The History and Science of Cannabis
The use of cannabis for medicinal purposes can be dated back to as early as 2700 B.C.; the Chinese, European, and Indian populations would use the plant for its healing effects as an antidepressant, antiseptic, antibiotic, analgesic, anesthetic and sedative.
The spread of the cannabis plant first started in China, where hemp – one of the varieties of the cannabis plant – was grown as an agricultural crop because of its high protein, seeds, oil, and fiber properties. It was used to make clothes and ropes, along with many other daily-use items. Having a THC concentration of less than 0.03%, hemp is a non-psychoactive plant.
In 2723 B.C., the Emperor Shen Nung prescribed cannabis for various medical conditions such as gout, rheumatism, and poor memory. Shen Nung was known as the “father of Chinese Medicine” as he was recognized to be a strong believer in healing being achieved through the use of herbal remedies.
From China, the spread of the cannabis plant made its way to other regions of the world, including Asia, the Middle East and Africa.
In India, ancient use of the cannabis plant can be dated back to as early as 200-1400 B.C. Devotees of the Hindu Gods would use cannabis as a way to connect with religion. Others would use it for medical, recreational, and spiritual purposes.
India is also known for the popular drink, “bhang” – this is a mix of cannabis paste which is made from the buds and leaves of the plant, mixed with milk, ghee (Indian butter), and various spices. Bhang is consumed during religious celebrations to “let loose” and feel happy.
Other reported benefits of bhang include the potential to:
- cure dysentery
- cure sunstroke
- clear phlegm
- improve digestion
- increase appetite
- improve mood
- heighten physical alertness
In Ancient Egypt, the Ebers Papyrus, an Egyptian medical textbook, includes scriptures describing the medical uses of cannabis. Some literature from as early as 1550 B.C. includes the use of cannabis for treating inflammatory conditions.
Modern uses of cannabis can be found as early as the 1500s, when the Spanish introduced cannabis to Latin America. The focus at the time was on the hemp industry – using hemp to make paper, bags, clothes, and ropes.
In the late 1700s, cannabis was receiving more recognition in countries such as America and England. Cannabis was a popular medical aid for patients suffering from rheumatic diseases and to help alleviate nausea.
Moving forward to the 1900’s, America was introduced to cannabis and it quickly became popular for its recreational use.
By 1970, cannabis was officially declared a schedule 1 drug, despite the fact that many medical journals were publishing research demonstrating the beneficial effects of the plant. The government halted all further research into the plant’s scientifically viable and medicinal properties.
By April 2015, 23 American states had legalized the use of cannabis for medical purposes only. Today, 33 American states have officially legalized medical cannabis use.
Meanwhile in Canada, the Canadian government added cannabis to the list of restricted drugs under the Opium and Narcotic act in 1923.
It was not until the 1990’s that the government felt the pressure of thousands of medical patients advocating and fighting for the use of cannabis. On July 30th, 2001, the government brought this into a legislative act known as the Medical Marijuana Access and Resources (MMAR). Canadians were able to purchase their medicine from Health Canada approved Licensed Producers. Patients also had the right to produce their own medicine or designate a grower to produce medical cannabis on their behalf.
Over the next several years, cannabis rules and regulations were reviewed, giving rise to the Marijuana for Medical Purposes Regulations (MMPR). This legislative act did not allow Canadian patients to grow their own medicine.
Eventually, the government bowed down once again, and released the guidelines set in the Access to Cannabis for Medical Purposes Regulations (ACMPR), the legislative act which once again allowed patients access to cannabis from both Licensed Producers, as well as the option to grow their own medical cannabis or assign a designated grower.
As of October 17th 2018, the Canadian government has decriminalized recreational use of cannabis under legislative bill C-45, also known as the Cannabis Act. The passing of bill C-45 has created a legal framework for recreational users and has also incorporated the rules and regulations of the ACMPR.
What Does the Legal Framework Mean for Canadians?
Bill C-45 outlines the rules and regulations set forth by the Canadian government which applies to all Canadians interested in consuming cannabis for recreational and/or medicinal purposes.
Canadians interested in becoming medical patients require a medical prescription completed by the prescribing physician or nurse practitioner. The medical prescription, referred to as the medical document, outlines the dosage of treatment (i.e. number of grams of cannabis per day) and the duration of treatment (for example, one month, three months, six months, or one year).
