8 ways to sober up from being high

Any cannabis consumer can tell you that if there’s one feeling no one enjoys, it’s the moment when you realize, “I’m too high.” Maybe the edible kicked in three hours late. Perhaps you tried to impress a group of friends by breathing in a little bit too deeply. You might have just tried concentrates for the first time and were caught off guard by their potency. Or maybe you are just a low-tolerance consumer.

There are a thousand ways it can happen, but once it does, the resulting experience can be uncomfortable and enough to turn off even the most seasoned cannabis lover.

After smoking weed, how long you stay high depends on a variety of factors: consumption method, dosage, and unique individual variables that can vary from person to person. Typically, the higher the potency of a cannabis product, the longer the high will last. Concentrates are the most potent form of cannabis, with flower and edibles following behind. This could mean that it would take longer to sober up from dabs than smoking a bowl, however dosage and your body’s chemistry would still be the decider here. It’s also important to note that the everyday smoker with a higher weed tolerance will sober up a lot faster than the occasional consumer who hits the party joint a couple of times.

Anecdotally speaking, the average cannabis high can last anywhere between 30 minutes to 2 hours at its peak, with some lingering effects still felt for a period of time after. Some highs have been known to last a lot longer. Thankfully, there are ways to help come back down and sober up when you feel too high, overwhelmed, or uncomfortable from excessive cannabis consumption.

what to do when you're too high, how to help when you're too high, smoked too much marijuana

(Amy Phung/Leafly)

1. Don’t panic

what to do if you're too high


Let us start with the infinite wisdom of Hitchhiker’s Guide to the Galaxy:


Most symptoms of “greening out” (imbibing too much cannabis) will dissipate within minutes to hours, with no lasting effects beyond a little grogginess. Give it some time and these feelings will eventually pass, trust us.

Also, contrary to what you may have heard, there have been zero reported cannabis overdose deaths in the history of ever, so despite how freaked out you may feel or how sweaty you get, you won’t expire from excessive consumption. (Don’t take that on as a challenge, just keep in mind that if you accidentally overdo it, you’ll be OK in a while.)

2. Try water and light snacks

what to do if you're too high


Water, water, water—don’t forget to hydrate! Whether you prefer water or juice, make sure you have a nice, cold beverage on hand (preferably non-caffeinated). This will help you combat dry mouth and allow you to focus on a simple and familiar act—sipping and swallowing.

Keep in mind that by “hydrate,” we don’t mean “knock back a few alcoholic beverages.” If you’re feeling the effects of your strain a little too aggressively, stay away from alcohol as it can increase THC blood concentrations.

Some people find that a light snack helps to feel a little more grounded. Consider grazing on some fruits, nuts, or cheese, and see if it’s a little easier to connect mind and body.

3. Know your limits before consuming

what to do if you're too high


If you can, try to prepare for your cannabis session according to your tolerance level. Okay, this tip won’t help you once you’re already over the edge, but it can help you avoid an uncomfortable situation next time.

Consume with friends you know and are comfortable with, and don’t feel pressured to consume more than you can handle. It’s all well and good to make new friends, but being surrounded by strangers when you can’t feel your face is unpleasant at best and anxiety-ridden at worst.

Take it slow, especially when consuming edibles. We recommend trying a standard dose of 10 mg (or even 5 mg if you really want to ease into the experience) and waiting at least an hour, if not two, before increasing your edibles dosage. The same goes for inhalation methods—if you’re used to occasionally taking one hit off your personal vaporizer, we advise not sitting in a smoking circle puffing and passing for an hour.

4. Keep some black pepper handy

what to do if you're too high


If you find yourself combating paranoia and anxiety, a simple household ingredient found in kitchens and restaurants everywhere can come to your rescue: black pepper. Many swear by the black pepper trick, even Neil Young! Just sniff or chew on a few black peppercorns and it should provide almost instantaneous relief.

5. Keep calm and rest

what to do if you're too high


Find a calm, quiet place where you can rest and breathe deeply. Remember, the intense discomfort you’re feeling will pass. Take deep full breaths in through your nose and out through your mouth. Focus on the sound of your breath and just rest a while.

Sometimes sleeping it off can be the best alternative to stopping a strong high, but it’s not always easy to turn your brain off. Once you’ve found a quiet area, lay down and let yourself relax. If drowsiness and sleep are quick to onset, take a little nap to rejuvenate yourself. Should you be unable to fall asleep, just get comfortable until you feel strong enough to spring back up.

6. Try going for a walk

what to do if you're too high


If you can’t turn your brain off, sometimes a change of scenery and some fresh air to get your blood pumping will help invigorate you. Just remember to stay close to your immediate surroundings—we don’t want you wandering off and getting lost while you’re feeling anxious and paranoid! And refrain from taking a walk if you’re feeling too woozy or light-headed to stand; instead, we recommend Option #5 and lay down for a while.

7. Take a shower or bath

what to do if you're too high


While it’s not always feasible if you’re out and about or at a friend’s house, if you’re at home, try taking a nice shower or bath as a really pleasant option to help relax while you wait for the effects of smoking too much weed to dissipate.

8. Distract yourself!

what to do if you're too high


All of the activities that seem so entertaining and fun while high are also a great way to distract yourself while you try to come back down to Earth. Some suggestions include:

  • Watch a funny cartoon
  • Listen to your favorite album
  • Play a video game
  • Talk to your friends (who are hopefully right by your side, reassuring you)
  • Snuggle with your significant other
  • Try coloring as a calming activity (seriously, adult coloring books are becoming all the rage lately)
  • Eat something delicious

Whatever distractions you prefer, make sure it’s a familiar activity that gives you warm, fuzzy emotions. Your brain will hopefully zone in on the positive feelings and give you a gentle reminder that you are safe and just fine.

Bonus tip: Try some CBD to counter the effects of smoking too much weed

CBD is an excellent anxiety-fighting compound, and for many people it can be used to counteract too much THC. Learn how CBD’s anti-anxiety mechanisms work by modulating the receptor signaling associated with THC.

If all of these suggestions fail and you find that you are still feeling alarmingly uncomfortable, you can always seek medical attention and tell a doctor or nurse that you are having a cannabis-induced anxiety attack. This option is always available, even in states where cannabis is illegal. From a medical perspective, physicians have your best interest in mind and want to do all they can to make sure you’re OK, even if it’s helping you come down when you’re too stoned.

Browse Leafly Market for CBD products

Hopefully, however, the above suggestions were just what you needed to counteract and hopefully stop that too-intense cannabis high. (Or, if none of these work, you could always follow Snoop Dogg’s advice and “put ur face in mayonnaise.”)

How do you stop being high and come down from overwhelming cannabis effects? Share your tips in the comments section!

Authors Lisa Rough and Dante Jordan contributed to this article. This post was originally published on August 15, 2015. It was most recently updated on February 5, 2020.

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Can cannabis alone cure cancer? We asked oncologist Dr. Donald Abrams


February 4, 2020

Early research on mice has been promising, but no human studies have shown dramatic curative powers. (Mitch/AdobeStock)

Can cannabis alone cure cancer?

The short answer is no. There are as yet no major studies that offer conclusive proof that cannabis alone can cure cancer.

The long answer is more complex.

Researchers are investigating some intriguing anti-carcinogenic effects of cannabinoids like THC and CBD. Pharmaceutical companies have tested cannabinoid medications on patients with aggressive brain tumors with positive but not dramatic results. Some cancer survivors have extolled the curative value of concentrated cannabis oil. Entire books have been written on the subject.

But there may be real risk and potential deadly harm in relying solely on cannabis as a cancer-fighting strategy.

Last week two of the world’s foremost clinicians and researchers in the field of cannabis and cancer, Dr. Donald Abrams and Prof. Manuel Guzmán, published a JAMA Oncology article aimed at clearing up the confusion.

Abrams is a renowned integrative oncologist, clinician, medical cannabis pioneer, and medical professor at the University of California, San Francisco. Guzmán and his lab at Spain’s Complutense University of Madrid have published a number of groundbreaking studies on cannabis and cancer.

In the article, they acknowledge that “many patients with cancer diagnoses are convinced, mainly by internet testimonials, that cannabis, particularly highly concentrated oils or tinctures of THC and/or CBD, may actually cure their cancers.”

The authors don’t mention it by name, but Rick Simpson Oil (RSO), a highly concentrated cannabis oil, is often mentioned in online cannabis forums as a tool to try in the treatment of cancer.

Cannabis has long been used by cancer patients—with actual proven efficacy—to manage the side effects of chemotherapy, such as nausea and lack of appetite. It also helps many patients manage cancer pain.

Meanwhile, a number of researchers conducting cell culture studies have published data indicating that THC and other cannabinoids may trigger apoptosis (naturally programmed cell death) in cancer cells.

In a recent interview, Guzmán said this about the state of research on cancer and cannabinoids:

“Practically all the research carried out to date on cannabinoids and cancer cells has used cancer cells cultured on plates or animal models of cancer (generally mice, sometimes rats). Based on numerous scientific studies, various cannabinoids…exercise a wide range of effects that inhibit the growth of cancer cells. These include: (a) Activating cell death through a mechanism known as “apoptosis”. (b) Blocking cell division. (c) Inhibiting the formation of new blood vessels in tumours, in a process known as angiogenesis. (d) Reducing the metastatic capacity of the cancer cells, preventing them from migrating or invading neighboring tissues. To sum up, cannabinoids appear to be effective substances for the experimental treatment of at least some types of cancer, at least in small laboratory animals.”

