cannabisnews.com: Review of Marihuana and Medicine


cannabisnews.com: Review of Marihuana and Medicine





Review of Marihuana and Medicine
Posted by FoM on August 17, 2000 at 11:14:54 PT
Book Review
Source: New England Journal of Medicine
To the Editor: At the end of his review of Marihuana and Medicine, Benson (Sept. 9 issue) (1) states, "The editors' drug-control bias obscures the promise of drug development." Dr. Benson is the senior editor of the 1999 report by the Institute of Medicine, "Marijuana and Medicine: Assessing the Science Base," (2) which recommends medicinal use of marijuana smoking, after describing its scientific basis. 
This scientific basis involves the assumption that there is an endogenous anandamide cannabinoid system, D9-tetrahydrocannabinol (THC), having a basic physiologic role. This rationale is described by Lichtman and Martin, in what Benson calls "the most compact and yet comprehensive chapter" in the book. However, it is not supported by our work and that of other investigators, described in other chapters of the book (Waser and Martin, (3) Sutin and Nahas, (4) and Nahas et al. (5)). This work challenges the cannabinoid hypothesis. Of 60 natural cannabinoids, THC is the only one that binds to a membrane receptor. This receptor (7TM) is present in every cell. In binding to it, THC displaces its natural ligand, anandamide, and persistently disrupts the physiologic signaling of the 7TM receptor. The anomalies observed clinically when THC is present in the cell membrane (i.e., impaired brain, immune, (6) cardiovascular, and reproductive (7) functions) are associated with the molecular disruption of membrane signaling. (5) Because of the disruption of this molecular mechanism by THC, it has not been possible to separate the adverse effects of THC and marijuana from their therapeutic properties. Benson does not mention the impairment of spermatogenesis in marijuana smokers, described in four chapters of Marihuana and Medicine, including one chapter that reports the inhibitory effect of THC on the acrosome reaction and egg fertilization. (6) Benson also dismisses the immunosuppressive effect of marijuana smoke on lung macrophages, an effect that raises questions about its utility in patients with AIDS. Acceptance of the unproved scientific basis adopted by Dr. Benson might have led to the development of THC-like drugs that lacked specificity and had adverse effects at therapeutic doses. The alternative putative molecular mechanisms of THC that we propose merit open discussion without allusion to a social bias. Gabriel Nahas, M.D. Kenneth Sutin, M.D. New York University Medical Center New York, NY 10016 William M. Bennett, M.D. Oregon University School of Medicine Portland, OR 97201-2940References The New England Journal of Medicine -- September 9, 1999 -- Vol. 341, No. 11 Marihuana and MedicineEdited by Gabriel G. Nahas, Kenneth M. Sutin, David J. Harvey, and Stig Agurell, with Nicholas Pace and Robert Cancro. 826 pp., illustrated. Totowa, N.J., Humana Press, 1999. $125. ISBN 0-89603-593-XThe medical use of marijuana has polarized public opinion, particularly because of its widespread recreational use over the past 30 years. Those in favor of its medical use point to the apparent safety of this ancient and "natural" remedy, the profusion of anecdotal and survey-based evidence of marijuana's effectiveness, and the importance in today's culture of personal choice. This view has been expressed at the ballot box since November 1996 by referendums in several states. Those opposed, troubled by this potential gateway to serious drug abuse, especially among adolescents, regard acceptance of the medical use of marijuana as the camel's nose under the tent, legitimizing a dangerous relaxation of the nation's "war on drugs." Both sides come from all age groups and levels of society, and both claim their own scientific evidence. In this rancorous climate of claim and counterclaim, both physicians and policy makers seek rational solutions based on credible evidence. Since 1986, basic science has helped enormously with discoveries of potent cannabinoid agonists; specific cannabinoid receptors and the correlation between their concentration in brain centers and their relevant functions; endogenous or natural substances that act on those receptors; and more recently, specific cannabinoid antagonists. Regrettably, societal concerns have focused attention on drug abuse rather than on the promise of drug development. Hence, a thorough scientific exposition of the medical value of marijuana would be welcome. But this book disappoints. Marihuana and Medicine, edited