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For the relief of certain kinds of pain, I believe, there is no more useful medicine than Cannabis within our reach. Sir John Russell Reynolds 1859

Cannabis - Johnnyet

Cannabis – a genetically diverse plant – is much more than THC and CBD. (by Johnnyet – Pixabay)

This is the third part of a five-part series on the use of Cannabis in chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM). Amber Ella started the series with a fascinating look at the science suggesting that Cannabis may be able to dampen inflammation, limit mast cell degranulation and reduce pain more.  Next in an introduction to using Cannabis, Amber discussed legal issues, the different subspecies available and different modes of administration.

Part III lays the groundwork for Part IV, the treatment blog, by taking by taking a deep dive into the plant and its many potential medicinal properties. Plus, we introduce Health Rising’s Cannabis Review program.

Part V looks at specific strains of the plant and how they may help. Parts 4-6 are taken mainly from three books, as well as articles on the web:

Health Rising’s Marijuana as Medicine for ME/CFS and Fibromyalgia Series

Health Rising’s  Fibromyalgia and Chronic Fatigue Syndrome Cannabis Review Program

when you get it right
you pass it on… 
Gary Snyder

Cannabis review program

Check out the first ever ME/CFS/FM focused Cannabis Review Program.

This is our first in-house, wholly created-by-us program!  Kudos to Stavya, HR’s technical ace, for putting it together.  Stavya, a young programmer from New Delhi, has moved forward in leaps and bounds since he began working for Health Rising at its inception. This is the first of three Stavya-produced Health Rising programs we hope to introduce this year.

This unique program allows you to, if you wish to, (you don’t have to), identify other constituents than THC and CBD, found in the Cannabis strains you’ve tried that might be helpful. Please let us know if something goes wrong or if you have any suggestions on how to improve the program in the comments or via the contact form.

Note that all answers are anonymous.
There is absolutely no way to tell who provided what answer.

A Close Connection

Endocannabinoids appear to be profoundly connected with the concept of homeostasis (maintaining physical stability) and help to redress specific imbalances presented by disease or injury. Backes

Cannabis has been used for thousands of years for medicinal (and other) purposes but it was not until 1992 that Dr. Raphael Mechoulam (the discoverer of THC) discovered the reason why. We have a close chemical connection to it: the  endocannabinoids our bodies produce are very similar to the phytocannabinoids found in hemp and Cannabis.

As explained by Dr Michael Moskowitz in “CBD: A Patient’s Guide to Medicinal Cannabis–Healing without the High”, the endocannabinoid system has two main purposes – to produce feelings of pleasure, energy and well-being and to nudge the body back to health after injury or disease.  (Moskowitz, a pain doctor, was also featured in Norman Doidge’s book, “How the Brain Heals Itself”, and in a recent blog on Moskowitz’s use of neuroplasticity exercises to reduce pain.)

Cannabis’s ability to produce states of bliss and enjoyment are, of course, well-known – both to the public and to researchers. Its first signaling molecule (the molecule which locks onto the endocannabinoid receptors on our cells and triggers them to react) was called anandamide after the Sanskrit word meaning bliss (ananda).

bliss lotus flower ananda cannabis

Cannabis was so associated with altered mental states that its signaling molecule was named after the Sanskrit word for bliss.

For a long time, Cannabis was thought of only in terms of bliss. It was only a little more than a decade ago that researchers got serious about understanding what Cannabis was doing in the body and to uncover the key elements of the endocannabinoid signaling system – its two receptors, the two signaling molecules that lock onto them, and the five enzymes responsible for regulating the process. Since then much has been learned – and much more remains to be learned about this unusual system.

Unlike some other systems in the body, the endocannabinoid system operates only “on demand”. Because endocannabinoids are derivatives of polyunsaturated fatty acids (i.e. fats), they’re not water soluble and don’t move efficiently through the body. Instead, they’re produced on demand from precursor molecules found in localized areas.

When the body goes out of balance or homeostasis, endocannabinoids are produced to pull it back into balance – after which they disappear back into the body.

Focus on the Plant

Cannabis Subspecies

Although the subject has provoked impassioned arguments among botanists, three distinct subspecies of Cannabis are generally believed to exist: Cannabis sativa, C. indica and C. ruderalis. Cannabis has been around humans for a long time. It appears to have originated in the steppes of the Tibetan plateau 20 million years ago and has been present in Europe for at least a million years.