That’s incredibly promising. But results from cultured cells or mice often fail to carry over to the human body.

The main takeaway from the JAMA Oncology article is this: Treatments like RSO may or may not be beneficial to individual cancer patients, but they should not be used as a substitute for all forms of conventional treatment.

Foregoing conventional therapy “for a curable malignant neoplasm while choosing cannabis as a therapy instead is disturbing,” wrote Abrams and Guzmán.

In a phone interview from his home in the Bay Area, Abrams told Leafly that he and Guzmán were asked to contribute the article by an editor at JAMA Oncology—indicating that clinical oncologists may be confronting the issue with increasing frequency.

In his own practice, Abrams said he too often encounters patients who have misguidedly abandoned conventional cancer treatment in favor of a cannabis-only regimen.

“As an integrative oncologist, I see patients who often have waited months to get an appointment with me,” he said. “One of the most painful things I have to deal with are people who have a potentially curable malignancy who choose to forego conventional cancer treatment, and instead choose to try to treat themselves with highly concentrated oils with either THC, CBD, or both.”

“They come to me, and by that time they have diseases that have spread and can’t be cured,” Abrams added. “I find that really tragic. They expect me to give them a pat on the back and say ‘Yeah, you’re doing the right thing, continue.’ But now they’ve lost their chance to be cured.”

The first study to show evidence of anti-cancer effect in cannabis came out in 1975. That study, which Abrams mentions in a 2019 article, “Should Oncologists Recommend Cannabis?”, showed that THC and CBD could inhibit the growth of certain lung cancer cells in test tube experiments. Subsequent studies found that cannabinoids selectively killed glioblastoma (brain cancer) cells in mice while leaving normal cells untouched.

But the results from studies on human subjects battling brain cancer have been mixed. One of Guzmán’s own studies looked at the use of THC by nine glioblastoma patients. It found no benefit beyond that observed with chemotherapy alone.

While other research has shown early signs of promise with regard to cannabis and cancer cells, Abrams offered some perspective on the gap between lab tests and clinical trials in actual human subjects.

“We know there are agents that work against cancer in the test tube that never [become drugs] that we use in fighting cancer, because they just don’t work in people,” he said. “I was an AIDS doctor for many years. We knew that soap suds and gasoline killed the virus in test tubes. But neither of those would be treatments I’d recommend a patient try.”

“Things that happen in vitro don’t necessarily translate into potential clinical benefits,” Abrams continued. “Taking cells in culture and adding chemicals to them is very different than digesting something in the human body. Humans have a digestive system, detoxification systems, and an immune system. All of those things contribute” to the interaction of a drug, the body, and cancer cells. It’s much more complex than what you see in the test tube.”

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What it’s like to be a kid who medicates with cannabis

It’s awful that there are sick children in this world, that someone so young could already be tied to grown-up matters like mandatory daily medicine. Unfortunately, it’s a very real situation for many families, and its complications are made considerably more so when that medicine is federally illegal. But, due to the extensive nature of the endocannabinoid system (ECS), cannabis can be used to fight many diseases—and many of these ailments can affect people of all ages, not just adults.

We talked with a couple of families with children who regularly medicate with cannabis, aiming to get a picture at what this lifestyle is like, what kinds of challenges they face, and how cannabis has transformed their lives. We discovered stunning stories of improvement, innovation, and a couple of families who’ll make you wish there was a bigger word for “inspiring.”

medical marijuana patient, children who medicate with cannabis, children and marijuana

(Courtesy of the Ryan family)

Sophie Ryan was born October 3, 2012 a perfectly healthy baby girl. But it wasn’t even a year before an MRI diagnosed an optic pathway glioma brain tumor, which doesn’t normally shrink with chemo. Things didn’t look good. Then her parents created a Facebook page called “Prayers for Sophie,” and a friend put them in touch with Ricki Lake and Abby Epstein, who were filming Weed the People, a documentary about the possibility of cannabis oils treating cancer in pediatric patients.

In a phone interview with Leafly, Sophie’s mother, Tracy, told us that Sophie took her first cannabis medicine at 9 months old in the film—a drop of high-concentrated CBD and THC oil on top of her food before beginning chemo treatment. Because Sophie was just a baby, they had to watch her mannerisms to try and gauge dosing, but the only side effects they’ve noted was sleepiness at the beginning, and a higher appetite, which is perfect for a chemo patient.

After 13 months of chemo and high doses of cannabis oil, Sophie’s “unshrinkable” brain tumor was about 85 to 90% gone. Tracy shared with Leafly that even Sophie’s doctor, who was originally skeptical about cannabis, had to concede that cannabis must have helped.

Its’ not just in results that Sophie’s cannabis treatment differs from chemo, her parents note. In addition to being more expensive, Tracy said, “Chemotherapy makes you very sick, it destroys your immune system, it causes organ failure. They lose their hair, they get sores all over their bodies and inside their mouths… Sophie was getting chemo burns when she was in diapers and we’d have to use gloves so we wouldn’t get the chemo acids on our skin—it’s that horrible. And then you have cannabis, and it’s doing the opposite of all that.”

Fortunately, Tracy hasn’t gotten much judgement. She works to ensure that she’s a trusted voice, making sure she’s on top of research and bringing Sophie to lots of speaking engagements to show proof of how healthy she feels, despite chemo. (Tracy said Sophie is a natural and loves doing these events, with rare exceptions.)

medical marijuana patient, children who medicate with cannabis, children and marijuana

(Courtesy of the Ryan family)

After discovering the incredible ways cannabis could heal, Tracy decided to create her own business, CannaKids. They’re now selling high quality tinctures and syringes throughout California and are working on expanding to Canada and Australia, as well as starting a nationwide hemp line with 6-9 cannabinoids. Like many, legalization presented some significant issues, with Tracy sharing that her business “almost didn’t survive the costs and demands of legalization.” For instance, they have had to change the name because of laws about marketing cannabis to children; CKSoul is the new product line, and CannaKids will continue to operate as a non-commercial resource.

They’ve also started a foundation called Saving Sophie, which has raised $60k but Tracy said, “That’s like a week’s work in a laboratory. They’ll need about a half million to get rolling.” And the Ryans have also started a podcast to promote awareness and raise funds—check it out here.

medical marijuana patient, children who medicate with cannabis, children and marijuana

(Courtesy of the Turner family)

Coltyn Turner developed Crohn’s disease when he was 11 years old, after a near-drowning incident led to a bacterial infection. For the next three years, he’d try various traditional treatments, which he and his mother, Wendy, say nearly killed him. In a phone interview with Leafly, Coltyn shared, “The pharmaceutical medications that I’ve tried [range from] pills that do absolutely nothing, to shots that gave me nosebleeds, profusely, for 15 minutes straight, [to] another chemo-like infusion treatment gave me medically-induced rheumatoid arthritis (RA) and lupus.”

You read that right. Coltyn and his family report that traditional medications left him with two more chronic illnesses, each capable of rendering a person debilitatingly ill on their own. Yet, there’s more.

They eventually tried cannabis. “When I got introduced to cannabis, within the first two weeks I was already out of my wheelchair. I felt like a normal kid again,” Coltyn said.

And he’s got proof of the positive changes. “I [went from] 22 centimeters of inflamed bowel with skin lesions, with everything you can imagine—inflammation, ulcers, scar tissue, granulation lymphoma—to a normal colon; no active Crohn’s disease, just using cannabis. So not only did cannabis treat the pain, which is important, but it also took care of what was causing the pain. It also helps with the RA and lupus I got from the [pharmaceuticals].”

medical marijuana patient, children who medicate with cannabis, children and marijuana

(Courtesy of the Turner family)

Coltyn is now 19 years old, having been on cannabis for five years. And his Crohn’s is in remission; they report hardly ever having to go to the doctor these days. He still occasionally gets symptom flares, but is able to control them by upping his cannabis dose during those times. They’ve a great handle on it these days, but they say there were some challenges early on.

Wendy said the main challenge is dosing and ensuring that Coltyn gets the right amount of cannabinoids without getting high. “We are constantly like, ‘How are you doing, how are you feeling?’” she said. “He must be really, really sick of it.”

But Coltyn isn’t phased. “Yeah, I am, but at the same time it’s very important because a lot of patients don’t really know their dose, especially earlier in their cannabis treatment, and you’re changing it pretty frequently,” he said. “When I first moved out of Colorado to start cannabis treatment, we kept a journal and wrote down every little thing that happened: what I ate that day, how many times I went to the bathroom–if I had a stick of gum, we wrote it down. Unfortunately that’s the only way to develop a regimen for people, through trial and error, trying everything under the sun until you find something that works best for you.”

Wendy shares that there were some learning curves on their path. “Sometimes we mess up. For instance, now we know to never give a Crohn’s patient THCV.”

Coltyn adds, “What we know about THCV is that it’s an appetite suppressant. For someone with a wasting syndrome, that’s not a good cannabinoid to have. But we didn’t figure it out until I lost 10 pounds. That’s the struggle with there being no research or anything.”

