Seasonal Episodes

Meet the Cannabis Plant: Exploring the Evolutionary History and Lifecycle of Cannabis | Feature #11

CAC feature episodes are back after a 2 year hiatus! In our 11th feature production – we dive into the science of the Cannabis lifecycle. We start with looking at the evolutionary history of Cannabis before we switch gears and look at how Cannabis is cultivated, dried and cured. We dive into the science involved in many of the changes Cannabis undergoes in its journey to a consumer’s grinder.

I hope you enjoy our return to feature episodes – I have many more planned!

If you’re curious about Cannabis, visit www.cacpodcast.com and check out more podcast episodes and educational content including courses, books, and more!

Stay curious and take it easy!

Show Notes / Transcription:

“It’s a plant that goes by many names. Some call it hemp. Some call it marijuana. Call it what you will, it’s cannabis. And it’s got a lot of people curious.

But what do you really know about the Cannabis plant and how it makes its way to your grinder? In this episode we will be taking things back to their roots, as we explore the science of the Cannabis plant’s lifecycle.

So get ready to get dirty as we meet the Cannabis plant!

[INTRO]

These days Cannabis is big business. It wasn’t that long ago that Cannabis was almost an entirely underground industry. Very few people were willing to talk openly about it, and those that did often had to disguise their identities to do so. Today Cannabis is legal in some form or another in most states in the United States as well as Canada, Mexico and many other countries around the world.

More people are using Cannabis than ever before. Chances are, if you are listening to this podcast, there is a strong possibility you are one of these people. But what do you really know about how that little Cannabis bud in your child-resistant pop top container got there. Every Cannabis flower has a story to tell.

In this episode we are going to follow the lifecycle of a Cannabis plant from early evolution, to seed all the way to consumption and chart out many of the fascinating bits of science that are involved along the way.

And to guide our curious quest, we will focus on a few key questions:

One, what is Cannabis and how did it get here? Where does it fit in the big kingdom of plants?

Two, How does a harvested Cannabis plant turn into the perfectly manicured, aromatic, resinous buds that you might find at a dispensary?

Three, How does the chemistry of Cannabis change over time from the moment it is harvested to the moment it reaches the hands of a consumer?

And now, without further ado, let’s get started!

So, what is Cannabis?

Cannabis is a genus – which is one rank above species – and it belongs to the Cannabaceae family, which includes up to 9 or 10 other genera, like Humulus, which you are already familiar with if you are a beer drinker, because Humulus lupus, or hops, is commonly used to flavor beer.[1]

Recent research examining fossilized pollen from around the world has indicated that Cannabis and Humulus split from the same ancient ancestor approximately 30 million years ago.[2]

The Cannabis plant is thought to have really started is evolutionary journey somewhere around the Tibetan Plateau in Asia.[3] From there it moved around, following humans wherever we went, traveling from Western Asia up into Eastern Europe[4], back down into Asia, West into Africa and Western Europe. Then on to South America, Atlantic and Pacific Islands and finally North America.

Cannabis is thought to be one of the earliest ethnobotanical plants that humans have relied on for food, materials, and medicines. The seeds have been eaten for their nutritional value for thousands of years. There are reports of Cannabis being used for religious and recreational purposes going back at least five thousand years ago.[5] [6] Because of its value as a multi-functional botanical, humans throughout history have stewarded the Cannabis plant.

In each of the places where Cannabis has travelled, it has naturalized. It doesn’t actually take very long for Cannabis to adapt to a new environment. Reportedly this can happen in as few as 50 generations.[7] Given that Cannabis is generally an annual plant, that’s just 50 years or so. In the context of evolutionary history, this is a flash. These different varieties of Cannabis that have naturalized to unique geographical areas are called “landrace” varieties. Forgive the unfortunate terminology – it is what it is.

[ANGUS]

This is Angus of The Real Seed Company. He has traveled all over the world studying landrace Cannabis varieties.

[ANGUS]

So these are plants that are naturalized – but not necessarily wild. In fact, botanists and other researchers that have gone searching for truly wild Cannabis have had a hard time finding it. There is evidence of domestication in seemingly all Cannabis plants on the planet at this point. But this should not be surprising, right? We also don’t see wild versions of many of the vegetables we eat, because they have been domesticated for so long.

It’s also worth noting that the commercial Cannabis that you find in a dispensary, has little to do with these naturalized varieties. Commercial Cannabis is the result of intense hybridization and inbreeding resulting in the types of plants we traditionally think of when we think of Cannabis, but there is a lot more to Cannabis than what you see at a dispensary – but we will have more on that in another episode.

The Cannabis plant itself grows in varying forms depending on how it is cultivated, the plant’s genetics, and more.

The Cannabis leaf has become one of the most well recognized leaves on the planet, presenting a leaf structure that resembles a hand and is referred to as palmate. The leaf consists of 3 or more leaflets that somewhat resemble fingers. Each leaflet features serrated edges and a characteristic vein pattern where each vein splits toward the outer edge of the leaf to spread to both the outer tip and inner notch of each serration.

It is typically thought that Cannabis plants grow as either male or female plants. Female Cannabis plants produce the sticky resins containing the prized cannabinoids and terpenoids that so many people are after.

However this idea of a female Cannabis plant may not be quite right, as the Cannabis plant keeps many tricks up its sleeves, including the ability to produce male flowers and produce seeds on its own if it thinks it is in danger.

[REGGIE GAUDINO][8]

This is Dr. Reggie Gaudino. He is a molecular geneticist and research scientist that has been studying Cannabis for years. And his research has led him to believe that the notion of a true female Cannabis plant is a myth.

[REGGIE GAUDINO]

We’ve talked a bit about what Cannabis is and where it came from, but how is it grown? To answer this, we will follow the lifecycle of a Cannabis plant, starting with the seed.

Cannabis seeds contain several primary parts – the endosperm, which is a special kind of food to help feed the plant as it first starts growing, the cotyledons, which are the very first leaves that the plant will push out, and the seed coat, which protects the cotyledons and endosperm. When the seed absorbs a certain amount of water, life kicks into motion.

This moment when the seeds crack and start to push out roots is called “germination”. During this process, the plant is producing all sorts of hormones to quickly build roots, shoots and true leaves so that the plant can start using energy from the sun and have a decent chance at surviving.

But you have to be mindful that you know your seeds well. As plants are bred, they fall into a particular fiial generation. F1 plants tend to have stable, dominant traits. F2 plants tend to contain such a mix of genetics that many recessive traits emerge. With enough breeding through more filial generations, it is possible to eventually get to a stabilized inbred line of plants that are always consistent when grown from seed – however, this takes a lot of work and some debate whether it has ever happened in Cannabis yet.

Back in 2019 I spoke with a Cannabis farmer that had a nightmare scenario happen with Cannabis seeds that were supposed to be F1 hemp seeds.

[SAM MOORE][9]

Within a few weeks, depending on how much light the plant is getting, it will start to produce the earliest signs of sex organs – giving you a bit of insight into whether the plant is a male or female.

Cannabis produces two types of flowers – staminate flowers, which are the “male” flowers that produce pollen, and pistillate flowers, which are the “female” flowers that contain ovaries and produce resin.

If you don’t want to wait the 3 to 6 weeks it can take to sex your plants by eye, there are molecular tests available that can identify with varying degrees of accuracy whether your plants are male or female presenting.

Each bud is actually an inflorescence, which is the scientific word for a group of flowers. Each inflorescence of Cannabis contains lots of small irregular flowers, signified by a pair of what look like small hairs coming from each flower. The stigma, along with the fused style found at its base, is used to help pollen travel down to the ovary for pollination and fertilization.

Generally male plants are culled from the garden quickly to avoid pollination and seed production in the resin-producing female Cannabis plants.

Once these female presenting Cannabis plants begin producing flowers, they also start producing tons of cannabinoid and terpenoid rich sticky icky resin. And as long as the plants are not pollinated, they keep producing resin until the plant prepares to reach the end of its lifecycle. At this point the resin starts changing color, from clear, to cloudy to amber.

When the majority of trichomes are getting cloudy or amber, it’s time to harvest the flowers and allow them to dry – usually to a moisture content of around 8 to 12%. Personally, I recommend letting Cannabis dry more than you probably think it should, almost to the point of being cracker dry. This can be a bit scary at first – but trust me – that material is going to soak up any moisture from the air while curing, ultimately rehydrating the buds. You should expect to see the moisture content of the plant material go up a couple of degrees or more during curing.

