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Wild Rose College of Natural Healing CANNABIS : An Introduction for Healthcare Providers By Terry Willard ClH, PhD & Jeananne Laing ClH Wild Rose College of Natural Healing Terry Willard Cl.H PhD. ©2019 1 Cannabis : An Introduction for Healthcare Providers Human First Uses of Cannabis Looking up from digging a root in the rich soil she caught a somewhat sweet, almost rotten smell on the chilled air of early autumn. Perhaps there was a wounded or freshly killed animal nearby. That would be a find. The men on the high central Asian steppes hadn’t been that lucky since they had been pushed out of their homeland into this new grassy environment. They had to learn everything anew. With a careful search she found the scent was coming from a plant almost twice her height. The plant was heavy with seeds. Crushed between her fingers, they were sticky and the aromatic smell quickly transferred to her skin. Taking a little taste, she realized that the seeds were full of much sought after oils. The insides of the seeds were soft, oily with a rich taste. She added handfuls to her small collection of roots as she headed back to the base camp. It wasn’t safe to wander off too far and be out a long time on one’s own in this new land. When she got back, she shared the new plants and seeds with her people, accidently dropping several seeds at the campsite when she was separating them. This was the first time her group had seen the cannabis plant. The next year she noticed that several of these new plants now grew around their seasonal campsite, especially near the dung heap. It didn’t take long before people started exploiting the plant for other uses. It made great fiber and if you ate enough seeds it gave an interesting feeling. The tribe’s medicine woman said that it could be used as a healing medicine, so cannabis went on the list of plants that were collected in their foraging journeys. This kind of scene, of discovery and usage, was playing out regularly some 30 – 40,000 years ago, as populations moved into new territory due to various pressures across the great Asian steppes. In 2016 it was hypothesized that the first cannabis originated upon the Northern Tibetan Plateau in Central Asia, around 27.8 million years ago, when it diverged from Hops (Humulus sp). 1 We know that human remains
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Wild Rose College of Natural Healing By Terry Willard ClH ... · thought to possess a spiritual essence). Cannabis played an important role in Aryan rituals. According to the Vedas,

Jun 20, 2020

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Page 1: Wild Rose College of Natural Healing By Terry Willard ClH ... · thought to possess a spiritual essence). Cannabis played an important role in Aryan rituals. According to the Vedas,

Wild Rose College of Natural Healing CANNABIS: An Introduction for Healthcare Providers By Terry Willard ClH, PhD & Jeananne Laing ClH

Wild Rose College of Natural Healing Terry Willard Cl.H PhD. ©2019 1

Cannabis: An Introduction for Healthcare Providers

Human First Uses of Cannabis Looking up from digging a root in the rich soil she caught a somewhat sweet, almost rotten smell on the chilled air of early autumn. Perhaps there was a wounded or freshly killed animal nearby. That would be a find. The men on the high central Asian steppes hadn’t been that lucky since they had been pushed out of their homeland into this new grassy environment. They had to learn everything anew. With a careful search she found the scent was coming from a plant almost twice her height. The plant was heavy with seeds. Crushed between her fingers, they were sticky and the aromatic smell quickly transferred to her skin. Taking a little taste, she realized that the seeds were full of much sought after oils. The insides of the seeds were soft, oily with a rich taste. She added handfuls to her small collection of roots as she headed back to the base camp. It wasn’t safe to wander off too far and be out a long time on one’s own in this new land. When she got back, she shared the new plants and seeds with her people, accidently dropping several seeds at the campsite when she was separating them. This was the first time her group had seen the cannabis plant. The next year she noticed that several of these new plants now grew around their seasonal campsite, especially near the dung heap. It didn’t take long before people started exploiting the plant for other uses. It made great fiber and if you ate enough seeds it gave an interesting feeling. The tribe’s medicine woman said that it could be used as a healing medicine, so cannabis went on the list of plants that were collected in their foraging journeys. This kind of scene, of discovery and usage, was playing out regularly some 30 – 40,000 years ago, as populations moved into new territory due to various pressures across the great Asian steppes. In 2016 it was hypothesized that the first cannabis originated upon the Northern Tibetan Plateau in Central Asia, around 27.8 million years ago, when it diverged from Hops (Humulus sp).1 We know that human remains

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have been found in this region from 40,000 years ago. Cannabis might have attracted first settlers for its food and fiber use. The earliest direct evidence for human use is 10,200-year-old cannabis seeds found in clay jars at a Jomon Japanese archaeological excavation on the island of Okinoshima, near the city of Munakata. Others believe that its first use was around 200,000 years ago during the first occurrence of Homo sapiens- anatomical modern humans (AMH).

A Brief History of Cannabis Use Cannabis was widely spread across Eurasia 5,000 years ago. This plant played a prominent role in many cultures of that era. The earliest known written source of information was in the Shen-Nung some 4,700 years ago. The knowledge of it medicinal uses were incorporated into the Pen-ts’ao Ching (1758 CE) of China. From 1500 – 200 BCE cannabis was used as a medicine in the Mediterranean region, in Egypt, Greece and India. Some scholars believed it was the key ingredient in the holy anointment oil referred to in the Hebrew Old Testament as q’neb bosm. It is safe to say it has played a prominent role as a medicine, fiber and sacramental drug in many cultures throughout the world across millennia. The Aryan religion of India was animistic (that is, it focused on non-human entities—such as animals, plants, and inanimate objects—which were thought to possess a spiritual essence). Cannabis played an important role in Aryan rituals. According to the Vedas, the four seminal books of the Hindu faith written in Vedic (early) Sanskrit, around 1100 BCE the god Shiva brought cannabis down from the Himalayas for the pleasure of mankind. According to legend, cannabis was created when the gods stirred the heavenly oceans with the peak of Mount Mandara, possibly Mount Everest. A drop of celestial nectar, amrita, fell to earth and a hemp plant sprouted from the spot. It became the favorite drink of Indra, the Lord of Kings, and was subsequently consecrated to Shiva. When evil demons tried to acquire it, they were defeated, hence cannabis is also called vijaya meaning ‘victory’. Another myth has it that Shiva went into the fields and lay under a cannabis plant for shade. Being hungry, he ate some of it and decided it was his favorite food. He is, consequently, sometimes known as the Lord of Bhang as well as by his more common title, Lord of the Dance. The Atharva Veda, the fourth book, says one communes with Shiva through the use of cannabis; calls it one of the five sacred plants and contains a prayer asking it to deliver mankind from disaster, disease and demons. Through its use, mankind is cleansed of sin. The Venidad, one of the volumes of the Zend-Avesta, the ancient Persian religious text was written around the

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seventh century BCE purportedly by Zoroaster (or Zarathustra), the founder of Zoroastrianism. It is heavily influenced by the Vedas, mentions bhang, and lists cannabis as the most important of 10,000 medicinal plants. In early Islamic medicine, cannabis was heavily used. The great Persian physician Mohammad-e Zakaiã-ye Rãzi (865-925 CE) lists a wide range of medicinal uses for cannabis. In 1929, the Russian archaeologist Rudenko excavated a fourth century-BCE high-status burial site at Pazyryk in western Mongolia. That excavation uncovered censers that had been fashioned for inhaling smoke, perhaps as part of the burial ritual. These censers were small cauldrons filled with stones and covered by awnings of leather or felt. Amidst the stones, cannabis seeds were discovered. In addition, clothing made from hemp fiber was found. More recently, in 1993, the Russian archaeologist Natalya Polosmak conducted an excavation of the tomb of a Scythian woman of position in which were found personal possessions including a pot containing cannabis. Both graves fitted the description of Scythian burial rites given by the Greek historian Herodotus. Claudius Galen (circa CE 129–99) was born to Greek parents in Pergamum, a Roman city in what is now Turkey. After studying medicine at the behest of his wealthy father, he became a doctor who attended gladiators. Their wounds often being horrific, he learnt much about anatomy and physiology, publishing his findings and thereby elevated his influence on the medicine of the time to that of Dioscorides. In about 160 CE, Galen wrote that hemp cakes, if eaten in moderation, produced a feeling of well-being but, taken to excess, they led to intoxication, dehydration and impotence. Both the Greeks and the Romans traded in hemp for its fiber. At first, the latter raised virtually no domestic hemp crop at all, importing it from the far-flung corners of their empire which reached as far east as the Caspian Sea, well into the heartland of cannabis. But by the first century BCE, the rapid expansion of the Roman navy created such a demand for hemp fiber for the making of rope and sails that Roman settlements in the region of the Volga started growing hemp along with those in Palestine and Mesopotamia. It was only a matter of time before the Romans decided to begin cultivating their own hemp supply closer to their imperial center in Italy. The Greek historian Pausanias stated that hemp was being grown around Elis, in the west of the Peloponnese in southern Greece, in the second century BCE. The Roman satirist Lucilius wrote of it in 120 BCE. In his thirty-seven-volume Historia Naturalis published soon after his death in AD 79, Gaius Plinius Secundus (Pliny the Elder) noted that hemp made exceptionally strong rope and went into detail about how it was prepared and graded. Hemp as a source of quality fiber had well and truly arrived in western Europe. In the Western world, very little was written down about its medicinal attributes until the 17th century, even though there is strong evidence of use

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by the common folk before this era. In The Anatomy of Melancholy, Robert Burton (of England) included ‘hemp-seeds’ in a list of plants for depression. Nicholas Culpeper (1616 – 1654) described its use as an anti-inflammatory in The English Physician (1652). By the early 19th century many physicians, (especially ones that spent time in colonial India) started employing cannabis as part of their practice and wrote about it in several books. It was listed in the National Dispensary 1880 for USA as: • Analgesic • Anti-seizure medication • To help break addictions • To treat sexual dysfunction • routinely used in veterinary medicine to dress wounds, relieve pain

and ease digestive issues

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Early 20th century cannabis medicine

• some of the medicine included questionable ingredients in today’s standards: strychnia sulphide (CNS stimulant and often used to quell cholera epidemics) and zinc phosphide (also a CNS stimulant?), both now used as rodent poison!

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Prohibition in Canada • a series of events led up to 1923 prohibition • 1908 opium was criminalized in Canada’s first drug prohibition law • “Proprietary and Patent Medicine Act 1908” prohibited the use of

cocaine in medications & introduced mandatory disclosureif product contained opium, heroin, or morphine

• Emily Murphy (1868 - 1933), Canada’s first female magistrate, is a celebrated women's rights advocate who was instrumental in pushing for recognition of women as ‘persons’ under the British North America Act.

• Murphy as one of the “Famous Five” group of women, fought for, and eventually won political equality for Canadian women.

• However, Murphy played a crucial role in having cannabis added to the Opium and Drugs Act of 1923.

• Under the pen name Janey Canuck, Murphy wrote a series of articles for MacLeans magazine & subsequent book “The Black Candle”

"When coming from under the influence of marijuana, the victims present the most horrible condition imaginable. They are dispossessed of their natural and normal willpower, and their mentality is that of idiots. If this drug is indulged to any great extent, it ends in the untimely death of its addict.” This claim caught the attention of the lawmakers and without any parliamentary debate, cannabis was quietly added to the list of other prohibited drugs under the “Act to Prohibit the Improper Use of Opium and other Drugs”.

