Cannabis topicals and your pet

With medical cannabis research unveiling exciting solutions for so many human health conditions, it’s not a stretch to imagine similar benefits could apply to an ailing pet.

In fact, cannabis therapy actually does appear positive for animals, according to Dr. Sarah Silcox, an Ajax, ON-based veterinarian and president of the Canadian Association of Veterinary Cannabinoid Medicine (CAVCM).

The problem is, prescribing cannabis for pets isn’t legal in Canada (yet).

“While many veterinarians are supportive of using cannabis as part of the total treatment plan, many people don’t realize that legally, veterinarians cannot authorize (prescribe) medical cannabis. And this puts them in a very difficult spot,” says Silcox.

Surprised? Well, dogs just aren’t the litigious type: legal pressure by human patients put the original medical cannabis regulations into effect. Then, when the Cannabis Act came along, Silcox explains existing medical regulations were simply rolled into the new cannabis regulations, “without consideration of our animal friends.” To date, there is no legal framework for animal care providers until the Cannabis Act is reviewed again in 2022.

While vets cannot prescribe cannabis, many are open to advising on treatment options you could independently provide for your pet. Just don’t play Doc McStuffins on your own: Silcox warns administering cannabis without some guidance can pose serious adverse effects and potential drug interactions–even pure CBD.

Here, she plays out a few scenarios:

Not really. “The biggest concern surrounds the risk of your pet licking the cream off,” she explains. Not only will fur likely get in the way (wasting your product), when your pet licks or grooms the area they risk ingesting something meant to be used externally. It’s not just the THC, other cannabinoids or terpenes she worries about, but potential effects from other compounds found inside the topical. If you have a topical that you think could help your pet feel better, bring it in to your vet for advice.

Again, it’s about the side effects and possible drug interactions that pose a risk. However, this is not to say you can’t discuss CBD with your vet. While Silcox says there aren’t published studies on CBD for treating cats specifically, she says they do appear to tolerate CBD well. Talking to your vet will ensure the product you’re using is safe and that the dose is appropriate. “Your veterinarian may also want to do some testing to ensure there are no underlying physical causes to your pet’s behaviour changes,” she adds.

Maybe. Seizures, along with chronic pain, age-related changes, sleep disturbances, and cancer are the most common reasons people request cannabis therapy for their pets, according to Silcox. Again, while they can’t yet prescribe, veterinarians can discuss cannabis therapy as an option and help monitor the outcome.

“In this emerging area of medicine, documentation is important for many reasons. We want to track any unexpected effects, document your pet’s response to treatment, and learn from each case in the hopes that it will help other patients that follow.”

She says cannabis remains a viable option for treating pets, especially when other available treatments are not effective. This is why the CAVCM and the Canadian Veterinary Medical Association (CVMA) have been advocating to change current regulations.

Whether it’s a ripped dewclaw, sore joints, or something more serious, work with your vet to find the right cannabis therapy for your furry loved one. And if it’s important enough, Silcox encourages you to let your MP know you support changes to the Cannabis Act allowing veterinarians to authorize medical cannabis.

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We tried ‘CBD-infused clothes’ to see if they did anything

Strains & products

November 5, 2019

(Courtesy of Nufabrx)

I came here to talk shit, and I’m honestly sad that I won’t be able to. Because the Nufabrx CBD-infused (and capsaicin-infused) compression elbow and knee sleeves have not wronged me. In fact, using them has been a positive experience, one that may benefit others as well. *Deep sigh.*

The CBD craze has rendered many a trash product in its time (a company once sent us CBD toothpick samples and I almost went home for the day). So when the thought of CBD-infused clothing accessories came across my company-issued Gmail account, I figured we’d reached the newest level of “let’s cash in on cannabis with BS products that help no one.”

(Courtesy of Nufabrx)

The Nufabrx medicated compression and knee sleeves are suggested for the use of “temporary pain relief of minor aches and pains or muscles and joints associated with simple backache, arthritis, strains, bruises and sprains.” So to test the product, I figured ya boy needed to get active.

I woke up at 5 a.m., like I always do, and hit the gymy gym for a lil’ chest-day-plus-stairmaster-and-jump-rope action. I needed something that would apply pressure to the elbow and knee regions.

Usually, towards the end of my 30 minutes on Level 10 of the Fat Burner stairmaster circuit, my left knee feels a little sore. And because of the triceps engagement, chest day usually hurts my elbow a bit, too. (What I’m telling you is aging sucks, and I can’t wait to replace my human body with all kinds of fiber optics and beep-boop-beeps.)

Surprisingly, after a full hour and change of sweat equity, I had no pain in any region touched by my Nufabrx sleeves. In fact, my ‘bow and knee felt very loosey goosey in a way that many of the sleeves during my basketball years could not provide. But is the experience catalyzed by CBD? And what the hell is capsaicin, anyway?

Active ingredients include synthetic capsaicin, while inactive ingredients include acrylate copolymer and hemp. According to Jordan Schindler, CEO and founder of Nufabrx, the CBD is implemented into the sleeves during production of the yarn.

“We do everything at the yarn stage,” he tells me. “So that allows us to get 3-dimensional relief [from] the ingredient. Versus at the fabric [stage], you can’t control the dose, and it typically washes out very quickly. We treat base yarn, and then that’s knitted into end garments.”

Schindler goes on to tell us that there’s at least 150mg of CBD in each product, depending on the size of the product, as the CBD is implemented on a milligram-per-square-inch basis. The reason CBD/hemp is not listed as an active ingredient under Drug Facts is because it’s not considered a drug by the FDA.

“The ‘Drug Facts’ label is a requirement for a drug product,” Schindler says. “Capsaicin is a pain reliever and it falls under the monograph,” he says when asked why cannabidiol is not listed under Drug Facts.

So yeah, there was hemp extract used in production at one point, but it’s hard to say how much it’s influencing the loosey goosey-ness of my joints. Capsaicin is more likely the main pain reliever here.

According to WebMD, capsaicin is the stuff in chili peppers that makes your mouth feel hot. It’s the primary ingredient in many creams and patches meant to relieve joint pain, muscle sprains, and even migraines. This explains the tingly feeling under the sleeved areas. It also explains why the product limits use to a max of 8 hours per day, 4 days per week.

So, in the end, do “CBD-infused clothes” do anything? The truth is we don’t know, and the Nufabrx CBD and capsaicin medicated compression sleeves don’t exactly help us answer the question. Ultimately, this feels like another product being marketed with CBD, although the true nature of its effects likely derive from other chemicals. But until cannabis comes under FDA regulation, we’ll never be able to really hold companies to any true show-me-what-you’re-made-of standards.

Again, *deep sigh.*

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Suck or chew? With cannabis edibles, method matters

When it comes to edibles, there are different ways to dose, and we’re not talking about cookies versus brownies. Edible cannabis products can be consumed orally, meaning they are swallowed, or sublingually, meaning they are held under the tongue to be absorbed directly into the bloodstream.

Typically, food products containing cannabis are intended for oral dosing, while sprays, tinctures, and oils may be used sublingually or orally. Some companies are even producing purpose-built sublingual cannabis strips.

The method of delivery can affect the onset, duration, and intensity of the effects of cannabis. Sublingual dosing offers a fast onset, shorter duration, and lower intensity than traditional oral cannabis edibles, while also offering a discreet, smokeless experience.

Sublingual administration is a method of delivery for many common pharmaceuticals. One of the most well known of these is Ativan, a fast-acting benzodiazepine used to treat acute anxiety. Sublingual administration involves holding the active substance under the tongue for a certain amount of time, usually until the tablet or strip dissolves. Another related drug delivery method is buccal administration, where the active substance is held against the cheek.

