What Types of Pain Can Cannabidiol (CBD) Treat?

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

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

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

Types of Pain

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

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

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

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

How CBD Works for Pain

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

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

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

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

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

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

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

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What Getting High Alone Can Teach You About Yourself

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

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

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

Harms, but What About Benefits?

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

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

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

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

Is Solo Smoking Making Me Psychotic?

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

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

The answer to both questions is pretty clearly yes.

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

A Link Is Not a Cause

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

Getting High Alone Linked to Psychosis, Dependence, Study Suggests

Can you can spot the fudge term?

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

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

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

In Defense of Crutches

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

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

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

A Therapeutic Option

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

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

Loneliness as a Public Health Issue

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

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

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

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

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

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

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

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

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

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

Enlighten Up Yourself

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

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

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

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

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

He found real value in using cannabis introspectively:

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

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

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

Tips for a Solo Flight

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Study Reveals How Marijuana Components THC And CBD Affect Chronic Pain

Photo courtesy of WeedPornDaily.

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Cannabis Awakening: A Matter of Life or Death

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

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

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

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

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

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

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

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

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

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

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

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

Bench: Yes.

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

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

Project CBD: And you told him?

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

Project CBD: How did the doctor respond to that?

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

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

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

Project CBD: You’re talking about building contractors?

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

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

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

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

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

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

Bench: You’re welcome.

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

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ICRS 2018: Report from Leiden (Part 2)

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

Fatty acid binding proteins

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

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

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

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

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

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

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

CB1 antagonists 2.0


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

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

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

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

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

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

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

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

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

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

Metabolic tune-up

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

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

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

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

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

Food as medicine


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

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

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

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

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

Looking ahead

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

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

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


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

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ICRS 2018: CBD Shines in Leiden (Part 1)

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

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

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

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

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


THC & CBD for brain health

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

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

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

CBD synergies

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

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

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

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

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

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

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Trade-In Your Ibuprofen for Cannabis

By Bonni Goldstein, MD On August 15, 2018

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

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

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


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

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

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

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

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

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


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

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Should You Use Cannabis to Prevent Illness?

Our bodies consist of many unique physiologic systems whose sole purpose is to maintain an internal balance called homeostasis. We know the pancreas releases insulin to balance glucose levels between the bloodstream and cells. The thyroid gland releases thyroid hormone, which regulates vital bodily functions related to metabolism, body temperature and much more. Simply put, our bodies are working constantly to stay balanced in response to our external environment.

In the quest to understand how THC causes its well-known intoxicating effects, scientists discovered that we have yet another regulatory physiologic system, called the endocannabinoid system (ECS), whose role is to maintain homeostasis of the messages sent between our cells. Further research has shown that sickness, inflammation, and injury will trigger the ECS to take action, working to reset our internal environment back to homeostasis. This system has been described as being protective and necessary for life. What if we could target this system to prevent illness and maintain better health?


The ECS is the most widespread receptor system in the human body. It is made up of three main parts: cannabinoid receptors; compounds called endocannabinoids; and the enzymes that make and break down the endocannabinoids.

Endocannabinoids, often referred to as our “inner cannabis,” are synthesized on demand from healthy sources of dietary fat. Cannabinoid receptors sit on the membranes of cells in certain parts of the brain and body, namely areas in the brain that control pain, memory, emotion, motor control, nausea, and appetite, as well as the gut, immune system, and peripheral nervous system. When there is a trigger that causes an imbalance, such as an injury or illness, endocannabinoids are released, acting as “keys” that bind to the receptors, which act as “locks” on our cells. Once the receptor is activated, a chemical reaction takes place in the cell, telling the cell to change its message.

ECS functioning depends on many factors, including genetics, age, stress levels, diet, and overall level of health. There can be variants in the genes that code for the ECS which can lead to propensities for certain conditions, such as ADHD and PTSD. Additionally, chronic illness, chronic stress and/or chronic sleep deprivation may lead to depletion of the endocannabinoids. These disruptions in the normal functioning of the ECS interfere with its ability to regulate cellular imbalances and achieve homeostasis.