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Cannabis Is a Whole Community of Personalities – an “Entourage” In many herbal traditions, personalities are assigned to botanicals to help students remember their qualities. This lets the beginners understand a deeper nuances of a herb and develop a fuller appreciation of its attributes. In the case of a complex plant like cannabis, especially with its modern uses, it is more accurate to say that his plant represents a whole community of personalities and functions. Cannabis has always worn a cloak of mystery and mystique. It has been represented in so many cultures and traditions, in many different ways. But one of the oldest and longest standing is an image from the Hindus of India and its worship as part of the energy of the deva Shiva. Again, many traditions assign nature spirits to plants. Powerful plants have very powerful nature spirits or devas. The energy of cannabis is two-sided: with both a benevolent and wrathful nature similar to an internal battle between Kali and Shiva. This nature can be one of the reasons that some people find cannabis very blissful, euphoric, even producing lovely images; while others find it rough, creating paranoia, nightmares and ugly visions. As long as you are under its benevolent energies, it can be a beneficial aid. But once you perceive its wrathful nature, it can be a very rough teacher and it might be time to give it space and not partake of it for a while. Sometimes a wrathful teacher is just what you need, but user be warned – it’s your choice. We will look at these attributes quite bit during this course and show ways for you to get the best for you out of cannabis. This complex nature of cannabis is one of the reasons I have said for many years before Cannabis became legal in Canada, that it was such a useful herb that; “If it was legal, I would prescribe it to about 25 – 30 % of my patients, but I would like to equally ‘unprescribe’ it to about 30% of my patients.” Meaning that many people consume it either in the wrong way, or for the wrong purpose. For these people, it is not giving them the benefit that it should. With the widespread access and use has scaled up some problems and we are seeing many more cases of heart disease, metabolic syndrome, hyperinsulemia, cognitive dysfunction, etc…than ever before. People want their weed, but they want protection. Safe weed is the new safe sex, where abstinence is not being offered.

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While most people will go through their whole life without ever feeling or noticing the deva energy of a botanical, some substances have such power they have been lifted to sacrament level in various cultures. Alcohol (wine) is a sacrament to many Christians, being the ‘blood of Christ or the Host’. Tobacco has been, and still is a sacrament to many indigenous people of North, Central and South America, being used in many ceremonies. Cannabis has been used as a sacrament in many cultures from India, Jamaica, Taoist Asia to many modern-day smaller churches. It is felt by some people that the very act of using these substances as sacraments lends power to the plant’s devic energies. With strong energy comes strong responsibilities and varying responses. Notice that the first two sacraments I mentioned, alcohol and tobacco, have been abused by many and thus these sacraments will fight back and can cause some serious problems for the abusive consumers. Their strong nature can also invite abuse in some situations. I started off in this section by stating that the energies of cannabis are more like a community than that of a single personality, so let’s dive in deeper. Science would describe this “community” by the multitude of active ingredients found in cannabis. Now, as a herbalist, I am the first to state that the concept of an active ingredient is kind of absurd when it comes to botanical medicine. Yes, there may be prominent chemicals in a plant, but each plant comes with many thousands of chemicals that can also influence our body, mind and spirit. Botanical medicine is much more than a convenient delivery system for a single ‘active’ ingredient. That is akin to saying the active ingredient of a piano player, a baseball pitcher or a painter is the hand. Each one of these specialists has spent many hours perfecting the ability of using their hands, but there is much more to these people than just their hands. Botanical medicine can be seen in this same light. So, in this case we don’t want to say that cannabis is just a delivery system for THC, or CBD. Yes, these biochemicals contribute to our reaction to them, but there is a cast of literally thousands of other “support staff” to pull off their act. Let’s look at the nature of some the prominent players in this community to understand what they do. We will be going through a much more thorough understanding of these players in later material, but for now, we are just going to get to know some of the major characteristics or personalities of cannabis. The Shaman THC (also known as delta 9-Tetrahydrocannabinol) can be best described as a shaman. She has certain powers of enhancing euphoria, psychoactive,

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being a healer, and helps get you moving into the flow. Like most shamans, she doesn’t seem to conform to the full rules of society, being a bit wild in nature. Her levels of charisma and charm have gained her many followers. Understandably, she gets the most attention of her group, popular on social media for her powers, intensity and plain sexy mysteries. She can sometimes cause a strong reaction in a few, even sending them into paranoia, insomnia and nightmares. The Doctor CBD (also known as Cannabidiol) is the medical doctor. The healer; albeit a “hip” doctor, with lots of stories and great abilities to work deep in the body. He seems to conform more to social mores than THC. He does not have any of the euphoric and psychoactive properties of the shaman. He is steeped more in science than the mystical. He is beginning an upward trend now, especially with the older age group, because he seems to keep his feet on the ground. He calms down the mind, grounds a person in their body and helps with insomnia. Although THC also helps with pain, CBD specializes in it and has even helped people get off opiate pain medicine. He is intrigued with shamanism, but it is a little too ‘out there’ for him. The Student CBG (also known as cannabigerols) is the student. CBG is training to be either a shaman or doctor, he just hasn’t had time to decide which yet. He is not yet mature or educated enough to produce strong medicine or feelings. As an apprentice he is learning the process and can help a lot of people in his raw state. He does not have any of the euphoric and psychoactive properties of the shaman, but can give a calming healing effect in a raw juice form or a tea blend of prominent CBG. The Sports Car THCV (also known as Tetrahydrocannabivarin) is sometimes called the sports car of the cannabinoids. Its biggest fame to claim is being an appetite suppressant. Although it looks like and sound like THC; it is an antagonist to THC. A well-known fact is that cannabis gives most consumers the munchies, especially high carb, junk foods. Well THCV blocks this trend and many other aspects of the THC. This appetite suppression system is being employed to reduce some eating disorders. THCV has also shown strong anti-convulsant properties and has a potential to raise seizure thresholds in individuals with epilepsy and seizer disorder. Its nature also lends itself to work on reducing tremors improving motor control abilities. THCV has an ability to control glycemic levels thus can be used in assisting type 2 diabetics and people with metabolic syndrome.

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Of course, this is only a small list of the players that make up the community of cannabis, with over 200 cannabinoids currently identified and upwards of 200 varying terpenes contributing to the different personality of types of cannabis that one interacts with. This entourage or community of characters all contribute to our interaction with them, not just one ‘active’ individual.

Effects of The Underground Cannabis Industry Why does Cannabis have this complex personality varying between the benevolent aspects of Shiva and wrathful nature of Kali? I am going to use a set of analogies here to bring out this point, so it can be easily seen. I have to warn you ahead of time that on the surface the statements I am going to make might seem very sexist. I know I am skating on thin ice here, being a white male of dinosaur years, but I hope you get the point without too much offence. I personally have no agenda here of villainizing any lifestyle choices. The more variety the better. Just to be transparent I like the non- binary gender concept best. These fictitious scenarios are created just for analogy sake to bring home a point. You know how it goes, analogies with strong emotional context are the easiest ones to remember. Consider these analogies of the situation that started in the underground cannabis industry of 1970’s. Don’t get mad at the cultivators, they were just doing what they thought was best at the time. In retrospect, some of their decisions were at least not well thought out, and quite self-serving. But the pressure on this community, living in the shadows, took on some of the feelings of the time. Don’t blame me for these scenes that are just meant to give people a scene of the times, and mindset. Please keep reading on even if some of these statements evoke strong emotions. Like many analogies or fairytales, they are meant to stimulate emotions to bring home a point. Hopefully we can come up with resolutions to redirect these energies. Mary Jane (MJ) is going to high school, becoming a graduate of 1979. She is not quite mature yet, even though she certainly thinks she is. It doesn’t take long for her to notice that lots of her classmates are totally obsessed with physical looks. In fact, many guys and lots of girls only pay attention to physical appearance. MJ feels a bit conscious about this because her bust line is not as developed as some of her peers. So, during the summer holiday, she gets a breast augmentation. Not too big, just enough to be noticed. Well her social life changed immediately when she gets back to

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school. All of a sudden, she is more popular especially with the boys, but quite a bit with the girls also. Her social attention also took a large upswing, with people wanting to follow her and listen to everything she says. Life was good. Who would have known, just a bit of surgery and her whole life changed? But she did notice that people looked at her differently and didn’t see the real her. After graduating she started to wade into the job market, but with little success. The competition was strong. It was like she was invisible again. She just couldn’t get the employers attention. What to do? Well if the breast augmentation worked before, it might work again. So, under the knife again to a larger size and what do you know, she got more attention almost immediately. This worked well for a few more years. She kind of liked it, but she was a wee bit mad at how people related to her. She liked the flattery, but often found herself saying in her inner voice; ‘Hey, the eyes are up here.’ She was not that conscious of how her inner feelings were a bit in conflict with her outer appearance. But life went on until she noticed that a lot of the attention started to be focused on the younger girls over the years. Back to the knife to make a really big statement. This time she did a bit of Botox and other special surgeries. It did the trick again, but it also meant that the side effect of people not really seeing her as a person got stronger. Basically, she often felt that she was just some breast walking around for other people’s amusement. It made her realize that she didn’t really like people very much, because they were quite shallow, not interested in any depth of interaction beside objectifying her. During this time MJ started studying the esoteric arts, training as a shaman. This gave her a break from her day to day life and a new sense of meaning and power. This also pushed her into to working in the fringe market, where she could make more money. The problem is she always had to be looking over her shoulders, because it wasn’t really legal what she was doing. It was easy to rationalize that she wasn’t hurting anyone, so why didn’t they just leave her alone. Everyone was consenting adults. Privately this started to really bother her though, and she noticed she started taking on a more wrathful personality. If this just pissed you off with the whole scenario painted – Good! Now you know how cannabis would feel with the continued increased manipulation by breeders to escalate the THC levels, at the cost of other metabolites in the past. They just increased the sexy bit, as if cannabis was only a delivery system for THC. Just like MJ’s craving for respect, cannabis wants to be respected for more than just its THC content. It doesn’t like being forced into the shadows of semi-illegal world. Can we see a route to change this? Can we produce a better plant with a more natural ratio of cannabinoids?

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What appears to be a somewhat innocent attempt to increase the THC levels (sexy bits) in the plant and thus product, altered the plant’s genetics, appearance and reaction for the consumer. It also chanced the publics image of cannabis, marginalizing it in the minds of many. Now that it is coming out of the shadows, let’s celebrate the whole plant for its many contributions to people-kind over our millennia of interaction with it. Now don’t think the story stops there, because some of us humans learn slowly. It seems like we are doing the same thing with the CBD content. This time it is a boy named Charles that nobody paid much attention to in high school, as he is a geek who loves the sciences. He only started to get a bit of attention when he went out for some sport events. After his first year doing this, he realized he was nowhere near as big as most of the guys on the team who got more attention. What could he do about it? He looked to science, his first love and realized he didn’t have as strong of a hormone system as some of his teammates. Well that was easily be solved by taking some steroids and boom he was bigger and getting more attention, making more goals and his popularity started to trend. Wow, that was easy! It wasn’t until later when studying at university to be a medical doctor that he realized that he had started to compromise himself health-wise. Charles stopped the hormones, happy to have not done too much damage. Like most things from the natural world, it is all about balance. It is alright to breed organisms for certain attributes, but we have to be conscious of the side effects and try to work with those also. This isn’t a new thing that humans do. We have bred many plants like cabbages to get broccoli, cauliflower, kale, brussel sprouts, kohlrabi and several other cabbage-like cultivars out of the same species. We have done it with dogs, with a range between a small chihuahuas to a large Great Danes. We have created many cultivars of grapes for wine, or coffees for the artisan shops. The difference here is that we are dealing with a botanical that has a very strong nature, that can affect our mind and personality and the way we relate within the social context of our community.

How Cannabinoids Work How do these cannabinoids interact with us? After all these are just individuals, a community is made up of the interaction in a social context. This community has both an external aspect and an internal aspect. As many of you probably already know, the human body has a very sophisticated system to work with the plant cannabinoids. It is called the endocannabinoid system (ECS). This complex system was only discovered in the early 1990s, but only widely discussed since 2015. The ECS affects almost all aspects of our physiology and many aspects of our cognitive functions. As humans, we share this system with the rest of

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vertebrates so its origin must be far back, many millions of years, in our evolutionary history. There is a matrix of cannabinoid receptor sites found in various parts of our body. We produce our own endocannabinoids (endo = internal + cannabinoids) to help regulate many activities in our nervous and endocrine system systems as well as cognitive functions. Some plants, like cannabis have phytocannabinoids (phyto = plant based + cannabinoid) like THC and CBD. These interact with the same receptor sites that our natural internal ones do. There are several different types of receptor sites, but the two most prominent ones are: CB1 and CB2. They are either stimulated or sedated by various cannabinoids. The blend of these cannabinoids consumed are assisted by an entourage of terpene (scents) making up much of the nature of our reactions to these plants.

