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Cannabis:
Smoldering Considerations in
Chronic Pain Management
Burning questions…
Measure 91 vs
Medical
Marijuana?
Is it legal?
Is it beneficial?
SAFE?
How does it
work?
Drug
interactions?
Monitor?
How to quit
using?
Drug-Related ED Visits
Drug associated with ED visit 2011
Alcohol with drugs 606,653
Cocaine 505,224
Anti-anxiety/ insomnia meds 501,207
Cannabinoids
marijuana
synthetic
479,560
455,668
28,531
Opioids 420,040
Heroin 258,482
Methamphetamine 102,961
marijuana edibles
sinsemilla elixirs
hash oil cannabidiol oil
honey butane oil etc
Cannabis
Consideration #1:
Cannabis is “legal” in Oregon and Washington for medical
and recreational use, but federally is still a Schedule I
Controlled Substance.
Medical vs. Recreational
Medical Recreational
Registry ID card Yes (OR and WA) No; must be 21+ yo
Allowed to grow Yes (OR and WA) OR: up to 4 plants
WA: No
Limit to possession OR: 24 oz useable
MJ, 6 mature
plants, or up to 18
seedlings/ starts
WA: 24 oz useable
MJ, 15 plants, or
participate in
collective garden
OR: 8 oz of MJ, but no more
than 1 oz in public; 1 lb edibles;
72 oz infused liquids; 1 oz
extract. Cannot be used in
public or while driving.
WA: 1 oz useable MJ, 16 oz MJ-
infused product in solid form, 72
oz of MJ-infused product in
liquid form, or 7 grams
concentrate
Taxation No Yes
Consideration #2:
Cannabis has existed for >3000 years…
and yet we still lack high quality data for the efficacy of any
of its components for any medical indication.
Medical Marijuana Indications
(Oregon and Washington*)
Supporting Evidence(1)
Malignant neoplasm
-chemotherapy-induced N/V Low quality data. Mixed results, effective.
-loss of appetite Low quality data. Megestrol superior.
Glaucoma Insufficient data. Other tx options superior.
HIV or AIDS
-loss of appetite
Low quality data; favors efficacy.
Agitation d/t Alzheimer Disease Insufficient data.
PTSD Insufficient data.
Medical condition that produces:
-cachexia Low quality data. Mixed results.
-severe pain Low to moderate quality. Mixed results.
-severe nausea Low quality data. Mixed results. PONV favors
efficacy; operative N/V ineffective.
-seizures (+/- epilepsy) Insufficient data. (CBD studies in progress.)
-persistent muscle spasms (+/- MS) Low to moderate quality data. Inconclusive.
*Crohn’s disease, hepatitis C, renal failure requiring
hemodialysis, traumatic brain injury
Insufficient data.
COMPASS: Pain Results
Absence of Quality Evidence
• Few randomized controlled trials
• Poor study design
• Small n
• Short duration
• Difficult to blind
• Wide range of products, doses, routes of administration
• Poor tolerability, high drop out rates
Consideration #3:
The composition of cannabis varies depending upon
species, subspecies, growth manipulations,
exposure to heat, light, air, etc.
In general, cannabis contains hundreds of
pharmacologic entities.
See also references 5-8
Cannabis: A Chemical Stew
Cannabis
~480 pharmacologic entities
Cannabinoids
(~66-100)
Non-
cannabinoid
psychoactive
components
(~20-40+)
Other
(hundreds)
Combustion
~2000 chemicals
3 Cannabinoids Hitting the News
THC
(delta-9-
tetrahydro-
cannabinol)
CBD
(cannabidiol)
CBN
(cannabinol)
Psychoactive √ (√)
Anti-emetic √
Appetite stimulant √
Analgesic √ √
Anti-inflammatory √ √
Anti-seizure √ √
Anti-spasmodic √
Neuroprotective √
Consideration #4:
Cannabis has existed for >3000 years…
and yet we still don’t fully understand how it works or
everything it does.
How does it work?
Picture: Nature Reviews Cancer 3, 745-755 (October 2003)
CB1 and CB2: presynaptic receptors
Depending on site, inhibit neurotransmitter release
(GABA, glutamate, 5HT, DA, ACh)
?
Endocannabinoid System
Sites of Action
*affects nearly every major organ system*
As-of yet unidentified receptors?
Activity on non-cannabinoid receptors?
CB2:
Immune cells (T cells, B cells,
monocytes)
Spleen
Tonsils
Brain
Heart
Liver
Lungs
Other?
CB1:
Brain
Kidneys
Liver
Heart
GI Tract
Pancreas
Adipose
Muscle
Reproductive organs
Other?
