The Endocannabinoid SystemRead More
By Dr Nicola Davies
The isolation of plant-based cannabinoids in the 1960s led scientists to investigate the mechanisms by which these chemical compounds interact with the brain’s neurons (or nerve cells). Indeed, the lipid Δ9-tetrahydrocannabinol (THC), was different from other water-soluble neurotransmitters or neuromodulators known at that time, and the hypotheses was that the psychotropic effects of THC were made through membrane-related features. However, it became clear that cannabinoids did indeed work through receptors, when, in 1988, a cannabinoid receptor was identified in a rat brain. In the following decades further exploration was made on the constituents of the body’s own cannabinoid system.
Components of the Endocannabinoid System
The endogenous cannabinoid system (ECS) includes the cannabinoid receptors, endocannabinoids (eCBs), and enzymes (such as fatty acid amide hydrolase) that synthesize and degrade the endocannabinoids.,
CB1 and CB2: The Body’s Cannabinoid Receptors:
The first endogenous cannabinoid receptor, CB1, was successfully cloned in 1990, while the second one, CB2, was identified in the spleen and cloned in 1993. Both receptors are part of the supergroup of G-protein-coupled receptors (GPCRs), which are a large and diverse set of membrane receptors that respond to a wide range of external signals, making them essential in regulating numerous bodily functions., Modern medicine has benefited from the more in-depth understanding of GPCRs, with some researchers estimating that up to half of marketed drugs work by binding to these receptors.
The CB1 receptor was initially believed to be present primarily in the central nervous system and was known as a brain cannabinoid receptor. Currently, it is believed that CB1 is also found in peripheral organs, but only in very low levels in some places. In the brain, CB1 is the most common GPCR, with the highest concentrations (as seen in the brain of a rat) in the basal ganglia, hippocampus, cerebellum, substantia nigra, and globus pallidus. These receptors are believed to have an essential role in cognition and motivation, consistent with the high densities of CB1 in parts of the brain that govern sensory and motor functions.
On the other hand, CB2 receptors were previously thought of as the peripheral receptor because it was mainly found in immune cells, but the second type of receptor has also been found within the central nervous system, although at lower densities compared to CB1. It has been proposed that CB2 is part of a general protective mechanism within the immune system of mammals. Subsequently, drugs that act by binding to CB2 are being explored for some diseases, such as liver, cardiovascular and neuropsychiatric conditions.,
AEA and 2-AG: The Body’s Natural Cannabinoids:
The discovery of a network of cannabinoid receptors, activated by the plant-based THC (an exocannabinoid), suggested the possibility of naturally occurring lipid molecules (endocannabinoids, or eCBs) also being present inside mammals’ bodies. Since THC is lipophilic (or soluble in fat), the assumption was that endogenous cannabinoids would be lipophilic as well., Soon after the cloning of the cannabinoid receptors, two lipid neurotransmitters were discovered, namely, N-arachidonoylethanolamine or AEA (which is also known as anandamide, named after the Sanskrit word ananda, meaning “supreme joy”) and 2-arachidonoylglycerol, or 2-AG.
AEA and 2-AG differ from other neurotransmitters, like serotonin and dopamine, in that they are not stored within nerve cells, but are created by the body as and where they are needed. The eCBs are also unlike many neurotransmitters in that their actions are pre-synaptic instead of postsynaptic. This means that the eCBs’ chemical messages are sent “backwards” through the network of neurons. Normally, most neurotransmitters are released from one neuron (the presynaptic cell), travel through a gap called the synapse, and bind to receptors on a neighboring neuron (the postsynaptic cell); it is the activated postsynaptic neuron which then starts the events that allow the chemical “message” to be spread. On the other hand, eCBs are created “on demand” from fat cells within an activated postsynaptic neuron, and travel back to the presynaptic neuron, where they bind to cannabinoid receptors.,,
Enzymes in the ECS:
In the cell, eCBs are broken down by enzymes. Fatty acid amide hydrolase (FAAH) is responsible for breaking down AEA into arachidonic acid and ethanolamine. In addition, 2-AG is broken down by FAAH and monoacyl hydrolase. Endocannabinoids are quickly removed from the cell by a membrane transport mechanism that still needs to be further investigated. When these enzymes are suppressed, the effect of eCBs is prolonged.
The Importance of Understanding the Endocannabinoid System
The ECS is now widely believed to be responsible for regulating a wide range of bodily functions. It is essential for the normal operation of the central and peripheral nervous system, and has a part in the regulation of pain, chronic stress, blood pressure, and gastrointestinal activities. It also plays an important role in cancer therapy, obesity management, reproduction, liver disease management, and numerous other health conditions. Recently, eCBs have also been shown to be responsible for modulating affect (mood), motivation and emotions. Drugs targeting the ECS are being explored in the field of psychiatric disorders.
Further research, however, is needed to gain more in-depth understanding of the complex mechanisms of this system. For instance, a third cannabinoid receptor has been hypothesized by researchers, although its existence is yet to be fully demonstrated. Another example of a function of the ECS that requires more research is the membrane transport mechanism that is believed to remove eCBs from the cells.
Unfortunately, cannabis research still faces numerous barriers and challenges. In a January 2017 report on the state of marijuana research, the National Academies of Sciences, Engineering and Medicine identified several obstacles. One of these is the lack of funding and support for the development of a national cannabis research agenda. Other challenges include the difficulty of obtaining a large enough supply of cannabis for scientific investigation, as well as securing approval to conduct studies. The drug is highly regulated by government agencies, since it is classified as a Schedule I substance. Additionally, a more rigorous set of tools and standards for research must be formulated by the cannabis-focused scientific community. Data collection methods, as well as public surveillance tools (such as national health surveys), are also in need of improvement.