You might be surprised how much water is in the air around us most of the time. Even in arid places like California or Southern Oregon, the air can often rest at humidity levels around 35 to 50%. In humid areas like the Southeastern United States, those humidity levels can be much higher.

When the plants are being harvested, the large leaves are clipped off. This helps ensure that air can move around the drying plants better and this helps prevent excess moisture from filling the drying space, ultimately reducing the potential of mold growth and expediting the drying process.

This drying process is a delicate process. If it happens too fast with too much heat, many terpenes and other volatile compounds besides water will be lost or degraded. As long as the drying process happens slowly at a low temperature, excess terpene loss should be kept to a minimum.

While the plant is drying, the chemistry starts changing. Besides the water leaving the plant material, aromatic compounds like monoterpenes are also leaving the plant, leaving behind heavier terpenes like sesquiterpenes.[10] One study found that while monoterpenes dominate freshly harvested Cannabis, which often have sharp and gassy aromas, the terpene profile of a plant rapidly changes as it dries to favor sesquiterpenes like beta-caryophyllene and humulene. This is because much of those monoterpenes literally jump off the plant during the drying process, ultimately raising the concentration of heavier terpenes, which tend to have spicier aromas overall.

The plant also off gasses other things while it is drying, like carbon dioxide, methanol, and ethylene.

[ALLISON JUSTICE][11]

This is Dr. Allison Justice, a plant scientist based out of South Carolina that has made it her mission to better understand how the Cannabis plant grows, and particularly – how it grows differently in different parts of the world.

[ALLISON JUSTICE]

Once dry, the plants are due for a good bucking. Bucking is the process of removing buds off of the large stems of the plant. This can be done by hand, as is often the case for craft Cannabis that is being treated more delicately, or there are also machines that have been designed to strip buds off of Cannabis plants as is the case in large scale Cannabis cultivation. Once the plant has been bucked, the buds can be trimmed to remove excess plant material before being stored for curing.

Once Cannabis plants have been chopped down, dried, and allowed to cure – they are then packaged – often in glass jars or vacuum sealed bags – to preserve the flowers’ aroma and moisture content. It’s at that point that the product makes its way from a grower, to a wholesaler, to a dispensary, and then to a customer’s hands.

But the Cannabis plant is not done changing yet.

As Cannabis is moved from container to container and exposed to oxygen and light, the chemistry starts changing once again. Terpenes oxidize, forming new aromas and tastes. Cannabinoids decarboxylate a bit and transform. Once THCA decarboxylates to THC, it then begins transforming into delta-8-THC and CBN.[12] Likewise, CBDA will decarboxylate to CBD, then transform to CBND and other derivatives.[13]

By the time a dried, cured inflorescence reaches a consumer – the chemistry can be substantially different than when it was harvested. This is one reason why “live resin” has become so popular. “Live Resin” is an extract produced from freshly harvested Cannabis plants that have not been allowed to dry and cure. Typically plants are cut down and immediately frozen and then stored until ready to be extracted. Live resin is typically associated with very loud aromas and flavors, often including more monoterpenes than would normally be found in the extracts of cured flower.

This has led to interesting debates between passionate connoisseurs and brands over the benefits of live resin vs. cured resin.

To each their own.

And just when we thought we were done, the Cannabis plant is still not done changing. The way you consume Cannabis affects its chemistry and what chemicals actually make it into your bloodstream.

When Cannabis is heated, all those cannabinoids, terpenoids and other chemical compounds begin to further transform into different chemicals, some that were never present in the plant to begin with.

[RILEY KIRK][14]

On the other hand, if you eat Cannabis, the chemistry will change in a different way. Those chemicals will travel through your digestive system to your liver where they will be metabolized and transformed before being allowed to enter your bloodstream.

But all of that chemistry of the Cannabis plant and its constituents is only one piece of the puzzle when trying to understand how Cannabis and Cannabis derived products affect the body. The other piece of the puzzle…is you. Your unique body and the unique ways in which it processes food, drugs and other compounds is a huge piece of the puzzle that often gets ignored.

Beyond your basic physiology that you bring to the table, there is also your psychology.

The setting in which you consume Cannabis will affect your experience. Your intention while consuming Cannabis will affect your experience. Consuming when you’re upset versus when you are happy will yield different experiences.

Cannabis affects everyone differently for a host of reasons – and no one really understands all the variables involved to predict how Cannabis will affect you. While there are all sorts of genetic tests, organoleptic training, and special recipes out there claiming to help you find what will work perfectly for you – at the end of the day, YOU are the only one that can know what works best for you. And you gain that understanding through experience and careful observation and reflection about your experiences.

If you want to learn more about how Cannabis affects the body, I recommend checking out our episodes on the endocannabinoid system and the endocannabinoidome!

Now, let’s review what we’ve learned.

First, Cannabis is a plant with a rich evolutionary history. It’s closest ancestor is the hops plant, Humulus lupus, which shared an ancient ancestor with Cannabis approximately 30 million years ago.

Cannabis has been used throughout history for many different uses, and is most commonly used as fiber, food, and medicine.

It is the pistillate flowers of the Cannabis plant that produce cannabinoid and terpene rich resins.

There are no true female Cannabis plants, as they all seem to have the ability to produce male flowers under stress.

Cannabis plants generally show their sex within 3 to 6 weeks of growth, depending on lighting conditions and the genetics of the plant itself. This process can sometimes be expedited by limiting light to only 12 hours a day

Male Cannabis plants are kept separate from resin-producing female plants to avoid pollination and seed production, or fertilization.

The chemistry of a Cannabis flower changes considerably from the moment it is harvested to the moment it is consumed.

Fresh Cannabis flower is rich in monoterpenes which quickly volatilize during the drying process, moreso that heavier terpenes like sesquiterpenes.

As Cannabis dries, the cannabinoids and terpenes in the resin begin to transform as they are exposed to air, light and heat.

When Cannabis is curing, it releases a variety of volatile organic compounds that influence the way cannabinoids and terpenes transform.

Then after the flower is packaged and sold to a consumer, another chemical transformation takes place when the flower is heated – producing hundreds of chemicals that were not present in the flower before it was heated.

Once consumed, each person’s body processes Cannabis a little differently, sometimes leading to very different experiences person-to-person.

There are no tests, techniques or recipes that will automatically connect you with the perfect Cannabis product or chemical profile for your specific need. You know yourself better than anyone, and only you have access to the physiological and psychological variables that also influence how you experience Cannabis, beyond the chemistry of the product itself.

That’s our show for today. I’m Jason Wilson[15] with Curious About Cannabis[16] asking you to stay curious and take it easy.

[1] John M. McPartland.Cannabis Systematics at the Levels of Family, Genus, and Species.Cannabis and Cannabinoid Research.Dec 2018.203-212.http://doi.org/10.1089/can.2018.0039

[2] McPartland, J.M., Hegman, W. & Long, T. Cannabis in Asia: its center of origin and early cultivation, based on a synthesis of subfossil pollen and archaeobotanical studies. Veget Hist Archaeobot 28, 691–702 (2019). https://doi.org/10.1007/s00334-019-00731-8

[3] McPartland, J.M., Hegman, W. & Long, T. Cannabis in Asia: its center of origin and early cultivation, based on a synthesis of subfossil pollen and archaeobotanical studies. Veget Hist Archaeobot 28, 691–702 (2019). https://doi.org/10.1007/s00334-019-00731-8

[4] McPartland, J.M., Guy, G.W. & Hegman, W. Cannabis is indigenous to Europe and cultivation began during the Copper or Bronze age: a probabilistic synthesis of fossil pollen studies. Veget Hist Archaeobot 27, 635–648 (2018). https://doi.org/10.1007/s00334-018-0678-7

[5] Clarke, R., & Merlin, M. (2016). Cannabis: evolution and ethnobotany. Univ of California Press.

[6] Russo, Ethan B. “The pharmacological history of Cannabis.” Handbook of Cannabis (2014).

