Pain Management in Primary Care 2015: “Opium, Marijuana, Oh My!”

Pain Management in
Primary Care 2015:
“Opium, Marijuana,
Oh My!”
Andrew Kowal, MD.
Director, Pain Management Center
Assistant Clinical Professor of
Anesthesiology, Tufts Medical School
Lahey Hospital & Medical Center
Burlington, MA
Agenda
 A brief history of the medicinal use of marijuana
 A review of the pharmacology/physiology of the
endocannabinoid system
 Does marijuana actually have good (any?) data
supporting its utilization
 Adverse effects of marijuana
 Legal considerations for the clinician
 Opiates: updates and thoughts
 Everyone please grab a free brownie on way out
“Why drink and drive,
when you can smoke and fly.”
“If we all had a bong,
we’d all get along.”
• Listed in U.S
Pharmacopeia
1850-1941
– marijuana &
hashish extracts
were the 1st, 2nd, or
3rd most prescribed
meds in the US
from 1842-1890s
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neuralgia
gout
rheumatism
tetanus
hydrophobia
epidemic cholera
convulsions
chorea
hysteria
mental depression
delirium tremens
insanity
uterine hemorrhage
California's Proposition 215
1996
• First statewide medical marijuana ballot initiative
to pass in the USA
– allow possession and cultivation of cannabis for
‘debilitating’ medical conditions if
recommended by a physician
• provide a defense against prosecution under state
criminal laws
Venice Beach, CA
The Cleveland Clinic of Medical THC
Cannabis sativa
Common Forms of Cannabis

Hashish - dried resin and compressed
flowers
– ∆9-THC content ranged from 3 to 7% with rare
increases as high as about 20%
– Accounted for < 1% of all confiscated marijuana
samples in the past ten years

Marijuana - dried flowering tops and
leaves
– Wide range of ∆9-THC content with increases as high
as about 30%
– most common form
Marijuana Constituents

Contains a complex mixture of over 400
chemicals
– ~66 are cannabinoids
– ∆9-THC is the primary psychoactive constituent
(THC)
– Cannebediol (CBD) : up to 40% of plant, “good”
component, more widespread actions
– Ratio of CBD/THC critical (and variable)
Pharmacology

Receptors
– CB1 (primarily in brain)….THC active (partial
agonist)
– CB2 (peripheral, widespread, immune system,
inflammation/peripheral pain
pathways)……CBD active
Pharmacology
Anandamide is the endogenous ligand
that binds the CB receptors , named
after the Sanskrit word for bliss
“ananda”
 cAMP inhibition at target cells
 Inhibits release of dopamine,
acetycholine, glutamate with indirect
effect on opiate, serotonin, GABA
receptors

Brain regions rich with
cannabinoid (CB1) receptors
Function
Region
Nigrostriatal region
 Cerebellum
 Hippocampus
 Nucleus accumbens
 Cerebral cortex
Moderate Levels
 Hypothalamus
 Amygdala
 Brain stem
 Spinal cord
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Movement
Fine motor movements
Learning and memory
Drug reinforcement
Higher cognitive functions
Temperature regulation
Emotionality
Sleep and arousal, nausea
Pain
Routes of Administration
Smoked marijuana:
 Reaches the brain in minutes
 Effects last 1 - 3 hours
 Delivers a lot of THC into the
bloodstream
Eating or drinking marijuana:
 Takes ½ - 1 hour to have an effect
 Effects last up to 4 hours
 Delivers significantly less THC into
the bloodstream
THC Candy
Basic THC (Marijuana)
Pharmacology: Review of Acute
Effects
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Abuse Potential (high)
Positive subjective effects (increased)
Heart rate (increased)
Food intake (increased)
Cognitive effects (variable)
Driving ability (impaired)
Does marijuana cause psychotic illness (possibly)
Verbal Behavior (decreased)
Dry mouth
Reddened eyes
Driving

If drunk
–you run the RED lights

If stoned
–you stop at the GREEN lights
Driving
• THC impairs primarily automatic driving
functions, which can be compensated
effectively with behavioral strategies.
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• Alcohol impairs complex tasks requiring
conscious control.

• Combining THC with alcohol eliminates the
compensatory strategies and results in
impairment even at doses that would be
insignificant for either drug alone.

