Cannabis and autoimmune disease

David Bearman, M.D. Vice President of the American Academy of Cannabinoid Medicine

Artikel auf Deutsch: www.hanf-magazin.com/db5

Hemp, cannabis, marijuana; Call it what you will, is one of the oldest cultivated agricultural crops in human history. It’s agricultural production goes back at least 10,000 years to when humankind came out of the forests and turned from hunter-gatherers to being farmers. It is not overstating the case to conclude that cannabis is one of the earliest, and longest lasting pillars of civilization.

As Jack Herer pointed out in the Emperor Wears No Clothes, cannabis has many beneficial uses. Among its 25,000 uses, cannabis is a food, a neutraceutical, a building material, a medicine, and a fuel. In many ways it was too useful for its own good because hemp competes with so many industries. Hemp is used as fuel, a social lubricant, an entheogen, food, fiber, building materials (fiber, board, insulation, and concrete). There is strong circumstantial evidence that the petrochemical industry fears of competition from hemp, motivated them or possibly just Lamont DuPont to write the Marijuana Tax Act and get passed in 1937. The AMA in the person of Dr. William Woodward doctor, attorney from Health Commissioner of Washington D.C. (1893-1913 and Boston University 1913-1914 and past President of the American Public Health Association (1914) and Chief Council for AMA starters in 1924 testified against the act saying that the AMA knew of “no dangers from the medicinal sense of cannabis”. At that time doctors were writing hundreds of thousands of cannabis containing prescriptions a year and they were over 25 cannabis containing over-the-counter medications on the market.

In 1964, Dr. Raphael Mechoulam a professor of pharmacology at Hebrew University isolated and characterized the THC molecule. Since then, cannabis is once again proving to be an extremely useful and versatile therapeutic substance. Both the medical and industrial hemp uses cannabis's many valued uses. This article will examine just one aspect of cannabis' multi-pronged medicinal targets of cannabis and autoimmune disease. It will place the medical application in the context of an overview of a better understanding cannabis, cannabinoids, terpenes, and the endocannabinoid system (ECS).

Endocannabinoid System (ECS)

Plants are complicated. Coffee has 880 different molecules, tomatoes 380 molecules, and cannabis is no exception. The cannabis plant has at least 512 different molecules, 113 of which are cannabinoids. Cannabinoids are 21 carbon molecules that either block or stimulate the human body’s CB1 or CB2 receptors. These receptors are part of the endocannabinoid system. This system includes at least two neurotransmitters, (2AG and Anandamide) and two enzymes, FAAH and MYGL. These enzymes help metabolize both endomean derived from inside the body and phytomean cannabinoids, which stem from plants. The ECS interacts with other neurotransmitters such as dopamine and dopamine transporters to help generate important effects to help us be healthy. The CB1 receptors are found largely in the brain and the CB2 receptors are found largely in the immune system. The endocannabinoid system is arguably the largest neurotransmission system in the human brain. It is central to homeostasis and is important in modulating the speed of neurotransmission. It interacts with the dopaminergic system to effect how fast neural impulses are transmitted. The ECS helps to down regulate the body’s immune system.

Cannabinoids

There are 21 carbon molecules that can affect the endocannabinoid system and have many therapeutic attributes such as blocking or stimulating CB1 and CB2 receptors. The two we here hear the most about are THC and CBD, but there are many other cannabinoids with therapeutic value. Here are some examples:

CBN (Cannabinol)

• Pain reliever

• Sleep aid

• Anti spasmodic

• Anti inflammatory

• Antioxidant

CBG (Cannabigerol)

• Anti cancer

• Decrease BB

• Anti inflammatory

• Stimulates bone

CBC (Cannabichromene)

• Anti cancer

• Anti bacterial

• Anti fungal

• Anti inflammatory

• Stimulates bone

THC (delta 9 Tetrahydrocannabinol)

• Anti cancer

• Anti nauseant

• Analgesic

• Appetite stimulant

• Anti spasmodic

• Muscle relaxant

• Anti microbial

• Neuroprotective

• Treats Crohn Disease (anti spasmodic, anti inflammatory)

