The Endocannabinoid System: It s not just about weed J. Randle Adair, D.O., Ph.D. Diplomate, American Board of Interna

1. The Endocannabinoid System: It�s not just about weed!J. Randle Adair, D.O., Ph.D.Diplomate, American Board of Internal MedicineCertified, American Society of Addiction Medicine Attending, Adult Hospital Medicine Albuquerque VA Medical Center Albuquerque, NM

2. 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."

3. 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.

5. The Architecture: The Synapse from Mihic & Harris, 1997

14. Are there valid medical uses for endocannabinoid drugs?

15. 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

16. Rimonabanta/k/aAccomplia

18. Figure 1. Effect of Placebo or Rimonabant for 52 Weeks on Body Weight, Waist Circumference, Plasma Triglyceride Levels, and High-Density Lipoprotein (HDL) Cholesterol Levels. Body weight and waist circumference were measured at randomization (week 0) and every four weeks thereafter until week 52, and plasma HDL cholesterol and triglyceride levels were measured at randomization (week 0) and every three months thereafter until week 52. Values are shown as means {+/-}SE for all patients for whom measurements were taken at each visit (lines); P values were obtained after the repeated-measures analysis. P values correspond to the mean difference between the rimonabant groups and the placebo group.Figure 1. Effect of Placebo or Rimonabant for 52 Weeks on Body Weight, Waist Circumference, Plasma Triglyceride Levels, and High-Density Lipoprotein (HDL) Cholesterol Levels. Body weight and waist circumference were measured at randomization (week 0) and every four weeks thereafter until week 52, and plasma HDL cholesterol and triglyceride levels were measured at randomization (week 0) and every three months thereafter until week 52. Values are shown as means {+/-}SE for all patients for whom measurements were taken at each visit (lines); P values were obtained after the repeated-measures analysis. P values correspond to the mean difference between the rimonabant groups and the placebo group.

19. 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

20. 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

21. 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

22. Are there valid medical uses for marijuana?

23. 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

24. 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�

25. NM Medical Cannabis Program

26. NM Program Structure

27. 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

28. Numbers of Licensed Patients As of June 16 2043 cumulative approvals: 1909 active patients 791 have personal production licenses = 41%As of June 16 2043 cumulative approvals: 1909 active patients 791 have personal production licenses = 41%

29. 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

30. 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 1/3 of patients have personal production license1/3 of patients have personal production license

31. 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)

32. 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

33. 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!!

34. 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

36. 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

37. 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.

38. 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 Once enrolled yearly renewal for continued participation � requires signature from doctor each yearOnce enrolled yearly renewal for continued participation � requires signature from doctor each year

39. 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

40. 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.

41. Now, if nothing else, you understand���.. The �munchies�

42. Thank you!!!