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.


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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What Is CBDA (Cannabidiolic Acid) & What Are the Benefits of This Cannabinoid?

CBDA (cannabidiolic acid) is one of many compounds produced by cannabis and hemp. Abundant in the live plants of CBD varieties, it converts to the better known cannabinoid CBD (cannabidiol) over time and when exposed to heat.

Cannabinoids are cannabis compounds that interact with our bodies to produce medical and recreational effects, from pain and stress relief to euphoria. You’ve likely heard of CBD and THC–these are the most widely known cannabinoids, and both originally stem from the precursor “mothership” cannabinoid known as CBGA (cannabigerolic acid).

CBGA converts to three major cannabinoid precursor compounds, depending on which plant enzymes are activated to direct the synthesis:

  • THCA (tetrahydrocannabinolic acid)
  • CBCA (cannabichromenic acid)
  • CBDA (cannabidiolic acid).

When decarboxylation occurs by exposing the cannabis plant to either heat or sunlight, CBDA converts to CBD. In other words, CBDA is the raw form or predecessor to CBD.

These days, CBDA is typically found in capsules, tinctures, and topicals. Many people even juice raw cannabis to get a daily dose of CBDA.

But what does CBDA do and why is it important?

Potential Medical Benefits of CBDA

While most cannabinoids bind directly with either the CB1 or CB2 receptors, CBDA doesn’t work in this way. Instead, CBDA interacts with the endocannabinoid system by inhibiting the cyclooxygenase-2 (COX-2) enzyme. COX-2 enzymes are associated with inflammation after an injury or infection, so by blocking COX-2 enzymes, CBDA can relieve inflammation and associated pain.

In one rodent study, scientists found CBDA affected levels of serotonin, a chemical produced by nerve cells to aid in signaling between cells. Serotonin is vital to core human functions like motor skills, sleeping, eating, digestion, and emotions.

A number of stressors, including radiation and chemotherapy, trigger the body to release excess serotonin, causing nausea and vomiting. While vomiting can typically be controlled with medication, nausea is harder to control. Many cancer patients say that nausea causes much more distress than vomiting because nausea is a continuous sensation. In fact, one in five patients consider discontinuing cancer treatment so as to not experience the nausea.

Scientists have demonstrated that CBDA can affect the body’s 5-HT serotonin-producing receptors, hinting at a potential use for CBDA as a medication for chemotherapy-induced nausea/vomiting (CINV) and other conditions that induce these symptoms. However, more research is needed.

The Current Research on CBDA

Scientists have been studying CBDA for about a decade.

An early 2008 study looked at the potential of CBDA as an anti-inflammatory agent by specifically studying its COX-2 inhibitor qualities. The research team compared the molecular structures of CBDA with nonsteroidal anti-inflammatory drugs (NSAIDs) commonly used to treat inflammation and found their chemical structures remarkably similar; both are known to inhibit COX-2 receptors. This initial study showed that CBDA holds promise as a potential anti-inflammatory agent.

In the same way that it controls nausea, CBDA may also be a powerful anticonvulsive. In fact, scientists have shown that CBDA has 100 times the affinity for the 5-HT receptors compared to CBD; one reason is that CBDA has greater bioavailability, so the body can metabolize the compound with less effort and in less time.

This same receptor affinity could also mean that CBDA could perhaps effectively fight depression. After all, CBDA works on the 5-HT receptors in much the same way as a selective serotonin reuptake inhibitor (SSRI) antidepressant medication would.

To date, most CBDA studies are preclinical non-human studies. While human trials are needed, some medical cannabis companies like British-based GW Pharmaceuticals are paving the way. GW Pharmaceuticals manufactures a pharmaceutical-grade CBD oil called Epidiolex, the first cannabis-derived prescription drug to be approved by the US Food and Drug Administration (FDA).

Interestingly, the FDA required the company to not only conduct CBD research, but to also conduct research on the precursor CBDA, and GW’s own research shows that CBDA is an even more effective seizure treatment. The company has also filed two other CBDA medical-use patents: one for inflammatory skin diseases and the other for cancer treatment.

Although CBDA cancer research to date has only been on isolated cells, initial studies indicate that CBDA might stop the migration of a highly aggressive form of breast cancer cell known as MDA-MB-231.

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CBD for Autism: The Therapeutic Promise

By Wholistic Research & Education Foundation On August 20, 2019 (Updated on August 21, 2019)

From Wholistic Research & Education Foundation.

Responing to growing interest about CBD from families across the United States, the Autism Society of America and Wholistic Research and Education Foundation have co-costed this educational webinar to discuss whether CBD indeed holds a therapeutic promise for autism and other neurodevelopmental disorders. This webinar brings together renowned MDs and Researchers to explore just how medicinal cannabis therapies can alleviate symptoms in children with autism, and highlights the latest research-driven data driving a groundbreaking multi-disciplinary study on this highly topical issue at the University of California San Diego (UCSD).

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Can CBD Help Your Complexion?

Just a few years ago, most of the cannabis-infused topicals and skincare products available were jars of greasy green glop, handmade in someone’s kitchen and smelling suspiciously of bong water. Not so in 2019.

In today’s 17-billion-dollar “prestige beauty” industry, cannabis-infused skincare is the hottest trend since snail mucus, and the non-intoxicating cannabinoid known as cannabidiol (CBD) is its sparkly little darling. CBD is the reason why executives from top outfits like L’oreal and GOOP are leaving lucrative jobs to join forces with cannabis skincare start-ups.

