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Vol. 6, Number 7 July 2014 Contributors: cheryl riley, James Freire, Dr. David Bearman, Gradi Jordan, Ed Glick, Paul Armentano, Sunil K Aggarwal, Al Byrne, Amanda Reiman, Jim Greig, Joan Bello, Arthur Livermore |
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Two Steps Forward, One Step Back - David Bearman, M.D. In a recent DPA correspondence, Ethan Nadelman, Ph.D., Executive Director of the Drug Policy Alliance noted an interview on WNCN News regarding the anti-seizure properties of cannabis where a parent says, “I want to try the [Charlotte’s Web] oil. At one point, I was giving Zora 20 mg. of valium a day, to try to stop the seizures. That is a toxic, mind altering, addictive drug but that was sanctioned. That was OK.” Dr. Nadelman goes on the say that, “Indeed, the great irony of Charlotte’s Web is that because it is so low in THC, it doesn’t cause children to get high or drowsy like most FDA-approved anti-epilepsy drugs. Yet “thanks” to our nation’s backward drug policies, it’s only available in states like Colorado.” The history of government stupidity on the issue of hemp and medicinal cannabis policy would fill volumes. Notwithstanding the AMA’s testimony against the 1937 Marijuana Tax Act, the Congress passed it anyway and Roosevelt signed it into law. In 1972 the Nixon Marijuana Commission said legalize cannabis for recreational purposes, that did not happen. In 1974 Dr. Billy Martin at Virginia Commonwealth University showed that cannabis might cure cancer. The government gave these findings short shrift. Back in 1988, the DEA’s Chief Administrative Law Judge, Francis Young, ruled, “Marijuana, in its natural form, is one of the safest therapeutically active substances known to man. By any measure of rational analysis marijuana can be safely used within a supervised routine of medical care.” He recommended rescheduling it. That didn’t happen. In 1999 the federally funded Institute of Medicine (IOM) Report found the side effects of cannabis no greater than your average Rx. You still hear outrageous lies claiming cannabis is not safe. In 1971 the Under Secretary of Health for HEW, Dr. Rodger Egeberg, (former Dean of USC School of Medicine), in a letter to the Senate Committee considering scheduling under the 1970 Controlled Substances Act, suggested that the findings of the Nixon Marijuana Commission would be pivotal in determining what schedule cannabis should be placed in. Yet here we are 43 years later, and marijuana is still designated a “Schedule I” drug under the Controlled substances Act. The federal government, against overwhelming evidence to the contrary, finds that cannabis is a drug that supposedly has “no currently accepted medical use,” and “lacks accepted safety.” We in SCC/AACM know the contemporary clinical story of the medicinal value of cannabis. Most of us are familiar with both the ancient history of this incredible medicine and the disgraceful, modern history of government obstruction to the clinical use of cannabis. This is a case of the interests and power of the petro-chemical industry trumping medicine, agri-business and common sense. We must stand up against this unfounded, bigoted, unscientific insanity being perpetrated by the government in the name of protecting us from ourselves. In 2009 the AMA requested that cannabis be made Schedule II. A very conservative move considering that THC, the principal euphoriant in cannabis, is a schedule III drug. This could be done by President Obama. So far nothing, even though he has said he would follow the science. The DEA denies that marijuana is a medicine because it is not approved by the Food and Drug Administration (FDA). Yet the U.S. Drug Enforcement Administration (DEA) has a catch-22 for patients, doctors and scientists wanting to study cannabis like any other biologically derived medicine. The NIDA and the DEA repeatedly blocked attempts at research by respected researchers and clinicians. Simultaneously NIDA, often with FDA complicity, is busy obstructing the very research required for marijuana to gain FDA approval. Rick Doblin of MAPS has pointed out that marijuana is the only Schedule I drug prohibited by the DEA from being produced by private laboratories for scientific research. This is one more of the roadblocks thrown in the way of doing reasonable science. We are well aware that there are reams of scientific data establishing marijuana’s safety and efficacy. Nevertheless the DEA has effectively and consistently blocked the standard FDA development process that would allow for marijuana to be brought to market as a prescription medicine. But there are small signs of hope. The U.S. Public Health Service recently announced it would approve a University of Arizona study on medical marijuana for veterans suffering from post-traumatic stress disorder. This is one of the first times the federal government has allowed the entire marijuana plant – as opposed to isolated and synthetic cannabinoids – to be used for research to examine its potential benefits. Another piece of positive news comes from Attorney General Eric Holder’s recent statement that the Obama administration