There is a necessity to address these barriers as they are impeding the advancement of evidence-based knowledge on cannabis and the endocannabinoid system. The emerging importance of the ECS is already being seen. The capability to identify the potential ways of modulating its components could lead to the future development of a wide array of therapeutic innovations. The investigation of this important system will aid the public in understanding the numerous medicinal claims for cannabinoid-related products, as well as gain more objective insights into the potential dangers or benefits of cannabis. ♦
 Gaoni, Y., & Mechoulam, R. (1964). Isolation, structure and partial synthesis of an active constituent of Hashish. Journal of the American Chemical Society, 86, 1646–1647
 Alger, B. E. (2013). Getting high on the endocannabinoid system. Cerebrum: The Dana Forum on Brain Science, 2013, 14
 Devane, W. A., Dysarz, F. A. 3rd, Johnson, M., Melvin, L. S. and Howlett, A. C. (1988). Determination and characterization of a cannabinoid receptor in rat brain. Molecular Pharmacology, 34, 605–613
 Pazos M.R., Núñez, E., Benito, C., Tolón, R.M., Romero, J. (2005). Functional neuroanatomy of the endocannabinoid system. Pharmacology Biochemistry and Behavior, 81 (2), 239–47. DOI:10.1016/j.pbb.2005.01.030
 Murillo-Rodriguez, E. (Ed.) (2017). The endocannabinoid system: genetics, biochemistry, brain disorders, and therapy. London: Academic Press.
 Matsuda, L. A., Lolait, S. J., Brownstein, M. J., Young, A. C., & Bonner, T. I. (1990). Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature, 346, 561–564
 Munro S., Thomas, K.L., Abu-Shaar, M. (1993). Molecular characterization of a peripheral receptor for cannabinoids. Nature, 365, 61–65
 Mechoulam, R. & Parker, L. (2013). The endocannabinoid system and the brain. Annual Review of Psychology, 2013, 64, 21-47. DOI:10.1146/annurev-psych-113011-143739
 Scitable. (n.d.). GPCR. Retrieved from https://www.nature.com/scitable/topicpage/gpcr-14047471
 Mechoulam, R. & Parker, L. (2013)
 Cota, D., Marsicano, G., Lutz, B., Vicennati, V., Stalla, G.K., Pasquali, R., & Pagotto, U. (2003). Endogenous cannabinoid system as a modulator of food intake. International Journal of Obesity, 27, 289-301. DOI:10.1038/sj.ijo.0802250
 Alger, B. E. (2013)
 Mechoulam, R. & Parker, L. (2013)
 Howlett A.C., Barth F., Bonner T.I., Cabral G., Casellas P., Devane W.A., Felder C.C., Herkenham M., Mackie, K., Martin, B.R., Mechoulam, R., & Pertwee, R.G. (2002). International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors. Pharmacological Reviews, 54, 161–202. Retrieved from http://pharmrev.aspetjournals.org/content/pharmrev/54/2/161.full.pdf
 National Institute on Drug Abuse. (2011). The science of the endocannabinoid system: how THC affects the brain and the body. Retrieved from http://headsup.scholastic.com/students/endocannabinoid
 Mechoulam, R. & Parker, L. (2013)
 Griffing, G. & Thai, A. (2015). Endocannabinoids. Retrieved from http://emedicine.medscape.com/article/1361971-overview#a4
 Samson, M., Small-Howard, A., Shimoda, L., Koblan-Huberson, M., Stokes, A., & Turner, H. (2003). Differential roles of CB1 and CB2 cannabinoid receptors in mast cells. The Journal of Immunology, 170 (10), 4953-4962. DOI:10.4049/jimmunol.170.10.4953
 Mechoulam, R. & Parker, L. (2013)
 National Academies of Sciences, Engineering, and Medicine. (2017). The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. Washington, DC: The National Academies Press. DOI:10.17226/24625
CBD Fights Back: Lawsuit Filed Against DEARead More
by DJ Reetz
A lawsuit filed on January 13, 2017 aims to push back against a recent DEA decision to create a separate tracking number for “marihuana extracts” under the Controlled Substances Act, effectively codifying all cannabinoids derived from marijuana or hemp as Schedule I controlled substances. The lawsuit was filed by the Hoban Law Group in the federal 9th Circuit Court of Appeals in San Francisco on the same day the new ruling was set to take effect, and seeks judicial review of the decision, claiming that the DEA has overstepped their authority in adding this definition of “marihuana extract” to the controlled substance schedule without following proper procedures to do so as outlined in the CSA. Serving as plaintiffs in the lawsuit are the Hemp Industries Association, Centura Natural Foods, and RMH Holdings.
The DEA’s announcement in the federal registry published on December 14, 2016 raised concerns amongst many in the cannabis industry that the DEA would begin to target producers and distributors of hemp-derived CBD, which would fall under the definition of “an extract containing one or more cannabinoids that has been derived from any plant of the genus Cannabis” outlined in the DEA’s final ruling.
“This is an action beyond the DEA’s authority. This final rule serves to threaten hundreds, if not thousands, of growing businesses, with massive economic and industry expansion opportunities, all of which conduct lawful business compliant with existing policy as it is understood and in reliance upon the federal government," said Hoban Law Group Managing Partner Robert Hoban in a press release.
The DEA has claimed that the ruling presented in the recent federal register amounted to little more than a clerical decision carried out in order to make tracking cannabinoid extracts easier, but many in the hemp CBD industry saw it as the first step toward a federal crackdown on the non-psychoactive cannabinoid that has thus far operated nationally in somewhat of a legal gray area.
The true impact of the classification will likely be seen in the coming months and years.
Does CBD Convert to THC When Ingested? The findings from one study conclude it is possible.Read More
by Dr. Nicola Davies
Many people may be aware that cannabidiol (CBD) is a non-psychoactive constituent of the cannabis plant. New research, however, seems to indicate that this isn’t actually correct.