The area under the tongue (and the cheeks) can absorb various active substances into the bloodstream. This is similar to inhalation methods, which allow the active compounds to enter the bloodstream through the lungs. This is why sublingual delivery is fast-acting. Importantly, the substance has to be held under the tongue–not on it–and for long enough for its active compounds to dissolve into the bloodstream.

When dosing cannabis sublingually, people usually use products intended for this route of administration, such as sprays, tinctures, oils, or sublingual strips. You could try holding a chewed up cookie under your tongue, but results may vary.

The pharmaceutical cannabinoid medicine Sativex is delivered sublingually via spray. Sprays, tinctures, and oils may also be absorbed orally if they are swallowed. Some people like to hold a product under the tongue and then swallow it for maximal effect.

Traditional cannabis edibles–foods and drinks infused with cannabinoids–are usually consumed and processed orally. This means that a person swallows the cannabinoids, which are then absorbed in the intestine and processed by the liver.

Many people report edible cannabis to be a more intense experience than inhalation. Researchers believe this is because when THC is eaten, it is converted into 11-hydroxy THC, which is “particularly effective in crossing the blood-brain barrier, resulting in a more intense high.” A 2016 review on cannabis edibles calls 11-hydroxy-THC “a potent psychoactive metabolite,” especially compared with delta-9-THC, the converted form of THC that cannabis consumers experience by smoking, vaping, or sublingual absorption.

“11-OH-THC is more potent than ?9-THC and appears in blood in higher quantities when ?9-THC is ingested than when it is inhaled; hence, it may be responsible for the stronger and longer-lasting drug effect of edibles vis-a-vis comparable doses of smoked cannabis,” the review explains.

For some, 11-hydroxy-THC offers a way to stretch the effects of cannabis without having to consume more. For others, the effects might be too intense and undesirable.

Orally-consumed edibles take a while to kick in, because they have to be digested and processed in the gastrointestinal system before entering the bloodstream. If you’ve just had a large meal, it may take even longer for the cannabinoids to begin to affect you. This might mean up to 90 minutes before an edible starts to work, and even longer before it reaches peak effect.

The effects of edibles are also known to last longer than the effects of inhalation methods, and the same is true when compared to sublingual administration.

Sublingual administration is a convenient, discreet, fast-acting, and smokeless option for both recreational and medical cannabinoid use. Sublingual administration might appeal to someone who is looking for an alternative to edibles that is less intense, shorter, and that kicks in faster.

There are, of course, some downsides to sublingual administration. Consuming cannabis sublingually means a person must purchase specialized products designed for this method of administration, like sprays, tinctures, oils, or sublingual strips. The consumer must also hold the substance under the tongue for a certain amount of time, which may be uncomfortable if they dislike its taste.

In the end, traditional oral cannabis edibles are simpler to consume. But for those who want a smokeless option while avoiding a potentially intense and long-lasting high, or those who need something fast acting, sublingual administration might tick all the boxes.

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The science on cannabis topicals for headaches

If peppermint oil rubbed onto the forehead, neck or temples can provide headache relief, couldn’t a cannabis topical go the extra mile and dissolve the pain altogether?

For now, the health community says no, mainly because we’re missing human clinical trials to say whether cannabis applied to the skin is effective at all for headaches and migraines. But that’s not to say anecdotal data has been a dead end–in fact, just the opposite. A 2017 report amassed a large body of preliminary studies, concluding that we have enough evidence to start clinical trials on cannabis headache treatments. The report even made it a point to say that “cannabis is commonly used to self-medicate for headache disorders”.

Dr. Stefan Kuprowsky, a Vancouver-based naturopathic doctor specializing in ethnomedicine and ethnopharmacology, agrees the theory of topical cannabis relief for headaches is sound, especially given cannabis’s known anti-inflammatory benefits.

“Right now, topicals are most useful for joint-type pain, muscle pain and skin rashes such as eczema, acne and psoriasis,” he says. By extension, a cannabis product could also be helpful for headaches, which are often inflammatory in nature.

But before slapping CBD oil onto your forehead, know that there’s a catch: cannabinoids are not so easily absorbed into the bloodstream through skin, and most headaches are caused by blood vessels in the brain running amok. While there are promising pre-clinical trials for transdermal patches which breach the bloodstream, it’s not known whether they can treat headache pain.

As for topical creams or ointments, Kuprowsky offers a note of caution: “It’s not the same mechanism, like for osteoarthritis, where a topical would be useful right in the areas where it hurts. Headaches are a little bit more complicated, so just putting it on where it hurts doesn’t necessarily get at the underlying problem.”

However, not all headaches are created equal. For example, tension headaches often start at the base of the skull where neck muscles tighten, sending up an inflammatory response. Kuprowsky says a cannabis topical could theoretically be helpful for the muscle tissue, which could in turn reduce headache pain.

Kuprowsky adds that a range of migraine symptoms–including pain, nausea, and sensitivity to light and sound–could be mitigated by CBD, which he says may potentially act like triptans, a commonly prescribed migraine drug. Pre-clinical studies are promising, but we need clinical trials to confirm.

Cannabis has a well-documented entourage effect, meaning the cannabinoids in the plant work synergistically with each other, and with the plant’s terpenes, flavonoids, and other botanical components. Cannabis can boost active compounds in other ingredients, too, as when mixed into an ointment or cream.

Kuprowsky suggests that a cannabis ingredient might enhance other medicinal ingredients present, so you wouldn’t feel the cannabinoids per se, but could theoretically benefit from their ability to strengthen everything else. “If you combine CBD [with other ingredients], then you may have a synergistic effect. And if the CBD isn’t helping on its own, it’s complementing the other herbs.”

But he does warn against placebo effect, which he says people in pain are very susceptible to. “Placebo effect is actually a very effective treatment for pain,” he explains. So when it comes to CBD, he cautions that the hype may be responsible for some of the enthusiastic feedback regarding its ability to mitigate pain.

For now, we wait for science to confirm whether topicals are useful for aching heads, or better served as salves for muscles and joints.

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Most THC and CBD oil goes to waste in your body–here’s why

Health

October 28, 2019

If you knew that only 6% of your CBD gummies would enter your bloodstream to do their job, would you still purchase them? Amid the current frenzy surrounding cannabis and its therapeutic benefits, it’s easy to gloss over the bioavailability of cannabis products.

Bioavailability refers to the degree and rate at which a substance is absorbed into your bloodstream to be used where needed. Physiological processes and consumption methods can affect cannabis absorption, rendering its effects somewhat hit-and-miss.

It’s critical to get clued up about bioavailability in order to maximize the medicinal potency of cannabis. The more bioavailable your cannabis, the lower the quantity of the plant you need to reap its benefits.

The surge in cannabis popularity can be partly attributed to the range of consumption methods available. Edibles and tinctures can have less of the stigma traditionally associated with joints. However, when cannabinoids such as CBD and THC are ingested in oil form–oil is also used to make edibles–their bioavailability becomes compromised.

CBD and THC oils resist absorption into the bloodstream because the human body is up to 60% water. Basic science–and salad dressing–dictates that oil and water do not mix, and the same is true for cannabis oil and the human body.

“Cannabinoids are fat-loving molecules and have to traverse a cellular environment that is aqueous or watery,” explains Dr. Patricia Frye, a member of the Society of Cannabis Clinicians and chief medical officer at Hello MD. When cannabis is consumed as an oil, the onset of effects can become delayed and bioavailability limited.

Another phenomenon that limits oil-based cannabis extracts from reaching the bloodstream is the first-pass effect. When cannabis is ingested orally, it is absorbed in the gastrointestinal tract and transported via the portal vein to the liver, where it is metabolized. As a result of this process, only a limited quantity reaches the circulatory system. Since cannabis oil is often taken orally, its efficacy can be hindered.

There has been some investigation into CBD, THC, and less into cannabinol, or CBN. Studies have shown that the bioavailability of cannabinoids depends on the method of delivery.