Although Canadians are able to access recreational cannabis legally, a patient who is considering cannabis for medical purposes should be aware of the following key differences:
- Recreational users are allowed to carry and travel with up to 30 grams of cannabis within Canada.
- Medical users, with a medical authorization, are allowed to carry up to 150 grams (or a 30-day prescription, whichever is less) of cannabis within Canada.
Growing your own cannabis:
- Recreational users are allowed to order seeds from Health Canada approved Licensed Producers and are allowed to legally grow up to four plants per household.
- Medical users are able to grow an abundant amount of plants, per patient, as per the allowance of their medical prescription.
- Medical Cannabis is considered a medical expense and can be claimed on a patient’s income tax.
- Many insurance companies offer coverage for a patient’s medical cannabis.
As more and more Canadians are interested in learning about how cannabis may help their medical conditions, the challenge in the cannabis industry now becomes how to inform and educate the medical community about the medical benefits of cannabis.
With recent legalization, the limelight has been heavily focussed on the scientific properties of cannabis, and its involvement in the Endocannabinoid System.
The Discovery of Endocannabinoids:
Although cannabis use for medical purposes all over the globe dates back to thousands of years B.C., the natural plant received much stigmatization from world governments, often resulting in prohibition. This was due in part to the fact that the plant was considered a recreational substance, causing users to become “high”.
The scientific properties of the plant remained elusive and mysterious until Dr. Raphael Mechoulam and his team of researchers discovered and isolated specific molecules within the cannabis plant called “phytocannabinoids” or simply, plant cannabinoids.
In 1964, the first phytocannabinoid, tetrahydrocannabinol (THC), was isolated. This historic discovery laid the foundation for Mechoulam’s team and propelled them to research and investigate the effects of THC on the human body.
In 1988, another important discovery was made. The human body showed significant evidence of harboring specific receptors, aptly known as cannabinoid receptors. The team continued to make advances in science and medicine, and In 1992 it was discovered that the human body was actually capable of producing its own cannabinoids. These endogenous cannabinoids would ultimately come to be referred to as “endocannabinoids.”
Since the discovery that yet another anatomical and physiological system exists within the human body, research and evidence has been flourishing within the scientific community.
Dr. Raphael Mechoulam and his team had uncovered the Endocannabinoid System.
What is the Endocannabinoid System (ECS)?
The Endocannabinoid System (ECS) is an adaptive response to cellular stress, aimed to re-establish cellular homeostasis.
According to researchers, the ECS is found in all mammals, and can be identified as early as in the embryonic stage of life.
The ECS is shown to monitor all physiologic and regulatory functions of the human body. Over time, the alternation in the mechanics of the ECS leads to pathological diseases as the human body is challenged by both internal and external stimuli.
How does the ECS function?
To understand the functionality of the ECS, it is important to grasp the concept of a “lock and key” system. The analogy of the “lock and key” in layman’s terms reflects the concept of a neurotransmitter (the “key”) targeting a receptor (the “lock”) within the human body. Once the key interacts with the appropriate lock, a signal occurs; this signal will either inhibit or stimulate a downstream process.
In the ECS, the “keys” are referred to as endogenous cannabinoids.
To date, there have been five distinct endocannabinoids discovered:
- Anandamide (N-arachidonoyl ethanolamide) (AEA)
- 2-arachidonoylglycerol (2-AG)
- 2-arachidonyl-glyceryl-ether (Noladin ether)
- O-arachidonoyl-ethanolamine (Virodhamine)
- N-arachidonoyl-dopamine (NADA)
The two most researched endocannabinoids are 2-Arachidonoylglycerol (2-AG) and Anandamide (AEA).
To understand the functionality endocannabinoids, it is important to understand the basics of the nervous system.
The Nervous System
The Nervous System is the “umbrella term” for the two systems, the Peripheral Nervous System and the Central Nervous System. The Central Nervous System (CNS) is composed of the brain and spinal cord. The Peripheral Nervous System (PNS) includes the Autonomic Nervous System and Somatic Nervous System. The Autonomic Nervous system is further categorized into the Parasympathetic Nervous System, the part of the brain that is responsible for keeping the body calm and relaxed, and the Sympathetic Nervous System, the signalling system of the brain that prepares the mind and body for handling difficult and emergency situations.