[7] McPartland, J. Cannabis: the plant, its evolution, and its genetics—with an emphasis on Italy. Rend. Fis. Acc. Lincei 31, 939–948 (2020). https://doi.org/10.1007/s12210-020-00962-2

[8] The Curious About Cannabis Podcast behind-the-scenes #53 Reggie Gaudino PhD of Front Range Biosciences on Cannabis Genetics, Functional Cultivars, Landrace Biodiversity https://cacpodcast.com/bts-53-reggie-gaudino-phd-of-front-range-biosciences-on-cannabis-genetics-functional-cultivars-landrace-biodiversity/

[9] The Curious About Cannabis Podcast behind-the-scenes #21 Samuel Moore of Hillside Hemp Oregon on Sustainable Farming, Seed Sourcing, CBD https://cacpodcast.com/bts-21-samuel-moore-of-hillside-hemp-oregon-on-sustainable-farming-seed-sourcing-cbd/

[10] Ross, S. A., & ElSohly, M. A. (1996). The volatile oil composition of fresh and air-dried buds of Cannabis sativa. Journal of Natural Products, 59(1), 49-51. https://doi.org/10.1021/np960004a

[11] The Curious About Cannabis Podcast behind-the-scenes #77 The Science of the Cannabis Plant with Allison Justice PhD https://cacpodcast.com/the-science-of-the-cannabis-plant-with-allison-justice-phd-77/

[12] Russo, E. B. (2011). Taming THC: potential cannabis synergy and phytocannabinoid‐terpenoid entourage effects. British journal of pharmacology, 163(7), 1344-1364. https://doi.org/10.1111/j.1476-5381.2011.01238.x

[13] Van Ginneken, C. A. M., Vree, T. B., Breimer, D. D., Thijssen, H. W. H., & Van Rossum, J. M. (1973). Cannabinodiol, a new hashish consituent, identified by gaschromatography-mass spectrometry.

[14] The Curious About Cannabis Podcast behind-the-scenes #79 What’s In a Toke? Exploring the Chemistry of Cannabis Smoke and More with Dr. Riley Kirk https://cacpodcast.com/whats-in-a-toke-exploring-the-chemistry-of-cannabis-smoke-and-more-with-dr-riley-kirk-bts-79/

[15] www.jasonwilsonms.com

[16] www.cacpodcast.com | http://masterclasscannabis.com | http://learn.cacpodcast.com

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S2E2 Into the Endocannabinoidome

In this episode we journey beyond Cannabis and the endocannabinoid system into the endocannabinoidome! The endocannabinoidome is a relatively new concept used to describe the vast hundreds of compounds involved in the functioning of endocannabinoids and cannabinoid receptors. Learn about how this concept of the endocannabinoidome was formed, what clinicians think about its discovery, and what we can expect from the future of endocannabinoidome research! Plus hear an often overlooked story about the origin of “the entourage effect” and how the concept has been redefined for popular culture.

Featuring a contribution from Raphael Mechoulam, PhD via email and relevant excerpts from behind-the-scenes episodes:

BTS #5 Ethan Russo, MD

BTS #31 The Doctors Knox

BTS #35 Vincenzo Di Marzo, PhD

Stay curious, and take it easy!

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#08 The Strain Game: What’s In a Name?

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/

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#07 Cannabidiol (CBD): Hype or Hero?

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!

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#06 A Brief History of The Endocannabinoid System (ECS)

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).

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#05 Cannabis as Medicine – Part Two: Medical Research and Clinical Outcomes

Episode Description: Continuing from our previous episode where we began exploring the idea of Cannabis as medicine, in this episode we dive into exploring how medical claims are derived, what it takes to develop a Cannabis-based 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.
nLet’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.

1. 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?

1. 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

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#03 Is Cannabis Safe? Part Three: Adolescent Use and Harm Reduction

Episode Description: In this episode of the Curious About Cannabis Podcast we wrap up our three-part series on Cannabis safety and harm reduction by exploring the question, “Is Cannabis Safe?”. First we talk about adolescent Cannabis use before discussing ways in which Cannabis users can minimize or eliminate many of the risks associated with Cannabis. Make sure you listen to episodes 1 and 2 prior to listening to this episode!

Episode Transcript:

#03 Is Cannabis Safe? Part Three: Adolescent Cannabis Use and Harm Reduction

You’re listening to the Curious About Cannabis Podcast.

[Reefer Madness Clip]

[Shutter]

Hey everybody, this is Jason Wilson with the Curious About Cannabis podcast, thanks so much for tuning in once again. Over the last two episodes we have been exploring the topic of Cannabis safety and harm reduction. We explored the toxicity of some of the major chemical constituents of Cannabis resins, how Cannabis can interact with medications, and contaminants that could be found in Cannabis products. Now, for this third and final part of this series, we are focusing on the topics of teen Cannabis use before diving into some of the ways that Cannabis users can minimize the potential risks associated with Cannabis use.

So here we go, the third and final part of our series where we explore the question: “Is Cannabis Safe?”

[INTRO MUSIC]

What about adolescent Cannabis use?

What are the risks of exposing children to Cannabis at an early age? As you might imagine, this is a very complicated question. For this episode we are going to ignore the topics of Cannabis use during pregnancy, while breastfeeding, or medical Cannabis use in children. We’ll explore those topics in other episodes. For this episode, we are going to focus on looking at the health risks of adolescent Cannabis use during the teenage years.

The topic of adolescent Cannabis use is a complicated and sensitive topic. Kids today have become very wary of drug education of any kind, primarily because kids have been exposed to tales of exaggerated harms or outright lies about drug use for decades as part of prohibition and abstinence-based drug education programs.[1] [2]

[MATT VOGEL SEGMENT]

This is Matt Vogel. Matt is a health and wellness educator that works with high school and college students to teach about health, substance use, and harm reduction strategies.

[MATT VOGEL SEGMENT]

Regarding Cannabis, kids have been told that it will kill brain cells, lead to schizophrenia or other mental health issues, make them lazy or stupid, or cause them to move on to other drugs like cocaine or heroin.

It should first be pointed out that there are big differences between acute or occasional Cannabis use and chronic Cannabis use. In general, acute Cannabis use is pretty safe, physiologically, with the biggest risks being risks of motor discoordination, which is why it is not a good idea to drive after using THC-rich Cannabis, memory disruption, and psychological distress.[3] However, most of the major risks that adolescents learn about Cannabis are associated with chronic, or repeated, Cannabis use.

While chronic Cannabis use can alter the way the brain functions[4] [5] [6], and we need to understand the consequences of that more, to say that it kills brain cells is dishonest. Cannabis can make some parts of the brain less active while making other parts of the brain more active.[7] In fact, in some cases Cannabis can actually encourage new brain cells to grow in a process called neurogenesis[8] [9].

While Cannabis can exacerbate or reveal underlying mental health problems in adolescents, there is not strong evidence that it actually causes these problems.[10] [11] And the only time that Cannabis seems to act as a gateway to other drugs seems to be when users are exposed to those other drugs on the black market.[12]

The issue of adolescent Cannabis use and IQ is a more complicated problem. Research has confirmed that there does not seem to be a link between Cannabis use and low IQ, but there does seem to be a link between early onset Cannabis use and poor cognitive performance.[13] [14] If you dig through the research, a common theme emerges. The issue is that THC in Cannabis can, in some people, interfere with the learning process, by disrupting attention and memory. Ultimately users that are affected in this way have to work harder to perform as well as they typically would without Cannabis.

Depending on the situation, Cannabis use can also cause kids to avoid social interactions, which can cause problems with the development of emotional intelligence and social skills.[15] [16] [17] Chronic THC-rich Cannabis use can interfere with learning processes at a time when a person is going through critical developmental stages, resulting in poor development into adulthood. Although the brain is not actually a muscle, it acts like one in the sense that if you don’t exercise it, it won’t perform well.

But a lot of these possible outcomes are difficult to assess[18] because there are a lot of variables that affect a person’s cognitive development including social factors, concurrent drug use, such as alcohol use, and underlying mental health disorders to name a few. In addition, everyone responds to Cannabis differently. There are also a wide variety of Cannabis products, with different risks associated with them.

It has to be noted here, that the context of Cannabis use has a lot to do with outcomes. There are children, teens, and adults throughout the world with qualifying medical conditions that are using Cannabis medically and exhibiting very few adverse events.[19] [20] In addition, CBD rich Cannabis or Cannabis products that don’t have intoxicating effects do not present the same psychological health risks as THC rich Cannabis products. Dose is also an important factor to consider. Lower dosages of either THC or CBD present fewer risks than higher doses.

So if Cannabis can be used responsibly, while minimizing adverse events, then what does that look like?[21] When does Cannabis use become Cannabis abuse?

