NHL Alumni Study Centres on CBD, Puts THC on Ice

When Glenn Healy, head of the NHL Alumni Association, recently announced that a hundred retired players would be given CBD in a study examining the compound’s possible role in treating pain and post-concussion neurological disorders, many former athletes celebrated–especially those struggling with depression, post-traumatic stress disorders (PTSD), and dementia from chronic traumatic encephalopathy (CTE). But one question lingered in the minds of some people: “What about THC?”

“I know some former players who are using THC instead of CBD to cope,” said Rob Frid, who suffered dozens of concussions while playing junior and minor league hockey and now suffers from chronic pain and debilitating neurological problems. (The 43-year-old has been diagnosed with dystonia, a disorder that causes painful muscle spasms.) “There is no doubt in my mind that studying THC would be beneficial,” he told Leafly.

Researchers have been pointing to THC as a possible treatment for brain injuries for decades. In 1998, the Proceedings of the National Academy of Sciences of the United States published a report outlining the neuroprotective properties of cannabidiol (CBD) and tetrahydrocannabinol (THC). Those findings formed the basis of a US government-held patent on cannabis compounds as antioxidants and neuroprotectants. The government stated that both compounds could play a role in limiting neurological damage following stroke and trauma.

In 2013, Israeli researchers discovered that cannabis may prevent long-term brain damage when THC is administered before or shortly after injury. They found that doing so induces the biochemical processes necessary to protect critical brain cells while preserving long-term cognitive function. In fact, Israel Defense Force doctors have administered CBD or low-dose THC as a first-line treatment to soldiers who suffer brain trauma.

In recent years, a professor of psychiatry at Harvard University, Lester Grinspoon, has made waves by stating his belief that cannabis can make athletes more CTE-resistant. Grinspoon, who made his case for cannabis in an open letter to the NFL in 2014, also believes that THC stimulates healing after traumatic brain injury.

THC plays a role in pain management, according to Tony Iezzi, a psychologist who specializes in treating patients dealing with brain injury and chronic pain. “CBD alone won’t always cut it when it comes to treating pain. You need something more, and that is where THC comes in,” he told Leafly, adding that the two compounds work in tandem to treat pain.

Iezzi, who is affiliated with the London Health Sciences Centre in London, Ontario, believes that only CBD is front and centre in the NHL Alumni Association study in part because of the stigma associated with THC, which has psychoactive properties. “I think they chose to focus on CBD because it’s the more socially acceptable of the two cannabis compounds. They have to start somewhere,” he added. “At some point they will have to devote some attention to the effects of THC.”

His views are echoed by Mark Ware, the chief medical officer at Canopy Growth, an Ontario-based licensed producer that has partnered with the NHL Alumni Association and Neeka Health Canada to conduct this clinical research.

Ware, who has been an associate professor of family medicine and anesthesia at McGill University and is a well-known cannabis researcher, sees potential in THC to treat pain and post-concussion neurological disorders.

But it’s not front and centre in this study partly because of the stigma, he told Leafly. “There is a long history of people thinking of THC as a substance of abuse. We have to be conscious of that.” He cites another factor, too. Having THC in their system might pose a problem for study participants required to undergo drug tests for employment or insurance purposes. “There are many reasons to be careful with regards to THC, especially among those who must test clean for it,” he said.

That being said, Ware has not ruled out incorporating THC into this study, which is expected to begin this summer and take a year to complete. He explains that the study has three arms. The first group of participants will take CBD, the second group will be given a placebo and the third group will administer CBD along with one other element–one that is yet to be determined. Will it be THC?

“Nothing is written in stone at this point,” said Ware, adding that the goal of the study is to help determine “the secret sauce” that can be used to treat pain and post-concussion neurological disorders.

Ware said that if THC isn’t examined in this study it could very well be incorporated into a future study. “There is no scientific reason for not looking at it,” he conceded.

Though Frid is disappointed that THC is not at the fore of the upcoming NHL alumni study, the former hockey enforcer sees the initiative as a positive development. “NHL alumni are no longer saying, ‘Let’s wait for the science.’ They are making it happen. They are taking a step forward,” said Frid. “It’s amazing news.”

