Cannabidiol CBD is a compound in Cannabis that has medical effects but does not make people feel stoned and actually counters some of the effects of THC. After decades in which only high-THC Cannabis was available, CBD-rich strains are now being grown by and for medical users.
The reduced psychoactivity of CBD-rich Cannabis may make it an appealing treatment option for patients seeking anti-inflammatory, anti-pain, anti-anxiety and/or anti-spasm effects without disconcerting euphoria or lethargy.
Scientific and clinical studies indicate that CBD could be effective in easing symptoms of a wide range of difficult-to-control conditions, including: rheumatoid arthritis, diabetes, alcoholism, PTSD, epilepsy, antibiotic-resistant infections and neurological disorders. CBD
has demonstrated neuroprotective effects, and its anti-cancer potential is currently being explored at several academic research centers in the U.S. and other countries.
In the spring of 1998, the British government licensed a company called GW Pharmaceuticals to grow Cannabis and develop a precisely consistent plant extract for use in clinical trials. GW's co-founder Geoffrey Guy, MD, was convinced and had convinced the Home Office that by using CBD-rich plants, GW could produce a Cannabis-based medicine with little or no psychoactive effect. That summer Guy described his approach at a meetingof the International Cannabinoid Research Society. In addition to countering the psychoactivity of THC, Guy said, CBD conferred benefits of its own. Queen Victoria had used CBD-rich Cannabis for menstrual cramps. Indeed, animal studies suggest that CBD lessened anxiety and reduced the severity and frequency of seizures.
It was assumed that generations of breeding for maximum THC had reduced CBD in California cannabis to trace levels. GW had gotten its CBD-rich strains by acquiring the genetic library of HortaPharm, a Dutch seed company run by American ex-pat naturalists, David Watson and Robert Clarke. Tod Mikuriya, MD, founder of the Society of Cannabis Clinicians, expressed hope that "our Burbanks in the hills" would have preserved or could develop CBD-rich strains if and when an analytic test lab began serving the medical Cannabis industry.
As the years went by, more and more promising studies involving CBD were described at meetings of the ICRS, the International Association for Cannabinoid Medicine, and Patients Out of Time. California doctors kept abreast of the research and
O'Shaughnessy's reported on it, but we were merely observers, not participants until the fall of 2008, when Oakland's Steep Hill Laboratory began testing samples provided by Harborside Health Center.
Approximately one in 750 samples of Cannabis being grown for medical use is turning out to be CBD-rich. (For data collection purposes, "CBD-rich" has been defined as 4% or more by dry weight.) Doctors and patients now have a unique opportunity to evaluate its effects.
12/11/10 SCC HEARS McALLISTER ON CANCER RESEARCH
Barriers between pro-Cannabis MDs and the medical establishment are falling. Doctors who monitor cannabis use by patients were bursting with questions yesterday during a talk by
Sean McAllister, PhD, who has been studying the anti-cancer effects of cannabinoids in the laboratory (on a grant from NIH and with a license from the DEA). The occasion was the winter meeting of the Society of Cannabis Clinicians. "That's a very good question," McAllister would say, and provide the answer, and tie it back into his main thread.
Researcher Jahan Marcu at Temple University wrote up a recent presentation by McAllister, covering the same ground. Here's Jahan's account:
Dr. McAllister and colleagues at the California Pacific Medical Center Research Institute have discovered that
CBD (Cannabidiol) is a very potent inhibitor of breast cancer. They have reported findings on the cumulative effect of
CBD and THC in blocking proliferation of brain-cancer cells, and on
CBD's mechanism of action in blocking breast-cancer metastasis.
A new study by McAllister et al in the Journal of Breast Cancer Research and Treatment is an in-depth look at how CBD kills breast cancer cells in an animal model. CBD affects a protein called ID-1, which appears to be a major conductor of cancer cells. ID-1 is thus is an excellent target for a cancer treatment.
When cancer spreads it can eat through tissue (the process is called "metastasis"). CBD appears to inhibit the cells' aggressive behavior. The image above is from an experiment by McAllister testing how CBD can stop the invasion of cancer cells. The cancer cells are placed on a gel which contain small holes. The cells are dosed with a drug and after a few days you can count the number of cells that have made it through. This simulates what a tumor does as it eats its way through human tissues. The little black triangles are the cells. You can see that only a half-dozen or so made it through the gel when dosed with CBD (on the right). The control on the left shows that in the absence of CBD, the cancer cells easily chew through the gel.
