Cannabis In Health Disease Presented at Omnilore Forum

Cannabis In Health & Disease Presented at Omnilore Forum January 31, 2019 Rancho Palos Verdes, California David Bearman, MD Executive VP, AACM Santa Barbara, California www. davidbearmanmd. com

Presentation Overview Introduction ● History ● Nutraceutical ●

Introduction

David Bearman, M. D. ● Worked at all levels of government ● 18 years clinical practice in Cannabinoid Medicine ● Executive Vice President, AACM ● Named Doctor of the Day by Wall Street Journal ● Author—Drugs Are Not The Devil’s Tools: Greed, Discrimination, The War on Drugs and How Medical Marijuana is Changing the Paradigm ● Author—Demons, Discrimination, and Dollars ● Author—Cannabis Medicine: A Guide to The Practice of Cannabinoid Medicine

This Lecture Will Address ● History Of Medicinal Cannabis ● Prohibition Propaganda & Folly ● Modern Medicinal Cannabis

Medical Marijuana States

Brief History

Shen Nung Ping Ts’oa Ching 2637 B. C. ● Estimated date of the first known pharmacopeia. Yes, it contained cannabis. ● A recent Chinese excavation provides evidence of medicinal use in 2600 B. C.

Historical Use ● One of many grains used in porridge or gruel ● Nixons made gruel sound bad but it is nutritious ● Beer is made from cannabis and is actually a cousin to hops

Ancient Uses of Cannabis ● Cannabis medical attributes were well known in the ancient world. It was used as an analgesic, a childbirth anesthetic, for treating migraines, indigestion, and insomnia.

Cannabis is a Nutraceutical ● It contains: ◦ 512 molecules ◦ 113 cannabinoids ◦ 200+ terpenes

Endocannabinoid System Neurotransmitters ● Enzymes ● Receptors ● Dopaminergic system ●

Health Benefits ● ● ● ● Antioxidant Anti inflammatory Anti anxiety Omega-3 & -6 fatty acids Stress Reduction Sleep Aid Anti epileptic Anti proliferative

Treats movement disorder ● Anti nauseate / appetite stimulant ●

1839 Dr. William Brooke O’Shaughnessy ● He reintroduced cannabis into western medicine in 1839, upon his return to England from India. ● While in India he studied animals and treated human patients with cannabis.

USP 1854 -1941

U. S. /English 19 th Century ● 1839 O’Shaughnessy reintroduced Cannabis to Western Medicine ● 1854 -1941 Cannabis in the USP ● 1890 Queen Victoria- Sir Joshua Reynolds (PMS) ● 1898 Sir William Osler- migraine ● Patent Medicines-Lilly, Squibb, Merck, Parke-Davis (1870’s -1942 ● Early 1900’s 3 rd or 4 th most common drug ingredient

Sir William Osler The Father of Modern Medicine ● He wrote in the first textbook of internal Medicine (1892) that Cannabis was the best migraine treatment

Asthma Cigarettes ● There were several cannabis containing cigarettes for treatment of asthma available in the 1920 s. (They included Cannadonna , Cigares De Joy. And Grimauldi) ● Like Advair, cannabis is both an anti-inflammatory and a bronchodilator.

1920’S American doctors notes millions of Rx per year contained cannabis in the 1920’s L. Greensman Marijuana Recommended Collide: The Blunt Trush – Joshua Blight and Mark Miller, Dec. 5, 2012

University of Minnesota ● Both my father and my uncle graduated in the 1920 s from the U of M School of Pharmacy. Each, in different years , were assigned to make tincture of cannabis. ● My father said that they “had to be very careful because the ALCOHOL was illegal. ”

Major Pharmaceutical Companies Marketed Cannabis ● Eli Lilly, Squibb, Merck, Sharp and Dohme, Smith Bros. all sold numerous forms of Cannabis in the late 19 th and early 20 th century

Cult of Modernism ● Plant Based herbal medicine was in decline in the 30’s. It wasn’t modern and was not standardized. ● Modern – ◦ ◦ ◦ ◦ Telephone Phonograph Electric lights Automobile Camera Movies Flexner Report Manufactured pharmaceuticals

Muckrakers and Patent Medicine • Patent medicines were a mixed bag. Many worked. These nostrums often contained alcohol, cocaine, opium and/or cannabis. • Others were not only useless but could be downright dangerous. In 1903, Colliers, a mass market publication with wide circulation ran a multi-part expose on patent medicines

Phytochemicals Go Out of Style ■ Hundreds of thousands of cannabis containing Rxs were written per year in 1920 s and 30 s ■ 28 OTCs contain cannabis ■ The use of herbal remedies(including cannabis) was eclipsed by the cult of modernism ● Manufactured pharmaceuticals seen as modern ● Cannabis was not standardized ● Herbs =multiple compounds vs single compound

