Green Zebra CBD and buycbdsafe.com team have a strong belief that people have a right to the highest quality, fairly priced hemp derived CBD. We aim to provide more than just exceptional products and service, we are on a mission to provide hemp derived CBD to all through the #CBDMOVEMENT, by providing access to education, research and testimonials.
How This Activist Launched the CBD Revolution | NowThis - YouTube
[This activist is the reason you know about CBD. Now he’s telling the history behind the cannabinoid.]
Martin Lee: It has really changed the whole conversation about medical cannabis. Where previous to the advent of CBD, or the reappearance of CBD, really, the discussion was about, “Is this for real? Does this really work, this medical cannabis? Isn’t it just people wanting to get high and using that as an excuse? Well, once CBD is part of that, you can’t – that conversation changes, because no one’s using CBD to get high.
[Martin A. Lee is a California-based author and activist. His book Smoke signals: A Social History of Marijuana was published in 2012. Lee is also the co-founder and director of Project CBD, a nonprofit established in 2010 that promotes research into the medical uses of CBD and components of the cannabis plant.]
ML: We were the first group, actually, to advocate to the medical marijuana community in California about CBD. We were involved in introducing CBD, both physically, the plants, and in terms of education to emphasize that there are other options besides the THC orientation – the “get high” orientation – for medical cannabis. We were instrumental in introducing CBD into the medical marijuana world in California 10 years ago, and it spread from there.
[CBD can now be found just about everywhere, from CBD-infused vanilla lattes to CBD-infused cheeseburgers. But that wasn’t always the case.]
ML: It was really only scientists talking to each other, describing what happens when pure CBD, single-molecule CBD was given to mice. And the reports were jaw dropping, the implications. And the immediate thought was, well, wow. If people could have this, this could really be something. As that began to catch hole, word spread outside of California. There were some reports very early on that it was good for epilepsy, particularly for children.
[Lee says that in 2013, the potential benefits of CBD really entered the national spotlight with the CNN special Weed, which focused exclusively on CBD and significantly changed public discourse.]
ML: It’s a very powerful documentary. That was a really profound message that nationally was broadcast in 2013, picked up internationally, that you can use cannabis therapeutically without getting high.
[CBD has been touted as THC’s ‘non-psychoactive cousin.’ While CBD won’t get someone ‘high’ in the traditional sense, non-psychoactive might not be the best definition.]
ML: CBD has anti-anxiety properties, it’s an antidepressant. And anything that can change the mood from depression to a better mood, or can relieve anxiety clearly is affecting the psyche, so I don’t think it’s really correct to describe it as non-psychoactive. I think non-intoxicating would be a more appropriate description.
[Lee said he’s not entirely sure how to feel about CBD’s current popularity, but he emphasizes that cannabis has far more to offer.]
ML: I think part of the problem is that the whole CBD industry that has emerged. And that’s not a bad thing, necessarily, but when you’re trying to simplify your message to sell a product, it can distort what’s really going on, because it’s not just about CBD. CBD, yeah, you can kind of think of it as kind of a medical rock star, but when you really get down into it, it’s the combination of CBD and the other parts of the plant. That’s really where the magic is.
Originally posted on Now This Weed. May not be reprinted without permission from the source.
Shop now https://www.projectcbd.org/now-this-marin-lee-cbd-revolution https://buycbdsafely.com/shop/
The rise of CBD products has sparked a new question in law enforcement circles:
How should police departments treat aspiring cops who admit to using or test positive for CBD (cannabidiol), the active ingredient in cannabis known for its soothing qualities?
CBD, unlike THC (tetrahydrocannabinol), is not psychoactive. Read: It does not get you high.
Nevertheless, the board that regulates police certifications in Arizona has historically regarded the use of over-the-counter CBD products — such as balms for aches and pains — the same as pot you’d find in a medical marijuana dispensary.
Until last month.
On June 19, the Arizona Peace Officer Standards and Training Board (AZPOST) issued a statement clarifying that it “does not view the use or possession of over-the-counter products containing CBD as constituting the illegal use or possession of marijuana, a dangerous drug, or a narcotic drug.”
