Saturday, February 22, 2014
On Wednesday the Senate Health and Welfare Committee held a hearing on Cannabidiol Oil. Dr. Bret Smith from The University of Kentucky Epilepsy Department testified about cannabidiol research. Committee chair, Senator Julie Denton, will call this bill up for a committee vote with enough support. If it clears the Health and Welfare Committee it will go to the Senate floor for a full vote.
How To Help
Call the legislative hotline at 1-800-372-7181 and tell the operator to leave a message for all members of the Health and Welfare Committee asking them to pass SB 124 favorably from committee.
Medical Hemp and Medical Cannabis
There are differing opinions among activists about the merits and shortcomings of CBD only bills. Though I appreciate all sides of this argument, I come down in support of both the medical cannabis and medical hemp bills (CBD bill). I see these as separate issues because under state and federal guidelines many CBD strains qualify as hemp and not cannabis. Why advocate for hemp as marijuana, especially if doing so could unnecessarily delay access, possibly for years?
Passage of Medical Cannabis Bills Equally Important
Though CBD strains are helpful for conditions like cancer, epilepsy, Crohn's and colitis, and diabetes, many conditions, including some of those mentioned, also benefit from the addition of a full spectrum cannabis strain. Hemp and cannabis strains appear to work in synergy and make one another's components work even better.
For example, as a cancer patient CBD could help me, but the THCA in full spectrum strains would add additional cancer fighting properties. As a mother and a teacher I don't want to smoke anything or get high. But even with the cannabis strains there are options. I could take a full spectrum cannabis oil extract from raw plant. This method would leave THC in its precursor THCA form, which has no psychoactive components but retains the medicinal properties of THC.
For other conditions the smoked form is the most medicinal means of delivery. You never know which configuration your doctor will find works best for you. That's why it is important to keep all strains and delivery method options open in legislation. Please support SB 43 and HB 350, The Cannabis Compassion Act, as well.
Press the Fight,
Suzanne De Gregorio
February 22, 2014
Sunday, February 9, 2014
This week in Kentucky a CBD Oil bill was introduced by Senator Julie Denton (R-Louisville). If passed, doctors affiliated with Kentucky universities that have medical school will be able to prescribe CBD and it may also be used in clinical trials.
This does not limit by age or condition, which is good since science suggests cannabidiol may help a wide array of conditions, not just epilepsy. Anything from cancer, strokes, Crohn's Disease, Multiple Sclerosis, Parkinson's Disease, and Diabetes to name a few. I will link some of that research at the bottom of this page and the sheer volume will overwhelm you. Read it then answer this question: don't you want the laws already in place in case God forbid yourself or a loved one develops one of these all too common illnesses?
Sick people need relief, especially given many are exhausting pharmaceutical options. Since beginning this campaign in November my son has failed another pharmaceutical anticonvulsant. This time an adverse reaction to the medication itself gave him the impulse control of a toddler. He was running in front of cars, trying to pull boiling pots of water onto himself, sticking his hand in the garbage disposal, and otherwise harming himself and others. This drug carries the risk of suicidal impulses. Is doing dangerous stuff how suicidal impulses manifest in the minimally verbal? How am I supposed to even know? Thankfully, he has calmed down since we titrated down that drug, but there is still the matter of complete epilepsy control, which we've never attained with anything except steroids. CBD oil can't come to Kentucky fast enough!
Special thanks to Senator Denton and the other co-sponsors of SB 124.
Please read the bill and support SB 124. Call your Senator at 1-800-372-7181 and ask him or her to support SB 124. If you don't know who your senator is give the operator your zip code and she will deliver the message. Thank you.
Suzanne M. De Gregorio
February 9th, 2014
Research into Cannabidiol for various conditions. This list is by no means complete. I just had to stop somewhere.
Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis
Breast Cancer Res Treat. 2012 May;133(1):401-4.
Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells.Mol Cancer Ther. 2007 Nov;6(11):2921-7.
PLoS One. 2011;6(9):e23901. doi: 10.1371/journal.pone.0023901. Epub 2011 Sep 7.
Crosstalk between chemokine receptor CXCR4 and cannabinoid receptor CB2 in modulating breast cancer growth and invasion.
Anti-tumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinomaAmerican Society for Pharmacology and Experimental Therapeutics
Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibitionMolecular Cancer 2010, 9:196
Cannabinoids: a new hope for breast cancer therapy?
Cancer Treat Rev. 2012 Nov;38(7):911-8.
The endogenous cannabinoid anandamide inhibits human breastcancer cell proliferationProc. Natl. Acad. Sci. USAVol. 95, pp. 8375–8380, July 1998
Cannabis Compound May Stop Metastatic Breast Cancer - ABC News
*There is research for cannabidiol and other types of cancer, but in the interest of space I'm focusing on the most common one. For a more complete list click here.