When applied as a topical ointment or transdermal patch, CBD can penetrate the tissue ten times more effectively than THC. The same is true of CBN.

THC, however, is more bioavailable than CBD when administered orally or delivered via the lungs. A clinical study found that concentrations of THC in the bloodstream appeared 30-50% higher than CBD following oral delivery as a sublingual spray.

However, the bioavailability of THC is still limited when consumed orally, averaging only 4-12%. When smoked or vaped, the bioavailability of THC leaps to an average of 30%.

Some of the most common and convenient cannabis products, such as capsules, soft gels, tinctures, and edibles, limit bioavailability due to the first pass through the liver. “With edibles, absorption is slow, unpredictable, and highly variable,” says Frye. “Only about 6% of the dose is absorbed. The onset of action can be as long as 6 hours; it’s very easy to take too much, and the effects can last as long as 20 hours!”

Oral administration lasts longer than smoking, eliminating the need for frequent dosing. Oral methods also avoid irritation to the airways and the risk of malignancies associated with smoking or vaping.

That said, inhaling cannabis guarantees increased bioavailability because molecules are transported by vapor particles directly to the alveoli in the lungs. This allows cannabinoids to rapidly enter the bloodstream without being metabolized by the liver.

Another lesser known method of administration is intranasal delivery, which enables cannabinoids to be easily absorbed with a rapid onset of ten minutes or less. “Intranasal methods are highly bioavailable at 34-46%,” says Frye. “It’s a particularly helpful mode of delivery for patients who are having a seizure or for patients trying to abort an impending seizure or migraine.”

Transdermal patches can be super effective at targeting localized or systemic pain. They allow for a steady infusion of active ingredients to the delivery site, so the patient is unlikely to experience spikes of THC in the bloodstream.

Finally, nano-emulsions and micro-emulsions can dramatically increase the stability and bioavailability of cannabinoids. These novel formulations use nanotechnology to offer up to 100% bioavailability. Frye cautions, however, that the research is still scarce. “We don’t know the full extent of how these manipulations affect cannabinoid activity at the cellular level,” she says.

One method that boosts the absorption of edibles is to combine cannabis product with fats. Frye recommends combining edibles or tinctures with healthy fats such as guacamole, hummus, or dark chocolate. If you’re feeling less virtuous, however, ice cream works as a treat. The same goes for alcohol-based tinctures.

For those who smoke or vape, bioavailability can be enhanced by minimizing sidestream loss and increasing the number of puffs. “Using a desktop or handheld vaporizer with flower will eliminate sidestream losses,” Frye advises. If you think you get more bang for your buck by holding your breath, think again. “There is no evidence supporting holding one’s breath for more than 10 secs,” says Frye.

Some final words of advice from Dr. Fyre, for those looking to optimize cannabis bioavailability: “The most cost-effective way to use cannabis is not to use more than you need. Less is more,” she says. Due to its biphasic nature, excessive dosing may exacerbate the symptoms you’re trying to alleviate.

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CBD: Hemp-derived, isolate, full spectrum and beyond

Cannabidiol (CBD) is a naturally-occurring ingredient in both cannabis and its cousin, hemp. In medicine, it is used to treat a variety of symptoms and conditions, from epileptic seizures to chronic pain to insomnia and anxiety.

CBD is lauded for its ability to calm inflammation without creating an intoxicating high. No wonder, then, that it’s also an increasingly buzzy ingredient in health, wellness, and beauty products.

In its simplest form CBD is a molecule, and that molecule is the same regardless of whether it’s derived from cannabis or hemp. But not all CBD extraction methods are created equal, and not all hemp or cannabis products contain CBD.

Here to sort science from marketing, and the truth from misinformation, are the factors you should consider before buying a CBD–or so-called CBD–product.

Full spectrum, broad spectrum, and isolate are common terms used to describe CBD and other cannabis products. Although they sound like marketing buzzwords, they represent real and important distinctions about the cannabinoid(s) inside.

Full-spectrum CBD

Full-spectrum products, sometimes called whole plant extracts, contain CBD as well as other ingredients extracted from the same plant matter. Full-spectrum CBD products are believed to benefit from the ‘entourage effect,’ a theory that the ingredients in cannabis work better together than in isolation.

Full-spectrum CBD products contain flavonoids and terpenes–ingredients that bring therapeutic benefits, along with scents and flavours–and may include other cannabinoids such as CBD, CBG, CBN, CBDa, THC, and THCa. Full-spectrum products are not recommended for people with THC sensitivity, as trace amounts of that cannabinoid may be present.

CBD isolate

CBD isolate is pure CBD, and is produced by removing all other compounds, including terpenes, flavonoids, and other cannabinoids. It usually comes in the form of an odourless, flavourless powder, and is often used in clinical trials.

While CBD isolate doesn’t offer the potential benefits of the entourage effect, it is attractive for its ease of use and because it carries little to no risk of intoxication. However, at the time of writing, CBD isolate was not available to consumers on the Canadian market.

Broad-spectrum CBD

Broad spectrum CBD has no traces of THC, which are removed during the extraction process. Unlike CBD isolate, broad spectrum retains other cannabinoids and terpenes, enhancing its therapeutic potential through the entourage effect, the theory that the sum of cannabis’s natural ingredients is more effective than its parts.

Cannabis and hemp are two varieties of the same plant species, cannabis sativa. Hemp-derived CBD isolate vs cannabis-derived CBD isolate is an apples-to-apples comparison, because, again, it’s the same molecule.

But things get a little more complicated when comparing full and broad spectrum CBD derived from hemp versus their counterparts derived from cannabis, says cannabis scientist, educator, and speaker Alexzander Samuelsson.

Also known as Alex The Chemist, Samuelsson says that agricultural hemp has been bred over the years to be more fibrous and contain a lower cannabinoid content. Generally speaking, cannabis contains more cannabinoids, terpenes, and flavonoids, offering more therapeutic potential than its hemp counterpart.

Full-spectrum hemp CBD will still provide benefits from the entourage effect, but will likely have a lower concentration of terpenes and flavonoids, and require more plant matter to produce the same amount of those ingredients. Other factors that can affect the potency and proportions of cannabinoids, terpenes, and flavonoids include genetic heritage, or strain, and growing conditions.

Hemp oil is a popular ingredient in the skincare industry. It is known to be anti-inflammatory, it contains super-hydrating lipids, and it can heal skin issues such as eczema, psoriasis, rashes, and acne. However, it is not the same as CBD oil.

Products labeled ‘hemp oil’ or ‘hemp seed oil’ are derived from hemp seeds, not the whole hemp plant, and therefore contain little to no CBD. This doesn’t mean that hemp oil isn’t useful, simply that it is not a CBD product, even if the packaging shows pictures of hemp leaves, or displays the term cannabis sativa, which is simply the botanical name for hemp and cannabis.

Yes, CBD is CBD no matter which side of the border you’re on, but regulations and laws vary widely between these neighbouring nations (and vary quite a bit from state to state in the US, too). At the time of writing, CBD is a regulated phytocannabinoid under the Cannabis Act, regardless of whether it’s sourced from hemp or cannabis. This means it is illegal to bring it across national borders, possess it underage, or order it from unlicensed providers.

CBD health products from the US are illegal in Canada, and it is illegal to bring Canadian CBD products into the US. It’s easy to get confused, so always be sure to check with local laws before traveling with any hemp or cannabis based products.

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Using Cannabis to Treat Cancer

Cancer doesn’t play favorites. It doesn’t care what color you are, if you’re young or old, or whether you live in a penthouse apartment or a shanty town. When the diagnosis comes, as it will for half of us in our lifetime, we pin our hopes on accessing the best treatment to maximise our chance of survival.

