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Health – Can cannabis fight tumors?

Primer:

  • Cannabinoids interact with your body by way of naturally occurring cannabinoid receptors embedded in cell membranes throughout your body. It has a long history of use for pain and seizure disorders
  • Doctors working with medical cannabis are also using it to treat cancer-related side effects, and evidence suggests the herb may even have antitumor effects all on its own
  • Cannabis is proapoptotic, meaning it triggers cellular suicide of cancer cells while leaving healthy cells untouched, and antiangiogenic, meaning it cuts off a tumor’s blood supply
  • CBD and THC together appears more effective against cancer than either of them in isolation. The sequence of administration also matters; when administered after chemotherapy, it induced greater apoptosis (cell death) than when administered prior to chemo
  • Another recent study suggests CBD from hemp may be helpful against ovarian cancer, reducing metastasis and slowing ovarian cancer better than the current ovarian cancer drug Cisplatin

 

Medical cannabis has a long history as a natural analgesic,1 and is now legal in 30 U.S. states,2,3 the majority of which allow limited use of medical marijuana under certain medical circumstances. The medicinal qualities of marijuana are primarily due to high amounts (about 10 to 20 percent) of cannabidiol (CBD), medicinal terpenes and flavonoids.

Tetrahydrocannabinol (THC) is the psychoactive component of marijuana that makes you feel “stoned,” but it too has valuable medical benefits, so depending on your problem, you may want higher or lower levels of THC. Cannabinoids interact with your body by way of naturally occurring cannabinoid receptors embedded in cell membranes throughout your body.

There are cannabinoid receptors in your brain, lungs, liver, kidneys, immune system and more. Both the therapeutic and psychoactive properties of marijuana occur when a cannabinoid activates these cannabinoid receptors.

Cannabis Has Long History of Use for Pain, Seizures and More

The U.S. government, through the Department of Health and Human Services (HHS), actually holds a patent on CBD as an antioxidant and neuroprotectant — an ironic and paradoxical situation considering the U.S. Drug Enforcement Administration has classified cannabis as a Schedule 1 controlled substance, which by definition has no accepted medical use.

This federal classification also makes it very difficult, time consuming and expensive to study the health effects of marijuana. Labs have to jump through a lot of legal hoops before being granted permission to study Schedule 1 drugs. Despite such difficulties, a number of studies have found a wide range of uses for the herb. For example, The Journal of Pain,4 a publication by the American Pain Society, has a long list of studies on the pain-relieving effects of cannabis.

Cannabis also has been used for over 80 years for drug-resistant seizure disorders. In January 2015, the American Academy of Pediatrics updated its policy statement on marijuana,5 acknowledging that cannabinoids “may currently be an option for … children with life-limiting or severely debilitating conditions and for whom current therapies are inadequate.”

According to the National Institute on Drug Abuse,6 which also has information relating to the medicinal aspects of marijuana, preclinical and clinical trials are also underway to test marijuana and various extracts for the treatment of a number of diseases, including autoimmune diseases such as multiple sclerosis and Alzheimer’s disease, inflammation, substance use disorders and mental disorders.

CBD oil has also been shown7 to protect the brain of stroke patients and those with Parkinson’s. It may also slow neurodegeneration caused by alcohol abuse.

Cannabis Shows Promise as Anticancer Agent

Doctors working with medical cannabis are also using it to treat cancer-related side effects, and evidence suggests the herb may even have antitumor effects all on its own, with dozens of studies pointing to marijuana’s effectiveness against many different types of cancer, including brain cancer, breast, prostate, lung, thyroid, colon and pituitary cancer, melanoma and leukemia.

It fights cancer via at least two mechanisms that make it difficult for a cancer to grow and spread: It’s proapoptotic (meaning it triggers apoptosis or cellular suicide of cancer cells while leaving healthy cells untouched) and antiangiogenic (meaning it cuts off a tumor’s blood supply). As recently reported by Scientific American:8

“… while the available data are limited, research that has been conducted around antitumor effects of cannabinoids so far shows great promise. The International Journal of Oncology published a study9 last year, for example, indicating that cannabinoids successfully kill cancer cells, and the benefits increase when combined with chemotherapy.