[MATT VOGEL SEGMENT]

One thing I really appreciated about my conversation with Matt was his attention to how complicated this topic is, and that there is no one size fits all answer regarding teen Cannabis use and the potential risks involved. Even just finding reputable information about Cannabis can be challenging in the age of internet headlines and memes

[MATT VOGEL SEGMENT]

So, let’s assume an adolescent has decided that they want to experiment with Cannabis. How long should they wait in order to stay safe?

[MATT VOGEL SEGMENT]

How can people minimize the risks of using Cannabis?

This all begs the next question, what can people do to reduce the risks associated with Cannabis use? From Matt’s perspective, that begins with cultivating a healthy amount of self-awareness regarding not only substance use, but health and wellness in general.

[MATT VOGEL SEGMENT]

And beyond all of that, Matt had a simple recommendation to reduce risk that was echoed by many of my other guests.

[MATT VOGEL SEGMENT]

I asked veteran Cannabis and cannabinoid researcher, Dr. Ethan Russo, about his thoughts on minimizing risks associated with Cannabis use. Right away he wanted to bring attention to the diverse and sometimes uncertain quality of Cannabis products on the market.

[ETHAN RUSSO SEGMENT]

So it’s clear that the first step of minimizing risk is to ensure you find clean, high quality products. But what comes next? Many people understand that it can be a very uncomfortable and unpleasant experience to take too much Cannabis, so what can people do to avoid this?

I spoke with Dr. Jason Miller about this issue. Jason is a doctor of acupuncture and Chinese medicine that is an expert regarding the clinical use of medicinal plants. Recently he started having a lot of patients coming to him to ask about Cannabis, so he began taking note of what their experiences and outcomes were like in order to be prepared to counsel others on the potential pitfalls and promises of Cannabis use.

The first goal, he noted, was to develop strategies to avoid taking too much in the first place…

[JASON MILLER SEGMENT]

Okay, so let’s say you’ve done your best to find your minimum effective dose, and you still went too far and are in the midst of an uncomfortable Cannabis experience. What can be done?

[JASON MILLER SEGMENT]

In case you don’t know, Acetylcholine is a neurotransmitter in our brains that among many things is responsible for influencing things like sleep, arousal, memory, and attention.[22] [23] [24] [25] [26]

[JASON MILLER SEGMENT]

And if you forget all of these suggestions, there are some products on the market now that claim to combat Cannabis intoxication.

[PEGGY ANDERSON SEGMENT]

That’s Peggy Anderson, the founder of a company called Canna Help You? Which is dedicated to providing seniors with education about Cannabis. In one recent study, it was found that the demographic of Cannabis users over the age of 65 is growing faster than any other demographic of older adults. Many of these users don’t want to be intoxicated and are particularly concerned about taking too much THC. Peggy shared some of her experience with this issue.

[PEGGY ANDERSON SEGMENT]

The feedback I got from some of my guests mirrors some of the suggestions found in literature dating back all the way to the 10^th century. See Taming THC by Ethan Russo.[27]

I asked some of my guests whether they thought that Cannabis products, overall were safe or not. The response was consistent. In places where Cannabis is legal and the quality of Cannabis products are regulated, Cannabis seems to be safer than it has ever been.

[ANTHONY SMITH SEGMENT]

[PEGGY ANDERSON SEGMENT]

Alright, Let’s review what we’ve learned, across these past three episodes:

- While the exact level of toxicity of cannabinoids is unclear, we know that cannabinoids are orders of magnitude less toxic than caffeine or nicotine. It is physically impossible to lethally overdose on herbal As far as extracts and concentrates are concerned – there are a lot of unknowns. There is no long-term safety data available yet to understand how chronic consumption of Cannabis concentrates might affect health, however we do know that a variety of contaminants in Cannabis can become concentrated in Cannabis extracts, presenting greater risk to consumers – particularly those that have pre-existing health problems.

- Although Cannabis is unlikely to present the risk of a lethal overdose, there are still health risks to users, including risks to lung health, heart health, mouth health, immune system health and mental health.n
  - - Many of these health risks stem from smoking and can be minimized or eliminated by using other consumption methods like vaporizing[28] or using edibles, tinctures or sublingual products.
  n
  - - Naïve users are at greater risk for experiencing psychological adverse effects than experienced users.[29] Start low, go slow.
  n
  
  n

- Cannabis can potentially interact with other medications.[30] Usually this leads to sedation, but in some cases, particularly with CBD, Cannabis could slow down the body’s ability to metabolize drugs, resulting in elevated concentrations of those drugs in the blood. For anyone taking medications with narrow safety windows, this could be dangerous.

- Some people with pre-existing health conditions could be at greater risk to suffer adverse events from Cannabis use. If you are using Cannabis and have a heart condition, compromised immune system, diabetes, or mental health condition – it’s best to work with a health care professional to make sure you stay safe.

- Cannabis use in adolescents can exacerbate underlying mental health issues. In general it is best for young people to wait as long as possible before trying Cannabis, ideally until the age of 25, as this is the age when the brain is thought to have reached maturity.

- If you decide to use Cannabis, start with a low dose and slowly work your way up. If you end up getting too high, there are a number of home remedies to counteract the effects of THC, including drinking water or warm milk, eating peppercorns or black pepper, taking tinctures of passionflower or calamus root, chewing on pine nuts, or drinking lemonade. There are even some targeted Cannabis antidotes now on the market. In addition, CBD may help curb the effects of THC to some extent.

- Finally, if you consume Cannabis regularly, it’s important to perform regular abstinence breaks and wellness audits to evaluate your relationship with Cannabis to ensure that your Cannabis use is not negatively impacting your health.

So, is Cannabis safe? In toxicology it is well known that nearly anything can be toxic when consumed in a particular way or in a particular dose. In the early 1500s, the swiss physician, alchemist, and astrologer Paracelsus said, “All things are poison, and nothing is without poison. It is the dose alone that makes a thinit so a thing is not a poison.”[31] Today this is often simplified to the saying, “The dose makes the poison.” This applies to everything, including the water we drink and the air we breathe. Nothing in life is without risk, but in general Cannabis is safer, physiologically, than many substances we engage everyday, like coffee.

While there are some rare exceptions and contraindications to be aware of, Cannabis, as long as it is clean, seems to be pretty safe and well tolerated by most people, especially at low doses. Deaths attributed to Cannabis are extremely rare[32] [33], and most adverse events that could arise from Cannabis use, like hyperemesis syndrome[34], are usually reversible. To minimize risk, wait as long as you can to try Cannabis for the first time, avoid smoking, only use Cannabis of a known quality, start with low dosages, and slowly increase dosage to find a minimum effective dose. And remember, if you do take too much THC and are having an uncomfortable experience, there are a variety of things you can do to help ease that uncomfortable feeling, and, most importantly, the feeling will eventually pass and you will be fine.

I know that some of you listening might be wondering about the issue of substance abuse and addiction as a risk, which I did not cover in these episodes. Don’t worry, there will be an episode dedicated to that issue, as well as issues like pediatric Cannabis use and Cannabis use while pregnant or breastfeeding. So stay tuned as we revisit the issue of Cannabis safety in other episodes.

And with that, I’m your host, Jason Wilson. Until next time, stay curious.

[OUTRO Music]

Special thanks to our guests that were so gracious in spending time with me for interviews. To check out the citations for this episode, and there are plenty, you can check out the show notes by visiting CACPodcast.com. If you want to learn more about Cannabis, you can check out the Curious About Cannabis book, available on Amazon.com and other online book retailers. If you like what we are doing and want to support the show please consider supporting the podcast by liking and sharing this episode. You can also support us on Patreon at patreon.com/naturallearningenterprises where you can get access to the full-length guest interviews, behind-the-scenes content, and more! You can also connect with Curious About Cannabis on social media on Instagram, Facebook, Twitter, and YouTube.

[OUTRO Music continues]

Citations:

[1] Rosenbaum DP, et al. Cops in the Classroom: A Longitudinal Evaluation of Drug Abuse Resistance Education (DARE). Journal of Research in Crime and Delinquency. 1994. 31(1): 3-31.

[2] Birkeland S et al. Good reasons for ignoring good evaluation: the case of the drug abuse resistance education (D.A.R.E.) program. Evaluation and Program Planning. 28(3): 247-256.

[3] Karilla L et al. Acute and long-term effects of cannabis use: a review. Curr Pharm Des. 2014. 20(25): 4112-4118

[4] Ashtari M et al. Medial temporal structures and memory functions in adolescents with heavy cannabis use. Journal of Psychiatric Research. 2011. 45(8): 1055-1066.