CBD blasted into the entrepreneurial stratosphere after the passage of 2018 Farm Bill, which removed hemp from the Controlled Substances Act and supposedly made it legal to grow, produce and market any part or derivative of a cannabis sativa plant containing a minuscule amount (0.3 percent or less) of tetrahydrocannabinol (THC). These days, CBD-spiked skin products are everywhere. Vogue, Vanity Fair, and Forbes sing their praises. Gwyneth Paltrow and Martha Stewart are big fans. And while it’s not surprising that Bob Marley’s daughter has her own cannabis-infused skincare line, you can also buy CBD-infused lotions, massage oils and lip balms from Amazon or at the mall in stores like Sephora, CVS, and Walmart.

Manufacturers, distributors and investors are flinging themselves onto the CBD bandwagon, while the Food and Drug Administration (FDA) dithers, trying to figure out how to respond to the CBD upsurge. Given the uncertain regulatory environment and the FDA’s qualms about ingestible CBD supplements, topicals are a safer bet for those seeking business opportunities in the CBD market. It appears that the FDA is much less concerned about the safety and efficacy of CBD topicals than CBD edibles and beverages. In general, FDA policy with respect to cosmetics and deodorants is shamefully lax, fostering widespread exposure to carcinogens, endocrine disrupters, and other toxins that pose a serious threat to public health.

Thus, it’s important to carefully scrutinize all the ingredients listed on the label before you drop a couple of Benjamins on CBD-infused facial creams or bath bombs. Don’t assume that it’s a high-quality product just because it contains CBD.

Slick marketing campaigns are touting CBD as a miracle compound for the skin, with healing properties that range from relieving pain to soothing rashes and eradicating acne. The most alluring (and profitable) CBD-related promises pertain to anti-aging and beautifying the skin. But is there anything substantive behind all the hype? Can CBD really protect, heal and restore the skin? What, if anything, does the science say about all this?

imagediagram showing the multiple layers of the skin

Skin, Our 22-Pound Organ

Human skin is a complex, multifunctional, protective barrier for the body. It’s also the heaviest organ we carry around — about one seventh of our total body’s weight, or 8 to 22 pounds on average — with a surface area of about 2 square yards. (Apologies to the rest of the world that measures in terms of meters and kilos.)

The skin is comprised of three layers. The outermost, called the epidermis, is like a fortress wall, a strong-yet-flexible barrier made up of constantly-renewing skin cells known as keratinocytes that shield the body from physical assaults — everything from sunburn and irritating substances to attacks from invading pathogens; from biting and stinging creatures to burns, punctures, cuts, abrasions, and other inflicted traumas.

Below the epidermis is the dermis, which houses a complex collection of nerves and capillaries. Most of the body’s sensory cells (those that feel pressure, heat and cold, touch, vibration and pain) are found here, as well as sweat glands, hair follicles and sebaceous (oil-producing) glands. The dermis is also where collagen and elastin are made, substances that support the epidermal outer layer and gives it that youthful, spring-back-when-pinched quality so coveted by the older set. Seniors are particularly vulnerable to manipulative advertising that banks on society’s obsession with youthfulness to sell beauty products that promise to rejuvenate the skin’s once-glowing exterior.

And then there’s the deepest layer, known as the hypodermis, which attaches the skin to the rest of the body. Composed mostly of fat, connective tissue and water, it helps to insulate the body from temperature extremes and cushions bones and joints. Vitamin D and other essential hormones are synthesized in the hypordermis.

The many different cells contained in all three layers of skin work together in a complex, interconnected, delicately-balanced neuro-immuno-endocrine network that is regulated by the endocannabinoid system (ECS). Comprised of endogenous compounds that bind to cannabinoid receptors (CB1 and CB2), which are expressed in all types of skin cells, the ECS engages in a homeostatic process called cutaneous cannabinoid (“c[ut]annabinoid”) signaling. This signaling mechanism promotes healthy skin renewal and barrier function.

The Skin’s Guardian

The ECS regulates numerous physiological functions, including cellular apoptosis (cell death), a process that allows the body to eliminate aging and damaged cells, enabling regenerated cells to take their place. Cannabinoid receptor signaling can slow abnormally high skin cell production (thereby lowering the likelihood of cancer) and can also soothe the skin’s sensory nerves, reducing pain and inflammation.

The ECS also regulates the activity of pro-inflammatory cytokines and chemokines (proteins in the body involved in immune activity), and helps to maintain the action of Treg cells, a type of T cell that modulates immune response in the skin.


diagram of skin inflammation

Hungarian scientist Tamas Biro has documented how the ECS influences the production of sebum (the skin’s natural oil), increasing it to keep the skin’s waterproof barrier intact or decreasing it, which helps to keep acne at bay.

A recent report by German scientists in Experimental Dermatology noted that a “disruption of the delicate balance in cannabinoid signaling might facilitate the development of multiple pathological conditions and diseases of the skin such as atopic dermatitis, irritative allergic contact dermatitis, acne, seborrhea, psoriasis, itch, pain, hair growth disorders, systemic sclerosis, and cancer.”

The report goes on to explain how skin barrier dysregulation can delay wound healing and concluded that a “depletion of CB1 or CB2 receptors resulted in enhanced contact allergic inflammation, while cannabinoid receptor activation resulted in a reduction of inflammation.”

Based on their preclinical findings, the report suggests that pharmacological intervention to delay the breakdown (and thereby prolong the action) of endogenous cannabinoid compounds, which activate CB1 and CB2, could be a viable strategy for treating skin disease.

Enemies of Healthy Skin

Most negative aspects of the skin’s appearance are due to years of accumulated damage to cutaneous cells. Wrinkles and roughness, for example, can be caused by environmental and lifestyle factors such as excessive sun exposure, alcohol consumption, smoking, and poor diet. In addition to these epigenetic intrusions, the dryness common in a mature woman’s skin is associated with the drop in hormone production that occurs after menopause. All of these factors can cause biochemical changes in our cells’ DNA, which in turn can trigger DNA methylation, a process that alters the function and expression of genes in our skin and throughout the body.

