EPISODES

What's in a name?

​In our final episode for Season One, we explore the ways in which Cannabis is named and represented in the market place - by strain name and indica/sativa designation. How do strain names and indica/sativa designations relate to genetic lineage and chemical profiles? Where did the indica vs. sativa model come from? How should confused consumers navigate the strain game?

Contributions from: Angus of The Real Seed Company; Steve Albarran and Brad Bogus of Confident Cannabis

The Real Seed Company: www.therealseedcompany.com
Confident Cannabis: www.confidentcannabis.com
Connect by Confident Cannabis: connect.confidentcannabis.com
Phylos Galaxy: https://phylos.bio/galaxy/
Kannapedia by Medicinal Genomics: http://www.kannapedia.net/


​
EPISODE TRANSCRIPT

​You’re listening to the Curious About Cannabis Podcast.
 
Hey everybody,

Before we get started, I have a short announcement.

This is the last episode of our first season, and I want to just take a moment to say thank you so much for coming on this journey with me over the past several months. We will be taking a small break from episodes like these to get new content ready to share with you for season two, which will start this Summer. We will be restructuring the podcast a bit, based on your feedback. Going forward we will be releasing the behind-the-scenes interviews regularly throughout the entire year, but we will only be releasing seasons of our topical episodes, like this one, twice a year, with one season starting in late Fall, and one season starting in Summer.

If you can’t wait for the next season, consider becoming a patron at patreon.com/curiousaboutcannabis where you will get access to a secret patron’s only podcast feed with content you won’t hear on our public feed as well as early access to Season Two content. You’ll also get access to other educational content, early releases of videos, exclusive videos, discounts for the Curious About Cannabis Book, and more. Check it out at patreon.com/CuriousAboutCannabis.

Thanks again for your support and tuning in throughout this season.

Now, without further ado, let’s get on to the episode.

[Shutter]
 
Gorilla Glue. Grape Krush. Blue Dream. Koala. Mr. Nice. OG Kush. Skywalker Haze. Moonshine Haze. AK-47. Trainwreck. Tangie. Hash Plant. Trinity. Vortex.

What’s in a name?

Go into any legal Cannabis dispensary in Oregon and your head is likely to spin trying to keep up with the seemingly limitless numbers of names of different varieties of Cannabis on the shelf. It’s enough to keep Cannabis connouisseurs on their toes, while the Cannabis curious are sometimes left confused and bewildered. And beyond these various strain names, we have other labels, like indica, sativa, and hybrid. Supposedly some make you sleepy. Some make you feel awake. Others are supposedly balanced for a productive lifestyle. But is there really anything to this system of naming and categorizing Cannabis varieties? What do all of these names mean?

In this episode, we will be taking a look into the world of Cannabis names, The Strain Game.

[INTRO MUSIC]

Hey everybody this is Jason Wilson with the Curious About Cannabis Podcast.

If you have been involved in the Cannabis industry for any amount of time or have visited a dispensary, you may be familiar with the company and website, Leafly.[1] Leafly was originally started as a way to collect information on Cannabis strains. Over time they have evolved, but their core focus on strains has certainly not gone away. Here is some copy from their website describing Cannabis strains:

“Marijuana strains are organized into three primary types: sativa, indica, and hybrid. Each type of strain has unique effects on both the mind and body. For example, sativa strains are uplifting and pair well with activities like social gatherings and being physically active. On the opposite end of the strain spectrum, indica strains are relaxing and can help amplify a deep level of physical sedation - making indica great for those times when you need deep sleep. Lastly, there are hybrid strains which fall between indicas and sativas. Hybrid strains offer a combination of both energizing and relaxing effects. Hybrid strains are great for the times when it’s too late for an energizing sativa or too early for a sedating indica strain.”

But is this legit? Or could this be a well-intentioned, but ill-fated effort that is ultimately misleading consumers and promoting bias and placebo in the consumer market?

Many claims are often made surrounding the name of a Cannabis variety including information about the plant’s genetic lineage, it’s chemical profile, and the effect it will have on a consumer. In today’s episode we are going to be taking a critical look at the way Cannabis is commonly categorized – by strain name and indica/sativa designation.

