The Great Debate

Great Debate:

Opioid Treatment Agreements or Just Another Piece of Paper? and

By All Means Inhale! Marijuana and Pain Management Mary Lynn McPherson, Pharm.D., BCPS, CPE Kathryn Walker, Pharm.D., BCPS, CPE University of Maryland School of Pharmacy

Disclosures • Nothing to Disclose

Learning Objectives • Review the pros and cons of opioid treatment agreements • Recognize the potential benefits and consequences of medical marijuana

Opioid Treatment AgreementsMore than a Piece of Paper!!

Kathryn Walker, Pharm.D., BCPS, CPE University of Maryland School of Pharmacy Union Memorial Hospital Palliative Medicine Specialist

Contract or Agreement?

• “Contracts” fallen out of favor ▫ No legal merit

• Agreements include aspects of informed consent but may also include additional information ▫ ▫ ▫ ▫

Responsibilities of provider and patient How opioids are prescribed and administered Expectations for follow-up appointments and monitoring Possible grounds for tapering or discontinuing treatment (including failure to progress toward goals, intolerable adverse effects, or repeated/serious aberrant behaviors) and the strategy for doing this humanely ▫ Role of opioid therapy as only one part of a multimodal treatment plan ▫ Realistic expectations in terms of therapy outcome Chou R, et al. J of Pain. 2009; 10(2): 113-130.

No One LOVES Having More PAPERWORK!

Informed Consent • “Informed consent is more than simply getting a patient to sign a written consent form. It is a process of communication between a patient and physician that results in the patient's authorization or agreement to undergo a specific medical intervention.â€? (AMA)

http://www.ama-assn.org/ama/pub/physician-resources/legal-topics/patient-physician-relationshiptopics/informed-consent.page

More from the AMA • “To protect yourself in litigation, in addition to carrying adequate liability insurance, it is important that the communications process itself be documented.

• Good documentation can serve as evidence in a court of the law that the process indeed took place.”

http://www.ama-assn.org/ama/pub/physician-resources/legal-topics/patient-physician-relationshiptopics/informed-consent.page

OA Goals 1.

2.

3.

4.

5.

Describe agreed upon course of treatment Improve adherence Increase practice efficiency Manage legal risk Enhance care through communication

Can these goals be met?

1.

2.

3.

4.

5.

Describe agreed upon course of treatment1 Improve adherence2 Increase practice efficiency3 Manage legal risk Enhance care through communication1

Plus: Increases providers’ comfort (and sense of mastery) in prescribing controlled substances4 1. Chou R, et al. J of Pain. 2009; 10(2): 113-130.

2. Hariharan, et al. J Int Med. 2007; 22(4): 485-490.

3. Fagan, MJ et al. The Clinical Journal of Pain. 2008; 24(1): 35-38.

4. Touchet B, et al. J Opioid Manag. 2005; 1(4): 195-200.

Can these goals be met?

• Documents communication ▫ Reinforces expectations and roles ▫ Makes plan clear for patient, family, other providers ▫ Patient education

• Increases providers’ comfort (and sense of mastery) in prescribing controlled substances

Chou R, et al. J of Pain. 2009; 10(2): 113-130.

Touchet B, et al. J Opioid Manag. 2005; 1(4): 195-200.

http://www.painpolicy.wisc.edu/matrix.htm

Example: Guidelines within Statutes • Informed Consent and Agreement for Treatment. The physician should discuss the risks and benefits of the use of controlled substances with the patient, persons designated by the patient, or with the patient's surrogate or guardian if the patient is incompetent.

• The patient should receive prescriptions from one physician and one pharmacy where possible.

• If the patient is determined to be at high risk for medication abuse or have a history of substance abuse, the physician may employ the use of a written agreement between physician and patient outlining patient responsibilities including ▫ 1.urine/serum medication levels screening when requested ▫ 2.number and frequency of all prescription refills; and ▫ 3. reasons for which drug therapy may be discontinued (i.e. violation of agreement).

Who’s in Favor • • • • • • •

American Academy of Pain Medicine American Academy of Pain Management American Pain Society Federation of State Medical Boards Pain and addiction experts Regulatory agencies (DEA) Clinical Guidelines ▫ Chronic Opioid Therapy (Chou, et al; 2009) ▫ Universal Precautions (Gourlay, et al; 2005)

OA for Everyone?

• Limit to high risk patients?