Let’s face it, as we age, everything slows down and becomes less efficient, including our skin’s ability to generate the fresh new cells that give us that healthy, youthful look we took for granted during all those summers on the beach, when the only sun block we wore was a bikini.

As we get older, our cellular functions start to go a little haywire. And when this starts showing up on our faces, it can be truly sobering. There’s even a scientific term for time’s cruel ravages upon the body: inflammaging, the continuous, low-grade inflammation associated with aging. A 2019 article in the journal Cosmetics linked many skin conditions with such inflammation, and suggested that natural, anti-inflammatory compounds might help.

Some people will do crazy things to themselves in hopes of slowing down the inevitable decline that occurs with aging. But consider other options for restoring skin function and appearance before you go shooting your face with laser beams, injecting it with tiny spheres of polymethylmethacrylate or sandblasting it with diamond-shaped crystals.

Maybe there’s some hope-in-a-bottle you could try, thanks to cannabis.

CBD Isolate or CBD Oil?

Cannabis-infused skincare has a long history. According to Dr. Eduardo Munoz, professor of immunology at the University of Cordoba in Spain, topical preparations of cannabis were used to treat various skin disorders in ancient China, Egypt, and the Arab world. Unlike the dubious efforts of some U.S. and British women of yore, who tried to beautify their skin by ingesting arsenic tablets, for example, or applying lead-based face paint, there are no known side effects from using topical cannabis.

Pure CBD has demonstrated anti-inflammatory activity in preclinical models of skin inflammation. But how does the efficacy of single-molecule CBD in a topical compare to a full spectrum CBD-rich oil extract containing hundreds of other cannabis compounds?

A 2019 in vitro study by Italian scientists in Phytotherapy Research found that the anti-inflammatory impact of cannabis oil exceeded that of pure CBD, indicating that compounds other than CBD contribute to the inhibition of pro-inflammatory triggers in the skin. The Italian team determined that the cannabis oil downregulated several genes involved in wound healing and skin inflammation, whereas the anti-inflammatory effect conferred by the CBD isolate did not involve the same molecular mechanisms.

Since CBD can calm inflammation, it makes sense that it might be a useful ingredient in topical skincare products. But can CBD penetrate human skin deeply enough to really make a difference? A recent in vivo study by University of Kentucky scientists suggests that it can.

Published in the European Journal of Pain, this report found that a topical gel containing CBD significantly reduced pain and inflammation in a rodent model of arthritis. Moreover, it appears that CBD is much more permeable through the skin than THC. According to a 2004 article in the Journal of Pharmacy and Pharmacology, the transdermal permeability of cannabidiol is 10-fold higher than delta-8 THC. (The permeability of delta-9 THC is very similar to that of delta-8 THC.)

The Hundred-Dollar CBD Face Cream Question

So, should you buy a CBD skincare product? It depends. Just because a product has a fancy label and a high price doesn’t mean it will deliver what it claims. CBD products are still unregulated by the FDA, and according to a report in the Journal of the American Medical Association (JAMA), a significant number of CBD products surveyed contained less of the compound than labeled.

A lot depends on what else is in a CBD-infused topical. CBD skincare products may include a “full spectrum” cannabis oil extract containing CBD, THC, and all inherent cannabinoids, fatty acids, and terpenes, which combine synergistically to create a therapeutic entourage effect that’s greater than the impact of CBD alone. Or a skincare salve might contain an infusion of “broad spectrum” cannabis oil without any THC. Or, more likely, it will include a less effective CBD isolate that could be synthetic or naturally-sourced.

Keep in mind that studies on how CBD and other cannabis compounds affect the skin are mostly pre-clinical. Randomized, controlled clinical trials have yet to verify anecdotal accounts (and marketing claims) of CBD’s efficacy for skin ailments. Given the paucity of clinical research, it’s hard to know exactly how many milligrams of CBD per milliliter would be optimal for a skincare product or what a recommended dose should be.

So, if you decide to try a CBD skincare product, do your own research first. Buy from a reputable source – preferably one with a good track record of making cannabis-infused products from organically-sourced ingredients. If possible, make sure it’s third-party lab-tested for consistency and purity. Or you might also consider making your own CBD topical.

Part 2: How to Make a CBD Topical for Healthy Skin

Melinda Misuraca is a Project CBD contributing writer with a past life as an old-school cannabis farmer specializing in CBD-rich cultivars. Her articles have appeared in High Times, Alternet, and several other publications.


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  13. Sangiovanni E, Fumagalli M, Pacchetti B, Piazza S, Magnavacca A, Khalilpour S, Melzi G, Martinelli G, Dell’Agli M. Cannabis sativa L. extract and cannabidiol inhibit in vitro mediators of skin inflammation and wound injury. Phytother Res. 2019 Aug;33(8):2083-2093. doi: 10.1002/ptr.6400. Epub 2019 Jun 27.
  14. Stander S, Schmelz M, Metze D, Luger T, Rukwied R. Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin. J Dermatol Sci. 2005 Jun;38(3):177-88.
  15. Stinchcomb AL, Valiveti S, Hammell DC, Ramsey DR. Human skin permeation of Delta8-tetrahydrocannabinol, cannabidiol and cannabinol. J Pharm Pharmacol. 2004 Mar;56(3):291-7..
  16. Toth KF, Adam D, Biro T, Olah A. Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System. Molecules. 2019 Mar 6;24(5). pii: E918. doi: 10.3390/molecules24050918. Review.
  17. Turcotte C, Blanchet MR, Laviolette M, Flamand N. The CB(2) receptor and its role as a regulator of inflammation. Cell Mol Life Sci. 2016 Dec;73(23):4449-4470. Epub 2016 Jul 11. Review.
  18. Zhuang, Yong & Lyga, John. (2014). Inflammaging in Skin and Other Tissues – The Roles of Complement System and Macrophage. Inflammation & Allergy-Drug Targets (Formerly Current Drug Targets – Inflammation & Allergy). 13. 10.2174/1871528113666140522112003.