An early preclinical study10 we recently conducted also found that cancer cells derived from patient blood samples were differentially sensitive to the two main active compounds in cannabis — tetrahydrocannabinol (THC) and tetrahydrocannabinolic acid (THCA).

A number of other laboratory and animal studies have been conducted in recent years on colon, breast and brain cancers.11 They indicate that cannabinoids may inhibit tumor growth by blocking cell growth, causing cell death and blocking the development of blood vessels that tumors require to grow.”

CBD and THC Combo Improve Anticancer Drug Effectiveness

According to the International Journal of Oncology study mentioned, phytocannabinoids ” possess anticancer activity when used alone, and a number have also been shown to combine favorably with each other in vitro in leukemia cells to generate improved activity.” The best results were obtained when the cannabinoids were paired with the leukemia drugs cytarabine and vincristine.

“Results show a number of cannabinoids could be paired together to generate an effect superior to that achieved if the components were used individually,” the researchers write, noting that CBD and THC together appeared to be more effective than either of them in isolation.

They also found that the sequence of administration mattered a great deal. When cannabinoids were administered after chemotherapy, it induced greater apoptosis or programmed cell death. When administered before, the opposite effect was achieved. According to the authors:

“Our results suggest that when certain cannabinoids are paired together, the resulting product can be combined synergistically with common anti-leukemia drugs allowing the dose of the cytotoxic agents to be dramatically reduced yet still remain efficacious. Nevertheless, the sequence of drug administration is crucial to the success of these triple combinations and should be considered when planning such treatments.”

Hemp CBD Shows Promise Against Ovarian Cancer

Another recent study suggests CBD from hemp may be helpful against ovarian cancer. Hemp and marijuana plants are in the same family but differ in their THC content. While marijuana plants contain varying amounts of THC, hemp contains very little or none of this psychoactive ingredient. According to a report in Medical News Today,12 Sullivan University College of Pharmacy in Louisville, Kentucky, is “a hotbed of research into hemp’s potential ability to fight cancer.”

Two of its laboratory researchers recently presented findings from two of its studies at the American Society for Biochemistry and Molecular Biology conference in San Diego. In the first,13 a strain called Kentucky hemp was found to reduce the ability of ovarian cancer cells to migrate, suggesting it could eventually be used to help prevent ovarian cancer metastasis.

The second study14 found Kentucky hemp reduced secretion of interleukin IL-1 beta in ovarian cancer cells, thereby lowering inflammation associated with cancer progression. What’s more, the researchers found Kentucky hemp “slows ovarian cancer comparable to, or even better than, the current ovarian cancer drug Cisplatin.” The team is now planning additional studies using mice, with the hope of eventually graduating into human trials.

Cannabis Versus Opioids

As mentioned, cannabis has well-proven analgesic properties, and evidence suggests it can be very helpful for those struggling with opioid addiction as well, easing withdrawal symptoms. In one recent study,15,16,17 138 seniors (ages 61 to 70) with osteoarthritis, stenosis or chronic hip or knee pain were prescribed medical marijuana to assess the effectiveness of the herb against pain, and whether it would have any impact on opioid use.

Eighteen percent of the patients moderately decreased their use of other pain killers; 20 percent significantly reduced opioid use and 27 percent stopped using opioids altogether. In all, 91 percent said they would recommend cannabis to others. Forty-five percent of the patients in this study used vaporized oil, 28 percent used pills and 17 percent used marijuana-laced oil topically. Twenty-one percent used cannabis once a day, 23 percent twice a day, and 39 percent used it more than twice daily.

The results were presented at the May 3 annual meeting of the American Geriatrics Society in Orlando, Florida. In an anonymous statement, one of the participants wrote, “My quality of life has increased considerably since starting medical marijuana. I was on opiates for 15 years, and six months on marijuana, [I’m] off both completely.”