• Limit to certain type of treatment?

• Based on providers’ judgment?

http://www.opioidrisk.com/node/766

And the Survey Says‌ • 88% physicians felt treatment agreements are important tools in reducing risk of substance misuse in chronic opioid treatment.

I’ll Concede to OA Limitations: • Limited evidence of effectiveness • Wide variation in design, content, tone, implementation

Arnold R, Han P, Seltzer D. Am J Med. 2006; 119: 292-296.

I’ll Concede to OA Limitations, HOWEVER… • Misuse of OA • Over-reliance to solve diversion issues

Compton P. Emerging Solutions in Pain. 2009.

Brushwood D. American Society of Law, Medicine and Ethics (ASLME).

OA is an Important Part of Providing BASIC Quality Care • • • •

Make good clinical decisions Involve the patient Educate patients DOCUMENT!!!

• Consistent with use of OA!! http://mikuzen.blogspot.com/2010/02/touhou-bad-appleliterally-on-apples.html

Opioid Treatment Agreements – Oh Please, Pull My Good Leg!

Mary Lynn McPherson, Pharm.D., BCPS, CPE University of Maryland School of Pharmacy

21 Growing public health threat of opioid misuse, abuse, addiction, diversion and unintentional overdose

116 million Americans suffer from chronic pain

You are here

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Opioid Agreements  Opioid agreements, opioid contracts  A “contract” is held to rigorously high standards and creates a sense of mutual legal obligation  An “agreement” leaves room for greater flexibility

 Opioid medication agreements  Patient opioid agreements (POA)  “…formal and explicit written agreements between physicians and patients that delineate key aspects regarding adherence to opioid therapy…” with the intent being to improve care Arnold RM et al. Am J Med 2006;119:292-6

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Why are OA so popular?

• Reflects a belief among clinicians that OA:

▫ Improve the quality of care for patients on chronic opioid therapy ▫ Address concerns about opioid abuse and diversion among these patients  Legal protection for the prescriber?  Prescriber sense of “mastery” in opioid prescribing

• A recommended strategy by: ▫ ▫ ▫ ▫ ▫

American Academy of Pain Medicine American Pain Society Federation of State Medical Boards Pain and addiction experts Regulatory agencies

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What’s in the small print?  Information on opioid use and abuse (risks and benefits)  Goals of treatment, side effects, concerns related to opioid therapy

 Potential behavioral concerns    

Patients repeatedly “losing” medications Unwilling or unable to store medications in a safe place Repeatedly running short/asking for early refills Multiple prescribers and/or pharmacies

 Rules of conduct

 Random urine drug screens  Having only one opioid prescriber  Having only one pharmacy to fill prescriptions

 Criteria for treatment termination (“you’re fired!”)  More draconian content/consequences?

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Justifications for Opioid Agreements  Adherence

 Primary goal of an AO is to promote patient adherence to opioid therapy  Adherence is defined as “self-administration of medications in prescribed amounts and at prescribed intervals” and “includes obtaining a drug from a single prescriber and avoiding the use of other licit or illicit abusable drugs other than those approved by this single prescriber.”

 Informed consent

 Are most OA truly structured in a fair-balanced fashion to discuss the risks and benefits of opioid therapy?  Or, are prohibited behaviors and points of treatment termination the most commonly included elements of the opioid contract?

Arnold RM et al. Am J Med 2006;119:292-6

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Justifications for Opioid Agreements • Legal Risk Management

▫ Thought that documenting the disclosure of potential risks and harms of opioid therapy to patients through OAs may protect prescribers from legal liability in the event of adverse outcomes.  Do we do agreements for chemotherapy? Warfarin?

Amiodarone?

▫ Thought an OA may diminish the changes of patients initiating tort actions against clinicians

• Practice Efficiency

▫ Proponents argue that OAs help systematize and coordinate the care of opioid-requiring patients ▫ OA is a readily accessible “rule book” Arnold RM et al. Am J Med 2006;119:292-6

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What’s the harm in OAs? (even if they don’t HELP?)

 OAs may not be enforceable, and may be considered an “unconscionable adhesion contract”

 Adhesion contract – “a standard-form contract prepared by one party, to be signed by the part in a weaker position, usually a consumer who has little choice about the terms.”  Unconscionable – “an absence of meaningful choice on the part of one of the parties together to the other party”

 The patient –physician relationship is asymmetrical

 Large power disparity  “Sign this if you wish me to prescribe the medication that we hope and expect to relieve your pain. If you refuse you will need to find another doctor.”

