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Your Beginner's Guide to the 9 Major Cannabinoids

By Dr. Jessica Knox
on May 30, 2016


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Phytocannabinoids are revolutionizing how we think about medicine.

Have you ever wondered how cannabis actually works in the body?

If you’ve read up on the endocannabinoid system, you’ll know that our bodies are full of receptors that interact with cannabinoids. Cannabinoids are chemical compounds that act directly and indirectly on cannabinoid receptors to help the body maintain stability and health.

Our bodies make their own cannabinoids – called endocannabinoids because they are produced internally – to work on cannabinoid receptors. By some happy coincidence of nature, cannabis and other plants also produce cannabinoids that interact with our receptors. These plant cannabinoids are known as phytocannabinoids.

Phytocannabinoids are just one of the cannabis plant’s active ingredients. Other plant compounds known as terpenes and flavonoids also direct how cannabis will work for you.

But the phytocannabinoids are the cornerstone of your medicine’s effect.

What do you need to know about phytocannabinoids?
There are over 85 known phytocannabinoids – some sources put the count well over 100! Here, we will tour the nine phytocannabinoids that have been most thoroughly documented, starting with the two most prominent compounds: THC and CBD.

The ins and outs of THC
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Newcomers to cannabis are finding a lot of guidance through knowledgeable physicians.

THC is famous for its psychoactive effects and while those cognitive effects can have a variety of advantages or disadvantages depending on the situation, THC offers additional health properties that should not be overlooked.

THC is particularly valuable for managing pain and reducing inflammation, the compound directly addressing the underlying drivers of chronic pain and inflammatory disorders. THC also has great effect in reducing nausea and vomiting, and on the flip side of that coin, stimulating appetite.

Other common uses for THC include aiding sleep, managing glaucoma, reducing muscle spasms, and protecting the nervous system. The nervous system protection has made THC a useful tool in helping to manage autism, ADHD, and post-stroke symptoms.

THC does have some side effects to be aware of – especially if you take too much.

The most common side effects of THC include rapid heart rate, anxiety and paranoia, sleepiness, increased appetite, dry mouth and dry eyes, forgetfulness, dizziness, reduced blood pressure, and potentially hallucinations if you take a lot. For the most part, side effects resolve when the medicine wears off and are generally considered benign.

Getting your THC dosage just right can help you get the most benefit from your medicine while avoiding unwanted side effects, which typically arise when a patient has dosed over their tolerance. The side effect profile of THC is why cannabis doctors counsel their patients to start with a very low dose – around 2.5 – 5 mg of THC, and to gradually increase the dose according to how well they tolerate it.

Finally, you may have noticed that some of the uses for THC are the same as some of the side effects! This is because cannabis is the ultimate personalized medicine. A negative side effect for one person may be a positive side effect for another. A classic example is a patient with cancer regaining his appetite after medicating – what a blessing for him! Similarly, an insomniac will be deeply grateful for THC’s ability to cause sleepiness after an exhausting day.

CBD – the “new kid” on the block
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CBD has changed how a lot of people view cannabis and for good reason.

While it has been around just as long as THC, CBD has only in the past few years become very popular in the medical cannabis world due to its effectiveness against epilepsy and cancer without the head high effects of THC. Though some would argue the claim that CBD is psychoactive because it promotes relaxation and anxiety relief, it is generally accepted that CBD does not cause the euphoric high that THC does.

In addition to reducing or eliminating seizures and fighting the growth of tumor and cancer cells, CBD is an excellent treatment for anxiety. CBD is also an antipsychotic agent, which is why cannabis can actually be a useful tool in managing mental illness, contrary to mainstream belief.

Other popular uses for CBD include reducing muscle spasms and spasms of the small intestine, and application as a pain reduction and anti-inflammatory agent. Finally, even more so than THC, CBD protects the nervous system, making it a great tool for managing dementia and Parkinson’s disease, and essential for use with THC in autism and post-stroke care.

While typically much better tolerated than THC, CBD can have side effects of its own at very high doses, such as dizziness or lightheadedness, anxiety, decreased appetite, drowsiness, increased heart rate and palpitations, and jitteriness.

A really amazing fact about CBD is that it actually reduces undesirable effects of THC, such as inebriation, sedation, and racing heart. Specifically, in medicines with phytocannabinoid content of 4 parts or more CBD to 1 part THC (a 4:1 CBD:THC ratio or higher), CBD will dampen the head high and side effects caused by THC.

Not only that, but CBD can enhance the pain-relieving, nausea-reducing, and anti-cancer effects of THC (yes – THC is quite active against cancer cells too!).

Bottom line – your medicine is better when it contains both THC and CBD!

You said there were 9 major phytocannabinoids…
Though THC and CBD are the most well known phytocannabinoids, we continue to learn more about the characteristics and applications of the other seven.

#1) THCA is the acidic parent of THC found in the raw cannabis plant. When exposed to heat, sunlight, or time, the THCA in the harvested plant will convert to THC. THCA is non-psychoactive and is particularly useful for reducing nausea, reducing seizures, reducing muscle spasms, and fighting tumor and cancer cells.

#2) CBDA is the acidic parent of CBD found in raw plant. CBDA converts to CBD when it is exposed to heat, sunlight, or time. Like THCA, CBDA is non-psychoactive. CBDA is also great for reducing nausea, reducing inflammation, and fighting tumor and cancer cells.

#3) CBN is a breakdown product of THC. As harvested cannabis ages, THC will gradually be converted to CBN. CBN is known to be particularly useful for aiding sleep, and also good for reducing pain and muscle spasms.

#4) CBGA is actually the precursor molecule that is turned into THCA and CBDA as the cannabis plant develops, so it is found only in tiny amounts in the mature plant. In the harvested plant, remaining CBGA converts to CBG with exposure to air and light.

#5) CBG is useful as an antidepressant, a muscle relaxant, an antibiotic and antifungal agent, and as a blood pressure reducer.

#6) CBC is also found only in tiny amounts in the cannabis plant. CBC has pain reducing, anti-inflammatory, antibiotic, antifungal, and anti-cancer effects.

#7) THCV does have psychoactive properties, but much less than THC. THCV has been found to suppress appetite and can aid weight loss, and also has antiseizure effect.

Which phytocannabinoids are right for you?
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An experienced physician can guide patients to getting the most out of cannabis.

Your goal should be to tailor the phytocannabinoid content of your medicine to the conditions and symptoms you want to treat. As noted before, cannabis is a very personal medication, with every person requiring a different medicine composition for even the same condition. As such, there is often much trial and error that goes into finding your ideal phytocannabinoid content.

You can use the details outlined above to help get you started in finding the best composition for your medicine, and here are some examples of the phytocannabinoids that may be useful for the most common conditions seen in many cannabis clinics:

Chronic pain: There are several different forms of chronic pain. Nerve pain may be best managed with CBD and THCA. Muscular pain often responds well to THC. A combination of THC and CBD can be useful for bone pain. Inflammatory pain can be managed with THCA or THC. Skeletal and internal muscle spasms can be relieved with CBD.

Insomnia: THC and its breakdown product, CBN, are particularly useful for aiding sleep. And spoiler alert for the follow-up article on terpenes and flavonoids: the terpene called Myrcene is a great tool for improving sleep!

Anxiety: CBD is the best remedy for anxiety, but at high doses can actually increase anxiety. THC can also be useful for anxiety, but only at low doses. Again, whether you’re using high CBD or high THC medicine, you should always start at a low dose and increase only gradually as needed to achieve the relief you’re seeking.

How do you know which phytocannabinoids are in your medicine?
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Precise lab-testing is critical to optimizing one’s cannabis regimen.

The only way to know the phytocannabinoid content of your medicine is to have it lab tested! Lab testing of cannabis is still underutilized and under regulated, making it challenging to always know what it is in your medicine.

However, lab testing is a critical component of optimizing your cannabis regimen for at least two reasons:

  1. It enables the informed selection of medicine specific to your condition or symptoms.
  2. It allows you to feel confident that you are getting consistent medicine from one batch to the next, which is crucial when using cannabis medicinally.
The spreading legalization of cannabis and the growing interest in using cannabis medicinally will ultimately drive routine and regulated lab testing of the plant. In the meantime, look for lab tested medicine and encourage your grower or dispensary to test their products.


 
The Truth on THC
THC Is Good for More than the High

Delta-9 tetrahydrocannabinol, otherwise known as THC, has suffered from an image problem since its discovery in 1964. Famous for the high it causes, the public has a hard time looking beyond its psychotropic effects.

Novices to cannabis therapeutics are often astonished to find that THC has more than recreational value. In fact, it is responsible for helping an overwhelming majority of medical cannabis users with a wide range of conditions, in addition to having contributed to a wealth of medical knowledge[1] for the past several decades.

By the last count, THC is one of over 100 identified cannabinoids, special chemical compounds, in the cannabis plant. However, it is the most active, matched so far in medical and research significance only by CBD, the other well-known cannabinoid. Although CBD is currently the compound of choice for seekers of medical cannabis treatment, THC remains the powerhouse of medicinal cannabis.

