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

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  • 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.
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  • ElSohly, M.; Waseem, G. Handbook of Cannabis, Oxford University Press, Oxford, United Kingdom, 2014, pp. 3.
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What Types of Pain Can Cannabidiol (CBD) Treat?

Pain, when used as an umbrella term, is more vast than the Pacific Ocean. Using CBD to treat pain can be effective only under the pretense that the type of pain is well-understood and properly diagnosed.

Most of us have crossed paths with the loud, piercing, cuss-worthy persona of acute pain: an elbow dings the edge of the table or a pinky toe that has found the bed frame yet again at 3 a.m. Other types of pain produce less shock value but are no less odious in nature.

For the sake of this article, I’ll simply go into the types of pain that CBD has shown to treat effectively: neuropathic and inflammatory pain.

Types of Pain

CBD treats neuropathic pain like Cinderella’s foot fit the magic shoe–a blissful, but unexpected, union. Neuropathic pain is largely created and sustained due to the glutamenergic system, which is a major excitatory neuronal pathway. Glutamate is the neurotransmitter that is responsible for turning neurons on, which is great, sometimes.

Inflammatory pain is related to neuropathic pain, except it is not limited to neurons. Examples of inflammatory pain include all types of arthritis, a few autoimmune diseases such as Crohn’s and ulcerative colitis, and simple conditions like headaches, cramps, muscle aches, and pains.

For humans, communication is key, not only interpersonally but also molecularly. Problems arise in paradise when cells become damaged due to injury or chronic illness. When the body senses this damage, it cranks inflammation to HIGH and begins pumping inflammatory agents on its cells.

The point is to promote death of the damaged cell, otherwise called apoptosis. Our bodies don’t enjoy malfunctioning cells and would prefer that they throw in the towel–this is important in ridding ourselves of possible cancer and maintaining optimal functioning. However, when this becomes a chronic condition, it is named inflammatory pain.

How CBD Works for Pain

CBD inhibits glutamate release and other inflammatory agents, which makes it ‘neuroprotective‘ and excellent at dulling the prickling, tingling and burning sensations that neuropathic pain is characterized for. CBD can be used as a supplement to help manage neuropathic pain, alongside other natural supplements such as magnesium glycinate.

Pain due to inflammation is not as easily characterized as other types of pain, mostly because its origins of pain vary and so does the experience. On the bright side, CBD is good at calming inflammation, no matter what the root cause.

The anti-inflammatory mechanism of cannabidiol is unique to cannabis. It doesn’t work like other anti-inflammatory drugs by inhibiting COX-1 and COX-2 receptors, which means you don’t run the risk of developing gastrointestinal ulcers or heart attacks, hooray! Some studies have shown that cannabinoids (CBD and THC) are up to twenty times more potent anti-inflammatory agents when compared to NSAIDs (eg. ibuprofen).

When taken regularly alongside other natural anti-inflammatory supplements (eg. curcumin, Omega-3), CBD can provide systemic relief of inflammation. Usually taken three times per day, dosing at each interval depends on your unique needs. Typically patients start with 0.5 ml per dose and increase until maximum relief.

Cannabidiol can be an effective, non-psychotropic alternative to THC when used correctly. However, we are still in the infancy stage of incorporating CBD into health and medicine, so it is important to consult your physician when contemplating the use of CBD to treat pain.

It’s important to remember that CBD, like other nutraceuticals, can interact with medications.

The takeaway? CBD isn’t effective in treating all types of pain–for that reason, it’s important to understand your pain: does it worsen with the weather, cause swelling, or is it persistent and stabbing? If you feel that you experience inflammatory or neuropathic pain, talk to your doctor. CBD supplementation could be right for you.

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What Getting High Alone Can Teach You About Yourself

A Canadian study published last month in the journal Drug and Alcohol Review looked for differences between people who consume cannabis socially versus those who consume cannabis solo, and found:

Compared to individuals reporting their most recent cannabis-using occasion as social, solitary users were significantly more likely to screen positive for psychosis, endorse more symptoms of cannabis abuse/dependence, report using cannabis to cope, and use cannabis on more days within the previous 30 days.

In its own words, the study “sought to examine the extent to which the social context of cannabis use is related to patterns of use and associated harms.”

Harms, but What About Benefits?

Please note that this statement of purpose doesn’t even consider the possibility that there may be associated benefits to cannabis in addition to associated harms. In fact, Toni Spinella–a master’s student in psychology and neuroscience and the study’s lead author–seems to think anyone who uses cannabis for “coping” treads in dangerous waters.

The study’s author seems to assume that anyone who uses cannabis for ‘coping’ treads in dangerous waters. But don’t we all cope with something?

“It’s possible that they lack other coping strategies,” Spinella told the CBC. “If you’re alone, why are you using alone? That’s something that you might want to ask yourself and if you realize, ‘OK, I’m using alone because I’m sad tonight or I’m stressed,’ then maybe that’s a red flag that you should think more about.”

Fair enough, but a red flag compared to what other coping mechanisms? Whiskey? Junk food? Internet scrolling? Gambling? Binge watching? Xanax?

Is Solo Smoking Making Me Psychotic?

As for the idea that consuming cannabis alone might lead to psychosis, allow me to start by asking a couple of common sense questions:

  • Is it possible that people with mental health conditions are more likely to use cannabis in an attempt to self-medicate that condition?
  • Is it possible that people using cannabis to treat mental health conditions would be more likely to do so alone rather than in a social setting?

The answer to both questions is pretty clearly yes.

Studies have shown that cannabis and cannabinoids can improve the symptoms of schizophrenia, PTSD, depression, anxiety, and other mental health conditions. And if you’re using cannabis to treat one of these conditions, doesn’t that seem like something you’re more likely to do at home with some frequency (compared to someone who smokes weed maybe once a month whenever it’s offered to them at a party)?

A Link Is Not a Cause

So while there may indeed be a correlation between psychosis and getting high alone, that’s a far cry from causation. Even the study’s author admits this. That’s why the CBC had to use a fudge term in its otherwise alarming headline:

Getting High Alone Linked to Psychosis, Dependence, Study Suggests

Can you can spot the fudge term?

Trick question. There are two of them: linked to and suggests.

