“Good and bad in every group.” O’Shaughnessy’s $5.95 The Journal of Cannabis in Clinical Practice Summer 2010 Doctors to Study Effectiveness of CBD By Fred Gardner Tod Mikuriya, MD, did not live to see “Placeholder” Questionnaire it, but his dream of investigating the Why is this plant different medical potential of compounds in the from all other plants? INTRODUCING PROJECT CBD cannabis plant other than THC is now within the grasp of his successors. Our collective is involved in a research project to assess the The Society of Cannabis Clinicians, effects of strains relatively rich in cannabidiol (more than 4% the group Mikuriya founded in 1999, has CBD). Collective members who medicate with CBD-rich can- drafted a “Strain Evaluation Survey” to nabis are encouraged to take part in this research by report- collect data from patients who medicate ing your observations on the back of this form with cannabis in which cannabidiol Is CBD-rich Cannabis right for you? (CBD) is predominant Research suggests that CBD could be effective in easing CBD-rich cannabis will be available the symptoms of rheumatoid arthritis, diabetes, nausea, and at California and Colorado dispensaries inflammatory bowel disorders, among other difficult-to-con- by late summer —and soon thereafter, trol conditions. CBD is non-psychoactive and may counter inevitably, in other states where patients certain effects of THC. Patients who want the anti-inflamma- can legally use cannabis as medicine. tory, anti-pain, anti-anxiety, or anti-spasm effects of cannabis Twelve strains rich in cannabidiol delivered —possibly— without disconcerting euphoria or se- (CBD) have been identified in the year dation might prefer CBD-rich Cannabis. and a half since an analytic chemistry How to conduct an N=1 Trial lab began testing cannabis samples pro- CBD-RICH CANNABIS PLANT is A simple way to collect information about effects is called vided by California dispensaries, grow- held lovingly by Ralph Trueblood of the “N-of-1” trial, in which one patient is both the test subject ers, and edible makers. Buds from five the Wo/men’s Alliance for Medical and the control. All you have to do is medicate with a CBD- of these strains have been available in- Marijuana. It was cloned from a True rich strain for a set period of time —say, a week— and then termittently at Harborside Health Cen- Blueberry/OG Kush cross found to medicate with your regular high-THC strain for the same pe- ter in Oakland. Herbal Solutions in Long contain approximately 10% CBD and riod. Use this form to describe any differing effects that you Beach also has provided CBD-rich can- 6 percent THC by weight. The strain notice: “less anxiety,” “more stoney than I want,” “less sedat- nabis to patients. was developed by Wendell Lee of Full ing,” “better sleep,” “no difference,” etc., etc. Eight of the CBD-rich strains are cur- Spectrum Genetics. rently being grown out. The others can- not be reproduced because the growers Various studies published in the medi- INFORMATION FOR PATIENTS appears on front page of a form developed hadn’t saved or couldn’t regain access cal and scientific literature suggest that to involve dispensaries in data collection. Patients getting CBD-rich strains to the genetic material that yielded their CBD could be effective in easing the are asked to describe their dose and use pattern, as well as “Conditions/symp- buds of interest. symptoms of rheumatoid arthritis, dia- toms used to treat” and “Effects observed.” A more detailed and formal ques- More than 9,000 samples have been betes, nausea, and inflammatory bowel tionnaire is being developed by the Society of Cannabis Clinicians. tested to date by the Steep Hill lab in disorders, among other difficult-to-con- Oakland. Other start-up labs in Califor- trol conditions. CBD also has demon- Inside this issue nia, Colorado, and Montana have begun strated neuroprotective effects, and its testing for the burgeoning industry. The anti-cancer potential is being explored Martin Lee and Gregory Gerdeman Full Spectrum lab in Denver has tested at several academic research centers. On The Endocannabinoid System some 4,500 strains and identified seven An even wider market would emerge CBD-rich strains. if the reduced psychoactivity of CBD- A strain that is roughly 6% CBD and rich cannabis makes it an appealing treat- The O’Shaughnessy’s Review 6% THC, “Cannatonic,” has been devel- ment option for patients seeking anti-in- of Books oped by Resin Seeds in Barcelona and flammatory, anti-pain, anti-anxiety, and/ is being grown from seed by several col- or anti-spasm effects delivered without lectives. Its name may be misleading, disconcerting euphoria or lethargy. since CBD supposedly cancels the se- The Blue-Ribbon Plant dating effects of THC. The plant richest in CBD is a “True For purposes of the data collection Blueberry/OG Kush” cross grown in the OVEL REATMENT FOR UTISM being planned by the Society of Can- A N T A mountains south of Yreka by Wendell nabis Clinicians, “CBD-rich” cannabis Lee of Full Spectrum Genetics (not to BY LESTER GRINSPOON is being defined as more than 4% can- be confused with the lab in Colorado). nabidiol by weight (without respect to Dried buds of TB/OGK have been sent THC content) or more than 2.5% CBD for testing on four occasions by The Changing Nature of My Practice if CBD exceeds THC. Harborside, the dispensary with which By Christine Paoletti Potential Usefulness of CBD Lee is associated. Samples were consis- Until testing for cannabinoid content tently found to contain about 10% CBD On Issuing Cannabis Recommendations began, it was widely assumed that CBD, (with THC levels around 6 to 7%). On which is non-psychoactive, had been the only occasion that a crop grown out- By Stacey Kerr bred out of all the cannabis in California doors by Lee was tested by Steep Hill by generations of growers seeking maxi- lab, it was found to contain 13.9% CBD. mum THC content. Two other labs have confirmed the Dale Gieringer: CBD content of Lee’s TB/OGK. What Would “Legalization” Mean? What benefits did G.W. sci- Lee is now working to “stabilize the genetics” and produce TB/OGK seeds. entists expect a CBD-rich ex- Several plants he provided to Project