And to guide our curious quest we will be focusing on several key questions:

1. What do these names mean? What is a strain? What is indica versus sativa, really?
2. How do strain names and indica/sativa designations relate to the genetic lineage and chemical profile of the plant?
3. How do any of these labels indicate the effects a product may have on a user?

So, without further ado, let’s get started.
 
What is a Cannabis Strain?
If you ask different people in the Cannabis industry what they think of the concept of Cannabis strains, you are likely to get mixed reactions.

Some people think that strains are completely useless, outdated ideas. Some think they are concepts reserved for the craft Cannabis cultivators that have an in-depth understanding of the source of the genetics that they cultivate. While others think that strain names are vitally important for understanding the effects that a product may have on them. So, what’s really going on here?

First let’s talk about the word “strain”.

In biology, the term “strain” is generally only used when talking about micro-organisms. There are various strains of E. coli, for instance. But in botany, the term “strain” is not typically used to describe different varieties of plants. Instead, the term “variety” is commonly used. More specifically, the term, “cultivar”, meaning “cultivated variety” is often used to refer to different plant types of the same species and subspecies. An additional taxonomical rank used in botany is “form” which is a level lower than variety and is often used to distinguish slightly different varieties of a variety.

Let’s take the Cannabis strain Gorilla Glue, or GG, for example. There are different varieties of Gorilla Glue, like Gorilla Glue #4, and Gorilla Glue #12, etc. But Gorilla Glue itself is a variety of a subspecies of Cannabis. So, GG #4 and #12 would be considered forms of the Gorilla Glue variety.

So, if we want to be botanically correct, we should replace the term “strain” altogether, with the term “cultivar”. And if there are variations of a particular cultivar, then those variations should be called “forms”.
 
Indica vs Sativa

But what about these terms Indica and Sativa? The old colloquial wisdom states that there are three species of Cannabis plants: sativa, indica and ruderalis. Indica Cannabis plants are short, bushy, and produce heavily sedating effects, whereas sativa plants are tall, airy, and produce stimulating effects.[2] And ruderalis plants are often either considered wild plants or perhaps wild and autoflowering plants. But where did this idea come from?

Let me begin by saying that Cannabis researchers have long debated how to categorize Cannabis and how many species of Cannabis there are. The terms sativa, indica, and ruderalis are only a few of many terms that have been used throughout time to organize Cannabis. These terms have been used inconsistently by different researchers throughout time to describe different types of Cannabis plants.

This basic idea of sativa plants being tall and wide branched and indica plants being short and densely branched comes from a researcher named Richard Schultes in the early 1970s. Schultes suggested that there are three species of Cannabis – sativa, indica and ruderalis.[3] Each of these species was associated with basic morphological characteristics – that the tall Cannabis plants were Cannabis sativa, the short bushier plants were Cannabis indica, and the very small, sometimes unbranching, forms of Cannabis plant often seen in the wild were considered Cannabis ruderalis.

However, a few years later another taxonomical model for Cannabis would be presented that focused on the plant’s chemical profiles, rather than morphology. This taxonomic model, presented by Small and Cronquist, suggests that Cannabis is one single species, Cannabis sativa, with at least two subspecies, sativa and indica.[4] Under this model, the sativa subspecies consists of fiber-type and low THC varieties of Cannabis, while the indica subspecies consisted of high THC and 1:1 THC,CBD ratio plants. Genetic research performed by John McPartland and Geoffrey Guy confirmed that THC-rich varieties of Cannabis are all of the same species. So if we accept this model, which I should point out that not everyone believes this model is accurate, but we’ll save that for later, If we accept the Small and Cronquist model, then all THC-rich varieties of Cannabis should be Cannabis sativa subspecies indica.

Some researchers felt it made little sense to organize a plant based on its intoxicating properties, and so later on in 1980, a researcher named Loran Anderson would refine Schulte’s taxonomical model, taking Schultes’ focus on the growth form of Cannabis varieties and adding details about leaf characteristics to the picture.[5] Anderson characterized Cannabis indica as short broad leaf plants, Cannabis sativa as tall narrow leaf plants, and Cannabis ruderalis as small, weedy plants. Anderson also pointed out that these distinctions between sativa, indica and ruderalis have little to do with chemical profiles.

