EPISODES

In this behind-the-scenes conversation we speak with Janice Bissex, a registered dietitian nutritionist and holistic Cannabis practitioner who has dedicated her time lately to helping patients find high-quality and safe cannabinoid products after she discovered the therapeutic potential of Cannabis first-hand. Janice discusses how she wrestled with the stigma around Cannabis on multiple fronts, first as a college student fearful of Cannabis due to a lifetime of Cannabis prohibition propaganda, and then again as she struggled to "come out" to her community of nutritionists and healthcare professionals about her own advocacy.
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Today Janice is the CEO of Jannabis Wellness and is also a professor at John Patrick University focused on teaching students about Cannabis therapy from a nutritional perspective. Janice also recently authored the book Simple Guide to CBD: Fact, Fiction, and a Path Forward to educate consumers on the potential benefits of CBD and cannabis therapy.

Learn more about her work at https://www.jannabiswellness.com/

In this behind-the-scenes conversation we are joined by Tanja Bagar, PhD, the founder and CEO of the International Institute for Cannabinoids, a multi-national research and education cooperative based out of Slovenia. Tanja holds a PhD in Biomedical Sciences and has spent the past several years focused on studying and teaching about cannabinoids throughout Europe. Tanja and I have been collaborating for years as co-authors on conference abstracts, book chapters, etc. Tanja was also one of my early students in the early iterations of my workshop series which I still teach today, so it was great to reconnect on the podcast.

Our conversation explored her experience discovering the therapeutic potential of cannabinoids, how Cannabis regulations vary throughout Europe and the effects that has on research collaboration, why she has become fascinated with the endocannabinoid system, clinical outcomes that ICANNA and their collaborators have seen in patients using cannabinoids, her thoughts about the future of Cannabis research, and much more!
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You can learn more about ICANNA by visiting https://www.institut-icanna.com/en/index.html

​In this behind-the-scenes conversation we join Dedi Meiri PhD, a researcher at the Israel Institute of Technology focused on examining how Cannabis and its chemical constituents may influence cancer and other disease states. His labs have made important discoveries regarding the relevance of "minor" constituents of Cannabis in influencing cancer activity, among many other things. In this 2+ hour conversation we dive deep into Dedi's background, why he finds Cannabis so interesting, what he has learned from his cancer research, methods that his labs have developed for quickly assessing the activity of plant extracts, the future of Cannabis research, and much more!
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Learn more about Dedi's lab at Technion at https://dmeiri.net.technion.ac.il/

In this behind-the-scenes conversation we sit down with Elisabeth Mack, the founder and CEO of Holistic Caring, a company dedicated to providing clinical Cannabis education to patients and clinicians.

After a bicycle accident in early 2015, Elisabeth Mack found relief with high-dose CBD and targeted THC therapies. She used that year to move away from various prescription drugs that she had taken since 1994 for a previous shoulder surgery. The cannabis pain management process was enlightening for her as she dove into research, attended conferences and networked her way through the cannabis industry.

Realizing that nobody was interpreting anything for true medical cannabis patients, she founded Holistic Caring in May 2016 to serve the educational, supportive and logistical needs of patients and began training other nurses to help.
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Learn more about Holistic Caring at www.HolisticCaring.com

In this behind-the-scenes conversation we are joined by another returning guest, Cannabis nurse Janna Champagne. Nurse Janna recently founded Autism Safe Haven, a nonprofit focused on making Cannabis inclusive autism care services available wherever medical Cannabis is legal. In this conversation we focus on the intersection between Cannabis and autism, why current autism care models are often ineffective, how cannabinoids may affect autism symptoms, and more!
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Learn more about Autism Safe Haven at www.autismsafehaven.org 

In this behind-the-scenes conversation we speak with The Doctors Knox, aka The Knox Docs, including Drs. Janice, David, Rachel, and Jessica Knox to talk all about the endocannabinoid system and how our understanding of the endocannabinoid system and the endocannabinoidome is revolutionizing healthcare.

This was our first interview with four people at the same time, so it was quite a different experience and allowed for some unique dynamics that I hope you enjoy.
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You can learn more about The Doctors Knox at  https://doctorsknox.com/ 

In this behind-the-scenes episode we talk with Dr. Genester Wilson-King, a board certified OB/GYN, Cannabis clinician, and hormone expert. Our conversation spanned many topics including how cannabinoids and hormones interact with one another, how Cannabis affects women differently than men, how Cannabis affects women after menopause differently than women experiencing cyclical hormones, how Cannabis affects cis gender people different than trans gender people, how Cannabis affects fertility, Cannabis during pregnancy and breastfeeding and much more!

Learn more about Dr. Wilson-King here: https://www.victoryrejuvenationcenter.com/
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Enjoy and stay curious!

In this behind-the-scenes (BTS) episode we talk with Dr. Junella Chin, a physician that has specialized in Cannabis and cannabinoid medicine. Our conversation spanned a variety of topics including pediatric Cannabis use, how Cannabis interacts with sexual hormones like estrogen and testosterone, how people of different ethnicities respond differently to Cannabis, the state of cannabinoid education in the modern healthcare system, and more!

​You can learn more about Dr. Junella Chin by visiting www.DrJuneChin.com

In this behind-the-scenes (BTS) episode we talk with Wendy Nguyen of Wendy’s Lookbook and Artemis – a premiere CBD shop in New York City. Wendy has a fascinating story of surviving trauma, navigating the foster care system, dodging homelessness to later become a famous YouTube content creator, fashion blogger, and social media influencer. While battling several medical issues, Wendy discovered Cannabis and CBD, going on to focus her work on opening and operating New York City’s only minority woman-run CBD shop. Artemis focuses on science and education and is supported by science and medical advisors to provide patrons with a unique introduction to legal hemp products.
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Wendy’s Lookbook: www.wendyslookbook.com
Wendy’s Lookbook on YouTube: https://www.youtube.com/wendyslookbook

In this behind-the-scenes (BTS) episode we sit down with Peggy Anderson, the founder of Canna Help You?, a company that provides education to seniors about Cannabis. In this conversation we discuss common reasons why seniors are turning to Cannabis, how to minimize the chance of an uncomfortable Cannabis experience, what to do if a Cannabis experience becomes overwhelming, and much more.
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Enjoy, and stay curious!

In this behind-the-scenes (BTS) episode we speak with Dr. Jason Miller, an expert in traditional Chinese medicine with a focus on the treatment of cancer. In this conversation we explore how Dr. Miller conceptualizes Cannabis in relation to other medicinal plants, historical uses of Cannabis in Chinese medicine, the promise and limitations of Cannabis as a medicine, his experience with Cannabis as a cancer treatment, bridging the worlds of eastern and western medicine, and much more!
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Enjoy, and stay curious!

Episode Description: 
In this episode of the Curious About Cannabis Podcast, we take a look at CBD, the cannabinoid that has been all the rage lately. We are joined by neurologist and cannabinoid researcher, Dr. Ethan Russo, anesthesiologist and pain physician, Dr. James Taylor, and co-owner of Artemis, a premier CBD shop in New York City, Wendy Nguyen, to discuss the history of CBD, what people are experiencing with CBD, and how CBD affects the body.

Look for the associated behind-the-scenes (BTS) episodes for each of our guests to hear our full conversations!


Episode Transcript/Show Notes:
 
You’re listening to the Curious About Cannabis Podcast

Before we get started let me share a little disclaimer here. In this episode we are going to be discussing the medical uses of Cannabis. All of the information I present to you in this podcast is for education and entertainment purposes only and should not be considered medical advice. Never make decisions about your health based on anything you hear me or any other podcast host talk about. I’m simply sharing information that I’ve collected from talking with professionals with relevant experience or from research studies that are available. But I’m not a doctor, and you should always get your medical advice from a licensed health care professional. Now with that out of the way, let’s move on.
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These days, CBD is all the hype.

[NEWS CLIP]

The 2018 Farm Bill paved the way for legal hemp production in the United States, seeming to open up a multi-billion dollar hemp market that was now up for grabs.[1] Of all the potential surrounding legal hemp, there was one section of the hemp market that had everyone’s attention – the CBD market. It is estimated that over 1000 CBD brands came onto the market in 2019, and it’s estimated that approximately a quarter of the US population has tried CBD.[2] [3] Health claims have been boasted and promoted by CBD companies, doctors, entertainers, and social media influencers. So what’s the deal? Is CBD legit? Or it just another snake oil? And what does CBD actually do to your body?
In this episode we explore the history and science of the cannabinoid that’s all the craze – Cannabidiol, or CBD.

[INTRO MUSIC]

Hey everybody, this is Jason Wilson with the Curious About Cannabis Podcast. Thanks so much for tuning in once again! In this episode we are going to be taking a close look at one of the most popular cannabinoids produced by the Cannabis plant, Cannabidiol – or as it is better known, CBD.
And to guide our curious quest, we are going to explore several primary questions:

1. What is CBD?
2. How does CBD affect the body?
3. What are CBD’s potential therapeutic applications, as well as its limitations?

So let’s get started!

What is CBD?

[News Clip Compilation]

For the past few years, CBD has been big business. The price of a single one-ounce bottle of CBD tincture can range anywhere from $50 to $200 or more. Compare that to the average cost of a one-ounce bottle of a different herbal extract tincture like Echinacea or Elderberry that would typically cost somewhere between $10 and $20.
So, why is CBD getting tagged with such a high premium?

But what is CBD?

CBD, or Cannabidiol, is an oily compound produced in the resins of the Cannabis plant. Whether the Cannabis plant is considered hemp or marijuana – they both produce CBD, outside of some uncommon exceptions. In the United States, hemp is classified as Cannabis plants that contain less than 0.3% THC. In other countries the limit can be even lower, commonly 0.2%. Instead of THC, the primary cannabinoid that hemp varieties of Cannabis tend to produce is a cannabinoid called Cannabidiol, or CBD. Thanks to intentional breeding efforts, CBD can now be found in concentrations as high as 20 or 25% in hemp plants intended for CBD-rich resin production.