Linked to means there’s no actual evidence to show that cannabis causes psychosis. Rather, someone with psychosis may be more likely to use cannabis than someone without psychosis.

Suggests means that even the evidence showing a “link” between the consumption and the medical condition is pretty paltry.

In Defense of Crutches

Toni Spinella’s aversion to using cannabis as a coping mechanism reminds me of a joke by Doug Benson, a longtime cannabis comedian and the host of Getting Doug With High.

Some people say marijuana is a crutch. Yeah. Crutches help people walk.

Someone should tell Spinella that while we’d all like to live in a world where nobody ever gets stressed out or feels sad, that just ain’t happening. In the meantime, we need to find relatively healthy ways to cope.

A Therapeutic Option

Even if you live the life of a fully-optimized self-actualizing perfect person, you’re still going to be touched by trauma, depression, and anxiety–all of which can be treated with cannabis, a therapeutic option that’s demonstrably safer and less habit-forming than pharmaceutical drugs.

Cannabis has even been shown to help those suffering from loneliness itself, which the medical establishment increasingly sees as a real and growing epidemic. A recent study by Cigna, a health insurance company, found that a full 47 percent of Americans often feel lonely or left out. Thirteen percent say not one person knows them well. This has serious health consequences.

Loneliness as a Public Health Issue

In 2010, researchers at Brigham Young University published a groundbreaking study that showed chronic loneliness can take about 15 years off of a person’s life expectancy–roughly the same impact as obesity, or smoking nearly a pack of cigarettes per day.

But the good news is cannabis can greatly diminish the negative impacts of loneliness.

In 2013, researchers at the University of Kentucky published findings from a study that asked, “Can marijuana reduce social pain?” The answer was yes:

Marijuana buffered the lonely from: negative self-ratings of self-worth and mental health, depression over time, and even distress following exclusion… Marijuana has been used to treat physical pain, and the current findings suggest it may also reduce emotional pain.

Again, the researchers make clear that cannabis also has potential harms. And that coping with loneliness is not the same as overcoming it.

Put another way: You don’t want to use crutches for the rest of your life, but it’s better than trying to walk on a broken leg

You Don’t Have to Be Lonely to Be A Lone Stoner

“The Lonely Stoner seems to free his mind at night.”Kid Cudi

We’ve already pointed out that Toni Spinella’s research ignores the considerable evidence that cannabis may be a therapeutically beneficial treatment for someone dealing with loneliness and depression. But she also fails to recognize that a relatively healthy person may find significant benefit from a little alone time with the bong.

I don’t have a study to back me up here, but I do speak from personal experience when I say that just as getting high together can help two or more people connect in a profound or at least interesting way (i.e. “get on the same wavelength”), cannabis can also help us connect with our own authentic selves.

Enlighten Up Yourself

“When you smoke the herb,” Bob Marley once said, “it reveals you to yourself.”

What’s revealed is not always flattering, but even a difficult realization about one’s self can yield helpful insights and spur true psychological growth.

Again, I can’t cite a study for this since most cannabis research continues to ignore the plant’s benefits, but I can call in an expert witness: Famed astronomer Dr. Carl Sagan, best known as the host of Cosmos, a 13-part exploration of far-out space science that became the most widely watched series in the history of American public television.

Astronomer Carl Sagan, professor of astronomy and space science at Cornell University, was one of the first scientists to speak out about the positive properties of cannabis. (AP Photo/Lennox McLendon)

Sagan contributed an anonymous essay to Marijuana Reconsidered (1971), a book written by eminent cannabis researcher Dr. Lester Grinspoon, one of Sagan’s closest friends. Identified only as Mr. X., Sagan explained that his support for ending cannabis prohibition was not just political, but also deeply personal.

He found real value in using cannabis introspectively:

Sometimes a kind of existential perception of the absurd comes over me and I see with awful certainty the hypocrisies and posturing of myself and my fellow men. And at other times, there is a different sense of the absurd, a playful and whimsical awareness… that we spend a lifetime being trained to overlook and forget and put out of our minds.

A sense of what the world is really like can be maddening; cannabis has brought me some feelings for what it is like to be crazy, and how we use that word ‘crazy’ to avoid thinking about things that are too painful for us.

There is a myth about such highs: the user has an illusion of great insight, but it does not survive scrutiny in the morning. I am convinced that this is an error, and that the devastating insights achieved when high are real insights; the main problem is putting these insights in a form acceptable to the quite different self that we are when we’re down the next day.

Tips for a Solo Flight

As the author of a book called How to Smoke Pot (Properly), I feel compelled to close with a few practical thoughts on how to optimize your solitary cannabis experiences.

  • Before you get stoned, decide what you’re going to do after you get stoned, and then do it.
  • If possible, get out into nature before you spark up. This is particularly good advice if you’re battling depression.
  • Turn off your phone and instead utilize an archaic technology known as a “notebook” to jot down all your brilliant highdeas before they slip away.

In his hit song “Day and Night,” Grammy winner Kid Cudi introduced The Lonely Stoner, an alter-ego based on a period in his life when he spent a lot of time engaged in what jazz musicians used to call woodshedding. Which back in the day literally meant spending a few months holed up in a woodshed practicing your instrument nonstop. Often with the help of a little reefer to keep in the flow.

You probably don’t have a few months to spare right now to fully focus on a creative pursuit, but why not try it for a day? Find a time and place to be alone for 24 hours without distraction, track down some strains known to boost creativity, and set the intention of creating or learning something new.

Then drop a note in the comments and let us know how it went.

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This Is The Best Way To Store Marijuana For The Apocalypse, According To Science

You may want to rethink how you’re storing your marijuana stash long-term.

Many enthusiasts will tell you the best place to keep cannabis is in an air-tight container stowed somewhere cool and dark. But according to the results of a new four-year study, the freezer may actually be a better place–especially if you’re concerned about maintaining that all-important THC content.

Researchers in Italy were interested in understanding how time and various storage conditions (involving light, oxygen and temperature) affected the chemical composition of high-potency cannabis products. Past studies have also investigated this topic, but the authors of new research published in Forensic Science International last week noted that the potency of cannabis in today’s market is “extremely different” from years past.

Using six cannabis products of herbal and resin materials (which were seized by law enforcement and given to researchers to analyze), the study’s authors created 24 primary samples.