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Sploofs 101: How to Reduce the Smell When Smoking Cannabis

Regardless of whether weed is legal where you live, we still have to contend with roommates, parents, and neighbours, some of whom might take issue with the conspicuous scent of smoking cannabis.

So, strike a compromise: Continue smoking but take actions to minimize the risk they’ll smell it in the first place.

We all know about the trick of stuffing a towel under the crack of your closed door. But there’s something else that helps that you need to look into: a sploof.

These are handheld devices that typically contain carbon filters. You blow through one end, and out the other comes a whisper of the smoke you exhaled into it. They’re never 100% effective but using a sploof should be the difference between having happy roommates and getting an eviction notice.

Smokebuddy

Photo by Jesse Milns for Leafly

We couldn’t write a sploof review without first bringing up the Smokebuddy. You’ve probably seen them being sold at your local headshop–this brand really seems to have a stranglehold across North America, as you can find the device in smoke shops across Canada and the US.

While the SmokeBuddy can be held in your hand, it is probably too big for your pocket.

It comes in a variety of visually designs, including tie-dye, camo, or your favourite primary and secondary colours.

The company boasts that it can last up to 300 exhales through regular use, at which point you’ll find a ton of resistance when you try to blow into the Buddy.

We won’t lie, we didn’t count how many exhales it lasted us, but the Smokebuddy easily lasted more than a month of regular use.

What didn’t we like? The plastic packaging is a real pain to open: You’ll need a pair of heavy duty scissors and a calm mind. And Smokebuddies are for one-time use: there is no replaceable filter system and the device’s outer plastic shell makes it nearly impossible to recycle.

Americans can buy the Smokebuddy right on Amazon for $12.50 USD, while Canadians will need to shell out $24.95.

The Smokebuddy also has a smaller “junior” model as well as a larger “mega” model. So if portability or long-lasting use are your top wants, you might want to try those variations.

Eco Four Twenty

sploof
Photo by Jesse Milns for Leafly

This small, cylindrical, device is a heavyweight that exudes, “I am unbreakable.” It’s billed as a sploof made with “aircraft grade aluminium casing” and including a “2 stage medical grade filter.” While it costs a bit more than the Smokebuddy, the Eco Four Twenty also boasts a replaceable cartridge system that uses activated carbon as well as HEPA, good for 500 exhales.

The Eco Four Twenty feels good in your hand. And the thought of buying replacements that are cheaper than purchasing a new Smokebuddy really piqued my interest.

There’s just one problem: The filter lasted for less than a week of regular use–we tried twice. There is no way in hell this thing lasts anywhere close to advertised 500 exhales. If we had to guestimate it lasted us a fifth of that, at most. Maybe they’re testing it on bong-smoking ants?

Still, the Eco Four Twenty does have some positive points, especially due to its small size and the sleek design that makes it the sploof you would most want to see on your coffee table. That replaceable filter, also makes it one of the more eco-friendly options.

The creators behind the EFT are Canadian, so if you live north of the US border chances are you can find it in your local headshop. You can also expect fast shipping from Toronto if you order it directly from the company.

The device costs $26.95 USD and a pack of two replacements

Sploofy

sploof
Photo by Jesse Milns for Leafly

One of the first competitors of Smokebuddy, the Sploofy, has a legion of fans. The device has now gone through three iterations, begging the question–how much did the first version suck? Well, pretty badly, at least when we first tried it. A significant amount of smoke leaked from the front of the device before it even had a chance to go through the filter.

Having recently released a third generation, the V3 redeems itself with a re-designed mouthpiece, and in our tests it alleviated the problems that we had with the first version. The V3 also boasts a HEPA filter that the Smokebuddy doesn’t.

While Sploofy’s website doesn’t estimate how many exhales you get, this bad boy lasted us quite a while. It’s even taller in size as the Smokebuddy and just as wide, and it appears that the filter is bigger than the SB–meaning you may get even more use out of it.

The device is covered with a sheath of hard plastic, which reveals an ugly undercarriage containing the filter and a big wad of glue holding a mesh screen on to the filter. But hey, does anyone’s car look clean under the hood?

