By Fred Gardner, Originally published in O’Shaughnessy’s
Tod Mikuriya, MD, did not live to see it, but his dream of investigating the medical potential of compounds in the cannabis plant other than THC is now within the grasp of his successors.
The Society of Cannabis Clinicians, the group Mikuriya founded in 1999, has drafted a “Strain Evaluation Survey” to collect data from patients who medicate with cannabis in which cannabidiol (CBD) is predominant.
CBD-rich cannabis will be available at California and Colorado dispensaries by late summer —and soon thereafter, inevitably, in other states where patients can legally use cannabis as medicine.
Twelve strains rich in cannabidiol (CBD) have been identified in the year and a half since an analytic chemistry lab began testing cannabis samples provided by California dispensaries, growers, and edible makers. Buds from five of these strains have been available intermittently at Harborside Health Center in Oakland. Herbal Solutions in Long Beach also has provided CBD-rich cannabis to patients.
Eight of the CBD-rich strains are currently being grown out. The others cannot be reproduced because the growers hadn’t saved or couldn’t regain access to the genetic material that yielded their buds of interest.
More than 9,000 samples have been tested to date by the Steep Hill lab in Oakland. Other start-up labs in California, Colorado, and Montana have begun testing for the burgeoning industry. The Full Spectrum lab in Denver has tested some 4,500 strains and identified seven CBD-rich strains.
A strain that is roughly 6% CBD and 6% THC, “Cannatonic,” has been developed by Resin Seeds in Barcelona and is being grown from seed by several collectives. Its name may be misleading, since CBD supposedly cancels the sedating effects of THC.
For purposes of the data collection being planned by the Society of Cannabis Clinicians, “CBD-rich” cannabis is being defined as more than 4% cannabidiol by weight (without respect to THC content) or more than 2.5% CBD if CBD exceeds THC.
Potential Usefulness of CBD
Until testing for cannabinoid content began, it was widely assumed that CBD, which is non-psychoactive, had been bred out of all the cannabis in California by generations of growers seeking maximum THC content.
Doctors in the SCC have watched with great interest in recent years as a British company, G.W. Pharmaceuticals conducted clinical trials of cannabis-plant extracts. G.W. has a license from the British government and backing from Otsuka, a Tokyo-based multinational.
G.W.’s flagship product, Sativex, is a plant extract that contains approximately equal amounts of CBD and THC. What benefits did G.W. scientists expect a CBD-rich extract to confer?
Various studies published in the medical and scientific literature suggest that CBD could be effective in easing the symptoms of rheumatoid arthritis, diabetes, nausea, and inflammatory bowel disorders, among other difficult-to-control conditions. CBD also has demonstrated neuroprotective effects, and its anti-cancer potential is being explored at several academic research centers.
An even wider market would emerge if the reduced psychoactivity of CBD-rich cannabis makes it an appealing treatment option for patients seeking anti-inflammatory, anti-pain, anti-anxiety, and/or anti-spasm effects delivered without disconcerting euphoria or lethargy.
The Blue-Ribbon Plant
The plant richest in CBD is a “True Blueberry/OG Kush” cross grown in the mountains south of Yreka by Wendell Lee of Full Spectrum Genetics (not to be confused with the lab in Colorado). Dried buds of TB/OGK have been sent for testing on four occasions by Harborside, the dispensary with which Lee is associated. Samples were consistently found to contain about 10% CBD (with THC levels around 6 to 7%). On the only occasion that a crop grown outdoors by Lee was tested by Steep Hill lab, it was found to contain 13.9% CBD.
Two other labs have confirmed the CBD content of Lee’s TB/OGK.
Lee is now working to “stabilize the genetics” and produce TB/OGK seeds. Several plants he provided to Project CBD (a nonprofit organized by writer/activist Martin Lee to promote research) are being grown out by experienced hands. Processed medicine and clones will be available at dispensaries in the months ahead. Details will be available on ProjectCBD.com, a website that will be launched by mid-August, according to Martin Lee (no relation to Wendell)
The California strain richest in CBD proportionally, “Women’s Collective Stinky Purple,” tested at 9.7% CBD and 1.2% THC. It was brought to Harborside by Grower #1 who also grows a strain called “Cotton Candy/Diesel” that was found to contain about 6% CBD and 6% THC. Grower #1 gets her starter plants from friends in Northeastern Mendocino County. Is there something in the genome of plants that have been swapped over the years by growers in those hills that encourages expression of CBD?