Srewell, Am J Addictions, 2009
Opiates / Marijuana
Papaver
somniferum
(poppy)
 opium
 Endorphins
 Mu, kappa
 Percocet

Cannabis Sativa
(marijuana)
 THC,
Cannebediol
 Anandamide
 CB1, CB2
 ?Sativex

The Players (forms of MJ available)
 Oral Tab Formulations: dronabinol (marinol),
nabilone (casamet), cannabis extracts
 Oral Spray: nabixemols (sativex)
 Marijuana Plant : smoked, vaporized,
ingested in brownies
Nabixemols (Sativex)
 Mouth spray containing 1:1 ratio of THC:CBD
 Approved in 24 countries for spasticity from
MS, neuropathic pain, cancer pain
 Phase 3 trials in US for cancer pain
 Absorption through buccal mucosa and
metered dosing may mimic smoked
marijuana without as many psychotropic
effects
 20 times lower peak plasma THC
concentrations
Glaucoma
May cause transient decrease in
IOP, provide neuroprotective effect
THC but not CBD lowered IOP in
rabbits
Currently available therapies are
more effective
Volkow et al ,n engl j med 370;23 nejm.org june 5, 2014
Nausea
 Chemotherapy induced nausea one of
first things treated with THC, which is
effective but no better than currently
available therapies
 Smoked THC is perceived more
effective than oral, but paradoxical
hyperemesis can occur
Ssallan, N Engl J Med 1975;293:795-7
Inflammation
 CBD has shown potential to be anti-
inflammatory by its effect on reducing
cytokine production and cell
proliferation
 ANIMAL studies have shown promise
in RA and Crohns/UC
Rev Bras Psiquiatr 2008;30:271-80
Phytother Res 2013;5:633-6.
Neurologic Disorders
 AAN Koppel etal…34 studies found that met
criteria with 8 Class 1 stringent criteria
 Spasticity in MS: cannabis extract works for
reducing patient reported scores, ineffective
for objective measures at 15 weeks, maybe
at 1 year. Smoked “uncertain efficacy”
 Pain in MS: extracts/nabiximols probably
effective. Smoked “uncertain efficacy”
 Unknown efficacy in epilepsy, tremors
Neurology 82 April 29, 2014
Chronic Pain
 Smoked THC MAY be effective in
neuropathic pain syndromes through
central and peripheral modulation of
nociceptive pathways.
 No long term studies beyond 3 months
 Worrisome population prone to exposure
to multiple addictive/sedating substances
 94% of RX in Colorado for chronic pain,
21-35 yrs old
J Pain 2008;9:506-21
Anesthesiology 2007;107:785-96
Adverse Effects: Short Term
 Impaired short-term memory, making it difficult
to learn and to retain information
 Impaired motor coordination, interfering with
driving skills and increasing the risk of injuries
 Altered judgment, increasing the risk of sexual
behaviors that facilitate the transmission of
sexually transmitted diseases
 Paranoia and psychosis with high doses
Volkow et al ,n engl j med 370;23 nejm.org june 5, 2014
Adverse Effects: Long Term or Heavy
Use
 Addiction (in about 9% of users overall, 17% of
those who begin use in adolescence, and 25 to
50% of those who are daily users)
 Altered brain development
 Poor educational outcome, with increased
likelihood of dropping out of school
 Cognitive impairment, with lower IQ among
those who were frequent users during
adolescence
Volkow et al ,n engl j med 370;23 nejm.org june 5, 2014
Adverse Effects: Long Term or Heavy
Use
 Diminished life satisfaction and achievement
(determined on the basis of subjective and
objective measures as compared with such
ratings in the general population)
 Increased risk of chronic psychosis disorders
(including schizophrenia) in persons with a
predisposition to such disorders
 Symptoms of chronic bronchitis
Volkow et al ,n engl j med 370;23 nejm.org june 5, 2014
ASAM 2010 Medical Marijuana White
Paper
 “Controlled substances are drugs that have
recognized abuse potential. Marijuana is high on that
list because it is widely abused and a major cause of
drug dependence in the United States and around
the world. When physicians recommend use of
scheduled substances, they must exercise great
care. The current pattern of “medical marijuana” use
in the United States is far from that standard “
 All cannabis‐based and cannabinoid medications
should be subjected to the rigorous scrutiny of the
Federal Food and Drug Administration (FDA)
regulatory process
MA Medical Society (MMS)
“That until such time as marijuana is approved
for use by the Food and Drug Administration
and is no longer classified in schedule I by the
Drug Enforcement Administration, the MMS
cannot support legislation intended to involve
physicians in certifying, authorizing, or
otherwise directing persons in the area of
medicinal marijuana outside of scientific clinical
trials.” 12/2013
MA Marijuana Law
 For Whom? Patients with certain “debilitating
conditions” like cancer, glaucoma, HIV, AIDS,
hepatitis C, ALS, Crohn’s Disease, Parkinson’s
Disease and Multiple Sclerosis along with other
conditions “determined in writing by the qualifying
patient’s physician”
 While the law protects patients and providers from
state criminal or civil actions, it does not protect
patients, healthcare providers or healthcare
institutions from FEDERAL criminal or civil
prosecution
MA Marijuana Law
 It is ILLEGAL for a physician to write for/
prescribe a Schedule 1 drug (heroin, thc),
doing so one can lose DEA number and be
banned from Medicare patients etc…
 Physicians can “recommend” or certify
patients for Marijuana, under the belief that
this is not a prescription
 Case Law: Pearson vs. McCaffery 2001,
federal court determined “a physician
recommending marijuana is writing a
prescription for marijuana and…a violation of
federal law”
MA Marijuana Law
 The MA law does not require healthcare
providers or hospitals to provide written
recommendations for medical marijuana
 The MA law DOES NOT protect someone from
being terminated or the refusal to hire someone
because they use medical marijuana
 No protection against federal prosecution
 The use of medical marijuana is not protected
under the Americans With Disabilities Act
 ONE provider breaking federal law can cause
entire health system to lose Medicare eligibility
What do the “Big Boys” Say about
Medical THC… procon.org (2012):
 Johns Hopkins: ”no position”
 MGH: did not respond
 Mayo: “consider risks”
 Cleveland Clinic: “…does not recommend
use of illegal substances”
 UCLA: “we have no stated position”
 UCSF: “no position”
 BWH: “no position”
 Duke: “we will not be participating”
A (very) Local “Certifying Clinic”
 “Bring all your records”
 $200 (cash/debit/credit) for intake evaluation
 $150 for required 6 month follow ups,
“relationship as required” ($75 for any patient
requested office visits/BOV)
 State certification Card fees, cost of cannabis
are all separate and extra and how much THC
you get depends on whether you have
“physical or psychological problems”
 Don’t screen for substance abuse, try to sell
all kinds gadgets
A (very) Local “Certifying Clinic”
Education & Training