Some Medical Benefits
The website, MedicalJane.com, has reported on the following promising medical benefits of THC in recent research:

  1. An Israeli study finds that THC can cause remission of Crohn’s disease.
  2. THC is instrumental in treating symptoms of PTSD.
  3. THC is showing success in exposure-based phobia treatment.
  4. A study from the Netherlands shows that THC may help relieve depression.
  5. A study shows how THC can aid in treating eating disorders.
  6. THC can help in fighting obesity and preventing diabetes.
  7. THC can help prevent heart attacks.
  8. THC can help encourage neuroplasticity, the way the brain develops over time and regenerates itself.
  9. THC may help treat Parkinson’s disease.
  10. Low doses of THC may protect against neurodegenerative diseases.
  11. THC may inhibit the progression of AIDS.
  12. A Spanish study suggests that THC may delay retinal degeneration and vision loss.
More reports of current research from the website, NORML.org:

  1. THC reduces the symptoms of sleep apnea.
  2. THC is shown to possess gastroprotective qualities and may reduce incidences of hospitalization due to gastric inflammation induced by NSAIDs (non-steroidal anti-inflammatory drugs such as ibuprofen).
Therapeutic Properties of THC
THC is particularly well suited for:

It should be noted though that THC, or CBD for that matter, is not often at its best acting alone. Research has found that CBD relates to THC in a synergistic way by boosting THC’s function and mitigating its psychotropic effects. Moreover, cannabinoids are equally enhanced by other components in the cannabis plant, such as terpenes – a phenomenon known as the entourage effect.

THC in Pharmaceuticals
Ironically, while the prohibition on cannabis has essentially been due to THC and the historical fears of its physical and social harms, pharmaceutical companies have quietly been reaping its pharmacological benefits with government approval.

Synthetic versions of THC have been available in prescription drugs, such as Marinol, since 1985. Marinol was first used for treating nausea and vomiting in cancer patients and then for appetite stimulation in AIDS patients. It is also used as an analgesic to ease neuropathic pain in Multiple Sclerosis patients.

Sativex, an oral spray launched in the UK in 2010, is currently on the “fast track” for approval with the Food and Drug Administration as pain treatment for cancer patients. When it does become available, it will be the first cannabis-based prescription medication in the world, containing both THC and CBD.

Continue browsing our knowledge center and blog to learn more or contact us today to find out how our extracts may meet your medical needs.

[1] Close to 6500 research articles appear on PubMed.gov, the website of the US National Library of Medicine and National Institutes of Health, with the keyword “delta9-tetrahydrocannabinol.” Over 13,000 articles appear with the keyword, “cannabis.”
 
Know Your Medicine: THC

The claim that THC is recreational only and has no medicinal value is bogus. It is time to move on from the “Reefer Madness” propaganda.

Delta-9-tetrahydrocannabinol (THC) is the most prominent cannabinoid in the cannabis plant and is responsible for the psychoactive “high” effects. The THC molecule was not isolated until 1964 but our ancestors utilized THC-rich cannabis for its many medicinal effects. The claim that THC is recreational only and has no medicinal value is bogus. It is time to move on from the “Reefer Madness” propaganda. Many medical cannabis patients report significant and life-changing relief of medical conditions with THC-rich cannabis.

All humans have an endocannabinoid system which relies on the synthesis of endocannabinoid compounds, often referred to as our “inner cannabis,” which bind to receptors on our cells in a key and lock fashion. The role of this system is to maintain balance — homeostasis — of the cells in our brains and bodies. Mood, appetite, sleep, immune function and other important physiologic functions are under control of the endocannabinoid system. This system cannot function well if one cannot make enough endocannabinoids, resulting in an “endocannabinoid deficiency.” The causes of endocannabinoid deficiency are many: genetically inherited or a result of illness, chronic stress, sleep deprivation, and other causes. The deficiency causes cells to remain in an imbalanced state. Mother Nature gives us the cannabis plant that is full of phytocannabinoids which can replace the deficiency naturally, with THC mimicking the effects of the endocannabinoids, resulting in balance.

Scientifically, THC is made up of carbon, hydrogen, and oxygen atoms in a three-ring structure. The cannabis plant is thought to make THC in its flower as a defense mechanism and as UV protection. THC is a result of the decarboxylation of tetrahydrocannabinolic acid, which occurs when the flower is heated. The potency of the cannabis plant is usually measured by the content of THC, which can range from 0.5% up to ~30%. Concentrated forms of THC-rich cannabis can have potencies up to ~90%. The average potency of cannabis in the 1970s was 2-5% and now ranges between 10-25% in states with medical cannabis laws.

THC is the most studied of the phytocannabinoids. It binds directly to the two types of cannabinoid receptors located in our brains and bodies, mimicking our natural endocannabinoids. In addition to relieving pain and increasing appetite in patients, THC has also been shown to be a potent anti-inflammatory, antioxidant, antidepressant, antianxiolytic, neuroprotectant, anti-proliferative (kills cancer cells), anti-nausea and anti-emetic (stops vomiting). Although psychoactivity is the most famous effect, it can be avoided using low-dose THC products that are currently available. These products allow for THC dosing of about 1 – 10 mg, giving patients better control over the effects and permitting for careful experimentation to find the right dose. Multiple long-term studies document the excellent safety profile of THC-rich cannabis, with the DEA’s own judge, Francis Young, calling it, “one of the safest therapeutically active substances known to man.” Tolerance to the effects of THC can develop with higher doses and long-term use but are easily reversed with abstinence.

There are a few things to keep in mind when using THC-rich cannabis medicine:

  • Different people respond differently to THC — some people feel significant effects and some do not
  • Patients should use the lowest dose that gives the desired effects so that tolerance can be limited
  • Daily users of THC should take breaks, either skipping use 1-2 days per week or 1 week every few months to allow the number of cannabinoid receptors to remain as close to normal as possible
  • Only tested cannabis products should be used
  • Patients should make sure to keep THC-rich cannabis medicine away from children and pets
  • The most common side effects from THC-rich cannabis are dry mouth, feeling lightheaded or dizzy, rapid heartbeat, reddening of the eyes, coughing from inhalation of smoke or vapor; although not dangerous, new patients may feel anxious or even panic with some of these effects
THC-rich cannabis alleviates many symptoms and medical conditions with little to no side effects. Its use is growing exponentially as we move toward science- and evidence-based research and away from propaganda. Knowing your medicine is the best way to find success with it.

Sources:

El-Alfy, Abir T., et al. “Antidepressant-like effect of Δ 9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L.” Pharmacology Biochemistry and Behavior 95.4 (2010): 434-442.

Falenski, Katherine W., et al. “FAAH−/− mice display differential tolerance, dependence, and cannabinoid receptor adaptation after Δ9-tetrahydrocannabinol and anandamide administration.” Neuropsychopharmacology 35.8 (2010): 1775-1787.

Gaoni, Yechiel, and Raphael Mechoulam. “Isolation and structure of. DELTA.+-tetrahydrocannabinol and other neutral cannabinoids from hashish.” Journal of the American Chemical Society 93.1 (1971): 217-224.

Hampson, A. J., et al. “Cannabidiol and (−) Δ9-tetrahydrocannabinol are neuroprotective antioxidants.” Proceedings of the National Academy of Sciences 95.14 (1998): 8268-8273.

Mechoulam, Raphael, et al. “Early phytocannabinoid chemistry to endocannabinoids and beyond.” Nature Reviews Neuroscience 15.11 (2014): 757-764.

Mechoulam, Raphael, and Linda A. Parker. “The endocannabinoid system and the brain.” Annual review of psychology 64 (2013): 21-47.

Russo, Ethan B. “Cannabinoids in the management of difficult to treat pain.” Therapeutics and Clinical Risk Management 4.1 (2008): 245.
 
Benefits Of THCA

Cannabinoids are the chemicals in marijuana that are responsible for its effects. The production of cannabinoids occurs in tiny, crystal-like structures called trichomes. These trichomes are heavily concentrated on the flowers or “buds” of female cannabis plants. Patients and physicians today know a lot about certain cannabinoids like THC and CBD. But THC and CBD are just two of over 113 cannabinoids that have been identified in marijuana.

The wide range of cannabinoids present in hemp, and other phytochemicals such as the terpenes, have demonstrated a variety of possible therapeutic uses, without causing a high. While cannabidiol (CBD) has been associated with the largest number of pharmacological effects, another cannabinoid that won’t cause the patient to get high is tetrahydrocannabinolic acid, or THCA.

You’ve heard of THC, and while they may sound similar, THCA actually has very different properties. Unlike THC, THCA is a non-psychoactive cannabinoid found in raw and live cannabis. As the plant dries, THCA slowly converts to THC. Heat expedites this conversion in a process known as decarboxylation, a fancy word that describes what happens when you smoke or vaporize flower.