A Closer Look at the Phytocannabinoids Some of the first questions that most people want to know about cannabis and cannabinoids is what makes them tick? What are the active ingredients? Is there any scientific proof that it works? To answer these questions, we need to wade into a vast forest of information in the area. With more than 700 chemical constituents that have some form of therapeutic activity and over 10,000 papers written on the scientific ins and outs of the plant and its constituents; it is not a question of finding information, it is a question of sifting through tons of information to find out what is relevant to our conversation. The two groups of constituents that have gathered the most attention over the years of research are: phytocannabinoids and terpenoids. We will be looking at what appears to be some of the most important ones. Two things we can say for sure:

1. Even though there are over 200 phytocannabinoids that have been studied, we are bound to find more and certainly discover more effects of the individual cannabinoids. This science is still pretty much in its infancy, having lived in the shadows for the last 50 plus years.

2. There is not a single or even a few active ingredients. It is the effect of the sum total of constituents in the plant. Even with isolates and synthetic compounds, we have a lot to learn from them.

As we have previously seen, the body itself produces its own cannabinoids – called endocannabinoids. The phytocannabinoids are produced by plants, primarily cannabis plants. The plants produce several forms of carboxylic

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acids: THCA, CBDA, and so on. Once these chemicals are heated to a high enough temperature through smoking, vaporizing, cooking or even stored at room temperature for long enough; they convert into more active forms of THC and CBD through a process called decarboxylation. (see diagram).

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Many consider THC the active ingredient, which does produce the principal psychoactive effect of cannabis. But since cannabis has such a large array of therapeutic uses, it partly comes down to what effect you want to have? That determines the important ingredients for the desired outcome. One of the important pieces to get out of the way right off the top is the extremely low toxicity of phytocannabinoids in humans. Which is why there has never been a fatal overdose directly attributed to cannabinoids. Until very recently, it was believed that phytocannabinoids only came from cannabis plants, thus they were often just considered simply cannabinoids. We now know that several other plants produce constituents in this family of chemicals including lichens, copaiba (a resin from the trunk of certain South American trees) including even black pepper and chocolate. So now we use the term phytocannabinoids to extend the category to include a larger array of natural plant compounds that interact with cannabinoid receptors in the body. Over the last 50 – 100 years, it was discovered that THC had an important role in some activities attributed to cannabis. But this didn’t fully explain why cannabis gave varying medical and psychoactive effects with different users and different plants. We now know these varying results are a combination of many factors. Some of which are:

1. The different variation of phytocannabinoids in each cannabis plant. 2. Other components of the plant, especially the essential oils (called

terpenoid or terpenes). 3. Variations in numbers, types and location of receptor sites in the

consumer. 4. Other social and even possible placebo effects.

It is now believed that a combination of the phytocannabinoids and terpenes acting in concert contribute to both the medical and psychoactive effects. While herbalists may think of cannabis as a community of personalities, science describes these combined influences as the ‘entourage effect’. This gives cannabis a broad effect on people instead of the ‘magic bullet’ targeting of many pharmaceuticals.

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Nine of the Phytocannabinoids Even though there was a comprehensive review in 2016, showing over 200 phytocannabinoids produced by cannabis, we are going to focus on 9 (nine) coming from 4 (four) cannabinoid families. • CBC (cannabichromene) • CBD (cannabidiol) • CBDV (cannabidivarin) • CBG (cannabigerol) • CBN (cannabinol) • THC (tetrahydrocannabinol) • THCV (tetrahydrocannabivarin) • CBDA (cannabidiolic acid) • THCA (tetrahydrocannabinolic acid) Delta 9 -Tetrahydrocannabinol (THC): is the most popular psychoactive phytocannabinoid. THC is not found in the plant itself, as stated earlier, it has to go through decarboxylation to turn into THC from THCA. Through the decades of selective breeding by recreational cannabis growers a few plants have moved from 2 – 9% THCA (potential THC) in the 1960’s up to as high as 25+% at current level. So, some of the cannabis today is very different from what was available in the past. (This isn’t your father or grandfather’s cannabis). This shows us that previously the cannabis industry was really only interested in this secondary metabolite. It is pretty impressive, that the breeders found the right pressures to change the metabolic functions of the plant. However, breeders where not focusing on the whole plant’s activities, just the THC potential. Besides being psychoactive, THC exhibits potent anti-inflammatory and analgesic activity, neuroprotective, reduce intraocular pressure, spasticity, and muscle tension. THC interacts with both CB1 and CB2 G-protein endocannabinoid receptors. Even though THC is nontoxic some consumers (especially novices) experience a “psycho-toxic” effect of panic, anxiety, sedation and rapid heartbeat. Cannabidiol CBD: is a derivative of CBDA, most common in the fiber cannabis or hemp varieties. A common misconception is that plants high in CBD are quite sedative. Most likely the reason people notice this reaction is because they often have high myrcene (a terpene we will discuss later) especially if cultivated under sunlight. Two of the most commonly found high CBD cultivars are Charlotte’s web and ACDC. Some feel they might be the same plant with almost identical genetic fingerprints. CBD is not psychoactive, but some people feel they get a little bit of a feeling of mild intoxication, though subjectively very different than THC. This effect

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is almost due to a terpene/CBD interaction. CBD interferes with THC’s ability to stimulate CB1 receptors (a negative allosteric modulator of THC). CBD has analgesic and autoinflammatory effect in a large range of symptoms and conditions. It is also a very potent antioxidant. CBD has evidence to work against brain and breast tumors, while simultaneously protecting normal tissue. CBD and its cousin CBDV are effective anticonvulsants. One of the reasons that CBD has such a wider range of uses than THC is that it interacts with a much larger range of receptor sites than THC, both inside the endocannabinoid system and outside of it. This gives it an ability to work on conditions ranging from acne to strokes. It also has a strong anti-bacterial effect on several bacteria like Staphylococcus aureus. Cannabigerol (CBG): comes from the mother constituent of Cannabigerolic acid (CBGA) through decarboxylation. Research on this constituent is fairly recent with most likely more results coming in the future. It has a potent appetite stimulant effect that has been employed when patients are on chemotherapy (cachexia). CBG can be used to treat IBS. Beside interacting with the endocannabinoid system, it interacts with several receptors outside it. It is an extremely potent antibacterial. It has been employed as an antitumor agent, especial prostate and oral cancer. Cannabigerolic acid (CBGA): is the third most prevalent cannabinoid produced in cannabis. It is a non-psychoactive ingredient that has an analgesic action. Little is found in the mature flower but can be still found in the leaves and fiber of the plant. Cannabichromene (CBC): is usually obtained by collecting immature flowers about 6 weeks before maturity as CBCA and then decarboxylated. CBC does not interact with the endocannabinoid system and has its major target transient receptor potential channels (TRP channels) found in plasma membranes. This is similar to the interaction of several plant constituents like garlic (allicin), chili pepper (capsaicin), wasabi (allyl isothiocyanate); others are activated by menthol, camphor, peppermint, and cooling agents. CBC exhibits a large range of effects including antifungal, antibiotic, anti-inflammatory and analgesic. It has also found promise as an antidepressant. Cannabinol (CBN): is the oxidation by-product of THC. It was commonly detected among poorly stored, old cannabis. Most considered it the sign of bad product, but it does give some patients a nice sedative effect. If taken orally and passed through the liver, it converts to a form (11-hydroxy-CBN) which binds better to the CB1 receptors. This produces a

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better action taken orally than inhaled. It has a significant antibiotic effect and has been used in treating burns because it reduces perceived thermal sensitivity. This shows that even poorly handled and storage, cannabis still retains some medicinal value. Cannabidivarin (CBDV): This propyl form of CBD has shown promise as an anticonvulsant, with and without CBD. Tetrahydrocannabivarin (THCV): is a derived from THCVA which has been shown to reduce appetite and thus is a potential diet supplement. It has been used to reduce delayed memory recall. It does increase connectivity in brain networks and therefore is being researched for tremors, dementia and Alzheimer’s. Even though some reports indicate that it has a strong psychoactive effect that is more intense than THC, but of shorter duration. Studies in the UK have shown that 10 mg of THCV is not psychoactive. THCV can inhibit THC action, making it less intense. CBDA (cannabidiolic acid): is the most common phytocannabinoid produced by fiber (hemp) plants. It has shown promise as an anti-nausea treatment, especially anticipatory nausea. THCA (tetrahydrocannabinolic acid): is the most common cannabinoid found in recreationally grown plants. Even though it is the precursor of THC, it is non-psychoactive until it is converted into THC. It was once thought to not have medicinal activity due to it being non-psychoactive, however we now know it is actually quite effective. It is anti-inflammatory, immune-modulating, neuroprotective and anti-tumor.

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Phytocannabinoid Abbreviation Action Notes

delta 9 -Tetrahydrocannabinol

THC Psycho-activity at just below therapeutic doses THC increases production of endocannabinoids in the brain (The Endocannabinoid System 2014 Medical Cannabis Institute. Dustin Sulak, DO)

Analgesic (reduces pain)

Micro-dosing THC enhances pain relief from endocannabinoids (in mice)

Antiemetic (manage nausea/vomiting)

Δ9 THC is the form of THC in heated cannabis (see boiling chart)

Sleep aid some Δ8 THC is created in

the plant …however

Appetite stimulant when we ingest Δ9 THC the body changes it into Δ8 THC which has much more potent potential for impairment (psychoactive properties)

Antispasmodic

Anticonvulsant

Antioxidant

Anti-cancer

Cannabidiol CBD Non-Psychoactivity ”CBD … does not appear to bind to either CB1 or CB2 receptors at physiologically meaningful concentrations, but there is some emerging evidence suggesting it may act as a non-competitive, negative, allosteric modulator of CB1 receptor”

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Analgesic (reduces pain)

works with a wide range of receptors (not just CB1 and CB2)

Anti-inflammatory very few side effects Anxiolytic (anti-anxiety)

counteracts some of the impairing/psycho-activity of THC, as well as THC induced anxiety (keep some handy as a first aid to THC overwhelm)

Neuroprotective studies into CBD’s

effectiveness as an antibiotic

Anti-epileptic

Antispasmodic

Anticonvulsant

Antioxidant

Anti-tumour

Anti-proliferant

Bone Stimulant

Immune modulating

Vasorelaxant

Antipsychotic

Anti-biotic

Cannabigerol & Cannabigerolic acid

CBG & CBGA Non-Psycho-activity the precursor to CBG, is CBGA

CBGA is also the precursor

to all the other acid cannabinoids (THCA, THCVA, CBDA, CBDVA, CBCA, CBCVA) CBGA is present in the developing plant … however not much remains in the fully mature plant

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Early studies show it may prove to stimulate brain cell and bone growth and shows promise as an anti-bacterial and anti-insomnia medicine

Early studies found to stimulate brain cell and bone growth

Demonstrates promise as an anti-bacterial and anti-insomnia medicine

strong appetite stimulant

in mice models, shown to be an effective treatment for IBS

antibacterial

shows promise as an anti-tumour agent, especially in cases of prostate and oral cancers

Cannabichromene CBC Non-Psycho-activity the acidic (unheated) form of CBC, called CBCA (Cannabichromenic acid) forms in the immature flowers, about six weeks before maturity

Anti-biotic

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Anti-fungal The effect of

cannabichromene on adult neural stem/progenitor cells. Noriko Shinjyo, VincenzoDi Marzo. 2013

Antiviral

Anti-inflammatory

Analgesic

Stimulates bone growth

Increases neurogenesis (development of new brain cells)

Study shows that CBC increases neurogenesis (development of new brain cells):

10 times more effective than CBD in treating anxiety and stress

Cannabinol CBN Mildly to Non-Psycho-activity

This cannabinoid is not produced by the cannabis plant, but occurs as a result of THC degradation, i.e. it is found in abundance in older samples of cannabis flowers and resin

Most sedating of all the cannabinoids

Demonstrates promise in treating glaucoma, and pain and may prove effective against MRSA infections

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Cannabidivarin CBDV Non-Psycho-activity Slightly degraded form of CBD

Anti-epileptic

Anti-nausea

shows promise on its own as an anticonvulsant, and seems to work synergistically with CBD

Tetrahydrocannabivarin THCV Great interest as an appetite suppressant

Pronounced energetic effects

May effectively counter anxiety, stress, & panic disorders without suppressing emotion

Reduces tremors associated with Alzheimer’s, Parkinson’s, and other neurological disorders

Diminishes appetite

CBDA (cannabidiolic acid)

Non-impairing for most people

THCA (tetrahydrocannabinolic acid)

the ‘raw’ cannabinoids

Anti-inflammatory

Antioxidant

Anticancer

Strong immune booster

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Improved intestinal function

Improved neural function

Neuroprotective

Rebuilds bone

The body does not convert THCA to THC (that happens through a heating process outside the body). However, the body can convert CBDA into CBD, especially when taking juice from the fresh leaves

Fresh Juice Drinking juiced fresh

cannabis leaves creates up to 4x more serum CBD than other methods of consumption. Juice has a short shelf life 4-12 hours. Best consumed with other fresh juices. Can be frozen.