From Popular to Pariah ● ● ● ● ● 1897 Aspirin 1 st Manufactured Pharmaceutical 1902 Colliers Article 1909 Sikhs Vilified By SF Chronically 1910 Flexner Report 1914 Hearst’s Sonora 800, 000 Acre Ranch 1916 Schlicten Decorticator 1920 s Cult 0 f Modernism and 1930 Anslinger named head of FBNDD 1934 Did Lamont Dupont lobby Oliphant? ● 1930 s Propaganda focus on word Marijuana

Prohibition Propaganda

Lots of Propaganda

Who Can Forget Reefer Madness

Beware The Friendly Stranger

Pulp Fiction Demonizes Cannabis

Marijuana Tax Act 1937 AMA Testimony ● Dr. William Woodward-Doctor and attorney AMA Chief ● Two hours testimony ● The AMA opposed the Marijuana Tax Act ● The AMA knew of no harm from the medicinal use of cannabis ● The AMA pointed out that the federal government had no credible evidence

Dr. Woodward’s Words ● “The AMA knows of no dangers from the medical use of cannabis” ● He checked with The Bureau of Prisons, Children’s Bureau, Office of Education and divisions of mental health and pharmacy in the USPHS. None of them had one shred of evidence to support Mr. Anslinger’s claims. ● He was critical of the use of the word marijuana because the American public was familiar with hemp and cannabis

1941 - Out of United States Pharmacopoeia

Controlled Substances Act 1970 ● Cannabis placed in schedule I ● Retired CIA Directed the formation of a commission to study drug abuse and marijuana

Nixon Marijuana Commission Recommends legalizing recreational cannabis. Nixon rejected the recommendation.

Nixon and Special Agent Elvis

1978 - Federal Compassionate Access Investigational New Drug Program ● The Compassionate Investigational New Drug program, or Compassionate IND, is a United States Federal Government-run Investigational New Drug program that allows a limited number of patients to use medical marijuana grown at the University of Mississippi. ● It is administered by the National Institute on Drug Abuse. Closed to new entrants, there are four surviving patients who were grandfathered into the program.

1992 – Federal Compassionate Use ( IND) New Access Ends ● Dr. Mason, acting Surgeon General, was concerned that if too many patients were on the IND program, the public might get the idea that marijuana was actually good for you. (1) ● 15 patients were receiving government cannabis and another 35 approved for the program at the time the program was suspended in 1989. The program was terminated in 1992 and the 15 were grandmothered in.

Introduction to Modern Medicinal Cannabis

Modern Research ● 1949 Seizures Ramsey and Davis ● 1964 THC Structure Characterized Dr. Raphael Mechoulam ● 1970 s & 80 s Nausea & Appetite studies(NM, CA, TX. Fl. Il) ● 1985 Synthetic delta-9 -THC (Marinol) FDA Approved ● 1992 Endocannabinoid System ● 1999 GW Pharmaceuticals-Grew 6 strains ● 2000 California Marijuana Research Center est. ● 2002 Donald Abrams, M. D. (UCSF) ● 2005 Dr. Ware (Mc. Gill) ● 2006 Donald Tashkin, M. D. (UCLA) ● 2007 Donald Abrams, M. D. (UCSF) ● 2010 Sean Mc. Allister, Ph. D. (CPMG)

1949 - H. H. Ramsey M. D. and Jean Davis M. D. ● The first modern study on the medicinal value of cannabis. Seven subjects with intractable seizures. After treatment with cannabis 5 of the 7 subjects had no or extremely few seizures. ● They concluded: ”The cannabinols herein reported deserve further trial in noninstitutionalized epileptics. ” ● Federation Proceedings, Federation of American Society for Experimental Biology, vol. 8, l. Y 49, p. 284.

Tod Mikuriya MD ● Psychiatrist ● Target of Federal government. ● Read 1894 India Hemp Commission Report ● 1968 Selected NIMH marijuana research grants ● Co-author of Prop 215 ● Pioneer in marijuana movement.

1964 – Raphael Mechoulam characterizes the structure of Delta 9 THC

Marinol – 1985 ● The AIDS Epidemic saw widespread use of cannabis by HIV/AIDS sufferers. Cannabis addressed appetite stimulation , relief of pain and depression ● The government’s response was to encourage the development of synthetic THC. It was approved by the FDA in 1985. It’s Trade name is Marinol, generic name is dronabinol.

