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Project CBD: Marijuana Specialists Plan To Study New Strains

  • by Allen St. Pierre, NORML Executive Director December 28, 2009

    By Fred Gardner, Editor, O’Shaughnessy’s, the journal of cannabis in clinical practice

    “You have to start somewhere.” —Willy Notcutt, MD

    Fifteen members of the Society of Cannabis Clinicians -the doctors’ group founded by Tod Mikuriya in 1999 and now led by Jeffrey Hergenrather- met in Oakland Dec. 11. UCSF professor Donald Abrams recounted the obstacles he faced in conducting clinical trials with government-issued cannabis and getting his results published in peer-reviewed medical journals. The ensuing discussion focused on how SCC doctors might go about evaluating the effectiveness of high-CBD strains as they become available to patients in the year ahead.

    CBD (cannabidiol) is a non-psychoactive cannabinoid. For many generations (of people and plants), cannabis in California and elsewhere has been bred to maximize psychoactivity, which is mainly a function of THC content. (Some  “minor” cannabinoids, terpenes, and flavonoids also affect a plant’s effect.)  Because CBD and THC are in an either/or relationship at the genetic level, breeding for high THC means breeding out CBD. So it was widely assumed that the Cannabis available nowadays in California contains only trace amounts of CBD.

    Surprisingly, six strains with buds ranging from 5% to 7% CBD by weight have been detected in the year since Steep Hill analytic lab began testing samples from dispensaries and individual growers.  Only two of these high-CBD strains have been made available to patients -and only intermittently, as the pounds delivered by the growers sell out in a day or two. “Soma A-plus” has been dispensed at Harborside Health Center in Oakland, and “Pineapple Thai” at Herbal Solutions in Long Beach. The other four strains are being grown out as clones and should be available by spring 2010 to collectives wishing to dispense them.

    The doctors want, eventually, to test the effectiveness of cannabis with consistent CBD/THC ratios in treating various conditions. One hoped-for advantage of high-CBD strains is reduced psychoactivity, which might enable patients to take larger doses while remaining functional. The California doctors are somewhat enviously and somewhat gratefully tracking the progress of G.W. Pharmaceuticals, the British company that has been growing cannabis and making and testing whole-plant extracts for medical use since 1998 —with government approval and backing from corporate partners Bayer, Almirall, and Otsuka.

    G.W.’s flagship product is Sativex, an oral spray that contains about equal amounts of CBD and THC. The rationale for the combination was set forth in “A Tale of Two Cannabinoids,” a 2005 article by doctors Ethan Russo and Geoffrey Guy in the online journal Medical Hypotheses. Here’s a summary:

    “CBD is demonstrated to antagonise some undesirable effects of THC including intoxication, sedation and tachycardia, while contributing analgesic, anti-emetic, and anti-carcinogenic properties in its own right. In modern clinical trials, this has permitted the administration of higher doses of THC, providing evidence for clinical efficacy and safety for cannabis based extracts in treatment of spasticity, central pain and lower urinary tract symptoms in multiple sclerosis, as well as sleep disturbances, peripheral neuropathic pain, brachial plexus avulsion symptoms, rheumatoid arthritis and intractable cancer pain. Prospects for future application of whole cannabis extracts in neuroprotection, drug dependency, and neoplastic disorders are further examined. The hypothesis that the combination of THC and CBD increases clinical efficacy while reducing adverse events is supported”

    Sativex has been approved by Health Canada for treating neuropathic pain in multiple sclerosis and cancer. It is obtainable by prescription in 22 countries. GW has applied for and is awaiting approval of Sativex as a treatment for MS spasticity in the UK and Spain. The U.S. FDA has given GW approval to conduct a clinical trial in advanced cancer patients whose pain is not adequately controlled by opioids. (GW is close to finishing an extensive study to determine optimum dosages.) The company hopes recruitment of subjects won’t take more than a year. When the results are in, assuming they’re favorable, GW will apply for marketing approval from the FDA

    Dr. Notcutt’s Encouraging Input

    The researcher who conducted Phase 2 trials on Sativex (to determine basic efficacy and optimum dosage range) back in 1999-2000 is Willy Notcutt, MD, a pain specialist at James Paget Hospital in Great Yarmouth, England. O’Shaughnessy’s recently asked Notcutt whether his approach could be adapted by California physicians and patients seeking to evaluate the efficacy of high-CBD strains. The setting was the International Association of Cannabinoid Medicine in Koln, and Notcutt was speaking for himself, not GW Pharmaceuticals, which expresses official corporate disdain for smoking as a delivery system and “the crude plant” as medicine.