Every high-THC strain that has not yet been decarboxylated contains THCA, and these cannabinoid levels are particularly high as a live or freshly harvested plant. For this reason, raw cannabis parts are popularly juiced for their THCA benefits (sweet potato pear smoothie, anyone?).
Some products are marketed specifically for their THCA content such as Present Naturals and Mary’s Medicinals transdermal patches. Products like these deliver THCA’s benefits without the risk of psychoactive effects, and as THCA gains traction, we’re likely to find more products like this emerging.

Research in the field of THCA is continuously progressing, but it is still too early to make definite statements about the therapeutic effects of this compound – which certainly does not mean there aren’t any. Preliminary studies point out potential medicinal benefits including:

• The reduction of nausea induced vomiting and appetite loss (anti-emetic)

• Protective capacities for treatment of neurodegenerative diseases (e.g. Parkinson)

• Anti-inflammatory effects beneficial for treating a wide range of diseases (e.g. Arthritis)

• Inhibition of prostate cancer growth (anti-proliferative)

Other possible medicinal avenues supported by patient stories include insomnia, muscle spasms, and pain. Unfortunately, we’ll have to wait for more studies to substantiate all of the above benefits before we can fully understand what THCA means for the future of cannabinoid-based medicines.
 
SCIENTISTS MAP THE RECEPTOR THAT MAKES WEED WORK
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CODY RASMUSSEN/GETTY IMAGES


ADD MARIJUANA TO humans, and you get some fairly predictable results: euphoria, hunger, introspection, anxiety, and a whole panoply of other effects. Also known as being high. Most of that complicated reaction is thanks to a single cellular structure known as cannabinoid receptor 1. Your body has CB1 receptors lacing the surfaces of cells in the brain, liver, lungs, fat, uterus, and sperm. And whenever your ... friend smokes, dabs, or eats an edible, the tetrahydrocannabinol molecules therein bind to these sites, stimulating the cells to release a cornucopia of chemical signals.

For a long time, scientists thought CB1 receptors worked like lock and key with THC and its chemical cousins—one size fits one. However, new research shows that CB1 receptors are actually quite malleable, stretching to fit a wider range of molecules. That could be useful knowledge as researchers try to synthesize chemicals that mimic the desirable effects of cannabis (such as pain relief) without the side effects (such as anxiety, weight gain, addiction, or federal prosecution).

"People have been using cannabis for a variety of therapeutic indications for centuries," says Alexandros Makriyannis, director of Northeastern University's Center for Drug Discovery, and a co-author of this new research, published in Nature. In the 1960s, scientists finally started to figure that out as well. And by the 1980s, Eli Lilly had developed a synthetic THC knockoff called Nabilone. "It was a good quality drug used for nausea from chemotherapy, and also pain," says Makriyannis. But other THC-based synthetics never took off, in part because pharmacologists couldn't eliminate all the unwanted side effects.

Still, cannabinoid receptors are such promising therapeutic targets that some researchers persist. Makriyannis has been at it for decades, and has discovered dozens of compounds that interact with either CB1 or its cousin, CB2. THC, the active ingredient in weed, is just one of those. Your body even makes its own, called endocannabinoids, that are involved with modulating your appetite, mood, memory, and pain. Scientists, including Makriyannis, have synthesized many more. And last year, he made an even more significant discovery: a compound that could turn the CB1 receptor off. An anti-high, if you will.

That discovery gave arise to this latest finding, of CB1's malleability. See, the molecules that switch CB1 on—THC and other cannabinoids—are about 100 times smaller than the receptor they turn on. Curious, Makriyannis and his Northwestern team, along with researchers in China, California, and Florida, set about visualizing the receptor in various states of activation and deactivation using a technique called X-ray crystallography.

If X-ray crystallography sounds familiar, it's probably because it's the same technique Rosalind Franklin used to visualize the structure of DNA in 1952. Most molecules are too small for a typical microscope to see. This method gets around that turning the tiny molecule into a crystal—its structure repeated over and over again in the exact same orientation. X-rays pass through the crystal structure, then collide with a sensor on the other side. The scientists collect that impression from the sensor, really just a bunch of data, and mathematically reconstruct the molecule's shape.

CB1 receptors looks like a bundle of microscopic sausage links. The sausages, seven in all, are spirals of amino acids that weave in and out of a cell's membrane. And they are very flexible. When a cannabinoid goes into the receptor, the sausage links—called helices—coalesce around that receptor's binding site. The big surprise came when Makriyannis' group crystallized CB1 as it was binding to the THC-like molecules meant to switch it on. The crystallography revealed that two of the helices twisted and collapsed to fit around the molecule, shrinking the receptor to less than half its size when it received the off-switch molecule. Never mind the lock and key: CB1 is like a door that opens to the tune of many different secret knocks.

Makriyannis says this is a big breakthrough for his work, and that he'll keep looking for new cannabinoid molecules. "We want to make compounds that will modify the receptor differently, so we can make better drugs," he says. (He and his co-authors will present more of their work at the Chemistry and Pharmacology of Drug Abuse annual symposium from August 9 to 12 at Northeastern University.) His hope is that he can create finely-tuned molecules that will trigger CB1 to send anti-nausea signals to the body, without things like irritability, anxiety, or addiction. You could say he has a higher calling.
 
Cannabis’s Entourage Effect: Why Whole Plant Medicine Matters

Take a close look at your cannabis buds. They’re covered in a sticky dusting of crystal resin, which contains hundreds of therapeutic compounds known as cannabinoids and terpenoids. We assume you’re well acquainted with THC and CBD, but these are just two among many important players working together to produce specific effects. This interactive synergy between cannabis compounds has been coined the “entourage effect,” and once you know what this is, you’ll see why medicines containing only THC or CBD aren’t always sufficient for many medical conditions.




What Are THC- and CBD-Only Medicines?
THC-only medicines primarily refer to synthetic renderings of THC, the two most popular being Marinol (dronabinol) and Cesamet (nabilone). These are legal pharmaceuticals primarily prescribed to treat cancer-related nausea, but their efficacy is questionable. A 2011 survey on forms of consumption found only 1.8% of 953 patients prefer synthetic THC pharmaceuticals over inhaled or infused methods. Furthermore, it can take hours for a THC-only pill to deliver relief whereas inhaled methods take effect immediately.

CBD-only medicines have been gaining momentum in recent years following the media frenzy around Charlotte’s Web, a non-psychoactive cannabis strain that was processed into a CBD-rich oil for an epileptic child. The miraculous remedy prompted several states to adopt CBD-only laws under which THC-rich medicines remain illegal. While CBD-only cannabis medicines have proven to be life-changing for many individuals, these laws mainly exist to help those suffering from seizures.

That is not to say that synthetic, hemp-based, and CBD-only medicines aren’t effective options for many patients, especially as laws limit access to alternatives. These types of products have served a monumental role both as medicine and as a legislative stepping stone. But what more can patients get from whole plant medicine?

What Makes “Whole Plant Medicine” Different?
“Whole plant medicine” is a term used to describe medicines utilizing the full spectrum of therapeutic compounds cannabis has to offer. A glimpse of the most abundant cannabinoids and terpenes is provided below in our two graphics illustrating the properties and benefits of each (click on each for enlarged versions).







As you can see, each of these therapeutic agents that are processed out of THC- and CBD-only medicines have so much to offer patients treating a wide breadth of symptoms and conditions. You’re already familiar with the most popular “whole plant medicine,” which is inhaling cannabis smoke or vapor. Although most cannabis today is bred to contain a disproportionately large amount of THC compared to other compounds, the importance of chemical diversity is being realized as new strains emerge. Hopefully, we’ll soon start to see strains that not only narrow the gap between THC and CBD profiles, but emphasize other important cannabinoids and terpenes as well.

Cannabinoids and Terpenes Work Together
The diverse chemical availability in whole plant medicines is remarkable in its own right, but research looking into how cannabinoids and terpenoids work together adds another level of intrigue.

Instrumental in this area of science is Ethan Russo, M.D., a neurologist who has long studied cannabis compounds and their role in the body. In his study “Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects,” he details how cannabis compounds influence each other’s mechanisms. We aren’t just talking about the well-known THC-CBD tag team here – even small amounts of terpenes (fragrant oils that give cannabis its smell) can make a difference.

The terpene myrcene, for example, can reduce resistance in the blood-brain barrier, enabling easier passage of other beneficial chemicals. Pinene helps counteract compromised cognition and memory caused by THC. A combination of terpenes pinene, myrcene, and caryophyllene help unravel anxiety. Mixing terpenes linalool and limonene with the cannabinoid CBG shows promise in the treatment of MRSA. THC plus CBN yields enhanced sedating effects. Linalool and limonene combined with CBD is being examined as an anti-acne treatment.

These examples only scratch the surface of all possible synergies made available to us by way of whole plant therapies. Think of all the medical possibilities waiting for us as the combinational potential of these compounds are unlocked. The thought of how many lives could be changed for the better by such discoveries is almost overwhelming.
 