CBD is markedly different than THC. To start, CBD does not cause intoxicating or euphoric effects like THC does.[4] This feature has gotten the attention of a lot of people, ranging from medical researchers looking to unlock the therapeutic potential of Cannabis without the risk of abuse to consumers interested in Cannabis but not looking to get high. Although CBD is not intoxicating, it is psychoactive, meaning that it elicits effects on neurons. This is a common misunderstanding about CBD.
 
A Brief History of CBD

The story of CBD goes back thousands of years – as cultures across time have used non-psychoactive varieties of Cannabis for different uses. But the most relevant part of our story really starts in 1940, when researchers Roger Adams, Madison Hunt and JH Clark published a report indicating the structure of a compound that they extracted and isolated from wild hemp in Minnesota.[5] (Shout out to listeners in Minnesota! You’re a part of CBD history.) These researchers named this compound, Cannabidiol, or CBD as it would become commonly known. CBD was only the second cannabinoid found in Cannabis at the time, the first being Cannabinol, or CBN – a degradation product of THC.
In 1944 it was discovered that the effects of barbiturates could be extended if administered with CBD, but not with CBN or THC.[6] There answer to why CBD had this effect would come almost 30 years later.

For a moment in 1963, scientists in Israel would shine light on CBD once again, before announcing their discovery of THC as the intoxicating components of Cannabis – a year later in 1964.[7] CBD would become a bit more ignored once again until around the 1970s and 80s when research into CBD really began to pick up steam.

In 1972 it would be discovered that CBD inhibited certain enzymes in the body, which affects how the body metabolizes certain foods and drugs.[8] This helped begin to complete the puzzle that stemmed from the barbiturate study three decades prior. In 1981 researchers were able to demonstrate anticonvulsant effects in humans – indicating that it might be an effective treatment for certain forms of epilepsy and spasticity.[9] In 1982 CBD was found to exhibit anti-anxiety effects, which would later be reconfirmed in 1993.[10] [11] In 1995 it was discovered that CBD improves symptoms of psychosis.[12] In 1998 the United States government filed a patent on the antioxidant and neuroprotective effects of CBD, as well as THC.[13]

The 2000s would become the decade of elucidating the activity of CBD. In 2001, researchers began to finally understand more about how CBD actually works in the body by revealing that CBD targets non-cannabinoid receptors in the body, stimulates the production of at least one endocannabinoid, Anandamide, and inhibits an enzyme responsible for breaking down Anandamide, effectively allowing it to linger in the body longer.[14]

In 2002 researchers would confirm that CBD exhibits anti-nausea effects, which had already been reported as far back as the 1800s when systematic Cannabis research really began to take shape.[15] In 2004 it was discovered that at certain dosages CBD can increase wakefulness and counteract THC induced sedation.[16] So if you are feeling sleepy after using THC-rich Cannabis, a little bit of CBD might wake you back up! However, be careful, because CBD exhibits what is known as biphasic activity, meaning it acts differently in low doses versus high doses. At high doses, CBD can actually be sedating.[17]

In 2005 it was discovered that CBD interacts with certain serotonin receptors in the body.[18] In 2006 researchers would go on to discover that CBD also enhances adenosine receptor signaling, which is associated with heart health, blood pressure, and body temperature regulation.[19] It was also in 2006 that researchers discovered that CBD can kill breast cancer cells – bringing significant attention to the compound as a potential anti-cancer drug.[20]

In 2007 researchers began to understand why CBD reduced the effects of THC in some of their prior research. It turns out that CBD changes the shape and activity of CB1 receptors, even though it does not exhibit much affinity for them directly.[21] In this way, it changes the way that THC binds to the CB1 receptor, modulating its activity. This kind of activity is called allosteric modulation, and CBD is considered an allosteric modulator of the CB1 receptor. This is why CBD is able to reduce the high associated with THC – it essentially deforms the CB1 receptor so that THC cannot stimulate the receptor as well as it normally would.

In 2008 it was discovered that CBD was a potent antibiotic against MRSA – a powerful infection that is commonly picked up in hospitals and often resists treatment.[22] In 2012 researchers discovered that CBD may be as effective as standard antipsychotics.[23] In 2014 it was discovered that CBD might be able to effectively treat acne in the skin by reducing inflammation, fighting bacteria on the skin, and changing the way that the skin produces oil.[24]

The Modern CBD Industry

In 2018 in the United States, The Agricultural Improvement Act of 2018, also known as the 2018 Farm Bill, was passed, which effectively legalized hemp across the United States, including all of the cannabinoids and other chemical constituents of hemp varieties of Cannabis with THC concentrations below 0.3%, and CBD was removed from the Controlled Substances list, as long as the CBD was hemp derived.[25] [26] Some may say that the CBD market began at this time, but CBD products had already been available in foods, cosmetics, and dietary supplements widely for years prior to the legalization of hemp, operating in somewhat of a regulatory grey area. In 2018, Epidiolex would officially become FDA approved for the treatment of certain forms of epilepsy in children.[27]

The status of CBD as a pharmaceutical drug presents a problem for the CBD industry as a whole. The FDA does not allow drugs to be added to foods or supplements unless they have been marketed as foods or supplements previously.[28] This is due to a set of laws in the Food Drugs and Cosmetics Act. Of course, the irony is that the CBD industry had been around for quite some time, not considering the exposure that humans have had to CBD throughout history. Cannabis in all its forms had been prohibited in the US for nearly 100 years, so of course Cannabis derived products were not openly marketed and sold. The Food Drug and Cosmetic Act was enacted in 1938, right around the same time that Cannabis prohibition began.[29]

Considering that Cannabis was included in the United States pharmacopoeia for many years all the way up until prohibition began, it’s clear that Cannabis derived products had been a part of society well into the 1930s, and would have persisted had it not been for Cannabis prohibition. So, in the 1930s the opportunity for Cannabis to mature alongside the food and supplement industries was eliminated, and the only pathway to get federally legal Cannabis derived products to the public, was through pharmaceuticals. And now that hemp derived CBD and other cannabinoids are federally legal, 90 years later, the government argues that it can’t be put into food or supplements because it’s a drug. It just seems like an awkward argument when you take the full history into account.

Another argument that the FDA argues for resisting making any exceptions for CBD and hemp derived cannabinoids in foods or supplements is that there is not adequate data available to show that CBD is safe.[30] They have argued that CBD could cause liver damage, and thus it should be researched longer before it is allowed to be widely available to be consumed. The study that they cite for this concern is a recent rodent study that looked at dosages that were orders of magnitude higher than the highest dosages used in comparable clinical trials for Epidiolex.[31]

I spoke with Dr. Ethan Russo, about his thoughts on the idea of CBD causing liver damage.

[ETHAN RUSSO]

I should point out that in the study, dosages of 15mg/kg or less were not found to exhibit these toxic effects. That’s approximately 930 milligrams of pure CBD for an average sized person.

It should also be noted that the World Health Organization issued a report on CBD very recently attesting to CBD’s remarkable safety profile.[32]
At the time of this recording, the future of the CBD industry is very uncertain as hemp farmers, CBD product manufacturers, and legislators plead their case for changes to allow the CBD industry to continue operating as it has, with CBD foods, dietary supplements and cosmetics readily available to consumers. States are taking matters into their own hands, just as they have had to do with anything related to Cannabis and set their own laws for CBD.

The greater question lingering around the FDA’s involvement in the CBD industry is whether the FDA will take enforcement action against CBD companies. To date, they primarily seem concerned with going after companies making medical or health claims about CBD, but that’s not surprising. The FDA will always go after companies making unapproved medical claims, because that is in violation of the Dietary Supplement Health and Education Act of 1994 which made it illegal to make such claims without FDA approval.[33] This is why you see an FDA statement on every dietary supplement label which says something to the effect of, “These claims have not been evaluated by the FDA and are not intended to diagnose, treat, cure, or prevent any disease.”

It seems as though the only pathway forward to a booming legal CBD industry, is through changes to federal law to allow an exception for CBD and other hemp derived natural products. Any law changes that are proposed should be carefully worded. Even if CBD is allowed in foods and supplements, if a law change does not also determine that CBD is Generally Recognized as Safe, or GRAS, then there could be another set of problems for the CBD industry to tackle.

Food additives like plant extracts and essential oils, have to have GRAS status to be freely added to foods or formulated into supplements. Until the FDA takes on the role of doing this research and granting GRAS status to CBD and other cannabinoids, it will be up to private companies to do their own expensive research to achieve what is called “self-affirmed” GRAS status, which only applies to their specific products, and not their competitors – essentially making a playing field where only the most well-funded CBD companies can survive long-term. To put this into perspective, gathering all the data needed to successfully achieve self-affirmed GRAS status can cost as much as a million dollars or more. At a time when the value of CBD as a commodity is rapidly shrinking, along with CBD product margins, this is a difficult task for small or medium sized hemp companies to pull off without coming together and pooling resources.

What are people experiencing with CBD?

Since the 2018 Farm Bill was passed, CBD shops have popped up across the country and even large retail chains like Kroger, Fred Meyer, CVS, and Walgreens are starting to carry CBD products.[34] [35] [36] Additionally, specialized hemp and CBD focused wellness stores have made their way into neighborhoods and cities across the US. I spoke with Wendy Nguyen, an owner of a premier CBD shop in New York City about her experience operating a CBD store.

[Wendy Clip]

I also had the chance to speak with a pain physician in North Carolina that has been working with patients that have chosen to try CBD as a potential solution to their chronic pain.