After collecting information about how much THC, CBD and CBN (that is, cannabinol, another non-intoxicating component in cannabis that occurs when THC degrades over time) each sample contained, the researchers stored the samples in four controlled conditions for a period of four years.

The testing conditions differed by light exposure (whether it was light or dark 24 hours) and storage temperature (including at room temperature, refrigerated at 4 degrees Celsius or frozen at -20 degrees Celsius). Over the span of the study period, the samples were tested 14 times.

In a finding that will likely be unsurprising to anyone who has stumbled upon an old stash of cannabis stored in a sock drawer, the study determined that the amount of THC decreased–thus increasing the amount of CBN–in the samples stored at room temperature. In the first 100 days of data gathering, the THC in the marijuana stored in both light and dark spaces at room temperature had degraded by 13 percent and 11 percent, respectively.

Meanwhile, the refrigerated cannabis did show some decline in THC and increase in CBN over time, though not nearly as pronounced as the samples kept at room temperature.

The THC content in the samples stored in below-freezing conditions, however, did not significantly change.

This finding indicates, as the authors write, “that freezing is the best storage condition to avoid the reduction of the cannabinoids content over time.”

As for CBD, the study found that the compound remained “relatively constant over time in all the considered samples.”

The authors point out that their findings could be important for forensic purposes. With their methods, they write, law enforcement may be able to figure out what the THC concentration might initially have been in degraded marijuana.

On a more basic level, the research could also help consumers better plan how to store their cannabis.

That said, with marijuana not exactly that hard to find–it’s not as if prohibition is very effective, and more states are legalizing cannabis stores in any case–most people probably won’t be seeking to intentionally store their supply for multi-year periods.

Unless, that is, you’re a prepper planning for hard times. In that case, just know that, according to this research, stuffing your stash in the freezer is best.

Study Reveals How Marijuana Components THC And CBD Affect Chronic Pain

Photo courtesy of WeedPornDaily.

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Cannabis Awakening: A Matter of Life or Death

In this edition of Cannabis Conversations, former municipal court judge Doug Bench discusses his transformation from ardent prohibitionist to medical cannabis advocate.

Project CBD: Hi, I’m Martin Lee with Project CBD and today we’re going to be speaking with Doug Bench, a retired lawyer and municipal court judge from Ohio, who’s been rethinking his ideas about cannabis. This is yet another edition of Cannabis Conversations … Welcome to Cannabis Conversations.

Bench: Thank you, Sir. It’s an honor and pleasure.

Project CBD: Now, you’re with a group called Rethink Green. You are the founder and co-director. We’re going to talk about your changing thoughts about marijuana – or as we prefer to say cannabis. Tell us about your attitudes toward cannabis when you were a judge and a lawyer.

Bench: When I was a judge and lawyer in Ohio, in one word: I was a prohibitionist. I had some experience with cannabis when I was a juvenile court referee and developed very negative feelings about it. Went to judicial college – was told it was horrible, it was bad, it wasn’t medicinal, it was addictive, it’s a gateway drug – all the crap we used to get fed. And as a municipal judge, I put over 300 people in jail for marijuana offenses, some of them for a year.

Project CBD: And generally, were these offenses for possession, or deals, or what?

Bench: Never for deals. Municipal Court is for misdemeanors. So it was never large amounts. It was usually personal use, frankly. They got it at school or they got it on the street corner, and we didn’t want them going the route that everybody we were told was going. So, we gave them some shock treatment in jail. I stayed a prohibitionist most of my adult life.

Project CBD: So what precipitated the change in your attitude toward this?

Bench: I went to our place in Colorado and tried to repair the deck and couldn’t breathe. Came back to Florida, went to the doctor, and did all kinds of tests, and the doctor said you have a terminal disease. You have COPD [Chronic Obstructive Pulmonary Disease]. You’re late stage. We’re going to put you on oxygen. You’re going to get steroids. We’re going to have to do this and that. And I begged him to tell me how long I had, and he told me up to 20 months. There’s no cure. And, when my wife and I left that office, I was feeling sorry for myself. My wife was angry. He had no right to tell her husband that he was going to die. And my wife was into essential oils, which I used to bitch about because they’re expensive. But frankly, her interest in essential oils saved my life because she went home and said I’m going to find an essential oil that will fix my husband. I ain’t done with him. And four months or so of research, she found cannabis oil as the “quintessential” essential oil. My wife flew to Colorado from Florida – she knew my attitude about cannabis – and she lied to me. Her real reason for going was to buy some cannabis oil in a predominant high-THC strain. And she committed a felony, brought it home on a plane, came to me and said, “Take this, I think it will help.” “What is it? “It doesn’t matter what it is, honey, take it.” “What is it?” I asked. “Well, it’s essentially an essential oil,” she said. Right! I told her to get the hell out of the house.

Project CBD: You knew what she had brought back at that point.

Bench: Yes. I said that’s unlawful. You just broke the law. It’s unlawful to have it in this house. Why don’t you leave with it. And that went back and forth for about a week. Then she’s coming down our spiral staircase with two suitcases. I said, what are your doing? She said, ‘I’m leaving you, unless you take this.’ I said, ‘How do I take it?’ And that night – I had no idea, I’d never touched it. When I was in judicial college they’d put it on a plate and burned some so the judge would know what it looked like.

Project CBD: You’re talking about flower? But oil is different from flower.

Bench: Yes.

Project CBD: So what happened when you first took it?

Bench: It tasted awful. Put a drop under my tongue. I told her it tasted like crap and I sat up in bed and said, ‘Am I going to get high?’ She says, ‘Honey it’s 8 in the morning, you just slept 8 hours for the first time in over a year’. I said, ‘Holy crap! I’ll take another drop.’ I never felt any high or anything. And in about two weeks my wheezing and crackling in my voice was dissipating. In about three months I was getting my strength back. And in five months, I went back to that same doctor and said I want you to do all those tests you did on me, that pulmonary function test, chest x-ray, everything. I want it done again. He said, ‘Why?’ I said, ‘Just do it.’ He did them all and came back in and said, ‘I don’t know what to say.’ ‘What are you talking about, Doc?’ ‘Well, your lungs are clear. I can’t even find any scar tissue’. I said, ‘I know.’ He shut the door and said, ‘What are you doing?’

