O’Shaughnessy’sThe Journal of Cannabis in Clinical Practice Summer 2010

By Fred GardnerTod Mikuriya, MD, did not live to see

it, but his dream of investigating themedical potential of compounds in thecannabis plant other than THC is nowwithin the grasp of his successors.

The Society of Cannabis Clinicians,the group Mikuriya founded in 1999, hasdrafted a “Strain Evaluation Survey” tocollect data from patients who medicatewith cannabis in which cannabidiol(CBD) is predominant

CBD-rich cannabis will be availableat California and Colorado dispensariesby late summer —and soon thereafter,inevitably, in other states where patientscan legally use cannabis as medicine.

Twelve strains rich in cannabidiol(CBD) have been identified in the yearand a half since an analytic chemistrylab began testing cannabis samples pro-vided by California dispensaries, grow-ers, and edible makers. Buds from fiveof these strains have been available in-termittently at Harborside Health Cen-ter in Oakland. Herbal Solutions in LongBeach also has provided CBD-rich can-nabis to patients.

Eight of the CBD-rich strains are cur-rently being grown out. The others can-not be reproduced because the growershadn’t saved or couldn’t regain accessto the genetic material that yielded theirbuds of interest.

More than 9,000 samples have beentested to date by the Steep Hill lab inOakland. Other start-up labs in Califor-nia, Colorado, and Montana have beguntesting for the burgeoning industry. TheFull Spectrum lab in Denver has testedsome 4,500 strains and identified sevenCBD-rich strains.

A strain that is roughly 6% CBD and6% THC, “Cannatonic,” has been devel-oped by Resin Seeds in Barcelona andis being grown from seed by several col-lectives. Its name may be misleading,since CBD supposedly cancels the se-dating effects of THC.

For purposes of the data collectionbeing planned by the Society of Can-nabis Clinicians, “CBD-rich” cannabisis being defined as more than 4% can-nabidiol by weight (without respect toTHC content) or more than 2.5% CBDif CBD exceeds THC.

Potential Usefulness of CBDUntil testing for cannabinoid content

began, it was widely assumed that CBD,which is non-psychoactive, had beenbred out of all the cannabis in Californiaby generations of growers seeking maxi-mum THC content.

What benefits did G.W. sci-entists expect a CBD-rich ex-tract to confer?

Doctors in the SCC have watchedwith great interest in recent years as aBritish company, G.W. Pharmaceuticalsconducted clinical trials of cannabis-plant extracts. G.W. has a license fromthe British government and backing fromOtsuka, a Tokyo-based multinational.

G.W.’s flagship product, Sativex, isa plant extract that contains approxi-mately equal amounts of CBD and THC.What benefits did G.W. scientists expecta CBD-rich extract to confer?

INTRODUCING PROJECT CBD

Our collective is involved in a research project to assess theeffects of strains relatively rich in cannabidiol (more than 4%CBD). Collective members who medicate with CBD-rich can-nabis are encouraged to take part in this research by report-ing your observations on the back of this form

Is CBD-rich Cannabis right for you? Research suggests that CBD could be effective in easingthe symptoms of rheumatoid arthritis, diabetes, nausea, andinflammatory bowel disorders, among other difficult-to-con-trol conditions. CBD is non-psychoactive and may countercertain effects of THC. Patients who want the anti-inflamma-tory, anti-pain, anti-anxiety, or anti-spasm effects of cannabisdelivered —possibly— without disconcerting euphoria or se-

dation might prefer CBD-rich Cannabis.

How to conduct an N=1 Trial A simple way to collect information about effects is calledthe “N-of-1” trial, in which one patient is both the test subjectand the control. All you have to do is medicate with a CBD-rich strain for a set period of time —say, a week— and thenmedicate with your regular high-THC strain for the same pe-riod. Use this form to describe any differing effects that younotice: “less anxiety,” “more stoney than I want,” “less sedat-ing,” “better sleep,” “no difference,” etc., etc.

INFORMATION FOR PATIENTS appears on front page of a form developedto involve dispensaries in data collection. Patients getting CBD-rich strainsare asked to describe their dose and use pattern, as well as “Conditions/symp-toms used to treat” and “Effects observed.” A more detailed and formal ques-tionnaire is being developed by the Society of Cannabis Clinicians.

Why is this plant differentfrom all other plants?

Doctors to Study Effectiveness of CBD

Inside this issue

“Placeholder” Questionnaire

Various studies published in the medi-cal and scientific literature suggest thatCBD could be effective in easing thesymptoms of rheumatoid arthritis, dia-betes, nausea, and inflammatory boweldisorders, among other difficult-to-con-trol conditions. CBD also has demon-strated neuroprotective effects, and itsanti-cancer potential is being exploredat several academic research centers.

An even wider market would emergeif the reduced psychoactivity of CBD-rich cannabis makes it an appealing treat-ment option for patients seeking anti-in-flammatory, anti-pain, anti-anxiety, and/or anti-spasm effects delivered withoutdisconcerting euphoria or lethargy.

The Blue-Ribbon PlantThe plant richest in CBD is a “True

Blueberry/OG Kush” cross grown in themountains south of Yreka by WendellLee of Full Spectrum Genetics (not tobe confused with the lab in Colorado).Dried buds of TB/OGK have been sentfor testing on four occasions byHarborside, the dispensary with whichLee is associated. Samples were consis-tently found to contain about 10% CBD(with THC levels around 6 to 7%). Onthe only occasion that a crop grown out-doors by Lee was tested by Steep Hilllab, it was found to contain 13.9% CBD.

Two other labs have confirmed theCBD content of Lee’s TB/OGK.

