Bioidentical Hormones 101 
The Book, by Jeffrey Dach MD

Chapter 52. Cannabis, Miracle Drug of the 21st Century

Section Fourteen.  The Future of Medicine

 

Cannabis, Miracle Drug of the 21st Century, Jeffrey Dach MDChapter 52. Cannabis, Miracle Drug of the 21st Century

Left Image: Cannabis plant photograph, courtesy of the United States Fish and Wildlife Service.

Although cannabis (marijuana) was a medicinal plant for thousands of years, its use was suppressed and banned throughout most of the 20th century.  Banned in England, Canada and the US in the 1930's, medical cannabis represents the first casualty in the war against natural medicine waged by the pharmaceutical industry.  While banned in the US, there have been major scientific breakthroughs in Israel, Spain, Italy and Brazil over the last two decades.  These breakthroughs have made cannabis "the wonder drug of the 21st century".

The Father of Medical Cannabis Research

The greatest cannabis researcher is unquestionably Raphael Mechoulam from Israel.(76)  In 1964, Mechoulam discovered the active ingredient in cannabis, THC (Tetra-Hydro-Cannabinol). (2)   In 1992, he discovered the first endogenous endo-cannabinoid, Anandamide, a sanskrit word translated as "bliss".(78)  Endo-Cannabinoids are marijuana-like compounds made by our own brain, and circulate normally in your body.

A Treasure Trove Waiting for Discovery

When asked why he devoted his entire lifetime studying the biochemistry of cannabis, Dr. Raphael Mechoulam said the following:

"The three major illicit drugs derived from plants were then (at the beginning of my career), and still are, opium, coca and cannabis. Morphine had been isolated from opium early in the 19th century and structure elucidated in the 1920s by Robert Robinson. Cocaine was isolated from coca leaves in the middle of the 19th century and structure described by Richard Willstatter in the last decade of the 19th century. I believe that the cannabinoids represented a medicinal treasure trove which waits to be discovered."(79-82)

Just Like the Opiate Receptor Story

In a story very similar to the discovery of opiate receptors in the brain, cannabinoid receptors have been discovered along with their endogenous cannabinoids, representing the largest neurotransmitter system in the brain and immune system.  This neurotransmitter system went undetected for decades because it involves an unheard of concept, retrograde transmission, or reversed flow of information from the post synapse to the pre-synapse.

A List of the Medical Uses of Cannabinoid Drugs:

Relieves Chronic Pain
Reduces need for narcotics in chronic pain or Narcotics Addiction
Anti-Cancer Activity
Relieves Post Traumatic Stress Disorder, Phobias
Relieves Nausea and Vomiting associated with Chemotherapy
Improves Appetite in Wasting Syndromes
Relieves Migraine Headache
Relieves Glaucoma
Relieves Bladder incontinence
Used as Anti-convulsant
Used as Anti-depressant
Used as Atypical anti-psychotic
Used for Bi-Polar Syndrome
Used for Multiple Sclerosis, ALS


The Cannabinoid Receptor Story

In the 1970s, Morphine was isolated from the poppy plant and found to bind to opiate receptors in the brain.  Scientists eventually discovered that people make their own opioids, called enkephalins and endorphins. Morphine simply hijacks the receptors for the brain's opioids.  It seemed likely that something similar was happening with THC and the cannabinoid receptors in the brain and the immune system.  The health implications of the endo-cannabinoid system are staggering.  Cannabinoids act as a bioregulatory mechanism for most life processes