plus tract to confer? CBD (a nonprofit organized by writer/ ROBERT C . CLARKE: HASHISH!! activist Martin Lee to promote research) Doctors in the SCC have watched are being grown out by experienced Jorge Cervantes Walks Into a Bookstore... with great interest in recent years as a hands. Processed medicine and clones British company, G.W. Pharmaceuticals will be available at dispensaries in the Louis Armstrong: More a Medicine Than a Dope conducted clinical trials of cannabis- months ahead. Details will be available plant extracts. G.W. has a license from on ProjectCBD.com, a website that will PREVIEWS FROM BLOCKBUSTERS IN MANUSCRIPT the British government and backing from be launched by mid-August, according Otsuka, a Tokyo-based multinational. to Martin Lee (no relation to Wendell). Excerpts from forgotten classics, & much more G.W.’s flagship product, Sativex, is The California strain richest in CBD a plant extract that contains approxi- proportionally, “Women’s Collective mately equal amounts of CBD and THC. Stinky Purple,” tested at 9.7% CBD and David West: A Call From Nebraska What benefits did G.W. scientists expect 1.2% THC. It was brought to Harborside a CBD-rich extract to confer? continued on page 41 O’Shaughnessy’s • Summer 2010 —41—

Project CBD from front page by Grower #1 who also grows a strain not have the typical ‘high’ that goes with Yreka! called “Cotton Candy/Diesel” that was these therapeutic effects.” found to contain about 6% CBD and 6% But patient 10, who has been smok- THC. Grower #1 gets her starter plants ing TB/OGK reported, “I enjoy the herb, from friends in Northeastern Mendocino enjoy being able to use during the day County. Is there something in the ge- without getting too spaced out, but have nome of plants that have been swapped to watch out for memory lapses. I do stu- over the years by growers in those hills pid things like forget where I put stuff that encourages expression of CBD? because I think I’m not affected, but I Another strain containing more than am affected.” 8% CBD, grown indoors in the East Bay, CBD CONTENT of True Blueberry/OG HIGH-THC STRAIN, typical of the >9,000 was brought to Harborside in late April. “Dose level is going to be Kush is indicated by large spike at left of tested to date in California, has virtually “Omrita Rx3” is the name the grower very, very important.” chromatogram from Steep Hill lab. Spike no CBD. Scale at bottom gives amount of has given it after learning that it was of to its right shows THC. Small spike shows time heating in the urn of the gas special interest Patient Four in the Project CBD da- level of Cannabinol (a breakdown product chromatograph. Vertical scale indicates of THC). Spike at right in both chromato- amount of specific compounds evaporating to SCC doctors. tabase, a 70-year-old man with arthritis, grams is the lab’s internal standard. at known temperatures. A few weeks responded in detail: “Definitely anti-pain later a strain and anti-inflammatory. I would not call The Doctors’ Hopes re CBD that it has many medicinal uses and may called “Harle- the effect a ‘high’ but I’m not sure it’s The wide range of variables and “con- afford relief from their symptoms with quin” was found non-psychoactive. I would call it a ‘bal- founding factors” confronting doctors fewer adverse effects than conventional to contain about anced effect’ or a ‘calming effect.’ You who want to study the effects of CBD- pharmaceuticals. 8% CBD. And feel like you’re on a more even keel.” rich strains was discussed at the winter soon thereafter a For 10 days Patient Four ingested meeting of the Society of Cannabis Cli- Hergenrather hopes that pound of “Jamaican Lion” tested at 8.9% cookies made with trim from TB/OGK. nicians. CBD. Clones of these strains are being (The trim was 5.1% CBD, 2.5% THC but UCSF professor Donald Abrams, plant breeders will now try to grown out and will be available through we don’t know the amount used in the MD, the featured speaker, recounted the lower THC content. Harborside and Project CBD in the butter from which the cookies were obstacles he faced in conducting clini- months ahead, along with the Soma A+ made.) He reports being“able to concen- cal trials with government-issued can- “I am seeing many older patients who that was first to be identified. trate for hours at a time and get up from nabis and getting his results published would like to try cannabis for pain, Pineapple Thai (5% CBD, 2.4% my desk without groaning... Once or in peer-reviewed medical journals. muscle spasms, insomnia, and manage- THC) is being grown out by Herbal So- twice as the effect was coming on, I be- SCC President Jeffrey Hergenrather ment of various cancers. One thing that lutions in Long Beach. gan to feel sedated, but that passed and volunteered to head the committee that most of these cannabis-naive patients are Anecdotal Evidence I then experienced about three pain-free will organize the group’s data collection not interested in is ‘getting high.’ My To get the ball rolling on data collec- hours... Once I ate an extra half a cookie effort. Abrams agreed to informally con- hope is that the CBD-rich strains will tion, Project CBD developed a form to and was definitely sedated. Fortunately, sult on the SCC study design. enable them to use cannabis and get its be given to patients purchasing high- it was bedtime... Dose level is going to The first step, a “Strain Evaluation benefit without —or with less of— the CBD cannabis at participating dispen- be very, very important.” Survey,” will soon be accessible on the usual ‘high.’” SCC’s website. It asks, among other Hergenrather thinks that patients who saries (see illustration on page 1). Feed- Caveat hemptor things, “What factors limit your use of “might benefit by maintaining a higher back has also been solicited from a group Some caveats as we begin our long cannabis at a frequency that affords op- blood level of active cannabinoids include of physicians who were given a small march towards collectively identifying timal relief of symptoms?” those with inflammatory bowel diseases amount of TB/OGK trim [leaves re- the effects of cannabidiol. The answer options are: “Cost,” (Crohn’s and ulcerative colitis), the