The Most Common Cannabinoids Found in Cannabis

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Tetrahydrocannabinolic Acid (THCA)

THCA is the main constituent in raw cannabis. THCA converts to Δ9-THC when burned, vaporized, or heated at a certain temperature. THCA, CBDA, CBGA, and other acidic cannabinoids hold the most COX-1 and COX-2 inhibition, contributing to cannabis’ anti-inflammatory effects. This cannabinoid also acts as an antiproliferative and antispasmodic.

Cannabinol (CBN)
CBN is a mildly psychoactive cannabinoid that is produced from the degradation of THC. There is usually very little to no CBN in a fresh plant. CBN acts as a weak agonist at both the CB1 and CB2 receptors, with greater affinity for CB2 receptors than CB1. The degradation of THC into CBN is often described as creating a sedative effect, known as a “couch lock.”

Cannabichromene (CBC)
CBC is most frequently found in tropical cannabis varieties. CBC is known to relieve pain, reduce inflammation, inhibit cell growth in tumor/cancer cells, and promote bone growth. The effects of CBC appear to be mediated through non-cannabinoid receptor interactions.

Cannabidivarin (CBDV)
Like THCV, CBDV differs from CBD only by the substitution of a pentyl (5 carbon) for a propyl (3 carbon) sidechain. Although research on CBDV is still in its initial stages, recent studies have shown promise for its use in the management of epilepsy. This is due to its action at TRPV1 receptors and modulation of gene expression.

Tetrahydrocannabinol (THC)
The most abundant cannabinoid present in marijuana, THC is responsible for cannabis’ most well-known psychoactive effects. THC acts as a partial agonist at the CB1 and CB2 receptors. The compound is a mild analgesic, or painkiller, and cellular research has shown that it has antioxidant activity.

Cannabidiol (CBD)
CBD has tremendous medical potential. This is particularly true when the correct ratio of CBD to THC is applied to treat a particular condition. CBD acts as an antagonist at both the CB1 and CB2 receptors, yet it has a low binding affinity for both. This suggests that CBD’s mechanism of action is mediated by other receptors in the brain and body.

Cannabigerol (CBG)
A non-psychoactive cannabinoid, CBG’s antibacterial effects can alter the overall effects of cannabis. CBG is known to kill or slow bacterial growth, reduce inflammation, (particularly in its acidic CBGA form,) inhibit cell growth in tumor/cancer cells, and promote bone growth. It acts as a low-affinity antagonist at the CB1 receptor. CBG pharmacological activity at the CB2 receptor is currently unknown.

Tetrahydrocannabivarin (THCV)
THCV is a minor cannabinoid found in only some strains of cannabis. The only structural difference between THCV and THC is the presence of a propyl (3 carbon) group, rather than a pentyl (5 carbon) group, on the molecule. Though this variation may seem subtle, it causes THCV to produce very different effects than THC. These effects include a reduction in panic attacks, suppression of appetite, and the promotion of bone growth. THCV acts as an antagonist at the CB1 receptor and a partial agonist at the CB2 receptor.
 
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Why Do We Have Cannabinoid Receptors?


Have you ever wondered why cannabis has such strong medicinal and psychoactive effects? The herb interacts with the body in ways that no other plant can. The plant contains chemical compounds that are unique to cannabis alone, making it an anomaly in the great wide world of flora. These compounds are called cannabinoids and they are able to engage with special landing locations on human cells. But, why do we have these cannabinoid receptors, anyway? Here’s the answer.

Why do we have cannabinoid receptors?
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Cannabis exerts its psychoactive and medicinal effects by engaging with special receptor sites on human cells. These receptor sites are called cannabinoid receptors. Sometimes, these landing locations are incorrectly called “cannabis receptors.”

Cannabis compounds engage with these receptors, but that doesn’t mean they were designed specifically for cannabis.

Instead, we have cannabinoid receptors because the human body creates its own version of cannabis compounds called endocannabinoids. Endocannabinoids are like the body’s own tetrahydrocannabinol (THC). THC is the primary psychoactive in the cannabis plant.

Endocannabinoids are often left out of medical textbooks, yet they are of infinite importance for human health. Endocannabinoids tap into what has been termed the endocannabinoid system (ECS).

The ECS is one of the largest neurotransmitter networks in the human body. Neurotransmitters are communication molecules that help the brain and the body communicate with each other via nerve cells.

What does the endocannabinoid system (ECS) do?
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The ECS is a neurotransmitter network that acts as a homeostatic regulator. This is a fancy term for a system that helps maintain optimal balance in the body.

The ECS helps coordinate messages between the brain and the body, ensuring that both respond appropriately to both internal and environmental stimuli.

For example, research suggests that the ECS helps maintain the sleep-wake cycle, ensuring that your body becomes tired at the right time and helps you wake up in the morning. Similarly, with appetite, endocannabinoid molecules tell when you’re hungry and signal that it’s time to eat during certain parts of the day.

Scientists are still exploring all of the ways the ECS, yet it’s know that the system regulates:

  • Sleep
  • Appetite
  • Pain
  • Pleasure
  • Cognition
  • Memory
  • Visceral sensation
  • Mood
  • Growth
  • Movement
  • Immune function
What makes cannabis so beneficial?
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It just so happens that the active compounds in cannabis, cannabinoids like psychoactive THC, directly engage with the ECS. The plant can produce at least 113 different cannabinoids, though not all samples will contain all of these different varieties.

This class of compounds has not been found in any other plant. Though, some herbs docontain compounds that act similarly to cannabinoids and also engage the ECS. However, none of these compounds function exactly like those found in cannabis.

All foods contain molecules that can have drastic effects on the human body. The cannabinoids found in the cannabis plant are like the plant versions of our own endocannabinoids. While these plant versions are surprisingly powerful, they do not fit into cannabinoid receptors or function quite like our natural molecules do.

However, plant cannabinoids can be an important supplement for the ECS. Other foods, like flax, also contain plant compounds that take the place of natural molecules in the body. Flax contains what are called phytoestrogens. These are plant-based estrogens that can engage with estrogen receptors in the human body, modulating their effects.

The phytocannabinoids in cannabis are similar, only they operate on cannabinoid receptors.

Cannabis and humans go way back
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Humans may not have been “meant” to consume cannabis, but the herb has certainly been a key part of the development of agricultural, medical, and spiritual history.

Some theorists even go as far as to suggest that cannabis cultivation may have played a major role in the transition from hunter-gatherer societies to farming communities. From the evidence thus far, cannabis is thought to have originated in the fertile crescent. This the same region that marked the beginnings of modern agriculture.

From there, the plant has since spread to every continent and has been used for thousands of years by cultures all over the world. Today, it remains the world’s most popular illicit substance.

Unlike many other plants commonly associated with the birth of modern agriculture, like wheat, cannabis is a multifunctional plant with many beneficial uses.

Stalks can be dried and harvested for fiber, which can be used as building materials and as fabric textiles.

Cannabis seeds are thought to have been an extremely valuable source of nutrition for early humans, providing an excellent source of essential fatty acids as well as protein.

On the medical side of things, there is a wealth of archeological and historical data that suggests that the plant has been used in a wide variety of ways by cultures throughout the world.

The plant was a popular choice for women’s health issues like menstrual distress and labor pains. It was also used by multiple societies as a pain relief tool and was frequently applied topically to wounds and injuries.

Thanks to the plant’s psychedelic properties, the herb was also used as a means to facilitate spiritual healing.

So what does this all mean?
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It’s estimated that cannabis is one of the oldest domestic plants. Researchers suggest that it has been used by humans for at least 10,000 years, if not longer. That’s a lot of time to coexist and utilize one particular crop.

While cannabinoid receptors might not mean that humans are “designed” to consume cannabis, there is no doubt that the several-millennia-long relationship we have had with the plant shows that it is an important part of human health.

Unfortunately, thanks to misinformed political policies over the last century, Western cultures have lost touch with a relationship that took over 10,000 years to develop. During the past 80 to 90 years, cannabis consumption has still been a regular part of everyday life for many individuals.

However, our relationship with this plant became taboo to discuss and was pushed underground like a dirty secret.

Thankfully, the word has finally gotten out about the amazing benefits of cannabis. It’s time to rekindle this long-lost relationship.
 

Know Your Medicine: CBG and CBGA


BY BONNI GOLDSTEIN, M.D. ON AUGUST 24TH, 2017

Experts report that there are at least 106 phytocannabinoids found in the trichomes of the cannabis flower. Most research has focused on the two most prominent “primary” cannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD). However, many of the so-called “secondary” cannabinoids are responsible for adding to the therapeutic effects of cannabis as part of the entourage effect, the term used to describe how the many cannabinoid and terpenoid compounds in cannabis work synergistically to deliver beneficial effects.