Collen M. J Law Med Ethics 2009

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Are OAs LIKELY to work? • If someone enters into a patient-prescriber relationship to obtain an opioid, with criminal intent in mind, do you THINK they would hesitate to sign an OA?

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Rock and a hard place  What happens when the patient doesn’t follow their part of the bargain?  “You can only get pain medications from me!”

 Patient tells you they had significant pain, went to ER the night before, and received a small number of opioid tablets or capsules.  Patient lives in a homeless shelter and someone stole their prescription. What if it happens again in several months?

• Do you wean them/discharge them?

• Do you care about their pain?

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• Identified studies of the association of treatment agreements and UDT with opioid misue • Search strategy

▫ Original research published in English, Spanish or French ▫ Outpatients with chronic noncancer pain prescribed opioids for at least 3 months ▫ Sample size of 50 patients or more ▫ Opioid misuse was defined as “…drug abuse, drug misuse, aberrant drug-related behavior, diversion, addiction.”

Starrels J et al. Ann Intern Med 2010;152:7120720

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 11 studies were identified

 None evaluated opioid overdose, abuse or dependence  Six were in pain specialty settings, five in primary care settings  Seven used OA plus UDT (+/- monthly visits)  Three used OA only (+/- monthly visits)  One used routine UDT only

 “Our systematic review reveals that weak evidence supports the use of opioid treatment agreements and urine drug testing to reduce opioid misuse, despite the theoretical benefits of these strategies.

This lack of evidence may explain in part why they have not been widely adopted in primary care.”

Starrels J et al. Ann Intern Med 2010;152:7120720

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Starrels J et al. Ann Intern Med 2010;152:7120720

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Editorial – Heit and Gourlay  “Despite the enthusiastic endorsement of treatment agreements and UDT by some regulators, educators and clinicians, there remains little evidence documenting their effectiveness in preventing or treating drug misuse or addiction.  The lack of clear definitions of these interventions makes comparisons of the few studies that do exist difficult.  Clinicians should not assume that there is no “down side” to the overzealous use of either of these tools. The potential harm from using these strategies include patients forgoing pain treatment because of undue stigma and clinicians undertreating pain because of the perceived burden of opioid risk management.  Overly restrictive treatment agreements can make it difficult for any patient to stay within accepted boundaries, resulting in inevitable departures from treatment adherence.”

Heit HA, Gourlay DL. Ann Intern Med 2010;152:747-8

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How does an OA make your patient feel?  OAs have the potential to stigmatize opioid therapy and the patients who receive opioids

 Opioid therapy already comes loaded with powerful social means and connotations that engender prescriber biases against opioid treatment and discrimination against patients requiring opioids

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Center for Practical Bioethics • April 2010 convened a panel of painmanagement professionals to consider the usefulness and the ethical propriety of “Pain Contracts” (OAs) ▫ Focused on professional, patient and policy issues regarding healthcare providers’ use of OAs

• Published November 2010 – panel debates whether OAs are used more for reducing potential risks of therapy to patients or managing perceived risks to prescribers from regulatory and law enforcement agencies.

American Journal of Bioethics Nov 2010

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Center for Practical Bioethics • Panel concludes: ▫ …the lack of data about the benefit of pain agreements/contracts, concerns about increasing disparities and further stigmatization of pain patients, and other possible unintended consequences, coupled with the importance of preserving the integrity of medicine from inappropriate outside influence, are all very strong reasons why the authors of this paper cannot support the universal utilization of pain contracts/ agreements at this time.”

So what shall we do instead? What’s the plan, Stan?

American Journal of Bioethics Nov 2010

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THINK When Assessing Opioid Risk

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THINK When Assessing Opioid Risk • T – Take advantage of various resources, including state prescription drug monitoring programs and urine drug screens • H – Have data in hand, such as the patient’s pain feedback based on visual analog scales and activity reports, along with imaging scan results • I – Don’t ignore your intuition, but remain attuned to your own “subconscious biases: • N – “No” is a valid answer if it’s not in the patient’s best interest • K – Know the panoply of related laws and regulations, including from the state and the US DEA. Pharmacy Practice News May 2011, Interview of Dr. Chris Herndon, source for THINK: Drs. JENNIFER STRICKLAND and ERNEST DOLE

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Bottom Line on OAs • There is limited evidence that such agreements significantly reduce opioid abuse • There are ethical concerns about their equitable implementation and enforcement • The objectives can be overly complex and illdefined • Their implementation can add time and cost to healthcare delivery

http://pain-topics.org/faqs/index1.php

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What do we REALLY THINK?