by a veteran in the field, New York University's Gabriel Nahas, and his colleagues, stems from the latest (March 1998) of several international conferences held since 1974. In the preface, Nahas states that "today the verdict of marihuana in medicine is finally at hand." In the last of 71 chapters by 109 authors, he concludes that "marihuana or THC [(Delta)9-tetrahydrocannabinol] do not qualify as safe and effective medications... [and] have no place in modern pharmacopeia," despite the interesting potential of cannabinoids described by several of the clinicians who have contributed to the book. Nahas does acknowledge that the "invaluable information" provided by the experimental use of THC and its synthetic analogues has facilitated "a better understanding of membrane signal transduction." It can be anticipated that there will be much to mine from research when its emphasis and funding shift from drug abuse to evidence-based medical use. Structurally, this book is flawed by its dependence on annoyingly brief contributions by so many of the authorities who participated in the two-day conference. Figures that were projected as slides and embellished by the conference's speakers often lack legends to assist the reader. Instead of critical editing, there are summary reports of previous conferences and reprinted articles, which add mostly outmoded data or opinions. Unbridled redundancy abounds, whether it concerns the history of marijuana use and regulation or the receptor story. Acronyms go unexplained, the index is incomplete, and there are scores of typographic errors. Organized progression through the chapters is frequently interrupted, too often by material unrelated to the medical use of marijuana. Some parts of the book are valuable. Though scattered and repetitious, the historical information is interesting. The reference lists after each chapter are extraordinarily complete, with many citations from the 1970s. The new chapters begin with helpful abstracts. Parts of the book should appeal to pharmacologists, particularly as a source of references. Molecular neurobiologists will generally be less gratified. Yet there are recognized, contemporary scientists among the contributors, including Mechoulam, Devane, and Glaser (on pharmacology), Pertwee (on receptors and their ligands), Gardner and Hiroi (on the activation of dopamine receptors to induce genes involved in brain reward systems), and Sutin and Nahas (on the interactions of THC with other drugs and anesthetics). Although conclusions about immune suppression by cannabinoids seem premature, if not unfounded, the chapters on the pathophysiology of the cardiovascular and pulmonary systems offer useful material. Paria and colleagues offer original data suggesting that activation of embryonic CB1 receptors by natural and synthetic ligands interferes with preimplantation development in embryonic mice. Parker and Zuckerman convincingly demonstrate that marijuana use during pregnancy is associated with impaired fetal growth and lower birth weight and that those effects are magnified by unhealthy lifestyles. Perhaps the book's most compact and yet comprehensive chapter -- and guide to potential drug development -- is provided by Lichtman and Martin, who focus on the receptor-mediated analgesic properties of THC and endogenous anandamide in animals and humans. They suggest coadministration of these compounds with opioids to escape the side effects of either agent and even pharmaceutical manipulation of the endogenous cannabinoid system to relieve pain. In a subsequent chapter, Clark describes an experiment in which habitual users smoked marijuana during the second of three months' surveillance in a research facility. Both the subjects' ability to discriminate among thermal stimuli of different intensities and the response bias (which reflects attitudinal and emotional factors that influence reporting bias, or responses based on expectation) were measured. Marijuana at low doses appeared to create both better discrimination among graded stimuli and hyperalgesia. Higher doses had no effect on the amount of pain experienced. Such sensory decision-theory models recognize the emotional side of pain and are recommended for future studies of analgesia. And analgesia has commercial value. Practicing physicians will gain most from six well-referenced chapters that address therapy for specific symptoms. Green dismisses cannabinoids for the treatment of glaucoma, despite their effectiveness in reducing intraocular pressure through aqueous outflow pathways; perhaps receptor-independent substances that are structurally related, such