Neurons and Neurotransmitters
Neurons are specialised cells within the nervous system which transmit neurotransmitters (chemical messages) from neuron to neuron, or from a neuron to another type of cell within the body.
The part of the neuron that receives the neurotransmitter is called the dendrite. A signal, referred to as an action potential is generated if a certain chemical voltage is met. The action potential travels along the axon, which is essentially the nerve fiber of the neuron. The action potential reaches the end of the axon (the axon terminal), which then stimulates the release of the neurotransmitter.
Neurotransmitters are synthesized and pre-packed into specialized pouches called vesicles. Vesicles are bound to the membrane of the neuron; this area is called the synaptic knob. The “inactivated” vesicles are kept in place by a group of proteins called the SNARES.
Once the action potential arrives at the axon terminal, specialized calcium gates embedded within the neuron open, causing an influx of calcium. Calcium then binds to a specific protein called the Synaptotagmin, which induces a change in the conformation of the SNARES. The SNARES will then release the vesicles, ultimately culminating in the fusion of the vesicles with the membrane terminal. Next, a process called exocytosis occurs, where the neurotransmitter is released into the synaptic cleft, the space between the two neurons.
The neurotransmitter from the first neuron (“the presynaptic neuron”) fuses with specific receptors embedded within the second neuron (“postsynaptic neuron”). The fusion of the neurotransmitter to its receptors is referred to as the “synapse”. The synapse may or may not generate an action potential; if an action potential is generated again, this will travel down the axon of the second neuron and continue the process of signal transmission as long as action potentials continue to generate.
How are Endocannabinoids Different from Neurotransmitters?
To reiterate, neurotransmitters found in the human body, such as Serotonin, Dopamine, Acetylcholine, and Glutamate, are pre-synthesized and stored in vesicles. Endocannabinoids on the other hand, are synthesized “on demand” from arachidonic acid, a precursor found in the protective layer of the cells of the postsynaptic neurons.
The endocannabinoids will then travel in a retrograde fashion to the presynaptic membrane where the cannabinoid receptors are located.
Once the endocannabinoid has interacted with the appropriate cannabinoid receptor, the endocannabinoid is degraded by specific enzymes. Through hydrolysis, AEA is degraded by the enzyme fatty acid hydrolase (FAAH) and 2-AG is degraded by Monoacyleglycerol lipase (MAGL).
The discussion on the “key and lock” system is only complete after reviewing the basics of receptor physiology. As mentioned above, the endocannabinoids are analogues to “keys” whereas as the locks are cannabinoid receptors, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2).
Both CB1 and CB2 are G-protein coupled receptors, and have many subtypes which include:
- ion channels abbreviated as “Go”,
- inhibitory receptors abbreviated as “Gi”, and
- stimulatory receptors abbreviated as “Gs”.
“Go” channels operate by opening and closing; the “Gi” receptors inhibit the neurotransmitter adenylate cyclase; whereas the “Gs” receptor stimulate adenylate cyclase.
The function of the cannabinoid receptors depends on which agonist activates the receptor.
One key opens many locks, but depending on what lock is targeted, a different door will open. This is called “Agonist Trafficking”.
For example, the phytocannabinoid, THC, stimulates “Go”, leading to the closure of the calcium channel. However, if THC stimulates “Gi”, this will lead to an inhibitory effect on adenylate cyclase.
Where are Cannabinoid Receptors Located?
Cannabinoid receptors can be found in almost every anatomical location of the human body. This includes different organs, tissues, and glands.
CB1 Receptors are found primarily in the Central Nervous System (CNS), reproductive organs (testes, uterus), heart, spleen, connective tissue, endocrine glands, exocrine glands, leukocytes, and throughout the gastrointestinal tract.
CB2 Receptors are found primarily in the liver, the immune system (monocytes, macrophages, B-cells, T-cells, spleen, and tonsils), the liver, the CNS and the Enteric Nervous System (ENS).
Nervous System: CB1 Distribution in the CNS:
The CB1 receptor is the most common g-protein coupled receptor in the brain. The highest densities are found in the hippocampus, cerebral cortex, cerebellum, amygdala nucleus and basal ganglia. This accounts for short-term memory, cognition, mood and emotion, motor functions, and nociception.