Lee is now working to “stabilize thegenetics” and produce TB/OGK seeds.Several plants he provided to ProjectCBD (a nonprofit organized by writer/activist Martin Lee to promote research)are being grown out by experiencedhands. Processed medicine and cloneswill be available at dispensaries in themonths ahead. Details will be availableon ProjectCBD.com, a website that willbe launched by mid-August, accordingto Martin Lee (no relation to Wendell).

The California strain richest in CBDproportionally, “Women’s CollectiveStinky Purple,” tested at 9.7% CBD and1.2% THC. It was brought to Harborside

CBD-RICH CANNABIS PLANT isheld lovingly by Ralph Trueblood ofthe Wo/men’s Alliance for MedicalMarijuana. It was cloned from a TrueBlueberry/OG Kush cross found tocontain approximately 10% CBD and6 percent THC by weight. The strainwas developed by Wendell Lee of FullSpectrum Genetics.

continued on page 41

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A NOVEL TREATMENT FOR AUTISM

BY LESTER GRINSPOON

Dale Gieringer:What Would “Legalization” Mean?

The Changing Nature of My PracticeBy Christine Paoletti

On Issuing Cannabis RecommendationsBy Stacey Kerr

O’Shaughnessy’s • Summer 2010 —41—

Project CBD from front page

by Grower #1 who also grows a straincalled “Cotton Candy/Diesel” that wasfound to contain about 6% CBD and 6%THC. Grower #1 gets her starter plantsfrom friends in Northeastern MendocinoCounty. Is there something in the ge-nome of plants that have been swappedover the years by growers in those hillsthat encourages expression of CBD?

Another strain containing more than8% CBD, grown indoors in the East Bay,was brought to Harborside in late April.“Omrita Rx3” is the name the growerhas given it after learning that it was of

not have the typical ‘high’ that goes withthese therapeutic effects.”

But patient 10, who has been smok-ing TB/OGK reported, “I enjoy the herb,enjoy being able to use during the daywithout getting too spaced out, but haveto watch out for memory lapses. I do stu-pid things like forget where I put stuffbecause I think I’m not affected, but Iam affected.”

“Dose level is going to bevery, very important.”

Patient Four in the Project CBD da-tabase, a 70-year-old man with arthritis,responded in detail: “Definitely anti-painand anti-inflammatory. I would not callthe effect a ‘high’ but I’m not sure it’snon-psychoactive. I would call it a ‘bal-anced effect’ or a ‘calming effect.’ Youfeel like you’re on a more even keel.”

For 10 days Patient Four ingestedcookies made with trim from TB/OGK.(The trim was 5.1% CBD, 2.5% THC butwe don’t know the amount used in thebutter from which the cookies weremade.) He reports being“able to concen-trate for hours at a time and get up frommy desk without groaning... Once ortwice as the effect was coming on, I be-gan to feel sedated, but that passed andI then experienced about three pain-freehours... Once I ate an extra half a cookieand was definitely sedated. Fortunately,it was bedtime... Dose level is going tobe very, very important.”

Caveat hemptorSome caveats as we begin our long

march towards collectively identifyingthe effects of cannabidiol.

1) The amount of CBD present willnot be the only factor influencing the ef-fects of a given cannabis-based medi-cine. The ratio of CBD to THC may beas important, and the terpenoid and fla-vonoid content may be as important.

2) We are capable of placebo-effect-ing ourselves individually and placebo-effecting ourselves collectively. Somemay exaggerate the potential benefits ofCBD and raise false hopes.

3) The line between physical effectand effect on mood is often indistinct.Improved mood might result, for ex-ample, if the man with arthritis experi-ences reduced inflammation and less ofthe “background pain” that afflicts olderpeople.

4) When a patient reports the effectof a drug on mood or pain, the report isinherently subjective.

5) How CBD in the liver affects themetabolism of other drugs has not beenstudied thoroughly. The Drug Warriorscould argue that Prohibition must remainin effect because “more research isneeded.”

The Doctors’ Hopes re CBDThe wide range of variables and “con-

founding factors” confronting doctorswho want to study the effects of CBD-rich strains was discussed at the wintermeeting of the Society of Cannabis Cli-nicians.

UCSF professor Donald Abrams,MD, the featured speaker, recounted theobstacles he faced in conducting clini-cal trials with government-issued can-nabis and getting his results publishedin peer-reviewed medical journals.

SCC President Jeffrey Hergenrathervolunteered to head the committee thatwill organize the group’s data collectioneffort. Abrams agreed to informally con-sult on the SCC study design.

The first step, a “Strain EvaluationSurvey,” will soon be accessible on theSCC’s website. It asks, among otherthings, “What factors limit your use ofcannabis at a frequency that affords op-timal relief of symptoms?”

The answer options are: “Cost,”“Can’t perform tasks,” “Family or so-cial reasons,” “Concern for having usediscovered,” “Get too sleepy,” “Get tooaltered/ spacey,” and “Concern for ha-bitual use.”

Hergenrather says that he is beginningto see in his practice, “a growing per-centage of patients, especially older pa-tients, who have not used cannabis be-fore, but they have come to understand

that it has many medicinal uses and mayafford relief from their symptoms withfewer adverse effects than conventionalpharmaceuticals.

Hergenrather hopes thatplant breeders will now try tolower THC content.

“I am seeing many older patients whowould like to try cannabis for pain,muscle spasms, insomnia, and manage-ment of various cancers. One thing thatmost of these cannabis-naive patients arenot interested in is ‘getting high.’ Myhope is that the CBD-rich strains willenable them to use cannabis and get itsbenefit without —or with less of— theusual ‘high.’”