Cannabis strains high in CBD are popularly used as anti-inflammatories, as muscle relaxants and as general analgesics. Cannabis plants with high levels of delta 9–tetrahydrocannabinol (THC), on the other hand, are often smoked or ingested in order to produce feelings of euphoria and concomitant reductions in stress. Though high-CBD strains are often associated with indica varieties and high-THC with sativa varieties, this is not necessarily the case.
Executive Director of Wo/Men’s Alliance for Medical Marijuana (WAMM), Valerie Corral, wrote in a 2007 unpublished study titled “Differential Effects of Medical Marijuana Based on Strain and Route of Administration: A Three-Year Observational Study” that, “Patients did not note major differences between the cannabis sativa and cannabis indica strains.” Corral concluded, “We hope that a reliable and accessible means of analysis will become available in the near future.”1 Corral’s hopes for the future are closer to being realized. New research carried out by Kazuhito Watanabe (PhD) and his associates at Daiichi College of Pharmaceuticals, Japan, resulted in a paper titled, “Conversion of Cannabidiol to Δ9-tetrahydrocannabinol and Related Cannabinoids in Artificial Gastric Juice, and Their Pharmacological Effects in Mice.”2 The research has shown that variations in gastric juices can lead to a different result from that expected when taking CBD. So far, testing has only been carried out on mice and artificial gastric juices have been used, but the results provide food for thought and may pave the way for further studies with human participants.
Essentially, the study by Watanabe and his team has demonstrated that when CBD comes into contact with an artificial gastric juice, the non-psychoactive CBD is converted by those juices to the
psychotropic element delta 9–tetrahydrocannabinol (THC), as well as 9α-hydroxyhexahydrocannabinol (9α-OH-HHC) and 8-hydroxy-isohexahydrocannabinol (8-OH-iso-HHC). These two latter cannabinoids, known together as HHCs (hexahydroxycannabinols), were found to have THC-like effects on the laboratory mice. The researchers do point out, however, that the effects of the HHCs were not as strong as those of actual THC.
The main objective of the research was to show that THC is not the only psychoactive component of cannabis. The results suggest that sufficient attention needs to be paid to HHCs and their effect when they are combined with gastric juices during the digestive process. This could explain the anomalies in results for previous studies when the effects of CBD were tested on humans. As studies have so far only been conducted on mice, further research is required with humans to establish its applicability in the real world.
What causes the change to occur?
When people ingest cannabis in cakes or cookies, these usually contain some kind of sugar. The stomach becomes more acidic due to the sugars in these foods, as well as in any alcoholic drinks consumed when smoking or ingesting CBD. This acidity accelerates the change from CBD into THC, two HHCs and cannabinol (CBN).
What did the scientists measure?
The researchers began from the baseline of what has already been established about the effects of THC on the body: loss of sensation, drop in body temperature, prolonged sleep and reduced pain perception. The four aspects they chose to test were catalepsy (the loss of sensation or consciousness, inducing a rigid body), hypothermia (an abnormal drop in body temperature), pentobarbital induced sleep (deeper sleep when a barbiturate is given) and antinociception (the reduction in sensitivity to painful stimuli).
How did they do it?
Watanabe and associates isolated and purified THC, CBD and CBN from cannabis leaves using previously tried and tested methods. They placed the cannabinoids into an artificial gastric juice to observe the effects. Using a gas chromatograph, a sample solution was injected into the instrument, which then entered a gas stream of either helium or nitrogen used as carrier gas. The sample was then directed into a tube that separated the components. Results showed that CBD broke down into THC, two HHCs and CBN. To test the effects of these CBD components, the researchers administered small quantities to their experimental mice.
...when CBD comes into contact with an artificial gastric juice, the non-psychoactive CBD is converted by those juices to the psychotropic element delta 9–tetrahydrocannabinol (THC)...
How were changes measured and what did they find?
To test catalepsy, 24 mice were separated into three groups of eight and injected with THC, HHCs and CBN. Researchers waited fifteen minutes for the cannabis to take effect, then placed the front paws of the mice on a bar. If the mouse did not move its paws within 30 seconds, it was regarded as having a rigid or cataleptogenic reaction. The injection of THC affected the mice the most, and the HHCs were less effective than THC, but more so than CBN, which had very little effect.
For the hypothermic reactions test, mice were again divided into groups of eight and injected with THC, HHCs and CBN, respectively. Two hours later, their rectal temperature was taken. The results were consistent with the test for catalepsy, with THC causing the highest temperature drop. HHCs had an effect, but not as pronounced as THC, while injections of CBN did not produce any significant drop in temperature. Through its action on the central nervous system, THC prolongs deep sleep, so for this test, the researchers injected the mice first with the cannabinoids, and then gave them sodium pentobarbital fifteen minutes later to see how their sleep was affected. As expected, the mice given the THC slept the longest, those given HHCs slept less and those given the
CBN were least affected.
For the sensitivity to pain test, the mice were again given injections of the various cannabinoids, then twenty minutes later were given a 0.7 percent acetic acid solution and assessed on the amount of writhing produced by measuring abdominal contractions. Again, the results were consistent: THC produced the strongest block to pain with least writhing, the HHCs were somewhat effective, but less than THC and CBN had very little effect on pain blocking compared to the placebo group.