Timeline for Cannabinoids and Receptor System

2,000 BC  to 1,800 AD Medicinal Cannabis used in Ancient China, Egypt, India, ancient Greeks.
800 AD to 1,800 AD Medical Cannabis was used extensively in the medieval Islamic World.
1800-1900 Medical Cannabis commonly used entire world as primary pain reliever until the invention of aspirin.
1925  England bans cannabis with Dangerous Drugs Act, and non-medicinal cannabis made illegal in Britain.
1927 Canada bans all forms of cannabis.
1937 Even though there are 28 cannabis pharmaceuticals on the American market, Cannabis banned in US with federal law, the 1937 Marijuana Tax Act.
1964 THC, tetra hydro cannabinol, the psycho-active component of cannabis, isolated by Raphael Mechoulam at Weizmann Institute in Israel.
1970 Marijuana fully outlawed in US by Controlled Substances Act of 1970.
1975 Munson shows anti cancer effects of cannabis in Lewis Lung Tumors.
1980-2000 Cannabis research banned in US (de facto).
1985 FDA approves Marinol drug, a pure THC drug.
1992
First endo-cannabinoid isolated by Hanuš and Devane in Raphael Mechoulam's lab at the Hebrew University in Jerusalem. This new substance is named Anandamide.
1992 endo-cannabinoid CB1 receptors cloned and found in brain
1993 endo-cannabinoid CB2 receptors cloned and found in the immune system.
1998 Di Marzo's in Naples Italy group found that cannabinoids (anandamide) inhibit breast cancer cell proliferation.
1999 Marinol (THC) was rescheduled from Schedule II to III of the Controlled Substances Act,
2000 Guzman's group in Spain found that cannabinoids inhibit the growth of C6 glioma cells.
2005 Sativex approved in Canada. Sativex is a whole cannabis plant extract, mouth spray approved for multiple sclerosis patients to alleviate neuropathic pain and muscle spasticity.
2006 Cannabindiol found useful as anti-psychotic drug São Paulo, Brasil.
2007 Sean D. McAllister - Cannabidiol inhibits aggressive breast cancer cells.
2008 Acomplia, Rimonabant (also known as SR141716) first CB1 receptor blocker suspended from the UK market because of adverse effects of suicidality, depression. This agent blocks the endo-cannabidiol receptors.
2009 Two components of cannabis plant identified. THC which is psychoactive, and the non-psychoactive Cannabidiol "CBD" represents up to 40% of extracts of the medical cannabis plant. Cannabidiol relieves convulsion, inflammation, anxiety, nausea, and inhibits cancer cell growth.  Cannabidiol as effective as atypical antipsychotics in treating schizophrenia.
2010 - 10 million people have been arrested for marijuana possession since 1967. In the US, 13 states have approved medical use of cannabis.


Safety of Marijuana:

There has never been a documented human fatality from marijuana. The respiratory depression from opiates does not happen with cannabinoids.  The active ingredient in cannabis is Cannabidiol, a Schedule I drug in the USA, despite having no psychoactive effects and no known abuse potential.  Cannabidiol kills cancer cells, relieves pain, serves as an anti-depressant, and has numerous other medical uses. In the US, 13 states that have passed laws legalizing medicinal cannabis. You can join the movement to legalize the medicinal use of cannabis by calling, emailing or writing your congressman today.

Warning and Disclaimer:

Marijuana is an illegal drug in many US states and other countries. It is illegal to grow or possess the marijuana plant, also known as the hemp plant.  Even when used as a prescribed medicine, marijuana use may result in arrest, fines or imprisonment.  Only use marijuana as a drug if it has been legally prescribed by a licensed physician in a state or country that has legalized the use of medical marijuana.

For references and links, see web site: www.bioidenticalhormones101.com

References for Chapter 52. Cannabinoids, Miracle Drug of the 21st Century

(1) http://www.altmd.com/Videos/Cancer-Cure--Cannabis-Cannabinoids
Video filmed in 2006, Dr. Robert Melamede, Professor of Biology at the University of Colorado, explains how the body's Endo-Cannabinoid system kills cancer cells and inhibits tumor growth.

(2) http://pubs.acs.org/doi/abs/10.1021/ja01062a046 Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish. Y. Gaoni, R. Mechoulam J. Am. Chem. Soc., 1964, 86 (8), pp 1646–1647.April 1964

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(5) http://www.cannabis-med.org/english/journal/en_2006_02_1.pdf Cannabinoids: potential antitumoral agents? Manuel Guzmán Madrid, Spain, 2006

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(11) http://jnci.oxfordjournals.org/cgi/content/abstract/djm268v1
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Cannabinoid receptor activation induces apoptosis through tumor necrosis factor alpha-mediated ceramide de novo synthesis in colon cancer cells. Cianchi F et al. University of Florence, Florence, Italy.