Coauthor Dr. Diana Martins-Welch, a physician in the Division of Geriatric and Palliative Medicine, Department of Medicine at Northwell Health, also noted she’s been able to get patients off opioids using medical marijuana.

Cannabis Legalization Has Led to Significant Decrease in Opioid Overdose Deaths

Another major benefit of cannabis is the fact that there’s no risk of overdose or death. In fact, research from the Rand Corporation shows a 20 percent decline in opioid overdose deaths in states that had legalized medical marijuana, suggesting legalizing medical marijuana nationwide could save up to 10,000 lives a year. Together, these benefits make it a lead contender in the fight against rampant opioid abuse and escalating overdose deaths.18

CNN chief medical correspondent Dr. Sanjay Gupta recently published an open letter to U.S. attorney general Jeff Sessions, urging Sessions to change his stance on cannabis to help rein in the opioid epidemic. “Not only can cannabis work for a variety of conditions such as epilepsy, multiple sclerosis and pain, sometimes, it is the only thing that works … It is time for safe and regulated medical marijuana to be made available nationally,” Gupta writes, adding:

“[P]erhaps most important, the compounds found in cannabis can heal the diseased addict’s brain, helping them break the cycle of addiction. There is no other known substance that can accomplish all this. If we had to … design a medicine to help lead us out of the opioid epidemic, it would likely look very much like cannabis.”

Cannabis Eases Depression, Anxiety and Stress

Other recent research19 shows cannabis can help ease symptoms of depression, anxiety and stress. Unfortunately, depression and high stress are not recognized as a qualifying condition for a medical cannabis card in most states that have legalized the herb for medical use. The reason for this is largely due to lack of scientific support, Carrie Cuttler, Ph.D., author of the study, says.

To evaluate the effectiveness of cannabis for mental health, the team analyzed data from Strainprint, a mobile application cannabis users can use to track changes in symptoms after using different doses and cannabis chemotypes. Overall, self-reported symptoms of depression decreased by 50 percent and perceived stress decreased by 58 percent with use of medical marijuana.

Of those who inhaled cannabis, over 89 percent reported a reduction in depression; nearly 94 percent reported lower anxiety and over 93 percent reported fewer stress symptoms.

The greatest stress reduction was achieved after 10 puffs or more, while just two puffs reduced symptoms of depression and anxiety. These are rather impressive results, but the authors do note that results “may be inflated in the present sample because those who regularly have symptom exacerbation following cannabis use may be less likely to continue to use it to treat their symptoms and track symptom changes over time.”

Other studies have also shown cannabis can be very helpful for those struggling with post-traumatic distress disorder.20,21 Marijuana suppresses dream recall, so for those having nightmares, it can be transformative. Marijuana is also reported to help individuals stay focused in the present, which is beneficial for those experiencing flashbacks.

THC Appears Particularly Beneficial Against Dementia

Interestingly, animal research22 has shown THC — the psychoactive component of marijuana — has a particularly beneficial influence on the aging brain.23,24 Rather than dulling or impairing cognition in the elderly, THC appears to reverse the aging process and improve mental processes, raising the possibility it might be useful for the treatment of dementia.

To test the hypothesis, mice were given a small daily dose of THC over the course of one month at the age of 2 months, 12 months and again at 18 months of age. It is important to understand that mice typically live to be about 2 years old. The dose was small enough to avoid any psychoactive effects.

Tests assessed the animals’ learning, memory, orientation and recognition skills. Curiously, the 18-month-old mice given THC demonstrated cognitive skills equal to 2-month-old controls, while the placebo group suffered cognitive deterioration associated with normal aging.

According to one of the authors, neurobiology professor Andreas Zimmer, University of Bonn, “The treatment completely reversed the loss of performance in the old animals. We repeated these experiments many times. It’s a very robust and profound effect.” Even more remarkable, gene activity and the molecular profile in the brain tissue was that of much younger animals.