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The Latest in Cannabis Research: Winter/Spring 2019

As the summer heats up, it’s worth taking a look back in the year when cannabis research was just as hot. Exciting new studies continue to come out with the global trend toward legalization and acknowledging the therapeutic potential of cannabis.

Research so far this year encompasses finding the region in the brain that gets you high to the medicinal benefits of CBD. Below are some stand-out research papers from the first half of the year.

Jump to a Study:

Opponents of cannabis legalization claim that increasing access will increase problematic cannabis use. However, that idea is based more on gut feelings than scientific evidence.

Public health scientists put it to the test by comparing state-level policy liberalism rankings over the last couple decades with data collected regarding cannabis use and rates of cannabis use disorder. Notably, this assessment was limited to medical cannabis legalization and didn’t incorporate data relating to the legal recreational market now available in many states.

Overall, more people used cannabis in states with liberal cannabis policies than conservative-policy states, but the prevalence of cannabis use disorders was highest in conservative-policy states.

It’s uncertain at this point why conservative policy states would have higher cannabis use disorder rates, but it suggests that strict restriction of access to cannabis is not the solution to eliminating problematic use, and instead, increasing access may lead to safer overall use.

Looking for the Brain Region That Causes the High

People have been experiencing cannabis highs for thousands of years. Only recently, however, have scientists uncovered how this effect occurs in the brain.

THC was isolated in the 1960s and the CB1 receptor wasn’t fully discovered until the 1990s. Shortly after, it was confirmed that activation of CB1 receptors by THC causes the feeling of being high. However, where in the brain this feeling comes from remained elusive.

Recently, scientists working in the United Kingdom added to this story by revealing that the posterior cingulate cortex in the brain is a key contributor to THC’s high.

Discovering the seat of the high was likely not the scientist’s intention. Instead, they were looking at the brain activity of participants given either 8 mg of THC alone or THC with 10 mg of CBD. They revealed that THC disrupted activity in numerous brain regions, but the posterior cingulate cortex was specifically disrupted by THC alone, and less-so by THC with CBD.

Importantly, the degree of disruption positively correlated to the feeling of being stoned and high. So while THC’s actions across many brain regions are responsible for the numerous outcomes of using cannabis (e.g., memory, munchies, mood), your high can be traced to the posterior cingulate cortex.

So where is the posterior cingulate cortex? If you were to split the brain right down the middle, front to back, you’d slice through a large band of fibers called the corpus callosum that allows the two sides of the brain to communicate with one another. The brain’s outer layer that sits right above the corpus callosum on each side of the brain is the cingulate cortex, and the posterior end is the part toward the back of your head.

Adolescent Cannabis Consumers Don’t Have Structural Brain Abnormalities

Numerous studies have investigated whether cannabis use during adolescence changes the way the brain looks. However, these studies are often limited by a small sample size or only compare frequent consumers who consume more than three times per week. Few studies have looked at structural brain differences across different levels of cannabis consumption.

In this study, the brains of 781 adolescents aged 14-22 were compared. 109 participants were classified as occasional cannabis consumers (two or fewer uses per week) and 38 were classified as frequent consumers.

The Philadelphia-based scientists used brain MRIs to look at structural differences on a brain-wide and region-specific level. They concluded that neither occasional nor frequent cannabis use significantly affected the size of the whole brain or any of the specific regions of interest.

Further, there were no group differences in the number of brain cells, their connections, or in the thickness of the cortex–the surface of the brain that contributes to the unique cognitive abilities of humans and higher-order species.

While these findings suggest that adolescent cannabis consumption doesn’t affect the way the brain looks, it doesn’t address questions relating to the effect of cannabis on the way the brain functions. Nonetheless, this study serves as further support for the less-damaging effects of cannabis use compared to other drugs (such as alcohol), which have been shown to affect brain structure.

CBD Protects Against THC’s Effects on Learning and Memory

It turns out that CBD blocks some of the effects of THC, and it has become clear that the underlying reasons extend beyond just CBD’s actions on CB1 receptors. Since THC itself has numerous therapeutic benefits, understanding how CBD blocks some of THC’s negative effects, such as impairing learning and memory, could elevate the utility of THC-based therapies.

A collaborative effort of scientists across Spain and Japan revealed that CBD can block THC’s activating effects on CB1 receptors indirectly by increasing the activation of another type of receptor, the adenosine type IIa receptor. The adenosine receptor appears to oppose the actions of CB1 receptors–when the adenosine receptor is active, the CB1 receptor is not. By increasing adenosine activation, CBD can therefore block THC’s effects.

Intriguingly, this mechanism only influenced THC’s actions in the hippocampus region of the brain, which plays a critical role in laying down long-term memories. As one can predict, CBD prevented THC’s impairing effects on new memory formation.

Narrowing Down the Culprit of Cannabinoid Hyperemesis Syndrome

Cannabinoid hyperemesis syndrome (CHS) is a somewhat newly recognized condition that is characterized by cycles of severe stomach cramping and vomiting in frequent cannabis consumers. The number of cases is on the rise and while there is no confirmed cause, increasing THC potency in average recreational strains has usually been deemed the culprit.

To address whether high levels of THC are responsible for CHS, cannabinoid content in hair samples was analyzed from patients with CHS admitted to emergency departments in Ontario, Canada, and compared with two other groups: patients admitted to the emergency department for an unrelated condition, and recreational cannabis consumers without CHS.