Almost exactly a year ago, 30-year-old George Gannon found himself facing a bleak future. Doctors had discovered more than 12 tumors in his brain. The melanoma he’d had removed three years previously had metastasized.

The aggressive nature of George’s BRAF positive melanoma meant that even with standard treatments of radiotherapy, immunotherapy, and chemotherapy, his tumors had increased in size. With a prognosis of six months and no options left on the table, cannabis seemed to be the only hope.

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George, a British cancer patient who turned to cannabis to shrink his tumors, smiles at the camera. He is standing in front of trees next to a river with a bridge in the background. He is a white man with a reddish-brown beard, blue eyes, and is wearing a rain jacket and a baseball cap.

George Gannon

George was determined to source a cannabis oil containing THC, the cannabinoid which until now has the most robust evidence for anti-tumoral effects.1 But living in the UK meant that anything other than the hemp-based CBD oils was illegal. So he turned to the black market.

George began taking his cannabis oil just before Christmas last year. By his next MRI scan in March, his tumors had stopped growing. For the next few months he resumed low doses of chemo, never once stopping his cannabinoid therapy.

The next scan in August, was a surprise to both George and his oncologist: the main mass on his left ventricle had disappeared and the other remaining lesions had decreased in size.

The oncologist – who had repeatedly told George to stop taking cannabis oil – said it was the best day of his professional career. But he wouldn’t acknowledge that cannabis may have played a part in the cancer’s reversal.

The oncologist’s reaction typified the skepticism of health professionals with respect to cannabis and cancer. Without solid evidence from clinical trials, most doctors dismiss the idea that cannabis could have antitumoral effects in patients. Which begs the question – How far away are we from getting the solid clinical evidence necessary to convince the medical profession that cannabis is a serious anticancer treatment?

Why so few clinical trials?

The only way for a drug to make it into the oncologists’ anticancer arsenal is for it to successfully pass through three phases of randomized double-blind placebo clinical trials testing safety, dosing, and efficacy.

Thirteen years have passed since the first small pilot study was conducted by Professor Manuel Guzman and his group at the Complutense University in Madrid.2 They tested the safety and antitumoral action of THC on a small group of patients with recurrent glioblastoma, an aggressive form of brain cancer – and the results were encouraging.

Project CBD spoke to Guzman to find why, more than a decade later, progress has been so slow. One answer lies in the nature of cancer itself.

“Cancer is a very complex disease,” says Guzman. “There are at least 150 different types of cancer from a histological point of view and there are hundreds if not thousands from a molecular or genetic profile standpoint. So when we speak about cannabis or any treatment for cancer, first you should define what type of cancer we are dealing with because it’s really unlikely that a unique substance or a mixture of related substances, as is the case in cannabis, will be effective in all types of cancer.

To this date, all cannabis-based clinical trials have focused on patients with glioblastoma. GW Pharmaceuticals followed up Guzman’s pilot study with a yet unpublished phase I/II trial using Sativex, a 1:1 THC:CBD sublingual tincture, alongside temozolomide, the standard chemotherapy treatment for glioblastoma.

According to a 2017 GW Pharma press release, administering a combination of Sativex and temozolomide increased one year survival rate by 30% and increased the median survival to 550 days from 369 days with temozolomide alone.3

“[The GW study] is the first and so far the only trial that has been conducted on cannabinoids and cancer that is more robust, that it is controlled by placebo, and is randomized,” says Guzman. “It’s also a double-blind trial in which neither the patient nor the doctor knows whether the patient is taking Sativex or the placebo.

“That trial was also promising. It has enhanced our optimism that maybe cannabinoid drugs can have an anti-tumour effect, at least in glioblastoma and at least in the relapsing phase. But we have very little clinical information only for one specific type of cancer. I hope that other cancers will be treated with cannabinoids in the frame of a controlled clinical trial. But to date we have nothing.”

Two further phase II glioblastoma clinical studies are also about to commence. This time, Guzman’s group will be assessing whether a 1:1 THC:CBD ratio combined with conventional cancer treatment is effective as a first line treatment rather than a relapsing state.4 And an Australian study (5) investigating tolerability of different cannabinoid combinations alongside chemo, radiotherapy or immunotherapy is also currently recruiting.5

Slow progress – pharma’s role

As exciting as these initial clinical findings might seem, progress is still painfully slow considering how long scientists like Guzman have been researching the antitumoral potential the cannabis plant holds. It seems like the odds are stacked against a cannabis-based anticancer drug ever making it to market.

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Dr. Manuel Guzman sits in his lab and smiles at the camera. He is wearing a thick cotton hoodie and jeans.

Dr. Manuel Guzman in his lab.

Guzman: “Doing clinical research with cannabinoids is very complicated because THC, which to me is the main active ingredient in cannabis, is controlled by the United Nations and is a schedule 1 drug. So, it is subjected to very strong restrictions in the production, manufacturing and exporting, etc. That means many clinicians and investors get frightened. They don’t want to get into so much bureaucracy and they prefer to go for substances that are not classified as schedule 1. In general, my experience is that the bar that is set for cannabinoid clinical trials is higher than for other substances.

Dr. Guzman suggests the notable absence of pharmaceutical companies in cannabis-based drug development may also be holding up progress.

“Clinical trials are very much controlled by Big Pharma companies who have the financial means and resources. Philosophically speaking, I’m against the protection of the drug, but on the other hand, the pharma companies are not going to make any movement in any field unless they have the possibility to protect, to patent their products or the indications of their products. So that makes cannabis research more complicated because cannabinoids are natural products and can be extracted from the plant by anyone.”

One way to navigate the intellectual property quagmire is to concentrate on rare conditions with an ‘orphan’ status. Developing a drug for orphan diseases can be an easier route to gaining FDA marketing approval and enjoys various incentives such as tax breaks. Orphan status also allows for usually unpatentable substances such as isolated cannabinoids to be awarded exclusivity – and is likely the reason why the likes of GW Pharmaceuticals are concentrating on rare cancers like glioblastoma.

Another avenue is to patent specific cannabinoid combinations and ratios. This is another speciality of GW Pharma.

Guzman: “Basically the whole cannabis field is mined with GW patents. So, whenever a new company starts to get interested in the field and they make a first overview of how the patent situation is, many times they leave because they realize that everything is basically controlled by GW Pharma. They have been very intelligent in that respect and they are basically the owners of all the intellectual property rights, all active rights and future rights in this field. So that also scares companies.”

‘Common sense’ approach for cancer patients taking cannabis

Strategic decisions made in drug company boardrooms stalling the development of cannabinoid-based anticancer drugs means patients like George Gannon have little alternative but to figure out how to source their own cannabis oil, with all the difficulties that entails. Given the life-or-death stakes involved, Guzman does not begrudge someone’s decision to use cannabis oil for cancer. But he feels that a patient’s decision should be guided by common sense.

“First try to get a standardized preparation,’ Guzman says. “One has to know at least how much THC and CBD is present in the preparation, not ‘I’m just taking cannabis.’ There are a million types of cannabis. So try to get to know how much THC, CBD and other well-known active ingredients are present.

“And if you are using cannabis oil as a treatment, know at least that the oil has been produced with good agricultural practices and is not contaminated by different types of toxic substances: organic solvent residues, pesticides, heavy metals, mould etc.”

“I would include a regime of administration starting from very little, increasing over 3 or 4 weeks, until one gets a standard dose that is well tolerated and at least overtly efficient. Second, I would combine THC and CBD, starting with more CBD and then including THC to get it to a final balanced preparation. I can’t say exactly what is a balanced. Usually you can go for a ratio of say 1:5 ratio of THC:CBD.