as HU211, will be proved neuroprotective. Gralla elaborates on one of the two approved uses of dronabinol (a synthetic THC): control of chemotherapy-induced nausea and vomiting, for which very effective serotonin-receptor antagonists with dexamethasone are superior therapy. He also forecasts the potential for neurokinin-receptor antagonists. Consroe summarizes the rationale for their use and the largely anecdotal evidence that cannabinoids relieve muscle spasticity in multiple sclerosis and spinal cord injury. In dealing with therapy for the cachexia associated with AIDS, the other approved use of cannabinoids, Timpone and colleagues carefully compare dronabinol and megestrol acetate therapy; the latter in high doses was critical for any weight gain, even though both drugs increased appetite in placebo-controlled trials. Negrete and Gill warn of troubling negative effects of marijuana in persons with schizophrenia. The book ends with brief attention to public policy and with repetition of the editors' conclusion that THC "deregulates the physiological signaling role of a receptor protein to which it binds and of the membrane bilipid layer which it permeates. This deregulation of membrane signaling will result in discordant and partial therapeutic effects coupled with unwanted side effects." One can agree that, to date, drugs more effective than cannabinoids have prevailed. But the editors' drug-control bias obscures the promise of drug development. John A. Benson, Jr., M.D. Oregon Health Sciences University Portland, OR 97201-3098 1. Benson JA. Review of: Marihuana and medicine. N Engl J Med 1999;341:854-5. http://www.nejm.org/content/1999/0341/0011/0854.asp2. Joy JE, Watson SJ Jr, Benson JA, eds. Marijuana and medicine: assessing the science base. Washington, D.C.: National Academy Press, 1999. 3. Waser PG, Martin A. Barbiturate potentiating, temperature reducing, analgesic, and behavioral effects of some synthetic tetrahydrocannabinol derivatives in comparison with D9-tetrahydrocannabinol. In: Nahas GG, Sutin MK, Harvey DJ, Agurell S, eds. Marihuana and medicine. Totowa, N.J.: Humana Press, 1999:527-39. 4. Sutin KM, Nahas GG. Physiological and pharmacological interactions of marihuana (THC) with drugs and anesthetics. In: Nahas GG, Sutin MK, Harvey DJ, Agurell S, eds. Marihuana and medicine. Totowa, N.J.: Humana Press, 1999:253-71. 5. Nahas GG, Harvey D, Sutin K, Agurell S. Receptor and nonreceptor membrane-mediated effects of THC and cannabinoids. In: Nahas GG, Sutin MK, Harvey DJ, Agurell S, eds. Marihuana and medicine. Totowa, N.J.: Humana Press, 1999:781-805. 6. Cabral GA. Marihuana and the immune system. In: Nahas GG, Sutin MK, Harvey DJ, Agurell S, eds. Marihuana and medicine. Totowa, N.J.: Humana Press, 1999:317-25. 7. Schuel H, Chang MC, Burkman LJ, et al. Cannabinoid receptors in sperm. In: Nahas GG, Sutin MK, Harvey DJ, Agurell S, eds. Marihuana and medicine. Totowa, N.J.: Humana Press, 1999:335-45. Direct Link To Above Article:http://www.nejm.org/content/2000/0343/0007/0514.aspThe New England Journal of Medicine -- August 17, 2000 -- Vol. 343, No. 7 Copyright © 2000 by the Massachusetts Medical Society. 
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Comment #11 posted by Dan B on August 19, 2000 at 01:11:28 PT:
I Do Have To Agree...
...with both freedom fighter and kaptinemo. My family has also suffered at the hands of incompetent or too-profit-oriented doctors. And lawyers. And insurance companies. And worker's compensation, care of the State of Washington.You are both right to decry the abuses brought on by these doctors, and I do empathize with your anger. I was just trying to offer a ray of hope, so to speak. And I hope it came across that way.Peace.Dan B
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Comment #10 posted by r.earing on August 18, 2000 at 09:34:08 PT:
New England Journal is becoming bogus!
This journal was always one of the best.Now,They are publishing studies that are way below the standards expected from first year liberal arts students.A good example is the "whiplash" study by David Cassidy,et al. An insurance company paid dr.Cassidy to find that people heal quicker under a no-fault auto insurance scheme.He dutifully found that people heal twice as fast when they can't recover ANY damages after a car accident.Two of his researchers are suing him for wrongful dismissal after they refused to fake data to reach their pre-arranged conclusion.(He threw out all the data for people who had been seen by a doctor after their accident and used only the data from the remainder).If you tried to pull this in psych 101, you'd flunk out!