McAllister and colleagues at California Pacific have posted a video showing cannabinoids selectively killing cancer cells.
(Video can be found here:
http://projectcbd.org/Science.html#First )
The therapeutic potential of CBD or a synthetic version thereof is, of course, of interest to pharmaceutical companies. McAllister mentioned that work may soon start on a CBD and breast cancer clinical trial with synthetic cannabidiol provided by a British company, STI pharmaceuticals.
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CBD MAY COUNTER THE MUNCHIES
The title of a paper published in
Neuropsychopharmacology earlier this year "
Cannabidiol Attenuates the Appetitive Effects of Delta(9)-Tetrahydrocannabinol in Humans Smoking Their Chosen Cannabis" suggests to us that CBD-rich Cannabis might work as an appetite suppressant. The authors, Celia Morgan and colleagues from University College London, tested 94 subjects on two occasions. The subjects smoked their own Cannabis and "while acutely under the influence" were offered more Cannabis, other drugs, and food. Morgan et al measured the eagerness with which the subjects responded to the offerings, and found that it correlated inversely with the CBD-to-THC ratio of the Cannabis the subjects were smoking. In other words, the higher the proportion of CBD they had ingested, the less desirous they became of more drugs and food.
In the great Prohibitionist tradition, Morgan et al concluded that "CBD has potential as a treatment for Cannabis dependence" and "possibly
for other addictive disorders."
Here's the abstract: "Worldwide Cannabis dependence is increasing, as is the concentration of Δ9-tetrahydrocannabinol (THC) in street Cannabis. At the same time, the concentration of the second most abundant cannabinoid in street Cannabis, cannabidiol (CBD), is decreasing. These two cannabinoids have opposing effects both pharmacologically and behaviorally when administered in the laboratory. No research has yet examined how the ratio of these constituents impacts on the appetitive/reinforcing effects of Cannabis in humans. A total of 94 Cannabis users were tested 7 days apart, once while non-intoxicated and once while acutely under the influence of their own chosen smoked Cannabis on dependence-related measures. Using an unprecedented methodology, a sample of Cannabis (as well as saliva) was collected from each user and analyzed for levels of cannabinoids. On the basis of CBD : THC ratios in the
Cannabis, individuals from the top and bottom tertiles were directly compared on indices of the reinforcing effects of drugs, explicit liking, and implicit attentional bias to drug stimuli. When intoxicated, smokers of high CBD : THC strains showed reduced attentional bias to drug and food stimuli compared with smokers of low CBD : THC. Those smoking higher CBD : THC strains also showed lower self-rated liking of Cannabis stimuli on both test days. Our findings suggest that CBD has potential as a treatment for Cannabis dependence. The acute modulation of the incentive salience of drug cues by CBD may possibly generalize to a treatment for other addictive disorders."
We'll look into the appetite-suppressant angle here at Project CBD
In animal studies another compound in the Cannabis plant, THC-V, has been found to suppress food cravings.
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CBD "ALERTING" EXCEPT IN HIGH DOSES
Nancy Sajben, MD, has shared a note from a patient about a CBD-rich strain purchased at Harborside Health Center (after he couldnt find any CBD-rich Cannabis in Southern California).
The patient wrote: Incredible Romulan, with a little vaping in the oven to remove THC, proved excellent for my chronic insomnia when made into a tincture.
Dr. Sajben wanted to know whether heating Cannabis would indeed remove THC.
Project CBD explains: Just a few comments on the concept of increasing CBD over THC I am afraid that this is not rational. Firstly, you cant create CBD when its not there to begin with. There are a lot of crazy misconceptions floating around along the lines of raw Cannabis has more CBD; that heating turns THC into CBD; or that you can differentially favor one over the other. None of these are true. The amount of CBD in a given chemotype is genetically determined, period. Generally speaking, drug strains of
Cannabis available in North America rarely have any significant amount of CBD.
THC has a boiling point of 157 Celsius, with CBD listed as 160-180 Celsius. However, both begin to sublimate off at even lower temperatures, and commercially available vaporizers, even the Volcano, do not heat evenly enough to allow fractionation of one component over another. What your patient is doing is wasting some cannabinoids and terpenoids by preheating. To get all of them out requires more prolonged heating, or a higher temperature. When the latter is done, it favors higher molecular weight sesquiterpenoids, many of which are sedating. That would account for the hypnotic effect along with whatever residual THC is left. Contrary to popular belief, CBD is actually alerting, except at exceptionally high doses.