Matt Giordano, the executive director of AZPOST, said CBD has been widely discussed since he started his job in 2018. In a memo explaining the policy directive, Giordano said would-be officers using CBD products aren’t trying to get blitzed.
“Police agencies have seen an increase in the number of applicants that have disclosed the use of products containing CBD during their backgrounds,” he said. “What we are finding is someone who might rub a product containing CBD oil on their elbow or knee before going out for a run.”
CBD products containing more than .3 percent THC that were purchased at a dispensary would not fall under the exemption. AZ POST will continue to prohibit medical marijuana products above that threshold.
In an email, Giordano said his office could not locate any cases in which a cop was denied certification for CBD use.
Haziness over CBD has also raised questions on the other side of law enforcement in Arizona. In October, Phoenix New Timespublished a report revealing that the Yavapai County Attorney’s Office charged two people with marijuana possession in 2017 for having CBD oil.
One of those charged, Robert Stapleton, tried to explain to the Prescott Valley officer who pulled him over how the CBD vape pen in his car was different than a product containing a higher concentration of THC.
The officer phoned a deputy attorney and asked how he should handle the case.
“Treat the CBD as marijuana instead of a narcotic,” the prosecutor told the cop.
Steven Hsieh is a staff writer for Phoenix New Times. He previously worked at The Stranger and Santa Fe Reporter.
A small study conducted by researchers at the University of Saskatchewan adds to the growing body of evidence that cannabis can be used to successfully treat seizures in children, according to the CBC.
A study funded by Jim Pattison’s Children’s Hospital Foundation monitored seven children suffering from severe pediatric epilepsy, in which up to 1,200 seizures a month are common.
On average, the overall reduction in seizures was close to 75%, while three of the seven children stopped having seizures altogether.
“Some people might say that’s not perfect, that’s not 100 per cent, but you have to take into consideration these are kids that have failed multiple anti-seizure medications, multiple treatments. The likelihood of getting a good result with another medication is really, really low,” said pediatric neurologist Dr. Richard Huntsman, one of the study’s authors.
During the study, the children were administered their typical medication in addition to the cannabis. No participant was administered a placebo.
After one month of observing their seizures, the children received increasing doses of an herbal cannabis extract. The dosage was then increased each month for six months.
A major barrier to the study was the notion that the cannabis-based medicine would make the children intoxicated.
But the actual medication consisted of 95 per cent Cannabidiol (CBD) and five per cent THC. CBD is derived from cannabis plants but does not create a high, whereas THC can be intoxicating. –CBC
“What we were able to show is that the THC levels, even at the highest doses in this study, remained low,” said Huntsman. “Based on this —and, again, this [is] preliminary data for seven patients of study so we have got to keep that in mind — but what we’re able to show so far is that the concerns about THC intoxication, maybe it’s not as much of a concern.”
And while this study may have been small, it confirmed a growing body of evidence supporting the known efficacy of cannabis for a variety of ailments. In fact, there are already FDA-approved treatments for seizures associated with certain conditions, such as Lennox-Gastaut syndrome, and Dravet syndrome, both of which are rare.
CBD for seizures is nothing new
The non-psychoactive CBD cannabinoid found in Marijuana was famously used in 2013 to treat seizures in Charlotte Figi, a 3-year-old from Colorado who suffered from severe, 30 minute seizures.
The twins were 3 months old when the Figis’ lives changed forever. Charlotte had just had a bath, and Matt was putting on her diaper.
“She was laying on her back on the floor,” he said, “and her eyes just started flickering.” –CNN
Charlotte’s doctors weren’t able to pinpoint what was going on; her blood tests and scans were all normal, telling the Figis “It is unusual in that it’s so severe, but it’s probably something she’ll grow out of.”
As the years went on, Charlotte got worse.
With medical and recreational marijuana having been approved in Colorado, the Figis – who had previously been against marijuana use – considered using cannabis to treat Charlotte after Matt Figis discovered an online video of a California boy whose seizures were mitigated using the alternative treatment.