[5] Demirakca T et al. Diminished gray matter in the hippocampus of cannabis users: possible protective effects of cannabidiol. Drug and Alcohol Dependence. 114(2-3): 242-245.

[6] Steel R et al. Delta-9-tetrahydrocannabinol disrupts hippocampal neuroplasticity and neurogenesis in trained, but not untrained adolescent Sprague-Dawley rats. Brain Research. 2014. 1548: 12-19.

[7] Jager G et al. Cannabis use and memory brain function in adolescent boys: a cross-sectional multicenter functional magnetic resonance imaging study. J Am Acad Child Adolesc Psychiatry. 2010. 49(6): 561-572.

[8] Wolf SA et al. Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis. Cell Communication and Signaling. 2010. 8:12.

[9] Jiang W et al. Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic and antidepressant like effects. Neuroscience. 2005. 115(11): 3104-3116.

[10] Rubino T et al. Adolescent exposure to cannabis as a risk factor for psychiatric disorders. J Psychopharmacol. 2012. 26(1): 177-188.

[11] Johns A. Psychiatric effects of cannabis. Br J Psychiatry. 2001. 178: 116-122.

[12] Hall W and Lynskey M. Is cannabis a gateway drug? Testing hypotheses about the relationship between cannabis use and the use of other illicit drugs. Drug and Alcohol Review. 24(1): 39-48

[13] Jackson N et al. Impact of adolescent marijuana use on intelligence: Results from two longitudinal twin studies. PNAS. 113(5):E500-E508.

[14] Harvey M et al. The relationship between non-acute adolescent cannabis use and cognition. Drug and Alcohol Review. 26(3): 309-319.

[15] Nehra DK et al. Emotional intelligence and self esteem in cannabis abusers. Journal of the Indian Academy of Applied Psychology. 38(2): 385-393.

[16] Nehra DK et al. Alexithymia and emotional intelligence among people with cannabis dependence and health control: a comparative study. Dysphrenia. 2013. 5(1): 49-55.

[17] Limonero JT et al. Perceived emotional intelligence and its relation to tobacco and cannabis use among university students. Psicothema. 2006. 18: 95-100.

[18] Pope HG et al. Early-onset cannabis use and cognitive deficits: what is the nature of the association? Drug and Alcohol Dependence. 2003. 69(3):303-310.

[19] Sznitman SR and Zolotov Y. Cannabis for therapeutic purposes and public health and safety: a systematic and critical review. International Journal of Drug Policy. 2015. 26(1): 20-29

[20] Blake DR et al. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology. 2005. 45(1): 50-52.

[21] Lau N et al. Responsible and controlled use: older cannabis users and harm reduction. International Journal of Drug Policy. 2015. 26(8): 709-718.

[22] Acetylcholine. Neuroscience. 2^nd Edition. https://www.ncbi.nlm.nih.gov/books/NBK11143/

[23] Miyazawa M and Yamafuji C. Inhibition of Acetylcholinesterase Activity by Bicyclic Monoterpenoids. J Agric Food Chem. 2005. 53(5): 1765-1768.

[24] Ryan MF and Byrne O. Plant-insect coevolution and inhibition of acetylcholinesterase. Journal of Chemical Ecology. 1988. 14(10): 1965-1975.

[25] Pattanaik J et al. Acorus calamus Linn.: A herbal tonic for central nervous system. Journal of Scientific and Innovative Research. 2013. 2(5): 950-954.

[26] Mukherjee PK et al. In vitro Acetylcholinesterase inhibitory activity of the essential oil from Acorus calamus and its main constituents. Planta Med. 2007. 73(3): 283-285.

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

[28] Abrams D et al. Vaporization as a Smokeless Cannabis Delivery System: A Pilot Study. Clinical Pharmacology and Therapeutics. 82(5): 572-578.

[29] Volkow ND et al. Adverse Health Effects of Marijuana Use. N Engl J Med. 2014. 370: 2219-2227.

[30] Bornheim LM et al. Characterization of cannabidiol-mediated cytochrome P450 inactivation. Biochemical Pharmacology. 1993. 45(6): 1323-1331.

[31] Paracelsus, dritte defensio, 1538.

[32] Gargani Y et al. Too Many Mouldy Joints – Marijuana and Chronic Pulmonary Aspergillosis. Mediterr J Hematol Infect Dis. 2011. 3(1): e2011005.

[33] Bachs L and Morland H. Acute cardiovascular fatalities following cannabis use. Forensic Science International. 2001. 124(2-3): 200-203.

[34] Simonetto DA et al. Cannabinoid Hyperemesis: A Case Series of 98 Patients. Mayo Clinic Proceedings. 87(2): 114-119.

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#02 Is Cannabis Safe? – Part Two: Contaminants in Cannabis

Episode Description: Continuing from our previous episode, we continue exploring the basic question, “Is Cannabis Safe?”, this time focusing on contaminants that could be found in Cannabis or Cannabis products. We speak with biochemist Dr. Anthony Smith about what contaminants labs are commonly finding in Cannabis. We also speak with herbal scientist, Travis Simpson, about his concerns regarding Cannabis processing operations and the potential contaminants that may be introduced to products through bad manufacturing practices. Finally we talk again with neurologist and cannabinoid researcher, Dr. Ethan Russo, to discuss the “vaping crisis” that has claimed the lives of as many as 37 people in the United States and affected nearly 2000 users. This is part two of a three part series exploring the question, “Is Cannabis Safe?”

Transcript:

You’re listening to the Curious About Cannabis Podcast.

[Intro Preview]

[Shutter]

Hey everybody, this is Jason Wilson with the Curious About Cannabis podcast. Thanks so much for tuning in once again. This episode is part two of a three-part series exploring Cannabis safety and harm reduction. If you haven’t listened to the first part of this series, I really recommend stopping this episode and going back to listen to this series from the beginning.

Previously we explored some of the main chemicals in Cannabis, the adverse health risks associated with Cannabis, and how Cannabis can interact with medications.[1] Today we will be focusing on a critical topic that has a huge impact on the safety of Cannabis products – Cannabis contaminants.

[INTRO MUSIC]

What contaminants might be found in Cannabis products?

Anthony Smith is a biochemist that has spent that last five years analyzing Cannabis products for potency and purity in labs all across the United States and Canada.

[ANTHONY INTERVIEW SEGMENT]

Before we continue, let’s talk a little more about pesticides. Many pesticides are designed to disrupt the nervous systems or hormone signaling in insects.[2] The problem is that this same effect can happen in humans, if someone is exposed to enough of a certain pesticide for long enough periods of time.[3] Additionally, some pesticides, like myclobutanil, a common fungicide[4], can degrade into toxic compounds like hydrogen cyanide when heated.[5]

You might be thinking, what’s the big deal about pesticides in Cannabis? Aren’t we already exposed to pesticides through our food? Well, that’s true, but the problem relates to the way in which Cannabis is consumed. When you eat something, your body works hard to ensure that any toxins are captured, broken down, and excreted from the body before they have a chance to reach your blood stream.[6] But when you smoke something, you are bypassing those metabolic processes, and the compounds that enter the lung will pass directly into the blood stream.[7] So essentially when you smoke you are bypassing your body’s natural defense systems that might otherwise keep you safer.

It’s also really important to point out that many pesticides, as well as mycotoxins, can become concentrated in Cannabis extracts. The process of making a Cannabis concentrate can elevate contaminants like pesticides as much as 5 to 10 times the concentration found in the Cannabis flower[8], meaning that if you are consuming a Cannabis concentrate, you are potentially being exposed to much greater doses of contaminants than if you were consuming the Cannabis flower used to produce that concentrate. I also want to point out that it’s not enough to simply test Cannabis flower for contaminants prior to making a concentrate. It is possible for there to be very trace amounts of pesticides or other contaminants present in the flower that won’t show up on a standard contaminant screening – but when concentrated they suddenly become present in dangerous levels.

[BACK TO ANTHONY SMITH SEGMENT]

The leaching of contaminants[9] [10] from cultivation, processing or packaging equipment is an issue that people working in the natural products industry have had to think about for quite some time. However some Cannabis companies are still learning about typical herbal processing and manufacturing best practices – putting consumers at risk. I spoke with Travis Simpson, an herbal scientist that has spent the past several years working with hemp in the Cannabis industry. He shared some of his concerns regarding contaminants from manufacturing and packaging equipment.