Specifically, neurons in the hippocampus grew more synaptic spines — points of contact necessary for communication between neurons. According to Zimmer, the THC appeared to have “turned back the molecular clock” in the THC-treated animals. (Previous research has also shown that the brain ages much faster in mice who do not have functional receptors for THC, suggesting THC may be involved in the regulation of the aging process.25) The team is planning tests to see if the same holds true in human subjects.

In an earlier study, researchers at the University of South Florida and Thomas Jefferson University found that low-dose THC also directly impedes the buildup of beta amyloid plaque in the brain,26,27 which is associated with the development of Alzheimer’s, and enhances mitochondrial function in the brain.

Medical marijuana is also known to reduce some of the non-memory-related symptoms typically experienced by Alzheimer’s sufferers, including anxiety, irritability and rage,28 so cannabis may well have multiple benefits for those with dementia and Alzheimer’s.

Is Cannabis Right for You?

While recreational use of marijuana is not advocated, it seems quite clear that certain strains grown specifically to boost medicinal qualities can have a significantly beneficial effect on a number of different ailments and diseases, including chronic pain. In 2010, the Center for Medical Cannabis Research released a report29 on 14 clinical studies about the use of marijuana for pain, most of which were FDA-approved, double-blind and placebo-controlled.

This report revealed that marijuana not only controls pain well, but in many cases, it actually does so better than pharmaceutical alternatives. When cannabis is inhaled, smoked or vaporized, its effects are rapid and short-lasting. Orally, it’s the most unpredictable and delayed. When ingesting it, it can take up to two hours to take effect, but if dosed appropriately, you can achieve once-a-day dosing with an edible medicine.

Compared to opioids and many other drugs, cannabis is also far safer. Cannabidiol has no toxicity and it’s virtually impossible to die from marijuana. It’s also self-limiting, as excessive doses of THC will provoke anxiety, paranoia and nausea. Such side effects will disappear as the drug dissipates from your system without resulting in permanent harm, but it’ll make you think twice about taking such a high dose again. Make the same mistake with an opioid, and chances are you’ll end up in the morgue.

Just be sure to seek out a knowledgeable cannabis physician, as the proper dosing needs to be carefully ascertained. If you are seriously considering medical cannabis for pain, please see my interview with Dr. Alan Frankel, one of the leading medical cannabis physicians in the U.S. He can do consultations on the phone if you need specific questions answered.

You can also learn more by reviewing my interviews with Dr. Margaret Gedde, who runs an alternative medical practice in Colorado where they specialize in the use of cannabis, and Todd Harrison, an attorney whose expertise is Food and Drug Law, in which he discusses the current legal status of CBD oil.

Research relating to the use of cannabis can also be found on cancer.gov30,31 (the U.S. government’s site on cancer). Simply enter “cannabis” into the search bar. You can also peruse the medical literature through PubMed,32 which is a public resource (again, simply enter “cannabis” or related terms into the search bar).

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Lifestyle – Cannabis and Working Out- Cannathletes

As marijuana legalization has pushed the drug further toward the mainstream — and a longstanding social stigma has begun to dissipate — more individuals are toking up before hitting the weight room, sports field, or mixed martial arts mat.

Sometimes dubbed “cannathletes,” those who regularly supplement a workout with some form of marijuana laud the benefits of the combination, claiming everything from improved focus and relaxation to help in recovery and pain management.

While the idea might seem inherently counterintuitive — weed, after all, is a substance more commonly paired with Doritos than dead lifts — there is a passionate contingent that swears by it.

“It’s a weird phenomenon, but it’s an increasingly common phenomenon,” says Peter Grinspoon, a primary care doctor at Massachusetts General Hospital and author of the book “Free Refills: A Doctor Confronts His Addiction.” “The fact that a lot of people are saying it helps them can’t be ignored.”

Signs of its influence are everywhere. In Boston and beyond, cannabis-themed yoga classes have become en vogue. On Reddit, users swap stories about their best (and worst) experiences working out under the influence. (“I toke up then go for a jog at night through the neighborhood,” writes one user. “It’s like a spirit journey.”)