By then, Charlotte had lost the ability to walk, talk, and eat, and was having 300 grand mal seizures a week. Her heart had stopped several times, only to be resuscitated over and over.
At just five years old, the Figis turned to CBD cannabinoid treatment as a last resort.
“They had exhausted all of her treatment options,” said Harvard-trained physician Alan Shackelford, who added: “There really weren’t any steps they could take beyond what they had done. Everything had been tried — except cannabis.”
The results were stunning…
Charlotte’s recovery was dramatic.
“When she didn’t have those three, four seizures that first hour, that was the first sign,” Paige recalled. “And I thought well, ‘Let’s go another hour, this has got to be a fluke.’”
The seizures stopped for another hour. And then for seven days.
Paige said she couldn’t believe it, nor could Matt. But their supply was running out.
Enter the Stanley Brothers
With the Figis expensive supply of CBD oil marijuana nearly gone, one of Colorado’s largest marijuana growers, the Stanley Brothers, stepped up to create a strain of marijuana containing high levels of CBD just for Charlotte – naming it Charlotte’s web.
“The biggest misconception about treating a child like little Charlotte is most people think that we’re getting her high, most people think she’s getting stoned,” Josh Stanley said, stressing his plant’s low THC levels. “Charlotte is the most precious little girl in the world to me. I will do anything for her.”
Years later, Charlotte was thriving – only having 2-3 seizures per month, mostly in her sleep. Not only can she walk, but she’s was riding a bicycle, feeding herself, and talking as of CNN‘s 2013 report.
“I literally see Charlotte’s brain making connections that haven’t been made in years,” Matt said. “My thought now is, why were we the ones that had to go out and find this cure? This natural cure? How come a doctor didn’t know about this? How come they didn’t make me aware of this?”
We want to express our gratitude to Yahoo Finance for featuring Laura Fuentes and enabling us to discuss some of the most pressing concerns facing the industry and the company. From claims to the latest FDA ruling prohibiting the sale of all food in which CBD has been added. Let’s recapitulate what was discussed in the interview.
Laura went on to talk about Green Roads’ partnership with the University of Florida to support the growth of hemp in the state as an initiative to make hemp a dynamic industry in Florida.
Unlike other new industries, the CBD market is ahead of the research and government regulations, but as discussed in the article with the farm bill now in effect, it has “opened up the gates so the other universities could start doing studies.” At this point, it’s only a matter of time before the true benefits of the compound are discovered.
One of the major hurdles facing CBD companies like Green Roads is the official classification of the compound. When asked if classified as a pharmacy or natural supplement, Laura confirmed that “we’re not classified as anything, we’re waiting for the FDA to make that decision.”
Growing in the Face of Uncertainty
The CBD industry is relatively new. From inconclusive state laws to lack of consistent research, Laura was asked how the company plans to keep on growing in the face of so much uncertainty.
She stated, “Green Roads is a wellness company. We really concentrate on the final end-user and putting out quality products that everyone can rely on.” She added, “As far as where we’re heading for the future, the public is going to tell us what products they are looking for and what’s working for them.”
Highlight: “It’s like with any new thing out there, we need to discover what is important about it and what is detrimental,” says @greenroadsworld CEO Laura Fuentes about CBD. Talks about how more research will reveal the benefits of CBD. Full interview: pic.twitter.com/8oIxtQa4HO
We are enthusiastic about the future of the industry and the research that is to follow. In 2017, Forbes placed us as one of the top 10 CBD brands in the country. We’ve also been highlighted in numerous publications including Cosmopolitan, ESPN, NBC, BuzzFeed, CBS, and now Yahoo Finance.
As a result of our commitment to potency and purity, we have been awarded “Best CBD Product,” “CBD Advocate of the Year” at the 2018 Cannabis Business Awards, and we are the largest private CBD company in the U.S.