[TRAVIS SIMPSON SEGMENT]

One of the important things to note regarding most of these contaminants, including pesticides, metals, and mycotoxins, is that you won’t necessarily have an immediate reaction when you are exposed to these toxins. They can build up in the body over time, and you may not exhibit any symptoms for a long time before the body finally reaches a tipping point.[11] So just because you may have consumed a Cannabis product and didn’t notice any adverse effects, that does not mean that you are not being exposed to harmful contaminants.

The takeaway from my discussions was clear – know the purity of your Cannabis before consuming. But this is easier said than done. There are still many places in the US and abroad that have not legalized Cannabis or established strict testing requirements for Cannabis.[12] For users getting their Cannabis from the black market, they are left at the mercy of their supplier’s quality.

Unfortunately, this can sometimes lead to tragic consequences.

[ETHAN RUSSO SEGMENT]

Dr. Russo is referring to a recent string of fatalities linked to lung infections or lung damage associated with vape pens.[13]

[“VAPE CRISIS” NEWS REEL]

At the time of this recording, there have been 29 recorded deaths, and over 1300 reported cases of lung infections or damage linked to vape pens[14]. And these reports are growing at a rapid rate. While the exact culprit responsible for these illnesses and deaths has not yet been identified, investigators suspect it has to do with additives or contaminants.

[CONTINUE ETHAN RUSSO SEGMENT]

There is other evidence that contaminants in Cannabis have caused very serious problems for some people, which in rare cases has led to death. There are several case studies available of patients that contracted fatal lung infections, such as a condition called aspergillosis.[15] [16] Aspergillosis is a condition where the spores of certain species of Aspergillus fungi get nestled in small scrapes and crevices in the lungs where they begin to grow, forming a fungal mass called an aspergilloma[17]. This ultimately starts to break down lung function and can be fatal. In some fatal aspergillosis cases reported, contaminated Cannabis was deemed to be a contributing factor, and possibly the sole cause.[18]

This is more common in immunocompromised users than regular healthy users, but that just highlights the tragedy here. Many people with serious health conditions are turning to Cannabis as a medicine – and those patients are the ones most vulnerable to the adverse health effects of consuming contaminated Cannabis.

So let’s review what we’ve learned so far:

- There are a lot of different contaminants that can appear in Cannabis and Cannabis products such as pesticides, residual solvents, metals, mycotoxins, molds, and bacteria.

- Metals and molds tend to appear most frequently in Cannabis flower, however metals do sometimes show up in extracts due to leaching from incompatible packaging

- Bacteria tend to appear most frequently in Cannabis infused products.

- Pesticides, solvents, and mycotoxins are more common in Cannabis extracts, because the process of making a concentrate actually concentrates these contaminants.

- Contamination is not always direct. Contamination can come from contaminated soil, water, drift from nearby farms, leaching from manufacturing equipment or packaging equipment.

- Contaminants or toxic additives have been responsible for fatalities associated with Cannabis consumption. Users with compromised immune systems are the most at risk.

By now we seem to be getting a pretty good picture about the safety profile of Cannabis. But we’re not done yet. There is one more issue that we haven’t discussed yet – and that’s adolescent Cannabis use. What unique risks might young Cannabis users face?

Find out in the third and final part of this series where we finish our curious quest to discover, “Is Cannabis Safe?”

[OUTRO MUSIC]

Citations and Resources

[1] “#01 Is Cannabis Safe? Part One”. The Curious About Cannabis Podcast. Natural Learning Enterprises. 2019. https://cacpodcast.weebly.com/episodes/01-is-cannabis-safe-part-one

[2] How Pesticides Work. Kentucky Pesticide Safety Education Program. http://www.uky.edu/Ag/Entomology/PSEP/12pesticides.html

[3] Kim et al. Exposure to pesticides and the associated human health effects. Science of the Total Environment. 2017. 575(1): 525-535.

[4] https://www.nbcnews.com/health/vaping/tests-show-bootleg-marijuana-vapes-tainted-hydrogen-cyanide-n1059356

[5] Product Safety Assessment: Myclobutanil. Dow Chemical. http://msdssearch.dow.com/PublishedLiteratureDOWCOM/dh_08d6/0901b803808d60fd.pdf?filepath=productsafety/pdfs/noreg/233-01023.pdf&fromPage=GetDoc

[6] Pond SM, Tozer TN. First-pass elimination. Basic concepts and clinical consequences. Clin Pharmacokinet. 1984. 9(1): 1-25.

[7] Huestis MA. Human Cannabinoid Pharmcokinetics. Chem Biodivers. 2009. 4(8): 1770-1804.

[8] Voelker R, Holmes M. Pesticide Use on Cannabis. Cannabis Safety Institute. 2015. https://cannabissafetyinstitute.org/wp-content/uploads/2015/06/CSI-Pesticides-White-Paper.pdf

[9] https://www.coleparmer.com/chemical-resistance

[10] https://www.scilabware.com/en/chemicalcompatibility/

[11] Williams et al. Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences, and interventions. The American Journal of Clinical Nutrition. 2004. 80(5):1106-1122.

[12] https://norml.org/laws

[13] https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html

[14] https://www.sciencenews.org/article/vaping-tied-nearly-1300-lung-injuries-29-deaths-united-states

[15] Gargani et al. Too Many Mouldy Joints – Marijuana and Chronic Pulmonary Aspergillosis. Mediterr J Hematol Infect Dis. 2011. 3(1): e2011005.

[16] Ruchlemer et al. Inhaled medicinal cannabis and the immunocompromised patient. Support Care Cancer. 2015. 23(3):819-822.

[17] https://www.mayoclinic.org/diseases-conditions/aspergillosis/symptoms-causes/syc-20369619

[18] Gargani et al. Too Many Mouldy Joints – Marijuana and Chronic Pulmonary Aspergillosis. Mediterr J Hematol Infect Dis. 2011. 3(1): e2011005.

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#01 Is Cannabis Safe? – Part One

Episode One: Is Cannabis Safe? Part One

Welcome to the very first episode of the Curious About Cannabis podcast! Briefly I wanted to introduce the podcast and let you know what to expect. There are two different types of podcast episodes that we’ll be presenting this season. Each primary episode, like this one, is a 20 – 30 minute beginner to intermediate educational episodes exploring a critical Cannabis topic or question. Accompanying the primary episodes are behind-the-scenes episodes. A behind-the-scenes episode features a full-length interview or conversation between myself and a guest, typically running anywhere from 45 minutes to two and a half hours. These behind-the-scenes episodes are more for anyone wanting a deeper dive into some of the content covered in the primary episodes.

Each primary episode has accompanying show notes that feature the show transcript and citations so you can explore any of the topics we present more deeply in your own time. You can find these show notes at CACPodcast.com

I am really excited to finally be sharing this content with you. I hope you enjoy it and find it valuable. And with that, I present the first episode of the Curious About Cannabis podcast.

– Jason Wilson

===========================================================

You’re listening to the Curious About Cannabis Podcast

[Shutter]

[NURSE JANNA SEGMENT]

The combined North American Cannabis market alone is expected to exceed 16 billion dollars in value in 2019.[1] People all over the world are taking notice and becoming more curious than ever about Cannabis. The momentum of Cannabis legalization across the world does not seem to be slowing down. And as more places legalize Cannabis, broader demographics of Cannabis users are emerging.[2]

As more and more people are trying Cannabis without fear of legal repercussions, I wanted to understand just how safe Cannabis products are or aren’t.

[INTRO MUSIC]

How safe is Cannabis, really?

Hey everybody, this is Jason Wilson with the Curious About Cannabis Podcast. Thanks for tuning in. Today we are going to be talking all about Cannabis safety and harm reduction in an effort to understand whether Cannabis is really as safe as many people claim.

To start our curious quest, we’ll be focusing on three main questions:

- How toxic is Cannabis? And as an aside, what the heck is in Cannabis anyway?

- What are the known health risks of Cannabis use?

- How can anyone that chooses to use Cannabis or Cannabis products minimize those risks?

Now, this is a really big topic that we could spend hours upon hours exploring. And in effect this topic will end up being woven throughout the podcast. As such, there are several aspects of Cannabis safety that we won’t be getting into in this initial series of episodes. So if there is a topic we don’t end up covering immediately – don’t worry. We’ll get there.