As far as medicating during school, Coltyn said, “Fortunately, I’ve been homeschooled my whole life, but there are kids who are having trouble having medicine in school. A lot of the time they aren’t even allowed to have it 200 or 1,000 feet from a school. There are kids with seizures who go to public school, and if they need a rescue med, they have to have their parent come to school, pick them up, drive off campus, administer it, then bring them back.”

medical marijuana patient, children who medicate with cannabis, children and marijuana

(Courtesy of the Turner family)

Wendy said that legalization has affected this issue negatively. “These newly legalized states emerging and creating regulation issues in schools with zero tolerance laws. Coltyn attended school for 38 days and we took him out because we couldn’t deal with it. There’s not a feasible option for it, not even in college.”

She added that there is a student suing their school over this issue, and said it’s crazy that pharmaceuticals, which can kill you if abused, are allowed in school, but cannabis isn’t.

Wendy said that without interstate commerce, medicating can also be a challenging task when getting medical care. “Every person who has a medical card is a prisoner of that state,” she said. “Most of Coltyn’s doctors are across state lines in Missouri and the second we cross that state line, Coltyn is illegal. And if he were to break his arm or something, I would have to tell them that he’s medicated with THC. And I cannot give him those meds for Crohn’s disease if he were to have to stay in the hospital for this broken arm for more than a day. So, there we go, into a flare with his Crohn’s disease.”

When asked if they’ve faced much judgement for medicating Coltyn with cannabis, they happily report that they don’t. Tracy shared that it probably has a lot to do with her being an intimidating mom, ready to get into the facts and statistics with doctors and other medical professionals as needed.

medical marijuana patient, children who medicate with cannabis, children and marijuana

(Courtesy of the Turner family)

And their advocacy for cannabis doesn’t end there. The Coltyn Turner Foundation is focused on research and raising the funds to get it done–their first project is a survey of Crohn’s patients using cannabis, which is aimed at getting solid data on how it’s working in their systems that can be used as a resource for other patients. “I felt like it was important, Coltyn said. “All the time I approach doctors and patients who don’t know that cannabis works, and the one thing they say is ‘there’s no research.’”

His mother added that that isn’t the whole truth, “One of the problems we have in the states is our ego, especially with these doctors who say ‘there’s no research,’ just because the research isn’t coming from the US, which has to go through the DEA and other enforcement agencies,” which, of course, aren’t big fans of approving studies with Schedule I drugs—an infuriatingly circular dilemma. But Coltyn’s up for the challenge.

“When the government doesn’t do something right, the people have to do it themselves,” he said. “I’d rather be illegally alive than legally dead.”

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Endocannabinology with Dr. Rachel Knox

Project CBD: Welcome to another edition of Cannabis Conversations. I’m Martin Lee with Project CBD and today we are privileged to have with us in the studio Dr. Rachel Knox, who is the co-founder of the American Cannabinoid Clinics, with other members of your family who are also physicians. Also, you are the chairwoman of the Oregon Cannabis Commission. We’re glad you can join us. I wanted to ask you about something you’ve been lecturing about to various audiences — you refer to endocannabinology. Maybe you can tell us what is endocannabinology?

Knox: In medicine we silo our fields into “-ologies” really. So people are familiar with cardiology and endocrinology, neurology – and really what we mean is the study of the function and dysfunction of those systems. So, in cannabis medicine the focus for a long time has been on the cannabis, but people come to us with physical conditions and we doctors are trained to treat the patient. What we’re really treating is the endocannabinoid system when we’re assessing different disease processes or symptoms. And, so it made sense to me and my family at the American Cannabinoid Clinics to call ourselves endocannabinologists who practice endocannabinology. And we use cannabis, which is probably as far as we know, the most versatile tool that works on that system, but along with lots of other things that help us treat that system. So endocannabinology means the study of the function and dysfunction of the endocannabinoid system and all the ways we can modulate it.

Project CBD: Let’s talk about the endocannabinoid system. What is its purpose? How do you break it down in terms of its components?

Knox: As far as we know, right, because there’s still so much more to know, but our understanding is that the endocannabinoid system is the maestro to the symphony that is every physiological system in the human body. And its role is to keep us in balance, to keep us healthy. So, a perfectly functioning and in tune endocannabinoid system keeps us in perfect health.

But the reality is that we’re inundated with toxic environments, and emotional and physical stress, and poor foods – you name it. This endocannabinoid system of ours is having to battle a lot of insults today. It’s really hard for it to keep us in balance, which is why so many people are struggling with so many diseases. But again, its role is to keep us in balance. And it does that through a very intricate feedback loop. It’s constantly in flux. It’s constantly adapting and reacting to everything that we’re throwing at it. And so it has to work in sort of a feedback system in response to what we’re throwing at it.

For a long time, we’ve talked about the endocannabinoid system in four components. We talk about the four components of it: The first components were discovered between 1988 and ’92, and those were the CB1 and CB2 receptors, mixed in there was the first endocannabinoid (or endogenous cannabinoid, cannabinoid made in our body) anandamide; shortly followed by 2-AG. So we have the cannabinoids that were on those cannabinoid receptors, like a lock in a key. And then we have the enzymes that create those endocannabinoids on demand when they’re needed; again constantly responding to stimuli. And we have the enzymes that break those cannabinoids down when they’re no longer needed. It is a system that runs all by itself. We call it auto-regulatory. And it works when it’s needed, on demand, in response to, again, what we’re doing to it.

Project CBD: So why, if we have this system and it’s working all the time, why do we need cannabis then?

Knox: Because – I mentioned the things that we’re doing to ourselves in today’s age – we talk about inflammation as the root cause of disease, and that’s true. We’re causing inflammation. But the endocannabinoid system is immunomodulating, it’s supposed to keep inflammation in check. It can’t do that when we’re constantly eating inflammatory foods or we’re constantly under stress, right.

The endocannabinoid system works like this. So if a cell is sending signals of pain or stress or inflammation to each other, well the receiving cell is supposed to create an endocannabinoid that it shoots back to the cells sending that signal to turn it off, to restore balance and harmony. Unfortunately, we’re getting in our own way in some respects. The system is being overwhelmed and overloaded with constant signal of stress, pain, inflammation. It’s very difficult under those conditions for it to properly make these endocannabinoids.

We need to eat Omega-3 and Omega-6 fatty acids to even make these cannabinoids. A lot of us are deficient in the foods that are essential to even create these endocannabinoids. And we’re working at a deficiency, right. So there comes in a very good place for phytocannabinoids. So THC – it’s been around for a long time in our colloquial world around cannabis. THC is an anandamide mimicker. Anandamide was that first endocannabinoid that was discovered. Well THC mimics it. So if we’re having trouble developing anandamide it makes sense to supplement with THC for it to take the place of anandamide and help restore some of that function by working on those cells that are constantly sending those signals of pain and stress and inflammation.

It’s kind of like in conventional medicine where we might recommend a supplement to a patient. If you’re deficient in Vitamin D, well we give you exogenous Vitamin D, you take it in a pill form. Using THC in that way to supplement anandamide is no different than what we already do in the conventional world.

Project CBD: So, it would be similar for CBD, cannabidiol, the non-intoxicating cannabinoid. How does CBD play into this?

Knox: Similarly, in general THC and CBD have a lot of overlapping downstream effects. But CBD does not mimic our anandamide or 2-AG. CBD does something very special with respect to THC and anandamide. And what that does, it blocks the breakdown of anandamide. So wherein we might use THC to supplement somebody who’s deficient in anandamide, we might use CBD to prevent the breakdown of anandamide and keep the anandamide levels higher indirectly.

CBD also binds what we call allosterically to the CB1receptor. And when it binds allosterically, meaning not at the same site THC binds to but maybe over here, it changes the conformation of that receptor site. So THC binds to it, but a little bit differently. And that’s one of the reasons we think CBD has such a significant impact on diminishing or dampening the intoxicating and euphorigenic properties of THC. That’s one of the reasons I think people like to say “use THC and CBD together, they work better together.” In truth, yeah, they work synergistically. Again, for patients who don’t want the intoxicating or euphorigenic effects, we can use them in concert to diminish those sometimes unwanted effects of THC – certainly sometimes they are wanted!

And then CBD works on 65 and counting other receptor targets, enzyme targets. It works on the serotonin system, on the opioid system, and I can list many other systems. But CBD works well throughout the body in so many ways. Phytochemicals in general do. We talk a lot these days about the entourage effect of cannabis, but in our clinics we talk about botanical synergy because we recognize also the benefit of including other botanicals in a formulation with cannabinoids or outside of it. We might be recommending your cannabis product plus your echinacea plus your mushrooms, along with a whole other host of things.

Project CBD: I was going to ask you about that. In terms of the patient populations that you are ministering to, how much of it is strictly cannabis-focused or is it generally that cannabis is a piece of the puzzle and other herbs or holistic healing modalities – or maybe non-holistic, maybe pharmaceutical modalities – would play into it. How does that work in your practice?

Knox: Well 100 percent of patients are coming to us looking for a cannabis solution. Our clinics are called the American Cannabinoid Clinics – it’s in the name. People know what they’re going to get when they come to us. But we do a lot of re-directing as soon as those patients hit the chair. We teach about the endocannabinoid system and all the things that stimulate it. And so, folks will leave with the understanding that nutrition comes first followed by, if not equal to, phytocannabinoids (cannabis). Because again, cannabis is the most versatile botanical that we know that works on that system.