References:
A Tale of Two Cannabinoids: The Therapeutic Rationale for Combining Tetrahydrocannabinol and Cannabidiol by Ethan Russo and Geoffrey W. Guy, and
Effect of D-9-Tetrahydrocannabinol and Cannabidiol on Nocturnal Sleep and Early-Morning Behavior in Young Adults" by Anthony N. Nicholson, Claire Turner, Barbara M. Stone and Philip J. Robson
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HOW DOES CBD COUNTER ANXIETY?
A new study by Jose A. S. Crippa and a team of Brazilian investigators confirms that symptoms of Social Anxiety Disorder can be reduced by treatment with CBD and identifies areas of the brain involved in the process. The paper by Crippa et al, "Neural basis of anxiolytic effects of cannabidiol in generalized social anxiety disorder: a preliminary report," was published online Sept. 9 in the Journal of Psychopharmacology. Ten men with severe Social Anxiety Disorder (SAD), ages 20 to 33, participated in the study, which was conducted at the University of Sao Paulo. Crystalline CBD from THC Pharm in Frankfurt was used. Prior to undergoing a neuroimaging procedure to measure blood flow in the brain, the subjects were given either 400 mg of CBD dissolved in corn oil and packed in a gel cap, or a placebo gel cap. A week later they were given the alternative treatment. The investigators assumed that the neuroimaging Single Photon Emission Computed Tomography (SPECT), which involves insertion of an intravenous tube and observation by a technician deploying a high-tech apparatus was in itself an anxiety-producing event. Subjects recorded their anxiety levels before, during, and after the neuroimaging by means of a "Visual Analogue Mood Scale (VAMS)." The researchers were able to correlate these subjective reports with blood-flow activity measured in the brain. "CBD was associated with significantly decreased anxiety," they concluded. They observed reduced radioactive tracer intake in the left parahippocampal gyrus, the hippocampus, and the inferior temporal gyrus. They saw increased uptake in the right posterior cingulated gyrus. "These results suggest that CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas," according to Crippa. If CBD-rich Cannabis exerts similar effects, Crippa's findings suggest that it can be useful in decreasing anxiety.
December 23 CBD Tops the Chart
Halent Labs has developed a spiffy, color-coded chart to help medical Cannabis users select strains best suited to treat their symptoms. The chart lists and defines desired effects, from "Analgesic" to "Vasorelaxant," along with 23 cannabinoids and terpenoids that supposedly contribute to those effects.
CBD is the most versatile tool in the Cannabis plant's kit, according to the Halent chart. It "reduces pain, slows bacteria growth, reduces blood sugar levels, reduces nausea and vomiting, reduces seizures and convulsions, reduces inflammation, reduces risk of artery blockage, inhibits cancer growth, treats psoriasis, is tranquilizing, suppresses muscle spasms, relieves anxiety, promotes bone growth, reduces function in the immune system, reduces small intestine contractions, retards nervous system degeneration, and reduces vascular tension." Reference to CBD as an anti-depressant is omitted.
The chart was developed by analytic chemist Don Land based on studies published in peer-reviewed journals. The 23 cannabinoids and terpenoids it refers to are the ones Halent is testing for.
Although the chart implies that the ability of the listed cannabinoids and terpenoids to provide the specified effects has been well established, the evidence of benefit ranges from very strong to very slight. Establishing (or disproving) efficacy was the impetus for both Project CBD and the SCC survey.
Halent plans to track patients' responses to CBD-rich Cannabis and strains containing other compounds of interest. They're undoubtedly aware that telling people what to expect from a given type of Cannabis will influence the effects reported, and that peer-reviewed journals would not publish data skewed in this way.
I say "Skew it." So what if the placebo effect accounts for 15 percent or even 30 percent of the reported benefit? If positive expectations alter brain chemistry in a way that makes drugs more effective, why go to great lengths to block positive expectations?
It's damn arrogant of the medical establishment to define the double-blind placebo-controlled, randomized clinical trial as "the gold standard of research," given all the deadly drugs the FDA has approved based on such trials. Corporate biomedicine is corrupt. Their most prestigious journals are full of ghost-written papers, they exclude studies showing adverse effects
Honest anecdotal evidence is far preferable to superficial rigor.