Project CBD: And you told him?

Bench: I told him I’m committing a felony every day – because it wasn’t legal in Ohio then. And I’m going to keep doing it because I’m getting better.

Project CBD: How did the doctor respond to that?

Bench: He put in my chart, he said I can’t put in the chart that you’re cured, we’re not allowed to do that, but I will put in your chart that you are now asymptomatic for unknown reasons because I can’t risk my medical license.

Project CBD: So going through this experience, how did that turn you around in terms of the way you were living your life and talking to people about cannabis?

Bench: I’ve got to tell you, that was hard. I mean 45 years of prohibitionist – now all of a sudden seeing personally, it saved my life. So my wife and I talked about it, the only audience I had were the contractors I was teaching Continuing Education required classes for the state of Florida.

Project CBD: You’re talking about building contractors?

Bench: Yes, plumbers, roofers, general contractors. And, I said I’ve got to tell them, honey. It might save a life. These guys are all old farts like me – it might save a life and you can’t tell them, you’ll lose your license. I’ve got to. If it saves one life, losing my license, I don’t care. That was the beginning because I’ll never forget the first class I told was on April Fool’s Day, April 1, 2016. And, I told them my story, and they were all conservative contractors, and what started happening is that they started coming up to me at the breaks – “Doug, my wife has COPD, can you help?’ ‘Doug, my husband has renal cell cancer, can you help.’ And, I kept saying, no. Until the contractor that came up, 6’4” guy, tears coming down his cheeks, can you help our daughter, she has intractable epilepsy, 20-25 seizures a day. I said, shit, yes I can help. And that was the beginning. I told my wife we’ve got to start doing webinars. I knew how to do webinars, I’d written several books on the brain and how to improve performance of your brain, I knew how they worked. So we’ve got to start doing these to educate our database list about cannabis. And that’s how it started. And my wife came up with the name “Rethink Green.” I thought it was a beautiful name. So that’s our website. That’s our organization. That’s our Facebook page. And we just have these webinars – we started out 5 or 6 people, and my wife and I sitting there teaching them all about cannabis. And then, 10-12 people.

Project CBD: Apart from these seminars, are you interacting at all with the state government in Florida? It does have a medical marijuana program, at least on the books, I don’t know how much in reality. But are you interacting with officials? Because, your story is very powerful. You come from the criminal justice system, and you bring a certain authenticity that’s hard to match. It’s indisputable what you’re saying.

Bench: Our first step, we went around the state speaking at Rotary Clubs, Lion Clubs, promoting passage of Amendment 2, which was our medical cannabis law – not law, but Constitutional Amendment. And, after it passed it became very apparent that the legislature, and the governor especially who was anti-cannabis (owned several pain clinics, imagine that!) and they didn’t want it. So I said, I’ve got to start going to Tallahassee. So we started going to Tallahassee during the session. There’s some wonderful people from NORML and other organizations in Florida that have what they call lobby days, where you go and lobby, and they set up appointments with all the legislators – and I’ve been doing that now for three years because they still don’t have it right. It’s a mess. The first thing that was a mess, they wanted to impose a 3-month waiting period. You can get your card making sure you’re eligible for one of the conditions that’s been approved, you can get your card, but you can’t get your medicine. There’s a 90-day waiting period, cooling off period. What a crock of crap that was. So I went in front of the hearings the Department of Health had and to their face called them murderers. Because of that requirement, people were literally dying, waiting their 90 days. So we got that thrown out. And other changes have been made, not the real good ones that protect employees and protect employers with a medical card, etc. So we’re going to be back in Tallahassee first of every year.

Project CBD: So you’re in Florida now, if people in Florida or elsewhere, as an educational organization Rethink Green offers, how do they contact you, how do they know about you?

Bench: They can go to our Facebook page, called Rethink Green. It’s on Facebook, there’s tons of information there, our contact information there. Or they can email me [email protected], and that’s our website, Rethinkgreen.org, which would give all of our contact information and everything they need to know to get a hold of us. We are going to expand beyond Florida. There are many states that have no such law that needs one – people are dying. I’d be dead right now. I don’t know, I think I’m still kicking!

Project CBD: We’re glad you’re not dead! Thank you very much Doug Bench.

Bench: You’re welcome.

Project CBD: It’s been another edition of Cannabis Conversations. We’ll see you next time.

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Recipe: Rich and Infused Cocoa Hazelnut Spread

Food and cannabis can be the perfect match. But, let’s be real here: certain kinds of food tend to rule them all–chocolate and hazelnuts being at the top. Nutty, chocolate-packed, and infinitely decadent, adding cannabis to your cocoa hazelnut spread is one of the greatest pairings to be discovered since PB&J. It’s versatile enough to go on just about everything (ice cream, cookies, cake, crackers, you name it), improves even the worst days in mere seconds, and can be eaten straight out of the jar.

Because this delectable spread is so delicious, I highly recommend using a low dose of THC for your oil–you may end up eating the jar much more quickly than anticipated.

Start to finish: 30 minutes

Yield: 1 1/2 cups

Ingredients

  • 1 cup hazelnut filberts
  • 8oz milk chocolate
  • 1 tablespoon cocoa powder
  • 1 tablespoon canna-oil*
  • 1/4 teaspoon sea salt
  • 3 tablespoons powdered sugar
  • 1/2 teaspoon vanilla
  • 4-5 tablespoons milk (plant-based milks are also fine)

Directions

  1. 1. Preheat oven to 350? Spread hazelnuts on a baking sheet and toast for 10-15 minutes. Let cool.
  2. 2. Place a towel over the hazelnuts and roll to create friction, removing the skins. Set aside.
  3. 3. Melt chocolate (ideally over a double boiler) until shiny and smooth. Add oil and vanilla then mix to combine.
  4. 4. Add hazelnuts to a food processor with salt, cocoa, and powdered sugar. Pulse for 2-3 minutes until the mixture resembles a paste.
  5. 5. Slowly drizzle in the chocolate mixture, scraping the sides of the bowl as necessary.
  6. 6. Add milk until the mixture is desired consistency. Store in a jar at room temperature for up to two weeks.