So this the work of Schultes and Anderson are largely why we refer to Cannabis plants as indica or sativa based on how they look. But why do we often use these terms to refer to chemical profile as well? Well, it’s a complicated story, and maybe too complicated to dive into too much in this episode.

But basically, the term Cannabis sativa was originally used by Carl Linnaeus in the 1753 to describe a non-intoxicating form of Cannabis commonly cultivated in Europe, which we would today call hemp.[6] Cannabis indica was originally used by Jean-Baptiste Lamarck thirty years later to describe Cannabis from India that was intoxicating.[7] The plants he reviewed had narrow leaves, not wide leaves, and the primary difference was that the plants were a little shorter, more aromatic, and intoxicating. Later on, the term Cannabis sativa would be used by a Russian researcher to describe forms of Cannabis from Afghanistan that were used to make hash – a significant departure from Carl Linnaeus. Then later on the term Cannabis indica would be applied to forms of Cannabis from Afghanistan that were used to make hash. So these uses of the terms Cannabis sativa and indica would become confused throughout time, and blended in the minds of many with the taxonomical models that Small and Cronquist and Schultes and Anderson put together, separately, ultimately resulting in a totally confused vernacular that we have been stuck with to this day.[8]

[ANGUS]

This is Angus from The Real Seed Company. Angus has spent years travelling around the world collecting seeds of Cannabis varieties often referred to as “landrace strains”, which are varieties which have naturalized to the region in which they grow. Through his travels, Angus has had the opportunity to get to know people from cultures all over the world that have been growing Cannabis for millenia, and along the way he has studied the issue of Cannabis taxonomy in depth as he has become a de facto Cannabis historian.

[ANGUS]

But the story gets even more confusing.

So far we’ve talked about two ways of categorizing Cannabis – one that categorizes Cannabis by morphology, and the other that categorizes Cannabis by chemotype. But there’s another way of categorizing Cannabis which we already hinted at. And that’s by the plant’s genes.

The researcher Karl Hillig performed several different experiments looking at the genetic and chemical variation among Cannabis varieties. In his genetic research, he made a scatter plot representing the differences between samples, and then compared the data to different indica/sativa taxonomical models.[9] What he found was that of the major taxonomical models that he reviewed, including those by Schultes and Small and Cronquist, none of them fit his data. His data showed two distinct clusters, seemingly representative of a split in the Cannabis gene pool.

In their book Cannabis Evolution and Ethnobotany, Robert Clarke and Mark Merlin present a revised taxonomical model that states that all THC-rich cultivars and broad-leafed hemp cultivars are Cannabis indica, and all narrow leaf hemp is Cannabis sativa.[10] This model also posits that all Cannabis varieties are ultimately derived from a single Putative Ancestor. In Clarke and Merlin’s model, THC-rich Cannabis varieties are separated on the subspecies level by their morphology and named after their presumed origins. So narrow leaf THC-rich varieties are Cannabis indica ssp. indica, representing their presumed origins of India, while broad leaf THC-rich varieties are Cannabis indica ssp. afghanica, referring to their presumed origin of Afghanistan. Broad leaf hemp varieties would be Cannabis indica ssp. chinensis, representing origins from China, and narrow leaf hemp varieties would be Cannabis sativa ssp. sativa.

Upon careful review, it appears that the colloquial use of indica and sativa is really just a bastardized synthesis of taxonomical systems, and it doesn’t accurately represent any single system of organizing Cannabis. In short – it’s made up. It seems to take elements from each of these systems that we have covered but fails to accurately deliver on any of them. It’s really quite a mess that should be abandoned.

When I was attending the University of Mississippi and spending time at the NIDA Cannabis lab there, I asked the researchers how many species of Cannabis they recognized, and I was given a firm answer that there was only one species of Cannabis. When reviewing the Integrated Taxonomical Information System, Cannabis is listed as a single species – Cannabis sativa.[11]

Perhaps as genomic research into Cannabis progresses, the taxonomy of Cannabis will evolve. Based on trends in biology, this is likely to be the case. Genetic research is leading to many changes in how all of life is categorized, across the board, and Cannabis is not likely to escape this rearrangement.

