Legal and socially acceptable … 2737 B.C. – Chinese ... · • Marihuana Act of 1937 makes it...
Transcript of Legal and socially acceptable … 2737 B.C. – Chinese ... · • Marihuana Act of 1937 makes it...
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• Legal and socially acceptable …• 2737 B.C. – Chinese Emperor Shen Neng proclaims it medicine• 1850s – Medical preparations available in pharmacies• 1880s – Estimated 500 hashish parlors in NYC
• And then it wasn’t …• Harrison Act of 1914 declares drug use a crime• Marihuana Act of 1937 makes it inaccessible• Controlled Substances Act of 1970 classifies it as Schedule I
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• In society …• 2013 – “Weed” series on CNN introduces Charlotte Figi
• In Work Comp …• 2014 – Vialpando v. Ben’s Auto. Servs
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http://news.gallup.com/poll/221018/record-high-support-legalizing-marijuana.aspx
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http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx
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• Perfect storm …• Rx opioids vs. cannabis vs. alcohol
• It’s personal …• Many people know someone for whom cannabis works
• Impaired workforce …• Presence <> impairment
• “Reasonable and necessary” …• Combined with “but for” compels Work Comp reimbursement
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>60 active cannabinoids –individual,
interactive, and entourage effects
>400 compounds including flavonoids
and terpenoids
Other
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Principal psychoactive compound
Partial CB1 and CB2 agonist
Low receptor efficacy and affinity
11–OH–THC main metabolite and psychoactive
Medical effects:
•Analgesic •Anti‐inflammatory•Anti‐emetic•Anti‐spasmodic•Sedation
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Considered to have more medicinal applications than THC
Very low affinity for CB1 and CB2
Minimal psychoactive effect
5‐HT1A receptor agonist
• Antidepressant, Anxiolysis
Allosteric modulator of µ‐ and δ‐opioid receptors
• Analgesia
Other: Anti‐psychotic, anti‐epileptic
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Found in trace amounts in cannabis
Weak psychoactive effect
Metabolite of THC
Weak agonist of CB1 and CB2 but high affinity for CB2
• Anti‐inflammatory effects
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Caryophyllene
• CB2 agonist• Anti‐inflammatory • Beta‐caryophyllene is an FDA approved dietary supplement
Humulene
• Anti‐inflammatory effects similar to dexamethasone
• Inhibits TNFa and IL1B
Myrcene
• Analgesic effect• Blocked by naloxone or yohimbine
• Anti‐inflammatory effect• Through PGE2 inhibition
Linalol
• Possible reduction of stress
Limonene
• Adenosine agonist
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Peripheral Cells: monocytes, B/T and mast cells CB2‐r:↓Inflammatory cell mediator release↓ Plasma extravasa on↓ Sensi za on of afferent terminals
Peripheral terminal of Primary afferentCB1‐r:↓ Terminal excitability↓ Release of pro‐inflammatory terminal peptides
CB‐r agonists: reduction of elevated terminal excitability otherwise induced by local injury and inflammation
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Spinal Dorsal Horn
CB1‐r: (intrathecal)
CB1 agonists: reduction of afferent evoked excitation of dorsal horn nociceptive neurons
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Supraspinal SitesCB1‐r (microinjection)Basolateral AmygdalaPeriaqueductal grayRostroventral Medulla
Local effects upon nociceptive processing
Activation of bulbospinal pathways… regulating dorsal horn excitability
CB1 agonists: reduction of afferent evoked excitation of dorsal horn nociceptive neurons.
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ALS Autism Cancer Crohn’s disease
Spinal cord injury with intractable
spasticity Epilepsy Glaucoma HIV / AIDS
Huntington’s Disease
Irritable Bowel Syndrome
Intractable Seizures
Multiple Sclerosis
Neuropathies Parkinson’s Disease
Sickle Cell Anemia
Post‐Traumatic Stress Disorder
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“Severe chronic intractable pain of neuropathic origin
or severe chronic or intractable pain in which conventional therapeutic intervention and opiate therapy is contraindicated
or ineffective.”