By all MEANS Inhale!

Marijuana for what Ails You!

Mary Lynn McPherson, Pharm.D., BCPS, CPE University of Maryland School of Pharmacy

42

Not A New Concept Evidence of medical marijuana in Ancient Chinese, Egyptian, Greek, and Indian history 1839: William O’Shaughnessy introduces cannabis to the UK as a sedative, hypnotic and anticonvulsant 1851: U.S. Pharmacopoeia • 1890: Sir John Russell Reynolds ▫ “…in almost all painful maladies I have found Indian hemp by far the most useful of drugs.”

1920’s: Mexican immigrants Fowler, CJ. Curr Drug Targets, 2005; 4: 685-696.

Bonta L, et al. Rev Bras Anestesiol, 2008; 58 (3): 267-279

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“Reefer Madness” 1935

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The Secret’s Out… • 1937: Marijuana Tax Act 1960’s: Cannabis as an act of youth defiance 1970: Controlled Substances Act 1970-72: National Commission on Marijuana and Drug Abuse (The Shafer Commission)

McCarberg BH, Barkin RL. Amer J Ther, 2007; 14: 475-483

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And The Decision Is… • “Marijuana, A Signal of Misunderstanding” ▫ “…The actual and potential harm of use of the drug is not great enough to justify intrusion by the criminal law into private behavior, a step which our society takes only with the greatest reluctance.”

– Raymond P. Shafer

• President Nixon buried this commission's findings and went on to sign the Controlled Substances Act Marihuana, A Signal of Misunderstanding, Commissioned by President Richard M. Nixon, March, 1972.

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Role of Endocannabinoid System • To maintain homeostasis in health and disease ▫ Results in increased endocannabinoid release or up-regulation of receptors in particular cells and tissues ▫ Provides “autoprotection”  Suppressing unwanted signs and symptoms or slowing diseases

Pertwee RG. Br J Pharmacol, 2009; 156: 397-411

This is Your Brain‌

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This Is Your Brain On Cannabinoids‌

CB1 receptors are also found in the dorsal spinal cord ganglia, intestinal nervous system, adipocytes, endothelial cells, hepatocytes, muscular tissue and GI tract http://scienceblogs.com/corpuscallosum/2007/07/rimonabant_acomplia_problems_w.php

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Potential Therapeutic Targets Neuropathic pain Anti-emetic Appetite stimulation Atherosclerosis/other cardiovascular disorders Inhibition of angiogenesis/ malignant tumor growth Anxiety disorders, ADHD, depression, PTSD Glaucoma, cough, cholestatic pruritis

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Types of Cannabinoids • Endocannabinoids (endogenous) • Exogenous cannabinoids ▫ Synthetic Cannabinoids ▫ Phytocannabinoids

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Endogenous Cannabinoids • Endogenous compounds ▫ Anandamide ▫ 2-arachidonylglycerol (2-AG) ▫ Palmitoylethanolamide (PEA) • Retrograde neuronal modulators on Ananda =“bliss” neurotransmitter systems affecting pain, movement, muscle tone, and emotion regulation • Rapid up-regulation and subsequent metabolism Martin WJ. IASP Newsletter, 1999:1-9.

McCarberg BH. J J Pain Palliat Care Pharmacother , 2007; 21(3): 19-28.

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Exogenous Cannabinoids 53

• Sixty-six cannabinoids derived from the Cannabis Sativa L. • Cannabidiol (CBD): 1934 ▫ Major cannabinoid component of marijuana ▫ Little affinity for CB1 or CB2 ▫ Antioxidant and antiinflammatory properties • Δ9 Tetrahydrocannabinol (THC): 1964 ▫ Primary active component of marijuana ▫ Partial agonist of CB1/CB2 ▫ Responsible for most common effects, especially psychoactivity Burns, TL, Ineck JR. Ann Pharmacother, 2006; 40: 251-60 McCarberg BH. J J Pain Palliat Care Pharmacother , 2007; 21(3): 19-28.

Cannabinoids and Pain Pathways Thalamus

+

Periaqueductal grey

Possible sites of action Endocannabinoids

+ +

Rostral ventromedial medulla ?