Why Can’t You “Overdose” on Cannabis?
Although cannabinoid receptors are heavily distributed in the CNS, they are essentially absent in the brainstem, the part of the brain where the cardiorespiratory center is found. The cardiorespiratory center is responsible for our brains to subconsciously control our breathing. Therefore, due to the absence of CB1 and CB2 in the brainstem, there is no lethal overdose capability due to cannabis.
On the other hand, opioid receptors are found in the brainstem. Opioids interact with its receptors located in the brainstem. As higher amounts of opioids are consumed, the receptors become saturated and eventually slow down breathing. Thus, there is a lethal overdose capability with opioid abuse.
The cannabis plant consists of two basic species, Cannabis Sativa and Cannabis Indica. The Indicas are known to have emerged from the Indian subcontinent, and are valued for their calming effects (“in the couch”). Sativas on the other hand have emerged from Eastern Asia, and generally cause uplifting effects. Depending on the ratio of THC to CBD, the user will experience a certain spectrum of psychoactive effects.
These two strains look different and contain different ratios of the primary cannabinoids (relevant for when selecting a strain for specific therapeutic purposes).
The following table highlights a few key differences between the Sativa and Indica species spectrum of psychoactive effects.
These two strains look different and contain different ratios of the primary cannabinoids (relevant for when selecting a strain for specific therapeutic purposes)
The following table highlights a few key differences between the Sativa and Indica species.
|Cannabis Sativa||Cannabis Indica|
|Higher THC to lower CBD/CBN ratio||Lower THC to higher CBD/CBN ratio|
|Tall in appearance (can grow up to 20 feet in height) with a fine leaf structure||Short and stocky in appearance, with wide leaves|
|Usually grown outdoors||Better suited for growing indoors|
|Generally stimulating, energizing, uplifting||Generally sedating, relaxing, grounding|
|Generally more mental/emotional (cerebral, spacey or hallucinogenic)||Generally more physical |
(body buzz or “couch lock”)
|Best for daytime use||Better after work is done, before bed|
|Usually more extrovert||Usually more introvert|
|Increase alertness||Sleeping aid|
|Consider with depression||Consider with anxiety and to reduce stress|
|Pain relief, muscle relaxant||Pain relief, muscle relaxant|
|THC binds both CB1 and CB2 receptors||CBD has greater affinity for CB2|
Hybrid strains refer to a crossbreeding of Indica and Sativa strains. This has led to a wide variety of newer, unique strains. The strain can either take dominance to one parent strain over the other (ex. Sativa-dominant or Indica-dominant), or be a balanced blend of both
Phytocannabinods, as introduced earlier, are cannabinoids that are naturally occurring in the cannabis family of plant. There are over 70 phytocannabinoids found in the cannabis plant. The two most talked about phytocannabinoids are tetrahydrocannabinol (THC), and cannabidiol (CBD). Other phytocannabinoids include: cannabigerol (CBG), cannabichromene (CBC), cannabinol (CBN), and cannabitriol (CBT).
THC is the compound that provides psychoactive and euphoric feelings (the “high”). It easily binds to CB1 receptors in the brain.
THC has been reported to have many medicinal benefits that can help with a number of conditions such as: pain, glaucoma, insomnia, anxiety, muscle spasticity and depression.
CBD, unlike THC, is the compound that is devoid of psychoactive effects. It does not easily bind to CB1 receptors in the brain and it functions by inhibiting THC’s ability to create the sensation of getting high, and reducing its effects.
The medicinal properties of CBD can help with the following medical conditions: psychosis, seizures, anxiety, depression, nausea, pain, inflammation, psychiatric disorders and migraines.
The cannabis plant is composed of thousands of biologically active molecules which not only include phytocannabinoids, but also include terpenes and flavonoids. These molecules all interact to enhance the medical effects of cannabinoids on the CB1 and CB2 receptors, which is known as the “entourage effect”
Terpenes, like phytocannabinoids, are biological compounds found in cannabis, and can provide additional medicinal benefits. Some well researched terpenes include:
- Beta-Myrcene, known for its analgesic, anti-inflammatory, antibiotic, and anti-mutagenic properties,
- Limonene, known for its antifungal properties,
- Pinene, known for its anti-inflammatory, bronchodilator, and antiseptic properties,
- Linalool, known to improve cognitive and emotional functions, decrease inflammation, and promote calming and relaxing effects, and
- Beta-caryophyllene, known for its anti-inflammatory and anti-nociceptive properties.