So along with nutrition, which is foundational, we need that to survive- none of us are going to survive on cannabis alone, we need to be eating natural whole foods that our body requires to even create new cells. We have to address that. But then, cannabis is a close second. We get into detoxification for the endocannabinoid system, supplementing with other botanicals to tone and help soothe the endocannabinoid system. We talk about stress reduction. We talk about spirituality. We’re talking about everything that modulates that system.

I haven’t said the fancy new word yet that I mentioned yesterday: cannabimimetics. We speak in terms of cannabinoids in cannabimimetics. Cannabimimetics really do encompass just about everything else that we talk about. Cannabimimetics are substances, non-cannabis substances, or practices that stimulate the endocannabinoid system, too. So again, we have our cannabinoids, then we have everything that falls under the cannabimimetic category, which is nutrition, detoxification, supplementation, physical activity, deep breathing, yoga, meditation, acupuncture – the list goes on there. We talk to patients about all of those things.

Project CBD: One last question, sort of food for thought. You have emphasized the significance of diet. And you mention specifically the Omega-3, Omega-6, the essential oils as being very, very important, if nothing else as building blocks for components of the endocannabinoid system. I’m not one who believes there is one perfect diet. Diets do vary in culture to culture, place to place, but if you were to outline some of the do’s and don’t’s in terms of a diet that facilitates healthy endocannabinoid functioning, what would that be? What would that look like?

Knox: Natural, whole foods. I agree, when we eat natural whole foods it doesn’t matter if you’re a vegetarian, a vegan, a paleo, or Keto subscriber, you are really – how can I say this – that’s like 50 percent of the battle right there. Just eating real food. Overly processed foods are hard to digest. You could make the case of using digestive enzymes to help us digest these overly processed foods, but the fact of the matter is these chemicals and preservatives are really hard to break down. And for the most part, we’re not getting the nutritional benefit from a lot of these processed foods because we just can’t break them down. We don’t have the capacity, the capability to break those things down. Prebiotics, probiotics, those are also great to supplement our diet with. But natural, whole foods, and I feel like when people convert to a truly natural and whole food diet, within 30 to 60 days they’re feeling 40, 50, maybe even 60 percent better than they did already. When we then shift some emphasis onto foods that are higher in fat, we see an even better outcome.

Project CBD: So healthy fats are really key.

Knox: Healthy fats, are so, so, so important. In our clinic we talk about the ketogenic diet a lot. But you can have a whole plant-based ketogenic diet that works really well for you. And then you can have what we call a traditional ketogenic diet, where you are eating protein from meat sources and do really well. For us, emphasis is on getting that fat, high-quality fats. Some really great high-quality fats are hemp seed oil, olive oil, coconut oil, avocado oils, are all really great to use daily. I typically recommend getting 5-7, if you’re a woman, and 6-9 tablespoons of high-quality fat every single day. You know, the preferred fuel of all of our cells is fat. Out of fat comes our Omegas that we need for the basic building blocks for anandamide and 2AG and our secondary endocannabinoids. By consuming a low-fat diet, even if it’s natural and whole in nature, we’re still behind the 8-ball. So, natural whole foods, step one. Step two begin to increase your healthy fat consumption. And that to me is a diet for, or a recipe for, modulating the endocannabinoid system.

Project CBD: I think a take-home message of what I’m hearing from you, is that cannabis is very important as a healing modality, but it really works best in conjunction with healthy diet, healthy lifestyle. I think that’s a good note to end on. I appreciate very much your insights and sharing that with us, Dr. Rachel Knox. That’s been another edition of Cannabis Conversations. Thank you.

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How cannabis can help with migraines

For those who regularly experience migraines, life carries unique challenges. Seemingly harmless sensory stimuli, like bright lights, strong aromas, or loud noises, can trigger unbearable pain. Stress, neck tension, and even jet lag can set a crippling migraine in motion too. This intense pain can be accompanied by a loss of sensation, nausea, or alarming visual changes. The disruption associated with chronic migraines can be so constant it can even erode one’s sense of self.

Although drugs commonly prescribed for the prevention and treatment of migraines help some individuals, they don’t offer relief for all migraineurs. Similar to many heavy-hitting medications, a host of unwanted side effects may ensue with use. However, evidence is accumulating that cannabis may be an effective treatment for migraines and chronic headaches.

A November 2019 study published in the Journal of Pain reported that cannabis could reduce migraine and headache severity by 50%, and although tolerance can increase, cannabis use does not exacerbate headaches or migraines over time. Concentrates appeared to offer more significant relief than flower.

Additionally, a 2019 retrospective study published in Neurology found that 88.3% of a sample of 279 patients reported an improvement in their headaches after using cannabis. More than half of the patients noted a reduction in headache frequency, and 38.3% found that their sleep improved. Fifty percent of those using opioid medications were able to reduce their use.

So now we know cannabis can ease migraine symptoms, what are the most effective ways to harness its benefits?

According to Dr. Jim Polston, who holds a PhD in neuroscience and is the Chief Science Officer at Helius Therapeutics, cannabis works on migraines via the endocannabinoid system.

“There is mounting evidence that the endocannabinoid system can directly reduce migraine pain when activated by naturally produced cannabinoids or medical cannabis taken by patients,” said Polston. Cannabis can help to reduce inflammation in the protective dura mater tissue covering the brain and minimize the release of pro-inflammatory substances, both of which contribute to the onset of a migraine.

Polston also points out that one cause of chronic migraines is anandamide deficiency. “Anandamide is one of two cannabinoids naturally produced in the brain and is associated with reduced inflammation and activation of pain centers in the brain,” he explained.

While the science supporting the use of cannabis for the treatment of migraines is piling up, practical knowledge regarding how, how much, and when to dose is still lagging. That being said, those who are already acquainted with cannabis for migraines have valuable tips to impart.

“I use cannabis both as a prophylactic, to prevent migraines by reducing stress and relaxing muscles, and as a rescue remedy once migraine hits, to reduce intense pain and nausea,” explained Boston Marathon survivor Lynn Crisci.

Dr. Debra Kimless, MD, Chief Medical Officer at Pure Green, observes that cannabis may be most effective when the signs of an impending migraine first become apparent. “The patients I have treated using cannabis enjoy tremendous success in reducing and eliminating the acute onset of their migraine symptoms, especially if they can dose when they first experience symptoms,” she said.

Cannabis can work as both a preventative and a treatment for migraines, because the triggers and symptoms of migraines are so varied.

“Migraines have a complex set of underlying causes, triggers, and various symptoms, noted Polston. “Cannabis may be an ideal migraine medication with its diverse compounds and widespread roles in many of the issues associated with migraines. It’s a potent anti-inflammatory agent, analgesic, and anti-emetic. Furthermore, CBD is a known anxiolytic [anxiety-reducer], thus its presence could be useful in the treatment of stress-induced migraines.”

Most studies investigating cannabis as a treatment for migraine are based on oral administration and inhalation delivery methods.

“Though more research comparing methods is needed, we can theorize from the current research that oral cannabis use may be sufficient and should be attempted first to avoid smoking in certain patients,” advised Polston. “However, some patients may find inhalation useful for more rapid pain reduction as the onset of effects is faster.”

That’s not to say that inhalation and oral delivery are the only effective methods though. “The complexity of migraines means that patient variability may lead to various methods being successful, but in a patient or symptom-dependent manner,” added Polston.

For Kimless, tinctures administered under the tongue also work successfully. “Most of my patients prefer to use a sublingual delivery method; it is fast, effective, and discreet,” she explained.

Crisci has experimented with many ingestion methods to determine what offers the greatest relief for her personally and has settled on vaping. “I prefer vaporizing cannabis oil, preferably in a vape pen, she said. “Vape pens allow me to microdose and control exactly how much medicine I am ingesting, while avoiding inhaling smoke into my lungs.”

The 2019 Journal of Pain study argues that different concentrations of THC and CBD do not impact efficacy. However, other recent research has found that migraineurs prefer hybrid strains with high-THC and low-CBD concentrations. This preference may be due to the potent analgesic, anti-inflammatory, and antiemetic properties of THC.

For Crisci, though, experience has led her to favor low-THC strains. “I prefer a sativa hybrid with a high CBD level as a prophylactic or preventative medicine, as a pure sativa can make some, myself included, feel anxious. I’ll microdose immediately, once I feel a migraine coming on.”

For full-blown migraines, Crisci prefers indica dominant high-CBD strains. “Indica strains lower pain levels more effectively for me, and CBD lowers the THC high. Personally, I do not want to feel high while suffering the effects of an intense migraine, she reflected.

Kimless notes that individual responses to cannabinoids vary—what works well for one may offer less relief for others. That said, some level of THC appears to offer greater alleviation. “Most of my patients require a small amount of THC and not just CBD alone to experience relief,” said Kimless.

Polston added that the therapeutic terpenes, flavonoids, and phytocannabinoids also present in cannabis may play a role in easing migraine. “More in-depth research is needed to determine what, if any, role these compounds may play,” he said.

The frequent use of prescription medication for migraines is often aligned with medication dependency and medication overuse headaches. Several studies, including a 2018 review, suggest that cannabis can reduce or even replace addictive opiate medications, something Crisci has experienced firsthand. “When I started to use cannabis to treat my migraines, I found I was able to stop using many of my prescription medications: no more opioid painkillers, muscle relaxants, or anti-anxiety meds,” she said.