-

Dorsal root ganglion

Dorsal horn of spinal cord

Peripheral terminals of primary afferent neurons Aβ, A§ & C-fibres

Adapted from Di Marzo 2001

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Commercial Cannabinoids • Nabilone (Cesamet® US 2006; Canada 1985) ▫ Synthetic analogue of THC ▫ Suppression of chemotherapy-induced nausea/vomiting ▫ Up to 6 mg daily in divided doses • Dronabinol (Marinol® 1985) ▫ Synthetic THC ▫ Anti-emetic/Appetite stimulant for AIDS patients ▫ 5-20 mg daily • Sativex® ▫ Extracted THC:CBD (50:50) ▫ Central neuropathic pain in MS ▫ Adjunct for adults with advanced cancer Pertwee RG. Br J Pharmacol, 2009; 156: 397-411

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Oral Cannabinoids • • • •

Dronabinol (Marinol®) and Nabilone (Cesamet®) Low, variable bioavailability (5-20%) Significant variability of response Unpredictable and delayed onset of action ▫ Onset 30-60 minutes, peak 2-3 hours ▫ Makes difficult for patients to effectively titrate • First-pass metabolism in liver results in psychoactive metabolite, 11-hydroxy-THC • Soft gelatin capsules – unable to be chewed/crushed

McCarberg BH. J Pain Palliat Care Pharmacother , 2007; 21(3): 19-28.

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Inhaled Cannabinoids • Not standardized ▫ Typical joint delivers ≈ 20 mg THC ▫ 10-35% bioavailability • Results in rapid rise/fall of plasma concentrations (peak at 30 minutes, duration 23 hours) ▫ Rapid onset of psychoactivity ▫ Significantly more reinforcing • Smoking associated with carcinogenesis • Vaporized formulations ▫ Do not remove polyaromatic hydrocarbons Squire, PL. Painview, 2009; 5(1): 4-5.

McCarberg BH. J Pain Palliat Care Pharmacother , 2007; 21(3): 19-28.

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CB1/CB2 Agonist Clinical Effects Common

Less Common

▫ Disorientation/“high” ▫ Altered perception ▫ Impaired memory/ concentration ▫ Tremor ▫ Impaired balance ▫ Hypotension ▫ Blurred vision ▫ Constipation/diarrhea ▫ Dysphoria ▫ Paranoia/hallucinations

Pertwee RG. Br J Pharmacol, 2009; 156: 397-411

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Clinical Significance • Smoked cannabis may be an effective option in patient with medically intractable neuropathic pain (e.g., HIV, cancer); other symptoms • Smoking is not an ideal formulation • Psychosis is also a concern in some patients • Dose limiting side effects should be monitored carefully

Number Needed To Treat **Dronabinol

Not able to calculate from study data

3.5

Smoked

Sativex速

8.5 2.6 4.4 4.9 2.7 3.3 2.0 4.8

Wu CL, Raja N. J Pain 2008; 9(1):S19-30.

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Medical Marijuana?

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Pot Politics ‌if it’s an issue of doctors prescribing medical marijuana as a treatment for glaucoma or as a cancer treatment, I think that should be appropriate because there really is no difference between that and a doctor prescribing morphine or anything else. . . .

- President Barack Obama Tribune,

As told to the Mail Oregon, 2008

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Liability • Addiction ▫ Evidence that occurs in heavy chronic users ▫ 10% of regular marijuana users become addicted Less than that of alcohol (15%), opioids (23%), or tobacco (32%) ▫ Use under supervision of licensed health provider?

• Diversion ▫ Google search results in 1,210,000 “hits” ▫ Contemporary phenomenon for FDA-approved controlled substances Cohen PJ. J Pain Palliat Care Pharmacother, 2009; 23: 1, 4-25.

Marijuana with Advanced Illness Question

%

MJ should be legalized for medicinal use

90%

See MJ being used in practice, or get questions from patients/family

47.8%

Would you “turn a blind eye” to patient smoking MJ with good effect

75%

Marijuana has medical benefits

86.1%

Nonphysicians “strongly agreed” with this statement Physicians more likely to “somewhat agree” with this statement Acquisition of marijuana “Obtain” small amounts for a loved one

70%

Get from a pharmacy

88.7%

Grow their own supply

51.2%

Is marijuana addictive?