[James Taylor Clip]

One question that was on my mind when I was speaking with people about CBD was, what dosages are needed to get an effect? CBD products on the market have potencies of anywhere from 100 to 1000s of milligrams per 1oz bottle. When I reviewed the available scientific literature – I found that there was not a lot of information available. Epidiolex clinical trials utilized dosages of 5mg/kg to 20mg/kg, or 310mg to nearly 1500 mg for an average sized person. In a 2019 review of dosages utilized in published CBD studies, it was found that dosages below 2.5mg/kg of body weight were largely ineffective at treating most conditions measured, except for sleep disorders.[37] That would be around 150mg of CBD for an average person. However, the research on CBD dosaging is complicated by the fact that CBD exhibits unique efficacy when it is administered in isolation versus when it is administered in the presence of other cannabinoids, terpenes, and other phytochemistry from the Cannabis plant. Many clinicians I spoke with commented that they were seeing better results at lower dosages with broad or full spectrum CBD versus isolate.

[JAMES TAYLOR]

Some of the people I spoke with that used CBD regularly claimed that they saw relief at much lower dosages, as low as 10 or 15 mg of CBD per day, if taken regularly.

[WENDY NGUYEN]

The frequency of dosing is very important because CBD, like THC, lingers in the body and can accumulate over time with repeated dosing. So it may be that low dosages of CBD might be effective when taken regularly, but when acute relief is required, higher dosages may be needed.

So clearly people are having profound experiences with CBD, but how does CBD actually affect the body?

How does CBD affect the body?

Like all other cannabinoids, CBD is not incredibly bioavailable in the body. Most of the CBD that anyone ingests is simply excreted either unmetabolized, or as a conjugated sugar – meaning that a glucose molecule adhered to the CBD molecule as it passed through the body. Some of the CBD that is ingested sticks to other lipophilic, or oil-loving, tissues in the body, which keeps it from circulating in the body and reaching sites of action. But for those molecules of CBD that do make it into the blood stream and get circulated throughout the body, and interesting series of events takes place.

First of all, it is important to know that CBD has very low affinity for either CB1 or CB2 receptors, which as you may remember from episode 6 of the podcast are two of the primary chemical receptors that make up the endocannabinoid system. Instead of directly affecting cannabinoid receptors, CBD stimulates these receptors indirectly by affecting the production and break down of endocannabinoids that the body produces on its own. As mentioned before, CBD stimulates the production of Anandamide, which is a partial agonist, or stimulator, of CB1 and CB2 receptors. Additionally, CBD inhibits an enzyme called Fatty Acid Amide Hydrolase, also known as FAAH, which would typically break down Anandamide, as well as a lot of other things in the body.[38] This allows the Anandamide that the body produces to linger in the body longer, thus stimulating cannabinoid receptors for a longer time.

You could think of this as CBD nudging the endocannabinoid system to do its own thing, rather than completely hijacking the system altogether, like THC does. That’s not to say that the activity of THC is bad or undesirable – it’s just very different.

CBD also interacts with a putative cannabinoid receptor called GPR55.[39] The GPR stands for G-protein coupled receptor, which is the type of chemical receptor that cannabinoid receptors are. GPR55 is thought to be responsible for some of CBD’s anti-epileptic activity, among other things.

In addition to these effects on endocannabinoids and cannabinoid receptors, CBD interacts with a lot of other chemical receptors including vanilloid receptors like TRPV1, which are also referred to as capsaicin receptors because capsaicin, the chemical responsible for the spiciness in peppers, also stimulates vanilloid receptors. CBD also interacts with serotonin receptors, commonly associated with mood, sleep and blood pressure. It also influences the activity of adenosine receptors, commonly associated with heart health, and PPAR-gamma receptors which are linked to insulin resistance and diabetes, among other things.[40]

In addition to inhibiting enzymes that break down anandamide, CBD also has potent inhibitory effects on a group of liver enzymes called the cytochrome p450 enzymes, which are responsible for metabolizing many common drugs.[41] This inhibitory effect is commonly referred to as “the grapefruit effect” because grapefruits are well known to also cause this same enzyme inhibition.[42] In fact, you may have once been prescribed a medication that featured a label on the bottle that cautioned against taking with grapefruit. One of the most well-known drug interactions with CBD is with a blood thinning drug called Warfarin.[43] CBD has also been demonstrated to exacerbate the negative side effects of some epilepsy drugs like Valproic Acid.[44]  Because of these kinds of interactions, it is important that anyone taking CBD with other medications do so under the supervision of a health care provider to stay safe.

One thing that should be mentioned here is that so far, we have been talking about how CBD, by itself, interacts with the body. When CBD is present in a complex mixture like a Cannabis extract with dozens or hundreds of other compounds, or when formulated in a food or topical product with other ingredients, effects can be different.[45] [46] A hemp extract product should be judged by the total formulation, not just the quality of the hemp extract used as an ingredient in the product.

It’s also possible to manipulate the absorption and bioavailability of CBD using technologies like nano-emulsion, which is a process of breaking up a CBD extract into tiny droplets the size of a nanometer, which is one billionth of a meter, and then surrounding those droplets with a water friendly casing.[47] This keeps the oil droplets from rejoining, maximizing their surface area and allowing the oil droplets to be suspended in water.

So far we’ve mostly been talking about how CBD affects the body when it’s ingested or inhaled, but what about the effects of CBD on the skin? There are all sorts of chemical receptors in the skin, just like you have in other parts of your body. In general, when CBD is applied to the skin, or topically, it only affects the area where it is applied. The exception is when CBD is applied transdermally, usually with a patch. These are like capsaicin patches or nicotine patches. They are specially formulated with ingredients that help carry things through the skin that normally would have a hard time penetrating. If CBD can soak through the outer layer of the skin, the epidermis, and reach the lower layer of the skin, the dermis, then it could end up reaching the blood where it could get distributed throughout the body.

So, does CBD help keep your skin healthy?

[WENDY NGUYEN]
 
Safety of CBD

So you can see that CBD’s activity in the body is diverse and complex – and we still don’t understand the whole picture yet. Yet, despite our lack of knowledge about CBD, evidence seems to indicate that it is a pretty safe compound – even if some regulatory agencies disagree. The most common adverse effects associated with CBD are things like lethargy, appetite disruptions, and gastrointestinal distress.[48] But everyone reacts to things differently, and in uncommon cases some people may react unfavorably to CBD. But, like THC, it is incredibly difficult, if not impossible, to overdose or die from using CBD.

At very high dosages of 15mg/kg of body weight or higher, it is possible to cause liver damage with CBD, but it is very uncommon for anyone to take dosages that high. That equates to a dose of around one gram of pure CBD for someone that weighs 140 pounds, or 62 kilograms. For someone like myself that weighs closer to 200 pounds, that dose would be closer to a gram and a half, or 1500 milligrams of CBD. To put this issue into better perspective, consider that most CBD products readily available on the market have serving sizes that feature doses of between 5 and 50 milligrams of CBD. According to the Safety Data Sheet for Epidiolex, CBD is tolerated well in humans orally at dosages up to 1500mg per day.[49]

[Ethan Russo]

Based on the history of research that exists, it is clear that CBD has a lot of potential as a medicine. Research indicates it may be effective at treating things like anxiety, depression, sleep, various forms of spasticity, pain, bacterial infections, and inflammation. When it comes to skin treatment, it might be effective in battling acne and regulating inflammation of the skin. The fact that CBD is available as a pharmaceutical in various forms across the world, including the United States, is a testament to its medical value.
It is true that a lot more research is still needed to understand how to best unlock the therapeutic potential of CBD, but CBD is certainly not another snake oil.

But like many things, there is a lot of nuance around the topic. One of the big issues that needs to be understood is what dosages are needed to elicit therapeutic effects. While we have a pretty good understanding of what dosages not to exceed to stay safe, we don’t have a clear picture of what dosages to shoot for to achieve targeted therapeutic effects under different conditions. This is why many consumers of CBD are leaving it up to trial and error to find the dose that works best for them.

Let’s review what we’ve learned.

• CBD is a common cannabinoid found in hemp varieties of Cannabis.
• CBD is not intoxicating like THC, however it is psychoactive because it effects neurons.
• Research into CBD really took off in the 1970s and 80s, and researchers did not really begin to understand how CBD affected the body until the early 2000s.
• CBD does not interact with cannabinoid receptors very much directly. But CBD does interact with cannabinoid receptors indirectly by stimulating the production of anandamide and inhibiting the enzyme, FAAH, that would typically break anandamide down.
• CBD interacts with a host of other chemical receptors in the body including miscellaneous g-protein coupled receptors, vanilloid receptors, serotonin receptors, adenosine receptors, and PPAR-gamma receptors.
• CBD inhibits enzymes in the liver that are responsible for breaking down many common drugs, which can lead to elevated concentrations of those drugs in the body. Because of this, it is important to communicate with your health care provider if you are taking CBD along with other medications that may be affected by the “grapefruit effect”.
• CBD is generally well tolerated by most people at dosages as high as 1500mg per day. Common side effects of CBD include lethargy, gastrointestinal distress, and appetite changes. At dosages above 15mg/kg of body weight, liver damage could begin to take place. The LD50 of CBD is thought to be somewhere above 200mg/kg of body weight, or over 12 grams of pure CBD for an average sized person.
• CBD has exhibited promise as a medicine to treat epilepsy, anxiety, depression, bacterial infections, pain, inflammation, and acne, among other things. More research is needed to properly understand exactly what CBD is effective at treating and at what dosages. Currently the only CBD pharmaceutical approved in the United States is a drug called Epidiolex for the treatment of certain forms of epilepsy in children. In other countries, you could also find CBD in the Cannabis derived pharmaceutical, Sativex, which features a standardized Cannabis extract with equal parts CBD and THC.
• CBD seems to be most effective at dosages above 2.5mg/kg of body weight, though there is evidence that some people may find relief at much lower dosages. The form of CBD can affect its efficacy, and every clinician I spoke to recommended broad or full spectrum CBD extracts over isolates. And it’s best to try to start at a very low, sub-clinical dose, and slowly titrate yourself up until you find your minimum effective dose.

