The Endocannabinoid System: It’s not just about weed!

J. Randle Adair, D.O., Ph.D.Diplomate, American Board of Internal Medicine

Certified, American Society of Addiction Medicine

Attending, Adult Hospital Medicine

Albuquerque VA Medical Center

Albuquerque, NM

What is weed?• Americans for Safe Access, a medical marijuana advocacy group,

stated in its website article "Research: Definitions and Explanations" (accessed Dec. 7, 2006):

• "...there are 483 different identifiable chemical constituents known to exist in cannabis. The most distinctive and specific class of compounds are the cannabinoids (66 known), that are only known to exist in the cannabis plant.

Other constituents of the cannabis plant are: nitrogenous compounds (27 known), amino acids (18), proteins (3), glycoproteins (6), enzymes (2), sugars and related compounds (34), hydrocarbons (50), simple alcohols (7), aldehydes (13), ketones (13), simple acids (21), fatty acids (22), simple esters (12), lactones (1), steroids (11), terpenes (120), non-cannabinoid phenols (25), flavonoids (21), vitamins (1) [Vitamin A], pigments (2), and elements (9).

The very most of these compounds are found in other plants and animals and are not of pharmacological relevance with regard to the effects exerted by cannabis preparations."

Are there differences in weed?

• Indica: Indica has a higher CBD (Cannabidiol) content than THC. CBD has a

sedative effect, producing a more relaxing/sleepy type of effect. According to extensive anecdotal evidence, Indica strains are more effective in treating ailments including anxiety, pain, nausea, appetite stimulation, sleep, muscle spasms and tremors, and much more.

• Sativa:Sativa conversely has a higher THC content making it much more potent. This creates a more cerebral, energetic, and soaring effect. These Sativa strains create more of a stimulant effect, which has shown to be effective in treating migraines, pain, nausea, depression, and is also good for appetite stimulation.

Camí, J. et al. N Engl J Med 2003;349:975-986

Neural Reward Circuits Important in the Reinforcing Effects of Drugs of Abuse

The Architecture: The Synapse

• from Mihic & Harris, 1997

Camí, J. et al. N Engl J Med 2003;349:975-986

Metabotropic Mechanisms of Action of Drugs of Abuse

Are there valid medical uses for endocannabinoid drugs?

Marinol• "Marinol (dronabinol) is the only cannabinoid with approval for marketing in the United

States.... • Marinol is manufactured as a capsule containing THC in sesame oil; it is taken orally. It

was approved by the FDA in 1985 for the treatment of nausea and vomiting associated with cancer chemotherapy. In 1992, the FDA approved marketing of dronabinol for the treatment of anorexia associated with weight loss in patients with AIDS. The preclinical and clinical research on THC that culminated in the FDA's 1985 approval was supported primarily from the National Cancer Institute (NCI), whose research support goes back to the 1970s....

• Marinol is synthesized in the laboratory rather than extracted from the plant. Its manufacture is complex and expensive because of the numerous steps needed for purification. The poor solubility of Marinol in aqueous solutions and its high first-pass metabolism in the liver account for its poor bioavailability; only 10-20% of an oral dose reaches the systemic circulation.

• The onset of action is slow; peak plasma concentrations are not attained until two to four hours after dosing. In contrast, inhaled marijuana is rapidly absorbed....

• Marinol's most common adverse events are associated with the central nervous system (CNS); anxiety, confusion, depersonalization, dizziness, euphoria, dysphoria, somnolence, and thinking abnormality."

• http://medicalmarijuana.procon.org/view.answers.php?questionID=000089

Rimonabanta/k/a

Accomplia

Despres J et al. N Engl J Med 2005;353:2121-2134

Effect of Placebo or Rimonabant for 52 Weeks on Body Weight, Waist Circumference, Plasma Triglyceride Levels, and High-Density Lipoprotein (HDL) Cholesterol Levels

Other scientific trials• Rimonabant improves tobacco cessation

and blocks inhibition produced by alcohol in amygdala projections

• Modulation of CNR1 gene receptor reduces cocaine dependence and IV drug use

• Stimulation/blockade of EC systems modulates GABA, glutamate and dopamine systems

More scientific studies• “Knockout” of CB1 receptors blocks social

withdrawal in PCP-induced schizophrenic activity in mice

• Chronic stimulation of CB2 liver receptors results in regression of fibrosis in cirrhosis

• High incidence of Q63R polymorphism of the CB2 gene in Japanese alcoholics and depressed subjects

CB2 and pain• CB2 agonists (AM1241) inhibit nociception

without producing CNS effects – The effects do not cross-over to morphine effects

• CB2 appears to modulate:– Acute pain– Chronic inflammatory pain– Post surgical pain– Cancer pain– Pain associated with nerve injury

Are there valid medical uses for marijuana?

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Medical Cannabis in the U.S.