Pharmaceuticals 2010, 3(7), 2197-2212; doi:10.3390/ph3072197
Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke
Cannabidiol Prevents Cerebral Infarction Via a Serotonergic 5-Hydroxytryptamine1A Receptor–Dependent Mechanism
Journal - Stroke
Autoimmunity. 2006 Mar;39(2):143-51.
Cannabidiol lowers incidence of diabetes in non-obese diabetic mice.
Curr Pharmacogenomics Person Med. 2009 September; 7(3): 215–222.
Cannabidiol As a Putative Novel Therapy for Diabetic Retinopathy: A Postulated Mechanism of Action as an Entry Point for Biomarker-Guided Clinical Development
Cannabidiol Arrests Onset of Autoimmune Diabetes in NOD MiceNeuropharmacology. 2008 January; 54(1): 244–249.
Rev. Bras. Psiquiatr. vol.30 no.3 São Paulo Sept. 2008
Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action
Am J Physiol Heart Circ Physiol. 2007 July; 293(1): H610–H619.
Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption
Eur J Pharmacol. 2013 Nov 15;720(1-3):376-82. 2013 Oct 8.
Cannabinoids alter endothelial function in the Zucker rat model of type 2 diabetes.
Free Radic Biol Med. 2011 Sep 1;51(5):1054-61. 2011 Jan 14.
Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress.
Crohns's Disease and Colitis
Cannabidiol Reduces Intestinal Inflammation through the Control of Neuroimmune Axis Mariateresa Cipriano, Published: December 06, 2011•DOI: 10.1371/journal.pone.0028159
Cannabidiol in Inflammatory Bowel Diseases: ABrief OverviewPHYTOTHERAPY RESEARCHPhytother. Res. (2012)
Z Gastroenterol 2011; 49 - A12
Effect of different dose cannabidiol treatment on experimental induced colitis
Cytokine. 2014 Feb;65(2):236-44. doi: 10.1016/j.cyto.2013.10.006. Epub 2013 Nov 13.
Interleukin 17A evoked mucosal damage is attenuated by cannabidiol and anandamide in a human colonic explant model.
Pharmacology. 2012;89(3-4):149-55. doi: 10.1159/000336871. Epub 2012 Mar 12.
Topical and systemic cannabidiol improves trinitrobenzene sulfonic acid colitis in mice.
J Mol Med (Berl). 2009 Nov;87(11):1111-21. doi: 10.1007/s00109-009-0512-x. Epub 2009 Aug 20.
Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa, is protective in a murine model of colitis.
Autism & Epilepsy
There are dozens of animal model studies and a case series report on epilepsy and a few on autism. Rather than re-list them all now click here for the full list.
**Please note: other sativa and indica strains can work in synergy with high CBD strains to produce even better medicinal impact for conditions like cancer and PTSD (which plagues our veterans at record numbers now). SB 124 legalizes the high CBD (cannabidiol) strain. Therefore, please also take a look at SB 43, which would legalize all of them for medicinal purposes only and consider supporting it as well. Thank you.
Saturday, February 8, 2014
This is an interview with cannabidinoid researcher, Pritesh Kumar. Mr. Kumar earned a B.S in Biology at The University of Kentucky and a M.S. in Pharmacology at The University of Louisville. In 2014, he will earn his PhD in Pharmacology from The University of Louisville. Since 2009, Pritesh has been a research scientist at The University of Louisville Department of Pharmacology and Toxicology. In 2013, he joined Quantum 9, Inc. Cannabis Consulting and Technology.
Kentucky is fortunate to have a scientist like yourself, with serious interest in the endocannabinoid system and cannabinoids, hailing from our state. Please tell us about your interest in the subject and the research you have done thus far.
I have always been fascinated in the endocannabinoid system for several reasons. The way this system modulates and regulates our homeostasis is truly breathtaking. Name any condition or pathology with an inflammatory component, and 95 % of the time the endocannabinoid system is found to play some sort of role. Even from an evolutionary perspective, it is truly amazing that this system has been found in many phylogenetically diverse organisms.
I apologize for the digression. So, our research currently focuses on how ligands (chemical compounds) bind and interact with the cannabinoid receptor 2 (CB2). This receptor is predominantly localized in the peripheral system in immune cells, T cells, B cells, etc. The reason why this receptor is an attractive therapeutic target is because of it’s minimal presence in the central nervous system (CNS). Therefore, any medication targeting this receptor will not elicit the “high.”
Recently, we have been testing the current FDA-approved medications on the market to determine if they have any effects on the endocannabinoid system. As I mentioned previously, we found that a commonly prescribed drug for osteoporosis in post-menopausal women (Raloxfiene) is acting on the CB2 receptor. This bring us to an important point. Patients should have access to all the information of the drug they are taking. For example, it is well known that Raloxifene acts through the estrogen receptor to produce its effects. However, we found that it also interacts with CB2. Now, this interaction could help explain some of its known therapeutic effects or it’s mechanism of action. Furthermore, this drug could be “repurposed” for a different indication for which CB2 is a target (pain, inflammation).