So, is CBD a hero, or just hype? Well, it certainly seems that for some, CBD is very much a welcome hero. There is no question that it is an effective treatment for some conditions. It can be quite safe and could help treat a wide variety of conditions without getting people high. However, I must point out that research has indicated that CBD tends to be much more effective in the presence of THC. So as THC-free CBD products hit the market, keep in mind that those products might not be as effective as a product that contains at least a little bit of THC.

But for all of the promise of CBD, there is still a lot of unfounded hype for consumers to wade through. It is critical that consumers pay attention to the quality of CBD products as well as the dosages. Many CBD products feature incredibly low concentrations of CBD that are likely sub-therapeutic. In addition, CBD products can be quite expensive, leaving consumers paying out fortunes for low-potency sub-therapeutic products. And this trend isn’t likely to go away anytime soon. New hemp extract products featuring other lesser known cannabinoids like CBG, CBC, and CBN are already quickly gaining market buzz. It won’t be long before CBD passes the hype torch on to these other cannabinoids.

And with that, I’m your host, Jason Wilson. Thanks for listening. Stay curious and take it easy!

[Outro Music]

Citations:

[1] United States H.R.2 115 Agriculture Improvement Act of 2018

[2] Brightfield Group 2019 U.S. CBD Market Report: https://www.brightfieldgroup.com/library/us-cbd-market-report-2019

[3] BDS Analytics Press Release: https://bdsanalytics.com/u-s-cbd-market-anticipated-to-reach-20-billion-in-sales-by-2024/

[4] Russo E. 2011. Taming THC: potential cannabis synergy and phytocannabinoids-terpenoid entourage effects. Br J Pharmacol. 163(7): 1344-1364.

[5] Adams R, Hunt M, Clark JH. 1940. Structure of cannabidiol, a product isolated form the marihuana extract of Minnesota wild hemp. I. J Am Chem Soc. 62(1): 196-200.

[6] Loewe S. 1944. Studies on the pharmacology of marihuana The Marihuana Problems in the City of New Yorked. The Mayor's Committee on Marihuana. pp. 149–212.Lancaster, PA: The Jaques Cattell Press

[7] Mechoulam R, Shvo Y. 1963. Hashish. I. The structure of cannabidiol. Tetrahedron. 19(12): 2073-2078.

[8] Paton WDM, Pertwee RG. 1972. Effect of cannabis and certain of its constituents on pentobarbitone sleeping time and phenazone metabolism. Br J Pharmacol. 44: 250-261.

[9] Carlini EA, Cunha JM. 1981. Hypnotic and antiepileptic effects of cannabidiol. J Clin Pharmacol. 21(S1): 417S-427S.

[10] Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG. 1982. Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology (Berl). 76(3): 245-250.

[11] Zuardi AW, Cosme RA, Graeff FG, Guimaraes FS. 1993. Effects of ipsapirone an dcannabidiol on human experimental anxiety. J Psychopharmacol. 7(1 Suppl): 82-88.

[12] Zuardi AW, Morais SL, Guimaraes FS, Mechoulam R. 1995. Antipsychotic effect of cannabidiol. 56(10): 485-486.

[13] https://patents.google.com/patent/US6630507B1/en

[14] Bisogno T et al. 2001. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol. 134(4): 845-852.

[15] Parker LA, Mechoulam R, Schlievert C. 2002. Cannabidiol, a non-psychoactive component of cannabis and its synthetic dimethylheptyl homolog suppress nausea in an experimental model with rats. Neuroreport. 13(5): 567-570.

[16] Nicholson AN, Turner C, Stone BM, Robson PJ. 2004. Effect of Delta-9-tetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults. J Clin Psychopharmacol. 24(3): 305-313.

[17] Zuardi AW, Guimarães FS, Moreira AC. 1993. Effect of cannabidiol on plasma prolactin, growth hormone and cortisol in human volunteers. Braz J Med Biol Res. 26(2): 213-7.

[18] Russo EB, Burnett A, Hall B, Parker KK. 2005. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem Res. 30(8): 1037-1043.

[19] Carrier EJ, Auchampach JA, Hillard CJ. 2006. Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression. Proc Natl Acad Sci U S A. 103(20): 7895 – 7900.

[20] Ligresti A et al. 2006. Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J Pharmacol Exp Ther. 318(3): 1375-1387.

[21] Thomas et al. 2007. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br J Pharmacol. 150(5): 613-623.

[22] Appendino G et al. 2008. Antibacterial cannabinoids from Cannabis sativa: a structure-activity study. J Nat Prod. 71(8): 1427-1430.

[23] Leweke FM et al. 2012. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2(3): e94.

[24] Olah A et al. 2014. Cannabidiol exerts sebostatic and anti-inflammatory effects on human sebocytes. J Clin Invest. 124(9): 3713-3724.

[25] Corroon J, Kight R. Regulatory Status of Cannabidiol in the United States: A Perspective. Cannabis Cannabinoid Res. 2018. 3(1): 190-194.

[26] United States H.R.2 115 Agriculture Improvement Act of 2018, Sec. 297A Definitions (1)

[27] https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-comprised-active-ingredient-derived-marijuana-treat-rare-severe-forms

[28] https://www.fda.gov/consumers/consumer-updates/what-you-need-know-and-what-were-working-find-out-about-products-containing-cannabis-or-cannabis

[29] https://www.fda.gov/about-fda/histories-product-regulation/1938-food-drug-and-cosmetic-act

[30] https://www.fda.gov/consumers/consumer-updates/what-you-need-know-and-what-were-working-find-out-about-products-containing-cannabis-or-cannabis

[31] Ewing LE et al. 2019. Hepatotoxicity of a Cannabidiol-rich cannabis extract in the mouse model. Molecules. 24(9): 1694.

[32] World Health Organization (WHO). Cannabidiol (CBD) Critical Review Report. Expert Committee on Drug Dependence Fortieth Meeting. June 2018.

[33] Dietary Supplement Health and Education Act of 1994. Public Law 103-417. 103rd Congress.

[34] https://www.supermarketnews.com/organic-natural/kroger-carry-cbd-products-945-stores

[35] https://www.nbcnews.com/health/health-news/cvs-sell-cbd-products-800-stores-8-states-n986016

[36] https://www.cnbc.com/2019/03/27/walgreens-to-sell-cbd-products-in-some-stores.html

[37] Millar SA, Stone NL, Bellman ZD, Yates AS, England TJ, O’Sullivan SE. A systematic review of cannabidiol dosing in clinical populations. Br J Clin Pharmacol. 2019. 1-13. Electronic publication.

[38] Deutsch DG. 2016. A personal retrospective: elevating anandamide (AEA) by targeting fatty acid amide hydrolase (FAAH). Front Pharmacol. 7: 370.

[39] Whalley BJ et al. 2018. A role of GPR55 in the antiepileptic properties of cannabidiol (CBD) (P2.277). Neurology. 90 (15 Supplement).

[40] https://www.projectcbd.org/science/how-does-cbd-work

[41] Yamaori S et al. 2011. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. Life Sci. 88(15-16): 730-736.

[42] https://www.healthline.com/nutrition/grapefruit-and-medications

[43] Grayson L et al. 2018. An interaction between warfarin and cannabidiol, a case report. Epilepsy Behav Case Rep. 9: 10-11.

[44] Szaflarski JP et al. 2018. Long‐term safety and treatment effects of cannabidiol in children and adults with treatment‐resistant epilepsies: Expanded access program results. Epilepsia. 59(8): 1540-1548.

[45] Gallily R, Yekhtin Z, Hanus LO. 2015. Overcoming the bell-shaped dose-response of cannabidiol by using cannabis extract enriched in cannabidiol. Pharmacology & Pharmacy. 6: 75-85.

[46] Russo EB. 2018. The case for the entourage effect and conventional breeding of clinical cannabis: no “strain,” no gain. Front Plant Sci. 9: 1969.

[47] Yen CC et al. 2018. Nanoemulsion as a strategy for improving the oral bioavailability and anti-inflammatory activity of andrographolide. Int J Nanomedicine. 13: 669-680.

[48] Iffland K, Grotenhermen F. 2017. An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies. Cannabis Cannabinoids Res. 2(1): 139-154.

[49] https://www.greenwichbiosciences.com/sites/default/files/Epidiolex%20Material%20Safety%20Data%20Sheet%20(MSDS).pdf

​In this behind-the-scenes (BTS) episode, we talk with Dr. James Taylor, an anesthesiologist and pain physician working in North Carolina. Since the Farm Bill passed, his patients began trying CBD products to treat their chronic pain. What Dr. Taylor witnessed next could be described as nothing short of transformative - but perhaps not in the way you'd think.

​Now Dr. Taylor has started a company called Integrated Hemp Solutions to bring physician-developed, clinically tested hemp based products to the public.

Episode Description: In this episode we begin to explore the ways in which Cannabis affects the body by exploring one of the primary physiological systems in our body's affected by Cannabis - the endocannabinoid system (ECS). Cannabis helped researchers discover it. Now medical science is trying to understand what to do with it. Discover the history of possibly one of the most significant medical discoveries of the past century, courtesy of Cannabis, in this episode of the Curious About Cannabis Podcast!

Interview contributions by endocannabinoid system researchers Dr. Kevin Spelman (BTS #04) and Dr. Ethan Russo (BTS #05).

Transcript: COMING SOON

In this behind-the-scenes (BTS) episode we talk with the world renowned Cannabis and cannabinoid researcher, Dr. Ethan Russo, to discuss a host of topics like the alleged toxicity of CBD, the research evidence for entourage effects, how to think about the endocannabinoid system, how Cannabis based pharmaceuticals are developed and more! We packed a lot of good conversation in this relatively short conversation. Enjoy and stay curious!
​
P.S. This will be our last episode until after the Christmas and New Year holidays, but we will be back and ready to go first thing at the turn of the New Year. Stay safe and happy holidays!