The results revealed that THC levels were similar across the three groups, ruling out the possibility that CHS arises due to high levels of THC in the body. Intriguingly, the THC:CBN ratio was 2.6 times lower in the CHS group than in the recreational consumers without CHS, suggesting a potential protective role of additional cannabinoids.

If THC is not the sole cause of CHS, then what is? There are at least two remaining hypotheses. The first is that some patients experience a build-up of toxins, such as pesticides and molds, from repeated consumption, which triggers the body’s emetic response (i.e., vomiting) through activation of certain cells in the brainstem.

The second is that THC weakens the action of certain CB1 receptors in some people more than others. It turns out that activating CB1 receptors (as THC does) in the brain has anti-emetic effects–which explains THC’s well-known anti-nausea effect.

But it’s believed that CB1 receptors in the brain are more prone to weakening than those in the gut–therefore, heavy THC use in some people could lead to a weakening of the anti-emetic actions in the brain while leaving the pro-emetic actions in the gut unaffected. The result may be hyperemesis.

CBD Could Effectively Treat Related Symptoms of Autism

There is plenty of anecdotal support for cannabis-based therapies in Autism Spectrum Disorder (ASD), but those claims have lacked clinical support until now. ASD is characterized by core deficits in social, communication, and motor behaviors.

While these symptoms present their own challenges, comorbid symptoms such as self-injurious behavior, hyperactivity, anxiety, and sleep disorders are especially burdensome to the patient and their caregivers. Children with ASD are often on several medications to help relieve these comorbid symptoms, and not always successfully. Given CBD’s therapeutic range, it represents a single treatment strategy for combating these comorbid symptoms in ASD.

The effect of a 20:1 CBD:THC oil was assessed on comorbid ASD symptoms in 53 children between the ages of 4 and 22 years of age. Parents were free to administer as much of the oil as they wanted (recommended daily dose was 16 mg CBD per kilogram of body weight), but children ended up consuming around 90 mg of CBD each day.

Despite consuming less than the recommended amount, CBD reduced hyperactivity, lowered the number of self-injurious behaviors, improved sleep, and reduced anxiety in a majority of patients.

An overall improvement in at least one of the comorbid symptoms was observed in 75% of the participants and only worsened overall symptoms in 4%. Although CBD didn’t improve any one of the symptoms better than conventional treatments, it represents a single pharmaceutical approach that can target a myriad of symptoms simultaneously with limited adverse events.

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Marijuana Legalization Causes ‘Significant Decline’ In Opioid Overdoses, New Research Finds

Two new studies find that opioid-related deaths decline when states legalize access to marijuana. In fact, when adult-use cannabis laws are in place, the rate of opioid overdoses declines by at least 20 percent.

Both papers, published in the journal Economic Inquiry, not only show the impact of passing such laws, but also how dispensaries play a role in helping to quell these deaths.

The first study, helmed by researchers in Massachusetts and Colorado, claims to be the first to show the causal effects of access to recreational cannabis on opioid mortality.

“We find that marijuana legalization causes a significant decline in opioid mortality– especially deaths from synthetic opioids–with particularly pronounced benefits in states that have legalized recreational usage,” the study’s authors write. “Yet it is not legalization, per se, that produces these gains; rather, states that have legal access via dispensaries see the largest reductions in mortality.”

“We estimate that [recreational marijuana laws] reduce annual opioid mortality in the range of 20%-35%, with particularly pronounced effects for synthetic opioids.”

The study used three main sources of data: death rates involving all opiates, prescription opioids and synthetic opioids from January 1999 through the end of 2017; the history of marijuana legalization in each state (including when legislation was passed and when dispensaries opened for business) and state-level demographic information. During the study period, 29 states had approved medical cannabis, while recreational marijuana was legalized in eight states plus the District of Columbia. According to the Centers for Disease Control and Prevention, the number of opioid-related deaths has increased six times over between 1999 and 2017. Additionally, 36 percent of the 47,600 opioid overdoes in 2017 involved prescription opioids.

After running several statistical and mathematical models that included checks to ensure their results were consistent, the study’s authors found that broader adult-use laws reduce a state’s opioid death rate between 20 percent (for all opiates and prescription opioids) to 35 percent (for synthetic opioids).

“Recreational marijuana laws affect a much larger population than medical marijuana laws, yet we know relatively little about their effects,” study co-author Nathan W. Chan, PhD said in a press release. “Focusing on the recent wave of recreational marijuana laws in the U.S., we find that opioid mortality rates drop when recreational marijuana becomes widely available via dispensaries.”

“Our estimates are sizable,” the study itself states. “For reference, the average never-legalizer state has 4.82 fatalities per 100,000 people from All Opiates (Synthetic Opioids) annually, while for the average [medical marijuana law] state, these are 6.067 and 0.856 per 100,000 people. Thus, our estimates imply annual reductions in All Opioid mortality between 1.01 and 1.27 deaths per 100,000 people for non-[recreational marijuana law] states, on average. For a state with a population of 5 million (near the nationwide median), this would save on the order of 50 lives per year, or roughly 10 averted deaths from Synthetic Opioids alone.”

Those are conservative estimates, the authors add.

Additionally, models showed that white people and women saw the highest reductions in synthetic opioid deaths in states that legalized recreational cannabis: Whites experienced a 32 percent decrease, while the statistical effect for women was larger and “highly statistically significant” compared to what they found for men.

The authors did not identify what mechanism is responsible for this reduction in mortality rates, though past research suggests people who can legally access marijuana may substitute it for opioids. A recent study, for example, found the majority of people who shopped at cannabis retail shops reported using marijuana to help with pain and sleep.

