light to moderate users who experienced a substantial "high" and a state of peaceful relaxation from the experimental dose. Analysis suggests an indirect effect of the drug associated with relaxation-a psychophysiologic state that can be produced by drug and nondrug means. [12]
4 AMERICANS GET MEDICAL POT FROM THE FEDS
FINDINGS
Based on reviews by the National Eye Institute (NEI), the Institute of Medicine (IOM), and on available scientific evidence, the American Academy of Ophthalmology Complementary Therapy Task Force finds no scientific evidence demonstrating increased benefit and/or diminished risk of marijuana use in the treatment of glaucoma compared with the wide variety of pharmaceutical agents now available.
PAIN
FINDINGS
18 studies (RCT) End date 2008
N: ?Outcome: reduction in chronic painAny Cannabinoid vs. Placebo
Only modest
improvement [14]
FINDINGS
11 studies (RCT) 2010-2014
n: 1185 Only 3 studies > 100 pts ( largest n: 339)
9 against placebo1: cannabis vs. ibuprofen1: cannabis vs. amitriptyline
…”current systematic review provides further support that cannabinoids are safe, demonstrate a modest an algesic effect and provide a reasonable treatment option for treatment chronic non-cancer pain.” [15]
SANCHEZ FINDINGS
“Currently available evidence suggests that cannabis treatment is moderately efficacious for treatment of chronic pain,…”
“… but beneficial effects may be partially (or completely) offset by potentially serious harms. More evidence from larger, well-designed trials is needed to clarify the true balance of benefits to harms.” [14]
LYNCH & CAMPBELL FINDINGS
“In conclusion this systematic review of 18 recent good quality randomized trials demonstrates that cannabinoids are a modestly effective and safe treatment option for chronic non-cancer (predominantly neuropathic) pain.”
“…More large scale trials of longer duration reporting on pain and level of function are required.” [15]
LYNCH & WARE
In summary the current systematic review provides further support that cannabinoids are safe, demonstrate a modest an algesic effect and provide a reasonable treatment option for treatment chronic non-cancer pain.
11 studies – all but 2 are against placebo control
1 Ibuprofen 1 amitriptyline [16]
KARST ET AL
CT-3 effective in reducing chronic neuropathic pain compared with placebo. [17]
Only Moderate Improvement [17]
TREATS CANCER
NATIONAL CANCER INSTITUTE’S CURRENT POSITION
Have any preclinical (laboratory or animal) studies been conducted using Cannabis or cannabinoids? Preclinical studies of cannabinoids have investigated the following activities:
Antitumor activity
Studies in mice and rats have shown that cannabinoids may inhibit tumor growth by causing cell death, blocking cell growth, and blocking the development of blood vessels needed by tumors to grow. Laboratory and animal studies have shown that cannabinoids may be able to kill cancer cells while protecting normal cells.
A study in mice showed that cannabinoids may protect against inflammation of the colon and may have potential in reducing the risk of colon cancer, and possibly in its treatment.
A laboratory study of delta-9-THC in hepatocellular carcinoma (liver cancer) cells showed that it damaged or killed the cancer cells. The same study of delta-9-THC in mouse models of liver cancer showed that it had antitumor effects. Delta-9-THC has been shown to cause these effects by acting on molecules that may also be found in non-small cell lung cancer cells and breast cancer cells.
A laboratory study of cannabidiol (CBD) in estrogen receptor positive and estrogen receptor negative breast cancer cells showed that it caused cancer cell death while having little effect on normal breast cells. Studies in mouse models of metastatic breast cancer showed that cannabinoids may lessen the growth, number, and spread of tumors.