In 2004, Ethan Russo, a neurologist and research scientist, published Clinical endocannabinoids Deficiency (CECD): Can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? in the journal Neuroendocrinology Letters. Russo theorized that certain individuals with the listed conditions responded to cannabis-based treatments because they had endocannabinoid deficiencies that allowed the condition to manifest in the first place.

Subsequent research has demonstrated that endocannabinoid deficiency plays a role in autoimmune diseases, epilepsy, complex regional pain syndrome, cardiovascular disease, depression, anxiety, schizophrenia, multiple sclerosis, nausea, Huntington’s disease, Parkinson’s disease, menstrual symptoms, failure to thrive in newborns, and other difficult-to-treat conditions.

The cannabis plant produces over 100 phytocannabinoids, including tetrahydrocannabinol (THC) and cannabidiol (CBD). These compounds mimic the endocannabinoids by interacting with the ECS and restoring homeostasis. Rather than wait until illness is present, there are many ways to take good care of your ECS, which will allow it to function properly, avoid deficiencies and maintain homeostasis.

It’s common knowledge that a healthy, balanced diet is necessary for emotional and physical well-being. Our bodies rely on our diet to produce the right amount of endocannabinoids to function at optimal capacity. Cannabinoids are synthesized from the fatty acids in our diets and require a specific balance of omega-6 and omega-3 in order to be produced in the right quantities.

For maximum bioavailability, the optimal ratio of omega-6 to omega-3 fatty acids from food is between 5:1 and 1:1, the lower the better for those with chronic illness. Western diets routinely consist of ratios of 20:1, mainly due to the overconsumption of omega-6 fatty acids which come from vegetable oils in many packaged foods. Western diets with higher ratios of omega-6 to omega-3 fatty acids results in a reduction of endocannabinoids, leading to the inability to maintain homeostasis.

Another factor that promotes well being of the ECS is aerobic exercise. Animal studies report that voluntary wheel running increases cannabinoid receptors in the brain and increases the sensitivity of the receptors to endocannabinoids. Human studies have shown that exercise such as running, biking and hiking enhance endocannabinoid levels in the bloodstream. In fact, endocannabinoids are likely responsible for the phenomenon described as the “runner’s high.”

Probiotics may also benefit the ECS. Lactobacillus acidophilus, a probiotic bacteria found in fermented foods such as yogurt and sauerkraut, was shown to induce the expression of cannabinoid receptors in the gut, promoting intestinal homeostasis.

Both acupuncture and osteopathic manipulation enhance the ECS. Yoga and meditation elicit the “relaxation response,” a physiological phenomenon whereby one can consciously engage in behavior that promotes mental and physical wellness; although no studies have been done to date, most experts suspect these stress management modalities enhance the ECS thereby promoting homeostasis.

Lastly, what about the ability of cannabis to prevent illness? Plant cannabinoids are well-known to be very safe and to have anti-inflammatory, antioxidant and neuroprotective properties. In cases of endocannabinoid deficiency, cannabis use may be the correcting compound, eliminating the symptoms of the condition. Regular cannabis use can decrease chronic inflammation and buildup of free radicals, both of which are thought to be the root causes of many conditions, including autoimmune and neurodegenerative disorders.

Cannabis is associated with lower fasting insulin levels and lower insulin resistance, suggesting protection against the development of diabetes. Early this year, German scientists found that chronic low doses of THC reversed the age-related decline in cognitive performance in old mice.

Additionally, research has documented the significant reduction of the use of prescription medications in states with medical cannabis laws, resulting in about a one quarter reduction in opiate deaths.

Many patients report that cannabis use enhances their overall health by promoting quality sleep, reducing anxiety and depression, and lessening pain and inflammation so that they can continue to be active participants in their lives. Although exact doses and cannabinoid combinations for preventive indications have not been researched, it is likely that low intermittent doses that include both THC and CBD will augment the ECS without causing adverse effects. A healthy diet (including fatty acids in the correct balance), aerobic exercise and stress management will help your ECS to maintain homeostasis.