The new study’s authors do stress, however, that the causal effect they identified is “highly robust.”

“Our bedrock findings remain unmoved by variations in modeling assumptions and selections of control variables, and our findings are further corroborated through placebo tests,” they write. “Our results show that there are substantial ancillary benefits to marijuana legalization, especially [recreational marijuana laws], and they offer important food for thought as many states continue to contemplate expansions to both medical and recreational marijuana access.”

Their findings support a growing body of research that has linked the availability of medical marijuana dispensaries with a drop in the rate of local opioid-related deaths.

In fact, that was the focus of the second cannabis-related study published recently in Economic Inquiry. According to its findings, after a medical cannabis dispensary opened in a county, prescription opioid deaths fell locally by approximately 11 percent. These results, the author writes, suggest “a substitutability between marijuana and opioids.”

“Furthermore,” the study concludes, “the unintended beneficial effects of allowing for marijuana dispensary operations should be considered by policymakers as they aim to curtail narcotic abuse and limit the impact of the opioid epidemic.”

New Analysis Explores Relationship Between Medical Marijuana And Opioid Overdoses

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Cannabis in Sports: Unpacking Exemptions for Therapeutic Use

For most adult Canadians, cannabis has never been easier to access. Meanwhile, our elite athletes must abstain while they are in competition or face aggressive fines or suspension.

Canadian MMA fighter, Elias Theodorou, suffers from bilateral neuropathic pain. He feels the pain from his condition in his upper extremities–his hands, wrists, and elbows are all affected.

When he fights, he says, the locations of these “flare-ups” come in direct contact with whatever he punches, elbows, and blocks. “Every time I punch there’s a shocking pain, it’s almost like a stinger.”

Sometimes Theodorou can’t feel these areas of his upper extremities and will push his training to the point of near-injury without realizing. This sort of overexertion could put any athlete into the danger zone.

Theodorou would like to add medical cannabis to his medicinal toolbox, but the rules set out by more than one anti-doping group bans cannabis in his sport.

Despite having a recommendation for medical cannabis from his long-time family doctor, Theodorou has been unsuccessful at securing a medical exemption from the US Anti-Doping Agency (USADA), which administers the UFC’s anti-doping program.

Theodorou has been training in mixed martial arts for the better part of a decade and fighting professionally for nearly six years, but some of the pain he feels today can be traced back to an adolescence spent skateboarding. He has arthritis in his wrists, likely due to a series of breaks and fractures sustained while skateboarding.

The aftermath of that damage leaves him with limited range of motion, and it has even forced him to change his fighting style. His access to medical marijuana in Canada helps, he says, but he must abstain for up to six weeks before a fight if he wants THC to be flushed from his body–the only way he can use cannabis and still qualify for his fights.

Fighters in the UFC are not tested for cannabis out of competition, as per the World Anti-Doping Agency code. But THC, the primary psychoactive compound in cannabis, is prohibited in the days leading up to the fight. If THC is detected in a fighter’s system close enough to the match–at the weigh-in, for example–they will face consequences.

Canada has a separate athletic organization that monitors athletes for potential doping. For both organizations, it is standard, under the World Anti-Doping Code, that they follow World Anti-Doping Agency (WADA) rules.

The Canadian Centre for Ethics in Sport (CCES) has several working groups and committees overseeing things like banned substance testing and issuing Therapeutic Use Exemptions (TUE) for banned substances, like cannabis.

Canadian athletes need to be careful not to confuse legalization of cannabis in Canada with permission to use cannabis in sport.

Canadian Centre for Ethics in Sports

The organization has–for years, they tell Leafly by email–recommended that cannabis be removed from the WADA Prohibited List because they do not believe it meets the standards to be included in the list.

“The CCES has in the past recommended to the WADA List Committee that cannabis [is] removed from the Prohibited List as we feel the evidence supporting its performance-enhancing properties is not conclusively supported by the scientific literature,” writes Paul Melia, CCES President and CEO in an email.

“The WADA List Committee has not followed our recommendation, and so cannabis use remains prohibited in sport. Therefore, even though cannabis was recently legalized in Canada, this does not affect the status of cannabis as a banned substance in sport.

“Canadian athletes need to be careful not to confuse legalization of cannabis in Canada with permission to use cannabis in sport. Canadian athletes also need to be aware that a positive test for cannabis use in competition may result in a significant sanction.”

A TUE application will be considered by the CCES if: “The use of the prohibited substance or method would produce no additional enhancement of performance other than that which might be anticipated by a return to a state of normal health following the treatment of a legitimate medical condition;” and, if “There are no reasonable therapeutic alternatives or other alternatives are ineffective.”

To apply for a TUE with either USADA or the CCES, extensive documentation of the athlete’s medical condition, assessments from several physicians, and proof that the athlete has explored to exhaustion all non-prohibited alternatives to prohibited medications is required.

Conventional prescription drugs, says Theodorou, don’t adequately address the sharp stinging pain and radiating heat he feels in his elbows and hands. As the intensity and frequency of his training ramps up before a fight, sometimes going five hours each day, he wishes more to have the option of using cannabis.

The irony of them telling me not to get hooked on opioids while telling me you need to try a lot more opioids before we can give you cannabis.

Elias Theodorou, Canadian MMA fighter

Despite his doctor’s recommendation, the legality of cannabis in Canada, and the legitimacy of his condition, Theodorou says he’s fighting an uphill battle with the USADA, an organization that receives funding from the Office of National Drug Control Policy (ONDCP), a US agency that must abide by the federal cannabis laws.

Without a TUE, Theodorou must rely on opioid painkillers six weeks before a fight, and laughs good-humouredly at “the irony of them telling me not to get hooked on opioids while telling me you need to try a lot more opioids before we can give you cannabis.”