Even the Massachusetts State Police gave a nod to the curious trend in a recent public service announcement.

“Working out high is legal,” read a tweet sent out by the department. “Driving is not.”

The union of sport and weed is not a new concept. In a famous scene from the 1977 documentary “Pumping Iron,” Arnold Schwarzenegger can be seen lounging on a sofa, joint in hand. And in a recent interview on a Bleacher Report podcast, former New England Patriots tight end Martellus Bennett estimated that — though it’s banned by the league — roughly 90 percent of current NFL players use marijuana, largely to deal with the physical pounding endured during the season.

What’s new, though, is the idea of working out while high.

“I call it a social movement,” says Jim McAlpine, the California-based founder of the 420 Games (the number is semiofficial code for pot), a multicity event that includes a 4.20-mile run and yoga class and invites participants to work out under the influence. “I’ll look on Instagram, and people define themselves as kind of ‘cannabis athletes.’ ”

Unlike traditional preworkout supplements — the caffeine and energy drinks designed to provide a jolt while exercising — cannabis has effects, say those who use it, that are largely psychological.

Proponents say that the drug gives them focus they otherwise can’t achieve, that it breaks up the monotony of a long run, or that it makes them more mentally nimble.

“When you’re high and training, it feels to me that options that might not necessarily be there when you’re sober might show up,” says a 28-year-old mixed martial artist from Saugus who asked to be identified by his nickname, Junior. “When I’m under the influence of cannabis and training, I find my game becomes more creative and less intentional.”

Cameron, from Boston, stumbled into the habit in college, when a friend suggested he smoke before a recreational soccer game and he found himself pleasantly surprised by the results — namely, how the typically grueling running suddenly didn’t seem so bad.

Today, it’s become such a part of his routine that rec soccer and basketball teammates sometimes jokingly check to make sure his eyes are bloodshot before games.

“Honestly, I think they are a little intrigued and amazed — like, ‘How are you doing this?’ ” he says. “But it’s what works for me.”

Tougher to determine is whether the perceived benefits have any scientific basis.

Research into marijuana’s benefits has been notoriously scant, due in large part to the drug’s federal classification as a Schedule 1 substance — meaning that, along with heroin, LSD, and ecstasy, it’s deemed to have “no currently accepted medical use and a high potential for abuse.” And the few studies that do exist offer relatively little insight into the drug’s effects during physical activity, beneficial or detrimental.

“The most critical finding from our review was that there are too few studies to draw any firm conclusions about the effects of cannabis on motor function,” said Shikha Prashad, a postdoctoral research scientist at the University of Texas Dallas’s Center for BrainHealth. Prashad coauthored a research review into cannabis’s effects on complex motor behaviors.

Indeed, even the most ardent spliff-and-lift advocates admit that the practice isn’t for everyone. Nor, they say, does it always go smoothly — particularly for the inexperienced. Junior remembers a competition in which he got too high beforehand — “by the second or third round I was just really, really, really high” — and was handily beaten.

“I do feel it’s really easy to fall into that lack-of-benefit zone,” says Junior, who says it took him years of trial and error before figuring out what amount best works for him. “It’s only useful when done correctly, and there’s a small window of correctness and a large window of error.”

At the same time, some insist, it’s a trend with staying power.

Eric Wilson, a personal trainer and owner of Movement Sciences in Boston, can envision a time in the next three to five years when there will be different cannabis oils or strains designed to enhance specific activities.

“If you’re going fishing, maybe you want an indica blend,” he says. “If you want to go for a long run, maybe a different one.”

In recent years, some advocates have called for professional sports leagues to allow marijuana use; former NBA commissioner David Stern said last year that medical marijuana should be removed from the league’s banned substances list.

The World Anti-Doping Agency, which provides oversight for athletic events ranging from the Olympics to the Boston Marathon, currently lists cannabinoids including marijuana as banned substances. And a spokesperson for the Boston Athletic Association said there are no plans to deviate from those rules.