    Notcutt:  Indeed… Those were “N of 1″ trials. [In N of 1 trials, data is collected from individuals as their use pattern changes. The number N of patients involved in each study is one, hence the name.]  The advantages of  N-of-1 trials were first described by a chap named Guyatt in Toronto. The fundamental thing is that the patient acts as his own control.

    O’S: Is there a standard design?

    Notcutt: It’s very flexible, you can design it any which way you want to. Presumably the patients are currently using a high-THC strain. First you establish the baseline: what’s the patient’s [self-reported score on a] pain scale or the sleep line, or whatever parameters you want to measure. Then you start them on the current drug for a week. Then you put them on the new one. Then you switch them back to the current one, and so forth. You can do it as many times as you like until you say…

    [Stefan offers to buy beer, thread not picked up]

    “It can be done as many times as you want and for any period -one week, two weeks, six weeks. You can leave it open, you can do it single-blinded [not letting the patient know what he’s taking], you can do it double-blinded [neither doctor nor patient knowing which strain is being used].  But by far the easiest way to start out is to do a straight observational study: open observation and open label. The patients are going to tell you pretty quickly whether they prefer current drug or new drug. The advantage of going from current drug to new drug is, that is what a clnician actually does. That’s how medicine is practiced. I say ‘try this…’ ‘Not much help.’ ‘Now let’s try you on this new drug…’ ‘Yeah, well I think that drug has helped me…’

    “I appreciate that you have a problem with standardization, but a lot of people [medical cannabis users] say, ‘I always get this type, I know how to work it, I fine tune it, if it’s a little weak or strong I smoke a little more or smoke a little less.’ Call that the current drug, which we assume is high-THC, and then compare it with high-CBD. That’s what you’re testing: the comparative efficicacy of high-THC and high-CBD cannabis.

    “You’re using the patient as his own control and you plot it out: How many times do they smoke each day? What effects are they getting?  It’s close to what you normally would do as a clinician. That’s how I evaluate a drug anyway. If you define your parameters, and gets reports from 20 patients, you can then get a feel for whether it works.

    “I would suggest that it be done completely open-label at first.

    “Guyatt’s is not the only paper on N-of-1 trials. I have one from the BMJ [British Medical Journal] from a few years ago sayng that this is the way we should be studying chronic disease. It’s a well-recognized, acceptable clinical approach. But people have gotten so fixated in the last 20 years on the randomized, placebo-controlled trial- (sarcastically) ‘the only way you can do it,’ ‘the gold standard.’

    “I think the N-of-1 trial is the only way you study this cohort at this time, because of your problems with standardization. You have people doing it different ways… But your individual patient becomes your study. And then you can aggregate your studies. You can do some simple statistics on it: of 20 patients that started, five found it didn’t work for them at all. Now let’s look at the 15 that reported effect…

    “Then you can go on and blind your subjects and not tell them which is which. Or blind the physician. Guyatt wrote about building in a placebo, but you needn’t go to that extent. That’s not how we do medicine. The RCT [randomized, controlled trial] is furthest from normal clinical practice.

    “The N-of-1 trial is a good way of generating some data where no data exists. The first two or three GW studies were all N-of-1, until we knew that it worked. If the first nine of ten patients had said, ‘This doesn’t work,’ then you don’t go further.

    “You have to start somewhere. An observational study has the force of common sense. It may be best suited when you have a longterm chronic illness and you need some information about whether a drug works…

    “Do we give an orthopedic surgeon and an eye surgeon the same tools? No. So should we statistically evaluate every medical problem by the same technique? If we’re evaluating a drug where the blood pressure goes up or down, or the sugar level goes up or down in diabetes, we use one technique. Why use the same technique for a drug that has a completely different spectrum of activity, in an area where you don’t get nice, number data, where you get much softer data, you get subjective opinion. There’s a whole difference in the quality of the data -why use the same statistical tools?