Taking a step back from all of these taxonomical models, let’s briefly discuss what terms like “sativa”, “indica”, “ruderalis” mean from a botanical perspective.

The term “sativa” is typically used to refer to cultivated plants. For instance, the common oat is Avena sativa. The term “indica” technically means “from India.” And the term “ruderalis” is derived from the word “ruderal”, usually used to describe plants that grow easily in disturbed areas. Cannabis researcher John McPartland has argued that we should take the meanings of these terms seriously when deciding how to talk about Cannabis. For instance, as far as we can tell, only domesticated varieties of Cannabis still exist in the world. Sure, there are plants that have escaped cultivation and re-naturalized, but are there really any varieties of Cannabis in existence that are untouched by human domestication? It’s highly unlikely.

So, does that mean that all Cannabis in existence today is technically “sativa”? And then what about the use of the term “indica”? McPartland has argued that we should actually split THC-rich Cannabis into two varieties based on their origins – one being indica, and one being called afghanica.

So regardless of how we want to categorize Cannabis, if we want our vocabulary to be consistent, we should use these terms intentionally according to the manner in which these terms have been applied to other plants.

In John McPartland’s 2018 review of Cannabis taxonomy and systematics, he provides a suggestion for fixing these labels in our cultural vernacular to make them more accurate. He states, “In summary, reconciling the vernacular and formal nomenclatures: “Sativa” is really Indica, “Indica” is actually Afghanica, and “Ruderalis” is usually Sativa. All three are varieties of one species, Cannabis sativa.”[12]

But, leaving the taxonomy debate aside for a moment, just how reliable are indica/sativa designations or strain names in terms of genetic lineage and chemical profiles?
Let’s start with genetic lineage. Do strain names and indica/sativa designations correlate with genetic lineage? The short answer is – not really.[13]
First let’s look at some basic issues.

First of all, strain names are often mislabeled. This happens intentionally and unintentionally. It’s common for Cannabis cultivators to cultivate multiple varieties – and it makes sense that in the hustle and bustle of harvesting and processing, some containers of plants may get mislabeled. However, on the more nefarious end of things, some cultivators will change the cultivar name of a batch of Cannabis in an attempt to make it more likely to sell.

Second, strain names are often inappropriately applied to plants propagated from seed.
These two issues alone have muddied the playing field so much, that the reliability of any strain name, just in terms of genetic lineage, is a real crap shoot.

The same issues can be said for indica/sativa designations. Even if we were to accept the colloquial definitions of indica and sativa – the fact of the matter is that cultivators and product manufacturers often uses these labels to indicate an anticipated effect more so than the genetic lineage or even morphology of the plant.

Additionally, there are several online tools that allow you to examine how genetically similar and dissimilar different Cannabis samples are. One is called the Galaxy by Phylos Bioscience[14], and the other is Kannapedia by Medicinal Genomics[15]. Using these tools, we can examine data related to samples that were labeled as “Blue Dream” for instance. On the Phylos Galaxy, right away we can see different unique genetic clusters, with some clusters being substantially unique. On Kannapedia you can search for all sorts of samples and see the hodge podge of “close relatives”, some that are labeled the same strain, and some that seemingly should be quite different based on colloquial wisdom.

Now, this isn’t to say that there is absolutely no consistency behind strain names. I want to point out that there are in fact genetic patterns among Cannabis varieties. For instance, going back to the Phylos Galaxy you’ll find that there are distinct genetic clusters of close relatives among any one strain name, but which cluster is “the true OG?” The “true Blue Dream”? Is it the biggest cluster? If so, why? Who decides what “Blue Dream” or “OG Kush” actually is, genetically?

In the Kannapedia database, while you will see a strain name listed, you also will see a unique identifier that is the true “label” associated with the genetics that were tested. From a genetic perspective, the strain name is largely irrelevant. However, if you focus on a sample that was labeled “Blue Dream”, for example, you will likely see that it has close relatives that are also labeled as “Blue Dream”. So there is some consistency. Just not enough consistency to trust the labels.

