© WBP2013 Made with Xara Marijuana Dangerous Drug or Medicine? John S. Phillips May 1994 Since marijuana was removed from the pharmacopoeia in 1937, there has been a continuous debate as to whether it has a value as a medicine.  There is perhaps, no other medical debate in which opinion is so divided.  One group of doctors views marijuana as one of the most dangerous substances known to man, a stepping stone drug that is unsafe for human consumption under any circumstance.  Robert Dupont, former head of the National Institute of Drug Abuse during the Reagan Administration, was a strong advocate of this position.  He concluded in a 1986 report that because marijuana breaks down into 2,000 chemicals when smoked, it will be a long time before it is possible to understand it's mechanism of action, and therefore it is unsafe for consumption.   Dupont, R. "Getting Tough on Gateway Drugs. Washington D.C. : American Psychiatric Press, 1986. In a recent article in the New York Times, "Debate on Using Marijuana as Medicine Turns to Question of Whether It Works,” the current medical opposition to the use of marijuana as medicine was summarized.  Dr. Bennett of Oregon Health Sciences University, an expert on high blood pressure and kidney disease whose son died suddenly with cocaine in his blood stated: "Marijuana has never been shown safe and effective for anything- not one single study. . . It is very second line therapy, surpassed by modern drugs . . . I have compassion, believe me, but desperation is not the basis for social policy."  Dr. Erye, chief medical officer at the American Cancer society states  "The bottom line is that the evidence to support marijuana as being superior to any other agent is very minimal to none. . .the scientific data, are very fragmented and poor."   Lolata, Gina, "Debate on Using Marijuana as Medcine Turns to Question oof Whether It Works," New York Times, Feb. 16, 1994, p.C14. In total contrast to this scientific position is another group of doctors who view marijuana as a medicine of unparalleled value and potential. Dr. Raphael Mecholam, a former researcher at Tel Aviv University who in 1964 first synthesized delta-9-tetrahydracannabinol (THC), the psychoactive ingredient marijuana, is one such researcher.  In a 1982 Omni magazine article he stated that marijuana was capable of replacing 10-20 % of all pharmaceutical prescription, and would most likely be included in 40-50% of all medicines when research was completed.   Herer, Jack, The Emperor Wears No Clothes, Van Nuys: HEMP Publishing, 1985, p.31.    Lester Grinspoon, Harvard Medical School,  began investigating  marijuana in the 1960's believing that young people who were turning to it for symptomatic relieve were endangering their lives.  By 1971 when he published his completed research in his book, Marijuana Reconsidered, his opinion had been radically transformed.  After a complete review of all scientific and medical evidence, he became convinced that he, like the rest of the public, had been brainwashed about the effects of marijuana on humans, concluding that all medical evidence clearly demonstrated that marijuana is safer than alcohol or tobacco.  He recommended its legalization.   Grinspoon, Lester, Marijuana Reconsidered, Cambridge: Harvard University Press, 1972.  While debates over the therapeutic efficacy of pharmacological  agents are not new to modern medicine, a unique feature of the debate  over the use of marijuana as a medicine is that it is the longest and most  expensive debate in United States Medical history.  Since the mid-1960's when marijuana became popular among college students, and strongly  associated with the Anti-war movement,  there have been over 6000  journal articles written concerning different aspects of the marijuana  issue.   No one could challenge the evidence that more studies exist on  the use and abuse of marijuana than any substance single illegal  substance in the world, and enough studies exist to construct an  argument for or against its use.  If science is an objective tool for  analyzing data and determining the ultimate truth, how are such  divergent opinions possible?  Paradigm and Scientific Revolution  In 1964 Thomas Kuhn provided a compelling look at history of  science in his book, The Structure of Scientific Revolution, which  examined how science evolves.   T. S. Kuhn, The Structure of Scientific  Revolution,  Chicago, 1964.  According to Kuhn's thesis, when anomalies or  new data arise which can not be explained by existing theories a crisis  slowly develops.  The reason a crisis develops is because unexplainable  data undermines scientists' theories of knowledge that is the foundation  of their training, and professional careers.  A crisis can only be abated  when a new theory capable of explaining all existing data comes into  existence.  Science itself is so stagnant and rigid in Kuhn's estimation  that frequently only when society becomes so frustrated that it demands  that science come out from its reclusive hiding place and addresses the  issues at hand, that most crisis get solved. According to Einstein, science  and religion shared a common goal; the elimination of pain and suffering for humankind.  In this sense for a scientist to accept crisis is to admit a  crisis in faith, never an easy thing for anyone to do, but for a scientist, it  sometimes means acknowledging that his entire career has been spent  pursuing a path that is not necessarily based on truth.  To symbolize the chief characteristic that was responsible for  making science stagnant and resistant to change, Kuhn coined the  phrase "paradigm."  Paradigm literally means to show by example.  It has  become a mainstay of the scientific community, as scientists frequently  refer to this or that paradigm when trying to describe different systems of science.  But to Kuhn paradigm was something much deeper than a  system of science.  A paradigm defined the conditions and initiation  process an individual must endure to become a member of the scientific  community.  The nature of the initiation rights are used to create the  world views and values that eventually define the problems and methods  for the study of science; Kuhn writes: ...to understand why science develops as it does, one need not  marvel the details of biography and personality that lead each  individual to a particular choice, ...What one must understand,  however, is the manner in which a particular set of shared values  interacts with the particular experiences shared by a community of specialists to ensure that most members of the group will  ultimately find one set of arguments rather than another decisive."   