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Proc Natl Acad Sci U S A. 1998 July 7; 95(14): 8375–8380.  PMCID: PMC20983
The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation. Luciano De Petrocellis and Vincenzo Di Marzo et al. Naples, Italy;

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Hemp Oil and Cancer By Mark Sircus Ac., OMD February 23,  see also
www.phoenixtears.ca 

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Cannabis, Cancer and Hemp Medicine by Rick Simpson

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(20) http://www.huffingtonpost.com/2009/02/26/holder-vows-to-end-raids_n_170119.html
Obama's Attorney General, Holder, Vows To End Raids On Medical Marijuana Clubs

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http://www.informapharmascience.com/
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Expert Opinion on Investigational Drugs February 2009, Vol. 18, No. 2, Pages 125-133
Cannabinoids against pain. Efficacy and strategies to reduce psychoactivity: a clinical perspective    Matthias Karst‌† MD PhD & Sonja Wippermann‌

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Russo and Grotenhermen report:  Review of Therapeutic Effects of cannabis. Relieves Nausea and vomiting, anorexia, and weight loss associated with chemotherapy or HIV/AIDS. Relieves spasticity, neurogenic pain, asthma, glaucoma.

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Chem Phys Lipids. 2000 Nov;108(1-2):191-209. Endocannabinoids and fatty acid amides in cancer, inflammation and related disorders.De Petrocellis L, Melck D, Bisogno T, Di Marzo V. Istituto di Cibernetica, Consiglio Nazionale delle Ricerche, Via Toiano 6, 80072 Arco Felice, Napoli, Italy.

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http://www.associatedcontent.com/article/
1524315/california_state_assembly_considering.html?cat=8

California State Assembly Considering Marijuana Legalization. March 03, 2009 by P. Trembeth. Could Widespread Marijuana Legalization Be Just Around the Corner? AP News

(27) http://newmexicoindependent.com/20182/feds-make-medical-marijuana-de-facto-legal Obama Administration makes medical marijuana de facto legal.  By Marjorie Childress 3/2/09 9:28 AM  U.S.

(28)
http://www.scielo.br/pdf/bjmbr/v39n4/6164.pdf  see also
http://www.scielo.br/scielo.php?pid=S0100-879X2006000400001&script=sci_arttext
Braz J Med Biol Res, April 2006, Volume 39(4) 421-429 (Review) Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug .A.W. Zuardi et al.

(29) http://finola.com/CBDreview2008.pdf Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action  Antonio Waldo Zuardi, Brazil

(30)  http://videos.med.wisc.edu/videoInfo.php?videoid=1107 Cannabis and Cannabinoids in the 21st Century: Medical Marijuana. David Bearman, MD

(31) http://americanmarijuana.org/ The American Medical Marijuana Association

(32)
http://www.nature.com/bjp/journal/v146/n7/pdf/0706415a.pdf see also
http://www.nature.com/bjp/journal/v146/n7/full/0706415a.html
Plant cannabinoids: a neglected pharmacological treasure trove.  Raphael Mechoulam. British Journal of Pharmacology (2005) 146, 913–915

(33) http://www.jleukbio.org/cgi/content/full/82/6/1390   Journal of Leukocyte Biology. 2007;82:1390-1392.) Endocannabinoids, cannabinoid receptors and inflammatory stress: an interview with Dr. Pál Pacher Helene F. Rosenberg1 Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA

(34) http://www.endocannabinoid.net/Mechoulam.aspx Excerpt from the journal, Addiction.
Conversation with Raphael Mechoulam. Addiction. 2007; 102(6), 887-893.

(34) http://www.bioteach.ubc.ca/Journal/V02I01/Cannabis.pdf
Half-Baked Science: A Primer on Medicinal Cannabis Ryan Philippe

(35) http://edrv.endojournals.org/cgi/content/full/27/1/73
Endocrine Reviews 27 (1): 73-100, 2006. The Emerging Role of the Endocannabinoid System in Endocrine Regulation and Energy Balance . Uberto Pagotto, Giovanni Marsicano, Daniela Cota, Beat Lutz and Renato Pasquali

(36) http://cancerres.aacrjournals.org/cgi/content/full/66/13/6748   Cancer Research 66, 6748-6755, July 1, 2006. Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress–Related Genes. Arkaitz Carracedo1, Meritxell Gironella2, Mar Lorente1, Stephane Garcia2, Manuel Guzmán1, Guillermo Velasco1 and Juan L. Iovanna2