CBD-A

CBDA shows promise as an anticonvulsant, anti-nausea and anti-emetic agent, analgesic and anti-inflammatory.

CBDA may also have antibacterial, antioxidant and cancer preventing properties

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Synthetic Cannabinoids

CAUTION! many who take these potent drugs recreationally end up with psychiatric conditions.

HU-210 - created in 1988 by Dr Mechoulam’s team

100s x more potent and longer acting than plant THC

used as an antidepressant, anti-anxiety & analgesic

shown to prevent the inflammation of Alzheimer’s disease

WIN 55,212 - in rat studies

shown to be a potent analgesic for neuropathic pain

Sativex (THC & CBD from cannabis plant extract)

analgesic for cancer pain

spasticity from MS

Dronabinol / Marinol (Synthetic Delta-9 THC.)

nausea/vomiting associated with cancer treatments

appetite stimulant for AIDS patients

analgesic for neuropathic pain in MS patients

Nabilone / Cesamet (similar to THC but much stronger)

nausea/vomiting associated with cancer treatments

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Dexanabinol (synthetic non-psychoactive cannabinoid)

neuroprotective after cardiac surgery

regain high level functioning (such as regaining memory) after brain injury

possible anti-cancer use (solid tumour) in future

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Terpenes and Terpenoids The scent that can be smelled when around cannabis or its flower buds is not associated with the cannabinoid. They have no aroma. We smell the terpenes, just like we would sniff the perfume of a freshly cut flower. There are over 200 known terpenes found in cannabis, but only about 30 of them are in significant enough quantities to be noticed and importantly, have therapeutic uses. These terpenes make up most of the essential oils of plants and are found in all spices, fruits, and vegetables. Many terpenes have significant therapeutic actions while working synergistically with cannabinoids. We will review a few of the terpenes here but, be certain that in the coming years more research will reveal additional information about this group of allied contributors to the cannabis community. There are 8 (eight) that we will look at here.

1. Alpha and beta-pinene 2. Limonene 3. Myrcene 4. Cis-ocimene 5. Terpinolene 6. Linalool 7. Humulene 8. Beta-caryophyllene

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Since the 2001 paper ‘Cannabis and Cannabis extracts: Greater than the Sum of Their Parts’ by John McPartland and Ethan Russo, it has been noted that some of the therapeutic attributes of various cultivars come from the terpene profiles. They of course give credit to the large range and differing effects that certain cultivars have on various consumers. One of the jobs of a practitioner is to match the right cultivar with the individual client. These effects are attributed to the entourage influence that the different cultivars have.

The terpenes are mostly found in the resin heads atop cannabis glandular trichomes. By their nature, terpenes are quite volatile, especially the fragrant monoterpenes which are often lost in the drying, extracting and storage stage without proper precautions. If the cannabis is gamma-irradiated to lower microbe counts, it will basically destroy much of terpenes in the same way as oranges lose their scent if irradiated. Terpenes do have therapeutic activity even at very low concentration like 0.05 % by weight. So, it only takes a little to have an effect. It has been shown that the cannabinoid can increase the ability for terpene to cross the blood/brain barrier, by increasing membrane permeability. This often means a terpene can have a stronger effect on humans when associated with a cannabinoid than either by itself of from other botanicals. Terpenes, like a cannabinoid, are lipophilic (fat-loving) and hydrophobic (water-hating) helping them interact with a wide range of receptors throughout the brain and body.

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Pinene: Alpha- and beta-pinene are monoterpenes found in most conifers as can be observed by the wonderful aroma of a Christmas tree. It can also be found as one of the major ingredients of turpentine. These terpenes can dissolve plastic, thus showing that storing cannabis in soft plastic bags is a poor idea. Pinene inhibits some enzymes in the brain responsible for deactivating memories and thus attributed to improving memory. This is why high-pinene levels in the cannabis will reduce poor-memory issues associated with high-THC varieties. There are high pinene levels in Kona Gold, Blue Dream and Pinene Kush. Limonene: is a common terpene found in citrus fruit, especially the peels (zest). Both limonene and terpinolene are responsible for the citrusy scent found in some varieties of cannabis. Limonene contributes to the euphoric effect and antidepressive effect of some varieties. Some cultivars high in limonene are Tangerine Dream and Gelato. Myrcene: beta-myrcene is a monoterpene that can be as high as 30% of the total essential oil content of some varieties. If the complex has THC also contains myrcene it displays a quality of analgesic (reduces pain) and muscle relaxant; enhanced sedative and tranquilization benefits. It helps relax the muscles and increases the sedative of other drugs. This can be so much so that it is often associated with ‘couchlock’ when a person can’t get up from the couch after consuming too much ACDC and Godfather OG cultivars. If myrcene is present with high CBD it has energies to help deal with decreasing inflammation, fighting cancer and reducing pain. With CBG it has been said to specialize as an anti-cancer energy. Large amounts of myrcene can be found in AK-47, Purps and Grape Ape. It should also be noted that large amounts of myrcene can inhibit anti-inflammatory and analgesic activity. Cis-ocimene: is a sweet and fruity scent that is associated with Skunk cultivars such as Skunk #1 and Pincher Creek. It has been described as having the ‘Goldilocks effect,’ not too stimulating and not too sedating. Ocimene is also released if the plant is attacked by spider mites. It attracts predator mites that eat the spider mites. Terpinolene: is a citrusy terpene associated with highly stimulating cannabis cultivars like Jack Herer, Trainwreck, Big Sur, Holy weed, S.A.G.E., and Zeta. It is both sedative but strongly associated with cognitive clarity. Linalool: is also found in lavender and can give a mild psycho-active effect. It gives a calming, anti-anxiety effect, with sedative, analgesic and

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anesthetic action. The cultivars that have high levels are Bubba Kush, several purple indicas. Humulene: This terpene is found in a wide variety of plants and has been used for centuries. Research has proven it to be an effective anti-inflammatory, antibacterial, and appetite suppressant. It’s partially responsible for giving the plant its distinct spicy, herbaceous, and subtly floral bouquet of aromas. A 2016 study shows that it may help terminate cancer cells when combined with phytocannabinoids and other terpenes.2 The oil was also shown to exhibit antibacterial properties in another study, proving to be active against the bacterium Staphylococcus aureus (a.k.a. golden staph) when administered in small quantities. S. aureus is a bacterium present in our bodies at all times, but it can play a role in a host of nasty infections and diseases when exposed. Caryophyllene: is a common sesquiterpene that is linked to a stimulating effect of some varieties. Sesquiterpenes are heavier, literally being 1.5 terpenes in size. The slight increase in weight makes them less volatile than the monoterpenes, thus they survive more reliably during the drying, extracting and storing process. It interacts strongly with CB2 receptors and can also be found in black pepper, cloves and hops. This also makes it really a cannabinoid. It has potent anti-inflammatory (both internally and topically), while inhibiting analgesic and immunomodulating activity. It has shown promise in anti-arthritis area. Some feel it is effective for reduced THC ‘hangover’. By the way, cannabis-sniffing dogs are trained to smell caryophyllene oxide that is released by many cannabis varieties.

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Terpenes Pinene analgesic

antibacterial

anti-inflammatory

anti-proliferative (inhibits cancer cell growth)

antioxidant

helps with focus & concentration

bronchodilator

may counteract THC induced short-term memory loss and paranoia

In some can cause anxiety

also found in pine trees and rosemary Limonene antidepressant

anti-fungal

anti-Inflammatory

anti-proliferative (inhibits cancer cell growth)

anxiolytic (relieves anxiety)

reduces acid reflux

immunostimulant

also found in the rinds of citrus fruit Myrcene analgesic

antibacterial

helps mitigate the effects of diabetes

anti-inflammatory

sleep aid

anti-proliferative/anti-mutagenic (inhibits cell mutation, including cancer cells)

antispasmodic

Increases absorption of cannabinoids

also found in mangos, hops, and sweet basil

Cis-ocimene ‘Goldilocks effect,’ Not too stimulating and not too sedating

Terpinolene antibacterial

anti-fungal

sleep aid

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anti-proliferative (inhibits cancer cell growth)

antioxidant

also found in apple, cumin, lilac and tea tree Terpineol antibiotic

antioxidant

anti-proliferative (inhibits cancer cell growth)

sedative (mild)

anti-inflammatory

antimalarial

anxiolytic (anti-anxiety)

also found in lilacs, pine trees, lime blossoms, and eucalyptus sap

Linalool analgesic

antidepressant

reduces seizures and convulsions

anti-inflammatory

anxiolytic (relieves anxiety)

sedative

also found in lavender Humulene analgesic

antibacterial

anti-inflammatory

anti-proliferative (inhibits cancer cell growth)

anorectic (appetite suppressant, promotes weight loss)

also found in hops, sage and ginseng Caryophyllene high affinity to CB2 receptors

some suggest that Caryophyllene is more a cannabinoid than a terpene (Cannabis Health Index 2015)

strongly anti-inflammatory

analgesic

antibacterial

antidepressant

anti-proliferative (inhibits cancer cell growth)

antioxidant

anxiolytic (anti-anxiety)

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neuroprotective (slows damage to the nervous system and brain)

also found in black pepper, bay, cinnamon, cloves, hops, rosemary, basil, caraway

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Flavonoids

• a group of phytonutrients found in fruits and vegetables • like terpenes, each flavonoid contributes to the healing profile of a

cannabis strain Cannaflavin A:

• unique to cannabis • strong anti-inflammatory

Quercetin: • also found berries, green tea and red wine • antioxidant, antiviral, and some anticancer properties

Apigenin: • also found in chamomile tea, celery and parsley • combats anxiety

anti-inflammatory

Endocannabinoid (EC) System As noted in the first sections of this course, it is pretty clear that humans have been using cannabis for tens of thousands of years if not longer. Just to recap, medications based on cannabis have been used for therapeutic purposes in many cultures for centuries.3 At the end of the 19th century cannabis was used to treat pain, spasms, asthma, sleep disorders, depression, and loss of appetite by main stream medicine. While the discovery of the first cannabinoid (CBD) was in the 1940’s, THC was not discovered until 1964 by Gaoni and Mechoulam in Israel.