• Anti inflammatory

• Antioxidant

CBD appears to have therapeutic applications. Here are some examples:

CBD (Cannabidiol)

• Protects against cancer

• Reduces nausea

• Pain reliever

• Sleep aid

• Relieves spasms

• Decreases seizures

• Reduces anxiety

• Muscle relaxant

• Antibacterial

• Protects nervous system

• Neuroprotective

• Anti seizure

• Anti diabetic

• Improves circulation

• Relieves psoriasis

• Relive Crohns Disease

• Anti inflammatory

• Bone stimulant

• Relieves rheumatoid arthritis

• Anti oxidant

• Anti psychotic

Terpenes and Terpenoids

The cannabis plant also contains over 200 terpenes. They give the plant its unique odor. Many of them have therapeutic value. The name “Terpene” is derived from the word “terpentine,” terpenes are also major biosynthetic building blocks found within nearly every living creature. Steroids, for example, are derivatives of the triterpene, squalene.

Terpenes often have a strong odor and may protect the plants that produce them by deterring herbivores and by attracting predators and parasites of herbivores. The difference between terpenes and terpenoids is that terpenes are hydrocarbons, whereas terpenoids contain additional functional groups. Terpenes are derived biosynthetically from units of isoprene. Terpenes are classified by the number of isoprene units in the molecule; a prefix in the name indicates the number of terpenes units needed to assemble to molecule. Isoprene units are C5H8 chains.

The basic molecular formula of terpenes are multiples of that, (C5H8) n where n is the number of linked isoprene units. This is called the biogenetic isoprene rule. Terpenes are the most ubiquitous molecules in nature with more than 20,000 terpenes found in nature. They are found in a wide range of plants from fruits (oranges, lemons, limes, mangoes) to flowers (lavender), vegetables (hops), and spines (pepper).

Entourage Effect

Many of the constituents of the cannabis plant have therapeutic value. They tend to work together so the whole plant is generally most effective than an insolated constituents. In 1999, Dr. Raphael Mechoulam, the Israeli scientist, who first isolated and characterized the THC molecule in 1964, postulated that the therapeutic constituents of the plant act together in a somewhat synergistic fashion that he calls the entourage effect.

Anti Inflammatory Constituents of the Plant

Many of the molecules in the plant here have anti inflammatory properties. This is why cannabis is helpful in treating such conditions of degenerative joint diseases, osteoarthritis, and Crohns disease. Some of the cannabinoids, which have been found to reduce inflammation, are THC, CBD, CBDA, CBC, CBG and CBGA. The A is short for acid. Cannabinoids in the new plant are all in the acid form, meaning they have a carbonyl group, that will become decarboxylated by heat. This decaroxylation creates THC which is a euphorogenic. THCA, although, is not. There are many terpenes that have an anti-inflammatoryeffect. These molecules include: beta pinene, eucalyptus, alpha pinene, limonene, delta 5 carene, beta-carophyllene, alpha humulene, linalool, alpha pinene, myrcene, and humulene. With this spectrum of therapeutic ingredients it’s no surprise that cannabis is affective in treating symptoms of autoimmunediseases.

Cannabis Effects on a Cellular Level

Scientists hypothesize that the THC found in cannabis has the capacity to affect DNA expression through epigenetic pathways. This is cutting edge science. That is a different mechanism of action than current anti inflammatories, like steroids, or aspirin, use to treat symptoms of autoimmune disorders. The MicroRNA Journal of Biological Chemistry published a study recently exploring how THC influences microR- NAs. “The micro-RNAs also called miR- NAs are single-stranded, small, noncoding RNAs which play an important role in the regulation of gene expression.” Cannabis’ ability to alter miRNA expression may help scientists to better understand how to treat autoimmune disease. In addition, cannabinoids are also active in effecting mitochanodira, an intercellular organelle.