​In this behind-the-scenes (BTS) interview, we sit down with Kevin Spelman, PhD, a molecular biologist and medicinal plant expert that has spent time studying the endocannabinoid system (ECS) and how medicinal plants affect the ECS. In this interview we discuss how to think about the "entourage effect", biases in science against medicinal plant research, the safety and efficacy of medicinal plants and dietary supplements, misconceptions about Cannabis, and much more! Stemming from the release of episodes 4 and 5 of the podcast where we explore the concept of Cannabis as a medicine, this interview contains a lot of content that got cut from those episodes for time that many of you will likely enjoy.

#05 Cannabis as Medicine - Part Two

Episode Description: Continuing from our previous episode, we dive into exploring how medical claims are derived, what it takes to develop a drug in the United States, and what outcomes health care professionals are seeing in their patients that are using Cannabis as a medicine.
​

TRANSCRIPT

You’re listening to the Curious About Cannabis Podcast

Before we get started let me share a little disclaimer here. In this episode we are going to be discussing the medical uses of Cannabis. All of the information I present to you in this podcast is for education and entertainment purposes only and should not be considered medical advice. Never make decisions about your health based on anything you hear me or any other podcast host talk about. I’m simply sharing information that I’ve collected from talking with professionals with relevant experience or from research studies that are available. But I’m not a doctor, and you should always get your medical advice from a licensed health care professional. Now with that out of the way, let’s move on.

[INTRO SEGMENT]

In the previous episode of the podcast we began exploring the concept of Cannabis as medicine. We looked at many of the ways in which Cannabis has been used as a medicine in the past, and some ways in which Cannabis based pharmaceuticals are being used as medicines today. Picking up where we left off, I wanted to explore the ways in which medical claims are derived. How do we determine that something is a medicine? And what results are clinicians seeing in their patients that are using Cannabis?

[INTRO MUSIC]

Hey everybody, this is Jason Wilson with the Curious About Cannabis Podcast, thanks so much for tuning in once again.

As we covered in the previous episode, there are a lot of medical claims swirling around Cannabis. If you go into just about any Cannabis dispensary, you are likely to see posters on the wall indicating the myriad of different chemicals in Cannabis and their supposed effects.[1] [2] However, many times these kinds of charts are built off of very simple, pre-clinical research data, that may not have any relevance in a real-life Cannabis use scenario.

How are medical claims derived?

So, how are medical claims derived?

There are several forms of medical research of varying degrees of quality.[3] On one end of the spectrum are anecdotal reports – these are basically eye-witness testimonies from a single person or small group of people. Up from that you have case studies, usually written by a professional describing an incident in detail. Moving along, there are observational studies, where a health care professional watches a patient engage in an activity and records the outcomes. On the other far end of the spectrum is the gold standard of randomized controlled trials.[4]

When a drug is being developed, typically the first way it is studied is through in vitro research.[5] In vitro studies are laboratory studies performed in test tubes or petri dishes. In vitro literally means, "in glass".

[JUSTIN FISCHEDICK]

This is Justin Fischedick. Justin is a natural products researcher that studies the activity of the chemical constituents of plants, including Cannabis.

[JUSTIN FISCHEDICK]

Then there are in vivo studies, which are in living animals.[6]

[JUSTIN FISCHEDICK]

But there are limitations to each of these types of studies, and the results of an in vitro study or an in vivo animal study cannot always be easily extrapolated to real-life human clinical situations.[7]

[JUSTIN FISCHEDICK]

I had a conversation with cellular and molecular biologist, Dr. Anthony Smith, about this issue regarding the limitations of animal studies.[8]

[ANTHONY SMITH]

A lot of Cannabis research has, up to a point, been primarily in vitro and in vivo rodent studies, but very few research projects with Cannabis have crossed into the world of placebo controlled double blind clinical trials with large patient populations, and many politicians and regulatory bodies continue to claim that because of this lack of clinical trial data, herbal Cannabis or Cannabis products cannot be deemed safe or a viable medicine for a condition.

Let’s break this phrase down. “Placebo controlled” refers to the fact that a compound is given to some of the patients in a trial which is intended to have no effect. In general, it is expected that if something is a candidate to be considered a medicine, it needs to perform better than a placebo. It can be difficult to adequately utilize a placebo in a THC-rich Cannabis study. Because THC has such distinct effects, it is pretty difficult to fool people into thinking they got the drug when they actually did not. This is referred to as “incomplete blinding” because the patients are not truly blinded to whether they received the drug or not. The gold standard for clinical trials is for a study to be “double blind”.

“Double blind” refers to the idea that both the clinician performing the study, and the patients participating in the study, are blind to whether they received the research drug, or the placebo. This is important because there are various biases that can enter a study if the physician knows who has had the placebo or not, and likewise, patients may react differently in a study if they know they are receiving a placebo – although some modern research is beginning to call this idea into question.

Lastly, large sample sizes are required in order to understand whether the results of a clinical trial are representative of a larger population.[9] A study that only examines the response of a couple dozen or even a couple hundred people is really small, and can’t really represent the hundreds of millions of people living in the United States, much less the billions of people living in the world.

There’s also the issue of repeatability that is worth mentioning. Even if a research study is placebo-controlled and double blinded with a good sample size – it is still important that the study be replicated by another set of researchers, in another location, with a different population of people. Research findings are much more robust when they have been repeated.[10] There is always the chance that there are some variables unaccounted for in a study that could explain the results differently than what the researchers were focused on.

When trying to interpret medical research, there is also the issue of deciphering what the clinical studies are trying to measure, and whether the significant effects that are identified in a study are relevant in a real-life clinical setting. This is the issue of statistical significance vs clinical significance.[11] Statistical significance is a measure of the likelihood that a result is not due to pure chance. Whereas clinical significance is a measure of the practical significance of a treatment in a clinical setting. Basically, just because a research study determines that something exhibits an effect that is statistically significant, it doesn’t mean that the effect will end up being significant in any practical sense when someone consumes that thing.

There is another similar issue also facing drug development and medical research, and that’s the battle between efficacy research and effectiveness research.[12]

[JASON MILLER]

So we’ve established that there are a lot of different ways to study medicine, and the results of some of these studies are not necessarily straightforward to interpret.

[ETHAN RUSSO]

All of these nuance details about research are important when it comes to the development of Cannabis based pharmaceuticals. To get a drug approved as a medicine in the United States, a company has to present lots of data that shows that the drug, and not a placebo, provide an intended therapeutic effect for a particular condition or set of conditions.[13] That takes a lot of time, a lot of energy, and a lot of money.

[ETHAN RUSSO]

Sativex, or Nabiximols as it is also known, is a particularly interesting drug to focus our attention on. Sativex is a mouth spray that consists of a standardized Cannabis extract with a 1:1 ratio of CBD to THC.[14] Unlike Epidiolex[15], which is often criticized for being an isolated cannabinoid drug like Marinol[16] – Sativex consists of a wide diversity of plant compounds extracted from Cannabis. This means that the clinical data on Sativex is likely to be more relevant when thinking about the therapeutic potential of herbal Cannabis or Cannabis extracts, than research on isolated THC, like Marinol, or CBD, like Epidiolex.

 [ETHAN RUSSO]

Dr. Russo makes a great point here. Just because cannabinoid and Cannabis-based pharmaceuticals are being developed, it doesn’t mean that herbal Cannabis and the use of Cannabis extracts is going away anytime soon.

And in fact, many people tend to prefer the use of herbal Cannabis or Cannabis extracts for a number of reasons. Sometimes it’s efficacy related, but sometimes it’s cost related. Pharmaceuticals can be extremely expensive.[17] When you can grow a plant at home and can easily make your own extract with as good or better efficacy than a pharmaceutical, it’s pretty hard to justify going the pharmaceutical route. However, pharmaceuticals are standardized and very consistent batch to batch. It’s possible that trying to treat a condition with homegrown Cannabis or black market (or even legal medical or recreational) Cannabis may not provide consistent outcomes because the products’ chemistry will be different batch to batch.

Unfortunately, there is really not much research available regarding herbal Cannabis or Cannabis extracts. This is for multiple reasons. One reason is that research tends to happen with products that can be patented. So, there is not a huge financial incentive to do expensive research on herbal Cannabis or unstandardized Cannabis extracts. Another issue is that Cannabis flower and extracts are very diverse and inconsistent in their chemistry batch to batch.

What are clinicians seeing in patients using Cannabis?

However, despite all of these issues, clinicians around the US are noticing striking results in many patients.

[JANNA CHAMPAGNE]

[JAMES TAYLOR]

All of this positive benefit that some of these health care professionals are seeing does not mean that Cannabis is without risks. For an in-depth review of the risks associated with Cannabis use, I recommend listening to the first three episodes of this season where we explored the question, “Is Cannabis Safe?”.

Cannabis can interact with other medications and it’s not for every person or every condition.

[JASON MILLER]

So despite some of the miraculous claims about Cannabis – it’s not a cure-all, and some of the claims made by advocates are overhyped. However, other clinicians I spoke with shared additional stories of the successes of the medical use of Cannabis – which begs a question – just how much evidence is required before Cannabis, or any other natural product, can be accepted as an effective medicine?

We’ve discussed that the gold standard of medical research is considered to be the randomized controlled trial – but it’s an extremely expensive process to get something through the drug approval process in the United States.[18] Because this process is so expensive, it is rare for a company to spend the millions, or sometimes billions, of dollars required to study a natural product alone that they cannot patent and capitalize on later. Additionally, natural products are challenging to standardize and control, which does not lend itself well to modern medical research schemes.

[JAMES TAYLOR SEGMENT]

We have also covered the fact that Cannabis has an extraordinarily long track record with humans, going back nearly 5000 years or more. Through that time, records of varying degrees of quality have been kept about the medical use and toxicity of Cannabis for thousands of years. The historical record indicates that Cannabis has been considered a potent medicine all the way up until the 1930s when Cannabis prohibition began. We haven’t even discussed the history of Cannabis prohibition here but let me just say – Cannabis prohibition was not backed by science, and many medical associations were unhappy when access to Cannabis was prohibited.