This was well after the time that cannabis medications fell into almost complete disuse, partly because scientists were unable to establish the chemical structure of the ingredients of the cannabis plant (Cannabis sativa) in the Americas. Research on them, an illegal substance at that time, was prohibited. But research did go on in other countries (like Israel) and the first cannabinoid (CB) receptor site was found in the late 1980s. This turned out to be the first steps into finding a mysterious and completely undiscovered homeostatic regulatory mechanisms within the body, which was named the endocannabinoid system (ECS). Until then, scientists believed a kind of generic interaction between cells and plant cannabinoids caused the psychological and physiological effects of cannabis. Now, we understand that there are highly specific chemical mechanisms responsible for those effects.

FUN FACT: the human ECS was not ‘discovered’ until the 1980s, even though cannabinoid receptors are found in the

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earliest organisms to appear on earth, some 600 million years ago!

In the earlier section “How Cannabinoids Work,” we took a first look at the special receptor sites in the human body that respond to phytocannabinoids. Now we’ll take a deeper dive.

Role of the Endocannabinoid System (ECS) The ECS — named after Cannabis sativa and its active ingredient delta-9-tetrahydrocannabinol (THC) — is a unique communication system in the brain and body that affects many important functions, including how a person feels, moves, and reacts. It is also a very complex regulatory system, with broad reaching functions and is found to various degrees within most complex animals, from fish to humans. It regulates such diverse functions as memory, digestion, motor function, immune function, inflammation, appetite, pain, blood pressure, bone growth and protection of neural tissue and the cardiovascular system, among others.

There are three principal elements of the ECS are:

1. Receptor sites

2. Endocannabinoids

3. Enzymes that either synthesize or metabolize endocannabinoids.

Endocannabinoid Receptors

There are two primary subtypes of classical cannabinoid receptors in the ECS; CB1 and CB2. These receptors are distributed throughout the CNS and immune system and within many other tissues throughout the body and brain, gastrointestinal system, reproductive and urinary tracts, spleen, endocrine system, heart and circulatory system.

We now know that cannabinoid interaction extends far beyond just CB1 and CB2 receptors and react with other receptors and ion channels. We still know very little about this system and how our bodies actually make their own endocannabinoids. But we do know what some of them are. Studying how our bodies’ endocannabinoids interact with the ECS and what effects these interactions are is crucial for advancing our understanding of the therapeutic and recreational effects the phytocannabinoids in cannabis.

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The cannabinoid receptor CB1 is prominent in the brain. Besides the brain, these receptors hang out in parts of the eye and retina and in both male and female reproductive systems. CB2 receptors exist primarily in the immune system with the greatest concentration in the spleen. Current research involving animal models indicates that these receptors are responsible for the significant anti-inflammatory properties of cannabis, especially the CBD cannabinoid. They may also be the cause of many other medicinal and therapeutic effects.

Cannabinoid Receptor Functions

• Generally speaking, both CB1 and CB2 receptors are involved in how we perceive pain

• CB1 receptors tend to influence our senses; things like appetite, memory and pain

• CB2 receptors tend to influence our immune response, including the inflammatory response

Cannabinoid Receptor Location

CB1 receptors are primarily found in: • Central nervous system (brain & spinal cord) • Reproductive system (testes, uterus) • Adipose tissue • Connective Tissue • Endocrine glands (pineal, pituitary, pancreas, ovaries, testes, thyroid,

parathyroid, hypothalamus, adrenals) • Exocrine glands • Leukocytes • Spleen • Heart • GI tract • Liver

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In the Brain

Areas of the brain with high numbers of CB1 receptors: • cerebellum (motor control, attention, emotions and thinking) • basal ganglia (habits) • hippocampus (memory) There is a very low concentration of cannabinoid receptors in the brain stem, the area of the brain that controls cardiorespiratory function. This is why high doses of cannabis won’t shut down breathing or stop the heart.

• Cannabinoid receptors are mainly involved in neurotransmitter activity.

They are also important for fat metabolism, energy production, inflammation, insulin sensitivity and immunity.

In the Immune System

• CB2 Receptor Locations found in the immune system:

• monocytes • macrophages • B-cells • T-cells • Liver • Spleen • Tonsils • CNS Enteric nervous system (in the gut)

Depending on which cannabinoid activates the receptor, different things can happen in other words: depending on what key (cannabinoid) is used, the door (receptor) will open to a different room (activate different responses)

Functions of the ECS

• memory & learning • decision making • reward perception

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• emotions • digestion • motor function • immune response • inflammation • appetite • pain • blood pressure • bone growth • connective tissue health • nerve protectant Discoverer of the ECS, Raphael Mechoulam • Israeli chemist • often described as the father of cannabis medicine ‘The Scientist’ documentary on YouTube

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Botany Cannabis is part of the plant family Cannabaceae. This is a small family of flowering plants. It includes about 170 species grouped together in 11 genera, including: Cannabis (hemp, marijuana), Humulus (hops) and Celtis (hackberries). The hackberries are by far the largest genus with about 100 species. There are theoretically three species of Cannabis (Cannabis sativa and C. indica, C. ruderalis), though there are contentious arguments about if they are in fact really one or two species. We will look at this question in more detail later. For now, let’s simply say that there is so much interbreeding that most cultivars are a hybrid mixture of these two groups of plants, making the distinction for consumers basically irrelevant. Cannabis’ basic life cycle is a medium to tall, erect, annual herb, but environmental influences strongly affect the growth habits of individual plants throughout its range. Provided with the right environment of an open, sunny environment; light, well-drained soil; and sufficient nutrients and water, Cannabis can grow to a height of 5 meters (16 feet) in a four-to six-month growing season. Exposed riverbanks, lakesides, and agricultural lands are ideal habitats for Cannabis since they normally offer good sunlight, moist and well-drained soil, and ample nutrients. Many plants have been selected to be only 1 meter in height, especially cultivars designated to be grown indoors. If grown in arid locations with negligible soil nutrients, Cannabis develops minimal foliage and may mature and bear seeds when only 20 centimeters (8 inches) tall. When planted in close stands on fertile soil, as with fiber hemp cultivation, plants do not branch but grow as tall, slender, and straight stalks. If a plant is not crowded (e.g., when cultivated for seed or medicinal production), limbs bearing flowers will grow from small axial meristems (growing points) located at the nodes (intersections of the petioles or leaf stalks) along the main stalk.

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In a temperate environment, seeds are sown outdoors in the springtime, germinating in three to seven days. They are often germinated inside to have early starts in many cool temperate zones with shorter growing season. The first true leaves arise about 10 centimeters (4 inches) or less above the cotyledons (seed leaves) as a pair of oppositely oriented single leaflets. Successive leaves arise, maintaining as opposing pairs, and a variously shaped leaf sequence develops. A common pattern is for the second pair of leaves having 3 leaflets, the third pair having 5, and so on up to 9, 11, and even 13 leaflets. This of course varies depending on growing environment. In some warm, sunny climates with favorable soil conditions, Cannabis can grow as much as 10 centimeters (4 inches) a day. The rapidly elongating stalks produce a strong bast (bark) fiber used for cordage and woven textiles.

Cannabis exhibits a dual response to day length (or dark periods). During the first vegetative stage of two or three months, it responds to increasing day length with more vigorous vegetative growth. The flowering stage requires shorter autumn days to complete its life cycle. Cultivated Cannabis produces flowers when it is exposed to a day length (photoperiod) of 12 to 14 hours, which varies with the strain, and all varieties have an absolute requirement of a minimum number of short-day lengths (or, more accurately, long nights) that will induce fertile flowering. In the temperate zone this happens naturally outside around the equinox of September 21 or so. Growers have capitalized on this by controlling the environment to start flowering earlier and to increase number of flowers by harvesting time. By shortening the light stage and increasing the dark phase (called light deprivation), they can often create a 90-day growing season instead of a 6 –

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8 month one. Many growers go with the 12 light hours and 12 dark hours around the 1.5-month mark for best results. Dark (night) cycles of 10 to 12 hours must be uninterrupted by light periods in order to induce flowering. This is all a product of trying to get the most THC out of the plant the fastest. If trying to produce other cannabinoid or terpenes, other strategies might be considered.

Cannabis is normally dioecious, which means that unisexual male or female flowers develop on separate plants, although co-sexual monoecious or hermaphrodite examples with both sexes produced on one plant occasionally do occur. Many cultivators have created feminized plants, auto-flowering plants and/or many other combinations to aid in the speed of obtaining seedless female flowers. Commercial pressures have produced many forms of cannabis. Cannabis is wind-pollinated and relies on air currents to carry pollen grains from male plants to female plants. The first sign of flowering is the appearance of undifferentiated floral primordia (giving rise to the flower) along the main stalk at the nodes, one primordium behind each of the paired stipules (leaf spurs), located one on each side of the base of each leaf’s petiole. (see pic) Before flowering, the sexes of Cannabis are indistinguishable except for general trends in growth habit—in less crowded conditions female plants tend to be shorter and produce more branches than male plants. When flowering is initiated, the male flower primordium can be identified by its curved, crab’s claw shape. Some people find these almost spherical flowers to look like the

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‘balls’ of the male plant. This is soon followed by the differentiation of dense clusters of round-pointed flower buds, each having five radial segments. The female primordium can be identified by the enlargement of a tapered curved tubular bract (floral sheath). In both sexes, when flowering begins, the pattern of increasing numbers of leaflets reverses, and as flowering progresses, the number of leaflets per leaf decreases until only a small single leaflet appears below each pair of flowers. The phyllotaxy (leaf arrangement along the main stalk) also changes from opposite to alternate (and remains alternate) throughout flowering regardless of sexual type. (see picture to the left)

Development of branches bearing flowering organs varies greatly between males and females. Female plants are leafy to the top with many small leaflets subtending the flowers tightly crowded within erect compact clusters, while male plants have only a few small leaves growing sparsely along the elongated flowering limbs. Male flowers hang from long, multibranched, loose clusters formed of small (approximately five millimeters, or 1/5 inch long) individual flowers along an axis up to 30 centimeters (12 inches) long. Tightly clustered female flowers have two long white, yellowish, or pinkish stigmas (female sexual organs receptive to pollen) protruding from each bract. The bract measures two to eight millimeters (1/12–1/3 inch) in length and adheres closely to the single ovary, completely surrounding it. The bract is covered with hundreds of glandular trichomes (plant hairs). These glands and their resinous secretion may protect the reproductive organs from excessive transpiration and may also repel pests.4 It is this aromatic resin that contains the psychoactive properties that have attracted human attention for millennia.5

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The differences in flowering patterns of male and female plants are expressed in many ways. Soon after pollen is shed, the male plant dies. The female plant may mature for up to five months after viable flowers are formed if little or no fertilization occurs and if it is not killed by frost, pests, or disease. Compared with female plants, male plants show a more rapid increase in height as well as a more rapid decrease in leaf size and leaflet number approaching the single leaflets that accompany the flower clusters. Many factors contribute to sex determination in flowering Cannabis plants. Under average conditions, with a normal day length of 12 to 14 hours, a Cannabis population will flower and produce approximately equal numbers of male and female plants, their sex determined by X and Y sexual inheritance. Pollination of the female flower results in the browning, shriveling, and eventual loss of the paired stigmas as well as a swelling of the tubular bract inside which the fertilized ovule is enlarging. After approximately three to six weeks, the seed matures and after some time is harvested and dispersed by humans or simply drops to the ground. This completes the normally four-to-six-month life cycle in as little as two months or as long as ten months, varying according to its biotype (group of organisms sharing the same genotype) or ecotype (group within a species sharing similar ecological adaptations) as well as ambient environmental conditions. Fresh and fully mature seeds approach 100 percent viability, but this decreases with age. For example, usually at least 50 percent of seeds will germinate after three to five years of storage at room temperature. Without refrigeration, viability of seeds rarely exceeds 10 years. On the other hand, uninterrupted freezing can preserve seeds for decades. We would expect viability over time to be much lower under most natural conditions. The mature, achene fruit (seed) is partially surrounded by the bract. The calyx is reduced to a seed coat variously patterned in gray, brown, or black. The seed is slightly elongated and compressed, measuring two to six millimeters (1/12–1/4 inch) in length and one to four millimeters (1/24–1/6 inch) in maximum diameter. Seed weights vary from 600 seeds per gram (16,800 seeds per ounce) in wild varieties to very large seeds comprising only 15 seeds per gram (420 seeds per ounce) in cultivated varieties. Larger seeds have long been used as edible and medicinal fruit. Cannabis seeds provide an excellent nutritional source of easily digestible protein and essential fatty acids.6 Confusions in Terminology One of the first things that a person with a botanical or herbal background will notice is the many inconsistencies of the cannabis industry with the rest of scientific terminology. A lot of this confusion centers on female flowers, which are the focus of most marijuana growers, who mainly grow plants for