Cannabinoid & Cannabis ● Marinol=1 cannabinoid ● Cannabis=113 cannabinoids

The Endocannabinoid System characterized circa 1992 ● ● ● Endocannabinoid system is found in the human body. It is central to homeostasis. It is the largest neurotransmitter in the human brain and interacts with the dopaminergic system. ● It is composed of: ◦ RECEPTORS ● CB 1 Receptors found largely in the brain ● LB 2 Receptors found in the immune system and the periphery ◦ NEUROTRANSMITTERS ● Anandamide (AEA) – an endocannabinoid ● 2 AG -another endocannabinoid neurotransmitter ◦ ENZYMES ● FAAH -enzyme that metabolizes endocannabinoids ● MYGYL -another enzyme for endocannabinoids

Amygdala & Nucleus Accumbens Hippocampus -

Retrograde Inhibition

Cannabis: The Plant

Chemistry ● Cannabis 512 chemicals ● 113 cannabinoids (21 carbon molecule) ● Over 200 Terpenes ● Phenoids ● Flavonoids

Terpenes ● Terpenes give cannabis its distinctive odor. There are over 200 Terpenes in cannabis. They are found extensively in citrus fruit

Entourage Effect ● Postulated by Mechoulam in 1999. It is the idea that the various constituents of the plant act in concert, that the effect of the whole is greater or more effective than the sum of its parts. ● Many cannabinoids, terpenes and flavonoids acting together to cause a therapeutic benefit is the entourage effect

GW Pharmaceuticals - 1999 ● In 1997 House of Lords Science and Technology Committee Report ● In 1999 GW started doing research on tincture of cannabis for relief of muscle spasms and neurological pain associated with Multiple Sclerosis.

Sativex( Nabixamol) ● A tincture of cannabis sublingual spray ● Available in Canada since 2005.

Therapeutic Applications Of Cannabis ● ● ● Antinauseant/Antiemetic Appetite stimulant Analgesic Antiepileptic Anti Inflammatory Anxiolytic Antispasmodic Anti-depressant Sleep Aid PTSD treatment ADD/ADHD treatment

Nutraceutical Possible Benefits ● ● ● Cancer prevention (Taschkin) Heart attack health Neuro-protective Anti-anxiety Osteoporosis

Why Such Broad Effect? ● ● ● Largest neurotransmitter system Critical for homeostasis Retrograde inhibition Anti inflammatory Anti anxiety

Top 6 Conditions or Symptoms ● ● ● ● Pain Sleep Difficulties (Insomnia) Nausea Arthritis & Connective Tissue Disorders Migraine Anxiety Suppository

Other Commonly Treated Conditions ● ● ● ● ● ADD/ADHD Seizures Glaucoma Fibromyalgia, Restless Leg Syndrome, Complex Reflex Sympathetic Dystrophy Diabetic Peripheral Neuropathy Crohn’s Disease, IBS, Cyclical Vomiting Syndrome Depression PTSD

Mental Health ● ● ● ● Depression Anxiety/Panic Attacks Stress OCD Bipolar Disorder PTSD ADD/ADHD Autism/Asperger's syndrome

Benefits to AIDS Patients ● Appetite stimulant ● Anti nauseant ● Anti-depressant

Benefits to Cancer Patients ● ● ● Analgesic Anti Nauseant Appetite Stimulant Anti Depressant Anti proliferative (experimental & anecdotal)

Benefits for ADD/ADHD ● ● Effective Retrograde Inhibition Fewer side effects than stimulants Can be used in conjunction with stimulants

Benefits for PTSD ● ● Treats and decreases anxiety Helps control anger Decreases nightmares Symptoms possibly related to increased dopamine transporter

Efficacy ● ● ● ● History Anecdotes State Studies in eight states GW Studies 1999 - present House of Lords Report IOM Report 1982 and 1999 CMRC Studies 2000 -2010 20, 000 Research Studies

Routes of Administration ● ● ● Respiratory 1 -smoking 2 -Vaporizing Sublingual Oral

Safety ■ Government reports from: India/Britain(1894), U. S. (1972), Britain (1968), Canada(1973), Australia, (1978) Panama Canal Zone(1916 & 1931) ■ 1985 Delta 9 THC, FDA Approved ■ 1986 -1988 FDA Chief ALJ Young’s Findings of Fact ■ 2005 Tincture of Cannabis, Health Canada Approval ■ 2006 FDA approves Phase III Sativex Clinical Trial ■ 2010 EU approves Sativex NOTE: Sativex is a whole plant alcohol extract from two strains of cannabis in a 1: 1 ratio

Cannabis Use In Pregnancy ● Dr. Melanie Dreher, Dean of The School of Nursing at Rush Medical School, did her study in Jamaica in 1968. ● This study documented that children of women who smoked cannabis during pregnancy did better in school and reached their developmental landmarks sooner than children of women who did not smoke cannabis during pregnancy.