Post Graduate Training
3/30/1999)

Boston Medical Center, Resident:Anesthesiology (7/1/1999 - 6/30/2000)

Massachusetts General Hospital, Fellow:Medical Informatics (7/1/2000 - 6/30/2002)

Brigham & Women's Hospital, Fellow: (7/1/2002 - 7/31/2003)

American Academy of Pain Research, Fellow:Acupuncture (6/1/2004 - 12/31/2005)

MediTech International Inc - Laser Therapy Certification, Fellow:Unspecified Specialty
(8/1/2004 - 10/1/2004)

Lymphatic Massage Therapy, (8/1/2004 - )

Zyto Institute, Fellow:Herbology (1/1/2006 - 12/31/2008)

First Line Therapy Certification, Fellow:Nutrition (1/1/2007 - 12/31/2007)

National Alliance of Wound Care, Fellow:Unspecified Specialty (10/31/2007 - 12/31/2007)

Quantum Reflex Analysis, Fellow:Nutrition (1/1/2008 - 12/31/2008)

Cardiff University, Fellow:Dermatology (3/1/2012 - 5/31/2012)

Area of Specialty Acupuncture, Addiction Medicine, Pain Management, Unspecified
Specialty
Boston Medical Center, Intern:General Surgery (7/1/1998 -
Board Certifications
Dr. X…. has reported no board certifications.
100mg Daily Total Morphine Equivalent is Key
Best Practices Opioids MMS May 2015
 90 days of opioid tx threshold to start
“chronic” guidelines (primary care)
 Reevaluation, objective pain assessment tool
 Substance abuse assessment, UTOX (in
development)
 Document functional improvement with visits
every 2-3 months (and check PMP)
 Discuss risks/benefits including addiction,
cognitive impairment , driving dangers etc..
Best Practices Opioids MMS May 2015
 Opioid Agreements
 Discuss/prescribe naloxone
 Don’t initiate treatment plane above 100 mg
daily morphine equivalent without consulting
specialist
 Use “abuse deterrant” formulations
 STOP if too risky, low benefit
Opioid-Induced Hyperalgesia (OIH) or
“Paradoxical Pain”
 Idea described in literature since at least 1986 in clinical
and pre-clinical settings
 OIH is a sensitization of pro-nociceptive pathways,
tolerance is a de-sensitization of anti-nociceptive
pathways. Genetics involved. (ELDERLY IMMUNE?)
 Upregulation of dynorphin (kappa), substance p (NK1),
glutamate (NMDA) receptors in spinal cord
 Upregulation of spinal substance P, CGRP content and
release in primary afferents
 RVM has increased CCK activity, inducing descending
facilitation
Hojsted. Curr Opin Anaesthsiol 2007;20:451-455
Lee, Pain Physician: March/April 2011; 14:145-161
The Effectiveness and Risks of Long-Term Opioid Therapy for Chronic
Pain: A Systematic Review for a National Institutes of Health Pathways
to Prevention Workshop
Annals of Internal Medicine 2015
 Purpose: to evaluate evidence on the
effectiveness and harms of long-term (>3 months)
opioid therapy for chronic pain in adults.
 667 articles from 2008-2014
 Good- and fair-quality observational studies
suggest that opioid therapy for chronic pain is
associated with increased risk for overdose, opioid
abuse, fractures, myocardial infarction, and
markers of sexual dysfunction, although there are
few studies for each of these outcomes
Chou et al. Ann Intern Med. doi:10.7326/M14-2559 epub 13 Jan 2015
The Effectiveness and Risks of Long-Term Opioid Therapy for Chronic
Pain: A Systematic Review for a National Institutes of Health Pathways
to Prevention Workshop