As I write this at the winter solstice, the New York Times is belatedly informing readers that numerous, rock-solid studies point to
Tylenol as a causal factor in asthma
But don't let 'em have any marijuana!
Fred Gardner
December 05 CBD Reduces Inflammation by Inhibiting Cox-2 Production
MAGL (monoacylglycerol lipase) is the enzyme primarily responsible for breaking down the endocannabinoid 2-AG (2-arachidonoylglycerol). Recent research shows that the Cox enzymes also break down 2-AG.
Researcher Gregory Gerdeman, PhD, elucidates:
"The products of 2-AG breakdown by MAGL (a hydrolysis reaction that literally cleaves the molecule) are different from the product of 2-AG breakdown by Cox-2 (an oxidation reaction... not accurately called a 'breakdown,' which is a generic term anyway, but a conversion into a product no longer active at CB receptors. I'm not sure if multiple Cox-2 oxidation products exist.
"Cox is not just creating the pain-mediating prostaglandins (which is the rationale for blocking Cox-2 with NSAIDs but at the same time it's breaking down 2-AG. Thus, when someone takes Ibuprofen, part of the pain- and inflammation-reducing effect is likely due to elevating 2-AG to act at the CB1 receptor (on pain-transmitting sensory neurons), or the CB-2 receptor (found on various leukocytes and which subsequently dampen inflammatory immune responses), or both."
According to Gerdeman, a study published in Science Nov. 11 by DK Nomura and colleagues, indicates that "endocannabinoids and neuroinflammatory prostaglandins seem to form a physiological axis of neuroprotection to neuroinflammation, which we are only beginning to understand. MAG lipase not only breaks down the protective 2-AG, but in so doing, turns it into a damaging prostaglandin that promotes neurodegenerative disease.
"Larry Marnett at Vanderbilt and his former student Kevin Kozak were first to show the oxygenation of 2-AG by COX-2 about 10 years ago.
Marnett recently published an important paper describing a new series of synthetic drugs that are 'substrate-specific' blockers of Cox-2, meaning that they block the 2-AG breakdown without affecting other substrates (like arachidonic acid).
"This stuff is sure to be getting the pharma folks busy thinking about new and plant-free ways to stimulate CB2 without influencing the central nervous system. Someone should be looking closely to see if CBD and other phytocannabinoids might interact in similar ways with the Cox-2 enzyme.
Gerdeman called our attention to
an earlier, related article showing that 2-AG can 'inhibit' neuroinflammation mediated by COX-2, by apparently blocking the cellular expression of the enzyme in response to toxic insults.
"Such 'inducible expression' is a hallmark of the COX-2 isoenzyme," he notes. "Taken together these studies point to a complex regulation of inflammatory processes by endocannabinoids, with the common downstream effect of neuroprotection.
"Could it be that CBD has similar effects?" he asks. "There is considerable evidence of CBD as a neuroprotectant, with multiple possible mechanisms. Chronic neuroinflammation is seen more and more to be an important player in the onset or progression of numerous age-related neurodegenerative diseases. It only makes sense to seriously investigate any non-toxic therapeutic possibilities."
Top O'Shaughnessy's News Service
October 21 Update on Omrita Rx3 CBD-Rich Offspring on the Rise
Miguel A., cultivator of Omrita Rx3, released clones of his strain to a handful of California collectives in August including WAMM and Harborside. The grower cracked 150 of the original strain backcross, 50 of which differentiated into females. All plants were grown indoors without direct light. For his analytical testing laboratory, Miguel tapped California Botanicals, providing 50 Omrita plant samples in April 2011, to be tested for cannabinoid content by HPLC.
Of the 50 Omrita Rx3 samples:
7 plants - CBD-rich (<1% THC) = 14%
18 plants - High THC (<1% CBD) = 6%
10 plants - 1:1 ratio CBD/THC = 20%
15 plants - 2:1 CBD/THC ratio = 30%
Even when a strain is stabilized, there is a varying cannabinoid profile in each seed. Not every seed of a "CBD-rich strain" will produce a CBD-rich offspring, just as not every seed of a "THC-rich strain" will produce THC-rich offspring. These latest results of the Omrita samples show that fully
64% of these plants yielded CBD-rich offspring. This is significantly higher than the 1-in-4 estimate that other CBD-rich strains have been proven to currently produce. This finding represents strong evidence that those genetic breeding programs specifically targeting higher CBD content (such as of Miguel A's) may indeed increase the likelihood of producing CBD-rich offspring.