Hergenrather thinks that patients who“might benefit by maintaining a higherblood level of active cannabinoids includethose with inflammatory bowel diseases(Crohn’s and ulcerative colitis), theneurodegenerative diseases (multiplesclerosis, ALS, Parkinson’s, Hunting-ton’s), epilepsy disorders, autoimmunedisorder, (Lupus, rheumatoid arthritis,etc.), stroke, concussion, and braintrauma, and cannabis-sensitive cancers —glioblastoma multiforme, thyroid cancer,lymphomas and some leukemias, coloncancers, neuroblastoma, and others).”

CBD CONTENT of True Blueberry/OGKush is indicated by large spike at left ofchromatogram from Steep Hill lab. Spiketo its right shows THC. Small spike showslevel of Cannabinol (a breakdown productof THC). Spike at right in both chromato-grams is the lab’s internal standard.

Yreka!

HIGH-THC STRAIN, typical of the >9,000tested to date in California, has virtuallyno CBD. Scale at bottom gives amount oftime heating in the urn of the gaschromatograph. Vertical scale indicatesamount of specific compounds evaporatingat known temperatures.

continued on next page

BIOSYNTHETIC PATHWAY bywhich THC and CBD are created with-in the plant from a part of the CBGA(Cannabigerolic acid) molecule isshown at right. THCA synthase andCBDA synthase are enzymes that pro-mote a reaction (“oxidative cycliza-tion”) whereby CBGA forms THC acid(THCA) and CBD acid (CBDA). THCand CBD are then generated fromTHCA and CBDA by non-enzymaticloss of CO2. Several labs are studyingthe mechanism by which the enzymespromote the reactions. One theory ofwhy the offspring of a plant whoseparents contain only trace amounts ofCBD may be rich in CBD: a geneticmutation resulting in excess CBDAsynthase or deficient THCA synthase.

GW Pharmaceuticals’ “Tale of Two Cannabinoids”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 andGeoffrey Guy in the online journal Medical Hypotheses. Here’s the summary:

“CBD is demonstrated to antagonise some undesirable effects of THC in-cluding intoxication, sedation and tachycardia, while contributing analgesic,anti-emetic, and anti-carcinogenic properties in its own right. In modern clini-cal trials, this has permitted the administration of higher doses of THC, pro-viding evidence for clinical efficacy and safety for cannabis based extracts intreatment of spasticity, central pain and lower urinary tract symptoms in mul-tiple sclerosis, as well as sleep disturbances, peripheral neuropathic pain, bra-chial plexus avulsion symptoms, rheumatoid arthritis and intractable cancerpain. Prospects for future application of whole cannabis extracts inneuroprotection, drug dependency, and neoplastic disorders are further exam-ined. The hypothesis that the combination of THC and CBD increases clinicalefficacy while reducing adverse events is supported.”

Sativex has been approved by Health Canada for treating neuropathic painin multiple sclerosis and cancer. It is obtainable by prescription in 22 coun-tries. After passing an important regulatory hurdle in March, GW expects im-minent approval of Sativex as a treatment for MS spasticity in the UK andSpain.

GW is close to finishing an extensive study to determinethe “therapeutic window” —the dosage level high enoughto relieve the pain but low enough to prevent the high.

The U.S. FDA has given GW approval to conduct a clinical trial in ad-vanced cancer patients whose pain is not adequately controlled by opioids.GW is close to finishing an extensive study to determine the “therapeutic win-dow” —the dosage level high enough to relieve the pain but low enough toprevent the high. The company hopes recruitment of subjects won’t take morethan a year. When the results are in, assuming they’re favorable, GW willapply for marketing approval from the FDA.

pound of “Jamaican Lion” tested at 8.9%CBD. Clones of these strains are beinggrown out and will be available throughHarborside and Project CBD in themonths ahead, along with the Soma A+that was first to be identified.

Pineapple Thai (5% CBD, 2.4%THC) is being grown out by Herbal So-lutions in Long Beach.

Anecdotal EvidenceTo get the ball rolling on data collec-

tion, Project CBD developed a form tobe given to patients purchasing high-CBD cannabis at participating dispen-saries (see illustration on page 1). Feed-back has also been solicited from a groupof physicians who were given a smallamount of TB/OGK trim [leaves re-moved when buds are manicured] forself-testing.

The anecdotal evidence coming fromthese two sources —about 12 people to-tal— has been generally but not entirelyconsistent. Frequent reference is madeto pain relief, a calming effect, and un-impaired —or improved— ability toconcentrate.

Patient G. is an experienced cannabisuser age 81 who regularly smokes ahigh-THC joint in the evening. He testeda CBD edible on three occasions and theresults were identical. He experiencedno noticeable effect after consuming abrownie in the late afternoon. He expe-rienced “diminished effect” from hissubsequent high-THC joint.“But thenext morning when I went for my walk,”he reports, “I went further and faster thanI had in a long time.”

Several people said they appreciatedthe relative lack of psychoactivity. AsPatient 9 put it after smoking TB/OGK,“CBD-rich cannabis seems relaxing andsoothing in regards to pain, anxiety,muscle tension and spasms, and it does

special interestto SCC doctors.

A few weekslater a straincalled “Harle-quin” was foundto contain about8% CBD. Andsoon thereafter a

—42— O’Shaughnessy’s • Summer 2010

Project CBD from previous page

Hergenrather hopes that plant breed-ers will now try to lower THC content.“Having an option to use a CBD-richstrain that is low in THC would not onlybenefit the patients who don’t want toget ‘high’ but also all of those patientswho would benefit with higher bloodlevels of cannabidiol.

CBD Helper?A simple way to raise the CBD-to-

THC ratio of a given batch of medicalcannabis is to blend in dried flowersfrom a CBD-rich hemp plant contain-ing only trace amounts of THC. That’show G.W. Pharmaceuticals producesSativex —by growing CBD-rich hempplants outdoors and THC-rich plants inglasshouses, then blending them.