Annals of Internal Medicine 2015
No study of opioid therapy versus no
opioid therapy evaluated long-term
(>1 year) outcomes related to pain,
function, quality of life, opioid abuse,
or addiction
Chou et al. Ann Intern Med. doi:10.7326/M14-2559 epub 13 Jan 2015
The Effectiveness and Risks of Long-Term Opioid Therapy for Chronic
Pain: A Systematic Review for a National Institutes of Health Pathways
to Prevention Workshop
Annals of Internal Medicine 2015
CONCLUSION
Evidence is insufficient to determine
the effectiveness of long-term opioid
therapy for improving chronic pain
and function. Evidence supports a
dose-dependent risk for serious
harms
Chou et al. Ann Intern Med. doi:10.7326/M14-2559 epub 13 Jan 2015
Opioids for Chronic Noncancer Pain: A
Position Paper of the
American Academy of Neurology
Whereas there is evidence for significant shortterm pain relief, there is no substantial
evidence for maintenance of pain relief or
improved function over long periods of time
without incurring serious risk of overdose,
dependence, or addiction.
Neurology. 2014 Sep 30;83(14):1277-84
ASIPP Opioid Guidelines Non-Cancer
Pain 2012
 Good evidence of extensive non-medical use
of opiates
 Long term effectiveness of opiates is limited
at best, short term (<3 mo.) fair
 Limited evidence of effectiveness of opioid
abuse screening tools
 Good evidence that even low dose opiates
(50mg MEQ) responsible for overdoses and
deaths
Pain Physician 2012; 15:S1-S66
ACOEM Practice Guidelines: Opioids and
Safety-Sensitive Work July 2014
Acute or chronic opioid use is not
recommended for patients who perform safetysensitive jobs. These jobs include operating
motor vehicles, other modes of transportation,
forklift driving, overhead crane operation,
heavy equipment operation and tasks involving
high levels of cognitive function and judgment.
Quality evidence consistently demonstrates increased
risk of vehicle crashes and is recommended as the
surrogate for other safety sensitive work tasks
Hegmann et al JOEM Volume 56, Number 7, July 2014
Dr. M…….: A Local Pill Mill
 Board certified anesthesiologist and critical care,
pain “clinics” in 3 states, open 3 years
 Ran Saturday clinic near Lahey, patients gathered
at 0700 until 2200, waiting 5 or 6 hours, billed
Medicare $3.5 MILLION 2012
 MONTHLY visits and refills: opiate/benzo/stimulant
for everyone, UTOX each month in his “lab” $$$$$
 NEVER addressed abnormal utox results,
addiction histories
 RI/MA license suspended, at least 6 people
overdosed and died/ arrested at Logan
Lahey Pain MOP Center
(Medication Optimization Program)
 100mg Morphine daily equiv/3 months
 Patient with chronic pain, get them to realize
that opiates not helping their pain
 EDUCATE about hyperalgesia, they will feel
LESS pain and side effects after detox!
 Guaranteed at worst MILD withdrawal sx
 Get adjuvants started
(pregabalin,milnacipran,etc..)
 Slow vs. Fast (using Suboxone)
 Family/Friends support, psych
A Recent Patient: “RSD”
ONE Month received 1344 30mg oxycodone,
784 60 mg Morphine ER, 336 Dilaudid 2mg IM
INJECTABLES, 14 50 mcg fentanyl patches,
240 soma (barbiturate), 168 2mg Ativan, 112
2mg Xanax
100 PILLS PER DAY
($120,000/month street value)
THANK YOU!
781-744-5090
[email protected]