Further studies needed
Much research has involved the administration of THC and CBD to patients for symptoms such as fibromyalgia, Crohn’s disease and insomnia, but researchers have been circumspect in declaring their results and have called for further testing. Watanabe’s research, though conducted on mice, may hold true for humans – but that must be the subject of future studies. As Georgetown University Medical School’s Dr. Robert du Pont pointed out, there are an estimated 400 components in the cannabis plant, making it difficult to determine exactly which component is providing relief when cannabis is ingested for medical reasons.3
Could anomalies in results have resulted from the way gastric juices break down CBD within the human body? In a 2016 study published in Cannabis and Cannabinoid Research, by John Merrick and associates, it was noted that, “In recent epilepsy research, pediatric subjects receiving orally administered CBD showed a relatively high incidence of adverse events (≤44%), with somnolence (≤21%) and fatigue (≤17%) among the most common.”4 This led the researchers to more closely investigate the accepted premise that CBD is non-psychoactive. They came to the conclusion that, “Gastric fluid without enzymes converts CBD into the psychoactive components Δ9-THC and Δ8-THC, which suggests that the oral route of administration may increase the potential for psychomimetic adverse effects from CBD.”
From recent studies, it seems that there is a need to find delivery methods that decrease the risk of psychoactive cannabinoids forming during the digestive process. To this end, Zynerba Pharmaceuticals Inc. has developed an innovative transdermal synthetic cannabinoid treatment that bypasses the gastrointestinal tract, thus avoiding bioconversion to psychoactive THC.5 This may be the way forward in using CBD to assist patients with medical conditions without them inadvertently experiencing unwanted psychoactive effects.
1. Corral, V.L., 2001. Differential effects of medical marijuana based on strain and route of administration: a three-year observational study. Journal of Cannabis Therapeutics, 1(3-4), pp.43-59.
2. Watanabe, K., Itokawa, Y., Yamaori, S., Funahashi, T., Kimura, T., Kaji, T., Usami, N. and Yamamoto, I., 2007. Conversion of cannabidiol to Δ9-tetrahydrocannabinol and related cannabinoids in artificial gastric juice, and their pharmacological effects in mice. Forensic Toxicology, 25(1), pp.16-21.
3. Kleber, H.D. and Dupont, R.L., 2012. Physicians and medical marijuana. American Journal of Psychiatry, 169(6), pp.564-568.
4. Merrick, J., Lane, B., Sebree, T., Yaksh, T., O’Neill, C. and Banks, S.L., 2016. Identification of Psychoactive Degradants of Cannabidiol in Simulated Gastric and Physiological Fluid. Cannabis and Cannabinoid Research, 1(1), pp.102-112.
5. Zynerba Pharmaceuticals, Inc., 2016. First and Only Synthetic CBD Formulated as a Permeation-Enhanced Gel Being Developed for Refractory Epilepsy, Osteoarthritis and Fragile X Syndrome. [ONLINE] Available at: http://zynerba.com/in-development/cbd-gel-zyn002/. [Accessed 21 July 2016].
Hemp Farming in ColoradoRead More
by Rebecca Chavez
In the months and years since the passing of Amendment 64, much has been made of the cannabis “green rush." There’s money in weed, or so we’ve been told, but while many investors focus on recreational uses for marijuana, the hemp industry is struggling to find a foothold with less infrastructure and many of the same restrictions.
The first hemp harvest was over a year ago, but that doesn’t mean that one can walk into a store and find products made with Colorado hemp. The majority of the hemp that we use in the United States is imported from Canada, where they have the processing plants that we need to propel the hemp industry forward in Colorado. Once this integral infrastructure exists, Colorado hemp is poised to be one of the biggest industries in the United States. Until then, hemp farmers have to improvise and forge their own path to commercial success.
One of the unlikely farmers doing just that is Bill Billings. Before the legalization of hemp, Billings was on a different side of the farming industry. He worked as a middleman, moving produce around the country for farmers and retailers. It was this position that helped him build relationships with the farmers around Colorado that would become incredibly important after the passing of the farm bill in 2013. Billings almost immediately saw the benefits of hemp. He didn’t just go after the obvious market of clothing and paper, but wants to ensure that hemp is a part of the growing medical market. He started the Colorado Hemp Project with the help of Jim Brammer, a farmer out of Sterling, Colorado.
Brammer and Billings are vastly different from the majority of cannabis entrepreneurs. They aren’t interested in the high. In fact, the association of hemp with cannabis almost scared Brammer off of the business. Fortunately, the Sanjay Gupta special aired right around the time that Billings approached Brammer and, with this in mind, Brammer offered Billings two acres in Yuma as a sharecropping opportunity, and their first hemp harvest quickly followed.
The medical aspect of hemp is one of the biggest draws for Billings. His passion is surprising at first, but quickly grows on nearly everyone he meets. While many look to hemp as a solution for paper or clothing, Billings really sees it as an opportunity to provide hope to people who may not want the high that comes along with the majority of medical cannabis. Though the first harvest was small, Billings is already thinking of ways to put hemp to use in the medical market. He wants to create CBD oils and tinctures that help medical patients. He’s already experienced a lot of health benefits thanks to hemp, and he’s hoping to pass that on to others.
Though hemp is different than what many people typically think of as medical cannabis, Billings is testing hemp strains that may have medical benefits. The difficulty comes from getting enough THC in the hemp plant to create an entourage effect. All hemp grown in the state must have less than 0.3 percent THC, a far cry from the medical marijuana plants that can contain upwards of 20 percent.
While Billings is passionate about the possibilities with hemp, the real problem quickly became apparent. There is no infrastructure available to process and distribute the plant. Hemp can’t be sent out of state for processing, and with no obvious options, The Colorado Hemp Project took matters into their own hands. Dani Billings, Bill’s daughter, started Nature’s Root, a company that makes hemp based beauty products. Right now the line is fairly small with a few scrubs, a lip balm, and a soothing salve, but there’s plenty of room to grow as the market expands.
Bill Billings also worked out a deal with some local natural grocers to carry whole hemp hearts in their stores. This relationship will likely grow as hemp expands, and expansion is on the horizon. Billings recently acquired a machine that separates out the different parts of the hemp plant. This gives him the ability to pull out the fibers that are important when it comes to making clothing and papers. These are items that are high in demand, but that no one can create just yet.