Take care of your endocannabinoid system and it will take care of you.

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

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Cannabis Science: What to Believe?

Alan was disoriented and his words were not making sense. His wife thought he might be having a stroke, so she took him to the emergency room where he was seen by the on-call neurologist. When asked, Alan admitted to using cannabis on a regular basis for many years. The neurologist then brought him a printout with the title: “Marijuana Use Associated with Increased Risk of Stroke, Heart Failure.” That was when I got the call asking me if this was for real.

I have not seen this dangerous trend in my clinical practice, but many of my patients have used cannabis for many years so I was motivated to track down the referenced article and review it. If this was a valid concern, I wanted to know so I could inform patients about the risk.


A valid study can inform, enrich, and save lives. Poor studies can create fear and ignorance. The bias can lean either pro or con. Either way detracts from our understanding of cannabis and our ability to provide patients with the best care. I obtained a copy of the original article and reviewed it carefully.

The first paragraph gave me a clue. “…cannabis is…the most widely cultivated, trafficked, and abused drug…” (emphasis added)

I had read similar statements in other scientific articles:

  • “Cannabis remains one of the world’s most widely used substances of abuse amongst pregnant women.” (emphasis added)
  • “Despite increasing public health concerns, cannabis remains the most commonly used illicit drug…” (emphasis added)

What do all these first paragraphs in published scientific articles have in common? Each one reveals a prejudice that makes the rest of the data that follows less trustworthy. Because cannabis has been illegal and vilified for so many years, many publications assume harm even before they are written.


The scientific literature is teeming with new publications every week reporting on cannabis, cannabinoids, and other medicinal uses for the plant. Some of these studies are well done, but how do you know which are valuable and which are faulty? Scary headlines like “Cannabis Use Predicts Risk of Heart Failure” are dramatic, and often circulate widely in the press and on social media.

Most health care providers know little about the medical use of cannabis; they are not taught the endocannabinoid system in medical schools and many avoid this sensitive topic altogether. Patients are educating themselves the best they can by reading news articles and reviewing scientific studies made available online, but not everything we read is accurate and not every study is well-designed. Here are a few guidelines to help you tell the difference between valid information and that which should be taken with a grain of salt.


A study of value to real people reports on a sample that is representative of most human beings. Humans are not mice, so valid conclusions shaping clinical care cannot be reliably based on how mice respond to cannabis. This does not mean that information derived from mice, rats, pigs or other animals is not useful, but the best we can say about animal studies is that further research may be indicated.


“Associations between regular cannabis use and both mental illness and lung cancer have been well established.” [1] This is an untrue statement. Dr. Donald Tashkin at UCLA designed a study intending to prove that smoking cannabis was associated with increased cases of lung cancer.

To his great surprise he found that this was not true, and eventually published an article that indicated just the opposite. [2] False statements based on poorly designed studies are sometimes referenced as fact, leading to further poor conclusions. Supporting a hypothesis with weak science is often an indication of prejudgment.


“Mortality post [myocardial infarction] may additionally be increased in cannabis users…” [1] This statement was used in a scientific article reporting on the damaging effects of cannabis in the cardiovascular system. The use of the word ‘may’ here makes this an opinion, not a fact.

It is also contradicted by other data. Look out for words like “may” or “could” as they indicate a guess, assumption, or opinion rather than a fact backed by observation. The accuracy of the above statement is questionable. In 2018 Johnson-Sasso [3] published a well-done study concluding: “(Our) results suggest that, contrary to our hypothesis, marijuana use was not associated with increased risk of adverse short-term outcomes following AMI. Furthermore, marijuana use was associated with decreased in-hospital mortality post-acute myocardial infarction.”


Science studies humans when possible, but selection of subjects is difficult, especially when studying the effects of cannabis. As long as the plant is federally illegal and socially suspect, most individuals will be apprehensive about disclosing information related to their use.