moved when buds are manicured] for 1) The amount of CBD present will “Can’t perform tasks,” “Family or so- neurodegenerative diseases (multiple self-testing. not be the only factor influencing the ef- cial reasons,” “Concern for having use sclerosis, ALS, Parkinson’s, Hunting- The anecdotal evidence coming from fects of a given cannabis-based medi- discovered,” “Get too sleepy,” “Get too ton’s), epilepsy disorders, autoimmune these two sources —about 12 people to- cine. The ratio of CBD to THC may be altered/ spacey,” and “Concern for ha- disorder, (Lupus, rheumatoid arthritis, tal— has been generally but not entirely as important, and the terpenoid and fla- bitual use.” etc.), stroke, concussion, and brain consistent. Frequent reference is made vonoid content may be as important. Hergenrather says that he is beginning trauma, and cannabis-sensitive cancers — to pain relief, a calming effect, and un- 2) We are capable of placebo-effect- to see in his practice, “a growing per- glioblastoma multiforme, thyroid cancer, impaired —or improved— ability to ing ourselves individually and placebo- centage of patients, especially older pa- lymphomas and some leukemias, colon concentrate. effecting ourselves collectively. Some tients, who have not used cannabis be- cancers, neuroblastoma, and others).” Patient G. is an experienced cannabis may exaggerate the potential benefits of fore, but they have come to understand continued on next page user age 81 who regularly smokes a CBD and raise false hopes. high-THC joint in the evening. He tested 3) The line between physical effect GW Pharmaceuticals’ “Tale of Two Cannabinoids” a CBD edible on three occasions and the and effect on mood is often indistinct. results were identical. He experienced Improved mood might result, for ex- G.W.’s flagship product is Sativex, an oral spray that contains about equal no noticeable effect after consuming a ample, if the man with arthritis experi- amounts of CBD and THC. The rationale for the combination was set forth in brownie in the late afternoon. He expe- ences reduced inflammation and less of “A Tale of Two Cannabinoids,” a 2005 article by doctors Ethan Russo and rienced “diminished effect” from his the “background pain” that afflicts older Geoffrey Guy in the online journal Medical Hypotheses. Here’s the summary: subsequent high-THC joint.“But the people. “CBD is demonstrated to antagonise some undesirable effects of THC in- next morning when I went for my walk,” 4) When a patient reports the effect cluding intoxication, sedation and tachycardia, while contributing analgesic, he reports, “I went further and faster than of a drug on mood or pain, the report is anti-emetic, and anti-carcinogenic properties in its own right. In modern clini- I had in a long time.” inherently subjective. cal trials, this has permitted the administration of higher doses of THC, pro- Several people said they appreciated 5) How CBD in the liver affects the viding evidence for clinical efficacy and safety for cannabis based extracts in the relative lack of psychoactivity. As metabolism of other drugs has not been treatment of spasticity, central pain and lower urinary tract symptoms in mul- Patient 9 put it after smoking TB/OGK, studied thoroughly. The Drug Warriors tiple sclerosis, as well as sleep disturbances, peripheral neuropathic pain, bra- “CBD-rich cannabis seems relaxing and could argue that Prohibition must remain chial plexus avulsion symptoms, rheumatoid arthritis and intractable cancer soothing in regards to pain, anxiety, in effect because “more research is pain. Prospects for future application of whole cannabis extracts in muscle tension and spasms, and it does needed.” neuroprotection, drug dependency, and neoplastic disorders are further exam- ined. The hypothesis that the combination of THC and CBD increases clinical BIOSYNTHETIC PATHWAY by efficacy while reducing adverse events is supported.” which THC and CBD are created with- in the plant from a part of the CBGA Sativex has been approved by Health Canada for treating neuropathic pain (Cannabigerolic acid) molecule is in multiple sclerosis and cancer. It is obtainable by prescription in 22 coun- shown at right. THCA synthase and tries. After passing an important regulatory hurdle in March, GW expects im- CBDA synthase are enzymes that pro- minent approval of Sativex as a treatment for MS spasticity in the UK and mote a reaction (“oxidative cycliza- Spain. tion”) whereby CBGA forms THC acid (THCA) and CBD acid (CBDA). THC GW is close to finishing an extensive study to determine and CBD are then generated from the “therapeutic window” —the dosage level high enough THCA and CBDA by non-enzymatic to relieve the pain but low enough to prevent the high. loss of CO2. Several labs are studying the mechanism by which the enzymes The U.S. FDA has given GW approval to conduct a clinical trial in ad- promote the reactions. One theory of vanced cancer patients whose pain is not adequately controlled by opioids. why the offspring of a plant whose GW is close to finishing an extensive study to determine the “therapeutic win- parents contain only trace amounts of dow” —the dosage level high enough to relieve the pain but low enough to CBD may be rich in CBD: a genetic prevent the high. The company hopes recruitment of subjects won’t take more mutation resulting in excess CBDA than a year. When the results are in, assuming they’re favorable, GW will synthase or deficient THCA synthase. apply for marketing approval from the FDA. —42— O’Shaughnessy’s • Summer 2010