If you’re already taking prescription medicines for migraines but contemplating cannabis as an alternative, it’s best to talk to a physician experienced in cannabis medicine. Kimless endorses the “start low, go slow” adage.

“A little bit goes a long way with cannabis medicine. The sublingual or inhalational method allows for incremental dosing, which will help patients learn how much is needed to be effective,” she advised.

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Cannabis in Palliative Care

End-of-life care is one of the less frequently discussed uses of medical cannabis. After all, most of us who turn to cannabis, want to continue living, right? And yet, thanks to the ability of cannabis to ameliorate the heavy symptom burden experienced by patients with minimal side effects, palliative care is perhaps the area of medicine that would most benefit from its clinical use.

Dying is a journey all of us will inevitably take, however how to ‘die well’ is something we tend not to consider. Dignity with dying is only possible, I believe, when there is a certain amount of consciousness and acceptance of the process. Something that a skinful of morphine doesn’t allow. But cannabis does, and I experienced this for the first time with a friend’s mother.

As Jose neared the end of her life after battling pancreatic cancer, morphine failed to control her pain, leaving her confused and unable to connect with loved ones. Thanks to an open-minded doctor who recommended cannabis oil, the last few weeks of her life became the gift her family longed for. The pain no longer troubled her, the anxiety lessened, sleep returned, as did her appetite. Not only that, Jose remained fully lucid until moments before she died.

This changed me forever and it’s why I’m sitting here today writing about cannabis.

Holistic medicine

Sadly, when my mother became terminally ill with advanced cancer, this option was not available in the UK. Sure, I had a few offers from my cannabis contacts. But for an 82-year-old Irish ex-nurse, trusting a funky tasting oil (that I couldn’t say for sure how much to take) over the pharmaceutical meds prescribed in precise dosages was never going to happen.

Instead, I found myself administering a list of medications that just kept growing and growing as the disease progressed. This included morphine for the pain (which incidentally my mum couldn’t tolerate), antiemetics for nausea, laxatives for the constipation caused by both the cancer and the pain medication, as well as Lorazepam for the middle-of-the-night agitation.

The frustration was overwhelming. I knew that instead of the sledgehammer approach to her symptom control, a far more holistic, person-centred alternative existed that could not only ease her pain, take the edge off her anxiety and agitation, stimulate her appetite and help with the nausea, but also allow her to be present for the time that remained.

What is Palliative Care?

According to the World Health Organization, palliative care is “an approach that improves the quality of life of patients and their families facing the problems associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual.”

In other words, palliative care encompasses end-of-life care, but a patient receiving palliative care is not necessarily approaching death.

However, when a patient enters the end-of-life stage in a hospice setting, the emphasis on quality of life means rules often get bent in a bid to fulfil a dying patient’s wishes and beliefs. Dogs and family pets are welcome guests in a patient’s room, and a glass of wine is not unheard of, if that’s what the patient wants. So why not allow access to medical cannabis if that will help ease the suffering of a dying patient?

In some countries and states in the US, palliative and end-of-life care is considered a qualifying condition for the prescription of medical cannabis.

Using Cannabis in Palliative Care

Since 2007, the Israeli Ministry of Health has approved medical cannabis for palliative care in patients with cancer. This led to a prospective study analysing the safety and efficacy of cannabis in 2970 patients and the responses were overwhelmingly positive.1

Ninety-six percent of patients who responded in the 6 month follow-up reported an improvement in their condition, 3.7% reported no change and 0.3% reported deterioration in their medical condition. Furthermore, while only 18.7% of patients described themselves as having good quality of life prior to cannabis treatment, 69.5% did six months later. Tellingly, just over a third of patients stopped using opioid pain medication.

While observational studies such as these suggest cannabis can improve symptoms commonly found in advanced cancer, as well as improving quality of life, in practice physicians often feel insufficiently informed to prescribe cannabis to their patients.

A 2018 survey found that of the 237 US oncologists interviewed, 80% conducted discussions with their patients about cannabis, while only 30% actually felt they had enough information.2 However, an encouraging 67% viewed cannabis as a helpful additional way to manage pain, and 65% said that it was equally or more effective than the standard treatments for the rapid weight loss often found in advanced cancer. And yet, only 45% of them actually prescribed cannabis to their patients.

These discrepancies mean that even in countries where cannabis can legally be prescribed for palliative care, many physicians prefer to stick to the usual methods of symptom control.

A Physician’s View

Claude Cyr, MD, a Canadian family physician and author of “Cannabis in palliative care: current challenges and practical recommendations,” believes palliative care is uniquely suited to cannabis.3

“If we’re going to integrate cannabis products in medicine,” he told Project CBD, “palliative care is the best port of entry because of the fact that doctors have more time, and patients also have the time to deal with possible issues of the medication.”

However, in order for cannabis to fulfil its potential in palliative care, Dr. Cyr believes a shift in how physicians view symptom control is needed.

“What seems to be coming through with the research for symptom control,” says Cyr, “is that cannabis is mildly effective for pain, mildly effective for nausea, mildly effective for insomnia and anxiety. It doesn’t treat any one of these conditions dramatically better than the other medications that we have. So, many physicians are like ‘why would we take a medication that is mildly effective when I can take a much more incisive approach with specific symptoms.’ Instead of saying ‘Do you have a bit of pain, a bit of anxiety, a bit of insomnia, a lack of appetite and a bit of nausea? So why don’t we start with something that’s mildly effective for all that and then we’ll be able to work on more specific symptoms in the long run’.”

Cyr is also critical of fellow physicians’ tendencies to rely on clinical evidence while dismissing the validity of their patients’ positive experiences.

“Palliative care is a specific situation where we can actually put into question the core philosophy of medicine which is the evidence based paradigm. I think physicians need to stop obsessing over the evidence when their patients are dying and clearly telling them, ‘I’m really enjoying this, I’m getting huge benefits from this, I’m sleeping better, I’m eating better.’ But the physicians are nodding their heads and saying, ‘I hear you, but I can’t accept this because I’m still lacking evidence.’

“But I think there is enough data out there to convince physicians that it’s safe for palliative care patients, and it’s predictable.”

Psychoactivity in palliative care

Cyr urges doctors to find peace with the idea that cannabis is psychoactive, which he believes could actually help patients process the existential anxiety often experienced at the end of their lives.

“When you look at the studies of psychedelics in depression and existential anxiety in cancer patients, some of these results have been dramatic,” says Cyr. “Although cannabis isn’t a true psychedelic, there are some similar experiences that patients tell us about.4 At smaller doses patients experience a psycholytic effect, a lowering of the defenses allowing people to explore other aspects of their psyche, and that’s when they start making connections between different aspects of their reality.”

THC’s ability to reduce activation of the default mode network, the area of the brain involved in cognitive processing and where our ego or sense of self is thought to reside, could also potentially bring a sense of peace to dying patients.56

Cyr explains: “Existential anxiety is rooted in the loss of the self, but when you can dissolve the ego temporarily and you realize it’s not all about me, that can be liberating.”

For the last fifty years, activists have been campaigning for the right to use cannabis to treat their health conditions in order to be well. This must also be extended to using cannabis to maintain quality of life in life-threatening illnesses, and when this no longer becomes possible, to die well and with dignity.

In memory of Jose and Agnes.

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

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


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The most important cannabis science stories of 2019

The biggest cannabis science story of 2019 didn’t take place in the laboratory. It happened in the emergency room, when all at once, consumers of counterfeit cannabis vape pens in the United States started to get seriously ill. The first cases of EVALI (e-cigarette, or vaping, product use associated lung injury) hit the media in August, and to date, at least 52 people have died from the condition, with thousands of cases reported across all 50 states.

At the outset, public health officials struggled to understand the cause of the outbreak and agree on a coherent response, and the mainstream media published all manner of confusing and conflicting reports. Until Leafly’s own team of investigative journalists broke a series of stories that accurately identified the source of the illnesses—additives like Vitamin E—then traced the supply line of tainted vape carts from Chinese counterfeiters to bootleg concentrate makers to illicit national distribution syndicates and finally to the local suppliers selling them on the underground market

Aside from the vaping story, numerous scientists and labs around the world published great new research on cannabis. Here are some of the most important studies on cannabis in 2019.

One vastly underreported study this year looked at cannabis as a potential treatment for Autism Spectrum Disorder (ASD) and for the first time produced clinical data showing clear benefits in pediatric cases.

The study, published in the journal Frontiers in Pharmacology, included 53 patients with a median age of 11 years old, and attempted to gauge improvement across a varied set of symptoms related to ASD after administering a daily does of THC and CBD.

Patients showed significant improvement in hyperactivity symptoms (68.4%), self-injury and rage attacks (67.6%), sleep problems (71.4%), and anxiety (47.1%)—with 74.5% reporting overall improvement and less than 4% reporting worsening of symptoms.

Well, we’ve all heard reports that cannabis “shrinks your brain,” a claim that was breathlessly reported across the media after a few small studies seemed to suggest that heavy adolescent use could lead to a decrease in brain size. The headlines and bad puns write themselves, after all.

But the press paid almost no attention this February when the journal Nature published a study with a large sample size that used MRIs to examine the brains of 781 youth aged 14–22—including both occasional and heavy cannabis consumers—and determined that neither group showed significant structural differences in their brains when compared to non-consumers.