Cannabinoid Biosynthesis Part 1 – CBG, THC, CBD, and CBC

Cannabigerol (CBG) and cannabigerolic acid (CBGA) are two of the many secondary phytocannabinoids found in the flower of the cannabis plant. The “A” in CBGA refers to the presence of a certain chemical structure called carboxylic acid. CBG was initially isolated from hash by Israeli researchers in 1964, with subsequent research in Japan elucidating that CBGA was its precursor. CBG is one of the five most common cannabinoids along with THC, CBD, CBN (cannabinol) and CBC (cannabichromene). CBGA plays an extremely important role as the parent compound in the maturing cannabis flower and undergoes a number of changes to create THC, CBD, CBC, and CBG. This process, called biosynthesis, starts when compounds in the maturing flower, geranyl pyrophosphate and olivetolic acid, bond together to create CBGA. Next, CBGA is exposed to three different enzymes, with the amount of each enzyme determined by the genetics of the plant.

  • The enzyme THCA synthase converts CBGA to THCA
  • The enzyme CBDA synthase converts CBGA to CBDA
  • The enzyme CBCA synthase converts CBGA to CBCA
As you can see in the chart below, all of the “A” forms are converted in a process called decarboxylation. CBGA itself converts to CBG when heated.

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There is scant research on the medicinal benefits of CBGA. In the plant, CBGA provides a defense mechanism, along with THCA, as an insecticidal agent. When released from the trichomes of the cannabis plant, CBGA, THCA, CBCA and CBDA can each produce plant cell necrosis which allows for natural fan leaf pruning. This allows for the plant to direct its energy away from the leaves to the flower.

Medicinal Properties of CBG
CBG is non-intoxicating and has the following medicinal properties, demonstrated in laboratory and animal studies:

  • Antifungal
  • Antibacterial with potent inhibition of MRSA
  • Anticancer (skin, prostate, and breast)
  • Antidepressant in animal models
  • Mild antihypertensive (lowers blood pressure)
  • Inhibits growth of certain skin cells that contribute to psoriasis
  • Blocks uptake of GABA, promoting muscle relaxation
  • Lowers intraocular eye pressure
  • Enhanced appetite
  • Neuroprotection
CBG is present in small amounts in the vast majority of drug-variety cannabis plants. However, it is more abundant in fiber variety plants (aka “hemp”). Recent breeding experiments in Europe have resulted in fiber variety cannabis containing a significant predominance of CBG, with content >80% in some. With the widespread legalization of cannabis for medical and recreational use underway, growers have the opportunity to focus on breeding CBG-rich varieties of cannabis paralleling the recent explosion of CBD-rich varieties. Having a broad array of products with a variety of dominant cannabinoids will allow for patients to customize their cannabis regimen to suit their individual needs.

Sources:
Appendino G, Gibbons S, Giana A, Pagani A, Grassi G, Stavri M et al. (2008). Antibacterial cannabinoids from Cannabis sativa: a structure-activity study. J Nat Prod 71: 1427–1430.

Baek SH, Kim YO, Kwag JS, Choi KE, Jung WY, Han DS (1998). Boron trifluoride etherate on silica-A modified Lewis acid reagent (VII). Antitumor activity of cannabigerol against human oral epitheloid carcinoma cells. Arch Pharm Res 21: 353–356.

Banerjee SP, Snyder SH, Mechoulam R (1975). Cannabinoids: influence on neurotransmitter uptake in rat brain synaptosomes. J Pharmacol Exp Ther 194: 74–81.

Brierley, Daniel I., et al. “Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats.” Psychopharmacology233.19-20 (2016): 3603-3613.

Cascio MG, Gauson LA, Stevenson LA, Ross RA, Pertwee RG (2010). Evidence that the plant cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist. Br J Pharmacol 159: 129–141.

Colasanti, Brenda K. “A comparison of the ocular and central effects of Δ9-tetrahydrocannabinol and cannabigerol.” Journal of Ocular Pharmacology and Therapeutics 6.4 (1990): 259-269.

De Petrocellis L, Di Marzo V (2010). Non-CB1, non-CB2 receptors for endocannabinoids, plant cannabinoids, and synthetic cannabimimetics: focus on G-protein-coupled receptors and transient receptor potential channels. J Neuroimmune Pharmacol 5: 103–121.

ElSohly HN, Turner CE, Clark AM, ElSohly MA (1982). Synthesis and antimicrobial activities of certain cannabichromene and cannabigerol related compounds. J Pharm Sci 71: 1319–1323.

Evans FJ (1991). Cannabinoids: the separation of central from peripheral effects on a structural basis. Planta Med 57: S60–S67.

Formukong EA, Evans AT, Evans FJ (1988). Analgesic and antiinflammatory activity of constituents of Cannabis sativa L. Inflammation 12: 361–371.

Ligresti A, Moriello AS, Starowicz K, Matias I, Pisanti S, De Petrocellis L et al. (2006). Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J Pharmacol Exp Ther 318: 1375–1387.

Maor Y, Gallily R, Mechoulam R (2006). The relevance of the steric factor in the biological activity of CBD derivaties-a tool in identifying novel molecular target for cannabinoids. In: Symposium on the Cannabinoids. International Cannabinoid Research Society: Tihany, Hungary, p. 1.

Musty R, Deyo R (2006). A cannabigerol extract alters behavioral despair in an animal model of depression. Proceedings June 26; Symposium on the Cannabinoids. International Cannabinoid Research Society: Tihany, p. 32.

Shoyama, Yukihiro, et al. “Biosynthesis of cannabinoid acids.” Phytochemistry 14.10 (1975): 2189-2192.

Sirikantaramas, Supaart, et al. “Tetrahydrocannabinolic acid synthase, the enzyme controlling marijuana psychoactivity, is secreted into the storage cavity of the glandular trichomes.” Plant and Cell Physiology 46.9 (2005): 1578-1582.

Taura, Futoshi, et al. “First direct evidence for the mechanism of. DELTA. 1-tetrahydrocannabinolic acid biosynthesis.” Journal of the American Chemical Society 117.38 (1995): 9766-9767.

Valdeolivas, Sara, et al. “Neuroprotective properties of cannabigerol in Huntington’s disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice.” Neurotherapeutics 12.1 (2015): 185-199.

Wilkinson JD, Williamson EM (2007). Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis. J Dermatol Sci 45: 87–92.
 
Why CBD Is Not Enough: The Entourage Effect

Several states have or are in the process of legalizing cannabis extracts, typically oils, high in cannabidiol (CBD) and very low in THC. Because these medicines lack THC (the cannabinoid in marijuana that produces the euphoric high), conservative politicians have been much more willing to embrace this approach to medical marijuana.

However, there are dozens of other cannabinoids and terpenoids (terpenes) in marijuana that have proven to provide medical benefit. New research is pointing toward a synergistic effect of these miraculous molecules, revealing that an isolated cannabinoid (like CBD) may provide benefit for some patients, but only a small minority. The combination of multiple, or all, cannabinoids may work best medicinally.

According to the National Institutes of Health, the delicate interaction of cannabinoids and terpenoids — sometimes called the “entourage effect” — can be used to treat “pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, [and] fungal and bacterial infections.”

With so much potential benefit from whole plant and multi-cannabinoid extracts, why is there such a mad rush to produce single cannabinoid oils for a small percentage of overall patients that might benefit from such limited cannabis therapy? Can states really claim to be helping patients if CBD-only laws are effective in treating only a relatively low number of patients who are suffering?

Helping Only Two Percent?
According to the Marijuana Policy Project (MPP), “…only two percent of the registered patients in both Rhode Island and Colorado report seizures as their qualifying conditions.” Unfortunately, the group reported that “The vast majority of [all medical marijuana] patients have symptoms that benefit from strains of marijuana that include more than trace amounts of THC.”

The media has focused much attention on children who use CBD oil to combat intractable epilepsy and other severe neurological disorders. Some of these patients gain significant relief from a single-cannabinoid extract. Children who have gone from hundreds of seizures per week to only a couple per month using only CBD oil have gained ample media attention.

One patient, nine-year-old Charlotte Figi of Colorado, experienced a 99 percent decrease in seizure activity using a CBD-only cannabis oil. Figi has been the unofficial poster child of advocates of CBD oil and efforts to legalize it. She is also the inspiration behind a CBD-only oil product called Charlotte’s Web from CW Botanicals in Colorado.

Reports from Parents
Desperate parents of other children with similar conditions have also experimented with CBD oils. Many, unfortunately, have reported that the lack of THC in CBD oils often doesn’t work for their children. Jason David has been treating his seven-year-oldson, Jayden, who has Dravet syndrome — a severe form of epilepsy that doesn’t respond to conventional treatments — with medical cannabis since 2011 (Charlotte Figi’s mother learned about CBD oil from David).

“I wish Charlotte’s Web worked for all epileptic kids, but it doesn’t. The worst seizures Jayden ever had on medical cannabis was while we were using Charlotte’s Web,” said David.

Brian Wilson, a former New Jersey resident who moved to Colorado in 2014 because of its liberal medical marijuana law, is another parent of a child suffering from Dravet syndrome. In an interview with Ladybud in 2014, he said:

“CBD is a very important part of the mix, but only part. We saw minor seizure control and developmental progress with CBD alone, but we didn’t see real seizure control until we added measurable levels of THC to the mix.”

Wilson continued:

“Others see great results with THCA added in. Some see very good results with no CBD, like in New Jersey, where there is little to no CBD available. The point is, this is highly individualized medicine. There is no magic bullet.”