Ibid,  2cd edition, Chicago, 1970. p. 200  Kuhn's insights that paradigm is responsible for the inherit inability science to adapt to change has important implications for government policy towards research, and the role the history of science plays in solving deep paradigmatic crisis  by alerting the scientific community to historical developments.  The historical difficulties in establishing a policy concerning marijuana as medicine is represented in the diagram above.  What are the differences between sacraments, drugs and medicines?  E.O. Wilson proposed in his 1975 best seller, Sociobiology, that much of sociological research up to that point in history had relied on observation, and labeling of phenomena, or culture, without a clear understanding of biology.  The major obstacle interfering in the establishment of a scientific policy concerning marijuana can be traced to a culture represented in the JUST SAY NO policy toward drugs that based its entire policy on labeling of phenomena and ignoring scientific data.  This not only effected the questions that were are asked, but ultimately influenced how experiments were arranged, and results were interpreted.    The importance of this is that up to this point in history our policy toward the medical use of marijuana has been based on labeling of cultural phenomena without regards to science.  E.O. Wilson proposed that neurobiology would in the end become an ultimate basis of sociology and psychology.  Neurobiology was the key to understanding normal and abnormal human behavior.  If you watch the nightly news human behavior appears to be at the root of the current crisis in our communities.    Kuhn demonstrates with a variety of historical examples that crisis has been the catalyst for many scientific revolutions of the past.  "a novel theory emerged only after a pronounced failure in the  normal problem-solving activity. .... (the) breakdown and  proliferation of theories that is its sign occurred no more than a  decade or two before the new theory's enunciation.  The novel  theory seems a direct response to crisis."   Ibid., p.75    A recent discovery challenges the entire foundation of the "Anti- marijuana paradigm introduced by Dupont, and signals the time for a dramatic change in the course of policy.    The first step in correcting our policy failures is this area require recognition that our early science in this area that dominated research dollars and programs of public mis- education were based on "cultural" reactions to drug use and not science.  Judging from the difficulties the US has in regards to drug use and abuse, How a society chooses between drugs, medicine and sacraments can have dangerous consequences for society?  It was originally assumed that marijuana's pharmacological action was non-specific like alcohol and that its effects were due to disruption of cellular membranes.  The discovery of a dose dependent curve for different cannabinoids was a sign that marijuana does not have a non- specific action.   The discovery of a cannabinoid receptor and endogenous ligand which appear to be specific for THC suggest that a novel theory that ends once and for all the debate over marijuana as medicine can finally be relegated to the museum of science. The Cannabinoid Receptor and Endogenous Ligand In 1988 William Devane, a post doctoral student working in the lab of Allyn Howlett proved the existence of the cannabinoid receptor.  On August 9, 1990 the debate over whether marijuana is medicine officially ended, when it was reported in Nature that a cannabinoid receptor had been successfully cloned, and a corresponding messenger RNA found in the cell lines and regions of the brain where the receptor has been located.    Matsuda, Lisa A., Lolaity, Stephen J.m Brownstein, M.J. Young, A.C. & Bonner, T.I., Nature, 346: Aug. 9, 1990, p. 561-564.    Receptors have now been located in the basal ganglia particularly the striatum, the hippocampus, the cerebellum, the cerebral cortex, the testes, the marginal zone of the spleen, and there is growing evidence that there are also spinal chord receptors.   Smith, P. & Martin, B., "Spinal Mechanisms of delta-9- tetrahydrocannabinol- induced analgesia," Brain Research, 578: 8-12, 1992.  In December 1992 Devane and Mechoulam reported the isolation and purification of an endogenous ligand which they named anandamide. It means "internal bliss" in Sanskrit.  After reviewing the data, Solomon Synder, famous for the discovery of the opiod receptors, called this a breakthrough of enormous consequence.     There has never in the history of neurobiology been the discovery of a receptor without biological, behavioral and medical significance.  Bill Martin Virginia Commonwealth University states “This has greater implications than just the study of marijuana.  We will be learning about an entirely new neurochemical system."   Barinaga, Maria,  Science, 258: 18 December 1992, p. 1882-1884.  The questions that remains are those that are asked after the discovery of any new neurotransmitter or 2cd messenger in the brain.  What are its neurobiological properties as a medicine?  Is it safe as a medicine?  What are its mechanism of action?  What are the doses responses?   What are the risks? And finally potentially the most intriguing question of all "What role do anadamide-making neurons play in the central nervous system."  This report attempts to reexamine previous medical research into the medical uses of marijuana in light of the new discovery of a receptor and an endogenous ligand.   I believe that it is in the realm of neurobiology that the entire of debate over the use of marijuana as medicine is laid to rest when we recognize that marijuana's therapeutic effects although complicated can be explained by its unique pharmacological properties.  Is it safe? During the Bush and Reagan administration substantial sums of money were spent trying to prove that marijuana impaired immune function.   A review of the literature shows that the majority of studies on the negative effects of marijuana on the immune system were done using concentrations of marijuana that are unscientific.   Pross, Susan, et al.,"Suppressive effect of THC on specific T cell subpopulations in the thymus, Thymus, 19:97-104, 102. Nakano et. al. "Modulation of Interleukin 21 Activity by -9-THC after Stimulation with Concanavalin A, Phytohemagglutinin, or Anti-CD3 Antibody," Society for Exper. Biology  and Medicine, 201: 165-168.  I will not list all the studies in this area which are numerous and as pointed out above scientifically worthless.  Marijuana concentration in the blood upon Button for full pdf of paper