As many rush to cash in on what is being called the “green rush” so many people are ignoring the possibilities of hemp. Conventions and expos have booth after booth of companies eager to help dispensary owners create a better product but there are very few options connected to the hemp market. We’ve all heard about what hemp is capable of, but the minimal processing of recreational and medical marijuana creates a market with a much faster return and a much shorter turn around.
The machinery necessary to create the hemp products that we’ve heard so much about in the past few years isn’t in the state yet. Without the capital to build the infrastructure, Billings and other hemp farmers have a long road ahead of them. Fortunately, the hemp farming community is strong. Instead of the investors hoping to make a quick buck that cannabis has seen, many hemp farmers in the state of Colorado are long-time residents who have turned to hemp as a compliment to their many other crops. The plant is good for the soil and easy to grow, making it a tempting crop for anyone who has been farming for a long time.
Billings told me that though the hemp farmers aren’t working together, they are all looking out for one another. The community is supportive enough to share ideas, but everyone appears to be innovating on their own. What this means for hemp in the future is that there is sure to be a wide array of products from different sources. Billings and The Colorado Hemp Project are on the forefront but, at this point, the possibilities of hemp belong to whoever is willing to invest in the infrastructure to bring the dream of the plant to a reality.
Lupus and Medical MarijuanaRead More
by Dr. Nicola Davies
Testimonies from people claiming that smoking a joint or taking hemp extract has helped their symptoms of lupus abound in the media with some users elevating the healing qualities of the cannabis sativa plant to almost magical status.
While authorities worry about the psychoactive properties of the THC content of cannabis sativa, researchers are honing in on the non-psychoactive components of the plant, particularly cannabidiol (CBD).
Compounds within cannabis and their effect
There are two types of cannabis sativa, one with more THC and the other with very small amounts. Usually the plants with less THC contain higher levels of CBD. As a medicine CBD is of great value, as it does not produce the side effects associated with plants with high THC levels. This substance is attracting more attention as doctors discover new effects on the human immune system.
The cells of our central nervous system contain type 1 cannabinoid receptors (CB1) and these are located mainly in the brain. Type 2 cannabinoid receptors (CB2) are spread around the body in the peripheral nervous system, together with some CB1 receptors. THC may interfere with CB1 to produce the high and giggles associated with the use of marijuana, whereas CBD does not interfere with the user’s psychological and psychomotor functions. Both substances, however, reduce the pain and inflammation associated with lupus, which is why some sufferers like to smoke a joint or use hemp extract to alleviate their symptoms.
To date, research has focused mainly on animal studies and has indicated that CBD has the following effects: it reduces nausea, suppresses seizure activity, combats tumor and cancer cell growth, combats inflammatory disorders, has anti-oxidant properties that help in neurodegenerative disorders and helps in cases of anxiety and depression – all good news for lupus sufferers.
How lupus affects the body
Normally, the body’s immune system creates proteins (antibodies) in order to fight off viruses and bacteria by identifying another type of protein (antigens) on their surfaces. Lupus confuses the immune system so that it cannot tell the difference between the antigens on viruses and bacteria and its own healthy tissue. The immune system then attacks and kills both the invaders and the healthy cells resulting in inflammation, pain, and long-term tissue damage. This is why lupus is called an autoimmune disease – the body’s immune system is attacking its own healthy cells
People with lupus have symptoms varying in severity. Most suffer from fatigue, weight loss and a slightly raised temperature. They may develop joint pains and stiffness that is worse in the morning. Usually the many small bones in the hands and feet are more severely affected. The pain also tends to move from area to area but fortunately, although a little swelling may be experienced, it does not usually lead to arthritis. Sufferers will find skin exposed to the sun, like hands and face, are often sensitive to sunlight and the cheeks and nose develop the red butterfly rash typical of lupus.
Systemic lupus erythematosus (SLE) patients will usually have joint pains, skin rashes and tiredness. Impaired kidney, heart and brain function can occur in severe cases. Discoid lupus results only in skin rashes and the typical red butterfly marking across the nose and cheeks.
Women more likely to suffer from lupus
Women are ten times more likely to develop lupus than men and it typically occurs in women between the ages of 20-40 years, although people of all ages can be affected. Reasons for the onset of lupus are unclear but it is thought that it may be triggered by some medication, infection and even sunlight. Hormonal changes in women are also thought to play a role, which might explain why the prevalence is higher in women.
Cannabis can help
Research has shown that both THC and CBD work by changing critical molecules of epigenomes called histones. A complete set of DNA in a cell is called an epigenome and it tells the cell what to do by encoding for certain proteins – basically if it is a skin cell it must behave like a skin cell. Histones are spool-like proteins that wrap the DNA molecules into chromosomes that are inside the nucleus of the cell. Certain chemicals can change how tightly the histones wrap the DNA. If too tight they can prevent the gene encoding a protein within the cell – effectively turning the gene off. If loosening occurs, due to the chemical attaching onto the tail of the histone, then a formerly inactive gene may be turned on. This alteration leads to reducing inflammation in the body, and it is this reduction that can help people cope with lupus.
Heart, lungs and kidneys can be affected
With lupus, the pleura and pericardium tissues that cover the lungs and heart respectively can be inflamed; however, it is uncommon for the organs themselves to be affected. About 33 percent of people with lupus develop kidney inflammation leading to protein and blood leaking into the urine. Again this does not cause problems unless the lupus is very severe. As with most debilitating illnesses, depression can follow but it is not usually caused by lupus itself.
Effect on the brain
Because lupus results in general inflammation the brain is not exempt. Lupus patients may experience headaches, dizziness, even seizures and psychosis where the patient may have delusions, paranoia and hallucinations. Roughly 50 percent of people with lupus find it difficult to concentrate, struggle to remember things and are sometimes confused. Although this may not be noticeable to others, the person to whom this is happening will realize that things are not quite right. It is important to establish whether this is caused by the lupus or whether there is another cause.