Rebecca Hamilton-Brown is the founder of Pediatric Cannabis Therapy, a support group for parents of epileptic children with more than 2,500 members. She has been treating her son with cannabis for two years and gaining feedback from the group’s many members.

“It is ignorance that leads people to believe that CBD only is the way to go.”

said Hamilton-Brown.

“They either have never dosed their children or they are totally naïve when it comes to how the political machine works.”

Are thousands of sick children and adults who would benefit from a multi-cannabinoid or even whole plant extract of cannabis being disregarded by state governments seeking to legalize CBD-only oil?

The miracle story of Charlotte Figi is certainly inspiring; all patients deserve medicine that relieves them of their suffering. However, are paranoid politicians afraid to legalize cannabis extracts containing THC simply because of an 80-year-old stigma? Is the legacy of Reefer Madness — and the perception that euphoria is a sin in some religions — responsible for the passage of state laws that, while helpful for a small number of patients, leave most suffering with no medicine?
 
Fair warning; the video at the end has some ridiculousness in it as well as info. The promotional blurbs about hashbar are obnoxious. But since it was part of this article I thought I might as well include it.

THC-A Crystalline: The Purest THC on the Planet

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Any concentrate you’ll be getting your hands on will not likely have a concentration higher than 50 to 80% THC. Until now.

THC Supercharged

THC-A Crystalline (not to be mixed up with the un-activated cannabinoid THCa) is believed to be the purest form of THC concentrate that is scientifically able to be made.

With a 99.9% pure THC content, this product rivals anything currently on the market, with no concentrates appearing over 80%. The strongest flower one can get on the market ranges from only 25-30% THC purity, which goes to show cannabis consumers how supercharged the THC content is in THC-A Crystalline.

Advancement of Concentrates & Extraction

In recent years, dabbing and the popularity of waxes, oils, rosin, and other concentrate products has left cannabis enthusiasts hungry for more concentrates that pack more of a punch.

THC-A Crystalline will probably be as punchy as it gets, in terms of the potency of the cannabis plant.

Manufactured in Southern California, the end product of the advanced extraction process reveals a rock-like substance that is clear in color.

The extraction process is so advanced, that there are no cannabinoids present in THC-A Crystalline, therefore, the medicinal or therapeutic benefits of this substance are low when compared to leaf.

On the other hand, users who have tried this concentrate report a different kind of THC-high. An energetic, stimulating, and mentally-clarifying high is reported as opposed to the mellow kind of high one gets with flower.

Benefits of THC-A Crystalline

With THC therapy becoming an important part of the medical marijuana movement, those who engage in THC therapy are guaranteed the purest and most fast-effecting treatment through THC-A Crystalline.

In addition, due to its purity, dosing is way more precise whereas with other concentrates, there is some variability in the potency of each dose.

 

Know Your Medicine: THCV


As access to cannabis widens and research into the medicinal effects of its compounds expands, we’re learning there’s much more to the cannabis plant than THC and CBD. One of the most interesting cannabinoids in cannabis is tetrahydrocannabivarin or THCV. Preliminary studies show promising therapeutic effects for different ailments including diabetes and Parkinson’s disease.

THCV results from a different chemical pathway than THC. Geranyl pyrophosphate joins with divarinolic acid to make cannabigerovarin acid (CBGVA), which changes to tetrahydrocannabivarin carboxylic acid (THCVA) when exposed to the enzyme THCV. When THCVA is heated, it decarboxylates to THCV.

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Like other cannabinoids, THCV has biphasic effects, meaning it has differing effects on the body at different doses and blood concentration levels. At low doses, THCV is a neutral antagonist of the CB1 receptor, binding to the receptor without causing any effects; however, at this low dose, it blocks other compounds (like THC) from binding to the receptor. THCV is also a CB2 agonist, binding to this receptor — which is mostly located in the immune system and gut — giving anti-inflammatory and analgesic effects.

Research shows at higher doses, THCV has the opposite effect at the CB1 receptor, binding to it and activating it, which expectedly should cause some psychoactivity. Interestingly, participants in a study who received THCV were unable to distinguish it from a placebo as they felt no intoxicating effects. In the same study, the subjects reported that when they were given both THC and THCV together, the effects of THC were weaker or less intense.

THCV is being investigated as an “anti-obesity and anti-type-2-diabetes” agent as it improved glucose intolerance and increased insulin sensitivity in obese mice. Additionally, the cannabinoid was shown to be a neuroprotective agent and relieved symptoms in an animal model of Parkinson’s disease.

Another animal study demonstrated that THCV may have potent anti-nausea effects.

Anecdotally, patients who have tried THCV-rich strains report appetite suppression, less anxiety, fewer tremors, and pain relief. These strains are often recommended to those suffering PTSD who want help decreasing anxiety without becoming intoxicated.

THCV is a secondary cannabinoid (THC and CBD being the primary cannabinoids) and most cannabis plants contain very small amounts. However, there are a number of strains that have, on analytical testing, shown to contain physiologically significant levels of THCV. These strains include Black Beauty, Doug’s Varin, Durbin Poison, and Malawi Gold.

Sources:
Englund, Amir, et al. “The effect of five day dosing with THCV on THC-induced cognitive, psychological and physiological effects in healthy male human volunteers: A placebo-controlled, double-blind, crossover pilot trial.” Journal of Psychopharmacology 30.2 (2016): 140-151.

Garcia, C., et al. “Symptom‐relieving and neuroprotective effects of the phytocannabinoid Δ9‐THCV in animal models of Parkinson’s disease.” British journal of pharmacology 163.7 (2011): 1495-1506.

Pertwee, Roger Guy, et al. “The psychoactive plant cannabinoid, Δ9‐tetrahydrocannabinol, is antagonized by Δ8‐and Δ9‐tetrahydrocannabivarin in mice in vivo.” British journal of pharmacology 150.5 (2007): 586-594.

Rock, Erin M., et al. “Evaluation of the potential of the phytocannabinoids, cannabidivarin (CBDV) and Δ9‐tetrahydrocannabivarin (THCV), to produce CB1 receptor inverse agonism symptoms of nausea in rats.” British journal of pharmacology 170.3 (2013): 671-678.

Wargent, E. T., et al. “The cannabinoid Δ9-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity.” Nutrition & diabetes 3.5 (2013): e68.
 
This line sums it up, "If THC alone were responsible for the benefits of cannabis, then Marinol (a synthesized version of THC that has been FDA approved since 1985) would have replaced pot. It hasn’t."

THC Is Not What You Think It Is

“Which one has the highest THC content,” is a question often heard by the ears of budtenders, suggesting that anything with a lower count isn’t worth their dollar. But that couldn’t be further from the truth.

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THC on its own is a crummy drug—people are generally not going to like it. It’s quite disorienting and it produces pretty severe short-term memory loss,” said Dr. Ethan Russo, a board-certified neurologist who lives on Vashon Island and has studied cannabis for decades.

If THC alone were responsible for the benefits of cannabis, then Marinol (a synthesized version of THC that has been FDA approved since 1985) would have replaced pot. It hasn’t. THC alone is not an effective medicine, and there’s reproducible science that shows the entire cannabis plant is more effective than any single compound derived from it.

Understanding THC’s limitations has implications for recreational users as well as medical users. Great cannabis is great not because of its THC potency but due to the right ratios of everything else other than THC.

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Those other compounds are known as cannabinoids and terpenes. Cannabinoids (of which THC is one) interact with the human brain’s endocannabinoid system. Terpenes are aromatic essential oils created by all plants, and cannabis has hundreds of them. If getting high was driving a car, then THC is the fuel and these other chemicals are the car. You need fuel to get anywhere, but the rest of the car’s complicated machinery determines how fast you go and how the ride feels.

Scientists know that the ratios of cannabinoids and terpenes have profound psychoactive effects, but there is still much to learn about the specifics, according to Jeffrey Raber, who has a PhD in chemistry and owns Bellevue’s Werc cannabis testing lab.

“Why do all the other things work? And which ones work? I think we’ve only just realized we should look at more than one thing at a time,” Raber said. “We’re not seeing any shortage of marketing claims, but I haven’t seen any definitive double-blind studies. There are so many ways that cannabis can interact, and there are so many variables going on.”

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Russo is one of the scientists investigating the specifics of terpenes in cannabis. He published a paper in the British Journal of Pharmacology that claims specific terpenes are responsible for much of the therapeutic effects of cannabis. For example, limonene, a terpene that smells like citrus, can be an antidepressant; linalool, which has a lavendar smell, can fight anxiety. And alpha-pinene, which smells like pine trees, can actually increase short-term memory.

Cannabis breeders haven’t waited for scientific consensus on terpenes—they’ve been breeding strains for specific terpene ratios for decades, giving us strains like Lemon Haze, which is chock full of that uplifting limonene, or White Widow, which is filled with a high ratio of sedating myrcene.