Green Roads CBD
Our obsession with the potency and purity of ingredients, our exclusive formulations, and third-party lab testing are all part of our devotion to our shoppers. It’s no surprise we lead the industry in transparency, and our products are proudly sold in more than 10,000 locations across the U.S.
Our CBD products are produced with hemp grown here in the United States. Each and every batch of our products are examined by an independent lab to guarantee that the contents always match what is on our labels.
In an extra effort to make the shopping experience more enjoyable, we regularly update the lab results on our website for everyone to access. We offer CBD in many forms; the choice is yours. But as Laura said, “Always consult with your physician or healthcare professional before adding CBD to your regimen.”
The huge popularity of cannabidiol (CBD), a non-intoxicating component of cannabis, has helped to destigmatize the plant and restore its reputation as an important medicinal herb. But bogus science and inept reporting continue to distort how we understand the benefits and risks of CBD and cannabis.
A recent article by Mike Adams in Forbes online rang alarm bells by asserting that CBD “could be damaging our livers in the same way as alcohol and other drugs.” This sensational claim was based on a dubious study of CBD and liver toxicity conducted by researchers (Ewing et al) at the University of Arkansas in Little Rock – except the damage discussed in the study was unrelated to alcohol toxicity and “our livers” actually refers to mouse livers.
The Little Rock study made no mention of humans, which is a hugely important distinction. Moreover, in the real world CBD consumers are not ingesting 0.25% of their body weight – the maximal dose that Ewing et al used in their study of liver toxicity.1
Nevertheless, according to Forbes, “People that use CBD are at an elevated risk for liver toxicity.” And “[CBD] may actually be just as harmful to their livers” as “conventional pain relievers, like acetaminophen.” Statements that are clearly unsupported in the current literature.
The breathless reporting in Forbes focuses on a single, flawed, preclinical study and exaggerates it to the point of falsehood. Yet if there’s a saving grace of the Forbes article, it’s that it gets much less wrong than the study itself. The study is freely available from Molecules, a journal published by the Multidisciplinary Digital Publishing Institute (MDPI).
A close examination of the Molecules study reveals a Pandora’s box of strange statements, problematic publishing and unreasonable experimental design. On the first page, the abstract makes a claim that is fundamentally impossible, stating that, with chronic administration of CBD, “75% of mice gavaged with 615 mg/kg developed a moribund condition.” But there were only 6 animals that received this dose! One doesn’t need an advanced degree in science or math to recognize that something is amiss. Seventy-five percent of six equals 4.5.
According to the Little Rock researchers, four-and-a-half mice died because of the dangerous drug known as CBD, while somehow one-and-half mice survived.
Reading on, it only gets worse.
The experimental set-up is succinct. Scientists force-fed mice a single dose of CBD, ranging from the supposedly “low” dosage of 246 mg/kg up to a mega-dose of 2460 mg/kg CBD. That means for every kilogram of body weight, they gave the mice about 2.5 grams of CBD, which had been formulated as a hexane extract2 from cannabis supplied by the National Institute on Drug Abuse (NIDA). Hexane, it bears mentioning, is a neurotoxin.
“According to the Little Rock researchers, four-and-a-half mice died because of the dangerous drug known as CBD.”
The maximum human dosage recommended for the CBD–isolate Epidiolex is 20 mg/kg, which is over 100x less than what the Little Rock researchers force fed their experimental mice. They also tried smaller doses (ranging between 61.5 to 615 mg/kg) of CBD, which was given daily for 10 consecutive days.
Despite these ridiculous dosages, Ewing et al.3 claim their study accurately represents human experience, insisting that the equivalent human dose is 12.3 times lower because of allometric scaling (which we will discuss momentarily). This is – at best – an unverified assumption. More likely, it’s just plain wrong.
Before presenting their results in Molecules, the introduction tips the authors’ hand, revealing that the study is a hit piece against CBD, not legitimate scientific work.
When it comes to cited evidence, a double standard is obvious. The authors disparage the significance of positive medical findings about CBD (such as CBD’s anti-inflammatory and antioxidant properties) by citing only in vitro research.4,5 Yet a sentence later, they tout a score of harms allegedly attributable to CBD based on… in vitro and preclinical work. Even these claims are muddled by misinterpretation.