Effects of Cannabis on the Brain
Consideration #5:
The widespread distribution of CB receptors explains the broad
array of adverse effects with cannabis.
Patients may experience different adverse effects with short-
term use of cannabis compared to chronic use.
See also references 5, 7, 8, 10-21
Adverse Effects: Short-term
• anxiety, panic attacks
• distorted perception, hallucinations
• increased heart rate and blood pressure
• decreased memory & learning
• difficulty thinking & problem solving
• decreased coordination
• visuomotor skills deficit
Natural Antagonism
CBD
no (or less) euphoria
anti-anxiety
anti-psychotic
neuroprotective
bradycardia
Loss of antagonism may lead to
increased side effects and poor tolerability.
THC
euphoria
anxiety
psychosis
cognitive impairment
tachycardia
Adverse Effects: Long-term, cont.
“associated with”
• Neurological changes
– sustained decreased IQ(17)
– adolescents: change in neuroanatomy?
– altered memory, esp verbal(19)
– decreased cerebral blood flow
– decreased neural efficiency
– increased DA neurotransmission, psychosis, anxiety
disorder(s), schizophrenia
genetics
mental illnessyounger age + extent of use
Consideration #6:
“The overwhelming consensus from mental
health professionals is that marijuana is
not helpful—and potentially dangerous—
for people with mental illness.”
Consideration #7:
Effects from cannabis vary widely depending upon:
• product
• duration/chronicity of use
• dosage form
• route of administration
• pharmacokinetics*
• pharmacogenetics
• drug interactions
Cannabis “raw materials”
hashish (~2-20%)
hash oil, marijuana concentrate (40-80%)
marijuana (up to 20%+ THC)
cannabidiol oil
• Inhalation (smoking, vaporizing)
– onset: immediate
– bioavailability: 20-37%
Route of Administration
Source:http://www.drugabuse.gov/publications/drugfacts/marijuana Source: www.dea.gov
• Oral
– Onset: 30-60 minutes
– Bioavailability: 10-20%
• Oro-mucosal: similar to oral; highly variable
Route of Administration
• Topical
– Onset: ? ~1-2h
– Bioavailability: ?
• Bypasses first pass
• Crossing aqueous layer is the rate limiting step,
then perfuses well
Route of Administration
Source:
http://www.jupitercompounding.com/
Any remaining burning questions?
A few reference slides…

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5 bästa marijuana stammar för ADHD

  • 2. Burning questions… Measure 91 vs Medical Marijuana? Is it legal? Is it beneficial? SAFE? How does it work? Drug interactions? Monitor? How to quit using?
  • 3. Drug-Related ED Visits Drug associated with ED visit 2011 Alcohol with drugs 606,653 Cocaine 505,224 Anti-anxiety/ insomnia meds 501,207 Cannabinoids marijuana synthetic 479,560 455,668 28,531 Opioids 420,040 Heroin 258,482 Methamphetamine 102,961
  • 4. marijuana edibles sinsemilla elixirs hash oil cannabidiol oil honey butane oil etc Cannabis
  • 5. Consideration #1: Cannabis is “legal” in Oregon and Washington for medical and recreational use, but federally is still a Schedule I Controlled Substance.
  • 6. Medical vs. Recreational Medical Recreational Registry ID card Yes (OR and WA) No; must be 21+ yo Allowed to grow Yes (OR and WA) OR: up to 4 plants WA: No Limit to possession OR: 24 oz useable MJ, 6 mature plants, or up to 18 seedlings/ starts WA: 24 oz useable MJ, 15 plants, or participate in collective garden OR: 8 oz of MJ, but no more than 1 oz in public; 1 lb edibles; 72 oz infused liquids; 1 oz extract. Cannot be used in public or while driving. WA: 1 oz useable MJ, 16 oz MJ- infused product in solid form, 72 oz of MJ-infused product in liquid form, or 7 grams concentrate Taxation No Yes
  • 7. Consideration #2: Cannabis has existed for >3000 years… and yet we still lack high quality data for the efficacy of any of its components for any medical indication.
  • 8. Medical Marijuana Indications (Oregon and Washington*) Supporting Evidence(1) Malignant neoplasm -chemotherapy-induced N/V Low quality data. Mixed results, effective. -loss of appetite Low quality data. Megestrol superior. Glaucoma Insufficient data. Other tx options superior. HIV or AIDS -loss of appetite Low quality data; favors efficacy. Agitation d/t Alzheimer Disease Insufficient data. PTSD Insufficient data. Medical condition that produces: -cachexia Low quality data. Mixed results. -severe pain Low to moderate quality. Mixed results. -severe nausea Low quality data. Mixed results. PONV favors efficacy; operative N/V ineffective. -seizures (+/- epilepsy) Insufficient data. (CBD studies in progress.) -persistent muscle spasms (+/- MS) Low to moderate quality data. Inconclusive. *Crohn’s disease, hepatitis C, renal failure requiring hemodialysis, traumatic brain injury Insufficient data.