Modern research has confirmed that, in fact, many of the traditional medical uses of Cannabis are well-founded and, compared to many foods and drugs, Cannabis is very safe. Where we lack clinical research, we have a host of anecdotal reports, case studies, and observational studies documenting the medical efficacy of Cannabis. And while these types of research may be considered lower quality, at a point these reports become overwhelming in their results. And yet, today in 2019 in the United States, people are still struggling to get legal access to medical Cannabis.

While many of you may already be familiar with a little girl named Charlotte Figgi[19] that brought nationwide attention to the treatment of CBD-rich Cannabis for seizures in a famous CNN special with Dr. Sanjay Gupta called Weed[20], you may be less familiar with another little girl that is fighting the same fight in my home state of Mississippi, and her name is Harper Grace[21]. Harper Grace is a little girl that also suffers from seizures, similar to Charlotte. Her parents found that CBD-rich Cannabis was an effective treatment. In 2014, after a lot of advocacy from Harper Grace’s parents and friends, the state legalized CBD oil, in a limited capacity for limited conditions in a limited selection of patients. Since the law passed, which is actually named after Harper Grace, that little girl still has not been able to get access to CBD treatment, and now her parents are fighting for statewide medical marijuana legalization for 2020.

[NEWS CLIP]

This issue is especially poignant considering the countries only federally sanctioned Cannabis research and development laboratory is located at the University of Mississippi.
Let’s review what we’ve learned.

• Cannabis has been used as a medicine for a lot of different medical conditions for thousands of years.[22] Up until the early 1940s, Cannabis was even part of the US Pharmacopoeia until prohibition began.
• Medical research comes in a lot of forms, and we have to be careful not to conflate the statistical significance of an effect measured in a research study with the clinical significance of an effect measured in a therapeutic setting.
• We can’t assume anything based on a single research result. Research findings always need to be replicated by a different group of researchers.
• The clinical research that is currently available about Cannabis indicates that it could hold promise for the treatment of conditions like nausea, loss-of-appetite, chronic pain, and spasticity.[23] [24]
• There are case studies and uncontrolled clinical research that indicate that Cannabis could be useful for a number of other conditions like autism, ADHD, PTSD, anxiety, depression, and immune system related disorders. While there are numerous case studies and observational reports documenting Cannabis’ efficacy treating conditions like these in patients, it is difficult to interpret that data and extrapolate it to a much larger population.
• There’s a lot we don’t know. Cannabis comes in a lot of different forms. There are many different chemical profiles of Cannabis, each with its own therapeutic index. We are just scratching the surface with understanding Cannabis and we have a long way to go.
• We do know that Cannabis is very safe when consumed responsibly. It is impossible to lethally overdose on Cannabis and many of the adverse health risks of Cannabis can be minimized by utilizing oral forms of Cannabis at low dosages. For more information about the safety of Cannabis, check out episodes 1-3 where we explore this topic at length.
• Clinicians working with patients using Cannabis are seeing positive effects, in general, and at times even profound results. But it’s not a silver bullet. It’s not a cure all. It’s not for every person or every condition. But it is a tool in the clinical tool chest that some people respond very positively to.

So, how is Cannabis a medicine?

Well, simply put, a lot of ways. There is still a lot we don’t know, but there is a lot we do know regarding the safety of Cannabis and the use of Cannabis traditionally as a medicine for thousands of years throughout human history. While, yes, some of the claims about cannabis as a medicine are over-hyped, a lot of them aren’t. A lot of people are finding relief from very serious conditions that they are having to live with every day through the help of Cannabis.

Today it seems like the rationale for restricting access to Cannabis or Cannabis products often comes down to an argument around safety and a lack of research. Harper Grace is fighting for access to CBD oil because lawmakers in Mississippi feel that Cannabis needs to be studied more to understand its risks. The FDA has stated that they are unlikely to allow CBD in foods because they want to better understand the potential risks.[25] This issue with CBD safety is particularly interesting considering the World Health Organization already issued a report in 2018 claiming “CBD is generally well tolerated with a good safety profile…To date there is no evidence of any public health-related problems associated with the use of pure CBD.”[26] Despite this determination, the FDA backs their stance by citing a recent rodent study that claimed to have identified the liver damaging effects of CBD[27] – however as we covered in episode one of the podcast – this study was a rodent study that utilized massive, unrealistic, doses of CBD before uncovering damaging effects. At doses more typical of what anyone might encounter in real life – these liver damage effects were not observed.

Very recently, democratic presidential candidate and former vice president Joe Biden stated that he believed that there needed to be more research into the risks of Cannabis, particularly as a gateway drug, before legalizing the plant federally.[28] Yet, as we also covered in episode one of the podcast, an administrative law judge in the US in 1988 made a formal statement attesting to the safety profile of Cannabis and the need to reschedule it to a more lenient drug schedule.[29]

So, what do you think?

Do we need more research into the safety of Cannabis before we legalize nationwide? How much evidence is enough before people are allowed open, legal access to Cannabis for medical purposes around the world?

Personally, I was left with a couple of questions:

1. Why are Cannabis and its cannabinoids still schedule I drugs in the United States? It’s clear Cannabis has therapeutic applications in certain contexts. Sure, Cannabis can be abused, but so can many other things which are totally legal. Many lawmakers claim we need more research, but how will that research ever take place if Cannabis remains schedule I? Ultimately, the legal status of Cannabis seems to be hurting people more than the plant itself could ever do.
2. Given the safety profile of Cannabis, and its potential efficacy, contrasted with the sometimes-harsh effects of some other medications, why is Cannabis often used as a last resort treatment option for patients, rather than one of the early options?
3. How much of the benefit that users claim they are getting from Cannabis is actually related to its therapeutic activity, and how much might be placebo? And if some of Cannabis’ therapeutic effects are placebo effects – does that matter, if people are finding relief and the treatment is relatively benign?

So far, we have been looking at the various ways Cannabis is used as a medicine. But what do cannabinoids and other chemicals in Cannabis actually do in the body to elicit these medicinal effects?

Join me in our next episode as we take our fantastic voyage into the human body to understand how Cannabis works. In the next episode we begin to explore the question, “What is the endocannabinoid system?”

Until next time, I’m your host, Jason Wilson. Thanks, and take it easy.

[OUTRO MUSIC]
 

CITATIONS

[1] https://www.coloradopotguide.com/images/blog/Health-Effects-of-Marijuana-Reduced.png

[2] https://miro.medium.com/max/1400/0*T-fJXuEjKW4qGUXM.jpg

[3] Rohrig et al. Types of Study in Medical Research. Part 3 of a Series on Evaluation of Scientific Publications. Dtsch Artztebl Int. 2009. 106(15): 262-268.

[4] Kabisch et al. Randomized Controlled Trials. Part 17 of a Series on Evaluation of Scientific Publications. Dtsch Artztebl Intl. 2011. 108(39): 663-668.

[5] Devlin RB et al. In vitro studies: what is their role in toxicology? Exp Toxicol Pathol. 2005. 57 Supple 1:183-188.

[6] Lorian V. Differences between in vitro and in vivo studies. Antimicrob Agents Chemother. 1988. 32(10): 1600-1601.

[7] Ghallab A. In vitro test systems and their limitations. EXCLI J. 2013. 12: 1024-1026.

[8] Geraghty RJ et al. Guidelines for the use of cell lines in biomedical research. 2014. Br J Cancer. 111(6):1021-1046.

[9] Waterbor JW et al. Considerations of sample size in medical research. JAAPA. 2008. 21(4)

[10] Mullane K et al. Chapter 1 – Reproducibility in Biomedical Research. Research in the Biomedical Sciences. Transparent and Reproducible. 2018. pp. 1-66.

[11] LeFort SM. The Statistical versus Clinical Significance Debate. 1993. 25(1):57-62.

[12] Singal AG et al. A Primer on Effectiveness and Efficacy Trials. Clin Transl Gastroenterol. 2014. 5(1): e45.

[13] https://www.fda.gov/drugs/development-approval-process-drugs

[14] https://www.gwpharm.com/healthcare-professionals/sativex

[15] https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-comprised-active-ingredient-derived-marijuana-treat-rare-severe-forms

[16] http://marinol.com/

[17] https://www.ama-assn.org/delivering-care/public-health/how-are-prescription-drug-prices-determined

[18] Fassbender M. Clinical trial cost is a fraction of the drug development bill, with an average price tag of $19m. 2018. https://www.outsourcing-pharma.com/Article/2018/09/26/Clinical-trial-cost-is-a-fraction-of-the-drug-development-bill

[19] https://www.cnn.com/2013/08/07/health/charlotte-child-medical-marijuana/index.html

[20] https://www.cnn.com/2013/08/08/health/gupta-changed-mind-marijuana/index.html

[21] Rowell N. Harper Grace’s Legacy. North Side Sun. 2019 Apr 11. https://www.northsidesun.com/news-breaking-news/harper-grace%E2%80%99s-legacy

[22] Russo E. The Pharmacological History of Cannabis. Chapter 2. Handbook of Cannabis. Oxford University Press. 2014. p.23-29

[23] Whiting PF et al. Cannabinoids for Medical Use. A Systematic Review and Meta-Analysis. JAMA. 2015. 313(24): 2456-2473.

[24] Hill KP. Medical Use of Cannabis in 2019. JAMA. 2019. 322(10): 974-975.

[25] https://www.fda.gov/consumers/consumer-updates/what-you-need-know-and-what-were-working-find-out-about-products-containing-cannabis-or-cannabis

[26] World Health Organization (WHO). Cannabidiol (CBD) Critical Review Report. Expert Committee on Drug Dependence. Fortieth Meeting. 2018. https://www.who.int/medicines/access/controlled-substances/CannabidiolCriticalReview.pdf

[27] Ewing et al. Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model. Molecules. 2019. 24(9): 1694.