Mitochondrial CB1 Receptors

Cannabinoid receptors are found on cell membranes. They are the most prevalent G-coupled protein receptors (GCPR) in the human brain and central nervous system and are the most popular cellular target for pharmaceutical treatment. An estimated 15 percent of all the CB1 receptors exist on the mitochondrial cell membrane. In muscle tissue containing CB1 receptors, half of these receptors are localized on the mitochondria.

Mitochondrial CB1 receptors are not structurally distinct from the CB1 receptors that are on the cell’s outer surface, but their effects are quite different. Research associate and science writer Adrian Devitt-Lee provides a useful analogy to explain this difference: “Light switches may look the same from room to room, but they are connected to different circuitry throughout the house, and so turning the switch on or off in different places causes different outcomes”

Nutritional Benefits of Hemp

Using cannabis as a nutraceutical or diet supplement, may improve a person’s overall long-term health. Cannabis can have a favorable effect on decreasing the risk of many health issues, including mental health, diabetes, osteoporosis, arthritis and heart disease. Cannabis was a major ingredient in the Middle Ages in gruel and a whole grain breakfast food and was also used in the making of beer (Cannabis is a cousin to hops).

Several constituents of the plant are useful in supporting well being. The anti-inflammatory attributes decreases the likelihood having a myocardial inflammation, it can treat diabetes. Hemp is a non-animal source of essential fatty acids and can contribute to a positive mental outlook. Hemp contains omega-6 and omega-3 fatty acids, which are antioxidants. Antioxidants help eliminate free radicals. Free radicals can cause damage to normal cells, which may lead to cancer. Cannabis can also contract cell loss from stroke and traumatic brain injury.

The Broad Therapeutic Range of Cannabis

Cannabis has been shown in basic science studies and clinical experience to beneficially treat a broad range of medical conditions. This is largely because the endocannabinoid system (ECS) is arguably the largest neurotransmitter system in the human body, the ECS is critical for homeostasis, helps down regulate immune system, and is important in modulating the speed of neurotransmission.

Cannabis’ amazingly broad therapeutic spectrum includes being an analgesic, anxiolytic, antiepileptic, anti-inflammatory, neuroprotector, sleep aid, anti nauseate, and appetite stimulant. It is useful in treating ulcerative Colitis, IBS, Migraines, seizures, fibromyalgia, and depression. It has been shown in annual studies and tissue cultures to kill cancer cells.

Anti-inflammatory

As noted above, some cannabinoids and terpenes have anti-inflammatory effects. As such cannabis can be a useful adjunctive treatment for much autoimmune and connective tissue disease. Cannabis helps to down-regulate the immune studies response. It’s long been known that cannabis with its many terpenes and cannabinoids, particularly CBD, is an excellent anti-inflammatory.

Cannabis also can work to reduce the risk of cancer, metabolic disorders, and nerve cell degeneration.

Hemp seed oil contains linoleic acid and gamma linoleic acid (GLA). The human body converts GLA (a metabolite of linoleic acid) into prostaglandins, which are hormone-like compounds that help to regulate inflammation.

Some studies have shown that GLA may help in reducing heart disease. This may be because of its anti-inflammatory properties. GLA has also been shown to have anti cancer properties. Cannabis’ anti-inflammation effect has proved beneficial in addressing auto immune diseases, such as RA (Rheumatoid Athritis), UC (Ulcer Colitis), SLE (Systemic Lupus Erythematosus), scleroderma, RSD, CRPS, RLS, fibromyalgia and the like. As pointed out earlier, not only are many of the cannabinoids such as CBD, CBDa, THCa, CBC, CBG, CBGa, anti inflammatory, but so too are many of the terpenes such as beta pinene, eucalyptus, alpha pinene, limonene, delta 5 carene, beta-caryophyllene, alpha humulene, linalool, myrcene, humulene.

Anti-inflammatory Benefits

Research suggests or in some cases shows that cannabis may help prevent conditions such as Alzheimer’s disease, heart disease, rheumatoid arthritis, and asthma partially by limiting the inflammatory process.