*Note: The amount of cannaoil specified in this recipe is a very loose suggestion; the actual amount you use should be modified based on the strength of your butter and the potency you desire. Dosing homemade edibles can be tricky (click here to learn why), so the best way to test for potency is to start with one portion of a serving, wait one to two hours, then make an informed decision on whether to consume more. Always dose carefully and listen to your body, and never drive under the influence of cannabis.

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ICRS 2018: Report from Leiden (Part 2)

During the first week of July 2018, five-hundred-and-thirty-five delegates from five continents met at the University of Leiden in the Netherlands for the 28th annual symposium of the International Cannabinoid Research Society (ICRS). The four-day conference showcased recent scientific discoveries about cannabis components and various ways of targeting the endocannabinoid system to improve health outcomes.

Fatty acid binding proteins

During his Young Investigator Award Presentation, Stony Brook University scientist Martin Kaczocha discussed the role of fatty acid binding proteins (FABPs) as critical components of the endocannabinoid system. This is an emerging area of medical science with exciting prospects for pharmaceutical development. Kaczocha’s talk focused on preclinical investigations that underscored the potential of targeting specific FABPs to treat pain, inflammation and prostate cancer.

Why are fatty acid binding proteins important? Because fats and water don’t mix well, and that means endocannabinoids (eCBs) and other endogenous lipids must rely on FABPs to get to where they need to go.

FABPs are transport molecules – think of them as a fleet of teleporting canoes – that shuttle eCBs through the cell membrane into the aqueous cytoplasmic interior. Within the cell, eCBs act upon nuclear receptors, which regulate gene expression and mitochondria, before they translocate to enzymes that metabolize eCBs into breakdown components as part of the natural life cycle of these pivotal neurotransmitters.

In 2009, Stony Brook scientists, led by Dale Deutsch, identified several FABPs as “intracellular carriers” for the endocannabinoid anandamide. Six years later Deutsch and Koczocha scored another breakthrough when they reported that the same FABP transport molecules also serve as intracellular carriers for CBD and THC.

What happens when plant cannabinoids like CBD and THC compete with endogenous cannabinoids for seats on the same FABP canoe? CBD and THC reduce eCB access to FABP transport molecules, which causes eCBs to stick around longer, resulting in an increase in eCB levels in the brain.

In effect, CBD and THC function as endocannabinoid reuptake inhibitors that amplify cannabinoid receptor signaling by delaying eCB deactivation. Enhancing eCB tone via reuptake inhibition appears to be a key mechanism whereby plant cannabinoids confer neuroprotective effects and other health benefits.

Pharmaceutical researchers, meanwhile, are experimenting with synthetic compounds that delay eCB intracellular transport and reuptake. Medical scientists hope that by targeting specific fatty acid binding proteins, synthetic reuptake inhibitors will increase eCB levels in a localized manner that causes clinically verifiable, eCB-induced protective effects.

CB1 antagonists 2.0

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Several posters and oral presentations at ICRS in Leiden addressed the therapeutic potential of peripherally restricted CB1 receptor antagonists, which show promise in preclinical studies for treating alcoholism, insulin resistance, and metabolic disorders.

First identified in 1988, CB1 cannabinoid receptors are not only the most prevalent G-protein coupled receptors in the brain and central nervous system; they are also expressed in peripheral organs such as the liver, kidneys, heart, bones, and gut.

CB1 receptors mediate the psychoactive effects of cannabis. When THC binds to CB1 receptors in the brain, it makes a person feel high. When THC binds to CB1 receptors outside the central nervous system, it confers non-psychoactive, anti-inflammatory effects.

CB1 receptors in the brain and gut play a critical role in regulating energy metabolism by controlling food intake. The notorious marijuana “munchies” are linked to CB1 receptor stimulation in the brain region that regulates hunger and satiety. If activated, these CB1 receptors induce appetite; if blocked, they reduce it.

The French pharmaceutical giant Sanofi-Aventis was the first to market a synthetic CB1 antagonist as an appetite suppressant under the trade name Rimonabant in 2006. But the much-hyped blockbuster diet pill proved to be a blunt instrument, and the drug was soon pulled from European circulation because of severe side effects – anxiety, nausea, vomiting, seizures, sleep disorders, headaches, increased blood pressure, mood swings, depression, and heightened risk of suicide. Blocking CB1 receptor signaling in the brain to shed a few pounds caused the same adverse neurological conditions that CB1 activity normally protects against — the same medical conditions for which cannabis provides relief.

Big Pharma’s initial foray into cannabinoid antagonists failed miserably. But the notion of modulating the endocannabinoid system without causing a high would live on as an idee fixe among drug company researchers. Now, a dozen years after the Rimonabant debacle, medical scientists are taking another look at CB1 receptor antagonists – from a different perspective.

Instead of targeting CB1 receptors in the brain, the current emphasis is on selectively blocking only CB1 receptors outside the central nervous system. Drug developers, accordingly, have invented a new generation of experimental CB1 antagonists that don’t cross the blood-brain barrier.

Whereas CB1 receptor antagonism in the brain produces detrimental neurological outcomes, CB1 inhibition in peripheral organs has shown therapeutic potential in various animal models. A team of scientists at National Institutes of Health (NIH) in Bethesda, Maryland, reported that CB1 receptor antagonism enhances insulin sensitivity in pancreas and liver cells and delays age-related muscle loss.

Another NIH study at ICRS 2018 found that a peripheral CB1 blockade may have therapeutic possibilities for treating alcoholism. And according to researchers at RTI International in North Carolina, CB1 receptor antagonists that lack central nervous system penetration should also be considered worthy drug development candidates for liver disorders.

But problems inevitably arise when selectively targeting a cannabinoid receptor subtype and treating it as an on/off switch. There may be better whole plant options.

Metabolic tune-up

In vitro studies indicate that cannabidiol functions as a negative allosteric modulator at the CB1 receptor, meaning that CBD antagonizes or inhibits CB1 receptor signaling without entirely blocking it. In other words, if the CB1 receptor functions as a dimmer switch, CBD turns it down but not all the way.