A laboratory study of cannabidiol (CBD) in human glioma cells showed that when given along with chemotherapy, CBD may make chemotherapy more effective and increase cancer cell death without harming normal cells. Studies in mouse models of cancer showed that CBD together with delta-9-THC may make chemotherapy such as temozolomide more effective. [18]
HEADACHE
“…small number of case reports and survey studies suggest a possible benefit of cannabis for the treatment of acute headache…”
“…benefit is plausible in view of the pharmacological effects of THC and synthetic cannabinoids…” [19]
“PERCEPTION OF SAFETY”
"There's an ongoing death rate from use of pain medications as prescribed. So, even as prescribed, they're highly dangerous and they are open to abuse. As far as medications used in the pediatric population to control seizures, there are also severe toxicities to organs. Many of them are very sedating. The children become unable to function or really to interact because of the sedating effects. Other medications have a side effect of rage and behavioral problems.
Unprovoked rage is actually a known side effect of some of the anti-seizure medications. Cannabis and in particular cannabidiol has none of these issues. No toxicities. The main side effect of cannabidiol is sleepiness. As a child gets accustomed to it, that does wear off and the child can be very alert and functional on the cannabis oil once they have worked into the dosing. Once you put them against each other, there really is no comparison in terms of safety." [20] [21]
MORE
“Because of the issues already discussed, it can sometimes be challenging finding accurate, science-based information about cannabis. Dr. Gedde offers the following suggestions for obtaining reliable information:
"The reason why it's difficult is that the preponderance of research funds have been to show harm related to cannabis, as a drug of abuse... [L]ook for the real research that's there on the endocannabinoid system and the ways that marijuana cannabis has been helping people for centuries. And look into the history of medical practice; that's where the information starts to come out.“”
[20] [21]
Table 1 Summary of major adverse health outcomes of recreational cannabis use.
Evidence Level of evidence Strength of effect
Acute effects Fatal overdose +++ No case reports 0Road traffic crashes ++ Cohort and case control 2-fold
Low birth weight ++ Cohort Chronic effects
Dependence +++ Cohort studies 1 in 10 among ever users
Educational outcomes ++ Cohort and case control 2-fold in regular users
Cognitive impairment ++ Cohort and case control Difficult to quantify
Psychosis ++ Cohort studies 2-fold in regular users
Depression +? Cohort studies Probable confounding
Suicide +? Cohort studies 2-fold in regular users
Chronic bronchitis ++ Cohort studies 2-fold in regular users
Respiratory impairment +? Cohort studies MixedCardiovascular disease ++ Cohort and case control 3–4-fold for MI
Cancers Testicular cancers ++ Case–control 2–3-fold
Respiratory cancers +? Case–control Confounded by smoking
SUMMARY OF ADVERSE EVENTS
[22][23][24]
CANNABIS & THE LAW
WHAT WE CAN SAFELY SAY
State As off July 1,2015 Recreational use of cannabis is legal
OLCC authority to tax, license, regulate recreational marijuana
Does not regulate personal possession or sales
Cannot be sold or smoked in public Allowed:
4 plants 8 oz at home 1 oz on their person [25]
Federal Classified as C-1 medication Cannot cross borders Cannot enter tribal lands
Currently the federal government is choosing to not exercise the law, instead to watch what happens. [25]
POTENTIAL PROBLEMS FOR HOSPICE
Hospice receives Federal FundsCannot support or promote cannabisCannot supply itCannot pay for itCannot store itCannot deny access to it(this is true of facilities also)
A REAL CONUNDRUM
THANK YOU
Questions
?