Flavonoids are pharmacologically active compounds found in all plants and flowers. In the cannabis plant species, flavonoids provide color pigmentation, odor, flavour, protection, and potential medicinal benefits. They also provide protection from harmful elements such as UV rays, pests, and diseases. In the cannabis plant, some noted flavonoids are:
- Cannaflavin A
- Cannaflavin B and C
Cannabis for Potential Medicinal Purposes
Overall, the “entourage effect” is crucial in potentially treating a number of medical conditions, including:
- Acute and chronic pain (i.e. fibromyalgia, pain from motor vehicle accidents, and pain due to various types of cancer),
- Controlling muscle spasms (i.e. Multiple Sclerosis),
- Stimulating appetite and relieving nausea,
- Controlling seizures in epileptic patients for both the pediatric and adult population (i.e. Dravet Syndrome and Lennox-Gastaut Syndrome),
- Controlling behavioural outbursts and reducing anxiety (i.e. Autism spectrum disorders (ASD),
- Improving mood and regulating sleep (i.e. depression, anxiety, and post-traumatic stress disorder (PTSD), and
- Reducing the gastrointestinal inflammation (i.e. Crohn’s disease and Ulcerative Colitis).
Various Forms of Cannabis
Whether you are a first time user or a devoted one, cannabis comes in a variety of forms that allow different consumption methods, comfortable to your health, upbringings, and value system.
Many are not aware, but the plant comes in a variety of forms which include:
- Dried buds, flowers, and leaves of the cannabis plant
- these are the most utilized forms
- Herbed butter, infused oils, or tincture.
- cannabis is usually added to recipes and cooked to create baked goods such as cookies and brownies or savoury dishes
- Fresh cannabis leaf
- usually consumed by home growers of cannabis
- consumed in the form of a salad (mixed with other green vegetables)
- can also be juiced (diluted with other vegetables juices to disguise the bitter taste)
- contains both CBD and THC in their acid form; THC is not psychoactive in this form as the decarboxylation process has not taken place
- Kief and Hashish:
- this is the collected resin of mature and ripe cannabis flower buds
- separating and collecting the resin can be accomplished by using a sieve or ice water
- kief is the resin crystal in their loose form
- hashish is the term used to describe heated and pressed kief
- plant material is dissolved in an alcohol or glycerin medium
- this produces a tincture that is useful in oral or topical presentations
- tinctures extracted using alcohol, glycerin, or oil form the basis of various medicinal creams, balms, and lotions
- alternatively, hemp oil, almond oil, or coconut oil may be mixed with cannabis as an additive to create topical skin creams and food products
Cannabinoids in the form of pharmaceuticals have also been approved in North America by the various trade names.
- Pharmaceuticals include:
- Rimonabant (no longer available)
- Other Synthetic cannabinoids primarily used in research are:
- CB1 Agonists:
- CP 55, 940 (works equally on both CB1 and CB2 receptors)
- HU 210 (primarily CB1)
- HU 239 (ajulemic acid)
- CB2 Agonists:
- AM 1241
- CP 50556-1
- CP 55, 940
- WIN 55,212-2
- Potential CB1 agonist
- WIN55,212-2 (binds with both but stronger at CB1)
- CB1 Antagonist
- SR 141716A (Rimonabant)
- AM 251
- CB2 Antagonist
- SR 144528 (blocks both but much stronger at CB2)
- AM 630
- CB1 Agonists:
Modes of Administration
Cannabis may be eaten raw, cooked into other goods, consumed as juice, inhaled after vaporization, smoked in a pipe, wrapped in paper and smoked, or rubbed into skin.
Depending on the method of intake, the bioavailability varies and so do the effects.
- Method: Inhalation of cannabinoids via smoking or vaporization
- Form of cannabis: Dried buds, flowers, leaves of the cannabis plant are the most utilized
- Vaporization: The use of a vaporizer to heat the plant to a precise temperature that will evaporate the cannabinoids just below the burning point of the plant matter.