At the same time, CBD augments CB2 receptor signaling, which regulates inflammation and immune cell activity. How and why CBD, a potent anti-inflammatory, acts like a CB2 agonist without directly binding to the CB2 receptor is still somewhat of a scientific mystery.[1]

But this much is evident: CBD can fine-tune metabolism by differentially modulating CB1 and CB2 receptor activity, down-regulating the former while boosting the latter. Both types of cannabinoid receptors, CB1 and CB2, are expressed in peripheral organs, where they may mediate opposing functions. Activating CB1, for example, has a pro-fibrogenic effect in the liver and kidneys; activating CB2 has the opposite effect, reducing fibrosis.

Fatty liver, diabetes, heart disease, obesity, and other diet-related metabolic disorders are associated with overactive CB1 receptor signaling and inadequate CB2 stimulation. Given that CBD differentially inhibits CB1 and amplifies CB2, cannabidiol appears to be particularly well-suited for treating lifestyle and diet-induced illnesses that are endemic in Western societies.

Several other plant cannabinoids, including tetrahydrocannabinolic acid (THCA), the unheated, non-intoxicating version of THC, also show promise as metabolic modulators. Spanish scientists reported on the effect of THCA in an animal model of metabolic syndrome. Daily administration of pure THCA (20 mg/kg) for 3 weeks resulted in “a significant reduction of fat mass and body weight gain” in mice fed a high fat diet. THCA also significantly ameliorated “glucose intolerance and insulin resistance.” These health-positive outcomes were attributed to THCA’s activation of PPAR-gamma, a receptor on the surface of the cell’s nucleus, which regulates energy homeostasis, mitochondria, and gene expression related to adipose tissue (body fat) accumulation. CBD also activates PPAR-gamma.

Food as medicine

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Western diet and a sedentary lifestyle are major risk factors for developing metabolic syndrome (characterized by high blood pressure, high blood sugar, bulging waistlines). It’s already a massive public health crisis: 34 percent of American adults meet the criteria for metabolic syndrome, including 52 percent of Americans 60 years and older. Several ICRS presentations examined non-pharmacological approaches – including exercise and nutritional intervention – that treat prevalent metabolic disorders by targeting the endocannabinoid system.

The therapeutic effects of regular moderate exercise (weight loss, improved mood, and more) may involve changes in the basal tone of peripheral eCB signaling, according to Brazilian scientists at the Federal University of San Paulo. Simply put, exercise improves endocannabinoid tone. So does a healthy diet – low on sugar and carbs, rich in leafy greens, polyphenols, probiotics, essential fatty acids, and high fiber foods.

Wageningen University in the Netherlands has been at the forefront of researching how omega-3 polyunsaturated fatty acids (PUFAs) impact the endocannabinoid system. Omega-3 dietary deficiency depletes eCB tone, impedes eCB-mediated neuronal functions, and is linked to the onset of neuropsychiatric diseases. But this deficiency can be mitigated by fish oil-derived PUFAs – such as DHEA and DHA-5-HT – which are known to have anti-inflammatory and cardiovascular benefits. Dutch researchers reported that these fish oil compounds help to attenuate tumor growth in animal models of cancer. An omega-3 PUFA-enriched diet favorably modulates eCB signaling during obesity.

Francesca Guida, a University of Naples scientist, discussed how Vitamin D deficiency “can lead to selective alterations in endocannabinoid signaling” that contribute to pain development and hypersensitivity. Moreover, according to Guida and her colleagues, “altered Vitamin D status is responsible for deep changes in microbiota composition.” Gut microbiota modulate intestinal eCB tone, and changes in Vitamin D levels “induce modifications in composition and functions of the intestinal bacterial community” that affects microbe-host interactions.

Gut dysbiosis is implicated in several diseases, including obesity, type-2 diabetes, and depression. Fermented foods promote healthy gut flora that balance endocannabinoid tone. Endocannabinoid signaling at CB1 receptors in the gut regulates feeding behavior. University of California scientists in Riverside report that overeating associated with diet-induced obesity is driven by dysregulated gut-brain eCB signaling. The interaction between gut microbiota and the endocannabinoid system is an up-and-coming area of research with vast implications for medical science and patient care.

Looking ahead

Next summer the ICRS conference will be hosted by the National Institutes of Health in Bethesda, Maryland. The chosen venue for ICRS 2019 is a major acknowledgement by the U.S. government of the importance of this burgeoning field of study. It’s also a belated honor for the community of scientific pioneers who discovered the endocannabinoid system and who continue to unravel its mysteries.

Read part 1 of this two-part series – ICRS 2018: CBD Shines in Leiden


Project CBD director Martin A. Lee is the author of Smoke Signals: A Social History of Marijuana – Medical, Recreational and Scientific.


FOOTNOTE

1. Why are CBD’s effects similar to those of CB2 activation? It may have something to do with CBD’s role as an antagonist at GPR55, a so-called orphan receptor, that signals inversely in relation to CB2. (CB2 is anti-inflammatory; GPR55 is pro-inflammatory.) Blocking GPR55 is one of several ways that CBD modulates inflammation. CBD can inhibit the reuptake of endocannabinoids and this may result in eCB-induced protective effects via heightened CB2 receptor transmission. Allosteric modulation of the the CB2 receptor could be a factor, as well. And scientists are also debating the role of receptor dimerization, whereby two receptors entangle, forming as novel signaling unit. Although CBD does not directly activate the CB2 cannabinoid receptor, CBD is a potent activator of the 5-HT1A serotonin receptor. Some researchers speculate that CBD functions like a CB2 agonist without being one because CB2 receptors “dimerize” with 5-HT1A receptors.

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ICRS 2018: CBD Shines in Leiden (Part 1)

Graft-versus-host disease (GVHD) is a common – and potentially fatal – complication following bone marrow and solid organ transplants. This life threatening condition can also occur after a patient receives a blood transfusion or other forms of transplanted tissue from a genetically different person.

The mortality rate for acute GVHD is over 80 percent. And there are no reliable molecular markers that indicate the onset or reflect the severity of a post-transplant reaction. Currently there are no FDA-approved therapies for this disease. The ability to treat acute GVHD is thus a major unmet medical need.

But hope is on the horizon, thanks to cannabidiol (CBD), a non-intoxicating component of cannabis, according to a team of Israeli scientists at the Rabin Medical Center. Data from three phase 2 clinical studies in Israel showed dramatic results when 150 mg of pure CBD was orally administered twice daily to ten patients with acute GVHD who did not respond to steroids. Although the sample size was small, the outcome proved noteworthy: “Consumption was safe and no significant adverse effects were reported. Nine out of ten patients responded to treatment, seven of them achieved complete remission and two achieved very good partial response.”