(37) http://www.fuoriluogo.it/medicalcannabis/documenti/bifulco2002.pdf
Targeting the endocannabinoid system in cancer therapy:
A call for further research  MAURIZIO BIFULCO1 & VINCENZO DI MARZO 
NATURE MEDICINE • VOLUME 8 • NUMBER 6 • JUNE 2002

(38) http://www.aapsj.org/articles/aapsj0802/aapsj080234/aapsj080234.pdf
Cannabinoid Receptors and Endocannabinoids: Evidence for New Players, AAPSJ, April 28, 2006 Ken Mackie 1 and Nephi Stella 2 1 Departments of Anesthesiology and Physiology.

(39) http://pharmrev.aspetjournals.org/cgi/content/full/58/3/389
The Endocannabinoid System as an Emerging Target of Pharmacotherapy. Pharmacol Rev 58:389-462, 2006. Pál Pacher, Sándor Bátkai and George Kunos .

(40)
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(41)
http://www.illinoisnorml.org/index2.php?option=com_content&do_pdf=1&id=104
Cannabis' Potential Exciting Researchers in Treatment of ALS, Parkinson's Disease - URB597.
Last Updated Friday, 15 June 2007

(42) http://jpet.aspetjournals.org/cgi/content/full/322/1/236
Journal of Pharmacology And Experimental Therapeutics Fast Forward . JPET 322:236-242, 2007. The Fatty Acid Amide Hydrolase Inhibitor URB597 (Cyclohexylcarbamic Acid 3'-Carbamoylbiphenyl-3-yl Ester) Reduces Neuropathic Pain after Oral Administration in Mice.  Roberto Russo et al Naples, Italy

(43) http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16352709
Proc Natl Acad Sci U S A. 2005 December 20; 102(51): 18620–18625.  The National Academy of Sciences. Neuroscience- Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis. G. Gobbi et al.

(44)  http://www.sciencedaily.com/releases/2005/12/051213172852.htm
New Antidepressant Drug Increases 'Brain's Own Cannabis. Science Daily 2005.

(45) http://www.doctordeluca.com/Library/WOD/BrainsOwnMJ-SA04-NoPix.pdf
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(46) http://cancerres.aacrjournals.org/cgi/content/abstract/64/16/5617
Cancer Research 64, 5617-5623, August 15, 2004, Cannabinoids Inhibit the Vascular Endothelial Growth Factor Pathway in Gliomas. Manuel Guzmán et al., Spain

(47) http://www.ncbi.nlm.nih.gov/pubmed/19047095
Clinical Cancer Research 14, 7691, December 1, 2008. Cannabinoid Receptor Activation Induces Apoptosis through Tumor Necrosis Factor –Mediated Ceramide De novo Synthesis in Colon Cancer Cells.  Fabio Cianchi et al, Italy

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(49) http://www.usdoj.gov/dea/ongoing/marinol.html MARINOL DEA Page

(50) http://www.marijuanalibrary.org/HT_Marinol_0794.html  High Times, July 1994, pp. 18-21  Marinol: The Little Synthetic That Couldn't.  By Elsa Scott

(51) http://www.iowatelecom.net/~sharkhaus/marinol_long.html
Marinol vs. Marijuana: Politics, Science, and Popular Culture Kambiz. Akhavan

(52)
http://www.endocannabinoid.net/ endocannabinoid system network

(53) http://www.icb.cnr.it/erg/ The Endocannabinoid Research Group (ERG) is a multi-disciplinary research group established in 1995 and based in the laboratories of several Institutes of the Italian National Research Council (CNR) and of Universities in the Naples and Salerno area.

(54)
http://www.cannabinoidsociety.org/ The International Cannabinoid Research Society.

(55)
http://www.ukcia.org/research/CannabidiolWonderDrug.html
Cannabidiol: The Wonder Drug of the 21st Century?

(56) http://www.smart-publications.com/articles/MOM-mechoulam.php
The New Science of Cannabinoid-Based Medicine: An Interview with Dr. Raphael Mechoulam By David Jay Brown

(57) http://www.endocannabinoid.net/Mechoulam.aspx Interview with Mechoulam .