“Third, as cannabinoids accumulate in the body because they are very lipophilic, in theory, receptors can desensitize and lose response. So, I’m in favor of including some ‘wash out’ periods from time to time when at least THC is taken out. I would say for instance 3 weeks of cannabis plus 4 or 5 days of wash-out, so there is time for CB1 [cannabinoid] receptors to get re-sensitized.”

Patients must share responsibility for normalizing cannabis

Many patients feel uncomfortable when faced with the question of whether or not to tell their oncologist about taking cannabis during cancer treatment. For Guzman, informing the medical team in charge of care is not only a matter of safety, but a major way of increasing awareness about cannabis within the medical profession itself.

“I think patients are very important, he says. “They are key players in this effort, and they have to push for cannabis to get into mainstream medicine. And one of the ways is simply by normalizing its use by patients. And yes, it’s likely that in some instances the physician is going to react negatively. But we have to try.

“Before I retire,” Guzman continues, “I’d like to know that using cannabis as a cancer treatment has been successful. But at the moment we don’t know. There are some preclinical signals, and also some very tiny clinical signals supporting that there may be an anticancer effect of cannabinoids.

“We have to improve that. And the evidence must come from different sites. Not only controlled clinical studies, but also observational studies, case studies that are reported by doctors about individual patients, and also the active role that I believe patients must play. They have to push. They have to speak about it. We are many different actors, and altogether we have to work hand in hand, otherwise it’s going to be almost impossible.”

Footnotes


Mary Biles is a journalist, blogger and educator with a background in holistic health. Based between the UK and Spain, she is committed to accurately reporting advances in medical cannabis research.


Copyright, Project CBD. May not be reprinted without permission.


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Cannabinoids for Scleroderma

When you cut yourself and start to heal, your body forms a matrix of tissue largely composed of collagen. It’s the basis of the scar tissue that forms where the cut was. For people with scleroderma, a rare auto-immune disease, their tissues continue developing even without an injury, resulting in the overproduction of collagen and other fibrous tissues, called fibroblasts, in the skin and internal organs.

People with scleroderma often experience pain and inflammation. As is the case with many autoimmune diseases, there aren’t any therapies that have been specifically developed to treat this condition. The scarcity of treatment options makes scleroderma an “orphan disease” – a special classification that the Food and Drug Administration (FDA) uses to incentivize drug-makers to develop new and innovative “orphan drugs” for the treatment of rare diseases.

Two compounds that target the endocannabinoid systeminfo-icon are currently in development to treat scleroderma – and they’re already in clinical trials. Scleroderma patients are hoping that these efforts will prove to be as successful as Epidiolex, the cannabisinfo-icon-derived CBD pharmaceutical approved by the FDA in 2018 as an orphan drug for two forms of severe pediatric epilepsy (Lennox-Gastaut Syndrome and Dravet Syndrome).

What is scleroderma?

Degenerative autoimmune diseases are often poorly understood, and such is the case with scleroderma. Medical scientists don’t really know what causes it, or how to treat it. It’s theorized that both genetics and environmental factors can play a role in its development.

The earliest symptoms of scleroderma usually involve a thickening of the skin and a condition known as Reynaud’s phenomenon, which constricts the arteries and turns the fingers blue when they’re exposed to cold.

There are two primary types of scleroderma – localized scleroderma (morphea), which affects specific areas of the skin; and systemic scleroderma, a potentially fatal condition characterized by the thickening of tissues around organs. Systemic scleroderma can lead to excess collagen and scar tissue in the lungs (interstitial lung disease), resulting in the constriction and blockage of pulmonary arteries (pulmonary artery hypertension).1

The endocannabinoid system and scleroderma

Scleroderma usually appears at first as an abnormal skin condition. Skin diseases typically involve a dysregulation of the endocannabinoid system (ECS). This is true for scleroderma, as well as for more common maladies like acne and psoriasis.

Comprised of endogenous compounds that bind to cannabinoidinfo-icon receptors – CB1 and CB2 – that are expressed in all types of skin cells, the ECS plays a vital role in maintaining skin homeostasis through a signaling mechanism that promotes healthy skin renewal and barrier function.2

There are several reasons why the endocannabinoid system might present a good target for scleroderma drugs. Both cannabinoid receptors subtypes are overexpressed in scleroderma fibroblasts,3 as is the endogenous cannabinoid 2-AG.4

Additionally, the expression of FAAH, the metabolic enzyme that breaks down the endocannabinoid anandamideinfo-icon, is abnormally low in the skin of scleroderma patients. This indicates that something is fundamentally out of whack with the endocannabinoid system.5

THC and fibrosis

In petri dishes and rodents, CB1 and CB2 receptors appear to play opposing roles in disease models of scleroderma. Activation of CB1 receptors actually promotes the growth of excess connective tissue.6CB2receptorinfo-icon activation, on the other hand, seems to limit that same growth. CB1 signaling in peripheral organs has a profibrotic effect (and also promotes wound healing); CB2 signaling has an antifibrotic (and blood-thinning) effect. A well-functioning endocannabinoid system maintains a balance between the pro and antifibrotic properties of CB1 and CB2.

Tetrahydrocannabinolinfo-icon (THC), the principal intoxicating component of cannabis, conveys therapeutic benefits by activating both cannabinoid receptor subtypes. When THC binds to CB1 receptors in the brain and central nervous system, it makes a person feel high and hungry, among many other effects. When THC binds to CB2 receptors on immune cells and in the peripheral nervous system, it eases pain and inflammation. THC can induce profibrogenic or antifibrogenic effects in the liver, where both cannabinoid receptor subtypes are present. So, too, in the skin.

WIN55,212, a synthetic cannabinoid compound that activates both CB1 and CB2, is commonly used instead of THC in experiments. Some scientists decided to see what WIN55 would do in a rodent model of scleroderma. They found that rodents treated with this synthetic cannabinoid developed less excess collagen and generally fared better compared to untreated animals.7

Would other compounds – such as THC – that bind to both cannabinoid receptors confer similar effects? Or would THC accentuate problematic tissue growth by activating CB1 receptors? Unfortunately, in the United States clinical trials involving THC have gotten short shrift because of marijuana prohibition, resulting in a paucity of data pertaining to scleroderma and many other conditions that might respond to cannabis-based therapies.

A single case study from Israel indicates that smoking cannabis helped to alleviate inflammatory pain and improve the quality of life of one young scleroderma patient.8 The condition of this cannabis smoker remained stable throughout observation, suggesting that consumption of THC at the very least didn’t have a harmful impact on his disease. But a chemical analysis was not performed on his stash, so we have no way of knowing the content of what he was actually consuming.

Clinical trials for cannabinoids

Given that CB1 receptor activation in preclinical research has been shown to promote excess tissue and collagen formation whereas CB2 receptor activation has the opposite effect, pharmaceutical researchers have their sights set on developing a drug that bypasses CB1 while boosting CB2. Referred to as a “selective CB2agonistinfo-icon,” such a compound would appear to have potential as a treatment for scleroderma.

What’s more, CB2 receptors are localized primarily outside the brain and therefore are not responsible for mediating THC-induced intoxication. A drug that selectively targets CB2 receptors would not cause any of the psychoactive side effects associated with CB1 activation – and that’s a big plus in terms of getting FDA approval.

Incentivized by the potential of developing an orphan drug for scleroderma, a couple of companies are betting on selective CB2 agonists that are currently in clinical trials. Ajulemic acid (AJA), under the brand name Lenabasum, is in a Phase 3 trial. And an orally administered, partially synthetic cannabinoid derived from CBD called EHP-101 (formerly VCE-004.8) is pursuing Phase 1. Both of these compounds have been shown to mitigate the production of excess tissues in rodent models, and both are well tolerated in humans.

It remains to be seen whether these efforts will bear fruit. Although earlier attempts to develop synthetic CB2 agonists into effective therapeutic modalities came up short, the progress of current clinical trials is encouraging. But there’s no telling if or when these scleroderma drugs might go to market. Meanwhile, readily available whole plant remedies may already be a viable option for scleroderma patients in states where medical cannabis and adult use are legal.