Since your PhD is in pharmacology you would be a great person to address a specific concern of many medical cannabis advocates. Various compounds in the plant appear to work together in an entourage effect to produce medicinal benefits. Many of us are concerned that once they start
isolating these compounds in labs and producing them synthetically for drugs that might not work as well as full plant and there will be more side effects. Are these concerns warranted?
These concerns are warranted. From a pharmacology perspective, it is attractive to isolate a single component and market that as most drugs on the market have a single active ingredient. However, the cannabis plant displays a rather unique pharmacology. Plant-derived cannabinoids often work in concert to produce what is known as the "entourage effect." In this sense, a defined concentration or mixture of cannabinoids is necessary to reach therapeutic effect. For example, Sativex is marketed in Canada for the treatment of multiple sclerosis and this drug contains a 1:1 mixture of THC to CBD.
As to your second question regarding if more side effects will be produced if only the synthetic form is available and marketed. This a bit of a grey area. For example, synthetic cannabinoids are already out on the market and are available at gas stations and corner stores in the form of "K2 or Spice." These synthetic cannabinoids (mainly JWH derived) are very dangerous and consumption has led to a rise in visits to the ER because the compounds in these products are chemical analogues of THC are significantly more potent than THC. Unlike THC which is a partial agonist, these compounds are full agonists for the cannabinoid receptor 1 (CB1).
From a pharmacological perspective, things get complicated when you have to predict how multiple cannabinoids will effect the body. It is often easier to investigate a single component or compound rather than a mixture. That being said, for the cannabis plant, there are multiple layers that often contribute to the beneficial effect of this plant (THC, CBD, CBG, CBN, etc). To answer your question, we still do not know if synthetics will have a worse side effect profile compared to the plant.
What is next in terms of your research? In what direction are you looking once your PhD is completed this year?
I am considering several options at the moment. I will continue to do research but from a slightly different perspective. I am personally interested in the plant cannabinoids as they may hold tremendous therapeutic benefit and represent an untapped source of potentially novel medications. I will stay on as consultant for Quantum 9, Inc. which is one of few companies out there that are legitimately interested in helping patients in the long run. Personally, I envision operating a company with a research facility in the state of Kentucky which will be heavily focused on the development of medications from plant cannabinoid extractions and perform laboratory testing for cannabis samples once this bill is passed.
Is there anything else you would like to say to our readers about the endocannabinoid system, cannabinoids, and the future of medicinal cannabis?
To the readers, I want to say that the endocannabinoid system is a beautiful network of receptors and enzymes that regulate a broad spectrum of signaling pathways in our bodies. The future of cannabis-based medications is still in its infancy and the rate at which we are developing these types of medications is rapidly increasing.
Cannabinoid Research Scientist
Quantum 9, Inc.
351 W Hubbard Suite 303 Chicago, IL 60607
888.716.0404 ext 809
Pritesh Kumar's Peer Reviewed Publications:
1) Kumar A, Qiao Z, Kumar P, Song ZH. (2012). Effects of Palmitoylethanolamide on Aqueous Humor Outflow. Invest Ophthalmol Vis Sci. Accepted doi: 10.1167/iovs.11-9294
1.Kumar A, Qiao Z, Kumar P, Song ZH. (2012). Involvement of a non-CB1/CB2 cannabinoid receptor in the aqueous humor outflow-enhancing effects of abnormal-cannabidiol. Exp Eye Res. Accepted http://dx.doi.org/10.1016/j.bbr.2011.03.031
2.Kumar P, Song ZH. (2013). Identification of raloxifene as a novel CB2 inverse agonist. Biochem Biophys Res Commun. doi: 10.1016/j.bbrc.2013.04.040. [Epub ahead of print]
3. Kotsikorou E, Navas F 3rd, Roche MJ, Gilliam AF, Thomas BF, Seltzman HH, Kumar P, Song ZH, Hurst DP, Lynch DL, Reggio PH (2013).The importance of hydrogen bonding and aromatic stacking to the affinity and efficacy of cannabinoidreceptor CB2 antagonist, 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2S,4R)-1,3,3-trimethylbicyclo[2.2.1]hept-2-yl]-1H-pyrazole-3-carboxamide (SR144528).
4. Kumar P, Song ZH. (2013). Structure-activity relationships of fatty acid amide ligands in activating and desensitizing G protein-coupled receptor 119. Eur J Pharmacol. doi: 10.1016/j.ejphar.2013.10.044.
Kumar P, Song ZH (2013). CB2 cannabinoid receptor is a novel target for third-generation selective estrogen receptor modulators bazedoxifene and lasofoxifene. Biochem Biophys Res Commun. Accepted.
1.Kumar P, Carrasquer C, Carter A, Song ZH, Cunningham AR (2014). A categorical structure-activity relationship analysis of GPR119. Journal of Molecular Modeling. In press.