2005 Dr. Donald Tashkin Lung Cancer? NO! ● He compared 1100 patients with respiratory wellness. ● He determined cannabis does not cause lung cancer.

AMA November 2009 ● Changes 2001 position that more research is needed ● Cannabis should be rescheduled so that more research can be done ● Joins over 100 health care organizations in support of MMJ ● Includes American College of Physicians, American Nurse Association, American Public Health Association

Legal/States Rights ● ● 1925 - Linder vs. U. S. States Rights 1942 -Wickert v. Filburn 10 th Amendment 2004 - Raich v. Ashcroft- 9 th Circuit 2005 - Gonzales v. Raich - U. S. Supreme Court ● 2008 -2016 Boma v. Haynes State rights ● 2014 Rohrbacha-Faut Budget Amendment

Clinical Standards

MBC Guidelines for Giving Approval/Recommendation ● ● ● Bonafide doctor-patient relationship Good faith H&P Review records Plan With Objectives A condition which will benefit from use of cannabis

Marijuana Research in the United States

Studies Available ● To date, there are over 20, 000 published studies or reviews in the scientific literature referencing the cannabis plant and its cannabinoids, nearly half of which were published within the last five years. ● These numbers are according to a key word search on the search engine Pub. Med Central, the US government repository for peer-reviewed scientific research.

California center For Medical Cannabis Research(CMCR) ● ● Founded 2000 Funded by the state of California Located at UCSD School of Medicine 18 FDA approved smoked cannabis studies ● The center’s report to the legislature came out in 2011

Sean Mc. Allister, Ph. D. ● He is a researcher at California Pacific Medical Center Research Group ● He had done research on the treatment of mice with breast cancer with THC. ● The study demonstrated that the THC cured the breast cancer ● Dr. Mc. Allister is presently preparing to do a human breast cancer study with a cannabinoid or cannabinoids

Center for Medicinal Cannabis Research (CMCR) The classification of marijuana as a Schedule I drug as well as the continuing controversy as to whether or not cannabis is of medical value are obstacles to medical progress in this area. Based on evidence currently available the Schedule I classification is not tenable; it is not accurate that cannabis has no medical value, or that information on safety is lacking.

PTSD Study By Dr. Suzanne Sisley ● This is going on in Colorado ● She was a long time physician in the VA system in Arizona ● Her study was a rare study approved by the federal government but was blocked in Arizona by several state legislators ● Her research is privately supported in Colorado

Things Are Changing

2018 Epidiolex ● This is a high CBD GW product. ● It was an anti seizure medication for treating Dravet’s Syndrome ● Approved by the FDA ● Schedule V

Top Needs ● Professionalism in growing, dispensing and prescribing ● More research on Cancer, PTSD & Autism ● Include ECS in medical school curriculum

Research Needs ● Conditions ◦ Cancer ◦ PTSD ● Terpenes ● Dosage for specific conditions ● THC CBD roles ● Contributions of other cannabinoids

Standards ● Integration in California ◦ All products ◦ Dosage ◦ Plant constituents contained ● M. D. Standards ◦ Marginalize minimalists ◦ SCC and AACM standards ◦ Request education on ECS and cannabis

Dispensaries ● ● Need to be professional Need to be regulated Should be like pharmacies Health spa model

Areas to Focus On ● Standardization – plant, labeling, product ● Professionalism – M. D. , dispensary ● Research ◦ PTSD ◦ Cancer ◦ Epilepsy ● Education ◦ Med School ◦ CME ◦ General Public

Thank you very much David Bearman, M. D. www. davidbearmanmd. com davidbearman@cox. net 7394 Calle Real, Suite C Goleta, CA 93117 (805) 961 -9988 American Academy of Cannabinoid Medicine (AACM) info. aacm@gmail. com

● History And Policy

References: Demons, Discrimination, and Dollars: A Brief History of The Origins of Drug Laws; by David Bearman, M. D. Cannabis by Martin Booth Reefer Madness by Eric Schlosser Cannabinomics by Christopher Fichtner, M. D. The Pot Book, edited by Julie Holland, M. D. Cannabis and Cannabinoids by Ethan Russo, M. D. and Franjo Grotenhermen, M. D. Drugs are NOT Tools of the Devil: How Greed and Discrimination Led to Dysfunctional Drug Policy and How to Fix it, by David Bearman, M. D. Marijuana Medical Handbook; by Dale Gieringer, Ph. D. , Ed Rosenthal, and Gregory T. Carter, M. D.