Disagree (> 50 years of age/< 50 years of age) J Pall Med 2011;14(12).

64%/47%

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Cannabinoids and PTSD • The endocannabinoid system is known to be an important regulator of stress and anxiety in PTSD • The automatic stress/fear body response is controlled by the four-part brain pathway called: ▫ Amygdala-hypothalamic-pituitary-adrenal axis  Amygdala – scans environment for threats to your existence  Remembers all fearful events from your past  Controls coping and adapting to stress of challenges in your environment

▫ Hypothalamus/pituitary gland – releases stress hormones (adrenalin, cortisol, epinephrine)

• Cannabinoids can wind this system back down

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Case of JB • JB is a 30 year AAM residing in the city of Baltimore, referred to the Pharmacotherapy Pain Clinic at UMMS • Patient involved in a fight 2 years previously, suffered a major knife wound, left with significant residual neuropathic pain • Pain eventually controlled on methadone, gabapentin and despiramine • Let’s check that urine…

http://ocnorml.org/medical_marijuana_humor.htm

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To Put It Bluntly…

• Evidence has begun to mount supporting medical marijuana efficacy • Medical marijuana needs to be evaluated scientifically by the FDA • Political ideology should not govern sound medical decisions • If standards of safety and efficacy are met, the drug should be approved and appropriately scheduled

Cohen PJ. J Pain Palliat Care Pharmacother, 2009; 23: 1, 4-25.

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Stop Blowing Smoke Up My Skirt!

DONâ&#x20AC;&#x2122;T Inhale! Marijuana and Pain Management

Kathryn Walker, Pharm.D., BCPS, CPE University of Maryland School of Pharmacy Union Memorial Hospital Palliative Medicine Specialist

Marijuana is a Schedule I Controlled Substance • “the clear weight of the currently available evidence supports this classification, including evidence that smoked marijuana has a high potential for abuse, has no accepted medicinal value… and there is a general lack of accepted safety for its use even under medical supervision”

The DEA Position on Marijuana. Jan 2011. http://www.justice.gov/dea/marijuana_position.pdf

The Wild, Wild West

“Medical” Marijuana?

• Active compounds +400 chemicals  THC, Cannabidiol, Cannabinol

• Today’s US marijuana twice as much THC (the active ingredient) as marijuana 20 years ago Amount of THC in seized samples= 10.1% <4% in 1983 In UK, some preparations contain 15-30% (resin) “New Report Finds Highest Levels of THC in U.S. Marijuana to Date.” Office of National Drug Control Policy Press Release. May 14, 2009. www.independent.co.uk.

Active Ingredient • Comparison to cigarettes (3 MJ= 1 pack Cig) ▫ ▫ ▫

Ammonia (x20) Hydrogen cyanide, nitric oxide, aromatic amines (x3-5) Tar and CO (x7)

“Marijuana Smoke Contains Higher Levels of Certain Toxins Than Tobacco Smoke.” Science Daily, December 18, 2007. http://sciencedaily.com/releases/2007/12/071217110328.htm.

10-74 “Cannabis More Toxic than Cigarettes: Study,” French National Consumers’ Institute, 60 Million Consumers (magazine) April 2006, www.theage.com.au

Are We Alone?

The Word on the Streetâ&#x20AC;Ś Organization

Summary of View

AMA

Need more research, not endorsed, does not meet current standards for prescription drug

ASAM

Should have to meet same standards as other Rx, no smoking

ACS

No smoking, no legalization of marijuana, needs research

AGS

Side effects, short duration, does not alter course of glaucoma- not recommended in any form

AAP

Research supported on cannabinoids, not smoked marijuana

NMSS

Studies do not demonstrate clear benefit in MS compared to existing medications

BMA

Too many harmful effects, cannot have the public thinking it is safe

IOM

Little future in smoked marijuana as a medication The DEA Position on Marijuana. Jan 2011. http://www.justice.gov/dea/marijuana_position.pdf

What’s the cost, literally?