Ulcerative Colitis

A study authored by Dr. Jeff Hergenrather on using cannabis for treating ulcerative colitis patients, found that they reported that their medicinal use of cannabis led to fewer bowel movements, better formed stools, less abdominal pain and the ability to decrease some or all of their prescription medications. The anti-inflammatory effect may help decrease coronary artery disease. It is useful in decreasing pain related to inflammation. For those with ulcerative colitis, cannabis is a potentially very helpful therapy. Cannabidiol (CBD) is a promising drug for the treatment of inflammatory bowel diseases (IBD). The cannabinoid THC helps modulating the speed of neurotransmission and the analgesic properties of cannabis, CBD and other cannabinoids and terpenes are anti-inflammatory. This makes a low-toxicity and low-cost cannabis drug an ideal medicine for treating Chron’s and IBS. In a study by Hergenrather, Mikuriya and me, many uc cannabis users were able to decrease their dose of Rx meds. Cannabis plant based preparations have been considered new promising pharmacological tools.

Cancer

While cancer is not an auto immune dis- ease, it would be remiss not including cannabis’ anti cancer effects. Studies have shown that cannabinoids have the ability to inhibit angio-enasis, formation of new blood vessels, inhibit the ID-1 gene responsible for metastasis, and to promote apoptosis, programmed cell death of old and abnormal cells. Cannabis has been shown in animal studies and cell culture to increase the effectiveness of cancer treatment. For example, GLA (a metabolite of linoleic) may enhance the ability of medications used to kill off cancerous cells in the treatment of breast cancer. In addition, GLA itself may help prevent certain cancers by inhibiting cell proliferation. Hemp is a source of the fatty acid gamma-linolenic acid.

The results of A 2017 study in the UK on globlastoma a very aggressive type of brain cancer are encouraging. This study used a 1:1 ratio, of THC:CBD in a whole plant alcohol extract. This tincture contained 25 mg. THC and 25 mg. CBD and was administered 3 times per day. It was used as adjunctive treatment to conventional treatment. This study group showed a 40% increase in survival time from time of diagnosis to demise than those control subjects only conventional treatment. The survival time for the control group from date of diagnosis to death was 330 days compared to 510 days for those treated with both conventional treatment and cannabis.

The dose used in this study is considered by many active in the use of cannabis for treating cancer to be a subtherapeutic dose. Lay healers who are using cannabis to treat cancer patients often use anywhere from 150mg THC usually with an equal amount of CBD to 750 mg of THC and CBD per day. These higher doses are likely to be more effective than the doses used in this clinical trial. As more studies of this type are done we will learn more about total cannabis THC and CBD dose and THC: CBD ratio.

The Future Looks Bright for Cannabis, Cannabinoids and Terpenes

As we learn more about the benefits of plant based medicines in general and cannabis in particular, cannabis is becoming more and more accepted in mainstream for is therapeutic benefits and safety medicine. We have more than 4,000 years experience with cannabis as medicine, and with modern research we are learning more and more about the medicinal attributes of many of the constituents of the plant.

Cannabinoid medicine is becoming a medical subspecialty with organizations such as the American Academy of Cannabinoid Medicine (AACM), the Society of Cannabis Clinical (SCC), American Society of Cannabis Medicine (ASCM), and American Society of Cannabis Physicians (AMMP) working to integrate cannabis into wider use in conventional medical practice. Well over 150 medical organizations (e.g. AMA, APHA, American College of Physician, American Nurse Association, Patient Out of Time) have endorsed the medicinal use of cannabis.

Several United States medical schools have set up institutes to study the medicinal value of cannabis. These include: UCSD, UCLA, UCI, University of Colorado, Thomas Jefferson Medical School. This is in addition to the many basic science studies that have occurred and are ongoing in medical institutions not only in the United States, but also around the world. These studies are often covered at the International Cannabinoid Research Society.

Europe is ahead of the U.S. in research. There is cannabis research not only in USA but also in Germany, Spain, Italy, and Israel. Research also goes on in Asia, Japan, and Korea. These scientists meet annually at the International Cannabinoid Research Society meetings.