Let’s get started.

What’s in Cannabis?

Cannabis contains a lot of different chemicals. Depending on what research paper you read, there are anywhere from 400 to over 500 compounds that have been characterized in Cannabis so far.[3] [4] [5] But some researchers think there are likely far more chemicals in Cannabis, as well as other plants generally, than have been identified so far.

[KEVIN SPELMAN SEGMENT]

That’s Kevin Spelman, a molecular biologist and phytochemist that has dedicated his professional career to understanding why plants affect the body the way they do. And lately, he has had his eyes on Cannabis.

[KEVIN SPELMAN SEGMENT]

So despite what the scientific literature says, there very well may be a thousand or more chemicals found in Cannabis.

When Cannabis is burned, however…[6]

[JUSTIN FISCHEDICK SEGMENT]

That’s Justin Fischedick, a natural products researcher that once burned Cannabis joints to see what was in the smoke…for science.[7]

[CONTINUE FISCHEDICK QUOTE]

Cannabinoids, like THC or CBD, are by far the most abundant compounds found in the resins surrounding the female Cannabis flowers. To be accurate, these compounds actually start off in the plant as THCA and CBDA. When heated, THCA and CBDA change into their well-known counterparts, THC and CBD.

So how toxic is THC and CBD?

How toxic are cannabinoids?

In one now famous study in 1973, dogs were given THC orally in escalating doses all the way up to 9 grams of THC per kilogram of body mass in an attempt to find a lethal dose.[8] To put that into perspective, it’s not uncommon for a lot of dogs to weigh somewhere between 20 and 30 lbs. In kilograms, that would be 9 – 14kg. For a 9kg dog, this study would have administered 81 grams of THC in a single dose. If we assume that a Cannabis cigarette, or joint, contains a gram of Cannabis containing 20% THC, that’s the equivalent of approximately 400 joints, or over 115 grams of concentrate…at once!

Now, let’s jump forward from 1973 to 1988 – there was a petition to try to reclassify the legal status of Cannabis. Cannabis was and is currently at the time of this recording considered a schedule one drug by the Drug Enforcement Agency. This category of drugs is reserved for drugs with no accepted medical use and a high propensity for abuse. Other drugs in this category include things like heroin and bath salts.

Well, in the 80s there was a push to reschedule Cannabis, and administrative law judge Francis young issued a report commenting on the issue. In his report, he stated: “…in order to induce death, a marijuana smoker would have to consume 20,000 to 40,000 times as much marijuana as is contained in one marijuana cigarette…A smoker would theoretically have to consume nearly 1500 pounds of marijuana within about fifteen minutes to induce a lethal response.”[9]

By that measure, the carbon monoxide and tar exposure would end up causing problems before the cannabinoids in the Cannabis would.

But that was THC. What about CBD? As recently as this year, in 2019, a report was issued claiming that CBD was identified as being toxic for the liver.[10] Publications like Forbes promoted headlines reading “CBD Causes Liver Damage”[11]. So is this something Cannabis consumers need to be concerned about?

[ETHAN RUSSO SEGMENT]

I had the chance to talk about the safety of CBD with Dr. Ethan Russo, a neurologist and cannabinoid researcher that worked as a medical advisor for the development of two cannabinoid pharmaceuticals, Sativex and Epidiolex. Epidiolex, specifically, is a pure CBD pharmaceutical.

[ETHAN RUSSO SEGMENT]

If you look up the LD50 for Cannabidiol, you’ll typically find data reporting intravenous doses of over 200mg/kg.[12] [13]It would be extremely difficult to get that much CBD in your bloodstream through typical consumption methods. For an average human that weighs 65kg, or around 144lbs, 200mg/kg equates to a dose of approximately 13,000mg, or 13 grams of pure CBD – in the bloodstream. Consider that CBD-rich Cannabis contains approximately 10-20% CBD, or 100 to 200 mg of CBD per gram of Cannabis flower. So if you consume a gram of CBD-rich Cannabis flower, you are getting exposed to maybe 200mg of CBD at best. Ignoring the fact that CBD is not very bioavailable and much of the CBD you consume is simply excreted[14] [15], 200mg is approximately 1.5% of 13 grams.

To put this into better context, for caffeine, the LD50 is 200mg/kg of oral caffeine (that’s not to say that it is the same as the 200mg/kg LD50 that I mentioned for CBD. Keep in mind that the CBD LD50 is intravenous. this is actually a lot lower than the CBD LD50, because not all of the orally consumed caffeine will make it into the bloodstream), which would be like drinking somewhere between 75 and 100 cups of coffee back to back.[16] While for nicotine, the LD50 is around 8 – 13mg/kg, or over half a gram of nicotine.[17] That’s about 40 cigarettes.[18] [19]

You may be saying, okay sure, it may be difficult to overdose on THC or CBD, but Cannabis contains a lot more chemicals than THC – and you’d be right! So just how many reported deaths are there associated with Cannabis use?

While many advocates of Cannabis claim that there have been no deaths attributed to Cannabis – that is not exactly true, however the number is still very low. Like extremely low. We don’t know the exact numbers, but there have been a handful of case studies reported that have linked fatal heart attacks and lung infections with Cannabis use, but these reports have been difficult to confirm definitively.[20] [21] [22] [23] [24] [25] [26]And yet according to some estimates there are nearly 100 million people in the United States alone that admit to having at least tried Cannabis once, and over 30 million are classified as regular users – and that’s just based on how many people are willing to admit their own Cannabis use on a survey.[27]

So, we are looking at a handful of possible fatalities linked to Cannabis use, compared to tens of millions of users in the United States alone. Let’s assume 1 out of 10 million users were to die from Cannabis use in some way, that would mean that you would have a 0.00001% chance of dying from Cannabis use, and even that’s an exaggerated number. You would have a much greater chance of dying by getting into a car crash[28] or getting struck by lightning[29].

What are the health risks of Cannabis?

So, okay, it is unlikely that anyone is going to experience a lethal overdose of Cannabis, but what about other health risks?

[REEFER MADNESS SEGMENT]

All reefer madness and propaganda aside,

There are a variety of research papers out there that have summarized the common health risks of Cannabis use.

One common symptom of Cannabis use is dry mouth, also called xerostomia. Xerostomia can negatively affect mouth health if not managed properly and can lead to changes to the bacteria and fungi that live in our mouths, potentially leading to gum disease, tooth decay, bad breath, and even an altered sense of taste.[30] Now, many may assume that the dry mouth effect from Cannabis use is related to smoking, but this does not seem to be the case. The dry mouth effect is directly linked to the stimulation of cannabinoid receptors in the body, regardless of how you choose to use Cannabis.[31]

Another thing Cannabis affects directly is blood pressure. Interestingly enough, Cannabis can lead to lower blood pressure with repeated use, but at high dosages, Cannabis can cause elevated blood pressure and heart rate[32], which can be particularly problematic for users that have a prior history of heart issues, such as high blood pressure or previous occurrence of heart attacks. This effect is made worse by smoking.

Additionally, if you are smoking Cannabis, you also run a greater risk of experiencing chronic bronchitis and emphysema.[33]

THC-rich Cannabis can cause motor coordination disruption, potentially increasing the risk of falls, home or workplace accidents, and car wrecks. However, this effect tends to be more mild in frequent users that have built up tolerance.

THC-rich Cannabis can present several psychological health risks to users, including memory disruption, anxiety, fear, and paranoia. When it comes to the negative psychological effects of Cannabis, new or infrequent users are more likely to experience these effects compared to regular users.[34] Additionally Cannabis can act as a precipitating event for mental health problems to reveal themselves in younger users – but we will talk more about that later.

Although Cannabis has gained popularity for being a potential treatment for seizure and tremor conditions like epilepsy and Parkinson’s, there has been some research that has revealed that Cannabis could actually exacerbate these conditions in as much as a third of the population.[35]

In addition to these risks, there is also a condition that can develop in chronic users, usually in users that have been using high THC Cannabis regularly for two years or more, called Cannabinoid Hyperemesis Syndrome.[36]

[CHS NEWS REEL]

The good news is that for anyone that may experience this condition, it typically goes away if you simply stop consuming Cannabis for a while. However, there are some reported cases where users that stopped using Cannabis to recover, re-experienced the nausea and vomiting symptoms when they starting using Cannabis again.