The bulky filter cartridge is also replaceable. The Sploofy V3 retails on online for $19.99 USD.

Angel

sploof
Photo by Jesse Milns for Leafly

A new competitor will soon be on the block, and Leafly was able to snag its hands on a prototype. Coming in a hot-red plastic casing, Angel hopes to disrupt the commercial sploof market and take on the Sploofies and Smokebuddies of the world with a design that easily slips into your pocket and allows for a tight grip when being used.

We didn’t test it to its limits, but if we had to guess, its smaller size likely makes it last for a shorter period of time than the Smokebuddy and Sploofy (but hopefully more than the Eco-Four Twenty).

Flow Filters, the developer behind the device, tells Leafly that they are hoping to sell it at the same or lower price than the Smokebuddy.

While not on the market just yet, we’re cautiously optimistic that the Angel sploofy will turn out to be a big hit: the team is taking months to perfect the design and the filtering medium, so you have a sense they want to put out a quality product when it comes time to hit the shelves.

A DIY Solution

sploof
Photo by Jesse Milns for Leafly

Need a sploof fast and at practically no cost?

All you need to McGyver your own is: a finished toilet paper roll, dryer sheets, and elastic bands.

Stuff the roll with dryer sheets, and then take a few more dryer sheets and lay them flat on one end of the roll. Use the elastic bands to secure the dryer sheets snuggly on to the end of the roll.

And there you have it, a sploof that doesn’t cost an arm and a leg.

You can even decorate it too. Want to call it “David Blowie,” in honour of the rockstar’s 1976 arrest for marijuana? Go right ahead! You can even bedazzle it with fake jewels if you’re into arts and crafts.

What’s great about the home-made sploof is that it masks and freshens the air around you, something none of the store-bought sploofs can do (we smell an opportunity). Conversely, the store-bought units may not do as good a job at masking but it

Look, your home-made sploof isn’t going to be as air tight as the chamber holding the filter of a manufactured sploof, so you’re always going to have at least a little bit of smell linger. But if you have marijuana-skeptic roommates or parents in your residence, the decision between no sploof and a home-made sploof is easy.

Which sploof is the best? That’s a hard question because there’s so many factors, and each sploof has its own pros and cons. In our tests, all of them were able to dissipate the smoke, leaving only a very transient whiff of cannabis odor. So whether you’re looking for something that fits in your pocket, starts a conversation while sitting on your coffee table, or that provides a long-lasting solution, there’s a sploof for you.

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THC versus Breast Cancer

By Alex Andia On March 18, 2019

It’s no secret that many cancer patients are using cannabis to help manage pain, fatigue, nausea, and other side effects of chemotherapy. Less well known is the fact that extensive preclinical research shows that plant cannabinoids – most notably, tetrahydrocannabinol (THC) and cannabidiol (CBD) – produce antitumor responses in various animal models of cancer.

The vast majority of this preclinical research has examined the anticancer activity of pure compounds, mainly THC isolates. But medical cannabis patients aren’t using pure, single-molecule THC to battle cancer. Instead, they are consuming whole plant cannabis oil extracts that include hundreds of compounds, many of which also have therapeutic properties. These artisanal cannabis oil preparations are available in licensed dispensaries in states where medical cannabis is legal and elsewhere via the unregulated black market.

Thus far, however, few rigorous studies have analyzed the effects of whole plant cannabis extracts. So a team of Spanish researchers, led by Cristina Sanchez at Complutense University in Madrid, decided to compare the efficacy of pure THC isolates and THC-rich oil extracts in a series of preclinical experiments that focused on breast cancer. (The oil extracts were provided by Aunt Zelda’s, a California-based medical cannabis producer.) The researchers also investigated the effects of pure THC and an artisanal THC-rich oil formulation when each was combined with standard chemotherapy drugs.

Their findings were reported in a 2018 article – “Appraising the ‘Entourage Effect’: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer” – which was published in the journal Biochemical Pharmacology. The phrase “entourage effect” in this context refers to the full-spectrum synergistic interplay between numerous cannabis compounds – cannabinoids, terpenes and flavonoids – that impart a therapeutic impact that’s greater than the sum of the plant’s individual components.