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Comment #9 posted by kaptinemo on August 18, 2000 at 08:10:30 PT:
There's science, and then there's 'science'
FF's rage against quackery is something I share; my mother died as a result of medical mismanagement resulting from massive qauntities of a known dangerous steroid being used to treat her Crohn's disease, causing severe myopathy. The Crohns and the wasting associated with it could have been ameliorated by cannabis... but that would be 'sending the wrong message to the chil-drun'. But she was also complaining of intense pain in her left arm.As a Civil Air Patrol Field Force troop, I had Advanced First Aid every 6 months. As a soldier in the Chemical Corps, I had it every year. The Force Instructors and the Army Medics hammered it into your brain at every opportunity the importance of that particular symptom: possible heart attack imminent. I asked her and my Dad as to whether she had been seeing a cardiac specialist; she had already had heart surgery a month before her death to relieve fluid on her pericardium. She told me that she told all the doctors she went to about it. They did nothing. No tests. No X-rays. No CAT scans. No MRI. Nothing. All that technology...wasted. She died from a blood cot (which would have been quickly detected with a CAT scan) that formed in her left arm, broke off during surgery (that she should never have had if they had listened to her and investigated the cause for her pain) and went straight for her brain stem. Her last moments of conscious life were absolute torture, and she was crying out in agony for someone to help her. My mother was no creampuff; being the wife of a Marine demands a lot. For her to cry so piteously tore my guts out.All because some idiots with medical degrees wouldn't look outside the confines of their tight, neat little worlds of clinical surety and consider that a bright, intelligent woman might have a legitimate reason for her complaints. She was a layman, and elderly lady... a GOMER (Get Out of My Emergency Room!). What could *she* or her family possibly know? They were *doctors*, they were *specialists*! The same kind of *specialists* who are so certain that cannabis has no medicinal value. The same kind of 'scientists' who ignore the tennets of their own profession and refuse to see the value of cannabinoids in treating all manner of diseases and acute, chronic pain. The truth of the matter is right in front of them, with thousands upon thousands of anecdotal instances of cannabis's therapeutic capacities.But they...won't...look. They stick their fingers in their ears and hum real loud when one of their own fold breaks ranks and speaks the truth. They cover their eyes to prevent themselves from being 'contaminated' by exposure to something outside of their peculiar orthodoxy. They are, ultimately, undeserving of the titles they have worked so hard to achieve - and demand that they be respected for having done so.I do not blame all doctors for the death of my mother and so many others. But when those who do not live up to the spirit of the Hippocratic Oath, when they do everything thay can to deliberately *cause* suffering by obstructing MMj research - as Gabriel Nahas and his cronies have done - I honestly hope and fervently pray that they themselves suffer the same agony that so many of their victims have. Some might decry my seeming vindictiveness. But always remember, people; the antis were the ones who fired the first shot in this war they declared upon us. They are the ones who built the concentration camps we call prisons. They are the ones who arrest the sick and the dying, and callously speed their demise by hiding behind the law as they did with Peter McWilliams. As they are trying to do to Todd McCormack right now.Yep, there's science in the service of humanity, and then there's 'science' perverted to serve temporal political gain. We know which side Nahas and Company are on.
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Comment #8 posted by rainbow on August 18, 2000 at 07:43:57 PT
Why in the New England Journal of Medicine 
Please help me understand why the prestigious New England Journal of Medicine would give this quack an opportunity to spread the misrepresentations?Maybe the New England Journal of Medicine is not as prestigious or valid as I thought it was.Rainbow
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Comment #7 posted by freedom fighter on August 18, 2000 at 07:00:21 PT
I agree 
that there are some good doctors.The trick is to find them.:) The third doctor did a good job on my wound. Boy, I was ticked off as it took me all day long to get it fix.I get mad when I hear or read about doctors preaching medical quackeries. Thanks to the good doctors who are doing all they can to expose those frauds. Not that they need to do that. It is sad that they have to waste their time trying to convince other doctors. They could be doing more research on cannabis.We know that our government is trying to base cannabis laws on science. It will not work either. Millions of folks are still going to smoke a toke or two. Yes, we do have better and smarter doctors than the other side of fence. I just feel that people put their trust too much on doctors.It is just that doctors like this fool dr.nahas make others look bad. I am not going to give up and would love to see the laws change in my lifetime. Thanks for the reply Dan.\/peace be with you 
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Comment #6 posted by Dan B on August 18, 2000 at 02:50:44 PT:
Hold On There, Freedom Fighter...