Another strain containing more than 8% CBD, grown indoors in the East Bay, was brought to Harborside in late April. “Omrita Rx3” is the name the grower has given it after learning that it was of special interest to SCC doctors.
A few weeks later a strain called “Harlequin” was found to contain about 8% CBD. And soon thereafter a pound of “Jamaican Lion” tested at 8.9% CBD. Clones of these strains are being grown out and will be available through Harborside and Project CBD in the months 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 Solutions in Long Beach.
To get the ball rolling on data collection, Project CBD developed a form to be given to patients purchasing high-CBD cannabis at participating dispensaries (see illustration on page 1). Feedback has also been solicited from a group of physicians who were given a small amount of TB/OGK trim [leaves removed when buds are manicured] for self-testing.
The anecdotal evidence coming from these two sources —about 12 people total— has been generally but not entirely consistent. Frequent reference is made to pain relief, a calming effect, and unimpaired —or improved— ability to concentrate.
Patient G. is an experienced cannabis user age 81 who regularly smokes a high-THC joint in the evening. He tested a CBD edible on three occasions and the results were identical. He experienced no noticeable effect after consuming a brownie in the late afternoon. He experienced “diminished effect” from his subsequent high-THC joint.“But the next morning when I went for my walk,” he reports, “I went further and faster than I had in a long time.”
Several people said they appreciated the relative lack of psychoactivity. As Patient 9 put it after smoking TB/OGK, “CBD-rich cannabis seems relaxing and soothing in regards to pain, anxiety, muscle tension and spasms, and it does not have the typical ‘high’ that goes with these therapeutic effects.”
But patient 10, who has been smoking TB/OGK reported, “I enjoy the herb, enjoy being able to use during the day without getting too spaced out, but have to watch out for memory lapses. I do stupid things like forget where I put stuff because I think I’m not affected, but I am affected.”
Patient Four in the Project CBD database, a 70-year-old man with arthritis, responded in detail: “Definitely anti-pain and anti-inflammatory. I would not call the effect a ‘high’ but I’m not sure it’s non-psychoactive. I would call it a ‘balanced effect’ or a ‘calming effect.’ You feel like you’re on a more even keel.”
For 10 days Patient Four ingested cookies made with trim from TB/OGK. (The trim was 5.1% CBD, 2.5% THC but we don’t know the amount used in the butter from which the cookies were made.) He reports being“able to concentrate for hours at a time and get up from my desk without groaning… Once or twice as the effect was coming on, I began to feel sedated, but that passed and I then experienced about three pain-free hours… Once I ate an extra half a cookie and was definitely sedated. Fortunately, it was bedtime… Dose level is going to be very, very important.”
Some caveats as we begin our long march towards collectively identifying the effects of cannabidiol.
1) The amount of CBD present will not be the only factor influencing the effects of a given cannabis-based medicine. The ratio of CBD to THC may be as important, and the terpenoid and flavonoid content may be as important.
2) We are capable of placebo-effecting ourselves individually and placebo-effecting ourselves collectively. Some may exaggerate the potential benefits of CBD and raise false hopes.
3) The line between physical effect and effect on mood is often indistinct. Improved mood might result, for example, if the man with arthritis experiences reduced inflammation and less of the “background pain” that afflicts older people.
4) When a patient reports the effect of a drug on mood or pain, the report is inherently subjective.
5) How CBD in the liver affects the metabolism of other drugs has not been studied thoroughly. The Drug Warriors could argue that Prohibition must remain in effect because “more research is needed.”
The Doctors’ Hopes re CBD
The wide range of variables and “confounding factors” confronting doctors who want to study the effects of CBD-rich strains was discussed at the winter meeting of the Society of Cannabis Clinicians.
UCSF professor Donald Abrams, MD, the featured speaker, recounted the obstacles he faced in conducting clinical trials with government-issued cannabis and getting his results published in peer-reviewed medical journals.
SCC President Jeffrey Hergenrather volunteered to head the committee that will organize the group’s data collection effort. Abrams agreed to informally consult on the SCC study design.