So strain names and indica sativa designations don’t mean much in terms of genetic lineage. But what about chemical profiles?[16]

To begin to tackle this issue, we need to review a lot of data. So I went to my friends at Confident Cannabis[17] to get their opinions on this issue. Confident Cannabis is a technology company that provides various software solutions to Cannabis testing labs, growers, producers, and dispensaries to bring transparency to the supply chain. Their platform captures a lot of data about products moving around in the Cannabis industry, and by analyzing that data, they have been able to glean some interesting insights.

[STEVE ALBARRAN]

This is Steve Albarran, the CEO of Confident Cannabis

[STEVE ALBARRAN]

I had Brad Bogus from Confident Cannabis go through the Connect platform[18] with me to explain how it works and what I was seeing.

[BRAD BOGUS]

But what about indica/sativa designation?

[BRAD BOGUS]

The ugly truth of the matter is that there are various plants labeled the same strain with distinctly different cannabinoid and terpenoid profiles. This can be for various reasons, like the mislabeling of strain names. But it can also be due to the fact that terpenes are highly influenced by environmental conditions and they can change rapidly when Cannabis is in storage. You could take a clone of a Cannabis variety and grow it in different conditions and get slightly different terpene concentrations. You could take plants grown in the same conditions and dry them or store them differently and end up with different terpene profiles.

So these names don’t seem to be strongly correlated with genetic lineage. And they don’t seem to mean much in the way of chemical profiles. So what gives?

Well, in short, we need a new system of a categorizing and talking about Cannabis. If we are interested in how something will affect somebody, we care about chemical profile, and we need a vocabulary for talking about patterns of chemical profiles. If we are interested in discussing plant morphology, we need a vocabulary to talk about that which is consistent, accurate, and separate from the vocabulary used to talk about chemical profiles. If we are interested in discussing genetic lineage, we need assistance from genetic mapping tools and some standardized names of Cannabis cultivars which are based on genetic data. Several researchers and companies, like Leafly, have proposed alternative methods to address these distinct problems, but none of these solutions have really taken a strong hold in the Cannabis industry yet.

Going back to where we started, with Leafly, they have attempted to produce a visual guide to understanding a strain’s chemical profile, represented by a series of shapes and colors with unique meanings.[19] The attributes that are associated with each strain are based on numerous lab tests, which is certainly a step in the right direction. The website then goes on to associate each strain with effects like “sleepy”, “relaxing”, “uplifted”, “energetic” – but this is potentially flawed in a number of ways. First, it assumes that a strain name is represented by one particular chemical profile, which as we have talked about in this episode, is not consistent. Even when basing the findings on aggregates of terpene data, you are still left with an average chemical profile that does not necessarily represent what someone will find in a dispensary.

And concerning the predicted effects, if you dive deeper into the data, you often find that even consumers don’t agree on the effects of a Cannabis variety. For many strains on Leafly’s website, close to 50% of people report the most commonly reported effects, meaning that nearly half of people that tried the strain did not feel those same effects.
Another issue that we haven’t really gotten into at all in this episode is: even if you know the chemical profile of a Cannabis variety – can you really predict the effects it will have on somebody? We’ll save that question for another time.

So as a consumer trying to find Cannabis products that work best for you, what do you do after you learn that all of these names are unreliable?

My takeaway is this – stop relying on strain names. Stop relying on indica/sativa designations. Start journaling. Pay attention to the chemical profiles and the organoleptic characteristics of what you consume and keep track of how you respond. You may find that a single chemical profile affects you differently at different times of the day, or in different settings. You may find that that Cannabis that your budtender told you would put you to sleep actually makes your heart race and wakes you up. You may find that a small toke produces very different effects than consuming a larger dose. There are so many variables at play that will influence how a person will respond to Cannabis. To dilute all of those variables down into a simplified model of Cannabis strains or indica/sativa designations is a fool’s errand.

There is also the hidden and impossible to quantify variable – which is you. The chemistry of the product is only part of the picture, and the biochemistry that your own body brings to the table is the other part of the picture. No one can tell you what will work for you, or how something will affect you. And there is no sure-fire way to predict it. It comes down to trial and error.

If you are looking for a good journal designed for this purpose, check out Gold Leaf’s Patient Journal.[20] I’ll be doing a review of Goldleaf’s journals and other educational materials that will be posted on the Curious About Cannabis YouTube channel soon.