What about CBD?

CBD-rich cannabis, which remains off-limits (with few exceptions) to medical researchers, has never been formally studied as a scleroderma treatment. But extensive preclinical investigations with molecular isolates suggest that cannabidiolinfo-icon could be helpful for a number of reasons.

In vivo studies indicate that CBD inhibits CB1 receptor signaling without completely blocking it. Imagine that CB1 operates like a dimmer switch – CBD turns it down but not entirely. In theory, this would impede tissue or collagen overproduction.

At the same time, CBD is a potent anti-inflammatory that augments CB2 receptor signaling, thereby boosting the antifibrogenic activity that’s sorely deficient in scleroderma patients. Scientists have yet to sort out exactly how CBD induces effects that are similar to CB2 activation without binding directly to the CB2 receptor.

But this much is known: CBD can differentially modulate CB1 and CB2 receptor signaling by down-regulating the former while amplifying the latter – a beneficial combination for treating scleroderma. CBD also holds promise as a remedy for several other disorders (including fatty liver disease, diabetes, heart disease, obesity, and metabolic syndrome) that are associated with overactive CB1 receptor signaling and inadequate CB2 stimulation.

Cannabinoid science suggests that scleroderma patients (and many others) could also benefit by increasing their dietary intake of ss-caryophyllene, a common botanical compound found in cannabis, bitter greens, and kitchen spices such as black pepper, oregano, and cinnamon. ss-caryophyllene, an aromatic terpeneinfo-icon, selectively activates the CB2 receptor without activating CB1.9

Perhaps a CBD-rich cannabis remedy – a topical and/or an ingestible – with a robust terpene profile that includes a healthy dose of ss-caryophyllene would be worth a try for scleroderma patients. Those who are using cannabis to treat an autoimmune condition should make sure their doctor knows; high doses of CBD and other plant cannabinoids may interact with pharmaceutical meds. And keep Project CBD in the loop, as well. If you use cannabis for scleroderma, let us know how it goes.

Footnotes

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Want the most from your cannabis terpenes? Temperature matters

Cannabis flowers contain hundreds of chemical compounds, including cannabinoids and terpenes. Terpenes are scented molecules that are responsible for the flavour and aroma of cannabis.

In addition to lending flavour to cannabis, they also contribute to its effects on the body, both individually and in combination with cannabinoids.

Most vaporizing temperature recommendations focus on the boiling point of THC (157?C) and other cannabinoids, such as CBD (180?C). But for an even more customized experience, you may want to consider the boiling points of terpenes, too.

Here, we’ll review the boiling points of five major terpenes, and explain how you might use this information to your benefit when vaporizing cannabis flower.

How to target terpenes while vaporizing

In order to preferentially vaporize specific compounds, you will need a vaporizer with an adjustable temperature control.

Keep in mind that altering the temperature you are vaporizing at may reduce the amount of THC, CBD, and other cannabinoids that are activated.

It’s important to look at the boiling points of the other major compounds in the plant and consider which ones are close to your target terpene. THC’s boiling point is 157?C, and CBD’s is 180?C.

It’s also important to note that compounds will begin to vaporize at temperatures lower than their boiling points, and will also vaporize at temperatures higher than their boiling points.

Given the diversity of compounds within cannabis, and the range of vaporization points, it’s impossible to target a single compound for vaporization. This is not necessarily undesirable, though, because scientists believe terpenes and cannabinoids work synergistically in what is called the entourage effect.

Playing with vape temperatures in this way will probably have more impact on flavour than effects, which will likely be subtle.

Regardless, vaporizing temperature will certainly alter the aromatic experience, and the perceived flavour of your cannabis. It’s also important to note that some of the effects you experience could be due to your beliefs and expectations about the effects of terpenes.

Ideal temperatures for vaporizing terpenes

Myrcene

Myrcene is a sedative compound that is thought to flip the effects of THC from energizing to couch-locking. If it’s relaxation or help sleeping you’re after, myrcene is the terpene you want to target. The boiling point of myrcene is 167?C.

Pinene

Pinene is an energizing scent that may contribute to a more alert, active high. Some scientists believe it may counteract the short-term memory deficits induced by THC. Preferentially, vaporizing pinene makes sense if you’re using cannabis during the day or at a time where you want to be mentally sharp.

The boiling point of pinene is 156?C.

Limonene

Limonene is thought to elevate mood, and some research suggests it might treat depression. This could be a good terpene to try targeting if you are feeling down. Regardless of its potential effects, this compound lends a pleasant lemon note to the cannabis experience.

The boiling point of limonene is 176?C.

Caryophyllene

Studies suggest that caryophyllene may have analgesic effects. It may be a good terpene to preferentially vaporize if you are using cannabis to treat pain. It offers a spicy, woody, and peppery scent.

The boiling point of caryophyllene is 130?C.

Linalool

Linalool is a sedative, relaxing compound, which may also elevate mood. Targeting the temperature for this terpene makes sense when using cannabis to relax or before bedtime. It also contributes a floral aroma to the vaporizing experience.

The boiling point of linalool is 198?C.

Optimizing terpenes for specific situations

Scenario 1: You’re using cannabis during the day, and you want to get some work done.

Let’s say you have some Tweed Penelope, which contains pinene and myrcene, on hand. Target the pinene (156?C) and stay below the boiling point for the highly sedative myrcene (167?C). Since THC vaporizes at 157?C, you’ll likely want to vape at this temperature.

Scenario 2: You’re home for the night and would like to use cannabis to relax.

If you typically reach for Houseplant’s Indica strain, which contains linalool and myrcene, you may want to start your session around the boiling point of myrcene (167?C), which will also vaporize THC. Later in the session, you can step up your temperature to 198?C, which will target linalool, another sedative terpene.

Scenario 3: You’re in pain, and you’re using cannabis to feel better.

Sour Diesel is available from several Canadian licensed producers, and frequently contains caryophyllene and myrcene. If that’s your go-to pain strain, start at 130?C to target caryophyllene. Step up to 157?C to add some THC to the mix, and finish up around 180?C to benefit from CBD’s pain-relieving effects. If you want to avoid sedation, skip the last step and stay below the boiling point of myrcene (167?C).

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How cannabis terpenes work on your body and mind

Terpenes are scented molecules found in cannabis and many other plants, and responsible for flavour and aroma. Some of the most well-known terpenes found in cannabis are linalool, limonene, pinene, myrcene, and caryophyllene.

In addition to providing an aromatic experience, terpenes are believed to contribute to the effects of cannabis, both alone and in combination with cannabinoids. There is a lot of talk about the potential effects of terpenes on the body, but less talk about the mechanisms that explain these effects.

Are the effects of terpenes psychological, meaning they are due to expectations, beliefs, associations, and emotional learning associated with the scent? Or are they pharmacological, meaning they are due to interactions with receptors and hormones in the body? Evidence suggests that both mechanisms play a role in explaining how terpenes work.

The effects of terpenes: Pharmacological or psychological?

A 2009 review published in the International Journal of Neuroscience suggests that the effects of aromatic compounds can be explained either pharmacologically or psychologically.

The pharmacological hypothesis argues that aromatic compounds such as terpenes affect mood, physiology, and behaviour because they interact with the nervous and/or endocrine systems (hormones).

The psychological hypothesis argues that a person’s beliefs, expectations, emotional associations, and perceptions are the real reasons behind terpenes’ effects, not their direct interaction with systems in the body.

There is evidence for both hypotheses, which we will consider in turn.

Pharmacological mechanisms

There is plenty of research to support the idea that terpenes operate pharmacologically in the body and brain.