In many studies, information is gathered by asking patients if they use cannabis, or any illicit substances (self-reporting). The substances are often listed: “Have you used any of the following: amphetamine, marijuana, methadone, heroin, LSD, PCP, cocaine, other?” Not everyone is going to admit to using a substance included in that list. Would you?

This problem was clearly illustrated in a study done in 1995. [4] This research collected data from both self-reports and blood tests. When tested, 585 women tested positive for THC, but only 31% of these women had self-reported use of cannabis. As expected, self-reporting clearly carries the risk of under-reporting. If data is collected only on those who disclose the personal use of an illegal substance, that data will be skewed.

Lab testing to select subjects has limitations as well. Serum drug tests may underestimate the use of cannabis because the THC metabolite they test for is only present for a short period of time. A study subject could have used cannabis last week, or a few days ago, and no longer test positive.

Selection skewing leads to statements like, “Compared with non-cannabis users, cannabis users were older and predominantly men [and]…had an increased prevalence of most risk factors including hypertension, tobacco use, and alcohol use.” [1] This is most likely true for that study’s selection, but not accurate for the general population.


Many, but certainly not all, who use cannabis also use other substances that include tobacco and alcohol. Separating out the subjects who are only affected by cannabis is difficult but must be done accurately for good data on the effects of cannabis alone. Because this task is so challenging, many study results are weakened by confusing the effects of more than one substance.


It is important to review scientific publications carefully and consider any weaknesses stated or implied. The risks and benefits of cannabis as medicine need to be known so the plant can be used safely to everyone’s best advantage. Fear and social attitudes have no place in well-done scientific studies. Unscientific enthusiasm for a widely used herb has no place in the science either. For cannabis to be trusted and appropriately used as medicine, we need impartial facts-well-collected and well-stated.

Thankfully, Alan had not had a stroke. It appeared he had a ‘TIA,’ which is a transient loss of blood flow to the brain with no long-term damage done. But they kept him overnight for tests and to make sure he was safe to discharge. He went home the next day and continued to use cannabis, knowing that the information shared with him by a well-meaning neurologist was not necessarily valid. For him, the personal benefits were worth the possible risks.

Stacey Kerr, M.D. is a teacher, physician, and author living and working in Northern California. After several years working with the Society of Cannabis Clinicians, and co-developing the first comprehensive online course in cannabinoid medicine, she now serves as Medical Director for Hawaiian Ethos. Dr. Kerr is a Project CBD contributing writer. This article was originally published by Hawaiian Ethos.


1. Kalla et al. Cannabis use predicts risks of heart failure and cerebrovascular accidents. J Cardiovasc Med, 2018, 19:000-000 doi:10.2459/JCM.0000000000000681

2. Tashkin. Effects of Marijuana Smoking on the Lung. Ann Am Thorac Soc Vol 10, No 3, pp 239-247, Jun 2013

3. Johnson-Sasso CP et al. Marijuana use and short-term outcomes in patients hospitalized for acute myocardial infarction. PLoS ONE 13(7): e0199705. 2018.

4. Shiono et al. The Impact of cocaine and marijuana use on low birth weight and preterm birth: A multicenter study. Am J Obstet Gynecol. 1995 Jan;172(1 Pt 1):19-27.

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Cannabidiol and Epilepsy Meta-Analysis

How often have we heard, “More research is needed,” from those who would prefer to see no change in policies that should be informed by science? From climate denial to cannabis prohibition, the demand for absolute scientific certainty is a call for inaction.

It begs the question: When is there “enough” research?

How about not enough to eliminate all uncertainties, but enough to recommend medical treatment or change policy?

Published in September 2018, a meta-analysis of CBD treatment for epilepsy provides “enough” research – both to say that CBD is effective in certain kinds of epilepsy, and that CBD-rich extracts are generally better medicine than CBD isolates1.