(58)
http://www.hempfood.com/IHA/iha01113.html Interview Professor Dr. Raphael Mechoulam, the discoverer of THC

(59) http://www.chipsbooks.com/cannabin.htm Cannabinoids as Therapeutics by Raphael Mechoulam, the book.

(60) http://www.youtube.com/watch?v=IgjLLHJdv3Q You Tube Video , Cannabinoid cancer treatment

(61) http://www.henriettesherbal.com/eclectic/kings/cannabis.html
Cannabis Indica (U. S. P.)—Indian Cannabis. Indian hemp. ILLUSTRATION: Bentley and Trimen, Med. Plants, 231.

(62) http://www.youtube.com/watch?v=VHWuD8a3INs&NR=1  You Tube Video April 4, 2008 - 5th Clinical Conference on Cannabis Therapeutics in Pacific Grove, CA, Deputy Director of NORML Paul Armentano talks Cannabis (marijuana) and the Endo-Cannabinoid system

(63) http://YouTube.com/SurvivingALS Cannabis Therapeutics Conference hosted by Patients Out of Time

(64) http://www.abc.net.au/quantum/poison/marijuan/lester.htm Interview with Lester Grinspoon 1997. 

(65) http://articles.latimes.com/2006/may/05/opinion/oe-grinspoon5
Puffing is The Best Medicine By Lester Grinspoon M.D.  Los Angeles Times - May 5, 2006.

(66) http://www.iht.com/articles/2007/03/01/opinion/edgrinspoon.php
Marijuana, the wonder drug of the 21st century. Lester Grinspoon The Boston Globe. March 1, 2007

(67) http://www.jimboland.com/2009/03/07/common-sense-compassion-overcome-marijuana-propaganda/ Common Sense and Compassion Overcome Marijuana Propaganda March 7th 2009

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Legalizing Marijuana Makes Sense, Cents by Steve Huntley

(69) http://www.neurology.org/cgi/content/abstract/68/7/515
Cannabis in painful HIV-associated sensory neuropathy A randomized placebo-controlled trial  D. I. Abrams, MD et al

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MEDICAL CANNABIS RESEARCH: WHAT DOES THE EVIDENCE SAY?

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After Two-Decade Halt, Marijuana Research Is Set By PHILIP J. HILTS. Dec 15, 2001. NY Times.

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British Journal of Anaesthesia 2008 101(1):59-68; Therapeutic potential of cannabis in pain medicine. R. D. Hosking and J. P. Zajicek* Neurology Research Group, Peninsula Medical School, Plymouth, UK

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Spring 2006. O'Shaughnessy's. Journal of the California Cannabis Research Medical Group

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A Day in the Life of a Cannabis Consultant. Philip A. Denney, M.D. Journal of the California Cannabis Research Medical Group.

(76) Cannabinoids As Therapeutic Agents by Raphael Mechoulam (Editor) Chapman and Hall/CRC; 1 edition (July 1, 1986)

(77) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1576036/ Br J Pharmacol. 2005 February; 144(4): 459–465.The expanding field of cannabimimetic and related lipid mediators by Heather B Bradshaw and J Michael Walker

(78) http://www.ncbi.nlm.nih.gov/pubmed/1470919  Science. 1992 Dec 18;258(5090):1946-9.Isolation and structure of a brain constituent that binds to the cannabinoid receptor.Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R.

(79) http://matters.ecnp.nl/number11/interview2.shtml  Interview with the winner of the first ECNP Lifetime Achievement Award:Raphael Mechoulam, Israel Maria Vrijmoed – de Vries, The Netherlands, editor

(80) http://www.druglibrary.net/olsen/HEMP/IHA/iha01113.html  Interview with Professor Dr. Raphael Mechoulam, the discoverer of THC, (June 17 1994)

(81) http://www.medicalmarijuana411.com/2010/05/07/dr-raphael-mechoulam_part-one/  Dr. Raphael Mechoulam – Medical Marijuana 411.com Interview – Part One

(82) http://www.lmreview.com/articles/view/new-developments-in-cannabinoid-based-medicine-an-interview-with-dr-raphael-mechoulam/  New Developments in Cannabinoid-Based Medicine: An Interview with Dr. Raphael Mechoulam by Lara Pizzorno, MDiv, MA, LMT

Author: Jeffrey Dach MD
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