Raber recommends using a trial-and- error process with different strains to find the right cannabis for your needs, but it’s important to remember there is no regulation on cannabis strains. When a grower sells their OG Kush to a retailer, they do not have to prove that their OG Kush is the same strain as another grower’s OG Kush.

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If we can’t trust strain names, at least we can turn to the paradigm of indica versus sativa, right? Indica relaxes and sativa uplifts? Wrong. Indica and sativa may have been distinct centuries ago, but there’s now no discernable distinction between the two.

“Even if they were two separate groups at one point, they’re all mixed up now. There’s so much hybridization,” said Mowgli Holmes, chief scientific officer for Phylos Bioscience, a Portland-based cannabis research firm.

It’s not always about the concentration of the psychoactive ingredients in the flower. It is the combination of the terpenes and cannabinoids that provide that effect. So if people are looking for something, they don’t need to go for that super high-potency strain. Yes, it may work for them, but there are other options that may or may not.
 
I'd like to see a study documenting terpene production vrs growing methods. My homegrown organic herb always seems stinkier and more flavorful than locally grown non organic. I don't think that's an accident.

My theory is my practice of adding sulfur helps. If you look at the molecules sulfur is close to terpenes in structure. I dont know how sulfur turns into terpenes, but i see anadotal evidence. So I add gypsum (calcium sulfate) early in flower and neem meal (high in sulfur) . Too much sulfur can kill a plant but plants do need small amounts.

I think good compost helps in terpene production as well. Study after study shows compost helps a plants defense and general well being. And one of a plants insect defenses is terpenes, another is trichomes. Win win for compost.

Another thing that may help with terpenes is enzymes. They help make elements more available for plants to take up. In organic growing elements must be broken down (by microbes) to be available for plant uptake, unlike soluble (chem) nutrients that a plant can't help but take up.

For enzymes I use malted barley that is also used for making beer. The beer heads know exactly when to sprout barley and when to stop sprouting for max enzyme production. Turns out our plants love beer, lol. At least the ingredients for beer. I havn't tried adding hops to my plants but.......

Along with enzymes each barley seed has enough energy to power (carbs in starch form) a barley plant for at least 3 weeks. So in effect it's a tonic and a food source that can turn around sick or slow growing plants, and fuel healthy plants.

And finally healthy plants are stronger, and stronger plants have more terpenes.
 
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Some interesting stuff about consuming raw cannabis.....

The World of Cannabinoid Acids Like THCa and CBDa Will Make You Re-Think Cannabis

You’re likely familiar with THC and CBD but how about THC-acid or CBD-acid?

You may also see them referred to as THCA and CBDA for short…

But what are they?

These are examples of cannabinoid acids – the acidic form of cannabinoids in cannabis.

Essentially, they are precursor molecules to THC and CBD found in raw or unheated forms of cannabis.

They do not produce psychoactive effects.

However, cannabinoid acids do offer a number of health benefits and promising medicinal qualities -- which we outline for you in this article.

So what’s the real story here?

Cannabinoid Acids Are Found In Raw Cannabis
Here are the essential facts:

In the plant’s raw state, only cannabinoid acids are present.

It is only with heat or time that THCA and CBDA convert to THC and CBD, respectively.

This transformation process is known as decarboxylation.

If you want to get technical about it:

When cannabis is heated, the “carboxyl group” detaches, aka it decarboxylates. This causes the cannabinoids to become active.

In simple terms, heat is what makes cannabinoid acids lose their ‘A’ and become the compounds we’re more familiar with like THC and CBD.

In other words, if you consume raw, unheated cannabis you won’t notice any psychoactivity – however you will be getting important medicinal effects unique to these cannabinoid acids.

THCA and CBDA though are not the only cannabinoid acids produced by cannabis.

There are, in fact several, including:

  • CBGA (Cannabigerolic acid)
  • CBCA (Cannabichromenenic acid)
  • CBGVA (Cannabigerovarinic acid)
  • THCVA (Tetrahydrocanabivarinic acid)
  • CBCVA (Cannabichromevarinic acid)
  • CBDVA (Cannabidivarinic acid)
Each cannabinoid acid offers distinct properties and benefits.

Let’s talk about that…

CBGA (Cannabigerolic acid) is the mother of all cannabinoids.
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International researchers are discovering new things about cannabis almost every day.
Here’s the scoop:

CBGA is considered to be a primary cannabinoid.

This is because it’s a precursor to cannabinoid acids like CBCA, THCA, and CBDA.

Synthases, natural enzymes in cannabis, break down CBGA into different types of compounds such as tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), and cannabichromenic acid (CBCA).

While not nearly as popular as its successors, CBGA does provide medical benefits.

It is primarily known for providing pain relief along with being antibacterial.

Some research even suggests CBGA displays antiproliferative, or cancer-fighting properties.

THCA (Tetrahydrocannabinolic Acid) has extremely underrated medicinal properties.
This is a big one:

THCA, like all cannabinoid acids, has no psychoactive effects.

Yet it does contain a number of astonishing benefits.

Studies indicate THCA displays anti-inflammatory, anti-emetic, and neuroprotective properties.

In fact, while the research is limited, THCA has shown to helpful in treating insomnia and encouraging appetite.

The diverse properties of THCA could potentially treat a wide range of conditions.

Of course, more research needs to be done to fully confirm THCA’s medical efficacy. Nevertheless, the current research appears promising.

CBDA (Cannabidiolic acid) could fight certain cancers.
Acids_In_Article_image_3.jpg

Different cannabis varieties have different levels of cannabinoid acids.
CBDA is the precursor to cannabidiol or CBD.

While few studies have taken place, CBDA has shown potential therapeutic value in treating certain cancers.

A recent study revealed CBDA inhibits the development of aggressive breast cancer cells.

CBDA has also demonstrated anti-inflammatory, antioxidant, and anti-nausea properties.

CBDA is most abundant in high CBD strains like Harlequin, Pennywise, ACDC, Cannatonic, Charlotte’s Web, and Critical Mass.

CBCA (Cannabichromenenic acid) shows promise, but…
CBCA is the predecessor to CBC.

And here’s the thing:

Currently, our knowledge of CBCA is limited.

The research we do have indicates CBCA possesses antifungal and anti-bacterial properties.

In fact, a 1981 study showed CBCA displayed strong antibacterial qualities and mild to moderate anti-fungal activity.

Some believe that like THCA and CBDA, CBCA is also anti-inflammatory.

However, more research is needed to confirm the validity of this claim.

CBGVA (Cannabigerovarinic acid) for leukemia treatment?
CBGVA is a naturally occurring compound found in cannabis.

Like CBGA, CBVA is a building block for other cannabinoids.

Through a process of biosynthesis, CBGVA produces tetrahydrocannabivarin carboxylic acid (THCVA), cannabidivarinic acid (CBDVA), and cannabichromevarinic acid (CBCVA).

Currently, the research on CBGVA is minimal at best.

However, a study published in the International Journal of Cancer Research and Treatment examined the effects of cannabinoids on leukemia cells.

Why is this study important?

Six different cannabinoids, including CBGVA were tested.

The study revealed cannabinoids had a positive effect in treating leukemia cells.

How to Consume Cannabinoid Acids?
To reap the benefits of cannabinoid acids you will need to consume cannabis in its raw form.

According to Dr. William Courtney – a leading expert on raw cannabis – juicing is an effective way to incorporate cannabinoid acids into your diet.

acids_In_Article_image_2.jpg

Juicing cannabis could be your ticket to great health!
Courtney suggests that juicing raw cannabis supplies the body with a nutritional dose of cannabinoid acids and terpenes.

He advocates these compounds in cannabis are essential to our health.

So, how the heck do you juice cannabis?
To juice cannabis, you will need to source fresh, clean cannabis leaves.

Ideally, you want to find as fresh of leaves as possible. Fresh cannabis leaves contain the highest concentrations of cannabinoid acids.

Before consuming, thoroughly cleanse the leaves.

Cannabis leaves can contain unwanted microbes, so you’ll want to soak and wash the leaves to avoid contamination.

Keep in mind the flavor of raw cannabis is fairly bitter. You can add vegetables or fruits to offset the flavor.

Here are a few cannabis juicing recipes to get you started.

It’s important to note that while juicing raw cannabis is the most popular method, it’s not the only way to consume cannabinoid acids.

You can also make raw cannabis salads, popsicles, salsas, and more!

THCa and CBDa tinctures are also slowly finding their way to the marketplace. However, they can be difficult to find.

What’s Next for Cannabinoid Acids?
We still have a long way to go when it comes to our understanding of cannabinoid acids.

The research we have up until this point has been primarily anecdotal. While a few studies exist, they are few and far in between.

Certainly, we are not at a point where we can claim the medical efficacy of these claims as absolute truth.

Yet, patient testimonials and research show us the potential here is huge! In fact, we may find that cannabinoid acids are key to supporting our optimal health.


 
Some interesting stuff about consuming raw cannabis.....

The World of Cannabinoid Acids Like THCa and CBDa Will Make You Re-Think Cannabis

You’re likely familiar with THC and CBD but how about THC-acid or CBD-acid?