Theodorou has made four attempts at a TUE from USADA, but they need him to exercise and exhaust all options of what they call “first-line medications,” which include the traditional antidepressants, opioids, and other medications that make up his pain management drug regimen.

“They never say no,” he says, describing the responses from USADA he receives by mail. “They just say you’re denied and we need more explanation.”

Both CCES and USADA are silent about whether any TUEs at all have been issued to athletes for the use of medical cannabis, but Theodorou isn’t giving up hope.

Beyond taking steps to further pursue his own TUE, he is watching the United States for changes to the nation’s federal laws regarding cannabis and whether that, in turn, encourages CCES to grant more (if any) TUEs in Canada.

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What Is CBDV (Cannabidivarin) & What Does This Cannabinoid Do?

CBDV, or cannabidivarin, is one of many molecules derived from cannabis and hemp plants. These molecules, commonly referred to as cannabinoids, are partially responsible for the many effects and therapeutic benefits cannabis has to offer.

CBDV is structurally similar to CBD (cannabidiol). Like CBD, CBDV is not intoxicating when isolated, so it won’t cause the euphoric high associated with high-THC cannabis.

Research has so far demonstrated that CBDV is found mainly in C. indica landrace strains sourced from Asia and Africa, as well as strains naturally lower in THC. Strains that are high in CBD also typically tend to be higher in CBDV.

Much of the research around CBDV has centered around its effect on seizures. GW Pharmaceuticals, which developed the first FDA-approved CBD drug called Epidiolex, is actively developing a CBDV-based drug known as GPW42006 to reduce or prevent epileptic and other forms of seizures.

Their research has shown that CBDV affects the neurochemical pathway of the capsaicin receptors involved in both the onset as well as the progression of several types of epilepsy. GW reports that CBDV has shown anti-epileptic results “across a range of in vitro and in vivo models of epilepsy.”

CBDV is also showing promise in several other areas of medicine:

  • According to a 2018 rodent study, CBDV has shown promise in helping the neurobehavioral issues associated with Rett syndrome. Rett syndrome is caused by an X chromosome mutation that affects girls with seizures, speech issues, and muscle spasticity. Interestingly, CBDV seems to help with both the genetically determined and chemically-induced forms of this and similar diseases.
  • In an animal study published in 2019 in the Journal of Psychopharmacology, CBDV was found to rescue memory defects in mice that have the same genetic defect as people with Rett syndrome. CBDV also helped with neurological defects, but the effects were transient.
  • In a similar 2019 study published in the British Journal of Pharmacology, CBDV was found to possibly benefit patients with Duchenne muscular dystrophy (DMD). This disease is characterized by chronic inflammation and irreversible skeletal muscle damage and degeneration. CBDV may reduce inflammation and restore and even enhance muscle function. CBDV also improved locomotion, highlighting the compound’s potential as a novel therapy for DMD.
  • Childhood intractable epilepsy and autism spectrum disorder (ASD) often go hand in hand. CBDV is being investigated as a potential treatment of some of the more significant ASD issues, such as repetitive behavioral problems, cognitive challenges, and communication and social functioning issues.
  • CBDV may also be a powerful anti-nausea agent. Initial research on rodents shows that CBDV likely acts as an agonist to the CB1 receptors, thereby blocking the nausea response.

Although CBDV was discovered 50 years ago, research is just commencing in an appreciable way. With GW Pharmaceuticals and their CBDV clinical trials underway, this is a hopeful beginning in unlocking the secrets of another potentially powerful cannabinoid.

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CBD Science Update

The 29th annual International Cannabinoid Research Society (ICRS) symposium, which convened last month in Bethesda, Maryland, featured new developments in CBD science that have far-reaching implications for many areas of medicine.

Over 200 scientists from around the world attended the four-day conference, which included 65 oral presentations and nearly 200 posters covering a wide range of topics – with the caveat that researchers had to present new, unpiblished data.

Harvard University scientist Staci Gruber shared encouraging results from “the first open-label to double-blind clinical trial” assessing the impact of a high-CBD, low-THC sublingual tincture in patients who experience moderate anxiety. None of the participants had been using any cannabinoid-based products prior to this study.

Preliminary data “suggests significant improvement following four weeks of treatment when compared to baseline,” Gruber noted. “Specifically, findings suggest that the use of a custom-formulated, whole plant-derived high CBD sublingual tincture results in less severe anxiety and fewer anxiety-related symptoms.”

After the completion of this open-label trial, Gruber intends to undertake a double-blind, placebo-controlled experiment that will generate “empirically sound data regarding the efficacy of sublingual CBD for anxiety.”

CBD for hypertension

Human subjects were also recruited for a CBD study at the University of Nottingham in the United Kingdom, where Saoirse E. O’Sullivan and her team examined the acute and chronic effects of cannabidiol on cardiovascular function.

Previously, the Nottingham scientists had shown that “acute oral administration of CBD (600 mg) causes a reduction in blood pressure at rest and in response to stress.” But would tolerance develop with repeated dosing, thereby mitigating CBD’s hypotensive effect?

To find out, twenty-six healthy males were given 600 mg CBD or a placebo orally for seven days in a randomized, placebo-controlled, double-blind, parallel study. The results were mixed. Measurements of resting blood pressure revealed that tolerance developed in response to chronic CBD administration, but CBD’s ability to lower blood pressure persisted during stress.

“The reduction of arterial stiffness, and improvements in internal carotid artery blood flow and endothelial function after chronic CBD treatment, indicate a positive effect in vascular function that warrants further investigation in relevant patient populations,” O’Sullivan reported.