REFERENCES
1) Physicians: Medical Marijuana Program. Oregon Health Authority. https://public.health.oregon.gov/DiseasesConditions/ChronicDisease/MedicalMarijuanaProgram/Pages/Physicians.aspx 2) www.goodrx.com
3) http://www.hightimes.com/read/legal-oregon-weed-will-cost-145-ounce
4) Mayo Clinic Dosing: http://www.org/drugs-supplements/marijuana/dosing/hrb-20059701
5) Mayo Clinic Evidence: http://www.mayoclinic.org/drugs-supplements/marijuana/evidence/hrb-20059701
REFERENCES
6) Motel, Seth (Apr 14,15). "6 facts about marijuana". Pew Research Center. Retrieved 26 June 2015 http://www.pewresearch.org/fact-tank/2015/04/14/6-facts-about-marijuana/
7) http://leilaworldblog.com/2013/04/12/9-major-health-bebefits-of-medical-marijuana/
8) Rocha M., Stefano S.C., De Cassia H.R., Rosa O.L.M.Q, Da Silveira D.X. The therapeutic use of cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systemic review and meta-analysis. European J of Cancer Care 2008: 17: 431-43
9) Lu M. L. R. Y., Agito M.D. Cannabinoid hyperemesis syndrome: Marijuana is both antiemetic and proemetic. Cleveland Clinic J of Med 2015:82 [7], 429-34
REFERENCES
10) Lutge E.E>, Gray A., Siegfried N. The Medical use of cannabis for reducing morbidity and mortality in patients with HIV/AIDS (review). The Cochrane Review. 2013, 4 http://www.thecochranelibrary.com
11) Gloss d., Vickery B. Cannabinoids for epilepsy (Review). 2014 The Cochrane Library, Issue 3 (www.thecochranelibrary.com)
12) Flom M.C., Adams A.J, Jones R.T. Marijuana smoking and reduced pressure in human eyes: drug action or epiphenomenon? Invest Ophthalmol1975 Jan;14(1):52-5
13) Schwab I.R., Chavis P.S., Holyk P.R., Husted R. Koller H.P., Liegner J.T., Mieler W.F., Moroi S.E Marijuana and the treatment of glaucoma CTA – 2014. http://www.aao.org/complimentary-therapy-assessment/marijuana-in-treatment-of-glaucoma-cta--may-2003
REFERENCES
14) Martin-Sanchez E., Furukawa T.Q., Taylor J., Martin J.L.R. Systemic review and meta-analysis of cannabis treatment for chronic pain. Pain Medicine 2009: 10[8]: 1353-68
15) Lynch M.E., Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systemic review of randomized trials. British J of Clinical Pharm: 2011: 72:5: 735-44
16) Lynch M.E., Ware M.A. Cannabinoids for the treatment of chronic non-cancer pain: An update systemic review of randomized controlled trials. J Neuroimmune Pharm: 2015: 10:293-301
REFERENCES
17) Karst M., Kahlid s., Burstein S., Conrad I., Hoy L., Schneider U. Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: A randomized controlled trial. JAMA Oct, 2003: 290[13]: 1757-62 (reprinted)
18) http://www.cancer.gov/about-cancer/treatment/cam/patient/cannabis-pdq/#link/_13
19) Baron E.P. Comprehensive review of medicinal marijuana, cannabinoids, and therapeutic implications in medicine and headache: what a long strange trip it’s been… Headaches. 2015 Jun.: 885-916
REFERENCES
20) Mercola J. Marijuana Research Supports Its Safety and Benefits. 2015, May 16 http://articles.mercola.com/sites/articles/archive/2015/05/16/research-supports-marijuana-benefits.aspx
21) Gedde M. Gedde Whole Health, LLC http://www.geddewholehealth.com/geddeclinics/index.htm
22) Hall W. Addiction Momography What has research over the past two decades revealed about the adverse health effects of recreational cannabis use? 2014; Addiction.10,19-35
REFERENCES
23) Van Os J., Bak M. Hanssen M., Bijl R. V., de Graaf R., Verdoux H. Cannabis use and psychosis: a longitudinal population-based study. Am J Epidemiol 2002; 156: 319-27
24) Henquet C. Krabbendam L., Spauwen J., Kaplan C., Lieb R., Wittchen H., et al. Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. BMJ 2004; 330:11
25) http://www.oregon.gov/olcc/marijuana/Pages/Frequently-Asked-Questions.aspx
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