  • 10. Absence of Quality Evidence • Few randomized controlled trials • Poor study design • Small n • Short duration • Difficult to blind • Wide range of products, doses, routes of administration • Poor tolerability, high drop out rates
  • 11. Consideration #3: The composition of cannabis varies depending upon species, subspecies, growth manipulations, exposure to heat, light, air, etc. In general, cannabis contains hundreds of pharmacologic entities. See also references 5-8
  • 12. Cannabis: A Chemical Stew Cannabis ~480 pharmacologic entities Cannabinoids (~66-100) Non- cannabinoid psychoactive components (~20-40+) Other (hundreds) Combustion ~2000 chemicals
  • 13. 3 Cannabinoids Hitting the News THC (delta-9- tetrahydro- cannabinol) CBD (cannabidiol) CBN (cannabinol) Psychoactive √ (√) Anti-emetic √ Appetite stimulant √ Analgesic √ √ Anti-inflammatory √ √ Anti-seizure √ √ Anti-spasmodic √ Neuroprotective √
  • 14. Consideration #4: Cannabis has existed for >3000 years… and yet we still don’t fully understand how it works or everything it does. How does it work?
  • 15. Picture: Nature Reviews Cancer 3, 745-755 (October 2003) CB1 and CB2: presynaptic receptors Depending on site, inhibit neurotransmitter release (GABA, glutamate, 5HT, DA, ACh) ? Endocannabinoid System
  • 16. Sites of Action *affects nearly every major organ system* As-of yet unidentified receptors? Activity on non-cannabinoid receptors? CB2: Immune cells (T cells, B cells, monocytes) Spleen Tonsils Brain Heart Liver Lungs Other? CB1: Brain Kidneys Liver Heart GI Tract Pancreas Adipose Muscle Reproductive organs Other?
  • 17.
  • 18. Effects of Cannabis on the Brain
  • 19. Consideration #5: The widespread distribution of CB receptors explains the broad array of adverse effects with cannabis. Patients may experience different adverse effects with short- term use of cannabis compared to chronic use. See also references 5, 7, 8, 10-21
  • 20. Adverse Effects: Short-term • anxiety, panic attacks • distorted perception, hallucinations • increased heart rate and blood pressure • decreased memory & learning • difficulty thinking & problem solving • decreased coordination • visuomotor skills deficit
  • 21. Natural Antagonism CBD no (or less) euphoria anti-anxiety anti-psychotic neuroprotective bradycardia Loss of antagonism may lead to increased side effects and poor tolerability. THC euphoria anxiety psychosis cognitive impairment tachycardia
  • 22. Adverse Effects: Long-term, cont. “associated with” • Neurological changes – sustained decreased IQ(17) – adolescents: change in neuroanatomy? – altered memory, esp verbal(19) – decreased cerebral blood flow – decreased neural efficiency – increased DA neurotransmission, psychosis, anxiety disorder(s), schizophrenia genetics mental illnessyounger age + extent of use
  • 23. Consideration #6: “The overwhelming consensus from mental health professionals is that marijuana is not helpful—and potentially dangerous— for people with mental illness.”
  • 24. Consideration #7: Effects from cannabis vary widely depending upon: • product • duration/chronicity of use • dosage form • route of administration • pharmacokinetics* • pharmacogenetics • drug interactions
  • 25. Cannabis “raw materials” hashish (~2-20%) hash oil, marijuana concentrate (40-80%) marijuana (up to 20%+ THC) cannabidiol oil
  • 26. • Inhalation (smoking, vaporizing) – onset: immediate – bioavailability: 20-37% Route of Administration Source:http://www.drugabuse.gov/publications/drugfacts/marijuana Source: www.dea.gov
  • 27. • Oral – Onset: 30-60 minutes – Bioavailability: 10-20% • Oro-mucosal: similar to oral; highly variable Route of Administration
  • 28. • Topical – Onset: ? ~1-2h – Bioavailability: ? • Bypasses first pass • Crossing aqueous layer is the rate limiting step, then perfuses well Route of Administration Source: http://www.jupitercompounding.com/
  • 29. Any remaining burning questions?
  • 30. A few reference slides…