The first step, a “Strain Evaluation Survey,” will soon be accessible on the SCC’s website. It asks, among other things, “What factors limit your use of cannabis at a frequency that affords optimal relief of symptoms?”
The answer options are: “Cost,” “Can’t perform tasks,” “Family or social reasons,” “Concern for having use discovered,” “Get too sleepy,” “Get too altered/ spacey,” and “Concern for habitual use.”
Hergenrather says that he is beginning to see in his practice, “a growing percentage of patients, especially older patients, who have not used cannabis before, but they have come to understand that it has many medicinal uses and may afford relief from their symptoms with fewer adverse effects than conventional pharmaceuticals.
“I am seeing many older patients who would like to try cannabis for pain, muscle spasms, insomnia, and management of various cancers. One thing that most of these cannabis-naive patients are not interested in is ‘getting high.’ My hope is that the CBD-rich strains will enable them to use cannabis and get its benefit without —or with less of— the usual ‘high.’”
Hergenrather thinks that patients who
“might benefit by maintaining a higher blood level of active cannabinoids include those with inflammatory bowel diseases (Crohn’s and ulcerative colitis), the neurodegenerative diseases (multiple sclerosis, ALS, Parkinson’s, Hunting-ton’s), epilepsy disorders, autoimmune disorder, (Lupus, rheumatoid arthritis, etc.), stroke, concussion, and brain trauma, and cannabis-sensitive cancers —glioblastoma multiforme, thyroid cancer, lymphomas and some leukemias, colon cancers, neuroblastoma, and others).”
Hergenrather hopes that plant breeders will now try to lower THC content. “Having an option to use a CBD-rich strain that is low in THC would not only benefit the patients who don’t want to get ‘high’ but also all of those patients who would benefit with higher blood levels of cannabidiol.
A simple way to raise the CBD-to-THC ratio of a given batch of medical cannabis is to blend in dried flowers from a CBD-rich hemp plant containing only trace amounts of THC. That’s how G.W. Pharmaceuticals produces Sativex —by growing CBD-rich hemp plants outdoors and THC-rich plants in glasshouses, then blending them.
In February a friend in Spain sent Project CBD seeds from a hemp strain whose flowers reportedly contain four to six percent CBD, depending on growing conditions. These were started indoors by a grower affiliated with the Los Angeles-based Cornerstone Research Collective —along with seeds of “Cannatonic” that had been donated by Resin Seeds of Barcelona. According to Project CBD’s benefactor, one in four of the Cannatonic seeds —available from resinseeds.com—should contain 6.5% CBD by weight, and the same amount of THC. “The perfect Sativex mix,” is how he describes the strain’s cannabinoid content.
Project CBD also has a line on industrial hemp seeds reported to contain 10% CBD and almost no THC!
Stacey Kerr, MD, of Santa Rosa has been doing home visits with cancer patients, “filling in the gaps that all their other doctors can’t fill. When you are getting care from several specialists, these gaps will sometimes happen. So I sit by the bedside and take the time to talk about therapy and side effects. Then we problem solve about how to deal with the side effects and how to best communicate with their treating physicians.
“Several of my patients are using cannabis for nausea and vomiting. However, they are hesitant to use it because of the psychoactive effects and we spend time talking about the most effective way to dose, the timing of their doses, and the medication itself.”
Kerr offers the example of Linda (not her real name) a patient with metastatic breast cancer in her bones, liver, and possibly her stomach. “She finished three weeks of intensive radiation and just now finished her first three weeks of intensive chemotherapy. She has lost over 30 pounds through the course of treatment. She is bedridden and extremely weak. This woman is a highly educated professional and a triathlete.
“I was at Linda’s home this past Saturday and on Easter Sunday discussing options for nausea/vomiting control. Her pain is well treated. The image she described to me when she drinks a glass of water is that of a boiling hot metal cauldron hit with cold water so the water erupts right back up and out because of the heat reaction. She is using several different prescription medications, but the medication that works most effectively for the vomiting is cannabis.
“She was not a regular user prior to her cancer needs. Her only complaint is that it does not seem to last very long when she uses the vaporizer, and she doesn’t want to be ‘stoned.’ She has two small children, an analytical mind, and is already stoned enough on the prescription meds she needs.
