• Summer 2010 —41—
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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 stuff because I think I’m not affected, but Iam affected.”
“Dose level is going to bevery,
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,
Some caveats as we begin our longmarch 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 of CBD 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 of the “background pain” that afflicts olderpeople.4) When a patient reports the effectof a drug on mood or pain, the report is
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 CBD
The 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 of cannabis 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 understandthat it has many medicinal uses and mayafford relief from their symptoms withfewer adverse effects than conventionalpharmaceuticals.
Hergenrather hopes that plant 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 oth
CBD CONTENT of True Blueberry/OGKush is indicated by large spike at left of chromatogram 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.
HIGH-THC STRAIN, typical of the >9,000tested to date in California, has virtuallyno CBD. Scale at bottom gives amount of time heating in the urn of the gaschromatograph. Vertical scale indicatesamount of specific compounds evaporatingat known temperatures.
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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 CO
. Several labs are studyingthe mechanism by which the enzymespromote the reactions. One theory of why the offspring of a plant whoseparents contain only trace amounts of CBD 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 equalamounts 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
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.
To 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 doesspecial interestto SCC doctors.A few weekslater a straincalled “Harle-quin” was foundto contain about8% CBD. Andsoon thereafter a