The Little Rock authors claim: “[n]umerous reports have demonstrated neurological, cardiovascular and reproductive toxicities subsequent to CBD use.” Yet, eight of the nine sources cited to buttress this claim do not involve humans. Only one of the citations is based on human research, and it did not show toxicity. The human study, led by Saoirse O’Sullivan, actually showed a decrease in blood pressure after consuming CBD (600 mg or roughly 10 mg/kg). O’Sullivan and her colleagues at the University of Nottingham concluded that perhaps “CBD has a role in the treatment of cardiovascular disorders.” Yet the Arkansas team misrepresents O’Sullivan’s work as proof that CBD is cardiotoxic.
When contacted by Project CBD, O’Sullivan said, “Our research study showing that CBD causes a small reduction in resting and stress-induced blood pressure does not support the authors claim that we demonstrated cardiovascular toxicity of CBD. In fact, most of our work is about the potential protective effects of CBD in the cardiovascular system.”
In contradiction to the claims Arkansas researchers made about her lab’s work, Dr. O’Sullivan says their work suggests protective effects of CBD in the cardiovascular system.
The madness of citations continues to develop with the Arkansas researchers noting that one trial of Epidiolex (an FDA-approved pharmaceutical CBD isolate extracted from cannabis) demonstrated 93% of CBD users experience adverse events (aka side effects). Wow! CBD must be problematic for nearly everyone! Until you read the primary source, which states that adverse events “were reported in 93% of the patients in the cannabidiol group and 75% of the patients in the placebo group” [emphasis added]. These patients take many anti-epileptic drugs in addition to their CBD treatment. The relevant number is the fraction of side effects attributable to CBD, not the total number. But the authors chose to ignore such subtleties in favor of aggrandizing harm. As a consequence, they overlook an opportunity to review problems that CBD could actually cause, according to this Epidiolex trial.
Reading on, halfway through the second page (of the 17-page Molecules article), problems continue to pile up. The authors appear to undermine their own conjured fears: according to one lab’s analysis, dosages of “commercially-available products ranged from as little to 2.2 mg to as much as 22.3 mg, further amplifying concerns of potential toxicity.” First of all, the lab report states the smallest amount was 1.3 mg, not 2.2 mg.6 Secondly, 22.3 mg is not a large dose by any means. Humans have been reported to ingest up to a few thousand milligrams of CBD without ill effect.
By the time the reader arrives at the results section of the Molecules article, the study’s credibility has already been thoroughly demolished by the issues described above. And then there are the results. According to the results section, huge doses (738-2460 mg/kg) of CBD caused problems, including altered levels of liver enzymes and gene expression related to metabolism. In the chronic administration group, the two highest doses caused similar problems. Dosages this high are unheard of in human studies. Some mice in the chronic administration group died from CBD treatment, but the authors neglect to include how many. The only number reported is the impossible four-and-a half-mice mentioned in the abstract.
New data, same old story
“Regardless of your feelings on this particular study, it is hard to argue with dead mice,” the Forbes article blithely asserts. Nonsense. Not enough attention is paid to that last word – mice. Even if we suspend our disbelief and look past every problem described thus far, a dead mouse (or half a mouse) isn’t proof of what happens to a human.
The search for a lethal dose of cannabinoids is nothing new – one of the earliest efforts to kill an animal with a gigantic dose of THC was described in a 1972 paper by scientists at the Mason Research Institute in Worcester, MA. In their quest to prove the dangers of THC, they attempted to kill almost 400 rats, a couple dozen beagle dogs, and some rhesus monkeys. The rat dosages ranged from 225-3600 mg/kg of orally administered THC, a higher amount than the CBD dosage used in the Little Rock experiment.
Early trials failed to find a lethal dose of cannabis in monkeys – even when they were dosed with nearly 1% of their bodyweight.