- This will minimize inhalation of burned carbon products (versus smoking)
- By smoking or vaporizing, the cannabinoids quickly reach the bloodstream
- Dosing: Inhale two puffs and wait 15 minutes before next puff (bid, tid)
- THC concentration: 10% or less (increase as tolerated and to reach therapeutic effects)
- Onset of effects: generally within seconds to minutes
- Duration of effects: last a short duration of time (may last up to 5 hours)
- Method: Sublingual administration of oil/tinctures or via ingestion of oil/tinctures (mixed with tea/juices and/or used to create edibles) AND ingestion of gel capsules
- Form of cannabis: Oil and tinctures – come in a dropper bottle which allows for precise dosing
- Dosing: start with a few drops; wait for at least one hour to feel the effects
- Slowly increase the dosage by a couple of drops, repeating the process until you have achieved the desired therapeutic effect
- Oils, tinctures, gel capsules:
- Cannabinoids are absorbed through the gastrointestinal tract
- Dosing: Start at 0.25 mg and increase as recommended (bid, tid)
- Onset of effects: generally within 30 minutes to 2 hours to feel the effects
- Duration of effects: Effects last a longer duration (may last up to 12 hours)
- Method: Topical administration of cannabis infused cream/lotion/balm
- Form of cannabis: cream/lotion/balm created from cannabis oil
- Used to deliver medicine to specific and isolated problem areas such as painful muscles or areas of inflammation
- Absorption rates – similar to that of ingestion
- More local effect versus systemic
- Method: Rectal administration of suppository
- Form of cannabis: suppository (a solid medical preparation designed to enter the rectum or vagina to dissolve)
- Used to delivery medicine to:
- those who may not be able to administer medicine orally
- infants with seizures
- target diseases of the rectal and pelvic regions
- Absorption rates are quite effective
- Rectal administration avoids the medication entering the gastrointestinal system; this means, THC is not further broken down into psychoactive metabolites, therefore not causing psychoactive effects.
Information from Health Canada
Like any medication, there are side effects and even adverse effects that users should be aware of. Health Canada approved Licensed Producers are morally obligated to report any major side effects and/or adverse reactions reported by their customers. As a medical patient or recreational user, you are entitled to complain about your cannabis product, and if warranted, Licensed Producers are ethically responsible to recall their product and halt further production and distribution.
According to Health Canada, healthcare professionals and patients should be aware of the potential side effects and contraindications to cannabis use.
Potential Side Effects and Adverse Reactions Due to Cannabis Use:
- Short and long-term effects in concentration and decision-making
- May cause or worsen depression and anxiety
- May lead to a psychotic episode
- May worsen or lead to cardiovascular or respiratory disease
- May negatively impact the reproductive organs and their functions for both males and females
Contraindications to Cannabis use:
- Are under the age or 18 (although it is also advised not to use until the age of 25 years old)
- Have a history of hypersensitivity to any cannabinoid or to smoke (if the cannabis is smoked)
- Have severe cardio-pulmonary disease with occasional hypotension (low blood pressure), possible hypertension (high blood pressure), syncope (loss of consciousness) or tachycardia (rapid heart rate)
- Have respiratory diseases such as asthma or chronic obstructive pulmonary disease (COPD)
- Patients with severe liver or renal disease, including chronic hepatitis C
- Have a personal history of psychiatric disorders or a family history of schizophrenia
- Have a history of substance abuse
- Are women of childbearing age not on a reliable contraceptive, planning to become pregnant, are pregnant, or are breastfeeding.
What’s Next in the Cannabis Industry?
The foundation for research and science has been laid down with many renowned physicians such as Dr. Rapheal Mecholum as mentioned in the beginning of the article, and other pioneers in the space such as Dr. Ethan Russo. As the medical community is understanding more and more about the scientific properties of cannabis, Canada is getting prepared for yet another historic event – the legalization of cannabis infused edibles and beverages.
This October, retailers across the country will be releasing creative product lines that many Canadians have been patiently waiting for.
At the end of the day, whether you are smoking a joint or eating a cannabis infused apple pie, it is the body’s Endocannabinoid System that will respond to the thousands of biologically active compounds of the cannabis plant.
Until then, consume safely.