Relief provided by cannabidiol
Relief from pain and inflammation can be achieved by taking capsules containing CBD but these are not easy to find. Hemp extract can be high in CBD but contains negligible THC and can be taken daily. Some people even juice the leaves of their CBD rich plants to obtain relief. It is reported that the cannabis allows them to regain their appetite and improve food digestion.
According to scientific studies, regulating inflammatory responses in lupus may be achieved through what is known as the peripheral cannabinoid receptor (CB2) coupled to G protein receptors primarily in immune cells. It is possible that when CB2 are stimulated, they induce leukocytes (cells within the blood and bodily fluids), to migrate to the sites of infection and inflammation thus playing a role in regulating the inflammatory response.
CBD does this through activating RHoA GTPases, which are a small group of G proteins. The G proteins act as molecular switches. A ligand is a signal-triggering molecule that binds onto a target protein at a particular site. The peripheral cannabinoid receptor (CB2) ligands may have a role to play in regulating the excessive inflammation of the body when lupus is present, causing the cells not to be so hyper responsive.
There is a need for more scientific research to be done on the effects on humans. Lupus patients in search of a cure, however, cannot wait for long-term studies to be completed and have been going ahead with self-medication if the country in which they live bans all products derived from cannabis sativa. In more enlightened countries they are able to buy medical marijuana products specifically for medical use.
Users are reporting that they are getting relief from the symptoms of their disease. Certainly they have a better quality of life. Meanwhile, research is on-going into whether, in addition to providing relief, the CBD in cannabis can actually cure lupus by causing cells to change the way they function.
MJNA vs. Project CBD and OthersRead More
by DJ Reetz
A recent settlement in the $100 million lawsuit filed by Medical Marijuana Inc. is being touted as a vindication of the company. In January, Medical Marijuana Inc., a publicly traded cannabis company that trades on the over the counter market under ticker symbol MJNA, filed a lawsuit aimed at a scathing report published by the non-profit advocacy group Project CBD that outlined some of the less than savory business practices that were involved in the formation of the company and notably contained several stark accusations about potentially harmful contaminants in Medical Marijuana Inc.’s flagship product, Real Scientific Hemp Oil. The lawsuit, filed in California’s Superior Court, targets several Colorado residents and business who contributed to the Project CBD report, as well as naming the report’s author, Project CBD’s founder, and the non-profit itself, all accused of libel, defamation and painting the company in a false light.
The recent settlement in the case centers on Stewart Environmental, an environmental testing lab that released a report to local cannabis activist Jason Cranford seeming to show a high amount of heavy metal contamination in a sample of RSHO submitted by Cranford. As part of the settlement Stewart CEO Dr. David Stewart released a video statement clarifying that the report issued to Cranford was preliminary, and that a follow up report showing acceptable levels of heavy metals was in fact the correct one. While the secondary report was noted in Project CBD’s critique, it is treated with skepticism, questioning as to whether it is authentic due to lack of a corrective action report, which is generally standard procedure when lab work is corrected. But the settlement with Stewart seems to be the definitive legal answer to the issue.
“It’s very unusual what happened,” concedes MMJ Inc. spokesperson Andrew Hard.
Also settling in the case is Jason Cranford, the Colorado grower and activist whose high-CBD strain Haleigh’s Hope gained national attention when it donated its name to a medical marijuana law passed in Georgia. Cranford played an integral part in the Stewart saga after he was approached by the parent of a child apparently sickened by a dose of RSHO. Cranford had previously left KannaLife shortly after the company had been acquired by MMJ Inc. and shortly thereafter began searching for problems with the products of the new parent corporation, according to the Project CBD report. In his search Cranford was contacted by a Colorado woman whose daughter had allegedly suffered gastrointestinal distress after ingesting RSHO. According to Project CBD, it was this syringe of RSHO that Cranford took to Stewart Environmental, where he received a report showing high amounts of lead among other potential contaminants and he then set out to make the findings known.
For his role in the situation Cranford was named as a defendant in MMJ Inc.’s lawsuit, and according to Hard, he has now recorded a video statement attesting to the validity of the statement from Stewart.
Cranford’s statement has yet to be released however, so its content remains unknown. Cranford himself seems defiant. Though barred from discussing the nature of the settlement, Cranford maintains that he believed the sample he was given to be genuine, and is adamant that the settlement was not the result of a jury or judge’s decision.
“They didn’t win a settlement in a courtroom,” says Cranford.
The settlement with Cranford and Stewart Environmental was quickly hyped by MMJ Inc., who spared no time in issuing press releases proclaiming victory. One story ran on the website cashinbis.com titled “Project CBD Report Confirmed False: Clearing the Air Around RSHO” touted MMJ Inc.’s settlement with Stewart and alluded to Cranford’s settlement and the video concession that a month later has still not materialized.
But while MMJ Inc. is claiming a victory, some of the claims in the Project CBD report remain unchallenged. Project CBD’s report also includes an accusation that a sample of RSHO tested by PhytaTech, a lab operating in Denver, contained hexane, an industrial solvent. According to Project CBD, this sample originated from Brandon Krenzler, an Oregon man whose daughter had allegedly been sickened by it, and while the provable chain of custody of the sample is nonexistent, neither PhytaTek nor Krenzler was included in MMJ Inc.’s lawsuit.
However, MMJ Inc. did see fit to include Cannlabs in its suit, as well as the company’s CEO Gennifer Murray. The Denver-based lab was responsible for an early test of Cranford’s sample that seemed to indicate a THC content above the .3 percent threshold set by the DEA as legally allowable for hemp products. Murray was also one of the first to pick up on Cranford’s accusations, and a Facebook post she made is the central exhibit in the case against her in MMJ Inc.’s lawsuit.