In February a friend in Spain sentProject CBD seeds from a hemp strainwhose flowers reportedly contain fourto six percent CBD, depending on grow-ing conditions. These were started in-doors by a grower affiliated with the LosAngeles-based Cornerstone ResearchCollective —along with seeds of“Cannatonic” that had been donated byResin Seeds of Barcelona. According toProject CBD’s benefactor, one in fourof the Cannatonic seeds —availablefrom resinseeds.com—should contain6.5% CBD by weight, and the sameamount of THC. “The perfect Sativexmix,” is how he describes the strain’scannabinoid content.

Project CBD also has a line on in-dustrial hemp seeds reported to contain10% CBD and almost no THC!

Overcoming HesitanceStacey Kerr, MD, of Santa Rosa has

been doing home visits with cancer pa-tients, “filling in the gaps that all theirother doctors can’t fill. When you aregetting care from several specialists,these gaps will sometimes happen. So Isit by the bedside and take the time totalk about therapy and side effects. Thenwe problem solve about how to deal withthe side effects and how to best com-municate with their treating physicians.

“Several of my patients are using can-nabis for nausea and vomiting. However,they are hesitant to use it because of thepsychoactive effects and we spend timetalking about the most effective way todose, the timing of their doses, and themedication itself.”

Kerr offers the example of Linda (nother real name) a patient with metastaticbreast cancer in her bones, liver, andpossibly her stomach. “She finishedthree weeks of intensive radiation andjust now finished her first three weeksof intensive chemotherapy. She has lostover 30 pounds through the course oftreatment. She is bedridden and ex-tremely weak. This woman is a highlyeducated professional and a triathlete.

“I was at Linda’s home this past Sat-urday and on Easter Sunday discussingoptions for nausea/vomiting control. Herpain is well treated. The image she de-scribed to me when she drinks a glass ofwater is that of a boiling hot metal caul-dron hit with cold water so the watererupts right back up and out because ofthe heat reaction. She is using severaldifferent prescription medications, butthe medication that works most effec-tively for the vomiting is cannabis.

“She was not a regular user prior toher cancer needs. Her only complaint isthat it does not seem to last very long

Willy Notcutt, MD, is a pain spe-cialist at James Paget Hospital in GreatYarmouth, England. He conducted thephase 2 clinical trials for Sativex in1999-2000.

Notcutt’s first step had been to as-sess the basic efficacy and optimumdosage range of Sativex (prior to clini-cal trials) by means of “N=1” trials. InN-of-one trials, as they’re called, datais collected from individuals as theiruse pattern changes. The number N ofpatients involved in each study is one,hence the name.

We asked Notcutt if there was anyreason why California doctors couldnot use a similar approach as CBD-richstrains become available to their pa-tients. This interview was conducted inKoln at the 2009 meeting of the Inter-national Association for CannabisMedicine. Notcutt was speaking as anindividual and the views expressedmay not represent G.W. Pharmaceuti-cals’ position. —F.G.

Notcutt: The advantages of N-of-1 trials were first described by a chapnamed Guyatt in Toronto. The funda-mental thing is that the patient acts ashis 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 currentlyusing a high-THC strain. First you es-tablish the baseline: what’s the patient’s[self-reported score on a] pain scale orthe sleep line, or whatever parametersyou want to measure. Then you startthem on the current drug for a week.Then you put them on the new one.Then you switch them back to the cur-rent one, and so forth.

It can be done as many times as youwant and for any period —one week,two weeks, six weeks. You can leave itopen, you can do it single-blinded [notletting the patient know what he’s tak-ing], you can do it double-blinded [nei-ther doctor nor patient knowing whichstrain is being used]. But by far theeasiest way to start out is to do a straightobservational study: open observationand open label [both doctor and patientknow what’s being used].

You’re using the patient ashis own control.

The patients are going to tell youpretty quickly whether they prefer cur-rent drug or new drug. The advantageof going from current drug to new drugis, that is what a clinician 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 prob-

lem with standardization, but a lot ofpeople [medical cannabis users] say, “I

“You have to start somewhere...”

always get this type, I know how to workit, I fine tune it, if it’s a little weak orstrong I smoke a little more or smoke alittle less.” Call that the current drug,which we assume is high-THC, and thencompare it with high-CBD.

That’s what you’re testing: the com-parative efficacy of high-THC and high-CBD cannabis. You’re using the patientas his own control and you plot it out:How many times do they smoke eachday? What effects are they getting?

It’s close to what you normally woulddo as a clinician. That’s how I evaluatea drug anyway. If you define your pa-rameters, and get reports from 20 pa-tients, you can then get a feel for whetherit works.

I would suggest that it be done com-pletely 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 fewyears ago saying that this is the way weshould be studying chronic disease. It’sa well-recognized, acceptable clinicalapproach. But people have gotten so fix-ated in the last 20 years on the random-ized, placebo-controlled trial, (sarcasti-cally) ‘the only way you can do it,’ ‘thegold standard.’

I think the N-of-1 trial is the only wayyou study this cohort at this time, be-cause of your problems with standard-ization. You have people doing it differ-ent ways... But your individual patientbecomes your study. And then you canaggregate your studies. You can do somesimple statistics on it: of 20 patients thatstarted, five found it didn’t work for themat all. Now let’s look at the 15 that re-ported effect...

Then you can go on and blind yoursubjects and not tell them which iswhich. Or blind the physician.

Guyatt wrote about building in a pla-cebo, but you needn’t go to that extent.That’s not how we do medicine. TheRCT [randomized, controlled trial] is

furthest from normal clinical practice.The N-of-1 trial is a good way of

generating some data where no dataexists. The first two or three studieswere all N-of-1, until we knew that itworked. If nine of the first ten patientshad said, “This doesn’t work,” thenyou don’t go further.