Moskowitz warns against placing too much stock in the below generalizations. While some basis for distinguishing them exists, Moskowitz asserts that the strain is the key – not the subspecies. Since dispensaries and Cannabis users often refer to subspecies, though, they are described below.

Cannabis sativa strains originated and are grown around the equator and tend to produce thinner, less densely leafed-out plants. On the whole, they may be more stimulative and thus may be better used during daytime.  While not all C. sativa derived strains have these properties, they are known for their ability to energize, increase focus, enhance creativity, improve mood, relieve headaches and – increase one’s appetite. On the downside, they can produce anxiety, paranoia and induce hyperactivity in some people.

Cannabis indica strains grow in cooler temperatures and in higher altitudes and tend to produce broader, more densely leafed-out plants. In general they tend to be more calming, better at reducing body pain, promoting sleep, reducing seizures and reducing anxiety or stress – and can increase one’s appetite.  Negative side effects can include producing feelings of tiredness, sluggishness, overeating and lack of motivation.

The least known Cannabis spp, C. ruderalis was discovered in the 1920’s, growing along roadsides in Russia. It has almost no THC but can have very high levels of cannabinol (CBN).

The Phytocannabinoids

THC and cannabidiol are the two most well studied phytocannabinoids in Cannabis and, are, as far we know, the two most medicinally active parts of the plant.  They also make up a very small portion of the plant.

THC – the great pain reliever

THC is responsible for the psychoactive experiences sometimes produced, and is the strongest pain-relieving component of the plant. So long as Cannabis was used primarily for getting high, growers excelled in producing strains with higher and higher levels of THC.

THC, interestingly, is actually not present in the plant itself – its precursor THCA is. Only when heated to 266 F (130 C) does THCA get converted to THC – hence the practice of burning the plant to access its psychoactive aspects.

THC

THC – the great pain reliever – is often used in conjunction with CBD to deliver the best results.

THC interacts with CB1 receptors in the brain to produce feelings of wellbeing, reduce pain and anxiety and improve mood via its effects on neurotransmitters such as norepinephrine, serotonin and dopamine, GABA, histamine, etc.  These CB1 receptors are particularly plentiful in the autonomic nervous system in both the brain and the body and may affect everything from decision-making to memory to movement to temperature. Few CB1 receptors, interestingly, are found in the brainstem – a recent focus of ME/CFS research.

THC, it turns out, is the greater pain reliever – not CBD. Studies indicate that THC relieves pain partially by disconnecting the sensory part of the brain from the emotional part of the brain – making the pain that is present less “hurtful” and anxiety-producing.

THC also appears to work by reducing the neuroinflammation that’s leaving the pain-producing nerves in our central nervous system twitchy and hyper-activated. Moskowitz calls THC a nervous system protectant.

Too much THC in your system, though, can produce anxiety, paranoia and actually increase inflammation. The key to using THC medically is using it judiciously; i.e. getting just enough of it boost your health while not producing negative side effects. Moskowitz asserts that just about everybody who’s ever had a bad Cannabis experience should be able to use the plant – and its THC component safely.   THC plays a important role in Moskowitz’s Cannabis protocols.

Cannabidiol (CBD) – the promiscuous molecule

When getting high was the main reason for using Cannabis, pot growers selected for strains with ever higher levels of THC and lower and lower levels of CBD. When lab testing for CBD began in 2009, only about 1/600 Cannabis samples had high CBD levels (>4% or 20:1 CBD/THC or higher). Since Cannabis’s reemergence as a medicine, however, growers have uncovered many more high CBD strains and have steadily been increasing CBD’s availability.

The second most studied phytocannabinoid, CBD doesn’t directly affect the endocannabinoid system at all. Instead, by blocking the enzyme that breaks down anandamide (the signaling molecule which turns on the endocannabinoid system), it essentially turns the endocannabinoid system on.

Like THC, CBD is not present in the raw plant. CBDA, the precursor to CBD, is converted into CBD by heat. The CB2 receptors that cannabidiol or CBD interacts with are less common in the brain but still play important roles in reducing neuroinflammation, regulating serotonin and can help with depression and/or anxiety.  CB2 receptors are ubiquitous in the body, particularly immune cells where they tend to downregulate the production of pro-inflammatory cytokines.

CBD

The “promiscuous molecule”, CBD is able to affect many systems across the body.