Many other states have legislation pending AL, AZ, CT, DE, IL, KS,

MD, MN, NH, NY, OH, PA, SD, TN, WI

Six states recognize or regulate medical marijuana production or dispensaries CA, CO, ME, NJ, NM, RI

Shift in public acceptance over time

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Purpose of the Program

The Lynn and Erin Compassionate Use Act:

“The purpose of the act is to allow the beneficial use of medical cannabis in a

regulated system for alleviating symptoms caused by debilitating medical conditions and

their medical treatments”

Established July 2007

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NM Medical Cannabis Program

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NM Program Structure

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Qualifying Conditions

Original Conditions Cancer Glaucoma HIV/AIDS Multiple Sclerosis Epilepsy Spinal Cord Damage with

Intractable Spasticity Patients in hospice care

Conditions Added Painful peripheral

neuropathy Intractable

nausea/vomiting

Severe anorexia/cachexia Hepatitis C infection

currently receiving antiviral treatment

Crohn's disease Post-traumatic Stress

Disorder Amyotrophic Lateral

Sclerosis Severe Chronic Pain Autoimmune mediated

inflammatory arthritis

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Numbers of Licensed Patients

0

500

1000

1500

2000

2500

Jul-07Sep-07Nov-07Jan-08Mar-08May-08Jul-08Sep-08Nov-08Jan-09Mar-09May-09Jul-09Sep-09Nov-09Jan-10Mar-10May-10

Date

Cu

mu

lati

ve

# A

pp

rov

ed

2043

7 conditions added

1 condition added

1 condition added

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Qualifying Conditions

Original Conditions Cancer Glaucoma HIV/AIDS Multiple Sclerosis Epilepsy Spinal Cord Damage with

Intractable Spasticity Patients in hospice care

Conditions Added Painful peripheral

neuropathy Intractable

nausea/vomiting

Severe anorexia/cachexia Hepatitis C infection

currently receiving antiviral treatment

Crohn's disease Post-traumatic Stress

Disorder Amyotrophic Lateral

Sclerosis Severe Chronic Pain Autoimmune mediated

inflammatory arthritis

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Distribution System in NM must provide for…..

Production facilities within New Mexico Housed on secure

grounds

Operated by producers licensed by the DOH

Distribution to qualified patients or their qualified caregiver

Licensed Non-profit Producers

Personal Production

License

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Supply Options

Any patients enrolled in the medical cannabis program may apply for a personal production license

Grants permission to grow 4 mature cannabis plants and 12 seedlings at any given time

$15 fee – waived if income <400% of the Federal Poverty Guidelines

Non-profit businesses that have been granted a production license from the Department of Health

Regulations for oversight by DOH

Allows up to 95 plants + seedlings in total

Purchase of product is an individual transaction between program participant and producer (DOH does not control pricing or product)

Personal Production License

Licensed Non-profit Producers

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What the Program is…..

What the program IS…. An opportunity for patients who have not

gained relief from other interventions (medical, surgical) to find relief of symptoms

Compassionate use

What the program is NOT…. A primary medical therapy for conditions

A naturopathic option for patients who prefer not to use allopathic medications

Legal cover for those who wish to use for non-medical or mixed purposes

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What does a provider certification mean?

A recommendation that you feel a patient may benefit from the use of medical cannabis to relieve symptoms

Verification That the patient has the diagnosis stated

That the patient has symptoms unrelieved by other treatments

That the potential benefits of cannabis use outweigh the risks

It is NOT a prescription for cannabis!!

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Application Requirements

Consent to Release Medical Information Government issued photo I.D. confirming

New Mexico residency for patient Medical Provider Certification

Provider information Qualifying medical condition Certification

Debilitating medical condition Symptoms requiring cannabis Risks vs. benefits

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Diagnosis and special requirements

Fill-in section

Provider Information

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Some Conditions have Additional Requirements

Severe Chronic Pain Requires a second certification from a specialist with

expertise in pain management or expertise in the condition that is causing the Severe Chronic Pain

PTSD Requires confirmation of the diagnosis from a

psychiatrist Glaucoma

Requires confirmation of the diagnosis from an ophthalmologist

Painful Peripheral Neuropathy Medical records must be sent to document objective

evidence of neuropathy Auto-immune mediated inflammatory arthritis

Certification must come from a rheumatologist

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Application Requirements

Applicants are sometimes asked to submit additional medical records

Medical Records are requested on a case-by-case basis

Records may be requested in order to verify prior treatments, verify the debility of the patient’s condition, etc.

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Review Process Program staff verify that all required documents are

present. If documents are missing, staff contact the applicant.

IDB Medical Director reviews application Verifies provider’s authority to certify If needed, calls certifying provider for verification of the

patient’s medical condition and need for compassionate use

If denied, a formal notice is mailed to the patient. If approved, a ‘new patient packet’ is mailed to the

applicant. This includes: Copy of the Lynn and Erin Compassionate Use Act, Patient’s registry I.D. card Contact information for state-licensed producers

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For More Information…….

Website www.nmhealth.org/IDB/

medical_cannabis.shtml Program Staff

Program Manager: Dominick Zurlo Medical Director: Linda Gorgos

Phone (505) 827-2321 Email medical.cannabis@state.nm.us

The 7% Solution to the Recession!!!

• Currently before the NM State legislature is a proposal to apply a 7% “gross receipts” tax on producer revenues

• Indistinguishable from tobacco or alcohol taxes

• Similarly “addictive” as a State policy• About as medically scientific as chewing

chicona bark to get the antimalarial effect of quinine.

Now, if nothing else, you understand………..

The “munchies”

Thank you!!!