I can see why you would have a distrust of medical doctors, and it is true that there are those out there who think only of profit margins (as the doctors you visited indicate) or propaganda (like Dr. Nahas), but there are some great ones out there as well. Of course, Dr. Ethan Russo is one of them (see the first message in this thread), and Dr. Lester Grinspoon is, too. Both of these doctors recognize and actively seek to study the positive effects of cannabis on a variety of medical conditions, and they should be applauded. And there are others.Check out these sites to see the kinds of things good, science-oriented doctors are doing to promote cannabis research:http://www.rxmarijuana.comhttp://www.medicinal-cannabis.orgArticles on Dr. Russo's work:http://www.maps.org/news-letters/v08n1/08115rus.htmlhttp://www.teleport.com/~omr/omr_russo.htmlhttp://www.norml.org/news/archives/99-10-07.shtmlI hope this gives you some hope for the medical profession. These doctors are genuinely concerned with helping people, and you are correct to note that such is not always the case. Keep hope alive; we have beter doctors on our side than the antis have on theirs.Peace.Dan B
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Comment #5 posted by freedom fighter on August 17, 2000 at 16:34:02 PT
thanks
Observer for the links.Just to prove that I cannot trust doctors. I once had an accident where I got a six-inch wound on my leg and about an inch deep. I had to drive around and visit three different doctors before the last one took care of it.First doctor said I had to go home and get my checkbook before he can fix my leg. He said, "Your wound is not a life threatening. You can go home and get your checkbook and then I will fix it." I flipped my middle finger!Second doctor said he could not do anything, I had to go to the emergency room.The third doctor was so suprised when I told him he was the third doctor I had to visit. What that has to do with marijuana? Nothing! It just has to do with trust of the America medical system. Sorry Doc!Barry said you were the best but sadly, I cannot believe him.
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Comment #4 posted by observer on August 17, 2000 at 15:05:33 PT
Gabriel ``I am an enemy of cannabis'' Nahas
links . . .NAHAS’ PRESCRIPTION FOR BLOATED POLICE BUDGETShttp://users.lycaeum.org/~sky/emperor/EMP/html/TCH15.HTM#NahasNahas versus KassirerFraud on Wall Street: How The Wall Street Journal defrauded the readers of its editorial page.http://www.marijuanamagazine.com/toc/nahas.htmRecent Nahas-Led Medical Marijuana Conference (1998)http://www.pdxnorml.org/980421.html#rnlNahas retractionshttp://www.lycaeum.org/drugs/Cannabis/nahas.htmlhttp://www.lycaeum.org/drugs/Cannabis/nahas.flawshttp://paranoia.lycaeum.org/marijuana/medical/nahas1970 - 1974 Nahas kommt, UN, Haschisch ist Modedrogehttp://www.datacomm.ch/virus/dbc/vbchis16.htm#TOPThe information that the Federal government is distributing is from the federally funded research conducted by Dr. Gabriel Nahas, who once declared openly, "I am an enemy of cannabis and I will use all means possible to fight against cannabis." His studies were so biased and unscientific that Nahas was fired by the National Institute of Health. Even Nahas said his own studies are meaningless. For one experiment, he suffocated monkeys for five minutes at a time with 63 joints lighted and using more smoke than the average user inhales in an entire lifetime. Under such conditions, the animals really died from asphyxiation. Smoke from burning wood would have caused the same brain damage. The other studies Dr. Nahas did claim that sensational health risks are also suspect. All his studies lack controls and produce results which cannot be duplicated nor confirmed. One false claim is that smoking marijuana damages the reproductive system. This claim is based chiefly on his experimentions with tissue (cells) isolated in petri dishes, and the work of researchers who dosed animals with near-lethal amounts of cannabinoids. Nahas's generalizations from his petri dishes to human beings have been rejected by the scientific community as being invalid. In the case of the animal experiments, the animals that survived their ordeal returned to normal within 30 days of the end of the experiment. Studies of actual human populations have failed to show that marijuana has a bad effect on the reproductive system (Hager, Paul, 1-2). MEDICAL MARIJUANA, Sara Phillips (1998?)http://www.pressuredrop.com/EyeSay/Essay.html . . .Sen. James Eastland (D-Miss.) convened hearings on the "marijuana-hashish epidemic" with the avowed purpose of countering the "good press" that pot had been receiving. Dr. Gabriel Nahas, author of Marijuana: Deceptive Weed and Keep off