CBD also binds to other receptors to counteract the psychoactive effects of THC, turn on serotonin and TRPV1, regulate gene expression, protect the bones, and fight cancer. Moskowitz believes CBD-rich strains can be helpful with many neurodegenerative diseases.

In fact, CBD affects so many systems in our bodies that it’s been called a “promiscuous” molecule. It may be able to lock onto (“embrace?”) as many as 65 different receptors. It’s subtler, broader-based effects may be able to ameliorate as diverse a set of symptoms as pain, tight muscles, insomnia, anxiety/depression and fight/flight issues.

CBD is a particularly intriguing possibility for FM and ME/CFS because it helps to turn off some of the some pathways associated with an over-activated flight/fight response that’s gotten turned on. Dr. Ginerva Liptan, who has fibromyalgia herself, believes an “always on” fight or flight response plays a key role in FM. That system appears to have responded to some danger in the past – an infection or injury or other stressor – but instead of turning off when the danger presumably passed, it stayed on, resulting in a hypervigilant state, pain sensitization, problems with sleep, immune exhaustion and other possible issues.

THC, with its strong nervous system-affecting properties, is more immediately powerful, but while CBD works in subtler ways, it may, in the end, affect more symptoms through its ability to calm hyper-activated neurons down, restore proper immune functioning, help with sleep, relax muscles, promote bone fusion, and affect the metabolism.  Thus, while CBD may not produce as dramatic results in the short term, it may be more helpful in the longer term.

Marijuana as Medicine for ME/CFS and/or Fibromyalgia Pt I: The Science Behind Cannabis

Other Chemicals in Cannabis

Knowing only the THC and CBD content of a strain is limiting; it takes away the blending of the entourage effect and doesn’t help in recommending something based on its medical values.  Michael Moskowitz MD

There’s much more to Cannabis than THC and CBD, though. In fact, researchers have barely scratched the surface of the 118 other phytocannabinoids or the 700 other chemicals present in the plant. Of these, about 50 are present in significant amounts.

Cannabis users should be aware that some of these chemicals may have powerful medical effects and consider including them when they make their Cannabis choices. People who use the plant are well aware of the dramatic differences that can exist between strains.

Having a strain with more CBN and linalool in it, for instance, could help more with sleep. Having more CBC in a strain might do better at reducing pain. If you’re after muscle relaxation, you might want to try a high terpene strain. If better mental focus is the idea, you could try a high limonene strain. This is just a smattering of the chemicals that exist in cannabis.

genetic diversity

The genetic diversity in Cannabis should lead to the development of more biologically targeted strains. (From https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0170522)

The outstanding genetic variety present in Cannabis with its many different strains is giving growers room to develop strains which have different effects.  One review asserted “plant breeders have nearly endless opportunity to create new varieties with specific or unique qualities in response to numerous and varied market demands.”

Serious people are at work understanding the genetics of the plant. The Phylos Certified Genotype project allows anyone to determine how one Cannabis strain is genetically related to other strains.

All this means is that we are likely at beginning of understanding and getting access to the medical enhancements lurking within the Cannabis plant, and will surely see more and more strains being targeted to specific symptoms over time.

We’ll use the reports below and others to produce a list of possible strains to aid with specific symptoms in the 5th article in this series.

Phytocannabinoids

Some research suggests that the very different effects the strains can produce may be more due to the less well studied phytocannabinoids described below than to their THC/CBD contents. Some of the other phytocannabinoids found in Cannabis which might be helpful include:

Cannabichromene (CBC)pain reliever and anti-inflammatory which blocks substance P, a neurotransmitter associated with increased pain in fibromyalgia. CBC also blocks the PPAR pain receptor and has anti-depressant effects. Try CBC-rich strains to reduce pain.

Strains: 3 Kings and Jorge’s Diamonds #1 are reported to be CBC-rich strains.

sleep Cannabinol

Cannabinol may be able to help with sleep.

Cannabigerol (CBG) – Clonidine-like effects – CBG is a chemical precursor to both THC and CBD, antagonizes CB1 (thereby reducing the effects of THC) and is both a potent a2-adrenoceptor agonist (such as Clonidine and Tizanidine) and moderate 5HT1A receptor antagonist (such as propanolol).  Animal studies suggest CBG is a potent appetite-inducer;  if you’re having trouble eating, a CBG rich strain might be helpful. CBG was also helpful with inflammatory bowel disease in another animal study.  Plants harvested at a certain time in the growing season contain more CBG.