Spoiler alert: Both THC and the artisanal THC-rich oil were shown to have antitumoral properties, but the oil worked better than the THC isolate for three different breast cancer subtypes.

Tricky to Treat

It is estimated that one in eight women will develop breast cancer. Breast cancer is tricky to treat because there are few biomarkers that signal when someone has the disease, and many patients show or develop resistance to current therapies. Moreover, several specific types of breast cancer respond poorly to modern treatment. These difficulties underscore the importance of exploring new treatments for breast cancer.

Two biomarkers frequently used to diagnose breast cancer are hormonal receptors (the estrogen receptor and progesterone receptor) and the HER2 oncogene (a gene which can transform a normal cell into a tumor cell). But a more aggressive malignancy, known as “triple-negative breast cancer,” doesn’t express hormonal receptors or the HER2 oncogene. No targeted therapy exists for triple-negative breast cancer, so patients are treated with harsh chemotherapies that indiscriminately kill proliferating cells, whether cancerous or not.

These three types of cancer – hormone-sensitive, HER2, and triple-negative – were used as models for “Appraising the entourage effect.”

In all models of breast cancer studied, in vitro as well as in vivo, the whole plant extract was significantly more effective at producing anticancer effects than single-molecule THC. These results were largely consistent for type of cancer and type of model. Researchers tested the compounds in cell cultures (petri dishes) and in rodent models (mice).

THC & Hormone-Sensitive Breast Cancer

In the case of hormone-sensitive breast cancer cells, whole plant extract was found to be 15-25% more potent than THC alone. In live-animal models single molecule THC exhibited no significant antitumor response, unlike the whole plant extract, which had a pronounced antitumor effect. Testing on lab animals is a necessary step towards establishing the efficacy of a specific clinical treatment.

When the cannabinoid preparations were added to tamoxifen, a standard chemotherapy drug, in a cell plate, the combined therapy was about 20-25% more effective than chemotherapy alone. But these results were not replicated in live-animal trials. Importantly, the cannabinoids also did not negatively impact the efficacy of the chemotherapy. This suggests that at the very least using cannabis as an add-on treatment to deal with common side effects of chemotherapy, like nausea and appetite loss, won’t impede chemotherapy’s ability to destroy cancer cells.

In hormone-sensitive breast cancer, it appears that THC produces effects via interaction with the CB2 cannabinoid receptor. CB2 receptor activation has received significant attention because of its potential to treat diseases while avoiding the “high” mediated by the CB1 cannabinoid receptor, which THC also activates. When THC binds to CB1, it causes the swimmy-headed feelings of intoxication associated with cannabis consumption.

THC & HER2-Positive Breast Cancer

Whole plant extract was found to be significantly more potent than THC for HER2-positive breast cancer cells. Both single-molecule THC and whole plant extract showed antitumor effects when the experiment was replicated in mice. Additionally, both THC and the whole plant extract amplified the anticancer effects of lapatinib, the standard chemotherapy drug for HER2 breast cancer.

As with hormone-sensitive breast cancer, THC’s antitumoral effect in HER2-positive breast cancer experiments was shown to be mediated by the CB2 cannabinoid receptor. Published in the Proceedings of the National Academy of Science, a subsequent report by Cristina Sanchez and other Spanish scientists noted that HER2 and CB2 receptors are often found in the same exact place on cells.

CB2 actually conjoins with HER2 – forming what is called a dimer – and this dimerization is associated with poor treatment outcome for breast cancer. The PNAS report shed new light on THC’s anticancer mechanism of action: When THC binds to the CB2 receptor, it breaks up the CB2-HER2 dimer, triggering a chain reaction of signals that culminates in tumor regression.

THC & Triple-Negative Breast Cancer

Triple-negative, the breast cancer subtype with the worst prognosis, does not generally respond well to chemotherapy. But the Spanish group found that THC and THC-rich cannabis oil both offer some hope in improving treatment outcomes for this highly aggressive cancer. Again, the whole plant extract was found to be more effective than THC alone in decreasing the viability of cancer cells in vitro as well as in mouse model studies.