According to the study’s summary:

There were no significant differences by cannabis group in global or regional brain volumes, cortical thickness, or gray matter density, and no significant group by age interactions were found. Follow-up analyses indicated that values of structural neuroimaging measures by cannabis group were similar across regions, and any differences among groups were likely of a small magnitude. In sum, structural brain metrics were largely similar among adolescent and young adult cannabis users and non-users.

To be clear, cannabis use is certainly not completely harmless—particularly for the developing brains of adolescents—but that’s no excuse for skewed and misleading news coverage.

The latest version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines cannabis use disorder as “continued use of cannabis despite clinically significant impairment.” There’s a lot more detail on what that means exactly, including symptomatic behaviors and risk factors, but at the end of the day it’s really a judgement call based on your interpretation of what “clinically significant impairment” really means.

Especially once you accept that compared to the chronic abuse of cocaine, alcohol, and heroin, the problems associated with cannabis use disorder typically appear relatively mild. Largely because cannabis is far less physically harmful than any of those other drugs.

Which does not diminish the fact that cannabis dependency is a very real issue.

But it’s also a diagnosis that’s largely in the eyes of the beholder, as an intriguing study published this year in the International Journal of Drug Policy showed by comparing states with thriving medical cannabis programs to states with less or no legal access to medical cannabis. Not surprisingly, they discovered that greater access to cannabis led to greater reported use. But they also found that those same states had lower instances of cannabis use disorder.

So how can you have more people consuming cannabis and less problematic use? One hypothesis is that as people come to accept cannabis socially and as a legal product, their idea of what constitutes “clinically significant impairment” adjusts accordingly. Which means less people forced into rehab because they got arrested or failed a drug test and more help available for people who legitimately need it.

If you find yourself facing a surgical procedure requiring sedation, you may want to discreetly let your anesthesiologist know that you consume copious amounts of cannabis. Because according to a new study from researchers in Colorado, you may need twice as much anesthetic to achieve the same effect as a non-user.

And that disparity could be a big enough to lead to serious problems in the operating room if not disclosed. As Corinna Yu, Assistant Professor of Clinical Anesthesia at the Indiana University School of Medicine, explained while encouraging patients to be forthcoming before undergoing a procedure.

“We have to destigmatize this so we can just be honest,” said Yu, who warns that withholding information about your cannabis use “could lead to intensive care unit stays and being on a ventilator. It’s a big deal.”

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Cannabis: A Medicinal Treasure Trove

Project CBD: Welcome to another edition of Cannabis Conversations. I’m Martin Lee with Project CBD and today we will be speaking to Dr. Ethan Russo, noted neurologist, a researcher in the cannabis field for many years, and author of quite a few peer-reviewed scientific papers. Welcome Ethan.

Russo: Thank you for having me.

Project CBD: Dr. Russo I recall reading your articles in various scientific journals about CBD – cannabidiol – many years ago, and yet today now we’re in the midst of a CBD explosion. It’s become a huge fad, a global phenomenon. How, as a researcher who is looking at CBD much earlier than the culture has embraced it – how do you relate to this cultural phenomenon?

Russo: I was aware of the psychopharmacological effects and other effects of cannabidiol from the early 70s. That was one of my interests in my early education. But at that time it was relegated to the back seat, at best, in relation to THC, which garnered all the attention. Certainly in medical school there was no attention to this topic at all. But, as developments accrued and there was the discovery of the endocannabinoid system it rekindled my interest in it in the mid 90s when I really delved back into the pharmacology of cannabis again.

It was apparent to me that a very important pharmacological agent had been overlooked – that being CBD. I was then quite aware of its potential medically, which had been, again, largely forgotten outside of Professor Mechoulam and his acolytes and perhaps the Brazilians who had studied the effects as an anticonvulsant. When I began my work with GW Pharmaceuticals in 1998, they had been prescient to realize that this was a very important component of a properly constituted cannabis preparation to be used therapeutically. So, it was like an equal partner to THC in their development program. And at that time the company was also funding basic research to investigate additional attributes of CBD, particularly as an anti-inflammatory and as an analgesic, a painkiller, but particularly its ability to reduce the side effects of THC. So at that time, along with interest in other components, I began writing about CBD, probably first in 2001.

Project CBD: Did you ever imagine it would get to this point where CBD would be this cultural artifact?

Russo: Well I always hoped so. I think that it was well-deserved status to finally be recognized for what it could do. At this point, however, I think certainly the hype has exceeded its real capabilities. Coupled with the fact that there’s so little regulation in the marketplace, I think it’s just incredibly confusing for the potential consumer that might be trying to get a proper cannabidiol preparation.

Project CBD: So, cannabis has been described by Dr. Mechoulam in Israel as a “medicinal treasure trove.” I assume he’s not just talking about THC and CBD, two of the major components of the plant. What else is in the plant that we should be paying attention to, and what else might become available to patients and consumers as something they can use therapeutically?

Russo: Well, we’re seeing history repeated. All of the attention has been on THC and CBD to the exclusion of what may be as many as 148 different cannabinoids that the plant produces, which seemingly are unique to it, although we’ve got a couple of exceptions from nature. But, on the horizon certainly I think cannabigerol which is the parent molecule to THC and CBD –

Project CBD: CBG.

Russo: That’s right. Cannabigerol (CBG), emphasis on the “G” as opposed to the “D”. I think this has great potential. So this is not an intoxicating agent. Rather, it does have a strong anti-anxiety effect and for people who have had access to it, this is an almost universal describer of the effects. Beyond that, it seems to be a powerful antibiotic that can work on bacteria that are normally resistant to antibiotics, especially Methicillin-resistant Staphylococcus aureus, which has caused some hospital-acquired infections.

Project CBD: And deaths, as far as I know.

Russo: Absolutely. Particularly in the immunocompromised patient, this is potentially fatal. Additionally, it works on a variety of cancers, especially prostate cancer, where it seems to have a specific effect, which really could be leveraged into an important medicine. Prostate cancer is one of the main killers of older men. So, it’s of interest to us, to be fair, because of our age demographic certainly. It’s an extremely promising agent. Finally, after again being ignored for decades, the acid cannabinoids, the form that are actually produced in the cannabis plant.

Project CBD: So you’re talking about CBDA and THCA. What is the “A” in this context in these molecules?

Russo: That’s right: cannabidiolic acid and tetrahydrocannabinolic acid. Those are the precursors that are made in the plant that normally will produce THC and CBD through a process called decarboxlyation, loss of a CO2 molecule, which normally happens by heating, either by smoking, vaporizing, baking, or in the lab. These [cannabinoid acids] were relegated to be inactive in the past, but again, they just weren’t looking in the right places, or didn’t have the right tools at the time. About 15 years ago, THCA was shown to have activity on tumor necrosis factor-alpha (that’s TNF-? for short).

Project CBD: And what is that exactly?

Russo: So, this is an important mediator of autoimmune effects. It’s important in diseases like multiple sclerosis, rheumatoid arthritis, ulcerative colitis, and Crohn’s disease; probably a lot of other autoimmune diseases that we’re seeing increasingly in our populations. As if that weren’t enough, though, a couple of years ago a group in Spain identified this as seemingly the most powerful of the cannabinoid agents on another receptor.

Project CBD: This, now we’re speaking of THCA.

Russo: Correct. Still on THCA. So THCA was shown to be an agonist, a stimulator of the PPAR-gamma receptor.

Project CBD: And what is that exactly?

Russo: PPAR-gamma is a nuclear receptor. It affects gene transcription – so how the inner workings of the cell really work. Now that sounds scary, although there are a lot of very important potential therapeutic effects from that, including helping with weight loss, the metabolic syndrome, Type 2 diabetes, and additionally again, treating cancer. So, what we’re seeing now is the science is actually catching up with people who have been using raw cannabis, particularly THCA, to treat a variety of conditions. And we knew before that a lot of patients with autoimmune conditions were getting benefit from raw cannabis products.

So, the other side of the coin is CBDA, cannabidiolic acid, the precursor in the plant to CBD. One of the effects of CBD that was discovered in 2005 by my colleagues at the University of Montana was that CBD exerts some of its effects, like on anxiety, through a different receptor, the serotonin 1A receptor – 5HT1A. That’s been fascinating and very important, but in fact CBDA works on the same receptor but it’s 100 times more potent. This leads me to believe that, again, this could be leveraged as an anti-anxiety agent, but also in treating nausea with tiny doses that would just present no likelihood of any toxicity at all. That one has been looked at in animals, but no clinical trials in humans. So, we’ve got a lot of work to do yet.

Project CBD: And just to clarify: When we’re speaking of the acid versions of the cannabinoids, even THC, these are all non-intoxicating?

Russo: That is true.

Project CBD: So why is THCA non-intoxicating, and yet THC you get high from it?

Russo: It just has to do with whether they bind to the CB1 receptor, which is the receptor in the brain that mediates intoxication in this instance – I never liked that word – because the CB1 receptor is the target for getting high. And because neither THCA or CBDA lodge there with any affinity, they don’t produce this kind of intoxication.

Project CBD: So, what word would you prefer rather than intoxicating or non-intoxicating? Is there a better phrase for this?