Murray was unavailable to comment for this story.
The Project CBD report also contains some insight into a short-lived venture between MMJ Inc. and Colorado-based Dixie Elixirs, a venture that contributed to the departure of Dixie’s chief scientist as well as the company’s head of production and extraction, allegedly over the potentially unsafe hemp paste Dixie was receiving from MMJ Inc. At the time, the hemp paste supplied to Dixie and used in the creation of MMJ Inc.’s own product was sourced by CannaVest, a company that is still partially owned by MMJ Inc.
“At the time this Project CBD report references, CannaVest was the sole exclusive supplier, it’s an important fact to note,” says Hard.
Despite owning 11.25 percent of CannaVest, MMJ Inc. and its subsidiaries are currently involved in several lawsuits against the company, one of which concerns the ownership of the RSHO trademark.
In addition to supplying the bulk material that went into the MMJ Inc.’s RSHO, CannaVest also shares origins with the company. Investment capital for both companies was secured by MMJ Inc.’s current CEO, Stuart Titus, according to Hard, and several of the central figures in CannaVest are mentioned by name in Project CBD’s report.
While the settlement in MMJ Inc.’s lawsuit may provide some closure, Project CBD isn’t backing down. The group has filed a motion to strike down the suit on the grounds that it is protected as free speech under the First Amendment. Project CBD Founder Martin Lee wouldn’t comment for this article due to the pending litigation beyond the following statement:
“Project CBD stands by its report 100 percent and we’re very proud of it.”
Whatever the outcome, the drawn out fight is sure to leave all sides bloodied, and definitive answers to the claims made against those involved may not come at all.
HEMPCO CBD PAIN SALVERead More
reviewed by Christianna Lewis-Brown
We have reviewed a couple of Hempco products in the past and our staff was impressed with the quality and effectiveness of those products. So we went into this review with high expectations and we were not disappointed. The CBD Pain Relief Salve is made of all natural and some organic ingredients, and each stick contains 20mg of active CBD, CBDA derived from hemp. The packaging is very handy for a pain salve. It comes in a clear, cylindrical dispensing container with a screw top lid, similar to a deodorant stick.
It was very convenient to use, you just rub the stick on the affected area. Pain salves I have used in the past came in a tub and you had to dig your fingers in to apply the salve. This is problematic if you don’t get it washed off all of the way. Have you ever rubbed your eyes after using topical pain relievers? Ouch! Not with Hempco. To be fair, you might have to rub it in a bit but at least it won’t get under your fingernails.
Upon first application, there is a cooling sensation that lingers for a bit. I did notice some relief in my joint pain after the first use but it really works its magic if you reapply it throughout the day. The pain was less and less after each application. Another win for Hempco! This and their other products are available for purchase on their website, cbdriven.com.
HEMP: The Anti-AntibioticRead More
By Dr Nicola Davies
Bacteria are becoming increasingly antibiotic resistant, giving rise to superbugs and making antibiotics obsolete. How can hemp and hemp derivatives (oil, milk, seeds) take over from the failing antibiotic industry?
The World Health Organization has called antibiotic resistance "one of the biggest threats to human health today." Bacteria that were once affected by antibiotics have grown resistant to the substances that were so efficient in stopping their growth in the past. This resistance has created ‘superbugs’ — strains of bacteria that are particularly resistant to both broad and narrow-spectrum antibiotics.
Resistance develops when bacteria come into contact with antibiotics or other bacteria that have been exposed to antibiotics and mutate into stronger genetic strains. Overexposure to antibiotics is largely due to misdiagnosis and overuse of common antibiotics, from a global right down to an individual level. However, new studies are showing that hemp, or cannabis sativa, can offset the danger of antibiotic resistance on many levels.
From the Farm to the Table
On a global scale, bacteria in food production, much like the bacteria in our bodies, are evolving to become increasingly resistant to commonly used antibiotics. Medium to large-scale farms producing meat and vegetables sometimes use antibiotics to compensate for crowded and unclean living conditions, even in the absence of infection. This is one reason for the rise in organic food awareness. Organic foods tend to cost more, as high standards of hygiene are required for the livestock and the soil for produce. As a result, farmers are looking for inexpensive organic alternatives for livestock and crops.
In a case in Denmark, the addition of hemp oil to piglet feed dramatically reduced the incidence of gastrointestinal infection. Gastrointestinal infection is the highest cause of mortality in piglets, and a key reason why farmers give antibiotics prophylactically. However, this builds resistance among bacteria, which may then be passed on to the consumer. This has spawned an academic study exploring the outcome of adding cold-pressed hemp oil and hemp protein to the diets of livestock throughout their lives. The project is part of a three-year ongoing study, targeted for completion in July 2017. The data is extremely promising for organic farms across the globe.
Hemp oil can also be used to replace antibiotics used on produce; helping to curtail the resistant strains by keeping antibiotics from spreading plant to plant via water and soil. The danger of antibiotics in produce is that if plants infected with a resistant strain of bacteria are sprayed with an antibiotic, only the susceptible bacteria will die, leaving the stronger, more resistant bacteria to multiply. Resistant genes exist for tetracycline and streptomycin, two common antibiotics used in agriculture. In addition, the antibiotic chemicals seep into the soil and create resistance in the bacteria on other plants. As part of a systematic investigation of central European plants, hemp oil was found to be more effective than streptomycin and penicillin in terms of anti-bacterial traits and natural antibodies, but without the danger of creating antibiotic resistance.
On a Personal Level
Resistant bacteria are not only being served to us via our food, but also via our personal choices. Simple decisions such as not taking a prescribed antibiotic for its full course can leave lingering live bacteria that grow stronger. Other times, antibiotics are prescribed when they aren’t needed. Colds and flu, for example, are caused by viruses that aren’t affected by antibiotics and shouldn’t be treated with antibiotics. Rather than overusing antibiotics, it has been suggested that adding hemp seeds to a person’s diet increases the body’s natural production of antibodies.