Cannabinoid hyperemesis syndrome is a somewhat controversial condition. Some people claim that it is likely caused by contaminants in Cannabis products, rather than the cannabinoids found in Cannabis. However, this has not been substantiated, as of yet. Also, in states that have legalized Cannabis use, reports of this condition are starting to become more prevalent as people become more comfortable talking about their Cannabis use with their health care providers. So, potentially this condition is actually more widespread than once thought. We just don’t really know, yet.

How might Cannabis interact with other medications?

The next topic I wanted to explore is drug interactions with Cannabis.

[NURSE JANNA INTERVIEW SEGMENT]

That’s Janna Champagne, a registered nurse who over the past several years has focused her attention almost exclusively on Cannabis.

[CONTINUE NURSE JANNA SEGMENT]

Other health care professionals I spoke with said that they are particularly concerned about interactions with things like blood thinning medications, chemotherapy drugs, epilepsy drugs, and immune system therapy drugs, like HIV treatments.

Some of this concern regarding drug interactions relates to CBD more than THC. And this has everything to do with a thing called “the grapefruit effect”.[37] It’s been long known that certain foods and medications can change the way the body metabolizes things, like other foods and drugs. This effect is so well known with grapefruit that some drugs even have a grapefruit warning on them. If you ever see a grapefruit warning on a medication, it is referring to this potential interaction that could occur where compounds in the grapefruit can slow down the liver’s ability to metabolize a lot of different medications by inhibiting a group of enzymes called the P450 enzymes. This inhibition will cause the levels of medications in the blood to rise. For people taking drugs with narrow safety windows, this can be very problematic.

Well, it turns out that CBD exhibits this same effect, the grapefruit effect. [38] Anyone using CBD, particularly high doses of CBD, along with other medications should be particularly cautious and work with a healthcare professional to stay safe.[39]

So, while it seems like Cannabis is relatively safe compared to a lot of other things, like coffee, there are some serious drug interactions that can occur.

[CONTINUE NURSE JANNA SEGMENT]

Let’s review what we’ve learned so far:

- The primary constituents of Cannabis resins, THC and CBD, are not toxic and it is virtually impossible to lethally overdose on Cannabis or Cannabis products.

- There are other health risks associated with Cannabis use, however, like risks to lung health, mouth health, mental health, and heart health. Many of these risks can be minimized by avoiding smoking and using low doses.

- Cannabis can interact with medications and anyone taking drugs with narrow safety windows or a grapefruit warning on them should work with a health care professional to stay safe.

So far everything we have explored about the health risks of Cannabis have ignored a critical element – contaminants.

Join me in part two of this series as we explore the health risks of contaminants and additives in Cannabis products. Until next time, thanks and take it easy.

[OUTRO MUSIC]

CITATIONS

[1] Legal marijuana industry had banner year in 2018 with $10B worth of investments. https://www.nbcnews.com/news/us-news/legal-marijuana-industry-had-banner-year-2018-10b-worth-investments-n952256

[2] Han et al. Demographic trends among older cannabis users in the United States, 2006-13. Addiction. 2017. 112(3): 516-525

[3] ElSohly MA. Chemical Constituents of Cannabis. Cannabis and Cannabinoids: Pharmacology, Toxicology and Therapeutic Potential. 2002. Chapter 3.

[4] ElSohly MA, Gul W. Constituents of Cannabis Sativa. Handbook of Cannabis. Oxford University Press. 2014. First Edition.

[5] ElSohly M.A., Radwan M.M., Gul W., Chandra S., Galal A. (2017) Phytochemistry of Cannabis sativa L.. In: Kinghorn A., Falk H., Gibbons S., Kobayashi J. (eds) Phytocannabinoids. Progress in the Chemistry of Organic Natural Products, vol 103. Springer, Cham

[6] O’Brien Fehr K, Kalant H. Analysis of Cannabis Smoke Obtained Under Different Combustion Conditions. 1972. Canadian Journal of Physiology and Pharmacology. 50(8): 761-767.

[7] Fischedick J, Van Der Kooy F, Verpoorte R. Cannabinoid receptor 1 binding activity and quantitative analysis of Cannabis sativa L. smoke and vapor. 2010. Chem Pharm Bull (Tokyo). 58(2):201-7.

[8] Thompson GR et al. Comparison of acute oral toxicity of cannabinoids in rats, dogs and monkeys. 1973. Toxicology and Applied Pharmacology. 25(3):363-372.

[9] Young F. In the Matter of Marijuana Rescheduling Petition. Opinion and recommended Ruling, Findings, of Fact, Conclusions of Law and Decision of Administrative Law Judge. Sep 6 1988. Part VIII.

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

[11] Adams M. Marijuana Study Finds CBD Can Cause Liver Damage. Forbes. Jun 18 2019. https://www.forbes.com/sites/mikeadams/2019/06/18/marijuana-study-finds-cbd-can-cause-liver-damage/

[12] Rosenkrantz H et al. Toxicity of short-term administration of cannabinoids to rhesus monkeys. 1981. Toxicol Appl Pharmacol. 58(1):118-31.

[13] Cannabidiol. ChemIDplus Database. https://chem.nlm.nih.gov/chemidplus/rn/13956-29-1

[14] Millar et al. A Systematic review on the pharmacokinetics of cannabidiol in humans. 2018. Pharmacol. https://www.frontiersin.org/articles/10.3389/fphar.2018.01365/full

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

[16] Caffeine. Toxnet Toxicology Data Network. https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+36

[17] Mayer B. How much nicotine kills a man? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century. 2014. Arch Toxicol. 88(1): 5-7.

[18] Taghavi S et al. Nicotine content of domestic cigarettes, imported cigarettes and pipe tobacco in Iran. 2012. Addict Health. 4(1-2): 28-35.

[19] Benowitz NL, Henningfield JE. Reducing the nicotine content to make cigarettes less addictive. 2013. Tobacco Control. 22:i14-i17.

[20] Yurtdas M, Aydin MK. Acute myocardial infarction in a young man; fatal blow of the marijuana: a case report. 2012. Korean Circ J. 42(9): 641-645.

[21] Hartung B et al. Sudden unexpected death under acute influence of cannabis. 2014. Forensic Science International. 237: e11-e13

[22] Sattout AH, Nicol MF. Cardiac arrest following cannabis use: a case report. 2009. Cases Journal. 2(208)

[23] Cappelli F et al. Cannabis: a trigger for acute myocardial infarction? A case report. 2008. Journal of Cardiovascular Medicine. 9(7):725-728.

[24] MacInnes DC, Miller KM. Fatal coronary artery thrombosis associated with cannabis smoking. 1984. J R Coll Gen Pract. 34(267): 575-576.

[25] Ruchlemer R et al. Inhaled medicinal cannabis and the immunocompromised patient. 2015. Supportive Care in Cancer. 23(3): 819-822.

[26] Gargani Y et al. Too Many Mouldy Joints – Marijuana and Chronic Pulmonary Aspergillosis. 2011. Mediterr J Hematol Infect Dis. 3(1): e2011005

[27] Yahoo News/Marist Poll: Weed and the American Family. April 17, 2017. Marist Poll. http://maristpoll.marist.edu/yahoo-newsmarist-poll/#sthash.VAK0GIiK.dpbs

[28] Traffic Safety Facts 2017: A Compilation of Motor Vehicle Crash Data. 2017. National Highway Traffic Safety Administration. US Department of Transportation.

[29] Lightning Safety Tips and Resources. National Weather Service. National Oceanic and Atmospheric Administration. https://www.weather.gov/safety/lightning

[30] Versteeg PA et al. Effect of cannabis usage on the oral environment: a review. 2008. International Journal of Dental Hygiene. 6(4): 315-320.

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Meet the Cannabis Plant: Exploring the Evolutionary History and Lifecycle of Cannabis | Feature #11

S2E2 Into the Endocannabinoidome

#08 The Strain Game: What’s In a Name?

#07 Cannabidiol (CBD): Hype or Hero?

#06 A Brief History of The Endocannabinoid System (ECS)

#05 Cannabis as Medicine – Part Two: Medical Research and Clinical Outcomes

#03 Is Cannabis Safe? Part Three: Adolescent Use and Harm Reduction

#03 Is Cannabis Safe? Part Three: Adolescent Cannabis Use and Harm Reduction

#02 Is Cannabis Safe? – Part Two: Contaminants in Cannabis

#01 Is Cannabis Safe? – Part One

Episode One: Is Cannabis Safe? Part One

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