is willing to work with Congress as lawmakers work to remove marijuana’s Schedule I designation. This would be a modest step in the right direction – one that could ease restrictions on medical marijuana research – though it would do nothing to stop marijuana arrests or prohibition-related violence and the related emotional and financial costs. The House recently voted not to fund the DEA’s anti-marijuana efforts in states where medical marijuana is legal. Now it goes to the Senate. You may wish to contact your Senator on this one. Just a few months ago the most recent federal Farm Bill legalized hemp in ten states for the first time in over three generations. The bottom line is this: We already know that marijuana can alleviate symptoms of a huge variety of serious medical conditions – not only epilepsy, but multiple sclerosis, cancer, HIV/AIDS, glaucoma, post-traumatic stress disorder, arthritis, Alzheimer’s, Parkinson’s and many other diseases and ailments. And it works without debilitating side effects, allowing patients moments of real relief so they can once again go about their daily life. Isn’t it time the laws and regulations of our federal and state governments were brought in line with empirical evidence rather than myth and prejudice? Isn’t it time for every patient who needs it to be able to receive the life-changing relief medical marijuana can provide? Nadleman summed up the impact of the CNN documentary which highlighted the anti-seizure capability of cannabis. He wrote that,
The Figi family’s breathtaking experience has been a beacon for similar families all across the country – and it helped change the views of Dr. Sanjay Gupta, the neurosurgeon and CNN correspondent who had previously believed the myth that marijuana has no medical uses. His conversation has helped move public opinion even more strongly in favor of medical marijuana. Please help DPA ensure every family access to Charlotte’s Web and other therapeutic uses of marijuana. In doing so, you will help make a profound, positive difference in the lives of millions.” The case for analyzing whole Cannabis, it’s extracts and preparations for terpenoid and “bio-flavinoid” components - James Freire Introduction: With an emerging body of knowledge proving the efficacy of whole plant Cannabis in a wide range of medicinal applications, much of the present focus is on cannabinoids and the emerging data is seriously challenging reductionist thinking which spurred the “single compound” approach taken by most mainstream pharmaceutical companies. Find a molecule that works, derivatize it by SAR and patent. This approach has been marked by failure to replicate the broad therapeutic range of whole Cannabis in the “single compound” approach. Further research has shown that within the cannabinoids is a synergistic system which ,in concert, produces impressive results. A prime example is the simplistic relationship between THC and CBD. Where research is lagging seriously behind is in the elucidation of the two other significant therapeutic species, the terpenoids and the “bio-flavinoids”. I hope to provide a case for the importance of analysis for these compounds in characterizing the therapeutic nature/value of a strain, extract or preparation. It is my assertion that terpenoids ,as precursors to the cannabinoids and as known therapeutic compounds structurally related to cannabinoids, are as important as the ’cannabinoid profile' in determining medicinal efficacy. The group of substances collectively known as “bio-flavinoids” are also vital and instrumental synergistic components to the overall effects of Cannabis as a medicinally important substance. The terpenoids The terpenoid constituents of cannabis are both precursors to the cannabinoids and potent stand alone compounds. Medically they are extremely useful broad range substances found in aromatic plants and thousands of others. Of primary importance in Cannabis as metabolic precursors to the cannabinoids they exert an influence on the cannabinoids expressed in the plant. Of secondary importance is their influence on the actions of the cannabinoids. From the The Linnean Society of London: “Sixty-eight compounds were identified by coupled gas chromatography and mass spectrometry (GC-MS) in the chemosphere of Cannabis sativa L. pollen and entire male and female plants of two cultivated varieties, Northern Lights and Hawaian Indica. Twenty-one and 28 substances, respectively, were present in pollen of the two forms. To conserve the natural composition of volatiles a delicate headspace method was employed. The two varieties represent different chemotypes which distinguish themselves, in the main quantitatively, in the setup of volatiles from pollen and entire male and female plants. Twenty compounds were monoterpenes, including the five major components: β-myrcene (E)-β-ocimene, terpinolene, β-pinene and limonene; 25 were sesquiterpenes, and the other 23 were of mixed biogenetic origin, including 3-methyl-1-butanol and benzylalcohol which occurred only in pollen; two pyrazines occurred only in Northern Lights females. Besides being of interest in natural products chemistry, the results should have relevance