The Israeli study, “Cannabidiol – An innovative strategy for the treatment of graft versus host disease,” was featured on Day One of the 2018 International Cannabinoid Research Society conference, which convened this summer in the picturesque Dutch city of Leiden. Over 500 delegates from around the world attended the annual four-day gathering, where they discussed cutting-edge developments in cannabis science and medicine.

This year’s ICRS conference featured 58 oral presentations, including four keynotes, and 235 posters that covered a wide range of topics. CBD figured prominently in many of these reports, which also explored the health benefits of tetrahydrocannabinol (THC) and other plant cannabinoids. But the main focus, as always, was on the endocannabinoid system itself, which mediates many of the effects of cannabis.

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THC & CBD for brain health

Andras Bilkei-Gorzo, a University of Bonn scientist, linked brain aging to a decline in activity of the endocannabinoid system (characterized by diminished endocannabinoid levels and reduced coupling with CB1 cannabinoid receptors). But animal models showed that normal, age-related, cognitive decline can be counteracted with a chronic low dose of THC: “Most strikingly, THC treatment facilitated a rebalanced hippocampal gene transcription in old mice so that their expression profiles closely resembled that of young THC-free animals … Thus, restoration of CB1 signaling in old individuals could be an effective strategy to treat or prevent age-related cognitive impairments.”

The neuroprotective properties of plant cannabinoids were noted in several other presentations at ICRS 2018:

  • Alzheimer’s. Australian scientists reported that chronic CBD treatment (50mg/kg) reversed cognitive deficits in animal models of Alzheimer’s. [Keep in mind that this dosage pertains to pure single-molecule CBD, whereas whole plant, full spectrum CBD-rich oils are effective at much lower doses.]
  • Parkinson’s. Brazilian researchers found that 30 mg/kg of pure CBD reduced the loss of dopaminergic neurons in the brain regions implicated in Parkinson’s.
  • Epilepsy. Researchers at the University of Sydney, working with a mouse model of Dravet Syndrome, an infant seizure disorder, found that “sub-threshold CBD” potentiated “the anticonvulsant potential of THC.”
  • Stroke. A University of Nottingham (UK) team determined that cannabidiolic acid (CBDA, the raw version of cannabidiol that exists in the plant before it is harvested, heated and decarboxylated into CBD), acting through the 5-HT1A serotonin receptor, is neuroprotective in a cellular model of a stroke.
  • Neonatal brain trauma. Spanish scientists studied CBD’s neuroprotective properties in a neonatal rat model of hypoxia ischemia (brain damage from oxygen and nutrient restriction) and linked these effects to the CB2 cannabinoid receptor. The researchers surmised that there was no “direct action of CBD on CB2 receptors,” but noted that the data was consistent with the possible involvement of “CB2/5-HT1A heteromers.” Heteromers occur when different receptors conjoin to form novel signaling mechanisms – in this case, the CB2 cannabinoid receptor (which CBD does not activate) and 5-HT1A, a key serotonin receptor (which CBD activates).

CBD synergies

Clara Andradas, a medical scientist at the Telethon Kids Institute in Western Australia, has been researching potential applications of cannabinoids for treating pediatric cancer, specifically malignant brain tumors. Her poster disclosed that CBD and THC reduced the viability of brain cancer cells, an effect mediated in part by the CB2 cannabinoid receptor. Moreover, “the combination of cannabinoids with conventional chemotherapies enhances the anti-proliferative effects in these cells,” she concluded.

Temple University scientists assessed the therapeutic impact of CBD combined with beta-caryophyllene (BCP), a versatile terpene present in many cannabis cultivars, kitchen spices, and green vegetables. Unlike cannabidiol, BCP directly activates the CB2 receptor, which modulates immune function and neuroprotection in response to brain trauma. The two compounds together “showed a statistically significant reduction in infarct size,” according to the investigators, who concluded that “combination therapies can provide a greater benefit than single treatments alone” and should be explored further for treating ischemic stroke and other diseases.

Mark Lewis, a plant scientist with Napro Research in California, provided additional evidence that whole plant cannabis medicine may be more efficacious than pure, single-molecule cannabinoids. Lewis has bred several CBD-rich and BCP-rich cannabis chemovars. In vitro analysis showed that various CBD-BCP ratios inhibited cellular inflammation. Co-administration of CBD and BCP “produced enhanced effects as compared to each compound alone.” Of particular interest, the anti-inflammatory impact “produced by certain CBD concentrations increased by up to ten times when co-administered with certain concentrations of BCP.”

Anecdotal accounts from cannabis consumers attest to the benefits of artisanal, terpene-rich remedies. Whistler Therapeutics, a boutique medical marijuana company in British Columbia, surveyed Canadian patients to assess the analgesic impact of different aromatic terpenes in cannabis. Imbued with their own medicinal properties, terpenes interact synergistically with CBD, THC and other plant cannabinoids. For pain management purposes, the best results were obtained using cannabis varietals with noteworthy concentrations of myrcene and trans-nerolidol.

Read Part 2: ICRS 2018: Report from Leiden – “Targeting the endocannabinoid system for therapeutic relief”


Project CBD director Martin A. Lee is the author of Smoke Signals: A Social History of Marijuana – Medical, Recreational and Scientific.


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Trade-In Your Ibuprofen for Cannabis

By Bonni Goldstein, MD On August 15, 2018

Pain from inflammation can and will likely affect all adults at some point in their lives, and for some, become chronic conditions that interfere with a normal quality of life.

Over-the-counter (OTC) and prescription anti-inflammatory medications are easily available, readily prescribed, and very commonly used. The most common anti-inflammatory medications are called NSAIDs: non-steroidal antiinflammatory drugs. Based on consumer survey responses, more than 17 million Americans take NSAIDs on a daily basis, with more than 70 million prescriptions and more than 30 billion OTC NSAID tablets sold annually in the United States.