Strains: Galactic Jack, Nurse Jackie, Magic Jordan, Destroyer, Mickey Kush, Allen Wrench, Blue Berries, Eldorado, Sweet Skunk and Blueberries are reported to be CBG-rich strains.

Cannabinol (CBN)sedating sleep enhancer – a by-product of THC breakdown whose levels rise the longer a Cannabis product has been stored or exposed to oxygen, CBN has pain-reducing and anti-inflammatory properties and may – because it typically comes from aged plants with more sequiterpenoids in them – help with sleep. It either has no or very mild psychoactive effects, and is generally thought of as having sedative properties, which may be amplified, interestingly enough, when combined with THC.

Strains: One way to increase CBN levels is simply to buy high-THC pot and leave it exposed to the air for awhile.  Leafly reports that “Cookie” strains tend to have high CBN levels. Other sites reports that A-Dub, Blue Blood, Strawberry Haze, Jorge’s Diamonds,  Amsterdam Flame, Death Star, Cataract Kush, Kosher Kush, Pineapple Chunk, Purple Sour Diesel, Red Dragon, and Shark Shock have high CBN levels. Check out a high CBN CBD oil tincture called “Beauty Sleep“.

Cannabidiolic acid (CBDA) – anti-inflammatory and anti-nausea properties.

Cannabidivarin (CBDVA) – strong anticonvulsant properties,  analgesic and anti-inflammatory, neuroprotective, anti-nausea and vomiting, bone health and bone formation, sleep-promoter,  anti-anxiety, possibly anti-psychotic. 

Found in very small amounts in Cannabis THCV, or tetrahydrocannabivarin, one California company is creating a THCV pill. Attempts are being made to incorporate THCV producing genes into hemp to increase availability.

Strains:  Black Beauty is the one strain known to have high THCV levels.

Other Plant Compounds

Cannabis also contains a number of other compounds, some of which have health effects – including anti-inflammatory effects -different from those found in the phytocannabinoids. In fact, a complete anti-inflammatory package would probably contain both the phytocannabinoids Cannabis is best known for, plus some of the other compounds found in the plant. They include:

Terpenesmuscle relaxant, sedative, anti-inflammatory and antibiotic.

Terpenes are oils secreted by glandular hairs on the leaves of Cannabis and other plants terpenes are responsible for Cannabis’s pungent odor. Myrcene, the terpene most commonly found in Cannabis has a musky, earthy smell.

Beta-caryophyllene – anti-inflammatory, anti-oxidant, possible neuropathic pain reliever.

Beta caryophyllene’s peppery odor also shows up in cloves, pepper and cinnamon. Backes reported that “beta-caryophyllene could be poised to to become the hottest cannabinoid since CBD”.  Because beta-caryophyllene activates CB2 receptors, it appears to be able to enhances CBD’s effects.

Strains – Cookies strains as well as Sherbert and Gorilla Glue.

Limonene – mood uplifter, improves mental focus, feelings of well-being, may even perk up your libido, and anti-fungal.

Limonene is also found in citrus fruit, rosemary, juniper and pine needles.

Strains: Tangerine Dream, Gelato, OG, Bubba Kush are reported to have high limonene varieties.

doig-hammock

Beta myrcene is reported to have a calming effect.

Beta-myrcene – calming, sedative effect, muscle relaxant and anti-inflammatory.

Backes believes that because some indica strains contain little CBD, the sedative effect derived from them is due to the myrcene terpendoid found in them.

Strains – ACDC, Godfather OG, AK-47, Purps, Grape Ape are reported to be high myrcene varieties.

Pinene – counteracts THC, may improve concentration, has some anti-inflammatory properties, and smells like, you guessed it, pine needles. Found in pine and balsmaic wood resin and some citrus fruits, pinene is nature’s most abundant terpenoid.

Strains – Pinene Kush is reportedly loaded with pinene.

Linalool – produces calming effects, reduces anxiety, sleep aid, possible immune booster. Linalool is also found in lavender.

Strains – Backes reports that high linalool strains are rare but that Bubba Kush is one.

Terpinolene – invigorating, cognitive enhancer.

Strains – Backes recommends Trainwreck, Big Sur Holy Weed, Jack Herer, S.A.G.E and Zeta.

Try Health Rising’s Fibromyalgia and Chronic Fatigue Syndrome Cannabis Review Program

when you get it right
you pass it on… 
Gary Snyder

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Health Rising’s Marijuana as Medicine for ME/CFS and Fibromyalgia Series

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