You have to start somewhere. Anobservational study has the force ofcommon sense. It may be best suitedwhen you have a long-term chronicillness and you need some informationabout whether a drug works...

Do we give an orthopedic surgeonand an eye surgeon the same tools? No.So should we statistically evaluate ev-ery medical problem by the same tech-nique? If we’re evaluating a drugwhere the blood pressure goes up ordown, or the sugar level goes up ordown in diabetes, we use one tech-nique.

Why use the same technique for adrug that has a completely differentspectrum of activity, in an area whereyou don’t get nice, number data, whereyou get much softer data, you get sub-jective opinion? There’s a whole dif-ference in the quality of the data —why use the same statistical tools?

People are now starting to say thatevidence-based medicine is becominga tyranny that’s killing off research.I’m very interested in this because I’mthe lead for research in our district I’malso the lead for research in my ownfield.

If you start insisting on these bigmulti-center big studies, all random-ized, and you don’t nurture the smallstudies -the little ones that come along,the N-of-1s that come along where theguy sits down and works on an idea,“Try this out, try that out” in a few pa-tients, and generates a little bit moreinformation that then leads to a bit ofa better study...

I still regard as one of the best stud-ies ever, the guy who treated pain af-ter shingles with amtriptyline ornortriptyline. All he did was he foundout that when he used the amitriptyline,60 percent of the patients hated it.When he used nortriptyline only about30 percent of the patients hated it.

A simple trial —but it changed our

WILLY N OTCUTT AND TOD M IKURIYA atAsilomar, June 2002.

Willy Notcutt on Evaluating Cannabis by N=1 Trials“An observational study

has the force of commonsense. ”

practice. We stopped usingamitriptyline, we usenortriptyline. And now weknow the reasons why. Thatwas 10, 15 years ago. I’venever seen that simplestudy replicated as a clini-cal trial of amitriptylineversus nortriptyline be-cause there’s no money init for the drug companies.

dren, an analytical mind, and is alreadystoned enough on the prescription medsshe needs.

“I was able to provide a legal recom-mendation for her use of medical can-nabis. I explained CBD strains to her andher caregivers (all of them are profes-sionals) and Linda’s caregivers were ableto obtain an ounce of TB/OGK bud fromHarborside in early April.

“My hope, says Dr. Kerr, “is thathaving a CBD-rich strain will allow herto use the medicine as often as neededwithout extreme side effects but with ex-cellent relief for nausea and vomiting.Oral intake would be beneficial withlonger-lasting effects and direct activityon the most inflamed tissue. If she wasnot afraid of the side effects, she wouldbe more willing to use the medication in

amounts that are most effective.”Kerr adds, “My patients who are pro-

fessionals without a history of usingmarijuana would be more likely to use itif it was specifically for medical uses andnot ‘tainted’ with a culture of illicit highs.This is a cultural block, I know, but it isreal, and I work hard to overcome it ev-ery time I counsel on the use of medical

when she uses thevaporizer, and shedoesn’t want to be‘stoned.’ She hastwo small chil-

continued on next page

O’Shaughnessy’s • Summer 2010 —43—

Project CBD from previous page

marijuana. CBD-rich strains that are ef-fective will support our efforts to legiti-mize cannabis as powerful, authenticmedicine.”

Possible mechanisms of actionMartin Lee explains that based on

published studies, CBD should provide“an enhanced endocannabinoid effecteven though it does not bind to a can-nabinoid receptor. CBD indirectly stimu-lates both CB1 and CB2 receptor sig-naling in at least two key ways:

“First, CBD inhibits the productionof FAAH, the enzyme that breaks downanandamide, and this results in higheranandamide levels (think runner’s high)and heightened CB1 receptor signaling,given that anandamide activates the CB-1 receptor (but not CB2.) At the sametime, CBD buffers the psychoactivity ofTHC by preventing THC from bindingwith the CB1 receptor.

“Also, it appears that CBD amplifiesTHC’s activation of the CB2 receptor.Several studies show that CBD and THCaugment each other’s analgesic and anti-inflammatory properties. A combinationof THC and CBD is much better thanTHC alone in providing pain relief.”

Project CBDThe goals of Project CBD are educa-

tional, according to Lee, but they canalso be seen as political and/or publicrelations for the Society of CannabisClinicians (whose studies the site willbe facilitating and publicizing). Some ofthe messages Project CBD hopes to getacross to the American people:

• A non-psychoactive component ofthe plant may have important medicalbenefits.

• Pro-cannabis doctors and their pa-tients want to see if this non-psychoac-tive component is effective in treatingvarious conditions.

• An honest data collection effort bySCC doctors and the medical marijuanacommunity is more trustworthy than the“rigorous” but corrupt clinical trials con-ducted by pharmaceutical corporations.

• Cannabis dispensaries, while com-peting for market share on one level, areunified in their commitment to research-ing the medical potential of the plant.

• Although pro-cannabis MDs are de-rided in the media as “potdocs” andprofiteers, some are serious specialistswhose understanding of human physi-ology is superior to that of their col-leagues (who did not learn about the en-docannabinoid system in med school andto this day may not have heard of it).

• SCC doctors, by keeping abreast ofthe data, will be better able to help pa-tients formulate their treatment plans.(The advent of CBD-rich cannabis willraise questions of efficacy and appropri-ate strain and dosage for every patientwho tries it.)

As we go to press...The Werc Shop, a new Los Angeles

based analytical testing lab, reports thatin early July a strain called “Poison OG”was found to contain approximatelyequal amounts of CBD and THC. Dr. JeffReber of The Werc Shop verified thefinding using two complementary ana-lytical techniques.

Full Spectrum lab in Denver, whichuses high-pressure liquid chromatogra-phy to measure cannabinoid levels, is re-porting slightly higher numbers thanSteep Hill, with three strains in the 10%CBD range. This may be a function ofthe different technology.