[28] https://www.washingtonpost.com/nation/2019/11/18/joe-biden-marijuana-gateway-drug-legalization/

[29] https://www.nytimes.com/1988/09/07/us/judge-urges-allowing-medicinal-use-of-marijauna.html

Episode Description: In this episode, we begin exploring the idea of Cannabis as a medicine. How has Cannabis been used as a medicine in the past? How is Cannabis being used as a medicine today? What does modern medical research have to say regarding what Cannabis can and can't treat? Featured guests include Ethan Russo MD, Jason Miller DACM, James Taylor MD, and Kevin Spelman PhD.

Transcript:

You’re listening to the Curious About Cannabis podcast.

Before we get started let me share a little disclaimer here. In this episode we are going to be discussing the medical uses of Cannabis. All of the information I present to you in this podcast is for education and entertainment purposes only and should not be considered medical advice. Never make decisions about your health based on anything you hear me or any other podcast host talk about. I’m simply sharing information that I’ve collected from talking with professionals with relevant experience or from research studies that are available. But I’m not a doctor, and you should always get your medical advice from a licensed health care professional. Now with that out of the way, let’s move on.

[Shutter]

[KEVIN SPELMAN CLIP]

Here in the state of Oregon, medical Cannabis has been available since 1998 for registered patients with a doctor’s recommendation. There are a variety of conditions that can qualify someone to join the Oregon Medical Marijuana Program, such as cancer, glaucoma, PTSD, or HIV, but the most common condition being treated with medical Cannabis, by far, is pain. At the time of this recording, in 2019, 88% of the 27,000 qualifying patients in Oregon’s Medical Marijuana Program reported severe pain as a condition that they intended to treat with Cannabis.[1] The remaining conditions ranked from most common to least common are spasms, PTSD, nausea, cancer, neurological disease, seizures, glaucoma, wasting syndrome, HIV/AIDS.[2]

Clearly people are trying to treat a wide variety of serious conditions with Cannabis. If Cannabis is an effective therapy for just some or all of these conditions, it could change the health and wellbeing for a massive amount of people currently suffering every day.
So what do we really know about Cannabis? How is Cannabis a medicine?

[INTRO]

Hey everybody, I’m Jason Wilson and you’re listening to the Curious About Cannabis podcast. Thanks for tuning in once again. In this episode we’ll be exploring the idea of Cannabis as a medicine.

And to guide our curious quest I wanted to explore several primary questions:

1. How has Cannabis been used as a medicine in the past?
2. How are Cannabis and Cannabis derived drugs being used as medicine today?
3. How are medical claims derived? How do we determine that something is a medicine?

Let’s get started.

In 2015 the Journal of the American Medical Association published a review, acknowledging a list of therapeutic applications of Cannabis, while also expressing skepticism over others.[3] The National Academy of the Sciences, Engineering and Medicine released a lengthy 400+ page review also identifying clear therapeutic applications of Cannabis and its constituents.[4]

[NEWS CLIP][5]

I have to point out here that when we talk about the medical use of Cannabis, we aren’t just talking about smoking Cannabis. There are lots of ways to consume Cannabis, and each consumption method affects the body differently. Sure, Cannabis can be smoked or vaporized, but it can also be eaten in the form of Cannabis infused foods or taken sublingually by taking drops of a Cannabis tincture under the tongue. Cannabis can also be administered on the skin, topically. Less commonly, Cannabis can also be taken as a suppository.

Anything consumed orally will take longer to take effect because it has to pass through the digestive system and undergo a process called first-pass metabolism before the cannabinoids are passed into the bloodstream. During this metabolic process, cannabinoids are chemically altered. For instance, when THC is ingested orally, nearly half of the THC is metabolized to a compound called 11-OH-THC, which is considered nearly four times as strong as THC.[6] This is why the experience of eating Cannabis products can be so unique and sometimes more powerful than consuming Cannabis by other means.

However, when smoking, vaping, using sublingual products, or suppositories, cannabinoids bypass the liver and pass straight into the blood, leading to a much faster onset and avoiding the chemical alteration that happens during metabolism.

So it seems among the scientific and medical communities, there is no doubt that in some contexts, Cannabis can be a medicine. But to what extent? For what conditions? At what dosages? In what form? That is where much of the debate currently resides.

According to the United States government, at the time of this recording in 2019, Cannabis and it’s cannabinoid constituents are classified as schedule I drugs, a classification reserved for drugs that are presumed to have no medical value and a high propensity for abuse.[7] Other drugs that are classified as schedule I include things like heroin and bath salts. To put this into perspective, drugs like cocaine and methamphetamine, which are schedule II drugs, are less controlled than Cannabis.

Despite the US government’s determination that Cannabis should be a schedule I drug and as such has no medical value – the government actually held a patent on the antioxidant and neuroprotective properties of cannabinoids up until this year.[8] To many, this patent represented deep hypocrisy.

Regardless of the legal status of Cannabis, there are many people across the US that have jumped on the Cannabis bandwagon, touting benefits so profound and diverse that it can’t help but sound like a pitch for the next snake oil.

[JASON MILLER]

That’s Dr. Jason Miller, a medicinal plant and Chinese medicine expert that has been noticing that more and more of his patients are talking about Cannabis.

[JASON MILLER]

So what’s the truth here? To start, let’s explore the ways Cannabis has been used as a medicine throughout history. Then we can look at some of the more modern Cannabis research and see how some of these traditional uses hold up against modern science.
 
How has Cannabis been used as a medicine in the past?

Cannabis has been used by humans for a long, long, long time. We’re talking thousands of years. We’re talking 5000 years. Half of a decamillenium. Decamillenium? Is that a word? It is now.

[JASON MILLER]

In Chapter 2 of the book the Handbook of Cannabis, Ethan Russo, a neurologist and cannabinoid researchers that has been studying Cannabis for over 25 years, summarizes some of the ways in which Cannabis was used therapeutically throughout the last several millenia.[9] Here’s an extremely condensed version.
​
Oral traditions of Cannabis use for appetite stimulation and fighting the effects of old age date back to nearly 3000 years BCE.[10] That’s 5000 years ago! In 1500 BCE, the Atharva Veda indicates that Indians were using Cannabis for anxiety relief.[11] Cannabis is suspected to even be a component of the holy anointing oil of the Hebrews as far back as 750 BCE.[12] [13] The juice of the leaves was noted to be a remedy for earaches in the first century.[14] In the second century Chinese records indicate Cannabis was used in wine as an anesthetic.[15] In the early 10th century Persian records indicate it was even used to stimulate hair growth.[16] In 1542 it was noted that the Cannabis roots could be boiled and used to treat gout and burns.[17] Throughout the 16th century records indicate Cannabis was used for sore muscles, stiff joints, burns, wounds, jaundice, colic and even tumors.[18]

In 1839 a researcher named O’Shaughnessy studied Indian use of Cannabis and performed experiments in dogs, and then later people, to determine if Cannabis was a suitable treatment for tetanus, rabies, epilepsy and rheumatoid disease.[19] Shortly after O’Shaughnessy published his findings, Cannabis began showing up in the European and United States Pharmacopoeias.

O’Shaughnessy is a particularly interesting figure in the history of medical Cannabis. We are going to be learning more about his work in future episodes.

As records become more easily obtainable, we can find records throughout the 18th and 19th centuries of Cannabis being used to treat migraines, pain, spasticity, anxiety, depression, and insomnia.[20]

Cannabis was even featured in the US Pharmacopoeia as a medicine until the 12th edition released in 1942 after marijuana prohibition had begun in 1937.[21] You can still look up old issues of the USP and look for Extractum Cannabis or Tinctura Cannabis aka Extract of Hemp or Tincture of Hemp. Upon the initial publication of Cannabis in the USP in 1851, the 9th edition of the US Dispensatory had this to say about the medical use of Cannabis: “It has been found to cause sleep, to allay spasm, to compose nervous disquietude, and to relieve pain…The complaints in which it has been specially recommended are neuralgia, gout, rheumatism, tetanus, hydrophobia, epidemic cholera, convulsions, chorea, mental depression delirium tremens, insanity, and uterine hemorrhage.”[22]

After Cannabis prohibition began, Cannabis became unavailable as a medicine, and research into the plant progressively slowed down into the late 1950s. Modern medical research into Cannabis really took off in the 1960s when THC was isolated and synthesized.[23] A little known fact – but CBD was actually isolated and characterized approximately 20 years prior to when THC was isolated.[24] But because CBD did not elicit an intoxicating effect, it was largely ignored at first.

As THC research progressed throughout the 1960s and 1970s, research confirmed that THC could reduce nausea and vomiting associated with cancer chemotherapy[25], that THC had the same analgesic activity as codeine[26], and that THC performed as well as the anti-asthma drug salbutamol aka albuterol or Ventolin as a bronchodilator.[27]

The 1980s ushered in renewed interest in CBD as well as continued research on THC. In 1981 CBD was identified as an anticonvulsant.[28] A year later it would be found that CBD could help relieve the anxiety brought on by THC.[29] In 1985, the unique flavonoid Cannflavin A was discovered, breaking Cannabis research away from the cannabinoid chemical class to encompass other types of plant compounds.[30] It was also in 1985 that the pharmaceutical drug Marinol was approved by the FDA for chemotherapy related nausea.[31]

[ETHAN RUSSO]

That’s Ethan Russo, and he knows a thing or two about cannabinoid pharmaceuticals.

[ETHAN RUSSO]

And then in 1988 scientists finally discovered a chemical receptor in the body that seemed to be responsible for most of THC’s effects – the cannabinoid type 1 receptor, or CB1 receptor.[32] This marks the beginning of piecing together a fascinating puzzle about a physiological system that had since been ignored – the endocannabinoid system, which wouldn’t be formally named for another 10 years.[33] But we’ll get into that story in another episode.