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Cancer Remission Spastic Movement Disorders
Neurodegenerative Conditions Substitute for Opioid Reduction
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“Gold Standard” in research is LARGE randomized, double‐blinded placebo‐control studies – otherwise concerns exist for bias and subjectivity ProCon.org lists 61 peer reviewed studies worldwide
› 27 double‐blinded – Only 17 had positive results 6 were short term studies – some less than 2 weeks Some had small number of participants Some were not Phase 3 trials Results were not definitive suggesting further research
› Over 40 clinical trials with quality of evidence highly variable› Despite variability of evidence many state policies allow many uses› Classification as Schedule I presents barrier to research
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Chemo related n/v
AIDS and cancer related anorexia/weight loss/pain
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Chronic Pain – such as headache, arthritis, back injuries ‐improves tolerance for pain but doesn’t reduce intensity
Neuropathic pain – includes diabetic and from spine Spasticity in Multiple Sclerosis – Sativex an oral spray formula
with strongest evidence not FDA approved yet so not available in US
Epilepsy – However Epidolex is a strawberry flavored oil containing CBD for conditions such as Dravet Syndrome and Lennox‐Gastaut Syndrome
Crohn’s Disease – Tel Aviv study of only 21 people. 45% remission with high THC cigarettes vs. 10% in placebo, but needed to stay on the drug. Other studies not completed or results known yet
Cancer – except in cases of above symptoms Parkinson’s Disease – poor studies
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Alzheimer’s Disease – only cellular studies Anxiety Disorders – Vanderbilt study suggests occasional use
may help but chronic use worsens condition Post‐Traumatic Disorder – Mixed results. May depend on mix
of THC/CBD Weight Loss – other measures safer Lupus – University of New Mexico found no difference over 5
years Glaucoma – positive effect only lasts 3‐4 hours Tourette’s Syndrome – weak studies to suggest reduction in tic
severity Amyotrophic Lateral Sclerosis – little evidence of effectiveness. Terminal Illness – if life expectancy < 1 year, severe or chronic
pain, N/V, or cachexia/wasting
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ACUTE EFFECTS
Short term memory loss
Motor coordination difficulties
Judgment impairment NOTE: Short term use of marijuana doubles the risk of involvement in a motor vehicle crash.*
Paranoid ideation and psychotic symptoms
*Hartman et al, Cannabis effects on driving skills, Clin Chem. 2013: 59(3): 478‐492
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LONG TERM EFFECTS
Impaired brain development
Addiction – 1 in 10 adults and higher among adolescents, effects on work, school and relationships
Tolerance and Down regulation/desensitization of receptors
Anxiety, depression, psychotic illnesses
Functional performance decline – school, lower income, unemployment, criminal behavior, decreased satisfaction with life
Physical – chronic bronchitis, URI, pneumonia, MI, stroke, PVD
Carcinogenic exposure in smoked form
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UNKNOWN EFFECTS
• Interactions with other medications or other medical conditions
WITHDRAWAL EFFECTS
• Anxiety, irritability, craving, dysphoria, insomnia
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SOCIETAL EFFECTS
Increased recreational use and abuse
Washington – increase in marijuana related poison control center calls. Many of products from UNREGULATED dispensaries as opposed to
LICENSED RECREATIONAL shops.
Two national surveys
Odds of marijuana USE nearly 2 times higher in states with medical marijuana laws.
Odds of ABUSE/DEPENDENCE nearly 2X higher in states with legalized medical marijuana.
National Survey on Drug Use and Health
33% increase in teens who smoked pot over the past month in medical marijuana states but only 6% in the rest of the country.
Between 2005 and 2011, only 20% of U.S. lived in medical marijuana states but accounted for >2/3rds of the increase in adolescent use.
Diversion –
Colorado i.e. school distribution of edibles and medicinal forms
74% of adolescents in substance treatment had used someone else’s medical marijuana
Of these adolescents, use of diverted medical marijuana was reported a median of 50 times.
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Is marijuana medicine?
If so, should Work Comp pay for it?