Project CBD from previous page Hergenrather hopes that plant breed- dren, an analytical mind, and is already “My hope, says Dr. Kerr, “is that amounts that are most effective.” ers will now try to lower THC content. stoned enough on the prescription meds having a CBD-rich strain will allow her Kerr adds, “My patients who are pro- “Having an option to use a CBD-rich she needs. to use the medicine as often as needed fessionals without a history of using strain that is low in THC would not only “I was able to provide a legal recom- without extreme side effects but with ex- marijuana would be more likely to use it benefit the patients who don’t want to mendation for her use of medical can- cellent relief for nausea and vomiting. if it was specifically for medical uses and get ‘high’ but also all of those patients nabis. I explained CBD strains to her and Oral intake would be beneficial with not ‘tainted’ with a culture of illicit highs. who would benefit with higher blood her caregivers (all of them are profes- longer-lasting effects and direct activity This is a cultural block, I know, but it is levels of cannabidiol. sionals) and Linda’s caregivers were able on the most inflamed tissue. If she was real, and I work hard to overcome it ev- to obtain an ounce of TB/OGK bud from not afraid of the side effects, she would ery time I counsel on the use of medical CBD Helper? Harborside in early April. be more willing to use the medication in continued on next page A simple way to raise the CBD-to- THC ratio of a given batch of medical cannabis is to blend in dried flowers “You have to start somewhere...” from a CBD-rich hemp plant contain- ing only trace amounts of THC. That’s Willy Notcutt on Evaluating Cannabis by N=1 Trials how G.W. Pharmaceuticals produces Willy Notcutt, MD, is a pain spe- Sativex —by growing CBD-rich hemp cialist at James Paget Hospital in Great “An observational study plants outdoors and THC-rich plants in Yarmouth, England. He conducted the has the force of common glasshouses, then blending them. phase 2 clinical trials for Sativex in sense. ” In February a friend in Spain sent 1999-2000. Project CBD seeds from a hemp strain Notcutt’s first step had been to as- whose flowers reportedly contain four sess the basic efficacy and optimum furthest from normal clinical practice. to six percent CBD, depending on grow- dosage range of Sativex (prior to clini- The N-of-1 trial is a good way of ing conditions. These were started in- cal trials) by means of “N=1” trials. In generating some data where no data doors by a grower affiliated with the Los N-of-one trials, as they’re called, data exists. The first two or three studies Angeles-based Cornerstone Research is collected from individuals as their were all N-of-1, until we knew that it use pattern changes. The number N of worked. If nine of the first ten patients Collective —along with seeds of WILLY N OTCUTT AND TOD MIKURIYA at patients involved in each study is one, “Cannatonic” that had been donated by Asilomar, June 2002. had said, “This doesn’t work,” then Resin Seeds of Barcelona. According to hence the name. you don’t go further. Project CBD’s benefactor, one in four We asked Notcutt if there was any always get this type, I know how to work You have to start somewhere. An of the Cannatonic seeds —available reason why California doctors could it, I fine tune it, if it’s a little weak or observational study has the force of from resinseeds.com—should contain not use a similar approach as CBD-rich strong I smoke a little more or smoke a common sense. It may be best suited 6.5% CBD by weight, and the same strains become available to their pa- little less.” Call that the current drug, when you have a long-term chronic amount of THC. “The perfect Sativex tients. This interview was conducted in which we assume is high-THC, and then illness and you need some information mix,” is how he describes the strain’s Koln at the 2009 meeting of the Inter- compare it with high-CBD. about whether a drug works... cannabinoid content. national Association for Cannabis That’s what you’re testing: the com- Do we give an orthopedic surgeon Project CBD also has a line on in- Medicine. Notcutt was speaking as an parative efficacy of high-THC and high- and an eye surgeon the same tools? No. dustrial hemp seeds reported to contain individual and the views expressed CBD cannabis. You’re using the patient So should we statistically evaluate ev- 10% CBD and almost no THC! may not represent G.W. Pharmaceuti- as his own control and you plot it out: ery medical problem by the same tech- cals’ position. —F.G. How many times do they smoke each nique? If we’re evaluating a drug Overcoming Hesitance Notcutt: The advantages of N-of- day? What effects are they getting? where the blood pressure goes up or Stacey Kerr, MD, of Santa Rosa has 1 trials were first described by a chap It’s close to what you normally would down, or the sugar level goes up or been doing home visits with cancer pa- named Guyatt in Toronto. The funda- do as a clinician. That’s how I evaluate down in diabetes, we use one tech- tients, “filling in the gaps that all their mental thing is that the patient acts as a drug anyway. If you define your pa- nique. other doctors can’t fill. When you are his own control. rameters, and get reports from 20 pa- Why use the same technique for a getting care from several specialists, O’S: Is there a standard design? tients, you can then get a feel for whether drug that has a completely different these gaps will sometimes happen. So I Notcutt: It’s very flexible, you can it works. spectrum of activity, in an area where sit by the bedside and take the time to design it any which way you want to. I would suggest that it be done com- you don’t get nice, number data, where talk about therapy and side effects. Then Presumably the patients are currently pletely open-label at first. you get much softer data, you get sub- we problem solve about how to deal with using a high-THC strain. First you es- Guyatt’s is not the only paper on N- jective opinion? There’s a whole dif- the side effects and how to best com- tablish the baseline: what’s the patient’s of-1 trials. I have one from the BMJ ference in the quality of the data — municate with their treating physicians. [self-reported score on a] pain scale or [British Medical Journal] from a few why use the same statistical tools? “Several of my patients are using can- the sleep line, or whatever parameters years ago saying that this is the way we People are now starting to say that nabis for nausea and vomiting. However, you want to measure. Then you start should be studying chronic disease. It’s evidence-based medicine is becoming they are hesitant to use it because of the them on the current drug for a week. a well-recognized, acceptable clinical a tyranny that’s killing off research. psychoactive effects and we spend time Then you put them on the new one. approach. But people have gotten so fix- I’m very interested in this because I’m talking about the most effective way to Then you switch them back to the cur- ated in the last 20 years on the random- the lead for research in our district I’m dose, the timing of their doses, and the rent one, and so forth. ized, placebo-controlled trial, (sarcasti- also the lead for research in my own medication itself.” It can be done as many times as you cally) ‘the only way you can do it,’ ‘the field. Kerr offers the example of Linda (not want and for any period —one week, gold standard.’ If you start insisting on these big her real name) a patient with metastatic two weeks, six weeks. You can leave it I think the N-of-1 trial is the only way multi-center big studies, all random- breast cancer in her bones, liver, and open, you can do it single-blinded [not you study this cohort at this time, be- ized, and you don’t nurture the small possibly her stomach. “She finished letting the patient know what he’s tak- cause of your problems with standard- studies -the little ones that come along, three weeks of intensive radiation and ing], you can do it double-blinded [nei- ization. You have people doing it differ- the N-of-1s that come along where the just now finished her first three weeks ther doctor nor patient knowing which ent ways... But your individual patient guy sits down and works on an idea, of intensive chemotherapy. She has lost strain is being used]. But by far the becomes your study. And then you can “Try this out, try that out” in a few pa- over 30 pounds through the course of easiest way to start out is to do a straight aggregate your studies. You can do some tients, and generates a little bit more treatment. She is bedridden and ex- observational study: open observation simple statistics on it: of 20 patients that information that then leads to a bit of tremely weak. This woman is a highly and open label [both doctor and patient started, five found it didn’t work for them a better study... educated professional and a triathlete. know what’s being used]. at all. Now let’s look at the 15 that re- I still regard as one of the best stud- “I was at Linda’s home this past Sat- ported effect... ies ever, the guy who treated pain af- urday and on Easter Sunday discussing You’re using the patient as Then you can go on and blind your ter shingles with amtriptyline or options for nausea/vomiting control. Her his own control. subjects and not tell them which is nortriptyline. All he did was he found pain is well treated. The image she de- which. Or blind the physician. out that when he used the amitriptyline, scribed to me when she drinks a glass of The patients are going to tell you Guyatt wrote about building in a pla- 60 percent of the patients hated it. water is that of a boiling hot metal caul- pretty quickly whether they prefer cur- cebo, but you needn’t go to that extent. When he used nortriptyline only about dron hit with cold water so the water rent drug or new drug. The advantage That’s not how we do medicine. The 30 percent of the patients hated it. erupts right back up and out because of of going from current drug to new drug RCT [randomized, controlled trial] is A simple trial —but it changed our the heat reaction. She is using several is, that is what a clinician actually does. practice. We stopped using different prescription medications, but That’s how medicine is practiced. amitriptyline, we use the medication that works most effec- I say, “ Try this.” nortriptyline. And now we tively for the vomiting is cannabis. “Not much help.” know the reasons why. That “She was not a regular user prior to “Now let’s try you on this new was 10, 15 years ago. I’ve her cancer needs. Her only complaint is drug.” never seen that simple that it does not seem to last very long “Yeah, well I think that drug has study replicated as a clini- when she uses the helped me.” cal trial of amitriptyline vaporizer, and she I appreciate that you have a prob- versus nortriptyline be- doesn’t want to be lem with standardization, but a lot of cause there’s no money in ‘stoned.’ She has people [medical cannabis users] say, “I it for the drug companies. two small chil- O’Shaughnessy’s • Summer 2010 —43—

Project CBD from previous page The “First-Ever ‘Medical’ Cannabis Cup” marijuana. CBD-rich strains that are ef- fective will support our efforts to legiti- mize cannabis as powerful, authentic High Times puts on a White Coat medicine.” High Times magazine organized the DJ Short, the renowned plant breeder Valerie Corral, DJ Short, and Possible mechanisms of action original “Cannabis Cup” in Amsterdam and seed merchant, had to judge 38 In- Martin Lee explains that based on in 1987. The event inspired plant breed- dica samples. He and Val each managed Jorge Cervantes felt impelled to published studies, CBD should provide ers, publicized their strains and seed to select a top five (in consultation with extol the virtues of the sun. “an enhanced endocannabinoid effect companies, and strengthened their sense High Times editors), and then Jorge even though it does not bind to a can- of community. It has been held annually Cervantes, the best-selling author of cul- line, almost every plant nowadays is a nabinoid receptor. CBD indirectly stimu- ever since —a fine excuse for a trade tivation guides, made the final call. hybrid. He cites the example of Flo, a lates both CB1 and CB2 receptor sig- show and an extended party at harvest Valerie Corral is a very positive strain he developed that is “a quick fin- naling in at least two key ways: time. woman. She said that every bud she isher but has narrower leaves and a Sa- “First, CBD inhibits the production The pretext of a cannabis cup is that evaluated was “a jewel grown with the tiva effect.” of FAAH, the enzyme that breaks down discerning judges will sample various best intentions.” But the chemical resi- Both Valerie Corral and DJ Short anandamide, and this results in higher strains and determine the best (to be an- due on some made her cough, and one were struck by the predominance of can- anandamide levels (think runner’s high) nounced at the climactic awards cer- gave her a