“I was able to provide a legal recommendation for her use of medical cannabis. I explained CBD strains to her and her caregivers (all of them are professionals) and Linda’s caregivers were able to obtain an ounce of TB/OGK bud from Harborside in early April.
“My hope, says Dr. Kerr, “is that having a CBD-rich strain will allow her to use the medicine as often as needed without extreme side effects but with excellent relief for nausea and vomiting. Oral intake would be beneficial with longer-lasting effects and direct activity on the most inflamed tissue. If she was not afraid of the side effects, she would be more willing to use the medication in amounts that are most effective.”
Kerr adds, “My patients who are professionals without a history of using marijuana would be more likely to use it if it was specifically for medical uses and not ‘tainted’ with a culture of illicit highs. This is a cultural block, I know, but it is real, and I work hard to overcome it every time I counsel on the use of medical marijuana. CBD-rich strains that are effective will support our efforts to legitimize cannabis as powerful, authentic medicine.”
Possible mechanisms of action
Martin Lee explains that based on published studies, CBD should provide “an enhanced endocannabinoid effect even though it does not bind to a cannabinoid receptor. CBD indirectly stimulates both CB1 and CB2 receptor signaling in at least two key ways:
“First, CBD inhibits the production of FAAH, the enzyme that breaks down anandamide, and this results in higher anandamide levels (think runner’s high) and heightened CB1 receptor signaling, given that anandamide activates the CB-1 receptor (but not CB2.) At the same time, CBD buffers the psychoactivity of THC by preventing THC from binding with the CB1 receptor.
“Also, it appears that CBD amplifies THC’s activation of the CB2 receptor. Several studies show that CBD and THC augment each other’s analgesic and anti-inflammatory properties. A combination of THC and CBD is much better than THC alone in providing pain relief.”
The goals of Project CBD are educational, according to Lee, but they can also be seen as political and/or public relations for the Society of Cannabis Clinicians (whose studies the site will be facilitating and publicizing). Some of the messages Project CBD hopes to get across to the American people:
• A non-psychoactive component of the plant may have important medical benefits.
• Pro-cannabis doctors and their patients want to see if this non-psychoactive component is effective in treating various conditions.
• An honest data collection effort by SCC doctors and the medical marijuana community is more trustworthy than the “rigorous” but corrupt clinical trials conducted by pharmaceutical corporations.
• Cannabis dispensaries, while competing for market share on one level, are unified in their commitment to researching the medical potential of the plant.
• Although pro-cannabis MDs are derided in the media as “potdocs” and profiteers, some are serious specialists whose understanding of human physiology is superior to that of their colleagues (who did not learn about the en-docannabinoid system in med school and to this day may not have heard of it).
• SCC doctors, by keeping abreast of the data, will be better able to help patients formulate their treatment plans. (The advent of CBD-rich cannabis will raise questions of efficacy and appropriate strain and dosage for every patient who tries it.)
Update from Fred Gardner
The Werc Shop, a new Los Angeles based analytical testing lab, reports that in early July a strain called “Poison OG” was found to contain approximately equal amounts of CBD and THC. Dr. Jeff Raber of The Werc Shop verified the finding using two complementary analytical techniques.
Full Spectrum lab in Denver, which uses high-pressure liquid chromatography to measure cannabinoid levels, is reporting slightly higher numbers than Steep Hill, with three strains in the 10% CBD range. This may be a function of the different technology.
Lester Grinspoon, MD, has been dismayed by some videos suggesting that cannabis concentrates can cure cancer. (One of the videos refers to an “all-CBD oil.”) Grinspoon e-mailed O’Shaughnessy’s: “Many people are taking this notion of the cancer curative powers of cannabis uncritically and I believe that this is fraught with danger for patients and for medical marijuana.
“Yes, the work of Guzman and others clearly demonstrates that cannabinoids can shrink tumor cells of some cancers and generally facilitate apoptosis. But it has never been demonstrated that any cannabinoid can cure any cancer. While the effects that have been described are encouraging and suggest that eventually something may come of this approach to some cancers, patients who interpret them as suggesting that cannabis can cure their cancer and ignore the generally more difficult and uncomfortable allopathic approaches to those cancers (which, depending on the type of cancer and its stage), may, if they delay too long, miss the opportunity of a genuine cure or at least the prolongation of life.”