for plant systematics and for the pharmaceutical and technical applications of Cannabis. We demonstrate that the pollen has a distinct chemical character in possessing two exclusive volatiles, while lacking seven compounds occurring in males and females of both variants. © 2005 The Linnean Society of London, Botanical Journal of the Linnean Society, 2005, 147, 387–397.” This is one example of completely different “strains” of Cannabis having unique terpenoid profiles. An example of how this is relevant is the example of β-caryophylline which is a CB-2 receptor agonist and non-psychoactive anti-inflammatory. So do higher levels of this terpene make for a more potent anti-inflammatory agent? Again this is reductionist thinking as it works in concert with CBD at the CB-2 site. So do they potentiate each other or compete for the receptor? This would become apparent with analysis as high levels of analgesia would correspond to a relationship between CBD (and possibly other compounds) with β-caryophylline in relation to effect. From Marijuana and the cannabinoids By Mahmoud A. ElSohly “7. MEDICAL VALUES OF TERPENES The terpenoid compounds found in C a n n a b i s resin are numerous, vary widely among varieties, and produce aromas that are often characteristic of the plant’s geographic origin. Although more than 100 different named terpenes have been identified from C a n n a b i s, no more than 40 known terpenes have been identified in a single plant sample, and many more remain unnamed(11). Terpenes are produced via multi-branched biosynthetic pathways controlled by genetically determined enzyme systems. This situation presents plant breeders with a wide range of possible combinations for developing medical C a n n a b i s varieties with varying terpenoid profiles and specifically targeted medical uses. Preliminary breeding experiments confirm that the terpenoid profiles of widely differing parents are frequently reflected in the hybrid progeny. Only recently have C a n n a b i s essential oils become economically important as flavorings and fragrances(17 ). Early C a n n a b i s medicines were formulated from alcoholic whole flower or resin extracts and contained terpenes, although they were not recognized to be of medical importance. Several of the monoterpenes and sesquiterpenes found in C a n n a b i s and derived from other botanical and synthetic sources are used in commercial medicines. Other as-yet unidentified terpenes may be unique to Cannabis. The highly variable array of terpenoid side-chain substitutions results in a range of human physiological responses. Certain terpenes stimulate the membranes of the pulmonary system, soothe the pulmonary passages, and facilitate the absorption of other compounds(15). Terpenoid compounds are incorporated into pulmonary medical products such as bronchial inhalers and cough suppressants. Casual studies indicate that when pure THC is smoked, it produces subjectively different effects than it does when combined with trace amounts of mixed C a n n a b i s terpenes. 
Fig. 3. Cannabinoid biosynthesis is mediated by enzymes controlled by individual genes Clinical trials using whole plant extracts of known cannabinoid content and varying terpenoid profiles will determine what effects terpenoid compounds have on the pharmacokinetics of the cannabinoids.” The determination by Mr. ElSohly that further investigation into the phamacokinetics of whole plant cannabis is important but still leaves out another powerhouse class of compounds collectively known as ”bio-flavinoids” . Bio-flavinoids The broad class of compounds called collectively “bio-flavinoids” are represented strongly in Cannabis. Known primarily as powerful anti-oxidant compounds their mode of action is disputed but their effects are not. Including such compounds like resveratol from red wine and quercetin and kaempherol from citrus have documented positive effects on cardiovascular health. Cannabis has particularly potent flavinoids called cannflavin A&B as well as quercetin and kaempherol. Cannflavin A&B have shown potent inhibition of prostaglandin in synovial cell cultures. This indicates a positive benefit for arthritic conditions. As mentioned previously Cannabis has two other potent anti-inflammatory agents, the cannabinoid, cannabidiol and the terpenoid, β-caryophyllene that work in synergy together in some fashion on the CB-2 receptor to mitigate inflammation. To this we now add a third component, the Cannflavins. Also another, apigenin, is a potent medicinal agent. “Flavonoid components of cannabis, especially likely to be of benefit in oral or sublingual administration, include apigenin, a unique agent that has strong anti-anxiety effects without sedation (Salgueiro et al. 1997).” Yet another example of the three part synergy is in the anxiolytic properties of CBD as it interacts with the mood elevating properties of limonene and the anxiolytic properties of the flavonoid apigenin. The Flavinoids also work in concert with the Canabinoids to handle cell damage. Cannabinoids act like triage for damaged cells and if the cell is too damaged to repair itself correctly it causes cell death to prevent abnormal growth (apoptosis). The flavinoids work with this system to help repair the less damaged cells that can survive healthily by scavenging free radicals. This helps prevent cancers and other abnormal cell proliferation. Bio-flavinoids play key roles in cardio-vascular health, prevention of atherosclerosis, activate key enzymes in mitochondrial respiration and protection in neuro-inflammatory events as well as improving blood circulation in the brain. Given the emerging information on the positive benefit of Cannabis in stroke and Alzheimer’s disease a closer look at the bio-flavinoids of Cannabis seems another vital piece of information that should be quantified by analysis. Conclusion: The clear overlapping of function by a number of the various chemical species gives rise to many questions regarding the true pharmacokinetics of Cannabis sp. The relatively undisputed assertion that whole plant products are much more medicinally effective than single components or even some crude extracts gives rise to the natural question, why? The only answers will come with analytical comparisons of all three major medicinally active groups in relation to each other. In absence of a quantifiable enumeration of all constituents, cannabinoid analysis is only providing 1/3 of the whole picture. While they produce the most marked effects due their psychoactivity they only are a part of a vastly complex synergistic mode of action. When the complete picture can be developed it will open the door to analysis of the actual nature of Cannabis phamacokinetics. In the mean time the information being available can help give a quantifiable means of strain comparison that goes beyond the limited information provided by cannabinoid profile alone.
Alabama: Considering a medical marijuana law.
Arkansas: Considering a medical marijuana law. Florida: Medical marijuana petition drive underway. Idaho: Considering a medical marijuana law. Indiana: Considering a medical marijuana law. Iowa: Considering a medical marijuana law.
Kansas: Medical marijuana petition drive underway.
Minnesota: Passed a restrictive medical marijuana law.
Missouri: Considering a medical marijuana law.
New York: The 23rd medical marijuana state.
North Carolina: Considering a medical marijuana law.
Ohio: Considering a medical marijuana law.
Pennsylvania: Considering a medical marijuana law.
South Carolina: Considering a medical marijuana law. South Dakota: Medical marijuana petition drive underway. Tennessee: Considering a medical marijuana law. Texas: Considering a medical marijuana law.
Wisconsin: Considering a medical marijuana law.
Featured Recipe - Marble Madness by Jay R. Cavanaugh, PhD A Canny Bus Quick Treat Some of the best things in life are so easy. Here’s a recipe that is ready in minutes and tastes just delightful. The only problem with this desert treat is the urge to eat more than is really good for you. The trick to this recipe is getting the consistency right. Whenever you use cannabutter in place of dairy butter the result will be that the product is more crumbly. For stand up firm cookies and cakes it is best to go to a 50/50 mixture of butters but Nancy Wife and I prefer straight cannabutter for potency. As usual, feel free to improvise and use what ratio is right for you. Now, some believe that when your cake crumbles that the calories leak out and it’s less fattening. Of course, this is true. You eat this cake by using a fork to push down on the moist blond/green/chocolate crumbs sticking them to the back of the fork or you can use your fingers and lots of licking. We used a special cannabutter for this recipe (see Kicked Up Better Bud Butter). A word of caution about this cake you’re about to make: Don’t leave it out for the kids! They will eat it and you will be in trouble! Ingredients:
¾ cups of Kicked Up Better Bud Butter
Directions: Melt the cannabutter in a sauce pan over low heat and pour it into a bowl containing the sugar and stir to mix. Beat in the eggs and vanilla and the liqueur of your choice. Use a double boiler to melt your chocolate chips. Stir often. This step is what gives you the “marble” effect. If you’re lazy (and I am) you can just add the chips to the final batter. In another bowl sift the dry ingredients together then mix with the wet ingredients then drizzle in the chocolate forming swirls or just mix in chips (some of you may prefer butterscotch chips or even white chocolate). Place the batter in a baking pan that has been lightly oiled and floured. Bake at 325 degrees (I know that’s low) for about 20-40 minutes. You can tell when the cake is done by sticking a toothpick in the cake. When the toothpick comes out relatively clean, the cake is ready. Remove from the oven and let the cake cool for a bit before attempting to remove from the pan. The cake is going to be crumbly so it’s tough to cut out nice squares but we don’t mind J Recommended Beverage: 20 year old Tawny Port served room temperature or Hennessy VSOP Cognac served slightly warmed.
Recommended Activities: Getting a good nights sleep
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May 8, 9, 10, 2014 Portland, Oregon USA
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