Three Brazilian scientists – Fabricio Pamplona, Lorenzo Rolim da Silva and Ana Carolina Coan – examined data from 11 different studies comprising 670 patients who were treated for an average of 6 months. The meta-analysis focused specifically on three kinds of childhood seizures (Dravet, Lennox-Gastaut, and those caused by CDKL5 deficiency), and sought to describe the effectiveness, required doses, and side effects associated with cannabidiol.

The authors further analyzed the differences between CBD-rich extracts and CBD isolates. Epidiolex (FDA-approved pharmaceutical CBD) and some unregulated, hemp-derived CBD products are considered isolates, as they lack the full spectrum of other cannabinoids and terpenes that are present in whole-plant extracts.

It works!

Seventy-one percent of people using CBD-rich extracts had reduced seizure frequency, compared with 46% of those using CBD isolates.1 Both of these numbers are incredible. What’s more, the population was treatment-resistant, having tried between 4-12 medications for three years before using CBD.

The authors also examine whether the improvements met specific thresholds: How many people had greater than 50% reduction of seizures (a typical threshold used in medicine)? How many had greater than 70%? Complete cessation of seizures?

Both the whole-plant extracts and CBD isolates helped cut the number of seizures in half for roughly 40% of patients, once again suggesting that both formulations – single-molecule and whole-plant – can be highly effective medicines.

Both formulations reduced seizures by 70% in about one quarter of the patients, but fewer studies recorded this. And roughly one in 10 patients using CBD became seizure-free, although not enough studies reported this metric to compare different formulations.

Less is more

Perhaps the most striking conclusion of this study is the dramatic difference in doses for isolates compared to full spectrum CBD-rich oil extracts. The mean dosage for people using pure CBD was 25.3 mg/kg/day, but for CBD-rich extracts it was 6.0 mg/kg/day.

In other words, CBD in a whole plant extract was over 4 times more potent than isolated CBD. This result is a reflection of what’s known as the “entourage effect,” whereby the therapeutic impact of the whole plant is greater than a single compound or even the sum of the plant’s individual medicinal components.

We can say that “more research is needed” to fully understand the biochemical basis of the entourage effect in epilepsy, but we are well past the point of questioning its existence and importance.

Adverse events

Whole-plant cannabidiol also distinguished itself from isolate CBD with a lower rate of side effects. Isolate CBD was associated mild adverse events2 in 73% of patients, whereas whole-plant CBD was associated with mild adverse events in only 33% of cases. The authors suggest that this difference is due primarily to the lower dose of CBD used when formulated as a whole-plant extract.

It’s worth noting that many of these “side effects” are present in the absence of CBD, and that adding CBD to treatment tends to reduce these side effects, so the numbers may be overestimates.

What’s a meta-analysis?

A meta-analysis is a specific kind of study meant to draw firmer conclusions once many papers have been published on a single topic. It is used to determine quantitative information, and can also help determine the basis for different results that the initial studies did not have the power to prove.

Meta-analyses, however, are prone to bias when the studies used very different designs, and there was one notable difference between the whole-plant extract and CBD-isolate research. All the isolate studies were prospective, meaning that participants were treated according to a protocol written by the researchers. The whole-plant extract studies, on the other hand, were retrospective analyses or surveys.

The lack of prospective studies with whole-plant extracts is due to the schedule 1 status of marijuana, which seriously hinders research into the medical uses of cannabis. Retrospective studies are slightly more prone to bias, such as underreporting of side effects. Despite the potential for bias, this meta-analysis demonstrates that whole-plant cannabidiol extracts are as effective as CBD isolates, if not more so, and can treat refractory epilepsy at much lower doses.

Adrian Devitt-Lee, a Project CBD contributing writer, is a graduate from Tufts University with a degree in mathematics and chemistry.


1. The numbers reported here are not exactly the same as those reported in the meta-analysis. There were a few minor mathematical errors due to complications when consolidating the various data. The mistakes do not change the conclusions of the original study, and the authors have issued a correction. The correct numbers are reported here.
2. “Adverse events” were defined by the authors of each individual study, which could lead to some bias. Mild events included weight loss, fatigue or sedation, gastrointestinal problems, and nausea. Severe events included alterations in liver function.