    “People are now starting to say that evidence-based medicine is becoming a tyranny that’s killing off research. I’m very interested in this because I’m the lead for research in our district I’m also the lead for research in my own field.  If you start insisting on these big multi-center big studies, all randomized, and you don’t nurture the small studies -the little ones that come along, the N-of-1s that come along where the guy sits down and works on an idea, ‘try this out, try that out’ in a few patients, and generates a little bit more information that then leads to a bit of a better study…

    “I still regard as one of the best studies ever, the guy who treated pain after shingles with amtriptyline or nortrypteline. All he did was he found out that when he used the amitriptyline, 60 percent of the patients hated it. When he used nortriptyline only about 30 percent of the patients hated it. A simple trial -but it changed our practice. We stopped using amitriptyline, we use nortriptyline. And now we know the reasons why. That was 10, 15 years ago. I’ve never seen that simple study replicated as a clinical trial of amitriptyline versus nortriptyline because there’s no money it for the drug companies.”

    Notcutt offered to review any study design that the SCC docs come up with.

    Fred Gardner edits O’Shaughnessy’s, the journal of cannabis in clinical practice, now online at www.pcmd4u.org

    37 Responses to “Project CBD: Marijuana Specialists Plan To Study New Strains”

    1. Bradson says:

      Given the abundance of medical marijuana patients in California and other states where it’s legal, can’t N of 1 studies be done to gather data right now? Why can’t we use these patients to get a grip on benefits and any ill-effects of regular cannabis use? I can’t imagine patients refusing to give information on how the plant has helped or not helped them and what varieties have what effects. Why don’t we just ask them in the systematic way this article describes?

    2. Stompedonmyrights says:

      It seems clear to me that the Constructive Fraud our wayward government has put upon us citizens has delayed proper medical treatment and blocked advances in the rediscovery of traditional canabis medicine once enjoyed by those who needed it. So our government in it’s fraudelent concern of our nation’s health has in fact endangered the public safety it swore to protect. By our government act of fraud it has hurt the safety of the public, it has endangered the public as a whole, and it has profit from the denial of our constitutional rights. This is a criminal act and we as people have the right to reject this and seek protection under Title 42, 1983-1986 of the United States Code. Our government has acted with treason, wanton disregaurd for human life and liberty.
      Jury Nullification is the way to remove power from the government and instill it back into the people. It is time to flood the Court of this Nation with Title 42s and Writs demanding the high courts take action aganist the executive and legislative branches of this wayward government. It is time to push, it is time to push the truth into the light for all to see. It is time to start the filing process throught the Country and show the government who really owns America, and NO! it is not Corp-America, it is you and me, it is our families and friend and our future generations. Time to put your foot down.

    3. please no says:

      Great. Whereas I’m all for testing cannabis and understanding more completely its effects on the body, the LAST thing we need is another goddamned pharmaceutical company patenting another cannabis pill. Am I the only one who hates Big-Pharma and how they try to sink their greedy little claws into everything?

      We can only hope cannabis will at least be state-legal before the next pill arrives on the market to the glee of the DEA.

      God forbid you are able to go directly to the source! How then will Phizer reap the profits?

      Goddamn crooks.

      Again I support research and the pursuit of knowledge, but this is just a step for the bastards to market another pill, while the DEA continues to demonize the plant.

      Sometimes I feel like I’m swimming in a sea of power wielding imbiciles.

    4. DB says:

      Good article. I hope it inspires more independent scientific studies for the efficacy of various plants cultivated for medical use. It’s the sort of end of the line for patients who are looking to zero in on what helps them the most for their unique conditions. Every patient needs the right strain to help them out. I hope to see many results that trickle their way down to all of the dispensaries located throughout the U.S. so that everyone gets what they need.

    5. Patricia says:

      If CBD is not psychoactive, then why does Romulan make me go to sleep?