A 2001 review about the synergistic effects of terpenes in cannabis lists many potential mechanisms of action for these compounds, with its authors suggesting that terpenes may increase serotonin, norepinephrine, dopamine, and GABA activity. They argue that these effects may “support synergistic contributions of terpenoids on cannabis-mediated pain and mood effects.”

Although the natural world produces thousands of terpenes, very few have been studied for their specific mechanisms of action. Two exceptions are linalool, also found in lavender, and limonene, present in citrus fruits.

Linalool is known for its sedative, analgesic, and anti-inflammatory effects. Researchers believe linalool creates a sedative effect by decreasing sympathetic nerve activity and increasing parasympathetic nerve activity. (The sympathetic nervous system is responsible for the fight or flight response, and plays an integral role in waking behaviours. The parasympathetic nervous system opposes this activity, calming a person down and activating rest and digest.)

The mechanisms behind the pain-relieving effects of linalool are complex. A 2014 review suggests that linalool influences at least 10 different pain-related systems in the body. Linalool increases the activity of opioid receptors, as well as dopamine receptors. Linalool is also thought to inhibit the production of inflammatory cytokines, which explains its anti-inflammatory effects.

As for limonene, a 2013 study found that oral administration of lemon essential oil, which contains 70% limonene, had a significant antidepressant effect in a mouse model of depression. Researchers determined that the lemon oil increased the activity of serotonin, dopamine, and norepinephrine in different regions of the brain, which may explain its antidepressant effects.

Evidence of terpenes’ psychological effects

There is also evidence suggesting that terpene compounds may exert their effects – at least in part – through psychological mechanisms.

Liking or disliking an odour predicts a positive or negative shift in mood respectively. A 2003 study found that the odours a participant liked improved their mood, decreased anxiety, and decreased the unpleasantness of pain, and the odours they disliked worsened their mood and the way they felt about their pain. Similarly, psychological mechanisms can impact the way a person experiences the effects of cannabis. For example, a person who has had negative experiences with cannabis might find the scent to be anxiety-provoking, while someone who uses it at parties or in a social setting might associate it with fun.

Preconceptions matter, too. A 2004 study measured participants’ reactions to the suggested effects of different aromatic compounds. The results showed that the suggestion that an odour was relaxing was associated with decreased heart rate and skin conductance (a measure of physiological arousal), while the suggestion that an odour was stimulating increased these measures. This was true regardless of odour, and it was even true when no odour was used. The no odour condition produced relaxation or stimulation based on what was suggested. Lavender, which is considered to be a relaxing scent, was able to cause stimulation when this was suggested.

All this is to say that it is very likely that suggestion, emotional learning, beliefs, and expectations play at least some role in the way terpenes work. This doesn’t make the effects any less “real”, except that they might vary more between individuals than expected.

The bottom line

Both psychological and pharmacological mechanisms seem to contribute to the effects of terpenes.

There is good evidence suggesting that terpenes have direct physiological effects on the body, especially for linalool and limonene. This means that linalool-rich strains are likely to have a calming effect, and to provide pain relief, while limonene-rich strains are likely to be mood-elevating.

There is also good evidence to suggest that psychological phenomena such as expectations, beliefs, and associations play at least some role in the way terpenes affect the human body. This means that it’s important to listen to your intuitions about smell. If you dislike the scent of a particular strain, you might find you don’t like the experience either.

Future research will reveal much more about the way terpenes interact with our bodies and minds. It will be particularly important to study terpenes in the context of the many other compounds in whole-plant cannabis, such as cannabinoids, since many researchers believe these compounds all work together to produce effects they could not create alone.Researchers have only begun to scratch the surface when it comes to the way the terpenes in cannabis affect the body.

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Endometriosis Is Painful as Hell. At Least There’s Cannabis

One night in 2014, intense menstrual cramping had driven me home from a dinner out with a friend, leading to full-on sobbing by the time I got back to my apartment. It wasn’t the first time I’d experienced severe endometriosis symptoms, I’d been diagnosed long ago, but I usually kept the pain from complete meltdown levels with cannabis. Unfortunately, this was pre-legalization, and “my guy” was dry.

As I Googled to see how much Ibuprofen I could take before endangering myself, the pain shot up again. Twenty minutes later, I’d broken out in hives, and waves of darkness flooded the corners of my vision. I prayed I’d lose consciousness, to no avail. It was a very, very long night.

When endometriosis pain gets like that, it feels like barbed wire has been looped all over your guts, and some jerk is slowly, yet fiercely, twisting the wire–pulling on the entangled tissues and organs, threatening to rip them apart. (And then someone dares to say, “It’s just your period,” and you claw their face off!)

It’s Actually Bodily Tissue Looped All Over Your Guts

Unfortunately, what endometriosis feels like is actually pretty accurate to what it is.

A woman’s period is a result of the shedding of endometrial tissue built up from the hormonal cycle. But in endometriosis, this tissue grows outside of the womb, where it’s unable to shed. This tissue is often described as looking like a web, wrapping itself over organs outside of the womb, and even connecting them. (In extreme cases, the organs actually become fused together, called “frozen pelvis.”)

Because this tissue becomes trapped in the body, when it’s time for the body to do its monthly thing–it really freakin’ hurts. But endometriosis doesn’t stop there. In addition to “severe menstrual cramps” (an infuriatingly minimizing description), this wandering tissue also leads to chronic lower-back, abdominal, and pelvic pain; painful intercourse; painful urination and/or bowel movements; IBS symptoms; and infertility. Endo fighters–an estimated 11% of women–also have increased rates of ovarian cancer.

The treatment options offered to fighters are paltry. Hormonal birth control is usually the first thing recommended, but many women react adversely to it. Painkillers are the next line of defense, from stomach-damaging NSAIDS to life-ruining opioids–none of which a great option for decades of ongoing use. Other fighters get the endometriosis tissue surgically removed, which obviously has substantial side effects, as well as doing nothing to keep it from growing right back.

Luckily, we have cannabis.

From Cannabis Concern to Convert

Foria is a cannabis company that specifically targets female health concerns, like endometriosis, offering innovative products like suppositories–an invention that’s arguably better than anything the pharmaceutical industry has offered sufferers in decades.

We spoke with Kiana Reeves, Director of Education at Foria, to see how their efforts are faring–and so far, so great. These sales are accompanied by thank you notes that serve as a testament to the power of cannabis to treat endo’s symptoms.

One such testimonial comes from Ashley, who was raised to fear cannabis, but worked her way to it from general herbal medicine after years of negative experiences trying to combat endo with pharmaceuticals. In addition to bringing back her sex life, cannabis treatment led to less endometrial tissue needing to be removed in surgery–to say the least, she’s now a convert. Her initial fears about cannabis were further compounded as a mother, but she now has a non-intoxicating arsenal of CBD and low-dose/topical THC tools at her disposal.

The Science on Endometriosis and Cannabis

Traditional methods of endometriosis treatment merely attempt to mitigate symptoms, but there’s evidence that cannabis can potentially treat the actual condition. Cannabis and the endocannabinoid system (ECS) work together to fight aspects of endo in many ways–and, for once, the science on why cannabis is so successful at treating endometriosis is (relatively) abundant.

Migration and Growth

Since the source of endometriosis is cells being where they shouldn’t be, tapping into the ways they migrate will be crucial in understanding, and eventually curing, endometriosis. The most promising development in regard to this area is how cannabis interacts with the N-arachidonyl glycine receptor (NAGly receptor), more commonly referred to as the GPR18 receptor, which works with the cannabinoids in cannabis as well as the body’s natural endocannabinoids.

The name of the game with the ECS is all about balance, and endometriosis is no exception to the rule. While the cannabinoid CBD blocks the activation of the GPR18 receptor, which can stop endometrial cells from migrating, there’s also evidence pointing to THC causing the migration of cells by activating this receptor. Because of this, it might be wise to counteract pain-relieving THC with CBD for treating endometriosis. Endometrial cells multiply, like cancer, and there’s also evidence that cannabinoids can also stop these cells from this proliferation.