headache. DJ Short, who is nabis grown indoors and felt impelled and heightened CB1 receptor signaling, emony). The truth is, it’s impossible for not partial to Indicas in general, didn’t to extol the virtues of the sun. So did given that anandamide activates the CB- judges, soon after sampling strain #1, to find any he especially liked among the Jorge Cervantes, who gave a talk on cul- 1 receptor (but not CB2.) At the same distinguish the effects of sample #2. The cup entrants. But the show must go on, tivation to a rapt SRO audience. Note time, CBD buffers the psychoactivity of body needs an interval of at least three and Cervantes made executive decisions that the Amsterdam cannabis cup is held THC by preventing THC from binding or four hours for a return to baseline can- in November, when the natu- with the CB1 receptor. nabinoid levels. Lester Grinspoon, MD, ral harvest has come in. In “Also, it appears that CBD amplifies thinks that evaluating only one sample a California, where most cultiva- THC’s activation of the CB2 receptor. day would make the most sense. tion goes on indoors, the cup Several studies show that CBD and THC High Times recently launched a glossy was held in June. augment each other’s analgesic and anti- quarterly called High Times Medical Mikki Norris said that her inflammatory properties. A combination Marijuana News and Reviews, edited in group eliminated from consid- of THC and CBD is much better than San Francisco. To celebrate their arrival eration those concentrates that THC alone in providing pain relief.” on the scene, the magazine staff orga- had been produced — nized a “medical” cannabis cup. They detectably— by solvent extrac- Project CBD billed it as the “first ever,” although simi- tion. (Like you could smell the The goals of Project CBD are educa- lar contests with medical themes have butane.) She was pleased to tional, according to Lee, but they can “NO TOBACCO SMOKING” signs did not deter ma- been held in Portand and at Area 101 ture hipsters from mixing some in with their cannabis learn from the producer of also be seen as political and/or public north of Laytonville for several years. at the High Times event in San Francisco. Ingrid hash, Gabriel Martin of relations for the Society of Cannabis The third-ever medical cannabis cup Clinicians (whose studies the site will based on appearance and aroma. Mendocino, that he had used the Ice-o- was held June 19-20 at Terra, an events be facilitating and publicizing). Some of And the winners were... Best Sativa: lator method, in which trichomes are center —an erstwhile factory with a large the messages Project CBD hopes to get “God’s Pussy,” from GreenBicycles up washed off the flowers by cold water. side-yard— on Harrison St., kitty cor- across to the American people: in Crescent City... Best Indica: “Cali High Times Medical News and Re- ner from the Sailors and Seamen’s Union • A non-psychoactive component of Gold,” from Mr. Natural, Inc.... Best con- views gave an award to Lester hall. The weather was okay on Saturday, the plant may have important medical centrate (chosen by Chris Conrad and Grinspoon, MD, for his enduring service perfect on Sunday, and a whompin’good benefits. Mikki Norris from among 16 entrants): to the cause. Grinspoon winced when time was had by about 2,000 medical • Pro-cannabis doctors and their pa- Ingrid, by the Leonard Moore collective, he learned the name of the winning Sa- cannabis users each day. Tickets cost tients want to see if this non-psychoac- Mendocino... Best edible: biscotti from tiva, and High Times promptly took the $50, vendors paid $1,500 for tables. It tive component is effective in treating Greenway in Santa Cruz. offensive term down from its website. was not the standard High Times demo- various conditions. Steep Hill lab in Oakland tested the Grinspoon has an idea to promote graphic —there were more middle-aged • An honest data collection effort by entrants for THC content. Steep Hill’s more dignified nomenclature in the fu- people and senior citizens. I figured SCC doctors and the medical marijuana David Lampach says that the cup entrants ture: judges should give weight to the maybe half the mature hipsters had done community is more trustworthy than the averaged 15-16% THC, whereas the name of a strain when evaluating its time; and for sure, all had lived in fear “rigorous” but corrupt clinical trials con- buds the lab ordinarily tests average 10- worth as a medicinal product. (At this of the cops and endured social contempt. ducted by pharmaceutical corporations. 12% THC. year’s cup the judges were “blinded” as Now they were passing joints in the sun- • Cannabis dispensaries, while com- “The winners all had high THC lev- to the names of the strains and their can- shine, ignoring the “no tobacco smok- peting for market share on one level, are els,” according to Lampach, “but not nabinoid profiles. They knew the entries ing” signs, enjoying a sliver of freedom. unified in their commitment to research- necessarily the highest.” God’s Pussy only by numbers affixed to the bags ing the medical potential of the plant. was found to contain 18.2%; Cali Gold they’d been given to sample.) • Although pro-cannabis MDs are de- 18.4%; and Ingrid hash 45.5% THC. Grinspoon’s brief acceptance speech rided in the media as “potdocs” and had been taped at his home in Wellesley, profiteers, some are serious specialists The taxonomy of cannabis is Mass. and was broadcast to the cannabis whose understanding of human physi- very loose, to put it mildly. cup crowd. In it he expressed strong sup- ology is superior to that of their col- port for Tax and Regulate 2010, Project leagues (who did not learn about the en- CBD, and the people of California, who Lampach points out that Cali Gold, have been in the forefront of the medi- docannabinoid system in med school and though classified as an Indica by the Cup to this day may not have heard of it). cal marijuana movement all these years. organizers, might actually be a sativa- Applause kept drowning out his words. • SCC doctors, by keeping abreast of dominant strain, based on its lineage. The the data, will be better able to help pa- taxonomy of cannabis is very loose, to tients