    6. “Sativex” is nothing but hemp oil. They have removed the m”medicine” from the plant,probably the same way Rick Simpson did or some other process that ends up being the same “medicine”,added a carrier fluid.probably alcohol,and are planning on selling it through the drug stores. After a suitable period,they will discover that Sativex blocks cancer,and we will have our first cancer blocking medicine made by the pharmaceutical companies and sold for billions to everyone. And they will try to do this while keeping marijuana schedule 1,so you can’t make your own.
      Combine this with the marijuana patch being developed and the “treatment” centers,owned by the same people owning the private prison systems and you have the next step in continuing making of money by the same industrial group. What a concept!

    7. =

      Yes but some people like me like the high both mind and body research can’t tell me what I already know from over 30 years personal experience what we need is research that informs people and legislators that cannabis is less harmless then other things like HIGH FRUCTOSE CORN SYRUP. If you are in Washington state or
      California you should call write and E-mail your state senators and reps and tell them they wont get your vote unless they support marijuana legalization we have to come out and do this or we will still be looking over our shoulders

    8. unknown says:

      as one with a neuro disorder with a lot of pain, I would love for this to take place…Few of us actually smoke the weed for those qualities…and I cant wait for this to go through…test it in california, some of the true patients need it, problem is thats about 10 percent of those with cards.

    9. unknown says:

      realize what is really positive is the research….its super important to find out why we get certain effects from certain cannabanoids, and then capture those, and we can almost create the relief we need…fantastic…I love it.

    10. Joel M. says:

      Why don’t they research the CBD/THC ratio of Rick Simpson’s oil.

      [Editor’s note: Obviously both patients and doctors are keen on finding so-called cures for cancer. As promising as some cannabinoid compounds are regarding possibly shrinking some types of cancer tumors, as NORML has been often the first to report on such for the last decade, crude cannabis (hash and/or ‘honey’) oils at this time can not be said to cure cancer.

      A note below from cannabis researcher, author and Harvard Medical School professor Lester Grinspoon, MD re his concerns about Simpson’s claims, in response to a recent High Times article about Simpson.

      ***
      Medical Marijuana: A Note of Caution re Rick Simpson’s claims
      by Lester Grinspoon, M.D.

      Like everyone else who has been working over decades to ensure that marijuana, with all that it has to offer, is allowed to take its proper place in our lives, I have been heartened by the rapidly growing pace at which it is gaining understanding as a safe and versatile medicine. In addition to the relief it offers to so many patients with a large array of symptoms and syndromes (almost invariably at less cost, both in toxicity and money than the conventional drugs it replaces), it is providing those patients, their caregivers, and the people who are close to them an opportunity to see for themselves how useful and unthreatening its use is. It has been a long and difficult sell, but I think it is now generally believed (except by the United States government) that herbal marijuana as a medicine is here to stay. The evidence which underpins this status as a medicine is, unlike that of almost all other modern medicines, anecdotal. Ever since the mid-1960s new medicines have been officially approved through large, carefully controlled double-blind studies, the same path that marijuana might have followed had it not been placed in Schedule 1 of the Controlled Substances Act of 1970 which has made it impossible to do the kind of studies demanded for approval by the Food and Drug Administration. Anecdotal evidence commands much less attention than it once did, yet it is the source of much of our knowledge of synthetic medicines as well as plant derivatives. Controlled experiments were not needed to recognize the therapeutic potential of chloral hydrate, barbiturates, aspirin, curare, insulin, or penicillin. And there are many more recent examples of the value of anecdotal evidence. It was in this way that the use of propranolol for angina and hypertension, of diazepam for status epilepticus (a state of continuous seizure activity), and of imipramine for childhood enuresis (bed-wetting) was discovered, although these drugs were originally approved by regulators for other purposes.

      Today, advice on the use marijuana to treat a particular sign or symptom, whether provided or not by a physician, is based almost entirely on anecdotal evidence. For example, let’s consider the case of a patient who has an established diagnosis of Crohn’s disease but gets little or no relief from conventional medicines (or even occasional surgery) and suffers from severe cramps, diarrhea and loss of weight. His cannabis-savvy physician, one who is aware of compelling anecdotal literature suggesting that it is quite useful in this syndrome, would not hesitate to recommend to this patient that he try using marijuana. He might say, “Look, I can’t be certain that this will help you, but there is now considerable experience that marijuana has been very useful in treating the symptoms of this disorder, and if you use it properly, it will not hurt you one bit; so I would suggest you give it a try and if it works, great — — if it does not, it will not have harmed you.” If this advice is followed and it works for this patient, he will report back that, indeed, his use of the drug has eliminated the symptoms and he is now regaining his weight; or that it doesn’t work for him but he is no better or worse off than he was before he had a trial of marijuana. Particularly in states which have accommodated the use of marijuana as a medicine, this kind of exchange is not uncommon. Because the use of cannabis as a medicine is so benign, relative to most of the conventional medicines it competes with, knowledgeable physicians are less hesitant to recommend a trial.