It turned out that rats could be killed by THC, though it took roughly 1000 mg/kg. Interpreting this with allometric scaling, we expect that monkeys would have a lethally toxic response to 500 mg/kg of THC (see table below for approximate scaling factors). This translates to about 10 grams of pure THC for a human. But it’s wrong. The researchers weren’t able to overdose the monkeys7 – not with an allometrically scaled dose, nor when they tried a much higher dosage of 9000 mg/kg (or just under 1% of the monkey’s bodyweight).
In a typical 65 kg human, 1% of body weight would amount to 585 grams of THC. That’s over a pound of pure THC. And that concentration wasn’t enough for a lethal outcome.8 The dose used in monkeys is the one most likely to translate to humans, and it underscores – if anything – the importance of not extrapolating from one species to another.
Small animals, like a mouse or humming bird, are more active than large animals, like a human or raven. It’s not just a matter of physical movement – metabolism is also faster among small animals. So a mouse will clear drugs out of its system more quickly than a human. This is one major reason why drug dosages are not the same between lab animals and humans in the clinic.
Allometric scaling is a useful rule of thumb that helps to overcome this issue. It assumes that drug doses can roughly be scaled from one animal to another based on their body weight and body-mass index (BMI).
To convert animal dose in mg/kg to HED in mg/kg, either:
Reference body weight (kg)
Working weight range (kg)
Body surface area (m2)
To convert dose in mg/kg to dose in mg/m2, multiply by Km
Divide animal dose by
Multiply animal dose by
Human equivalent dose calculation based on body surface area. Nair, A. J. of basic and clinical pharmacology. 2016.
This scaling factor is often used to find a starting dosage for drugs that have never been tested on humans, which is not the case for CBD, a compound with a well-established human safety record that the Little Rock scientists and the Forbes journalist studiously avoid mentioning.
Using allometric scaling to reinterpret preclinical work needs to be justified. And, in fact, allometric scaling of toxicity may not pertain to cannabinoids.9 The linear scaling factor is predicated on properties that these oily compounds do not possess. For example, it works best when the drug of interest floats freely in the bloodstream, yet over 99% of CBD (and THC) is protein-bound, not free. Furthermore, the ridiculously high doses in this study will saturate the body’s metabolic machinery, preventing relevant dose-extrapolations.
Without a doubt, the dose used in a mouse experiment does not translate directly to human dosing. However, by choosing a flawed scaling factor, the authors’ report of “human equivalents” becomes irrelevant. Recall that the THC study indicates we could increase a primate dose to 10x larger than the rat dosage without toxicity, the opposite of what allometric scaling suggests.
All this just underscores the importance of limiting conclusions to what we can establish. The Little Rock study shows that ingesting huge doses of CBD – on the order of 0.25% of one’s weight – is harmful to mice. It says nothing about humans. It says nothing about realistic dosing. What it does say is little more than a reflection of the authors’ biases.
How did this problematic article get published in Molecules? Isn’t peer review supposed to correct flawed science?
Ideally peer review is challenging and constructive, forcing scientists to do better research. But unfortunately, not all peer review aspires to the same goal.10 Peer review can also be a venue for reinforcing old boy networks and engaging in political power plays hidden behind anonymity. In some cases, peer review is just a rubber stamp of acceptance so long as the authors pay hefty “article processing charges.”
Science journals, much like the input provided by peer reviewers, vary in quality. MDPI, which publishes the journal Molecules, has been called a predatory publisher.11 MDPI has been criticized for publishing unsound articles, though this is too great a controversy12 to tackle here. Even if such allegations are true, it doesn’t mean that good work can’t end up in one of MDPI’s 213 journals. But it underscores the importance of checking scientific work, rather than diligently repeating and amplifying whatever claims are presented.
Another red flag: The turnaround from submission to acceptance of the Molecules article claiming CBD liver toxicity was 18 days, which, while not impossible, is nevertheless very quick.13 Unlike some other journals, Molecules does not report when – or if – reviewers requested revisions to the article. But in this case, revisions had to be requested, because the reference list states that some citations were accessed after the submission date: see references 25-27. These citations were viewed on the same day that Molecules accepted the article. At best, this means a revised draft was submitted and accepted on the same day, making it difficult to believe that a proper peer review was performed. The Little Rock authors did not immediately respond to a request for comment on this issue.