So let’s review what we’ve learned:

• The Cannabis industry uses a common colloquial vocabulary to talk about Cannabis varieties where “sativa” is used to describe tall wide branching plants which cause stimulating effects in users, and “indica” is used to describe short dense plants which cause sedating effects.
• Researchers currently don’t agree on the best way to categorize Cannabis, but they do agree that all THC-rich varieties of Cannabis are a single species.
• Even among most proposed taxonomical systems, the terms “indica” and “sativa” are used in inconsistent ways.
• The current colloquial indica/sativa model is not grounded in any scientifically recognized taxonomical model of Cannabis.
• Research indicates that strain names and indica/sativa designations do not strongly relate to genetic lineage.
• Although there are distinct groups of chemical profiles among Cannabis varieties, research indicates that strain names and indica/sativa designations do not strongly correlate to these chemical profiles.[21]
• It is important for the industry to define new vocabularies and systems of categorizing Cannabis which are more accurate and precise.
• In the meantime, the best thing you can do to find Cannabis products that work best for you is to keep a journal and track what chemical profiles, smells, tastes, dosages, etc that you have tried and what the experience was like. In this way, you can begin to transcend strain names.

And with that, I’m your host, Jason Wilson.

Thanks again for tuning in for this episode and this season. It’s been a great pleasure to have you join me on this journey. Until next time, stay curious, and take it easy.

[OUTRO MUSIC]


CITATIONS

[1] www.Leafly.com

[2] www.leafly.com/strains

[3] Schultes RE, Klein WM, Plowman T, Lockwood TE. 1974. Cannabis: An Example of Taxonomic Neglect. Botanical Museum Leaflets, Harvard University. 23(9): 337-367.

[4] Small E and Cronquist A. 1976. A Practical and Natural Taxonomy for Cannabis. Taxon. 25(4): 405-435.

[5] Anderson LC. 1980. Leaf Variation Among Cannabis Species From A Controlled Garden. Botanical Museum leaflets, Harvard University. 28(1): 61-69.

[6] Linnaeus C. 1753. Species Plantarum.

[7] Lamarck JB. 1788. Encyclopédie Méthodique, Botanique, Tome second, Part 2. Panckou>[8] McPartland JM. 2018. Cannabis Systematics at the Levels of Family, Genus, and Species. Cannabis and Cannabinoid Research. 3(1): 203-212.

[9] Hillig KW. 2005. Genetic evidence for speciation in Cannabis (Cannabaceae). Genetic Resources and Crop Evolution. 52: 161-180.

[10] Clarke RC and Merlin MD. 2013. Cannabis: Evolution and Ethnobotany. University of California Press.

[11] http://www.itis.gov/

[12] McPartland JM. 2018. Cannabis Systematics at the Levels of Family, Genus, and Species. Cannabis and Cannabinoid Research. 3(1): 203-212.

[13] Sawler J et al. 2015. The Genetic Structure of Marijuana and Hemp. PLoS One. https://doi.org/10.1371/journal.pone.0133292

[14] https://phylos.bio/galaxy/

[15] http://www.kannapedia.net/

[16] Piomelli D and Russo EB. 2016. The Cannabis sativa Versus Cannabis indica debate: An Interview with Ethan Russo, MD. Cannabis and Cannabinoid Research. 1(1): 44-46.

[17] www.confidentcannabis.com

[18] http://connect.confidentcannabis.com/

[19] https://www.leafly.com/strains

[20] https://shopgoldleaf.com/products/patient-journal

[21] Piomelli D and Russo EB. 2016. The Cannabis sativa Versus Cannabis indica debate: An Interview with Ethan Russo, MD. Cannabis and Cannabinoid Research. 1(1): 44-46.

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!
​
Enjoy, and stay curious!

​In this nearly 3 hour behind-the-scenes (BTS) conversation, I speak with Angus of The Real Seed Company, a company that collects the seeds of landrace strains from across Asia. Throughout the conversation we talk about misconceptions about landrace strains, how other cultures across the world use Cannabis, the spiritual use of Cannabis, how Cannabis is categorized and named, issues regarding Cannabis biodiversity, and much more! Visit www.therealseedcompany.com to learn more about The Real Seed Company. Enjoy and stay curious, my friends!

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.