      One of the problems of accepting a medicine, particularly one whose toxicity profile is lower than most over-the-counter medicines, on the basis of anecdotal evidence alone is that it runs the risk of being over- sold. For example, it is presently being recommended for many types of pain, some of which are not responsive to its analgesic properties. Nonetheless, in this instance, a failed trial of marijuana is not a serious problem; and at the very least both patient and physician learn that the least toxic analgesic available doesn’t work for this patient with this type of pain. Unfortunately, this kind of trial is not always benign.

      In the January issue of High Times Steve Hager published an article, “Rick Simpson’s Hemp-Oil Medicine” in which he extols the cancer-curing virtues of a concentrated form of marijuana which a Canadian man developed as “hemp-oil”. Unfortunately, the anecdotal evidence on which the cancer-curing capacity is based is unconvincing; and because it is unconvincing, it raises a serious moral issue.

      Simpson, who does not have a medical or scientific education (he dropped out of school in ninth grade), apparently does not require that a candidate for his treatment have an established diagnosis of a specific type of cancer, usually achieved through biopsy, gross and histopathological examinations, radiologic and clinical laboratory evidence. He apparently accepts the word of his “patients”. Furthermore, after he has given the course of “hemp-oil” there is apparently no clinical or laboratory follow-up; he apparently accepts the “patient’s” belief that he has been cured. According to Hager, he claims a cure rate of 70%. But 70% of what? Do all the people he “treats” with hemp oil medicine have medically established, well-documented cancer or is he treating the symptoms or a constellation of symptoms that he or the patient have concluded signify the existence of cancer? And what is the nature and duration of the follow-up which would allow him to conclude that he has cured 70%? Furthermore, does this population of “patients with cancer” include those who have already had therapeutic regimes (such as surgery, radiation, or chemotherapy) which are known to be successful in curing some cancers or holding at bay, sometimes for long periods of time, many others?

      There are patients who have a medically sound diagnosis of pre-symptomatic cancer (such as early prostate cancer) but who, for one reason or another, eschew allopathic treatment and desperately seek out other approaches. Such patients are all too eager to believe that a new treatment, such as hemp-oil medicine, has cured their cancer. Unfortunately, this cancer which was asymptomatic at the time of its discovery, will eventually become symptomatic and at that time the possibility of a cure is significantly diminished, if not no longer a conceivable goal.

      This lesson was brought home to me when I was asked by the American Cancer Society during a period early in my medical career when I was doing cancer research to participate in an investigation of a man in Texas who claimed that a particular herb that his grandfather discovered would cure cancer. I was able to locate two women who had well documented diagnoses of early (asymptomatic) cervical cancer who had decided not to have surgery but instead went to Texas and took the “medicine”. When I first met them some months after each had taken the “cure” they were certain that they were now cancer free. With much effort, I was able to persuade them to have our surgical unit perform new biopsies, both of which revealed advancement in the pathological process over their initial biopsies. Both were then persuaded to have the surgery they had previously feared, and there is no doubt that this resulted in saving their lives.

      There is little doubt that cannabis now may play some non-curative roles in the treatment of this disease (or diseases) because it is often useful to cancer patients who suffer from nausea, anorexia depression, anxiety, pain, and insomnia. However, while there is growing evidence from animal studies that it may shrink tumor cells and cause other promising salutary effects in some cancers, there is no present evidence that it cures any of the many different types of cancer. I think the day will come when it or some cannabinoid derivatives will be demonstrated to have cancer curative powers, but in the meantime, we must be very cautious about what we promise these patients.

      Dr. Grinspoon’s webpages are: rxmarijuana.com and marijuana-uses.com and ]

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