In 1993 CBD’s anti-anxiety effects that had been previously noted in the 1980s was again confirmed.[34]

In 1997 it was found that THC could help reduce agitation in patients with dementia.[35]
In 2003 clinical trials of the Cannabis based pharmaceutical Sativex began, investigating whether it could be effective in treating multiple sclerosis symptoms.[36] In 2005 Sativex would go on to be approved in Canada for the treatment of MS related pain.[37] Over the years Sativex would later be approved for other types of pain such as neuropathic pain and cancer pain.[38] [39] Eventually Sativex would be approved in the UK and Spain for spasticity in MS patients.[40] In 2010 it would be discovered that Sativex can also treat nausea related to chemotherapy treatments.[41]

 [ETHAN RUSSO]

Over and over, health care professionals I spoke with commented on the superior efficacy of broader spectrum Cannabis products over isolated cannabinoids.[42]

[JAMES TAYLOR]

This is Dr. James Taylor, a pain physician working in North Carolina. Ever since hemp became federally legal in the United States, he has been working with his patients to understand how hemp extracts, and CBD particularly, might be a tool to help treat chronic pain.

[JAMES TAYLOR]

This difference in therapeutic outcome between isolated compounds from Cannabis and the use of herbal Cannabis or broad-spectrum Cannabis extracts is attributed to something often called – the entourage effect.[43]

[KEVIN SPELMAN]

So far we have looked at the ways in which Cannabis has been used as a medicine in the past, and some ways in which Cannabis and cannabinoid drugs are being used as medicine today. Join us in part two of this series where we pick up on our quest to understand Cannabis as a medicine by examining the ways in which medical claims are derived. How do we determine that something is a medicine? And what results are clinicians seeing in their patients that are using Cannabis?

Until next time, I’m your host, Jason Wilson, stay curious and take it easy!
 
 
CITATIONS

[1] Oregon Medical Marijuana Program Statistical Snapshot October 2019. https://www.oregon.gov/oha/PH/DISEASESCONDITIONS/CHRONICDISEASE/MEDICALMARIJUANAPROGRAM/Documents/OMMP_Statistical_Snapshot_10-2019.pdf

[2] Oregon Medical Marijuana Program Statistical Snapshot October 2019. https://www.oregon.gov/oha/PH/DISEASESCONDITIONS/CHRONICDISEASE/MEDICALMARIJUANAPROGRAM/Documents/OMMP_Statistical_Snapshot_10-2019.pdf

[3] Whiting PF, et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015. 313(24): 2456-2473.

[4] National Academies of Sciences, Engineering, and Medicine. 2017. The health effects of cannabis and cannabinoids: Current state of evidence and recommendations for research. Washington, DC: The National Academies Press.

[5] CBS This Morning. New Report Finds Benefits and Risks of Marijuana. https://www.youtube.com/watch?v=Jx6ioVF5KhE&t=13s

[6] Huestis MA. Human Cannabinoid Pharmacokinetics. Chem Biodivers. 2007. 4(8): 1770-1804.

[7] Lists of Scheduling Actions Controlled Substances and Regulated Chemicals. United States Department of Justice. Drug Enforcement Administration. https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf

[8] Hampson et al. Cannabinoids as antioxidants and neuroprotectants. Patent US6630507B1. https://patents.google.com/patent/US6630507B1/en

[9] Russo E. The Pharmacological History of Cannabis. Chapter 2. Handbook of Cannabis. Oxford University Press. 2014. p.23-29

[10] Shou-Zhong, Y. The Divine Farmer’s Materia Medica: A Translation of the Shen Nong Ben Cao Jing. 1997. Boulder, CO: Blue Poppy Press.

[11] Grierson, GA. The hemp plant in Sanskrit and Hindi literature. Indian Antiquary. 1894. 260-262.

[12] Alter R. The Five Books of Moses: A Translation with Commentary. 2004. New York: W.W. Norton & Co.

[13] Russo EB. History of Cannabis and its preparations in saga, science and sobriquet. Chemistry and Biodiversity. 2007. 4: 2624-2648.

[14] Dioscorides P and Beck LY. De Materia Medica. 2011. Hildesheim: Olms-Weidmann.

[15] Julien MS. Chirugie chinoise. Substance anesthétique employée en Chine, dans le commencement du III-ième siecle de notre ère, pour paralyser momentanement la sensibilité. Comptes Rendus
Hebdomadaires de l’Académie des Sciences. 1849. 28:223–229.

[16] Lozano I. The therapeutic use of Cannabis sativa L. in Arabic medicine. Journal of Cannabis Therapeutics. 2001. 1: 63-70.

[17] Fuchs L. The great herbal of Leonhart Fuchs: De historia stirpium commentarii insignes, 1542 (notable commentaries on the history of plants). 1999. Stanford, CA: Stanford University Press.

[18] Gerard J and Johnson T. The Herbal: or, General History of Plants. 1975. New York: Dover Publications

[19] O’Shaughnessy WB. (1838–1840). On the preparations of the Indian hemp, or gunjah (Cannabis indica); their effects on the animal system in health, and their utility in the treatment of tetanus and other convulsive diseases. Transactions of the Medical and Physical Society of Bengal, 71–102, 421–461.

[20] Russo E. The Pharmacological History of Cannabis. Chapter 2. Handbook of Cannabis. Oxford University Press. 2014. p.23-29

[21] United States Pharmacopoeia 12th Edition. 1942

[22] George B. Wood and Franklin Bache, eds., 1851, The Dispensatory of the United States of America, 9th ed. Philadelphia: Lippincott, Grambo, 1851, pp. 310-311.

[23] Gaoni Y and Mechoulam R. Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish. J. Am. Chem. Soc. 1964. 86(8): 1646-1647.

[24] Adams R et al. Structure of Cannabidiol, a Product Isolated from the Marihuana Extract of Minnesota Wild Hemp. I. J. Am. Chem. Soc. 1940. 62(1): 196-200.

[25] Sallan SE et al. Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. New England Journal of Medicine. 1975. 293: 795–797.

[26] Noyes R Jr et al. The analgesic properties of delta-9- tetrahydrocannabinol and codeine. Clinical Pharmacology and Therapeutics. 1975. 18: 84–89.

[27] Williams, SJ et al. Bronchodilator effect of delta1-tetrahydrocannabinol administered by aerosol of asthmatic patients. Thorax. 1976. 31: 720–723.

[28] Carlini EA and Cunha JM. Hypnotic and antiepileptic effects of cannabidiol. Journal of Clinical Pharmacology. 1981. 21: 417S–427S.

[29] Zuardi AW et al. Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology. 1982. 76: 245–250.

[30] Barrett ML et al. Isolation from Cannabis sativa L. of cannflavin – a novel inhibitor of prostaglandin production. Biochemical Pharmacology. 1985. 34: 2019–2024.

[31] Russo E. The Pharmacological History of Cannabis. Chapter 2. Handbook of Cannabis. Oxford University Press. 2014. p.23-29

[32] Devane WA et al. Determination and characterization of a cannabinoid receptor in rat brain. Molecular Pharmacology. 1988. 34: 605–613.

[33] Di Marzo V. ‘Endocannabinoids’ and other fatty acid derivatives with cannabimimetic properties: biochemistry and possible physiopathological relevance. Biochimica et Biophysica Acta. 1998. 1392: 153–175

[34] Zuardi AW et al. Effects of ipsapirone and cannabidiol on human experimental anxiety. Journal of Psychopharmacology. 1993. 7: 82–88.

[35] Volicer, L et al. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease. International Journal of Geriatric Psychiatry. 1997. 12: 913–919.

[36] Wade, DT et al. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clinical Rehabilitation. 2003. 17: 18–26.

[37] Rog DJ et al. Randomized controlled trial of cannabis based medicine in central neuropathic pain due to multiple sclerosis. Neurology. 2005. 65: 812–819.

[38] Notcutt W et al. Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 “N of 1” studies. Anaesthesia. 2004. 59: 440–452.

[39] Berman JS et al. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain. 2004. 112: 299–306.

[40] Novotna A et al. A randomized, double-blind, placebo-controlled, parallel group, enriched-design study of nabiximols (Sativex®), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. European Journal of Neurology. 2011. 18: 1122–1131.

[41] Duran M et al. Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. British Journal of Clinical Pharmacology. 2010. 70: 656–663.

[42] Russo EB. The case for the entourage effect and conventional breeding of clinical cannabis: no “strain,” no gain. Front. Plant Sci. 09 January 2019. https://doi.org/10.3389/fpls.2018.01969

[43] Ben-Shabat S et al. An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. European Journal of Pharmacology. 1998. 353: 23–31.

In this behind-the-scenes (BTS) full-length interview, I sit down to talk with Janna Champagne (aka Nurse Janna), a registered nurse and health educator specialized in Cannabis and cannabinoid therapy. In this conversation we talk about managing risks associated with Cannabis use, Cannabis interactions with medications, clinical outcomes that she has witnessed in patients using Cannabis, the struggle to overcome social stigma regarding Cannabis use, and much more.
​

About Nurse Janna:
Nurse Janna's focus is educating patients about holistic approaches to health, and natural alternatives to pharmaceuticals including cannabis therapy, and genetic screening/nutrigenomics. Her specialties include: Autism, Autoimmune Disorders, Inflammatory/Chronic Pain Syndromes,Neurological, Gastrointestinal, and Mental Health conditions. Janna's introduction to the cannabis industry began as a cannabis patient when she suffered a health collapse in 2012.  Janna credits cannabis for helping to reduce her reliance on pharmaceuticals, and for supporting her ability to regain optimal health status.
​
Nurse Janna has worked with thousands of patients, with her combined focus of targeting epigenetic mutations (nutrigenomics) and addressing other causes of chronic illness (Endocannabinoid Deficiency) helps promote balance in the body systems naturally, with a goal of improved body synergy. Nurse Janna has completed the Cannabis Nurse courses at The Medical Cannabis Institute. She is also a founding member of the Cannabis Nurses Network, serving on their speaker’s bureau, through which she teaches at conferences and other events.  Janna is an award-winning author, and her daughter’s Cannabis/Autism article was featured on the front page of a nationwide cannabis industry magazine in December 2017.


To learn more about Nurse Janna, visit:

Integrated Holistic Care

Cannabis Nurse Approved
​
JannaChampagne.com