Russo: They would string together six syllables. I guess I would just say “active on CB1.” And that would explain a lot of other activity too, because to say that CB1 only is responsible for intoxication hardly does it justice to all its therapeutic effects. But, all of this indicates to me the importance of whole cannabis preparations, because basically cannabis is like a drugstore in one preparation, and so its effects are really going to depend on the ratios of the various components. We see a lot of companies invested now in single components, what people call isolates, CBD isolates, THC isolates, and these can be therapeutic. But to me they’re really lacking in having the full attributes that we can really achieve with a properly constituted cannabis preparation. THC on its own is a lousy drug. It’s very hard to tolerate, it’s very disorienting. It’s only with the addition of CBD that modulates those effects, or the terpenoids, that we really get an acceptable preparation that can do a much better job.

Project CBD: So, what about THCV and CBDV? What does the “V” stand for in these compounds, and what are the implications? What do they do therapeutically?

Russo: “V” stands for varin. And this is just a way of saying chemically that there’s a 3-carbon side chain instead of a 5 with THC and CBD. THCV is usually seen in small amounts in cannabis from southern Africa – very small amounts. Recently there’s been selective breeding to get much higher amounts of it, and it’s a fascinating compound. Contrary to THC, which is a weak agonist at the CB1 receptor, THCV is what’s called a neutral antagonist. So it means it weakly inhibits that receptor. So, when it’s combined with THC, what we hear experientially from people who are using such a product is that the high is clearer and more manageable.

We know that THCV, which has been tested in animals and humans, has a lot of other beneficial effects, again particularly for the person who may be obese, have the metabolic syndrome, or Type 2 diabetes. And it actually benefits the laboratory abnormalities of people with those kinds of problems, as well allaying hunger and leading to some reasonable degree of weight loss. But, this is without the terrible side effects that were seen with some of the prior weight-loss drugs like Rimonabant, which was yanked off the of European market and never approved by the FDA. It is different in its effects. It was what was called an inverse agonist.

An inverse agonist actually reduces the activity of the whole system, so it’s knocking down the benefits of the whole endocannabinoid system. And as many of us predicted years ago, that isn’t a good thing. That produces anxiety, it lowers seizure threshold making seizures more likely, it could increase the risk of cancer. Those kinds of drugs have dropped out of pharmaceutical research because of the side effects.

Project CBD: And Rimonabant – that was a cannabinoid-based diet pill, as it were, but it was thought to be.

Russo: Sure.

Project CBD: And a research tool, I would imagine.

Russo: It highlights the dangers – that was a synthetic, a very powerful inverse agonist. But it was one of those situations until it was really on the market, they really got stronger signals of these serious side effects. There were even a couple of cases of de novo multiple sclerosis where it developed in someone on this drug who had shown no signs of it before. Very scary stuff. It’s another instance where it’s clear that nature does it better.

So, going back to THCV, that’s not all. Basically it has a number of other interesting properties. In contrast to Rimonabant which could cause seizures, THCV is an anticonvulsant. Additionally, it seems to have a strong effect on neuropathic pain, nerve-based pain. That’s a really strong therapeutic profile.

Project CBD: Last question, coming back to CBD, but the varin version of CBD, CBDV, what do we know about that, what is its potential?

Russo: Like CBD, it seems to have an anticonvulsant effect, benefit on seizures, but a different type. Whereas CBD works in general pretty well, CBDV seems particularly good for what are called focal seizures or seizures of partial onset, that might be generated in one area of the brain, for instance an area that’s damaged after head injury. Really it looks like the combination of the two, which we see in some chemovars of cannabis, might be a really good place to start for that kind of treatment.

Project CBD: There are lot of other aspects of the plant I’d love to ask you about, but I don’t think we have time. We’ll have to do it next time. So I thank you Dr. Ethan Russo for joining us today on Cannabis Conversations.

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

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Cannabis and Chronic Fatigue Syndrome

In November 2005, my dependably robust health took a sudden swerve into the dark unknown. It started with an occasional dizzy spell. I’d be teaching a college writing class when suddenly I’d feel light-headed and woozy. Excusing myself to run to the restroom, I’d take deep breaths and splash cold water on my face.

My crash-and-burn had begun. Soon new scary symptoms were bursting forth every day or so like an evil menace in a sci-fi movie. I had room-spinning vertigo. All-over pain that made turning my head or biting an apple a self-inflicted torture. Rashes sprang up. Veins bulged. My hair fell out in clumps. Chewing or speaking would make my face throb and tingle before it went completely numb. When I did manage to talk, I struggled to find basic words or form a sentence. Lights, noise, and motion were dreaded enemies. I could hardly keep food down. Before long I had shrunk to a sack of bones. I felt as though I was being swallowed alive, my life-force squeezed out of me.

In a few weeks’ time I had morphed from a high functioning writer, professor, and parent into a sobbing lump of misery who could no longer drive a car, read a book, wash a dish, or hold a pen. I was so weak that a routine task — like taking a shower — would flatten me for hours. I spent my time lying motionless in bed, waiting for the day to end. But nightfall brought no respite. Restful sleep had become a distant memory.

“A very challenging disease”

My doctor ordered tests. And more tests. I saw a neurologist, an endocrinologist, an internist, an oral surgeon, several psychiatrists, and three ear-nose-and-throat specialists. I had an MRI and a CAT scan. My blood was analyzed by state-of-the art, high-tech labs. Various possible diagnoses were tossed around: lupus, Lyme Disease, a brain tumor, multiple sclerosis. mitochondrial dysfunction, temporal mandibular joint disorder… One physician tried to convince me that my illness was due to a buildup of wax in my ears, which he promptly removed and charged me $250.

One by one, all of these unfortunate scenarios were ruled out. But I was no closer to understanding what was happening to me – until my doctor uttered those fateful words: “Chronic Fatigue Syndrome.” He pronounced his diagnosis somewhat dubiously, as if he doubted its legitimacy. He may as well have said, “We don’t know what it is or what to do about it, and at the moment there’s no cure.”

According to the Centers for Disease Control (CDC), about 2.5 million people in the United States and 17 million worldwide suffer from myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS). ME/CFS is a serious condition that can cause significant impairment, rendering 75% of sufferers disabled, with 25% homebound and even bedridden. Eighty percent of Americans who meet the criteria for ME/CFS have not been diagnosed. Adding insult to injury, many sufferers are dismissed as addled with a somatic symptom disorder, which basically means, “It’s all in your head,” and prescribed anti-depressants.

“Chronic Fatigue Syndrome is a very challenging disease,” says Robert K. Naviaux, MD, PhD, who directs the Mitochondrial and Metabolic Disease Center at UC San Diego School of Medicine. “It affects multiple systems of the body. Symptoms vary and are common to many other diseases. There is no diagnostic laboratory test. Patients may spend tens of thousands of dollars and years trying to get a correct diagnosis.”

Drugs, desperation, depression

ME/CFS is now recognized as a real disease by World Health Organization, the CDC, and the National Institutes for Health, with working groups at Stanford, Harvard, and elsewhere. But many doctors still are not adequately trained to deal with a chronic condition like ME/CFS. There are no FDA-approved treatments for ME/CFS, and any medications doctors prescribe are off-label and fraught with adverse side effects.

Modafinil, prescribed to combat sleepiness, can cause severe skin rashes and psychiatric events like psychosis, mania, delusions, hallucinations, suicidal ideas, and aggression. Cymbalta, prescribed for pain and depression, is addictive and can trigger severe withdrawal, as well as suicidal thoughts, nerve damage, and weight gain. Vyvanse, an addictive amphetamine, is another problematic choice.

Like many ME/CFS sufferers, I was desperate. I tried pain, sleep, and anti-depressant medications, but nothing helped, and most made me feel worse. After several months on temporary disability, waiting and hoping to get better, I was forced to quit the teaching job I loved.

Though I hadn’t given up on life, I wondered if I should start planning my own funeral.

Taking a chance on cannabis

Due to the lack of effective FDA-approved treatments, many desperate ME/CFS patients resort to self-medicating. I was one of those people. I scoured the internet, dropping serious scratch on all kinds of alternative therapies in hopes of finding something — anything — that could help.

I gave up gluten, sugar, and animal products. I swallowed handfuls of supplements and gallons of a slimy green concoction I called “bug juice.” A highly recommended massage therapist pounded me to a pulp while tsk-tsking that I was “holding on to trauma.” I received weekly acupuncture from a dear old Chinese gentleman who refused my money when it became clear he couldn’t help me.

I’d heard that some people with ME/CFS found cannabis to be helpful. I hadn’t smoked weed in years, and, frankly, getting stoned sounded like the last thing a completely incapacitated person ought to do. But I was willing to try anything. A resident of California, I obtained a prescription for medical marijuana and went to a dispensary, where I bought a thimbleful of Purple Kush, a strain recommended by a young budtender for pain and sleep.

That night I rolled a shaggy THC-rich joint. I nervously took a hit and coughed. Within minutes something shifted. The background noise of paralyzing pain grew quiet, and something close to calm washed over me. I easily floated off to sleep for the first time in more than a year. In the morning I felt different — not cured, but hopeful. I’d finally found something that helped.

Enter CBD

According to ME/CFS researcher Dr. Nancy Klimas, drugs typically prescribed for sleep — like Ambien and Valium derivatives Restoril and Klonopin — can knock you out but won’t lead to the deep, restorative sleep so crucial for those afflicted with ME/CFS patients. Chronic insomnia inhibits the body’s ability to repair daily cellular damage, and this is especially destructive to ME/CFS patients. To fall asleep and stay asleep is a turning point for those who manage to achieve it, and most notice subsequent improvement in their symptoms.