There are several other examples where a combination of plant cannabinoids and standard chemotherapy agents have produced a heightened antitumoral response that exceeded the potency of either therapy alone. A phase 2 clinical trial tested the strength of Sativex, an equal THC and CBD mixture, combined with temozolomide, the “gold-standard” chemo for brain cancer, and the results were positive.

Cancer patients are often treated with several single-compound drugs in an effort to create a treatment that can hit multiple targets. “Although current medicine is mostly based on the use of pure compounds that have single targets,” the Spanish scientists write, “it is increasingly obvious that for diseases as complex as cancer, multi-target approaches could conceivably be more effective.”

The results of the Spanish study, along with compelling data from other researchers, suggest a promising future for whole plant cannabis oil extracts and multitarget cancer therapies. But the Western medical system and its typical drug development procedures are not conducive to the approval of complex botanical preparations as multitarget medicaments – in part because elucidating a precise mechanism of action when numerous compounds are involved is much more difficult than studying a single-molecule pharmaceutical that’s geared toward a single, primary outcome.

The Takeaway

The fact that both the THC isolate and the whole plant cannabis extract were shown to be effective at reducing tumor viability is truly groundbreaking and should be an impetus for advancing the development of nontoxic, cannabinoid-based treatments for breast cancer.

Cannabinoid therapies are particularly promising for tumor-producing cancers given that “no overtly cannabis-resistant tumors have been described so far,” according to the Spanish researchers. “Considering how different cancer subtypes are, and the fact that the viability of non-transformed cells is not affected by cannabinoids at the concentrations they kill tumor cells, it is tempting to speculate that these compounds tackle essential, as yet unidentified, cellular functions that all cancer cells share, and that are absent in their non-cancerous counterparts.”

The Spanish breast cancer study underscores the importance of the entourage effect by demonstrating that full spectrum artisanal cannabis oil extract with numerous components is more effective than pure THC.* “[A]lthough the pharmacology of cannabis drug preparation extracts is obviously more complex to study,” the researchers acknowledge, “this therapeutic approach has the potential to produce better therapeutic responses than pure cannabinoids.”

The Spanish scientists emphasize that the whole plant cannabis drug preparation “did not, in any case, diminish the antitumor efficacy of any of the standard treatments.” That’s good news for cancer patients who use cannabis to manage the adverse side effects of chemo. Cannabis is very likely a safe add-on therapy for treating pain and nausea and for appetite stimulation. And it may also increase the efficacy of standard chemotherapy treatments, which means that chemo could be more effective – requiring lower and less toxic doses – when used in combination with cannabis.

Alex Andia, who holds his PhD in Chemistry, teaches Organic Chemistry at the City University of New York – City College. He is also the brains behind Chemical Makeup, a non-profit dedicated to promoting the queer voice in science.

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

Footnote

*An interesting finding from the Spanish breast canceer study pertains to the not fully understood role of terpenes, the aromatic compounds that give cannabis its distinctive smell. The scientists created a “terpene cocktail” composed of the 5 most prominent terpenes in the full-spectrum cannabis oil extract: beta-caryophyllene, alpha-humulene, nerolidol, linalool, and beta-pinene. When added to the THC isolate, however, this terpene cocktail failed to increase the antitumoral efficacy of the single-molecule cannabinoid. This could mean that mixing a few terpenes with pure THC does not adequately recreate the qualities of a full-spectrum cannabis oil extract. Or it could be that other compounds in the oil extract are responsible for enhancing THC’s anticancer impact. The authors note that the whole plant cannabis oil extract used in the study also contained measurable amounts of cannabigerol (CBG) and tetrahydrocannabinolic acid (THCA – the ‘raw’ form of THC that won’t get you high). CBG has demonstrated effectiveness against colon cancer in preclinical models, and THCA is known to interact with a PPAR (nuclear) receptor that mediates apoptosis (cell death) in cancer cell lines. A combination of all these compounds may be required to achieve the antitumoral response observed in the Spanish breast cancer study.