You may also see them referred to as THCA and CBDA for short…

But what are they?

These are examples of cannabinoid acids – the acidic form of cannabinoids in cannabis.

Essentially, they are precursor molecules to THC and CBD found in raw or unheated forms of cannabis.

They do not produce psychoactive effects.

However, cannabinoid acids do offer a number of health benefits and promising medicinal qualities -- which we outline for you in this article.

So what’s the real story here?

Cannabinoid Acids Are Found In Raw Cannabis
Here are the essential facts:

In the plant’s raw state, only cannabinoid acids are present.

It is only with heat or time that THCA and CBDA convert to THC and CBD, respectively.

This transformation process is known as decarboxylation.

If you want to get technical about it:

When cannabis is heated, the “carboxyl group” detaches, aka it decarboxylates. This causes the cannabinoids to become active.

In simple terms, heat is what makes cannabinoid acids lose their ‘A’ and become the compounds we’re more familiar with like THC and CBD.

In other words, if you consume raw, unheated cannabis you won’t notice any psychoactivity – however you will be getting important medicinal effects unique to these cannabinoid acids.

THCA and CBDA though are not the only cannabinoid acids produced by cannabis.

There are, in fact several, including:

  • CBGA (Cannabigerolic acid)
  • CBCA (Cannabichromenenic acid)
  • CBGVA (Cannabigerovarinic acid)
  • THCVA (Tetrahydrocanabivarinic acid)
  • CBCVA (Cannabichromevarinic acid)
  • CBDVA (Cannabidivarinic acid)
Each cannabinoid acid offers distinct properties and benefits.

Let’s talk about that…

CBGA (Cannabigerolic acid) is the mother of all cannabinoids.
Acids_In_Article_image_4.jpg

International researchers are discovering new things about cannabis almost every day.
Here’s the scoop:

CBGA is considered to be a primary cannabinoid.

This is because it’s a precursor to cannabinoid acids like CBCA, THCA, and CBDA.

Synthases, natural enzymes in cannabis, break down CBGA into different types of compounds such as tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), and cannabichromenic acid (CBCA).

While not nearly as popular as its successors, CBGA does provide medical benefits.

It is primarily known for providing pain relief along with being antibacterial.

Some research even suggests CBGA displays antiproliferative, or cancer-fighting properties.

THCA (Tetrahydrocannabinolic Acid) has extremely underrated medicinal properties.
This is a big one:

THCA, like all cannabinoid acids, has no psychoactive effects.

Yet it does contain a number of astonishing benefits.

Studies indicate THCA displays anti-inflammatory, anti-emetic, and neuroprotective properties.

In fact, while the research is limited, THCA has shown to helpful in treating insomnia and encouraging appetite.

The diverse properties of THCA could potentially treat a wide range of conditions.

Of course, more research needs to be done to fully confirm THCA’s medical efficacy. Nevertheless, the current research appears promising.

CBDA (Cannabidiolic acid) could fight certain cancers.
Acids_In_Article_image_3.jpg

Different cannabis varieties have different levels of cannabinoid acids.
CBDA is the precursor to cannabidiol or CBD.

While few studies have taken place, CBDA has shown potential therapeutic value in treating certain cancers.

A recent study revealed CBDA inhibits the development of aggressive breast cancer cells.

CBDA has also demonstrated anti-inflammatory, antioxidant, and anti-nausea properties.

CBDA is most abundant in high CBD strains like Harlequin, Pennywise, ACDC, Cannatonic, Charlotte’s Web, and Critical Mass.

CBCA (Cannabichromenenic acid) shows promise, but…
CBCA is the predecessor to CBC.

And here’s the thing:

Currently, our knowledge of CBCA is limited.

The research we do have indicates CBCA possesses antifungal and anti-bacterial properties.

In fact, a 1981 study showed CBCA displayed strong antibacterial qualities and mild to moderate anti-fungal activity.

Some believe that like THCA and CBDA, CBCA is also anti-inflammatory.

However, more research is needed to confirm the validity of this claim.

CBGVA (Cannabigerovarinic acid) for leukemia treatment?
CBGVA is a naturally occurring compound found in cannabis.

Like CBGA, CBVA is a building block for other cannabinoids.

Through a process of biosynthesis, CBGVA produces tetrahydrocannabivarin carboxylic acid (THCVA), cannabidivarinic acid (CBDVA), and cannabichromevarinic acid (CBCVA).

Currently, the research on CBGVA is minimal at best.

However, a study published in the International Journal of Cancer Research and Treatment examined the effects of cannabinoids on leukemia cells.

Why is this study important?

Six different cannabinoids, including CBGVA were tested.

The study revealed cannabinoids had a positive effect in treating leukemia cells.

How to Consume Cannabinoid Acids?
To reap the benefits of cannabinoid acids you will need to consume cannabis in its raw form.

According to Dr. William Courtney – a leading expert on raw cannabis – juicing is an effective way to incorporate cannabinoid acids into your diet.

acids_In_Article_image_2.jpg

Juicing cannabis could be your ticket to great health!
Courtney suggests that juicing raw cannabis supplies the body with a nutritional dose of cannabinoid acids and terpenes.

He advocates these compounds in cannabis are essential to our health.

So, how the heck do you juice cannabis?
To juice cannabis, you will need to source fresh, clean cannabis leaves.

Ideally, you want to find as fresh of leaves as possible. Fresh cannabis leaves contain the highest concentrations of cannabinoid acids.

Before consuming, thoroughly cleanse the leaves.

Cannabis leaves can contain unwanted microbes, so you’ll want to soak and wash the leaves to avoid contamination.

Keep in mind the flavor of raw cannabis is fairly bitter. You can add vegetables or fruits to offset the flavor.

Here are a few cannabis juicing recipes to get you started.

It’s important to note that while juicing raw cannabis is the most popular method, it’s not the only way to consume cannabinoid acids.

You can also make raw cannabis salads, popsicles, salsas, and more!

THCa and CBDa tinctures are also slowly finding their way to the marketplace. However, they can be difficult to find.

What’s Next for Cannabinoid Acids?
We still have a long way to go when it comes to our understanding of cannabinoid acids.

The research we have up until this point has been primarily anecdotal. While a few studies exist, they are few and far in between.

Certainly, we are not at a point where we can claim the medical efficacy of these claims as absolute truth.

Yet, patient testimonials and research show us the potential here is huge! In fact, we may find that cannabinoid acids are key to supporting our optimal health.


@momofthegoons, thanks for posting these articles!

As I was reading the articles I was thinking, "Okay, but how, and how much". One question was answered. I think one thing that is unscientific is in what amounts can we ingest without ill effects.
I've been juicing for a very long time. 25 years or more. I started when I was a teenager. The downside of juicing is there can be a lot of waste. I started using 'the waste' in salads, some baking and composting.
Can positive effects be had from using leaves, stems, or just flower? If I drop a bud in a cup and pour in boiling water does that decarb the herb?
Hmm. Great thoughts for the day for the day while I'm at work.
 
As I was reading the articles I was thinking, "Okay, but how, and how much". One question was answered. I think one thing that is unscientific is in what amounts can we ingest without ill effects.
This is a good point. And it's all about dosage. What is the correct dosage medicinally?

Here's the thing.... the amount it takes for one person to feel effects might be different from another. The other person might need much more. So dosage is a very personal thing. And if a person is using cannabis for a disease, theory is that they use with a very high dosage; rather than the person who is maintaining their pain, etc.
 
This is a good point. And it's all about dosage. What is the correct dosage medicinally?

Here's the thing.... the amount it takes for one person to feel effects might be different from another. The other person might need much more. So dosage is a very personal thing. And if a person is using cannabis for a disease, theory is that they use with a very high dosage; rather than the person who is maintaining their pain, etc.

If its working you most likely won't feel anything, just less pain and or inflammation. Hard to quantify a negative.

I've juiced plants with my wife's somewhat antique juicer. Made a real mess, and even though it was a vegging plant, it made everything sticky. (the plant was not sprayed with anything) The juice didn't taste terrible, I added a little honey. I kind of felt energetic, but that's about it., and because of the mess I never repeated.

I've been making cannacaps using rosin. Rosin that I squeezed at 190F, and then mixing with coconut oil that I melted powdered lecithin in. I keep the mix on a coffee warmer just long enough to mix everything well. I've used rosin of gorilla glue, Jesus OG, super silver haze, blue dream, and I ussually always include some cannatonic unless otherwise specified.

I havn't tested the caps, but I doubt it's all cannabinoids in the A form, cause I do catch a slight buzz. It's hard to say the effects though, because I've been vaping a lot lately due to medical issues. I know they didn't hurt, lol. And I do think the few times I just took one and not vaping I believe they controled my pain fairly well, and I didn't seem to get crampy like I would otherwise.

They're simular in effect to the regualr cannatonic caps I make with rso and winterize in that you really don't feel much, but when you think back you had less pain doing things that normally would cause pain. Cannatonic mixed with most anything makes the effects more uplifting IMHO, plus it makes me more energetic.
 

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