Lester Grinspoon, MD, has been dis-mayed by some videos suggesting that

High Times puts on a White CoatHigh Times magazine organized the

original “Cannabis Cup” in Amsterdamin 1987. The event inspired plant breed-ers, publicized their strains and seedcompanies, and strengthened their senseof community. It has been held annuallyever since —a fine excuse for a tradeshow and an extended party at harvesttime.

The pretext of a cannabis cup is thatdiscerning judges will sample variousstrains and determine the best (to be an-nounced at the climactic awards cer-emony). The truth is, it’s impossible forjudges, soon after sampling strain #1, todistinguish the effects of sample #2. Thebody needs an interval of at least threeor four hours for a return to baseline can-nabinoid levels. Lester Grinspoon, MD,thinks that evaluating only one sample aday would make the most sense.

High Times recently launched a glossyquarterly called High Times MedicalMarijuana News and Reviews, edited inSan Francisco. To celebrate their arrivalon the scene, the magazine staff orga-nized a “medical” cannabis cup. Theybilled it as the “first ever,” although simi-lar contests with medical themes havebeen held in Portand and at Area 101north of Laytonville for several years.

The third-ever medical cannabis cupwas held June 19-20 at Terra, an eventscenter —an erstwhile factory with a largeside-yard— on Harrison St., kitty cor-ner from the Sailors and Seamen’s Unionhall. The weather was okay on Saturday,perfect on Sunday, and a whompin’goodtime was had by about 2,000 medicalcannabis users each day. Tickets cost$50, vendors paid $1,500 for tables. Itwas not the standard High Times demo-graphic —there were more middle-agedpeople and senior citizens. I figuredmaybe half the mature hipsters had donetime; and for sure, all had lived in fearof the cops and endured social contempt.Now they were passing joints in the sun-shine, ignoring the “no tobacco smok-ing” signs, enjoying a sliver of freedom.

DJ Short, the renowned plant breederand seed merchant, had to judge 38 In-dica samples. He and Val each managedto select a top five (in consultation withHigh Times editors), and then JorgeCervantes, the best-selling author of cul-tivation guides, made the final call.

Valerie Corral is a very positivewoman. She said that every bud sheevaluated was “a jewel grown with thebest intentions.” But the chemical resi-due on some made her cough, and onegave her a headache. DJ Short, who isnot partial to Indicas in general, didn’tfind any he especially liked among thecup entrants. But the show must go on,and Cervantes made executive decisions

The “First-Ever ‘Medical’ Cannabis Cup”

“NO TOBACCO SMOKING” signs did not deter ma-ture hipsters from mixing some in with their cannabisat the High Times event in San Francisco.

based on appearance and aroma.And the winners were... Best Sativa:

“God’s Pussy,” from GreenBicycles upin Crescent City... Best Indica: “CaliGold,” from Mr. Natural, Inc.... Best con-centrate (chosen by Chris Conrad andMikki Norris from among 16 entrants):Ingrid, by the Leonard Moore collective,Mendocino... Best edible: biscotti fromGreenway in Santa Cruz.

Steep Hill lab in Oakland tested theentrants for THC content. Steep Hill’sDavid Lampach says that the cup entrantsaveraged 15-16% THC, whereas thebuds the lab ordinarily tests average 10-12% THC.

“The winners all had high THC lev-els,” according to Lampach, “but notnecessarily the highest.” God’s Pussywas found to contain 18.2%; Cali Gold18.4%; and Ingrid hash 45.5% THC.

The taxonomy of cannabis isvery loose, to put it mildly.

Lampach points out that Cali Gold,though classified as an Indica by the Cuporganizers, might actually be a sativa-dominant strain, based on its lineage. Thetaxonomy of cannabis is very loose, toput it mildly. Sativas are said to havelonger, narrower leaves; to take longerto reach maturity (very important forgrowers); and to have a more cerebraleffect (as opposed to sedating Indicas).DJ Short says there is no clear dividing

line, almost every plant nowadays is ahybrid. He cites the example of Flo, astrain he developed that is “a quick fin-isher but has narrower leaves and a Sa-tiva effect.”

Both Valerie Corral and DJ Shortwere struck by the predominance of can-nabis grown indoors and felt impelledto extol the virtues of the sun. So didJorge Cervantes, who gave a talk on cul-tivation to a rapt SRO audience. Notethat the Amsterdam cannabis cup is held

in November, when the natu-ral harvest has come in. InCalifornia, where most cultiva-tion goes on indoors, the cupwas held in June.

Mikki Norris said that hergroup eliminated from consid-eration those concentrates thathad been produced —detectably— by solvent extrac-tion. (Like you could smell thebutane.) She was pleased tolearn from the producer ofIngrid hash, Gabriel Martin of

Mendocino, that he had used the Ice-o-lator method, in which trichomes arewashed off the flowers by cold water.

High Times Medical News and Re-views gave an award to LesterGrinspoon, MD, for his enduring serviceto the cause. Grinspoon winced whenhe learned the name of the winning Sa-tiva, and High Times promptly took theoffensive term down from its website.

Grinspoon has an idea to promotemore dignified nomenclature in the fu-ture: judges should give weight to thename of a strain when evaluating itsworth as a medicinal product. (At thisyear’s cup the judges were “blinded” asto the names of the strains and their can-nabinoid profiles. They knew the entriesonly by numbers affixed to the bagsthey’d been given to sample.)

Grinspoon’s brief acceptance speechhad been taped at his home in Wellesley,Mass. and was broadcast to the cannabiscup crowd. In it he expressed strong sup-port for Tax and Regulate 2010, ProjectCBD, and the people of California, whohave been in the forefront of the medi-cal marijuana movement all these years.Applause kept drowning out his words.