References

  • Blasco-Benito S, Moreno E, Seijo-Vila M, Tundidor I, Andradas C, Caffarel MM, Caro-Villalobos M, Uriguen L, Diez-Alarcia R, Moreno-Bueno G, Hernandez L, Manso L, Homar-Ruano P, McCormick PJ, Bibic L, Bernado-Morales C, Arribas J, Canals M, Casado V, Canela EI, Guzman M, Perez-Gomez E, Sanchez C. Therapeutic targeting of HER2-CB2R heteromers in HER2-positive breast cancer. Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3863-3872. doi: 10.1073/pnas.1815034116.
  • Blasco-Benito, S.; Seijo-Vila, M.; Caro-Villalobos, M.; Tundidor, I.; Andradas, C.; Garcia-Taboada, E.; Wade, J.; Smith, S.; Guzman, M.; Perez-Gomez, E.; Gordon, M.; Sanchez, C. Appraising the “Entourage Effect”: Antitumor Action of a Pure Cannabinoid versus a Botanical Drug Preparation in Preclinical Models of Breast Cancer. Biochem. Pharma. 2018, 157, 285.
  • Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R. L.; Torre, L. A.; Jemal, A. Cancer Statistics, 2018. Ca-Cancer J. Clin. 2018, 68, 394.
  • Caffarel, M. M.; Andradas, E.; Perez-Gomez, M.; Guzman, M.; Sanchez, C. Cannabinoids: a New Hope for Breast Cancer Therapy? Cancer Treat. Rev. 2012, 38, 911.
  • Campos, A. C.; Fogaca, M. V.; Sacarante, F. F.; Joca, S. R. L.; Sales, A. J.; Gomes, F. V.; Sonego, A. B.; Rodrigues, N. S.; Galve-Roperh, I.; Guimaraes, F. S. Plastic and Neuroprotective Mechanisms Involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders. Front. Pharmacol. 2017, 8, 269.
  • ElSohly, M.; Waseem, G. Handbook of Cannabis, Oxford University Press, Oxford, United Kingdom, 2014, pp. 3.
  • Harbeck, N.; Gnant, M. Breast Cancer, Lancet, 2017, 389, 1134.14
  • Ligresti, A.; De Petrocellis, L.; Di Marzo, V. From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology. Physiol. Rev. 2016, 96, 1593.
  • Ligresti, A.; Moriello, A. S. K.; Starowicz, I.; Matias, S. P.; De Petrocellis, L.; Laezza, C.; Portella, G.; Bifulco, M.; Di Marzo, V. Antitumor Activity of Plant Cannabinoids with Emphasis of the Effect of Cannabidiol on Human Breast Carcinoma. J. Pharmacol. Exp. Ther. 2006, 318, 1375.
  • McPartland, J. M.; Russo, E. B. Handbook of Cannabis, Oxford University Press, Oxford, United Kingdom, 2014, pp. 280.
  • Russnes, H. G.; Lingjaerde, O. C.; Borresen-Dale, A. L.; Caldas, C. Breast Cancer Molecular Stratification: From Intrinsic Subtypes to Integrative Clusters. Am. J. Pathol. 2017, 187, 2152
  • Russo, E. B. Beyond Cannabis: Plants and the Endocannabinoid System. Trends in Pharmcol. Sci. 2016, 37, 594.
  • Russo, E. B. Taming THC: Potential Cannabis Synergy and Phytocannabinoid-Terpenoid Entourage Effect. Br. J. Pharmacol. 2011, 163, 1344.
  • Schwarz, R.; Ramer, R.; Hinz, B. Targeting the Endocannabinoid System as a Potential Antticancer Approach. Drug Metab. Rev. 2018, 50, 26.
  • Siegel, R. L.; Miller, K. D.; Jemal, A. Cancer Statistics, 2018. Ca-Cancer J. Clin. 2018, 68, 7.
  • Velasco, G.; Sanchez, C.; Guzman, M. Towards the Use of Cannabinoids as Antitumor Agents. Nat. Rev. Cancer 2012, 12, 436.
  • World Health Organization. Global Health Observatory. Geneva: World Health Organization; 2018. Who.int/gho/database/en/.

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