• One joint weighs ~ 0.9 grams with 3.56% THC (Abrams study) • 0.9 g = 0.03 oz • ¼ oz = 7.1 g (1 oz = 28 g) • 1 oz = 31 joints • 3 joints per day = need 3 oz per month

$900-1,400/month

Red = abundant CB1 receptor expression Black = moderately abundant CB1 receptor expression

Cannabis Stats Cannabis form

Smoked Oral THC:CBD 1:1

Onset

Peak

Duration

Seconds to minutes 30–90 minutes 30–150 minutes

15–30 minutes

2–3 hours

2–3 hours

4–12 hours

1.5–4 hours

6-8 hours

Grotenhermen F (2003), Sativex® Product Monograph (2005)

Behind the Stats…

• RCT of chronic neuropathic pain (n=23) ▫ 5 days cannabis through a pipe at designated potency (0%,2.5%, 6%, or 9.4%) ▫ TID for 5 days then 9 day washout period ▫ Measured daily pain intensity and adverse effects

Ware MA, et al. CMAJ. 2010; 182:E694-701.

Behind the Stats…

• The average daily pain intensity…was lower on the…9.4% v. 0% THC (5.4 v. 6.1, respectively; difference = 0.7, 95% confidence interval [CI] 0.02–1.4, p=0.023).

• Conclusion: “reduced intensity of pain” Intensity

0%

2.5%

6%

9.4%

Average

6.1 (1.6)

5.9 (1.9)

6.0 (1.8)

5.4 (1.7) **

Highest

7.1 (1.4)

7.0 (1.6)

7.0 (1.5)

6.5 (1.6)

Lowest

5.1 (2.1)

5.0 (2.4)

4.8 (2.4)

4.4 (2.2)

* p<0.05 in comparison with 0% THC Ware MA, et al. CMAJ. 2010; 182:E694-701.

The Rest of the Story…

• 82% have used cannabis before • Adverse Events: 0% (n=21)

2.5% (n=22)

6% (n=21)

9.4% (n=22)

Dizziness

2

3

4

4

Headache

3

3

7

4

Burning Sensation/Pain at site of admin

5

4

6

5

Lack of Concentration

1

2

2

2

Throat Irritation

3

4

3

3

Nausea

1

2

2

1

Fatigue

2

3

3

2

Ware MA, et al. CMAJ. 2010; 182:E694-701.

Other Consequences • • • • • • •

Link to depression/suicidal thoughts (x2-3) 1 Link to psychosis/schizophrenia1 Cancer risk2 Bullous lung disease (>cigarette smokers) Infertility and affects infants after birth Risk of infection (r/t fungal spores) Driving “drugged”

1. The DEA Position on Marijuana. Jan 2011. http://www.justice.gov/dea/marijuana_position.pdf 2. State of California, EPA, “Chemicals Known to the State to Cause Cancer or Reproductive Toxicity, September 11, 2009. http://www.oehha.ca.gov/prop65_list/files/P65single091001.pdf.

The Blunt Truth…

• Phase II DB, PC crossover trial of chronic neuropathic pain in HIV (DSPN, n=28) ▫ Allowed titration of THC (1%-8%) ▫ 5 days cannabis cigarette  Each day had 4 smoking session every 90-120 min during 8h study period

• Measured pain quality and impact using Descriptor Differential Scale (DDS), McGill, VAS

Ellis RJ, et al. Neuropsychopharmacology. 2009; 34:672-680.

The Blunt Truth…

• Median difference in DDS pain intensity change: 3.3/20 points (effect size = 0.60; p = 0.016).

• The proportions of subjects achieving at least 30% pain relief with cannabis versus placebo were 0.46 (95%CI 0.28, 0.65) and 0.18 (0.03, 0.32). ▫ NNT: 3.5

• Median VAS changes -17/100 for THC v. -4/100 for placebo (p<0.001) • McGill results?

Ellis RJ, et al. Neuropsychopharmacology. 2009; 34:672-680.

The Blunt Truth…

• Most split between 2% and 4% THC after titration (some 1%, 6% and 8%) • 96% of patients had previous cannabis experience • No significant difference in analgesic use • “As measured by the POMS, SIP, and BSI, there were similar improvements in total mood disturbance, physical disability, and quality of life for the cannabis and placebo treatments (data not shown).”

Ellis RJ, et al. Neuropsychopharmacology. 2009; 34:672-680.

Put it in Your Pipe and Smoke it?

• Too many variables to prescribe or endorse as HC providers ▫ Questionable (possibly dangerous) delivery system ▫ No standards for dosing, potency, rate of delivery ▫ Administration variable  Technique  Method

▫ Response variable  History with THC  Types of pain  Drug interactions

Efficacy and Safety?

Cast Your Vote Todayâ&#x20AC;Ś 1-800-Approve-Rx

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What do we REALLY THINK?