I continued my nightly toke of THC-rich cannabis, and after a few days I was able to get out of bed and totter around. I left the house for short walks, which grew longer over time. My appetite improved, and I started to gain some much-needed weight.

Then a friend told me about CBD, a non-intoxicating cannabinoid, which was still a novelty in California’s medical cannabis community. He thought it might help my condition. CBD-rich cannabis hadn’t yet become available in most medical cannabis dispensaries, but he sourced some flowers with a 2-to-1 CBD-to-THC ratio.

When I added CBD to my cannabis regimen, more symptoms relinquished their stranglehold. The pace was slow but noticeable. I began to read and write again. One night, I went to see my daughter Melati’s theater performance, the first evening I’d been out in a year. Abundant, grateful tears fell as I watched her onstage. With the help of homegrown CBD-rich cannabis, I was coming back to life.

Biomarker breakthrough

How is it possible that cannabis could help my chronic fatigue when prescription medications couldn’t touch it, or did more harm than good? The answer might lie in new research that aims to explain what underlies the disease.

Until recently, one of the major challenges has been the lack of a clear biomarker — a measurable biological indicator of a disease’s existence — for ME/CFS. But soon there may be a reliable way to test for this disorder.

A 2016 study published in the Proceedings of National Academy of Sciences identified a “characteristic chemical signature” in ME/CFS sufferers, with an underlying biology similar to the state of dauer. “Dauer, like hibernation,” the study explains, “is a means of preserving survival by severely curtailing functions of ordinary life such as energy, digestion and movement.”

Mark Davis, an immunologist at Stanford University, has made some interesting discoveries with T cells, a type of lymphocyte that plays a major role in the immune system. T cell overactivation was found in the blood of ME/CFS patients, similar to what’s found in immunological cases like cancer, multiple sclerosis or infections. A 2015 paper by German scientists reported a marked increase in specific antibodies of chronic fatigue patients. And more evidence of a hyper-inflammatory response was presented in a 2017 study by Davis and Jose Montoya, showing elevated cytokines.

“There’s been a great deal of controversy and confusion surrounding ME/CFS – even whether it is an actual disease,” Davis says. “Our findings show clearly that it’s an inflammatory disease and provide a solid basis for a diagnostic blood test.”

Immune overdrive

With chronic fatigue, the immune system, spurred by who knows what, goes into full aberrant fight mode, activating a hyper-inflammatory response and setting off a carnival of nightmarish symptoms. A 2015 article in Science Advances reported heightened immune activity in ME/CFS patients during the early phase of the disease that was “consistent with a viral trigger or disrupted immune regulatory networks.” But in later stages of the disease, the levels of immune disturbance were much lower. It appears that whatever immunological threat initially triggered the disease could have been resolved – and yet the body continued its inflammatory, foe-fighting stance.

Why would the body keep shadow-boxing against an opponent that’s not really there? Robert Naviaux at UC San Diego explores this question in a beautifully-written article about his work on ME/CFS, mitochondria and “cell danger response” (CDR) — a term describing the body’s cellular metabolic response to chemical, physical and biological threats. Naviaux found that in ME/CFS patients, the CDR persists abnormally: “Whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results.”

In ME/CFS patients, inflammation and pain are like conjoined demon twins. When the body responds to a perceived threat, it sends out legions of chemicals into the blood and tissues to beat back foreign invaders. When functioning normally, this inflammatory response is an important, life-saving mechanism, but in ME/CFS sufferers it’s driving pedal-to-the-metal, with severe pain and other symptoms as a consequence.

Given that a runaway immune response and marked inflammation are major players in ME/CFS, it makes sense that both CBD and THC, two potent anti-inflammatory compounds, could be profoundly therapeutic. Anecdotal evidence bears this out. Do a search in any ME/CFS social media support group, and you’ll find accounts from people who have successfully used cannabis and hemp-derived CBD to improve their symptoms.

Anti-inflammatory cannabis

There are many published reports demonstrating the effects of cannabis on inflammation. A 2010 study in Future Medicinal Chemistry indicated that several cannabinoids were found to calm the inflammatory response through multiple pathways, which led to a reduction of associated symptoms. A subsequent report by scientists at the University of South Carolina disclosed that a combination of THC and CBD suppressed neuroinflammation (swelling of the brain) in patients with MS. The same neuroinflammatory symptoms have been observed in brain areas of ME/CFS patients with cognitive impairment and severe neuropsychological problems. Thus it’s reasonable to consider that cannabis could also be efficacious for treating neuroinflammation in ME/CFS.

CBD might also help to alleviate the difficult mood problems that ME/CFS sufferers experience. Brazilian scientists reported that CBD has “acute anxiolytic and antidepressant-like effects” and “therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis.” This assessment concurs with anecdotal accounts from people using CBD products that are widely available in state-licensed cannabis storefronts and elsewhere via unregulated sources.

There are many claims about CBD’s utility as a sleep aide, but the science is less clear. Several animal studies and some human studies suggest that CBD’s anxiety-relieving properties may help to improve sleep onset and quality. In one study, the administration of a generous dose of CBD (160 mg/day) increased total sleep time and decreased the number of arousals during the night. But low-dose CBD has been associated with increased wakefulness, underscoring CBD’s biphasic, dose-dependent effect.

Cannabis has been shown to be helpful for sleep – with some caveats. In a 2017 literature review pertaining to “cannabis, cannabinoids, and sleep,” THC was found to help patients fall asleep. But THC can also cause daytime drowsiness, and tolerance to THC can develop, rendering it less effective. The review notes that THC combined with CBD in a 1:1 ratio has been associated with sleep improvements among patients with chronic pain conditions. The synergistic interplay of plant cannabinoids can mitigate pain as well as insomnia, while reducing THC’s intoxicating effects.

A lifelong balancing act

If we blend what we know about the pathophysiology of ME/CFS with our current understanding of cannabis therapeutics, one overarching theme emerges: ME/CFS is a disease of total body disequilibrium, and cannabis is a biological equalizer with the potential to treat several symptoms simultaneously.

THC, CBD, and other cannabis components confer therapeutic effects by interacting with what scientists refer to as the “endocannabinoid system.” A principal function of this system is to maintain homeostasis, a state of dynamic equilibrium that keeps everything running smoothly. People with ME/CFS are the living antithesis of homeostasis, their biological processes have gone completely bonkers.

I know this all too well because I’ve been there. It’s been almost fifteen years since I was taken down by a mystery illness. These days I am functioning at about 80 percent of my biological capacity – and that feels like remission to me. I manage my health by eating a mostly plant-based diet, exercise, stress reduction, some supplements, and daily dosing with a CBD-rich tincture, with occasional THC-rich cannabis at night.

I won’t claim that cannabis completely cured my ME/CFS, but I will say that, as part of a broader healing protocol, it has helped immensely.

For more information on ME/CFS, including how to treat it with cannabis:
Health Rising: Finding Answers for ME/CFS and FM

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

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

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CBD research trends in 2019

Recent developments in how CBD (cannabidiol) is regulated in the US have made it much easier to purchase CBD products. Changes to how the federal government views CBD are also making it easier for scientists to conduct CBD research and understand how this cannabinoid interacts with the human body.

CBD isn’t just easier to research at the federal level–agencies like the FDA are paying attention and issuing warnings to help educate consumers, while the National Institutes of Health issued $3 million in grants to research teams looking to study CBD’s pain-relieving properties. And in states where cannabis is legal, state university systems are creating new think tanks and assembling research teams to collaborate on a new generation of cannabis research.

While CBD has demonstrated the potential to help address a wide variety of conditions and symptoms, many questions remain, including what conditions CBD has the most potential to treat, what proper doses might look like, and precisely how CBD brings about the effects it does.

Here are some of the major questions researchers around the world are asking about CBD, and a look at some of the early answers they’re finding.

What CBD research says about epilepsy treatments

We have a pretty good general understanding of the neuroreceptors that CBD interacts with in the body. We also know that CBD and drugs derived from it are effective in treating some forms of epilepsy, including Dravet’s Syndrome and Lennox-Gastaut Syndrome.

What we don’t understand is exactly why CBD helps epilepsy patients. With CBD easier to study–and CBD-based drugs entering the market–researchers are digging further into the molecular mechanisms responsible for CBD’s apparent seizure-reducing properties.

Differentiating CBD and THC

Increasingly, studies on cannabis are shifting focus away from studying effects of the whole plant and toward more focused studies on individual cannabinoids. This research is helping scientists learn more about how cannabinoids act in isolation, how different cannabinoids–for instance THC and CBD–behave in the brain, and more.

CBD research under review

Many studies on the impact of CBD and cannabis in general employ pretty small sample sizes, which limits the data researchers can gather and the conclusions they can draw from it. As the volume of these studies grows, though, researchers are employing that data to conduct review studies on the effects and efficacy of cannabis and its components, including CBD.

Rather than conducting a new experiment, review studies collate and compare the results of previously published, peer-reviewed studies. This allows authors to work with what is effectively a larger data set and more confidently answer questions about the subject.

2019 saw these studies become more common in the cannabis space with review studies aiming to shed light on the efficacy of cannabis–and specific cannabinoids like CBD–in treating pain, as well as the potential negative side effects of CBD.


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