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THC levels. Botanists and horticulturalists, generally speaking, correctly use the term bud to mean any newly emerging plant part when it first appears as no more than a nub or protuberance, whether it will become a branch, flower, or leaf. Cannabis growers commonly use the term bud to refer to a distinct cluster of female marijuana flowers. This is so universally ingrained in marijuana usage by consumers and growers alike that we will use this popular meaning of “bud” in this course. (After-all, ‘This Bud is for You’) Botanically, cannabis buds are actually the racemes. Female flowers usually form in pairs that are so tightly bunched together with succeeding pairs that such pairing is apparent only in “running” buds most commonly seen in Southeast Asian cultivars. Much more typically, female flowers grow closely together, forming compact, egg-shaped or teardrop-shaped clusters, typically about 25 – 50 mm (1 - 2 inches) long, consisting of dozens of densely packed individual flowers. The oldest flowers are found at the bud’s base and the youngest at the top making it an indeterminate inflorescence. Cola, another commonly used term for female flower clusters, more often refers to an aggregate of flowers that, having formed so closely together, looks like a single, very large bud. Colas form at the ends of stems and branches and can be well over a 300 mm (1 foot) long. Foxtail is another name for cola, but the term is rarely used these days except by those who grew plants in the 1960s and 70s. By definition, a perianth consists of a corolla and a calyx. In more familiar showy flowers, the corolla is the brightly colored petals we generally appreciate when looking at flowers and the calyx is the smaller green cup (sepals) at the flower’s base. Bright showy colors, large flower sizes, and enticing fragrances evolved to attract insects such as bees and flies, or animals such as birds and bats to collect and transfer pollen to other flowers. Cannabis flowers are not brightly colored, large, or enticingly fragrant (at least to most non - humans) because cannabis plants are wind - pollinated with no need to attract insects or animals to carry the males’ pollen to female flowers. The bracts are covered with trichomes, more so than the surrounding leaves. In most cases, the higher the bract / leaf ratio is, the higher the THC levels of the bud are. For example, a 60 / 40 calyx (bract) to leaf ratio is better than a 30 / 70 ratio and will produce superior buds / flowers both in quality and quantity of overall flavor, strength, and THC levels. Many seed companies use these ratios when they advertise their strains. One of the first things that most likely attracted humans to cannabis is as a food source. Cannabis seeds (hempseeds), which strictly speaking are really

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more a nut than a seed, are exceptionally rich in polyunsaturated fats, essential fatty acid and protein. This super food has been used in Asian cooking as both a food and as a medicine for at least 3 millennia.

Types of Cannabis When you first go into a cannabis dispensary these days, it is easy to get overwhelmed by all the selection. Typically, back in the 1960s and the 70’s, people where just happy to be able to get some marijuana. They usually didn’t really care what kind of cannabis it was. Once in a while they could get a named type like Acapulco Gold, Colombia gold, Maui Wowie, Santa Cruz Haze or the prized seedless sinsemilla varieties. One of the things people knew was if it was named, the price went up. Some people knew the difference between Cannabis sativa and Cannabis indica, but most didn’t.

Today there are walls or showcases full of many different types that mostly have names that seem to have been created while the person was consuming high THC cannabis. Well I am here to tell you that most of these confusing names are (excuse me for saying it) just smoke and mirrors of marketing. It really has very little to do with the genetics or the cannabinoid levels. Several famous cultivars have changed their cannabinoid content in various cultivation methods. Now saying that, we are still going to use many of the ‘marketing names’ throughout the material to designate different cultivars. The thing is when you do genetic testing, you find that there are very little differences between them. The difference is cultivation and epigenetics (genetic influences beyond DNA base-pair structure), in other words, specific cultivars.

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There are really only two terms that have a meaningful distinction – hemp and cannabis. For the most part hemp plants are used for fiber. Cannabis, higher in THC, has been used for medicinal and recreation use. There is even confusion over this as several hemp cultivars are also high in CBD, which would now make them medicinal plants. All of a sudden, a bunch of hemp farmers woke up and realized they were part of a CBD goldrush, and their plants are now valuable for more than just fiber. By growing these cultivars a bit differently, they have medicinal plants. To get a better handle on naming all of this, we have to be familiar with a few words – genotypes, phenotype, chemotypes and cultivar. This is not meant to add confusion. These names are thrown around a lot by people with different educational backgrounds and some definitions are warranted.

Genotype: is a complete heritable genetic identity; it has a unique genome that would be revealed by genome sequencing. However, the word genotype can also refer just to a particular gene or set of genes carried by an organism. Phenotype: is a description of the plant’s actual physical characteristics. This includes straightforward visible characteristics like size, shape of leaves, and growing patterns. Chemotype (sometimes chemovar): is a chemically-distinct entity in a plant or microorganism, with differences in the composition of the secondary metabolites. Minor genetic and epigenetic changes with little with no effect on morphology or anatomy may produce large changes in the chemical phenotype.

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Cultivar: is an assemblage of plants selected for desirable characteristics that are maintained during propagation. More generally, a cultivar is the most basic classification category of cultivated plants in the International Code of Nomenclature for Cultivated Plants (ICNCP). The reason that we introduced this set of terms here is that they can be applied more effectively to cannabis than some of the older systems. As mentioned earlier, it had been thought that there is a big difference between Cannabis sativa and Cannabis indica. It turns out that this is not true. Most plants are hybrids of the two, making this distinction really a bit irrelevant and we will have to leave it to the botanists to decide if these are actually separate species or the same species that have grown up in different environments and acquired some distinctive traits. That is why we are calling them all cannabis. Because of this modern reality, we can rule out the basic term genotype here to distinguish the varieties. As far as phenotype, there is no doubt that many different varieties have been bred for various physical attributes, but most of this breeding has focused on making it easier to hide plants indoors. Once plants are grown under direct sunlight, they take on completely different attributes. Here it shows that epigenetic influences takes on a prominent role. Plants with similar DNA patterns respond differently to different environments. Environment thus changes the phenotype. During the dark age of the WAR ON DRUGS, plants were selected solely for high THC content, ease of clandestine cultivation for high yield, short growing cycle and minimal space requirements. In future, some of these cultivation choices will ease or disappear entirely. Chemotype does have relevance for discussing modern varieties in cannabis though. Knowing the prominent constituent levels will often determine the results that a person wants. Many people are now using a numbering system similar to the following: Type I: prominent delta-9 THC Type II: equal ratio between THC and CBD Type III: prominently CBD Since many people are still interested in the community or entourage effect, sometimes the prominent terpenes are also listed. So, this leaves us with cultivar names of cannabis with a chemotype description of cannabinoid content, often with a terpene picture to describe potential entourage effects.

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Methods of Consumption There are many different methods to consume cannabis. The prominent ways for intake are:

1. Inhalation 2. Ingestion 3. Sublingual 4. Suppository 5. Absorption

A few things to consider when choosing the right method for the user: THE USER’s: • Age • Genetics • THC Experience (tolerance) • Purpose of use (goal) • Current & Past Health History • Current meds (pharma) • Form the cannabis is in It is important to note that it is not a ‘one-size-fits-all’ medicine. It can be a highly individualized to best fit the user’s goals. No matter which method of consumption, ‘low and slow’ is the most important thing to consider. Start with quite low dosage and slowly increase if the goal is not achieved. Starting with ¼ dosage is a good place to start and increase every 2 – 5 days if the goal is not achieved. As a person gets use to the cannabis, often the tolerance goes up and a person needs more cannabis to get the same effect. Some people take up to a week to acclimate to a dosage level.

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THE MEDICINE: • Strain Category (Indica, Sativa, Hybrid, CBD) • Cannabinoid Profile (THC, CBD, and others) • Ratio THC/CBD • Terpene Profile METHODS Juicing Some people like to take in the raw herb in the form of a juice. In the past this was considered a non-starter, as most people were looking for the THC levels. Since there is no THC in the plant (only its acid precursors), people said juicing didn’t work. True. If you want THC, cannabis material has to be carboxalized (transformed by heat). Nonetheless, the phytocannabinoid acids in the plant have an array of uses on their own. CBD can be made in the body directly from the acid. In most people, they obtain a critical dosage of CBD, with less amount of cannabis (a cost saving). CBDA (cannabidiolic acid) THCA (tetrahydrocannabinolic acid) • Non-psychotropic for most people • the ‘raw’ cannabinoids • Anti-inflammatory • Antioxidant • Anticancer • Strong immune booster • Improved intestinal function • Improved neural function • Neuroprotective • Rebuilds bone • The body does not convert THCA to THC (that happens through a

heating process outside the body) • However, the body can convert CBDA into CBD, especially when

taking juice from the fresh leaves • Drinking juiced fresh cannabis leaves creates up to 4x more serum

CBD than other methods of consumption • Juice has a short shelf life 4-12 hours • It can be frozen. • Best consumed with other fresh juices • CBDA shows promise as an anticonvulsant, anti-nausea and anti-

emetic agent, analgesic and anti-inflammatory.

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• CBDA may also have antibacterial, antioxidant and cancer preventing properties

Inhalation This is by far the most popular method of ingestion, partly due to tradition, but it does create the quickest effect. When taking cannabis into the body through the lungs there is a quick onset 3-5 mins, with effects lasting 2-4 hours. The problem is inhaling may aggravate chronic bronchitis. Vaporizing vs Smoking: • Vaporizers heat the dried cannabis enough to boil (turn to vapor)

cannabinoids, terpenes and some flavonoids, but not hot enough to combust, thus avoiding the carcinogens associated with inhaling smoke

• Easier for patients to manage their dosage • It is considered one of the best routes to get the entourage effect, as

on some vaporizers you can specify the temperature, thus obtain certain terpenes.

• It often increases scent and especially taste, increasing pleasure to many patients

• Patients that have problems with coughing from other forms of inhaling may find vaporizing less of a problem.

• The temperature is substantially lower in vaporizing than smoking • Plasma concentrations for THC and CBD are the same whether

smoked or vaporized • Vaporizing uses a lot less product

Vaping is not Vaporizing:

Do not confuse e-cigarette (with e-juice) type ‘vaping’ devices with cannabis vaporizers that are specifically designed for use with dried cannabis flowers.

• Note that the term ‘vaping’ has come to be associated with e-cigarette type devices,

• Several brands of cannabis e-cigarettes are available in the unregulated market,

• Often these cannabis e-cigarettes contain highly potent THC products dissolved in toxic solvents used in the manufacturing process.

• Vape products that contain a liquid form of cannabis are unregulated and currently not legal.