the Grass, led a group of researchers who testified that marijuana may cause lung damage, birth defects, genetic abnormalities, shrinkage of the brain, impairment of the immune system, reduction in testosterone levels, and sterility.Of these hazards, only lung damage has been well established by subsequent research. All the other claims have been discredited or remain controversial. Much of the research cited in the Eastland hearings was heavily criticized soon after it appeared. Some of it was laughably bad, with skewed samples and no control groups.Despite the poor quality of these studies, anti-marijuana activists continue to cite them. "Those papers, and the ideas they brought forth, are at the heart of the anti-marijuana movement today," says Dr. John P. Morgan, professor of pharmacology at the City University of New York Medical School. "Nahas generated what was clearly a morally based counter-reform movement, but he did a very efficient job of saying that he was actually conducting a toxicological, scientific assessment."The Eastland hearings left the impression that Americans had been duped by reformers about the nature of marijuana. The title of a piece in the June 10, 1974, issue of U.S. News & World Report is revealing: THE PERILS OF ‘POT’ START SHOWING UP. The writer was clearly confident that the speculation offered by Nahas and his colleagues was only the tip of the iceberg.Jacob Sullum, 1993http://www.reason.com/9306/fe.sullum.html 
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Comment #3 posted by Tim Stone on August 17, 2000 at 14:35:12 PT
Help, Dr. Russo.
Quote from Nahas above:"This scientific basis involves the assumption that there is an endogenous anandamide cannabinoidsystem, D9-tetrahydrocannabinol (THC), having a basic physiologic role. This rationale is described byLichtman and Martin, in what Benson calls "the most compact and yet comprehensive chapter" in thebook. However, it is not supported by our work and that of other investigators, described in otherchapters of the book (Waser and Martin, (3) Sutin and Nahas, (4) and Nahas et al. (5)). This workchallenges the cannabinoid hypothesis."Can you fill us in on the "cannabinoid hypothesis"? Is Nahas claiming that, well, yes, there is a naturally occurring cannabinoid molecule in the human body, designated by its discoverer (Dr. Mechulom(sp?)) as "anandamide," but this molecule couldn't possibly occur naturally in the human body, or if it does, it has no legitimate use in the human body and is some sort of foreign invader, like a virus, or infective bacteria? That might help sort out some of the doc-talk in the original post. Thanks for any help.
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Comment #2 posted by kaptinemo on August 17, 2000 at 12:25:29 PT:
Many thanks, Dr. Russo
As a layman, my understanding of the chemistry surrounding neurotransmitters is based solely upon what the Army taught me about the effects of nerve agents upon them. I must necessarily defer to those whose knowledge is vastly superior to mine. But I can and do appreciate it when someone presents me with the facts shorn of ideological bent (which Dr. Nahas seems completely unable to do) and allows me at least the chance to learn for myself, in an albeit limited way, to learn the truth for myself.It only goes to prove the idea that the vast majority of open-minded people reside in *our* camp; who else would take the time to struggle through the blather of ones' opponents out of a sense of fairness, but us? 
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Comment #1 posted by Ethan Russo, MD on August 17, 2000 at 11:44:53 PT:
Cannabis Book Wars
Although I hate this type of character assassination myself, Dr. Nahas is recognized in the field as an extremist and ideologue whose examination of the issues are sometimes biased, superficial, sloppy or even fabricated. Although there are some good chapters in his book, Dr. Benson's criticisms are well-founded. There are better books to be had. For the less technically oriented, Marijuana Myths, Marijuana Facts by Zimmer and Morgan is excellent and well-substantiated. The upcoming Cannabis and Cannabinoids from Haworth Press will be the kind of book that Marijuana and Medicine should have been: a balancedand in-depth discussion of the science. It would appear that I have a conflict of interest, in that I am the second editor of the book after Franjo Grotenhermen. In our defense, we both allowed the inclusion of material and opinions that differed from our own, sometimes markedly so, because we felt that the overall presentation would allow the reader the ability to engage in their own assessment and balance any conflicting concepts.
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