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Canadian Researchers Studying Hemp Protein to Treat Hypertension

Researchers at the University of Manitoba are investigating the use of hemp protein to prevent and treat high blood pressure, also called hypertension. The study of 35 hypertensive adult volunteers will also assess the effects of hemp protein on other physical attributes, including weight, cholesterol, body mass, hormones, and insulin production.

“Hypertension is a multifactor disease,” says Dr. Rotimi Aluko, the lead scientist for the clinical trial. “To get a full picture of the treatment, we need to know how the participants respond,” says Dr. Aluko, a professor in the Department of Human Nutritional Sciences at the University of Manitoba. “The why is sometimes more important than the results,” he says. The clinical trial follows previous studies at the University where hemp protein was found to be beneficial to hypertensive rats.

The World Health Organization calls hypertension a global health crisis, responsible for 45-51% of global deaths, annually. Worldwide, over 1.3 billion people are hypertensive. Untreated, hypertension can lead to heart attack, stroke, kidney disease, vision loss, and sexual dysfunction, among other conditions.

“Drugs can have side effects, if we can demonstrate that this protein works to reduce hypertension, then people could take a natural protein instead.”

Dr. Rotimi Aluko

Recently, studies have shown that high blood pressure between the ages of 45 and 65 could lead to a higher risk of dementia later in life. In 2011, the United States spent US$46 billion on medicines, services, and missed days of work due to high blood pressure. Blood pressure is considered normal when the systolic (top number) is 120 and the diastolic (bottom number) is 80.

In the 22-week hemp protein study, the 35 adult volunteers with high blood pressure will be divided into three groups. All groups will have three 42-day periods during which the only food they consume is a fruit smoothie with protein powder taken twice a day. Each group, however, will have a different form of protein powder in their shakes: hemp, hemp plus peptides, or casein, which comes from milk. Participants will not know what form of protein they are consuming.

Dr. Aluko says that a smoothie was chosen for two reasons: it’s not hard to drink, and people can’t tell what kind of protein is in it. “A smoothie is easier for volunteers to consume, and you need to make sure participants are blind to the study,” says Dr. Aluko.

If the clinical trial shows that hemp protein can be used to lower blood pressure, Dr. Aluko says that one day hypertensive patients could take hemp protein instead of the commonly prescribed medicines. “Drugs can have side effects,” he says, “if we can demonstrate that this protein works to reduce hypertension, then people could take a natural protein instead.” Common side effects of high blood pressure medicines include diarrhea or constipation, cough, headache, skin rash and erectile dysfunction, among others.

The hemp protein powder for the clinical trial is being supplied by Manitoba Harvest, a cosponsor of the study. The protein powder is commercially available in the USA and Canada as Hemp Yeah! Max Protein. Manitoba Harvest has provided materials for three studies at the University of Manitoba. A 2017 experiment compared the effects of hemp consumption in the form of hemp protein or hemp snacks vs non-hemp controls. The goal of the experiment was to see how hemp products vs non-hemp controls impacted blood glucose, insulin, appetite, and food intake in adults.

The hemp protein for hypertension clinical trial is a recipient of Grant-in-Aid from the Heart and Stroke Foundation of Canada. According to a Foundation spokesperson, the grant was awarded to the study because “experts in the field judged it meritorious amongst the hundreds of applications against our rigorous standards of scientific excellence and relevance.”

If the clinical trial shows that hemp can help reduce blood pressure, then other treatment areas will be examined. “Following this trial, if we see a positive effect, then kidney disease will be next,” says Dr. Aluko. A 2011 experiment, also conducted at the University of Manitoba, showed that hemp protein had positive effects on rats with kidney disease, including normalizing heart size.

Although the hemp protein for hypertension clinical trial has generated a good response, Dr. Aluko says getting 35 people to sign up might take 6 months. Volunteers must live within a 45-minute drive from the research center in Winnipeg.

Dr. Aluko anticipates completing the study in 2019. The results should be published by the end of 2020.

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