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BoilingtemperaturesofCannabis’commoncannabinoids,terpenes,flavinoids&phytosterolsCBG(Cannabigerol) 52°C 126°F

CBDV(cannabidivarin) 65°C 149°F

THCA(tetrahydrocannabinolicacid)decarbstartsat90°C* 90°C 194°F

Humulene 107°C 225°F

Caryophyllene 129°C 264°F

CBDA(cannabidiolicacid)decarbstartsat80°C* 130°C 266°F

Beta-sitosterol(phytosterol) 134°C 273°F

Pinene 155°C 311°F

THC(tetrahydrocannabinol) 157°C 315°F

Myrcene 167°C 333°F

Limonene 176°C 349°F

Apigenin(flavinoid) 178°C 352°F

CBD(cannabidiol)(160°C-180°C) 180°C 356°F

Cannflavin(flavinoid) 182°C 360°F

CBN(cannabinol) 185°C 365°F

Terpinolene 187°C 369°F

Linalool 198°C 388°F

CBC(cannabichromene) 220°C 428°F

THCV(tetrahydrocannabivarin) 220°C 428°F

Terpineol 221°C 430°F

Combustion(200°C-230°C) 230°C 451°F

Quercetin(flavinoid) 250°C 482°F*NOTE:Ittakes"3hoursat100°CtoconvertTHCAfullyintoTHCand4hoursat98°C.Athightemperaturesabove160°Conlyabout10minutesandat200°ConlysecondsareneededtoconvertTHCAfullyintoTHC."REFERENCES:1USNationalLibraryofMedicine,NationalCenterforBiotechnologyInformation,PubChemOpenChemistrydatabase.https://pubchem.ncbi.nlm.nih.gov/2McPartland,John&Russo,Ethan.(2001).Cannabisandcannabisextracts:Greaterthanthesumoftheirparts?.JCannabisTherapeutics.1.103-132.10.1300/J175v01n03_08.3Wikipedia.https://en.wikipedia.org/4ProjectCBD.www.projectcbd.org5CerilliantAnalyticalReferenceStandards.www.cerilliant.com6KerstinIffland,MichaelCarusandDr.med.FranjoGrotenhermen,nova-InstitutGmbH.DecarboxylationofTetrahydrocannabinolicacid(THCA)toactiveTHC.http://eiha.org/media/2014/08/16-10-25-Decarboxylation-of-THCA-to-active-THC.pdf

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Ingestion • Cannabis taken into the body through the digestive system. • Offers a slow onset 30 – 90 mins, due to being processed through the

digestive system and liver. • The liver enzymes can change the chemistry and metabolite of the

cannabis a great deal, thus the effect is often different than inhaling • Ingested cannabis can be much more potent than inhaled … always

use caution with a new product or a THC-sensitive person. • Effects last 6-10 hours • Oils, tinctures (alcohol/glycerin), baking, drinks, tea, gummies,

lollipops, capsules (oils, decarbed powder) • Wait at least 4 - 8 hours between doses • Must be taken with fatty food because cannabinoids are fat-soluble

and won’t be effective unless properly digested. • If ingested cannabis is not properly digested, the person may not

feel the effects from that dose until the next time they eat, which could be 12 – 14 hours later. Bad news if your cannabis dose for sleeping doesn’t kick in until you eat breakfast!

Sublingual • Taken into the body by allowing it to absorb under the tongue. • Medium onset 20 - 40 mins • The effects last 4 - 8 hours • Works best with alcohol tinctures better than oil-based infusion • High alcohol concentration can cause reactions with tender tissue

under the tongue • Technology used in the supplement industry will soon be used to

create truly sublingual cannabis tablets • Always inquire about the solvent used to create concentrates such as

phoenix tears or RSO • Though acetone (commonly used as nail polish remover) is a potent

solvent, and strips most everything from the plant (the good and the bad) into a concentration, it will also concentrate molds, leftover fertilizers and pesticides, and other contaminants.

Suppository • Taken into the body through the rectum or vagina • The potential for impairment can be more pronounced for some or

not impairing at all for others USE CAUTION!

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• Used in cancer treatment as a way to get larger amount of cannabis medicine into the body

Absorption (Topical Application) • Taken into the body through the skin. • Psychoactivity is rare with salves and creams but THC-sensitive

people are prone to impairment. • Best for surface or muscle conditions. • Can reapply as needed • Alcohol rubs / liniments absorb more readily and needs to be used

with caution as psycho-activity more likely to occur CAUTIONS Even though youths the under 18 years old are among the most common consumers of cannabis, unfortunately it is not recommended. The teenage brain is not fully developed until early to mid 20s. There has been significant evidence that brain development will be slowed down and even stunted. Inexperienced users may also have an uncomfortable first experience with cannabis which can turn a person away from the very medication that could help them. The elderly & frail are another group that caution should be around as they are often more sensitive, while they are also likely taking multiple pharmaceuticals. On the other hand, this is a group than can often obtain the most benefit of the medicinal use of cannabis. The old adage low and slow is especially important here. Check with qualified health care provider! Many elderly are experiencing amazing health gains with CBD! For those with advanced cardio-pulmonary disease, HC can cause tachycardia (rapid heartbeat), fainting & changes in blood pressure, any of which could be dangerous for patients with severe cardio-pulmonary disease. Type 1 Diabetics who use cannabis are nearly twice as likely to develop the potentially fatal complication ketoacidosis.7 Note: cannabis, specifically CBD, may actually help people with Type 2 diabetes reduce blood sugar levels and make their insulin more effective. • However, we must use caution with high levels of CBD for people

who exhibit symptoms of pre-diabetes High doses of CBD can lower blood sugar levels leaving a person dizzy, light-headed and lethargic.

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Some mental health disorders should be check with a qualified healthcare provider.

• Do not stop any medications without the supervision of a doctor. Always ask for help.

• Watch for emerging studies on CBD being used to help manage

some mental health issues. Pregnancy and lactation:

• a 2014 (animal) study shows that pure THC interferes with fetal brain development

• THC use during pregnancy may result in low birth weight - check with a qualified doctor

• pre-pregnancy -- heavy cannabis use may lower sperm count • Allergies to cannabis, Although rare, some people experience an

allergic reaction when using or being in contact with cannabis. Adverse Reactions • tachycardia (elevated heart rate) • paranoia • increased anxiety • dizziness • disorientation • perceived time alterations • impaired motor control • numbness • dehydration (red eyes, dry mouth, headache, etc) • decreased motivation • lethargy • low blood sugar • Hyperemesis Syndrome (cyclical vomiting) depends on frequency,

high dosages over time, and the user’s genetics • hot showers can provide some relief • abstinence for at least 30 days can reset the ECS to proper

functioning. To avoid recurrence, dosage must be set at the smallest amount that provides relief. Frequency of dosing should be spread out as much as possible

• It may turn out that this issue is a result of taking in toxins from improper growing and manufacturing techniques of the product. More study is needed.

Side-effect or Desired-effect? • Sedative or treatment for insomnia?

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• Appetite stimulant or treatment for loss of appetite (anorexia)? • Catalepsy (couch lock) or relief from nervous tension? • Impaired short-term memory or relief from PTSD?

INHALATION CAUTIONS • Smoke contains toxic by-products such as carbon monoxide,

polycyclic aromatic hydrocarbons (PAHs), and tar • 2nd hand smoke and 2nd hand vapor can be dangerous for others in

the room. Do not smoke, vaporize or vape around babies, children, teens or people sensitive to THC.

• Be aware of the solvent used to create concentrates. Smoked concentrates may contain trace amounts of solvents such as butane. Small amount of butane, over time can cause cumulative damage to lungs, liver and kidneys - similar to the effects of inhaling pollution

THC Tolerance • Aka “membrane receptor endosome internalization” the cell

literally pulls cannabinoid receptor inside, where it is no longer available to be stimulated

• Tolerance levels vary greatly for individuals (from 3-5mg to 300-500mg+)

• Tolerance can happen to any cannabis user within a few hours/day/weeks/months (have you ever ‘smoked yourself straight’?)

Certain conditions (cancer, chronic infection) may respond better to very high doses, so one may need to deliberately up their tolerance by slowly increasing dosage over a few days/weeks • “sensitization protocol” allows one to reset the sensitivity of the

ECS • 24 hours - 6 days abstinence from Cannabis is usually long enough

to reset the receptors • some require 3 months to reset, then keep to low doses with

reduced frequency If abstinence not an option,changing strains can help avoid or managetolerance levels.

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THC Sensitivity • Some people can become increasingly sensitive to ingested THC • Even small amounts (0.5mg THC) can leave them light-headed,

unable to focus on work, and lethargic. • These individuals can experience the same ‘couch-lock’ or ‘stare-

at-the-wall’ side-effects usually associated with high THC intake Microdosing • A technique for studying the behavior of ‘therapeutic agents’ in

humans through the administration of doses so low ("sub-therapeutic") they are unlikely to produce whole-body effects, but high enough to allow the cellular response to be studied.

https://en.wikipedia.org/wiki/Microdosing • Some people benefit from taking very small amounts of cannabis to

‘remind’ their endocannabinoid system to kick in • Small amounts of cannabis taken more often may help avoid psycho-

activity • By microdosing as a preventative, when an outbreak of symptoms

occurs a larger dose can be taken without experiencing tolerance Preliminary studies on microdosing cannabis suggest that low amounts of THC will up-regulate the endocannabinoid system “… ultra-low THC doses proved cardioprotective … given 2 h or 48 h before experimental MI in mice produced echocardiographic benefits on physiological measures, fractional shortening elevation, smaller infarct size, decrease in serum troponin and neutrophil infiltration to highly statistically significant degrees. Ultra-low doses of CBD have produced similar benefit as well as neuroprotective effects, and the combination is additive/synergistic, suggesting possible utility as protective agents prior to cardiopulmonary bypass.” Ethan B Russo, Synthetic and natural cannabinoids: the cardiovascular risk. The British Journal of Cardiology Vol 22 Issue 1 January–March 2015 http://cannabisclinicians.org/wp-content/uploads/2015/04/Russo-Editorial-Synthetic-and-natural-cannabinoids-the-cardiovascular-risk-Brit-J-Cardiol-2015.pdf Entourage Effect • Like all plant medicine, the whole plant is often more powerful than

its individual constituents.

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“Use the herb, the whole herb and nothing but the herb so help me Herbalist!” … Dr. Terry Willard, PhD

Cannabis Dosing How much in a dose? To answer this question, we have to consider many other factors first. One of the first factors to remember is that cannabis is a natural substance and not just a delivery system. As a natural product, the amount and variety of the various cannabinoids and terpenes can vary considerably. Some of the things that you will have to consider upon deciding the doses can vary due to the following factors:

1. Method of consumption 2. Potency of product 3. Age of the product 4. Contaminants 5. Packaging of product 6. Absorption rate 7. Target area of desired outcome

As a natural product, cannabis is perishable. This means that harvesting and storing can contribute to the shelf life of the product. During growing, ‘curing’ and packaging, various substances can be added to the product that might change its therapeutic values. Certainly fertilizer, pesticides, and other additives can affect the therapeutic end results, but some suppliers have been known to add various chemicals to ‘enhance’ the perceived potency of the plant. This is mostly an artifact of the grey and black-market use in the past, but it still does creep in. Bottom line here is; medicinal cannabis should be obtained from reliable sources. This might be a

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reputable company, a trusted artisan grower or at least someone you can trust who stands behind their product. Sometimes during the processing and storing procedures various issues can sneak up. Molds, mildew and bacteria can contribute to a poor product. Many people desire organically grown product in sustainable, non-contaminating packaging. The old idea of storing cannabis in a plastic sandwich bag is actually a bad one. It will lead to rapid bruising, deterioration and rupture of the trichomes resin heads. Plastic such as polyethylene and polypropylene are quite commonly used, but inappropriate for storing cannabis flowers that are high in terpenes like limonene, as they will dissolve the plastic. The most limonene-resistant plastic is polyethylene terephthalate (PET). Opaque glass storage containers are best and also reduce light degradation. All containers should have airtight lids to reduce oxidation. Both storage and solubility become an issue due to the nature of both the cannabinoids and terpenes. They both hate water and love oil; they are hydrophobic and lipophilic. When taking cannabinoids orally, this solubility poses a bit of a problem. Cannabinoids are poorly and erratically absorbed. There has been lots of research in this area over the last few decades, but few solutions. Dosage Most patients and even many practitioners have poor knowledge of dosage and administration of herbal cannabis. This is one of the reasons they like to stick to ‘pharmaceutical grade product’. This is often unfortunate as it might not give as good of an outcome for the consumer. This is further confused by the stereotypical media image that reinforces the absurd notion that cannabis use only results in befuddled intoxication. YouTube and reality TV have done little to counter this. The “befuddled” mime is just too tempting for media. Many consumers feel that they build up a tolerance to the cognitive impact of using high doses of THC. This has been proven wrong in 2016 upon testing those deficits.8 The most important mantra to observe when dosing is:

Low and Slow This method starts with the low dosage and slowly titrate up until therapeutic outcomes are reached. Yes, this technique takes a bit longer to get to the desired level, but it assures the consumer of getting the best results at the lowest cost for that form of consumption. This is supported by

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observations from pharmacologists that dosing levels (especially for THC) exhibit a biphasic effect; showing that a small dose may activate a receptor, whereas a high dose may inhibit the same receptor.9

Route of consumption It is important to note that the mechanism of consumption can radically change the outcome. The fastest result of outcome is through the traditional way of inhalation. Both the cannabinoids and the terpenes get into the bloodstream rapidly with initial affect in less than a minute and peak blood levels within 6-7 minutes usually. Vaporization of the powdered flowers seems to be the best. If using a sublingual (under the tongue) or oromucosal method, levels are reached in 5 – 15 minutes. THC absorbs faster than CBD. If ingested via the gastrointestinal system, cannabinoid absorption is both slow and inconsistent. It often takes 2 hours if consumed with some fatty food but may not be felt until the next meal 6 – 20 hours later. Peak levels are achieved after about 7 hours of first onset of outcome. For this reason, many patients use a hybrid of the two systems, with both ingest and inhalation. They will start to get some outcomes within a few minutes from the inhalation and continue getting more long-term results from the ingestion. This idea is great in concept and has worked for many, but it must be realized that the outcomes from inhalation and oral can vary a great deal. If the cannabinoids are routed into the bloodstream via the gastrointestinal tract, they do this via the liver. The liver can alter the metabolite a great

“biphasicdose-responsecurve”h3p://healer.com/cannabis-dosing-less-is-usually-more/

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deal. This level will vary from person to person and also with an individual’s liver health.

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M o n i t o r d o s a g e START LOW. GO SLOW. ! important for all intake methods!

• Watch for buildup of tolerance or sensitivity buildup • Monitor blood sugar imbalances • Dehydration symptoms (headaches, dry eyes/mouth, etc.) • As the endocannabinoid system tones, drop to maintenance dose • ‘Pulse’ product use to see if it is still required • Watch for signs of lethargy and demotivation as this may not be

apparent to the user

B a s i c D o s i n g G u i d e l i n e s C B D & T H C CBD (for treatment of anxiety, depression, pain, inflammation, spasms, etc.) • oral: 25mg - 75+mg daily in 2-3 divided doses taken with a little

fatty food; • dosage is increased until symptom relief; can be increased to

treat/slow down disease processes • inhalation: 2-10 inhalations as required to treat breakthrough

symptoms THC (insomnia, pain, nausea, depression & PTSD (sativa), etc.) • oral: start at 1-3mg taken with a little fatty food; increase based on

symptom relief and tolerance; monitor and change dose/strain as required

• inhalation: 1-5 inhalations when quick action required (induce sleep, stimulate appetite, etc.) and for breakthrough symptoms

No driving or operating heavy machinery when on THC. D o s i n g f o r S p e c i f i c H e a l t h C o n d i t i o n s • Anxiety • Appetite Loss & Nausea • Autoimmune issues (Arthritis, Fibromyalgia, Multiple sclerosis, etc) • Chronic Pain • Irritable Bowel (IBS) • Insomnia

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• Menstrual Issues (PMS, Cramps, Endometriosis) • Migraine Headaches • Social Anxiety • Seizure Disorders A n x i e t y CBD oral: • Start with 25mg daily with breakfast • Increase until symptom relief (25 - 75+mg/day) • Can be taken all at once but better in divided doses • If not getting relief after 2 weeks, add in 1-2mg THC with CBD in

morning • Inhalation: 2-10 inhalations as required to treat breakthrough

symptoms

A p p e t i t e L o s s & N a u s e a • THC affects smell, taste and the hormones that stimulates hunger • Endocannabinoids, produced by the body’s endocannabinoid system,

regulate hunger hormones • Smoked cannabis increases levels of key hunger-regulating

hormones, ghrelin and leptin, while not significantly altering insulin levels

• THC improves perception of taste and smell • Avoid strains high in the terpene Humulene and high in the

cannabinoid THCV • Use CBD as a daily ‘adaptogen’ supplement to tone and heal

digestive issues (25 - 75+mg daily)

A u t o i m m u n e I s s u e s Arthritis, Fibromyalgia, Multiple Sclerosis, etc. • Focus on anti-inflammatory factors: • CBDA and CBD • CBGA and CBG (the mama cannabinoid from immature plant) • Terpene Caryophyllene • Early studies are promising but more research required Long term oral administration of CBDA, CBD, CBGA and CBG is key! • Oral: • 50 - 100+mg daily CBD in 2-3 divided doses

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• Juice raw, young leaves and take 15 - 30 ml daily; dilute with fresh green juice

Inhalation: • Inhaled CBD in AM to help with stiffness and pain • Inhaled as required THC to treat pain: start with 1:1 THC/CDB;

increase THC potency if required to find relief • At around 3-6 months, noticeable changes should be experienced • May require lifelong supplementation

C h r o n i c P a i n • CBD manages pain by reducing inflammation • THC manages the perception of pain • Start with THC/CBD with ratio of 1:25 or 1:20 for the first day • Take 25 - 50mg, 1-3x daily for two weeks • If relief not adequate, increase amount of THC by small amounts

every second day. The goal is to find dose that treats pain without impairment.

Oral administration = long term relief (4-8 hours) Inhalation of THC/CBD 1:1 or 1:0 = instant relief

I r r i t a b l e B o w e l ( I B S ) • Long term oral administration of CBD is key • 50 - 75+mg daily in 2-3 divided doses For first few weeks: • Use inhaled THC to treat cramping and pain • Use inhaled CBD to after meals to help with digestion • At around 12 weeks noticeable changes should be experienced (less

urgency, better formed stool, reduction of food intolerances, etc.) • May require lifelong supplementation

I n s o m n i a Oral THC (1:0, 1:1 or 1:2 THC/CBD) • 2-10mg 30 - 90 before bedtime *take with a little fatty food* • Increase by 0.1mg nightly until sleeping well, without morning

grogginess • May be able to decrease to microdosing (drop doses) after a few

months Inhalation (THC potency dependent on tolerance)

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• 1-5 inhalations before bed or if waking in the night

M e n s t r u a l I s s u e s • Women’s natural cannabinoid cycling of anandamide (AEA - the

bliss molecule) peaks around ovulation and is at its lowest during menstruation

• During ovulation there is more AEA in the uterus than anywhere else in the body

• supplementation with plant cannabinoids can be helpful to ease inflammation, moodiness, and irritability

M e n s t r u a l i s s u e s : P M S • CBD taken as a toning/adaptogen will bring down inflammation in

the female reproductive organs • 50+mg daily for 3 - 6 months • Maintenance dose of 10 - 25mg daily M e n s t r u a l i s s u e s : C r a m p s • CBD taken as a toning/adaptogen will bring down inflammation in

the female reproductive organs • Inhalation of THC/CBD 1:1* = instant relief of cramping

M e n s t r u a l i s s u e s : E n d o m e t r i o s i s • Preliminary studies suggest THC can activate cell migration of

endometrial tissues if condition is present • This can be offset by the presence of CBD • Use 1:3 ratio THC/CBD or higher CBD • CBD taken as a toning/adaptogen will bring down inflammation in

the female reproductive organs • 50+mg daily for 3 - 6 months; maintenance dose 10-25mg/day • Inhalation of THC/CBD 1:3+ = instant relief of cramping

M i g r a i n e H e a d a c h e s THC is the first aid/band-aid CBD is the long-term solution • Start with THC/CBD with ratio of 1:25 or 1:20 • Take 50-75+mg daily for 6 - 12 weeks; then drop to maintenance

dose of 25 - 50+mg daily

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• If relief not adequate, increase amount of THC by small amounts • Oral administration = long term relief (4-8 hours) • Inhalation of THC/CBD 1:0 or 1:1 = instant relief. • Some may require high THC 20%+ when migraine takes hold • Consider electrolyte drinks when dosing high THC

S o c i a l A n x i e t y • Start with high CBD with ratio of 1:25 or 1:20 (THC/CBD) • Take 25-75+mg daily for 6 - 12 weeks; then drop to maintenance

dose of 15 - 25mg daily • If relief not adequate, add tiny amounts (1 drop) of THC, increasing

every day or two until desired relief • Oral administration daily for all-day relief • Inhalation of high CBD strain before stressful situations Be very careful with THC as it can exacerbate anxiety for people who are THC-sensitive.

S e i z u r e D i s o r d e r s Recent study: • 20mg of CBD per kg of body weight vs placebo • 43% of CBD participants had greater than fifty percent reduction in

seizures compared to 27% of those taking placebo • 3 of the CBD-only participants were seizure free during the study • Ongoing studies with CBG and THCV • Ensure the product has been tested for THC content as some people

are highly sensitive to THC which can bring on seizures in certain individuals

• Always work with a qualified medical practitioner • Refer children under 18 to a cannabis-educated physician

S u m m a r y • High CBD strains (under 2% THC or 2mg/ml THC) • Watch for possibility of low blood sugar when taking high doses of

CBD • Watch THC levels in strains marketed as ‘CBD’ • Monitor dosing - keep a journal • Required amounts will change as body changes

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• Cannabis is not a cure-all, however when used with respect it is an important tool in the herbal apothecary

End Notes

1 McPartlan J and Guy, G W; Cannabis May Have Evolved in the Northern Tibetan Plateau; 26th ICR Symposium 2016 p 61 2 Klaudyna Fidyt, Anna Fiedorowicz, Leon Strządała, and Antoni Szumny; β-caryophyllene and β-caryophyllene oxide—natural compounds of anticancer and analgesic properties; Cancer Med. 2016 Oct; 5(10): 3007–3017. 3 Vaney C, Heinzel-Gutenbrunner M, Jobin P, et al. Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study. Multiple Sclerosis. 2004;10:417–424.[PubMed] 4 RC Clarke – 1981; Marijuana botany: An advanced study: The propagation and breeding of distinctive cannabis: Ronin Publishing; 2nd edition

5 Michael Pollan; The Botany of Desire: A Plant's-Eye View of the World; 2001); Random House 6 Jean-Luc Deferne and David W. Pate.; Hemp seed oil: A source of valuable essential fatty acids: http://www.druglibrary.org/olsen/hemp/iha/iha03101.html 7 Akturk HK, Taylor DD, Camsari UM, Rewers A, Kinney GL, Shah VN. Association Between Cannabis Use and Risk for Diabetic Ketoacidosis in Adults With Type 1 Diabetes. JAMA Intern Med. Published online November 05, 2018. doi:10.1001/jamainternmed.2018.5142 8 J.G Ramacker, et al; Cannabis and Tolerance: Acute Drug Impairment as a Function of Cannabis Use History; Scientific Report 6 (2016) 9 Patel S, Hill MH, Hillard CJ; Effect of Phytocannabinoids on Anxiety, Mood and the Endocrine System; in: Handbook of Cannabis, editor RG Pertwee, New York; Oxford Press; 2014; p192