Valerie Corral, DJ Short, andJorge Cervantes felt impelled toextol the virtues of the sun.

Valerie Corral, the leader of WAMM,had been assigned to judge the strainsclassified as Sativas. She was given 42samples to evaluate six days prior to theevent. I saw her one day that week at ameeting —she was sampling #32 andconscientiously recording her impres-sions in a notebook.

La PasionariaDuring one panel discussion a mem-

ber of the audience asked why womenwere in the obvious minority at eventssuch as the Cannabis Cup. (Member-ship in California collectives is typi-cally 70% male.) Debby Goldsberry ofthe Berkeley Patients Group had theanswer and she didn’t mince words:

“Women are concerned about los-ing their kids. I have a daughter andevery day I wonder what is going tohappen to her if I go to jail. I’m a soloparent. The thought of losing your kidsis a heartbreaker. Like people in low-income neighborhoods, women are

more vulnerable and fearful. Everyday —almost every minute— I worryabout my child. I told her, ‘I might begoing to jail for cannabis. I hope thatit’ll be okay.You’ll stay withgrandma andyou’ll be okayand then I’ll bein a halfwayhouse and we’llbe okay…’ Ev-ery parent, espe-cially a solo par-ent, has thisfear.”

“We have potency down. That isunquestionable. Unfortunately, po-tency does not equal character. Agood comparison is the wine indus-try, where you have fortified winesand then you have fine Merlots. Myadvice is: focus on producing the finebottle of Merlot.” —DJ Short

LESTER GRINSPOON, MDEVALUATING STRAIN 32.

continued on page 63

O’Shaughnessy’s • Summer 2010 —63—

Contents1 Doctors to Study Effectiveness of CBD

2 On What Schedule Does Cannabis Belong?by Richard Bayer, MD

Pick up the Book!

3 The Changing Nature of My Practiceby Christine Paoletti, MD

4 On Issuing Cannabis Recommendationsby Stacey Kerr, MD

5 History of the Endocannabinoid Systemby Martin A. Lee

7 Clinical Studies With Cannabis and Cannabinoids, 2005-2009

by Arno Hazekamp and Franjo Grotenhermen

16 A Novel Approach to the Systematic Treatmentof Autism by Lester Grinspoon, MD

18 LaGuardia and the Truth About MarijuanaBy Fred Gardner

21 The Shafer Commission Report (1972)

22 Marijuana in the Treatment of GlaucomaBy John C. Merritt, MD

25 The Rediscovery of Hemp, The Launchof Ecolution by Steve DeAngelo

26 In the Lion’s Den by Irvin Rosenfeld

27 William Bennett, Voice of Virtue

28 The Institute of Medicine Report (1999)

29 Researchers Share Findings at ICRS Meeting

30 The Inadvertent Inventor of “Spice”Interview with John W. Huffman

31 Cannabidiol as a Treatment for Acne?Interview with Tamas Biro

32 Reviews: The United States Dispensatory,Books by DJ Short, Edward Grimé, RC Clarke

34 Preface to the Second Edition of Hashish!by Robert C. Clarke

35 Travel as a Political ActReviewed by Joe Joseph

36 A Gardener Walks into a Bookstoreby Jorge Cervantes

37 Alcoholism and the Endocannabinoid Systemby Martin A. Lee

39 Case Study by Hanya Barth, MD

43 High Times Puts on a White Coat

44 Patients Out of Time Welcome Disabled Vets

46 A Call from Nebraska by David West

48 Arrest and Prosecution Made Easyby Greg Goldman

49 Prospects for Legalization in Californiaby Dale Gieringer

51 Medicating with Edibles and Potables by Joanna LaForce

Review: Brownie Mary’s Marijuana Cookbook And Dennis Peron’s Recipe for Social Change

52 More a Medicine Than a Dopeby Louis Armstrong

54 On Pot Pulp by Michael Aldrich, PhD

56 Regulating Medical Marijuana by “Nuisance” Laws by Pebbles Trippet

57 Veterans Seek VA Policy that Allows CannabisUse by Michael Krawitz

58 Dr. Fride Leaves Us

60 Marijuana and Creativity by Ken Miller, MD

61 A Third Way by Mark Ware, MD

62 The Greatest Story Never Told, Continued

By The Managing Editor• What are O’Shaughnessy’s goals?O’S was launched in 2003 at the urging of Tod

Mikuriya, who essentially had created a new specialty—“cannabis clinician”— after Prop 215 passed. Todwas well aware that a medical specialty is defined byhaving a journal in which the practitioners can publishtheir findings and observations and keep up with de-velopments in the field. One goal was to establish thecredibility of the field itself — Cannabis Therapeutics.

• Then why doesn’t O’Shaughnessy’s try to look likea medical journal?

Prop 215 created this unique semi-legal status forcannabis —usable under California law but not underfederal law. Which is not to say that California law wasbeing implemented. The state medical board —whichlicenses physicians— accused Tod of violating a vague,arbitrarily applied “standard of care.” The complaintsagainst him were lodged not by patients or their lovedones, but by sheriffs, cops and DAs who resented hiswillingness to approve cannabis use by people they usedto bust. So O’S was conceived as a cross between amedical journal and a defense committee leaflet. And itcame out as a tabloid.

Tod said, “I’m a townie, not a gownie. I care aboutreaching rank-and-file patients and my fellow clinicians—my real peers. I don’t care about the so-called pres-tige of appearing in a peer-reviewed journal. Some pres-tige! Recent events have exposed them as hot-beds offavoritism and outlets for ghostwriters in the employ ofdrug companies.”