Painkiller

The pain involved with endometriosis is the most impactful aspect of the disease for most women. As described above, this literally “gut wrenching” pain is often completely debilitating–and for many women it lasts a whole lot longer 2-7 days, with pain extending outside of menses or a longer menses duration. But cannabis comes to the rescue again, fighting pain in several ways.

THC does its pain-squashing magic not by merely distracting from symptoms–which sure doesn’t hurt–but by deactivating nerves in endometrial cells via endocannabinoid receptors. CBD also has its own super power, desensitizing the pain receptor TRPV1. And cannabis has one more pain-fighting weapon in CBD with its ability to take down inflammation, which leads to less irritated nerves, thereby, less pain.

Improving the Tone of the Endocannabinoid System

There’s mounting evidence to show that imbalances in the endocannabinoid system (ECS) are the force behind many common chronic illnesses, and while endometriosis isn’t in the disease rubric, dysmenorrhea (painful periods) is–and the rubric isn’t thought to be comprehensive. The fact that cannabis is able to interact with the endocannabinoid system to help fight symptoms is another sign that a negatively impacted ECS could be the cause of endo, but more research is needed.

Tamas Biro, Professor and Director General of the Hungarian Center of Excellence for Molecular Medicine and Director of Applied Research for Phytecs told me via email that reaching optimal ECS tone (to balance endocannabinoid levels) is a balancing act of its own.

“The most important thing you can do to keep the ECS healthy is to avoid the extremes–to name a few examples: avoid extreme and chronic stress, avoid being overweight, control alcohol consumption, and try to curtail dependencies in general,” he said.

Though simply taking full-spectrum CBD may also help boost tone, all-in-all, getting a healthy ECS is all about living a healthy lifestyle. Other frequent advice on the matter entails eating right for your body (elimination diets are a great help here) and getting regular exercise. If that were the whole “cure” of endometriosis, we’d have a lot more cured patients out there. But, to this fighter anyways, it’s nice to know science might at least be close to the origin of this disease.

And in the meantime, at least there’s cannabis.

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Feds Award $3 Million In Grants To Study Marijuana Ingredients As Alternatives To Opioids

The federal government has awarded $3 million in grants for research into the therapeutic benefits of ingredients in marijuana other than THC, emphasizing their potential as alternatives to prescription opioids.

In a notice published on Thursday, the National Institutes of Health (NIH) explained why the studies were necessary and listed grant recipients and the subjects they will investigate. That includes research into the use of CBD for arthritis pain, which will be led by New York University School of Medicine.

“The treatment of chronic pain has relied heavily on opioids, despite their potential for addiction and overdose and the fact that they often don’t work well when used on a long-term basis,” Helene Langevin, director of the National Center for Complementary and Integrative Health (NCCIH), said in a press release. “There’s an urgent need for more effective and safer options.”

A total of nine grants were issued, with NIH stating that the funds will help identify alternative treatment options for pain and provide information about the impact of consuming cannabis compounds such as CBD and other lesser-known cannabinoids as well as terpenes found in the plant.

“The cannabis plant contains more than 110 cannabinoids and 120 terpenes, but the only compound that’s been studied extensively is THC,” the press release said.

But while THC is known to treat certain forms of pain, NIH is concerned that its intoxicating effects limit its medical applicability.

“THC may help relieve pain, but its value as an analgesic is limited by its psychoactive effects and abuse potential,” David Shurtleff, deputy director of NCCIH, said. “These new projects will investigate substances from cannabis that don’t have THC’s disadvantages, looking at their basic biological activity and their potential mechanisms of action as pain relievers.”

NIH first announced that it would be issuing grants for studies into minor cannabinoids and terpenes last year.

Federal health agencies aren’t the only institutions interested in learning about marijuana compounds other than THC. On Wednesday, a Senate committee issued a spending report that called for research into CBD and CBG while also criticizing the federal drug scheduling system for inhibiting such research.

Read descriptions of the federal cannabinoid and terpene research grant awards below:

Mechanism and Optimization of CBD-Mediated Analgesic Effects; Boston Children’s Hospital, Boston,; Zhigang He, Ph.D., B.M., and Juan Hong Wang, Ph.D. This project will investigate how the pain-relieving effects of cannabidiol (CBD) and other minor cannabinoids may be modulated by the activity of potassium-chloride cotransporter 2 (KCC2), a chloride extruder expressed in most neurons. (Grant 1R01AT010779)

Neuroimmune Mechanisms of Minor Cannabinoids in Inflammatory and Neuropathic Pain; University of California, San Francisco; Judith Hellman, M.D., and Mark A. Schumacher, M.D., Ph.D. This project will explore the effects of minor cannabinoids on inflammatory and neuropathic pain in vitro and in vivo, focusing on the interactions of the cannabinoids with the peripheral receptor called TRPV1 and a cannabinoid receptor, CB1R. (Grant 1R01AT010757)

Minor Cannabinoids and Terpenes: Preclinical Evaluation as Analgesics; Research Triangle Institute, Research Triangle Park, North Carolina; Jenny L. Wiley, Ph.D. This project will evaluate purified biosynthesized minor cannabinoids and selected terpenes alone and in planned combinations to determine their potential efficacy as pain relievers against acute thermal, inflammatory, neuropathic, and visceral pain. (Grant 1R01AT010773)

Identifying the Mechanisms of Action for CBD on Chronic Arthritis Pain; New York University School of Medicine, New York City; Yu-Shin Ding, Ph.D. This project will use neuroimaging studies and behavioral assessments to investigate the mechanisms of action of CBD in the modulation of chronic pain associated with osteoarthritis in a mouse model. (Grant 1R21AT010771)

Synthetic Biology for the Chemogenetic Manipulation of Pain Pathways; University of Texas, Austin; Andrew Ellington, Ph.D. This project will use a novel method to evolve individual variants of cannabinoid receptor type 2 (CB2) that interact with high affinity with minor cannabinoids and evaluate the new variants in a mouse model of pain. (Grant 1R21AT010777)

Exploring the Mechanisms Underlying the Analgesic Effect of Cannabidiol Using Proton Magnetic Resonance Spectroscopy; University of Utah, Salt Lake City; Deborah A. Yurgelun-Todd, Ph.D. This project will use proton magnetic resonance spectroscopy (1H-MRS) to evaluate changes in brain chemistry in critical pain-processing regions after short-term administration of a cannabis extract enriched in CBD. (Grant 1R21AT010736)

Mechanistic Studies of Analgesic Effects of Terpene Enriched Extracts from Hops; Emory University, Atlanta; Cassandra L. Quave, Ph.D. This project will take a multidisciplinary approach to investigate the analgesic effects of terpenes from Humulus lupulus (hops), a plant that is closely related to cannabis and has a very similar terpene profile. (Grant 1R21AT010774)

Systematic Investigation of Rare Cannabinoids With Pain Receptors; University of Illinois at Urbana-Champaign; David Sarlah, Ph.D. This project involves synthesizing several classes of rare phytocannabinoids, systematically evaluating their anti-inflammatory potential, and examining the effects of the compounds with the strongest anti-inflammatory potential on the major receptors involved in pain sensation. (Grant 1R21AT010761)

Analgesic efficacy of single and combined minor cannabinoids and terpenes; Temple University, Philadelphia; Sara J. Ward, Ph.D. This project will use rodent models of pain to evaluate the effects of four biologically active components of cannabis that may act synergistically to protect against pain development and to assess the interactions of these four substances with morphine. (Grant 1R01AT010778)

Senate Report Slams Drug Scheduling System For Blocking Marijuana Research

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