Like flax seeds, hemp seeds have all of the essential amino acids that the body needs to resist illness. They also have the highest content of edestin, a type of globulin, in the entire plant family. Globulins are one of the top three most abundant proteins in the human body and are responsible for acquired and natural immunity against harmful outside organisms. The body uses globulins to make antibodies, which attack infectious agents via their antigens. A person’s ability to resist and recover from infections and illness is directly proportionate to how quickly their body can generate large quantities of antibodies to defend against the initial onslaught of antigens. If globulins are in low supply, there is a higher chance of antigens overcoming the body’s immune response. As 65 percent of hemp seed protein is the globulin edestin, it is obvious how it can be used in place of antibiotics in many cases of infection.
The Destruction of Superbugs
Methicillin-resistant Staphylococcus aureus (MRSA) is a strain of bacteria that has become non-responsive to most antibiotics. Often carried on the skin and in the nose, Staphylococcus aureus is profoundly problematic when it has an opportunity to invade the bloodstream to cause "Staph" infections. When antibiotic-resistant strains of Staphylococcus aureus infect someone with a weakened immune system, such as the ill or elderly, the infection can quickly become life-threatening. As resistance to antibiotics increases, some strains of bacteria are becoming immune to vancomycin, the "last resort" antibiotic that is currently used when all others fail.
Recently, Simon Gibbons of the School of Pharmacy at the University of London and Giovanni Appendino of the Piemonte Orientale University in Italy tested five different cannabinoids with regard to their ability to kill MRSA. The results were impressive. Of the five cannabinoids tested, the two with the highest effectiveness in killing the resistant bacteria were extracted from industrial hemp with low THC content and non-psychoactive properties; meaning they would not produce a "high." This is encouraging, as most protests against the use of hemp products stem from the stigma around the plant’s cousin, marijuana. During their study, Gibbons and Appendino discovered that hemp extracts were as effective in treating infection as many known antibiotics, including vancomycin. More recent studies have shown that hemp extracts are effective in treating Mycobacterium tuberculosis, the bacterium responsible for tuberculosis.
Hope on the Horizon
The future of hemp products in the treatment of antibiotic-resistant bacterial infections is hopeful. With a growing number of U.S. states legalizing marijuana for medicinal purposes, the allocation of funds to researching hemp extracts is likely to rise. Hemp seeds and oil are available for purchase online or at some health food stores, and given their ability to boost the immune system and resist bacteria, their inclusion in daily diet should, arguably, be recommended - not only for personal health, but to reduce the need for antibiotics moving forward.
CBD Only Laws Leave Patients With Limited OptionsRead More
by Skyler Cannabaceae
After passing legislation in the New York State Assembly, the Empire State will become the 23rd state, including Washington, D.C., to allow medical cannabis after Gov. Andrew Cuomo signs the bill, which he is expected to do. Some states, however, are choosing to only take on the heart-wrenching issue of treating epileptic children with cannabidiol while ignoring the other benefits of the plant.
Some legislators want to prohibit THC, which is a part of the medicine that they consider undesirable. The problem is that THC shares many similar healing properties with CBD and even has some health advantages that CBD does not have. Most cannabis advocates favor a "whole plant solution."
Ten states already have CBD-only laws: Alabama, Florida, Iowa, Kentucky, Mississippi, Missouri, South Carolina, Tennessee, Utah and Wisconsin. The laws allow for the use of cannabis oil that contains mostly cannabidiol, or CBD, and only a minor trace of THC, the compound that causes the "high" feeling when cannabis is smoked or ingested.
There are other states with CBD-only laws in various stages of the legislative process. On June 20, North Carolina’s General Assembly passed the "North Carolina Compassionate Use Registration Act." The bill still has to pass the Senate and be signed by the governor to become law.
Martin A. Lee is Co-Founder & Director of Project CBD, a non-profit group based on raising awareness and furthering study of CBD for medical use. Lee wrote an article published on the Project CBD website on March 22, explaining that CBD is important, but it can’t do the job alone.
"Scientific research has established that CBD and THC interact synergistically and potentiate each other’s therapeutic effects," Lee wrote. "What’s more, marijuana contains several hundred other compounds, including flavonoids, terpenes, and dozens of minor cannabinoids in addition to CBD and THC. Each of these compounds has particular healing attributes, but when combined they create what scientists refer to as an ‘entourage effect,’ so that the therapeutic impact of the whole plant exceeds the sum of its parts."
Keith Stroup, Legal Counsel for the National Organization for the Reformation of Marijuana Laws (NORML), is another well-known cannabis activist who has made known his opinions of CBD-only laws. On June 17, Stroup published an editorial on the subject on NORML’s blog.
"[E]ven if a patient from out-of-state could find these products in California or Colorado," Stroup said after noting that the oil in question is mostly made in those two states, "it would be a violation of federal law (and also likely state law) to take the medicine back to their home state."
Stroup pointed out in his post what he sees as lessons to be learned from the swift passage of CBD-only laws. He cited claims that elected officials are heavily influenced by popular media, opining that lawmakers "would get their scientific understanding of the medical properties of marijuana from a popular television doctor" rather than research the matter themselves.
Cannabidiol is known to help control seizures, but Lee pointed out in his March article that it leaves people with other illnesses without relief. He said that people with cancer, chronic pain, Alzheimer’s and autoimmune disorders will not get relief with CBD alone.
While some advocates say that CBD-only laws are a good first step toward legalizing cannabis, others think that it sends the wrong message to the public. In the meantime, the focus on CBD is giving the impression that it is better than whole plant solutions - safer because CBD doesn’t get you high.
The war against THC rages on.