Preclinical promise

ICRS 2019 included several talks devoted to clinical studies, but most of the CBD presentations showcased cutting-edge data based on preclinical research. The astonishing depth and range of this research underscored CBD’s versatile therapeutic potential.

  • CBD for stroke. A meta-analysis by scientists at the University of Nottingham surveyed the effects of CBD in animal models of focal ischemic stroke. The study found that CBD limited the damage caused by induced brain injury: “CBD significantly reduces infarct volume and improved early functional outcome in experimental stroke in rodents.” University of Nottingham researchers also conducted hands-on, preclinical research that examined the anti-inflammatory and neuroprotective effects of cannabidiolic acid (CBDA), the raw, unheated version of CBD found in the cannabis plant. “Like CBD,” the researchers concluded, “CBDA is effective in reducing blood brain permeability and inflammation in a cellular model of stroke.” A compromised blood-brain barrier is a key factor in the secondary injury cascade that wreaks havoc on the brain during ischemia-reperfusion. CBD and CBDA restore BBB integrity by activating the 5-HT1a serotonin receptor, which also mediates CBD’s and CBDA’s anti-inflammatory effects. In Spain, neonatal animal experiments have paved the way for clinical testing of CBD on brain-damaged babies.
  • CBD for substance abuse. There are no FDA-approved medications to treat cocaine addiction. So, researchers at the National Institute on Drug Abuse (NIDA) set out to assess the CBD’s as an anti-cocaine remedy. The NIDA team gave CBD to cocaine-addicted rats and observed that systemic CBD treatment “shifted cocaine self-administration dose-response curve downward,” meaning that CBD tempered the rats’ craving for cocaine. “These findings suggest that CBD may have therapeutic utility to blunt rewarding effects of cocaine,” the NIDA researchers surmised. They also identified several molecular pathways whereby CBD conferred an anti-addictive effect on lab animals. These included the 5-HT1a serotonin receptor, the CB2 cannabinoid receptor, and an ion channel receptor known as “TRPV1” (pronounced trip-vee-one). When chemical “antagonists” were administered to block the signaling of these receptors, it negated CBD’s anti-addictive effects.
  • CBD for prostate cancer. Italian scientists conducted follow-up research into the combined effect of two plant cannabinoids – CBD and cannabigerol (CBG) – on aggressive prostate cancer. A previous study had shown that 1:1 combination of CBD:CBG “significantly reduced tumor relapse in animals with hormone refractory status, and, in vitro, inhibited cell proliferation and induced apoptosis.” Their latest findings, as reported at ICRS, disclosed “how purified plant cannabinoids (CBD and CBG) affect the metabolic system of malignant tumors,” leading to “notable shifts of specific oncogenic related signaling pathways” in prostate cancer cells. This proves “the efficacy of phytocanabinoids as metabolic reprogramming agents,” which could form the basis of a breakthrough therapy for “highly malignant hormone refractory prostate cancer,” according to the Italian researchers. Scientists at Auburn University reached a similar conclusion regarding the antitumoral properties of CBD and THC, which inhibited prostate cell proliferation in a dose-dependent manner. This is encouraging news for the one out of nine men who will develop prostate cancer, the second leading cause of cancer death among American males. The preclinical experiment at Auburn suggests “that cannabinoids could be developed as novel therapeutic agents for the treatment of prostate cancer.”
  • CBD for arthritis and gum disease. A team of Israeli, British, and American scientists analyzed the anti-inflammatory and painkilling effects of synthetic CBD in an animal model of arthritis. “CBD was shown to exert a potent analgesic effect” in preclinical research, which shed new light on CBD’s “anti-inflammatory mechanisms of action.” Another preclinical probe, conducted at the University of Leeds School of Dentistry in the UK, documented the potent anti-inflammatory effects of CBD on gum disease. The ability of CBD to modulate immune function “could provide possible therapeutic applications in the field of periodontal research,” the Leeds study concluded.

CBD oil products

There’s good reason to be excited about CBD’s potential health benefits, but a word of caution is necessary. Administering pure CBD to animals in a controlled laboratory setting is not the same as human consumption of a CBD oil product purchased from an unregulated internet storefront.

The Prague-based International Cannabis and Cannabinoids Institute (ICCI) analyzed the quality of 70 hemp-derived CBD oil samples available in the European Union, and the results reported at the ICRS symposium were sobering, to say the least. Twenty percent of the samples contained less CBD than indicated on the label. THC was present in 89 percent of the samples, but in most cases no amount of THC was provided. And traces of highly toxic polycyclic aromatic hydrocarbons were found in all the oils tested, underscoring the strong need for better extraction and processing practices by CBD product-makers.

Similar problems plague the CBD market in the United States. Inaccurate or incomplete CBD product labels undermine a consumer’s ability to make well-informed decisions. According to researchers at Thomas Jefferson University in Philadelphia and Washington University in St. Louis: “Recent studies have demonstrated that hemp-derived CBD products purchased over the internet are frequently mislabeled, contaminated, or are outright fraudulent (contain no cannabinoids whatsoever). Therefore, patients are more likely to receive medical benefit from products that are routed through state-licensed cannabis markets, where lab testing for CBD content is required.”

Licensed cannabis dispensaries and delivery services also need to up their game and improve their product offerings. “Despite the obvious medical benefits, the availability of CBD-containing products in state-licensed retail stores is highly variable and surprisingly sparse. In one Pennsylvania store only 20 of products (39 or 196) contained CBD,” the U.S. researchers noted. “Results highlight the need for expanded patient access to CBD products.”

Martin A. Lee is the director of Project CBD and the author of several books including Smoke Signals: A Social History of Marijuana – Medical, Recreational and Scientific and Acid Dreams: The Complete Social History of LSD – the CIA, the Sixties and Beyond.

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