Still, says McAlpine, “athletes for all of time have tried to find an edge to make them faster or stronger. And there will be people rushing to try this once they realize it’s not going to hurt them.”

Dugan Arnett can be reached at dugan.arnett@globe.com. Follow him on Twitter @duganarnett.

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Health – Cannabis versus Cancer

We know weed can mitigate the side effects of the disease and its treatments, but it might also fight malignancies directly.

As the legalization of medical marijuana becomes more common worldwide, medical cannabis is being prescribed by doctors and caretakers to help treat cancer-related side effects—either from the cancer itself or from treatments like chemotherapy. Countless scientific studies have shown that medical cannabis offers palliative care benefits, including appetite stimulation, pain relief and more.

But early research indicates that cannabinoids can do so much more. Data is showing that medical marijuana has antitumor effects and may one day be used as a cancer treatment, not just as a drug to ease symptoms of the disease. Well over 100 types of cannabinoids—the compounds within cannabis containing different properties and chemical profiles—have been identified to date, yet few have been studied for their specific effects. Medical marijuana’s proven palliative care benefits and the complexity of the drug indicate clinical studies are necessary to uncover the drug’s full potential.

In 2017 there were more than 1.6 million new cancer diagnoses in the United States, and by the year 2030, cancer cases are projected to increase by 50 percent worldwide compared to 2012 rates. Given these alarming statistics, new treatment options are now more important than ever. Chemotherapy, surgery, radiation, targeted therapy and immunotherapy are the most common cancer treatments, but side effects are often severe, ranging from fatigue, hair loss, nausea, infection and more. Medical marijuana offers important relief to patients dealing with these unwanted effects, but what if we were able to offer the drug to patients as an alternative cancer therapy? We may be able to avoid or reduce the severe side effects of other treatments, while combatting the cancer and its symptoms.

We’re not there yet, but while the available data are limited, research that has been conducted around antitumor effects of cannabinoids so far shows great promise. The International Journal of Oncology published a study last year, for example, indicating that cannabinoids successfully kill cancer cells, and the benefits increase when combined with chemotherapy. An early preclinical study we recently conducted also found that cancer cells derived from patient blood samples were differentially sensitive to the two main active compounds in cannabis—tetrahydrocannabinol (THC) and tetrahydrocannabinolic acid (THCA).

A number of other laboratory and animal studies have been conducted in recent years on colon, breast and brain cancers. They indicate that cannabinoids may inhibit tumor growth by blocking cell growth, causing cell death and blocking the development of blood vessels that tumors require to grow. We have yet to make the leap to study these promising effects on humans.

The current approach to medical marijuana research and treatment in the United States is limiting the potential for new discoveries in the cannabinoid field. The current impact of the U.S. market cannot be understated, as its responsible for 90 percent of all global cannabis sales. By 2021, the American share of the market is expected to drop to 57 percent as other countries like Israel and Canada adopt medical marijuana policies and more aggressively fund research.

Thirty states and the District of Columbia have legalized marijuana for medicinal purposes, but the federal government still classifies marijuana as a Schedule 1 drug—a category for substances with high potential for abuse and no accepted medical purpose. This categorization has clearly impacted the scope of research in the United States.

There is currently only one marijuana farm in the country currently approved for the cultivation and procurement of research-grade cannabis. The Drug Enforcement Administration previously restricted the total number of American research facility permits but relaxed these limitations in 2016. Even so, the attorney general has not approved permits for any of the additional 26 facilities that have applied. Despite a growing number of states legalizing medical marijuana, federal restrictions mean that scientists are unable to conduct high-quality research required for FDA approval that would provide necessary clarity on the benefits of cannabinoids for medical practitioners and the patients they serve.

With millions of new cancer cases each year, clear disadvantages to mainstream treatment options, and positive indications from preclinical antitumor medical marijuana studies, the benefit of gathering additional data is clear. We must conduct large-scale research studies to gain a better understanding of medical marijuana’s capabilities beyond palliative care.