Cannabis contains hundreds of compounds that can have various pharmacological effects. While cannabis has been used for thousands of years, the evidence for its medical efficacy is still limited due to poor study quality. Short-term cannabis use can cause adverse effects like anxiety and impaired cognition, while long-term use has been associated with sustained cognitive impairment. The effects of cannabis vary depending on factors like dosage, route of administration, and drug interactions. More research is still needed to fully understand how cannabis works and its risks and benefits.

1. Cannabis:
Smoldering Considerations in
Chronic Pain Management

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.

9. COMPASS: Pain Results

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?

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…