• Does O’Shaughnessy’s have a website?We hereby renew our pledge to create a strong web

presence for O’Shaughnessy’s News Service atpcmd4u.org. This time we have help. We’re going towork in concert with Martin Lee and webmaster NoahBiavaschi of ProjectCBD.com.

• What is O’Shaughnessy’s publishing schedule?Since our main distribution point is the pro-cannabis

doctor’s office, and since most patients come in once ayear, there’s a logic to being an annual. On the otherhand, developments that doctors and patients shouldknow about are occurring at great frequency. LesterGrinspoon wants us to appear quarterly. No matter howwe decide the print schedule, we’ll be reporting regu-larly online.

Are you for legalization of marijuana?We are for much more than legalization of marijuana.

We want our country to stop waging war in the name of“national security.” Our infrastructure needs rebuild-ing— that would be a mission worthy of our men andwomen in uniform. Americans who need work shouldbe able to get land and training to become small farm-ers. Growing our own —not just marijuana—seems likethe logical way out of the eco-crisis. The only way out.

Wouldn’t that require a big government program?We’re not against government of the people, by the

TOD MIKURIYA WITH AIDAN HAMPSON in front of Hampson’sposter, “Cannabidiol as a Selective Inhibitor ofInflammatory Lipoxygenases,” at ICRS ‘99. Hampson’sstudy was funded by the National Institute of MentalHealth. He was subsequently lead author on a patent,“Cannabinoids as Antioxidants and Neuroprotectants.”The assignee on the patent was Hampson’s employer,“The United States of America as represented by theDepartment of Health and Human Services.”

Correspondence from previous page

1848; resigned 1861. Knighted 1856. Changed hisname to O’Shaughnessy-Brooke in 1861. Professor ofChemistry at Calcutta. Director General of Indian tele-graphs 1853, and laid down first telegraphs in India.Died at Southsea. Published ‘Manual of Chemistry’1837; ‘Report on Poisoning’ 1841; ‘Galvanic Electric-ity’ 1841; ‘Bengal Pharmacopoeia’ 1844; ‘Electric-Telegraph Manual’ 1853, etc.”

Why William Brooke O’Shaughnessy legallychanged his last name is a mystery. A falling out withhis father? An offer he couldn’t refuse from the Brookefamily? W.B.O. deserves a full-fledged biography —too bad the book publishing industry is moribund. It’s alife made for the Ivory-Merchant treatment.

Another mystery is why the cannabis thatO’Shaughnessy sent back to his alma mater c. 1841 couldnot be made into effective potions. It is not knownwhether he sent seeds or seedlings. The latter would havebeen possible thanks to the Wardian case, a mini-green-house in which plants could withstand salt spray andextreme jostling on the deck of a ship, while requiringminimal fresh water. These artfully designed, sturdilyconstructed environments enabled the Brits to ship teaseedlings from China to India and rubber seedlings fromBrazil to Malaya and orchids from everywhere to col-lectors in England.

Mike Aldrich and Jerry Mandel have looked intowhy the cannabis O’Shaughnessy sent to his colleaguesin Edinburgh didn’t yield blockbuster extracts. “Thistopic was discussed in detail in the US Dispensatories

FAQs

people, for the people. That’s whatAmerica is supposed to stand for.We’re against government con-trolled by the corporations.

What do you think of BarackObama?

We don’t want to see our well-intentioned young president godown in history as a tragic figure.

Hell, man, I got to tell it like it was. I can’tgo around changing history.”

—Louis Armstrong

WARDIAN CASE , a portablegreenhouse, made possiblethe shipment of seedlingsacross the high seas.

of 1868 and 1899,” ac-cording to Aldrich. “Foot-notes in both editions sayGeorge B. Wood (Wood& Bache compiled the1868 post-Civil-War edi-tion of USD) went toEdinburgh and found thecannabis plant(s) there tobe like European hemp —only 4 feet tall, not resin-ous or sticky at all.

“At that point, in foot-notes quoted in both edi-tions, Sir Robert Christ-ison [renowned Edin-burgh toxicology professor, a teacher of O’Shaughnessy]said to Wood that the cannabis useful for medicine inIndia was grown in the hilly regions, not in the plains...a remarkably accurate comment for the time, pointingup the differences between Himalayan charas plants (C.indica) and the hemp type C. sativa, thinking that thegrowing of the (small) plant in the British climate mayhave caused it not to produce resin.”

Aldrich believes that the failure to grow potent off-spring and/or make effective extracts from O’Shaugh-nessy’s plants “killed the medical marijuana movement”all those years ago. “Neither the British nor the Ameri-can chemists,” he adds, “figured out that sinsemilla [theflowers of female plants shielded from pollen] shouldbe used, until Wood and others learned the sinsemilla-growing technique from India in about 1906.”

If things had worked out differently in Edinburgh inthe 1840s, resinous cannabis grown for medical pur-poses may well have taken its place alongside tea andrubber as major commodities controlled by British com-panies.

CBD from page 43

cannabis concentrates can cure cancer. (One of the vid-eos refers to an “all-CBD oil.”) Grinspoon e-mailedO’Shaughnessy’s: “Many people are taking this notionof the cancer curative powers of cannabis uncriticallyand I believe that this is fraught with danger for pa-tients and for medical marijuana.

“Yes, the work of Guzman and others clearly dem-onstrates that cannabinoids can shrink tumor cells ofsome cancers and generally facilitate apoptosis. But ithas never been demonstrated that any cannabinoid cancure any cancer. While the effects that have been de-scribed are encouraging and suggest that eventuallysomething may come of this approach to some can-cers, patients who interpret them as suggesting that can-nabis can cure their cancer and ignore the generallymore difficult and uncomfortable allopathic approachesto those cancers (which, depending on the type of can-cer and its stage), may, if they delay too long, miss theopportunity of a genuine cure or at least the prolonga-tion of life.”