OTC NSAIDS include aspirin, ibuprofen, naproxen and prescription NSAIDs include celecoxib, diclofenac, etodolac and ketoprofen. NSAIDs work by blocking enzymes called COX-1 and COX 2. These enzymes produce a group of compounds that our cells make called prostaglandins. Prostaglandins made by COX-1 enzymes activate your platelets (for blood clotting) and protect the lining of your stomach and intestines. Prostaglandins made by COX-2 enzymes are made in response to injury or infection, regulating inflammation. Most NSAIDs work non-selectively on both enzymes (except for celecoxib which is a COX-2 inhibitor). This lack of selectivity becomes an issue because pain and inflammation relief from NSAIDs come from blocking COX-2, but unfortunately COX-1 is also blocked, causing unwanted adverse side effects.

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Side effects and complications of NSAIDs are common and serious. In one study, the risk of NSAIDs adverse drug reactions was found to be 26% (Gor 2011). Complications include upper gastrointestinal bleeding and ulcers, heartburn, ringing in the ears, headaches, dizziness, liver or kidney problems, leg swelling, high blood pressure, heart attack, heart failure, stroke, and death. In June of 1999, The New England Journal of Medicine estimated that 16,500 NSAID-related deaths occur among Americans with rheumatoid arthritis and osteoarthritis every year (Wolfe 1999). Over 100,000 NSAIDs users are hospitalized per year for gastrointestinal complications A review of 17 studies found that 11% of preventable drug-related hospital admissions could be attributed to NSAIDs (Howard 2007). In 2005, U.S. Food and Drug Administration issued a public health advisory warning people of the increased cardiovascular risks of NSAIDS, and again in 2007 they published a medication guide for NSAIDs recommending the lowest dose possible for patients using these drugs. In January 2016, the FDA strengthened the existing label on all NSAIDs to warn that there was an increased chance of heart attack and stroke. Some NSAIDs, such as rofecoxib (brand name Vioxx) and valdecoxib (brand name Bextra) have been taken off the market due to their risks clearly outweighing their benefits and pharmaceutical company “misrepresentation.”

As a cannabis physician, I find these statistics and multiple FDA warnings appalling. Using dangerous drugs instead of a healing and non-toxic plant is simply ridiculous.

Over the past two decades, multiple studies have proven the anti-inflammatory benefits of phytocannabinoids and terpenoids, compounds that abound in the cannabis plant (Pertwee, 1999, Klein 2005, Nagarkatti 2009, Booz, 2011, Xiong 2012, Mecha 2013, and more). The plant cannabinoids have many different mechanisms of action in their anti-inflammatory properties, including the blockage of pro-inflammatory compounds that are made in the body as a result of injury or illness. CBDA, cannabidiolic acid, the raw non-psychoactive cannabinoid precursor to CBD, showed significant COX-2 enzyme blockage when compared to placebo, two NSAIDs and other cannabinoids (Takeda 2008). Dr. Ethan Russo and Dr. Geoffrey Guy, in their excellent 2005 study, report that the phytocannabinoids work synergistically (the “entourage effect”) to provide balanced and nontoxic medicinal effects when compared with single molecule anti-inflammatories (Russo and Guy, 2005).

Patients suffering with inflammation have many choices when it comes to cannabis medicine. Along with the ability to choose “non-smokable” delivery methods, such as tinctures, edibles, topical balms and vaporizers, patients now have many choices of which combination of cannabinoids to use. For instance, one can take cannabis medicine that is THC-rich, CBD-rich, combination CBD+THC, THCA, CBDA and/or CBG. Some cannabis medicine suppliers are combining raw and heated cannabinoids in tinctures to increase the anti-inflammatory benefits. Many patients are benefitting from drinking the juice of raw cannabis plants. In my medical practice, I have seen thousands of patients eliminate or reduce the need for NSAIDs, reducing their risks of side effects and possibly even death, with the use of cannabis.

A complete list of NSAIDs can be found here: www.webmd.com/osteoarthritis/guide/anti-inflammatory-drugs#1-5
If you have high blood pressure, heart failure or chronic kidney disease, this is why you should not take NSAIDs (see number 3): www.choosingwisely.org/societies/american-society-of-nephrology/


Dr. Bonni Goldstein, a Los Angeles-based physician, is the author of Cannabis Revealed and the medical diretor of Canna-Centers, which offers educational seminars and webinars on cannabis therapeutics.


SOURCES:

  • Booz, George W. “Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress.” Free Radical Biology and Medicine 51.5 (2011): 1054-1061.
  • Gor AP, Saksena M. Adverse drug reactions of nonsteroidal anti-inflammatory drugs in orthopedic patients. Journal of Pharmacology & Pharmacotherapeutics. 2011;2(1):26-29. doi:10.4103/0976-500X.77104.
  • Howard RL, Avery AJ, Slavenburg S, et al. Which drugs cause preventable admissions to hospital? a systematic review. Br J Clin Pharmacol. 2007;63(2):136-147
  • Klein, Thomas W. “Cannabinoid-based drugs as anti-inflammatory therapeutics.” Nature Reviews Immunology 5.5 (2005): 400-411
  • Mecha, M., et al. “Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: A role for A 2A receptors.” Neurobiology of disease 59 (2013): 141-150.
  • Nagarkatti, Prakash, et al. “Cannabinoids as novel anti-inflammatory drugs.” Future medicinal chemistry 1.7 (2009): 1333-1349
  • Pertwee, R. G. “Cannabis and cannabinoids: pharmacology and rationale for clinical use.” Pharm Sci 1997;3:539-45.
  • Russo, Ethan, and Geoffrey W. Guy. “A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol.” Medical hypotheses 66.2 (2006): 234-246.
  • Slone Epidemiology Unit. Prepared for McNeil Consumer Healthcare. Analgesic use in the adult population of the United States: Acetaminophen, aspirin, ibuprofen and naproxen. Results of a population-based telephone survey, 1998-2001. Report on file, 2001.
  • Takeda, Shuso, et al. “Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis.” Drug metabolism and disposition 36.9 (2008): 1917-1921.
  • Xiong, Wei, et al. “Cannabinoids suppress inflammatory and neuropathic pain by targeting ?3 glycine receptors.” Journal of Experimental Medicine (2012): jem-20120242
  • Wolfe M. MD, et al, The New England Journal of Medicine, June 17, 1999, Vol. 340, No. 24, pp. 1888-1889.

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