CBD and acetaminophen
Can we call this article one bad study and move on? Well, no, because Molecules has already published another similar article. The same journal and the same irrelevance, with a few more authors and a few more unbelievable claims.
The most recent study, published in Molecules a month after the first liver toxicity article, doesn’t improve on much. In their second report, they assess a potential interaction between CBD and acetaminophen (sold as Tylenol or paracetamol) in female mice.
Similar to the first study, they use hexane, a neurotoxin, to extract cannabinoids from NIDA-supplied cannabis. The amount of residual solvent is listed as < 0.5%, or 5000 μg/g. Such a product would not be legal to sell in California’s regulated marijuana market, which has set a limit of 290 μg/g of hexane in cannabis extracts. The authors did not immediately reply to a request for clarification of the hexane content.14
Cannabis flower sits next to a small pile of Tylenol on a white background.
The doses of CBD employed in the second Little Rock study are quite a bit lower than the first, since acetaminophen stresses the liver significantly on its own. A new oddity is the choice of administration. The researchers set up a feeding tube to administer high doses of CBD, but instead decided to inject 400 mg/kg acetaminophen into the mice. The authors do not state how this dosage would be allometrically scaled to a human taking Tylenol.
Three of the eight mice treated with acetaminophen and the supposedly low dose of CBD (116 mg/kg) died within a few hours. Curiously, none of the mice that were force fed a higher dose of CBD died. The Little Rock researchers explained this peculiar outcome by invoking the biphasic effect, also known as hormesis or a U-shaped dose-response curve, which refers to the existence of a sweet spot for optimal dosing. Outside of a particular dosage range – too low or too high – cannabinoids can lose their efficacy and even cause the opposite of an expected effect.
Cannabinoids often have a biphasic dose-response, but it’s unreasonable to claim without further explanation that this applies to CBD’s alleged toxicity. Imagine if you had drunk a poison and the cure was to drink a lot more of the same poison. That is essentially how the authors try to justify their results.
We could once again go through every citation, but the biases that undermine this publication are clear from the discussion, as Ewing et al. try to have it both ways. The consistency of their results (with a select choice of citations) shows that the model is accurate. The inconsistencies with other studies disprove any others’ claims to the safety of CBD.
The discussion after the first Molecules study displays the same bias. Positive preclinical results that suggest medical benefits don’t establish much, but absurd preclinical harms demonstrate that CBD “poses a risk for liver injury.” Ewing et al.’s research is valid because sometimes it seems to be consistent with data found in other papers. Yet when their findings contradict other research, it calls “into question [CBD’s] claimed ‘antioxidant’ properties” and other potential benefits.
One problem with these far-fetched studies that purport to demonstrate CBD’s harmful effects is that they undermine serious research into real risks.15 High doses of CBD – usually around 20-50 mg/kg – can cause issues with the liver, but there are important caveats. Numerous publications from the makers of Epidiolex have shed light on potential risks of CBD. Project CBD has been reporting on these dangers for years.16
While stress to the liver can be caused by CBD’s interaction with other drugs, it’s unreasonable to see temporary, reversible stress and insist that CBD is hepatotoxic.
Of greater concern is the reported elevation in liver enzymes called ALT and AST. This occurs in roughly 5-15% of kids in Epidiolex trials, and nearly every report involves the concurrent use of valproate, a powerful anti-epileptic drug, which can cause problems in and of itself.17 This could be viewed as a severe drug-drug interaction. However, many neurologists indicate that the combination of CBD and valproate can be an effective epilepsy treatment. Thus, doctors find it is worth adding CBD to a treatment regime that includes valproate, with the understanding that patients’ liver function will need to be monitored. The co-administration of CBD and clobazam, which also has a high likelihood of drug interactions, is another combination that pediatric neurologists..