formulate their treatment plans. put it mildly. Sativas are said to have (The advent of CBD-rich cannabis will longer, narrower leaves; to take longer raise questions of efficacy and appropri- to reach maturity (very important for ate strain and dosage for every patient growers); and to have a more cerebral who tries it.) effect (as opposed to sedating Indicas). As we go to press... DJ Short says there is no clear dividing EVALUATING STRAIN 32. LESTER GRINSPOON, MD The Werc Shop, a new Los Angeles Valerie Corral, the leader of WAMM, based analytical testing lab, reports that La Pasionaria more vulnerable and fearful. Every in early July a strain called “Poison OG” had been assigned to judge the strains During one panel discussion a mem- day —almost every minute— I worry was found to contain approximately classified as Sativas. She was given 42 ber of the audience asked why women about my child. I told her, ‘I might be equal amounts of CBD and THC. Dr. Jeff samples to evaluate six days prior to the were in the obvious minority at events going to jail for cannabis. I hope that Reber of The Werc Shop verified the event. I saw her one day that week at a such as the Cannabis Cup. (Member- it’ll be okay. finding using two complementary ana- meeting —she was sampling #32 and ship in California collectives is typi- You’ll stay with lytical techniques. conscientiously recording her impres- cally 70% male.) Debby Goldsberry of grandma and Full Spectrum lab in Denver, which sions in a notebook. the Berkeley Patients Group had the you’ll be okay uses high-pressure liquid chromatogra- answer and she didn’t mince words: and then I’ll be phy to measure cannabinoid levels, is re- “We have potency down. That is “Women are concerned about los- in a halfway porting slightly higher numbers than unquestionable. Unfortunately, po- ing their kids. I have a daughter and house and we’ll Steep Hill, with three strains in the 10% tency does not equal character. A every day I wonder what is going to be okay…’ Ev- CBD range. This may be a function of good comparison is the wine indus- happen to her if I go to jail. I’m a solo ery parent, espe- the different technology. try, where you have fortified wines parent. The thought of losing your kids cially a solo par- Lester Grinspoon, MD, has been dis- and then you have fine Merlots. My is a heartbreaker. Like people in low- ent, has this mayed by some videos suggesting that advice is: focus on producing the fine bottle of Merlot.” —DJ Short income neighborhoods, women are fear.” continued on page 63 O’Shaughnessy’s • Summer 2010 —63—

Correspondence from previous page 1848; resigned 1861. Knighted 1856. Changed his Contents name to O’Shaughnessy-Brooke in 1861. Professor of 1 Doctors to Study Effectiveness of CBD Chemistry at Calcutta. Director General of Indian tele- graphs 1853, and laid down first telegraphs in India. 2 On What Schedule Does Cannabis Belong? Died at Southsea. Published ‘Manual of Chemistry’ by Richard Bayer, MD 1837; ‘Report on Poisoning’ 1841; ‘Galvanic Electric- Pick up the Book! ity’ 1841; ‘Bengal Pharmacopoeia’ 1844; ‘Electric- Telegraph Manual’ 1853, etc.” 3 The Changing Nature of My Practice Why William Brooke O’Shaughnessy legally by Christine Paoletti, MD changed his last name is a mystery. A falling out with 4 On Issuing Cannabis Recommendations his father? An offer he couldn’t refuse from the Brooke by Stacey Kerr, MD family? W.B.O. deserves a full-fledged biography — too bad the book publishing industry is moribund. It’s a TOD MIKURIYA WITH AIDAN HAMPSON in front of Hampson’s 5 History of the Endocannabinoid System life made for the Ivory-Merchant treatment. poster, “Cannabidiol as a Selective Inhibitor of by Martin A. Lee Another mystery is why the cannabis that Inflammatory Lipoxygenases,” at ICRS ‘99. Hampson’s 7 Clinical Studies With Cannabis O’Shaughnessy sent back to his alma mater c. 1841 could study was funded by the National Institute of Mental and Cannabinoids, 2005-2009 not be made into effective potions. It is not known Health. He was subsequently lead author on a patent, by Arno Hazekamp and Franjo Grotenhermen whether he sent seeds or seedlings. The latter would have “Cannabinoids as Antioxidants and Neuroprotectants.” The assignee on the patent was Hampson’s employer, been possible thanks to the Wardian case, a mini-green- 16 A Novel Approach to the Systematic Treatment “The United States of America as represented by the house in which plants could withstand salt spray and Department of Health and Human Services.” of Autism by Lester Grinspoon, MD extreme jostling on the deck of a ship, while requiring 18 LaGuardia and the Truth About Marijuana minimal fresh water. These artfully designed, sturdily By Fred Gardner constructed environments enabled the Brits to ship tea seedlings from China to India and rubber seedlings from FAQs 21 The Shafer Commission Report (1972) Brazil to Malaya and orchids from everywhere to col- By The Managing Editor 22 Marijuana in the Treatment of Glaucoma lectors in England. • What are O’Shaughnessy’s goals? By John C. Merritt, MD Mike Aldrich and Jerry Mandel have looked into O’S was launched in 2003 at the urging of Tod why the cannabis O’Shaughnessy sent to his colleagues Mikuriya, who essentially had created a new specialty 25 The Rediscovery of Hemp, The Launch in Edinburgh didn’t yield blockbuster extracts. “This —“cannabis clinician”— after Prop 215 passed. Tod of Ecolution by Steve DeAngelo topic was discussed in detail in the US Dispensatories was well aware that a medical specialty is defined by 26 In the Lion’s Den by Irvin Rosenfeld of 1868 and 1899,” ac- having a journal in which the practitioners can publish cording to Aldrich. “Foot- their findings and observations and keep up with de- 27 William Bennett, Voice of Virtue notes in both editions say velopments in the field. One goal was to establish the George B. Wood (Wood credibility of the field itself — Cannabis Therapeutics. 28 The Institute of Medicine Report (1999) & Bache compiled the • Then why doesn’t O’Shaughnessy’s try to look like 29 Researchers Share Findings at ICRS Meeting 1868 post-Civil-War edi- a medical journal? 30 The Inadvertent Inventor of “Spice” tion of USD) went to Prop 215 created this unique semi-legal status for Interview with John W. Huffman Edinburgh and found the cannabis —usable under California law but not under cannabis plant(s) there to federal law. Which is not to say that California law was 31 Cannabidiol as a Treatment for Acne? be like European hemp — being implemented. The state medical board —which Interview with Tamas Biro only 4 feet tall, not resin- licenses physicians— accused Tod of violating a vague, ous or sticky at all. arbitrarily applied “standard of care.” The complaints 32 Reviews: The United States Dispensatory, “At that point, in foot- WARDIAN CASE , a portable against him were lodged not by patients or their loved Books by DJ Short, Edward Grimé, RC Clarke notes quoted in both edi- greenhouse, made possible ones, but by sheriffs, cops and DAs who resented his 34 Preface to the Second Edition of Hashish! the shipment of seedlings tions, Sir Robert Christ- willingness to approve cannabis use by people they used by Robert C. Clarke ison [renowned Edin- across the high seas. to bust. So O’S was conceived as a cross between a burgh toxicology professor, a teacher of O’Shaughnessy] medical journal and a defense committee leaflet. And it 35 Travel as a Political Act said to Wood that the cannabis useful for medicine in came out as a tabloid. Reviewed by Joe Joseph India was grown in the hilly regions, not in the plains... Tod said, “I’m a townie, not a gownie. I care about 36 A Gardener Walks into a Bookstore a remarkably accurate comment for the time, pointing reaching rank-and-file patients and my fellow clinicians by Jorge Cervantes up the differences between Himalayan charas plants (C. —my real peers. I don’t care about the so-called pres- indica) and the hemp type C. sativa, thinking that the tige of appearing in a peer-reviewed journal. Some pres- 37 Alcoholism and the Endocannabinoid System growing of the (small) plant in the British climate may tige! Recent events have exposed them as hot-beds of by Martin A. Lee have caused it not to produce resin.” favoritism and outlets for ghostwriters in the employ of 39 Case Study by Hanya Barth, MD Aldrich believes that the failure to grow potent off- drug companies.” spring and/or make effective extracts from O’Shaugh- • Does O’Shaughnessy’s have a website? 43 High Times Puts on a White Coat nessy’s plants “killed the medical marijuana movement” We hereby renew our pledge to create a strong web 44 Patients Out of Time Welcome Disabled Vets all those years ago. “Neither the British nor the Ameri- presence for O’Shaughnessy’s News Service at can chemists,” he adds, “figured out that sinsemilla [the pcmd4u.org. This time we have help. We’re going to 46 A Call from Nebraska by David West flowers of female plants shielded from pollen] should work in concert with Martin Lee and webmaster Noah 48 Arrest and Prosecution Made Easy be used, until Wood and others learned the sinsemilla- Biavaschi of ProjectCBD.com. by Greg Goldman growing technique from India in about 1906.” • What is O’Shaughnessy’s publishing schedule? If things had worked out differently in Edinburgh in Since our main distribution point is the pro-cannabis 49 Prospects for Legalization in California the 1840s, resinous cannabis grown for medical pur- doctor’s office, and since most patients come in once a by Dale Gieringer poses may well have taken its place alongside tea and year, there’s a logic to being an annual. On the other 51 Medicating with Edibles and Potables rubber as major commodities controlled by British com- hand, developments that doctors and patients should by Joanna LaForce panies. know about are occurring at great frequency. Lester Grinspoon wants us to appear quarterly. No matter how Review: Brownie Mary’s Marijuana Cookbook we decide the print schedule, we’ll be reporting regu- And Dennis Peron’s Recipe for Social Change CBD from page 43 larly online. cannabis concentrates can cure cancer. (One of the vid- 52 More a Medicine Than a Dope Are you for legalization of marijuana? by Louis Armstrong eos refers to an “all-CBD oil.”) Grinspoon e-mailed We are for much more than legalization of marijuana. O’Shaughnessy’s: “Many people are taking this notion We want our country to stop waging war in the name of 54 On Pot Pulp by Michael Aldrich, PhD of the cancer curative powers of cannabis uncritically “national security.” Our infrastructure needs rebuild- and I believe that this is fraught with danger for pa- 56 Regulating Medical Marijuana by “Nuisance” ing— that would be a mission worthy of our men and Laws by Pebbles Trippet tients and for medical marijuana. women in uniform. Americans who need work should “Yes, the work of Guzman and others clearly dem- be able to get land and training to become small farm- 57 Veterans Seek VA Policy that Allows Cannabis onstrates that cannabinoids can shrink tumor cells of ers. Growing our own —not just marijuana—seems like Use by Michael Krawitz some cancers and generally facilitate apoptosis. But it the logical way out of the eco-crisis. The only way out. 58 Dr. Fride Leaves Us has never been demonstrated that any cannabinoid can Wouldn’t that require a big government program? cure any cancer. While the effects that have been de- We’re not against government of the people, by the 60 Marijuana and Creativity by Ken Miller, MD scribed are encouraging and suggest that eventually people, for the people. That’s what 61 A Third Way by Mark Ware, MD something may come of this approach to some can- America is supposed to stand for.

cers, patients who interpret them as suggesting that can- We’re against government con- 62 The Greatest Story Never Told, Continued nabis can cure their cancer and ignore the generally trolled by the corporations. more difficult and uncomfortable allopathic approaches What do you think of Barack to those cancers (which, depending on the type of can- Obama? cer and its stage), may, if they delay too long, miss the We don’t want to see our well- Hell, man, I got to tell it like it was. I can’t go around changing history.” opportunity of a genuine cure or at least the prolonga- intentioned young president go —Louis Armstrong tion of life.” down in history as a tragic figure.