Welcome to Cannabis IQ, a space dedicated to education about cannabis, its uses and the laws relating to it. High Tide is dedicated to providing accurate and objective information on topics directly and indirectly related to cannabis, whether recreational, medical or industrial.
Cannabis is an annual flowering plant, indigenous to Asia and the Indian Subcontinent. It can be described generally as fitting into 1 of 4 main categories: Sativa, Indica, Afghanica, and Ruderalis. All 4 of these can and have been bred together in various combinations to produce Hybrids, Autoflowers, and complex Polyhybrids. The term Sativa is a Latin adjective which means 'cultivated', and was first given to Cannabis by Carl Linnaeus, back in 1753, when Cannabis cultivation was commonplace and widespread globally.
Palynological (pollen) evidence suggests Cannabis cultivation by Humans dates back to at least 30,000 years ago, with the Gravettian Culture in the Baltic region of Europe. The cultivation and selective breeding of Cannabis Landrace and Heirloom varietals has continued to modern day, spreading to every continent on Earth, with no fewer than 12,500 strains currently in existence.
Strains, and their phenotypes, can be thought of as containing a chemical signature, which are unique to that strain and contribute to the quality of the Cannabis experience, or in Layman’s terms: 'the high'. That signature - composed primarily of Cannabinoids and Terpenes - is often referenced as the 'Entourage Effect' which is a principle that explains how those constituents within a sample of Cannabis interact with one another - and your own individual biochemistry - to produce markedly different desired effects and outcomes.
There are over 20.000 terpenes in nature, and upwards of 200 have been associated with Cannabis, although typically only 20 are present in significant amounts in any particular sample. Myrcene, Limonene, Linalool, b-Caryophyllene, Humulene and a-Pinene are the terpenes you’ve most likely already heard of. In addition, there are more than 100 known Cannabinoids (Phytocannabinoid) in the Cannabis plant. The two most researched and understood are THC (Delta-9-tetrahydrocannabinol) and CBD (Cannabidiol), although CBG, CBN, CBC, and THCV can be present in significant amounts, depending on the strain.
Technically Hemp is Cannabis Sativa, but it has been bred to contain a maximum amount of THC which is determined to be non-psychoactive. In the Industrial Hemp Regulations, industrial hemp includes Cannabis plants and plant parts, of any variety, that contains 0.3% tetrahydrocannabinol (THC) or less in the leaves and flowering heads.
Industrial hemp also includes the derivatives of industrial hemp plants and plant parts. These do not include the flowering parts or the leaves. Examples of derivatives that are considered industrial hemp include: hemp seed oil (oil derived from seed or grain) and hemp flour.
Industrial hemp does not include:
- Non-viable Cannabis seeds, except for their derivatives. While the derivatives of non-viable Cannabis seeds are considered to be industrial hemp, the non-viable seeds themselves are not industrial hemp;
- Mature Cannabis stalks, when those stalks are stripped of their leaves, flowers, seeds, and branches;
- Fiber derived from such mature Cannabis stalks.
The new Industrial Hemp Regulations under the Cannabis Act set out the requirements for cultivators of industrial hemp. As is currently the case, cultivators of industrial hemp must grow from the hemp varieties approved for commercial cultivation.
While the new Industrial Hemp Regulations are generally consistent with the current Industrial Hemp Regulations:
- some changes have been made, with the goal of aligning licence requirements to the relatively low risk posed by industrial hemp as compared with other varieties of cannabis
- the sale of hemp plants (flowers, leaves and branches) to licensed cannabis processors will be permitted, to provide a source of low THC, high cannabidiol (CBD) cannabis products
You may have heard of the terms Hash, Shatter, Rosin, and Tinctures, and the list goes on. It can seem overwhelming at first, but as far as Health Canada is concerned all the selections can be boiled down to a few general forms, which can result in differential treatment under varying regulatory scenarios:
Germplasm: The materials used to start a new plant can fall into two major categories.
Seeds: For cannabis these can be produced to be exchanged in different forms when viable (to produce only female plants, to auto-flower, etc.) or to be exchanged in a form that is not viable (usually for food or fodder).
Cuttings: Similar to seeds, these are components of plants, which are used to grow further cannabis products.
Growing plants: Growing plants can be distinguished into two basic types.
Vegetative: This type consists of seedlings and plants in a vegetative stage of growth. Depending on the goals of the grower, or the cultivation technique being used, they may or may not be raised to the flowering stage when they will produce cannabinoids in quantity. They might instead be kept until their sex is known, then the male plants destroyed (e.g., crop “thinning”) or a female plant might be kept in the vegetative state to produce genetic stock or for other horticultural purposes (e.g., as a “mother” plant).
Flowering: This type consists of those plants that are either intended to become flowering plants or are flowering.
Harvested material: There are two basic types of harvested material.
Wet: This is a material that is in the process of being transformed into a dryer form (such as when marijuana is “cured”) or is a final product that will be consumed in a form that includes significant natural plant moisture (such as use in salads or smoothies).
Dry: This is a material that has been processed into a dry form that is the final form to be consumed, sold or processed (such as dried cannabis flower ‘buds').
Concentrates: There are two basic groups of methods for concentrating the active constituents of cannabis (i.e., the cannabinoids and terpenes):
Kinetic: Kinetic methods involve the simple mechanical extraction of cannabis concentrates at ambient atmospheric pressure, with or without water. This includes techniques that range from direct contact with undried or living plants (e.g. “charas” or “finger hash”), to dry sifting (e.g., “hashish”), to wet sifting (e.g., “bubble hash”), to mechanical pressure under ambient or hot conditions (e.g., “rosin” made with hair straighteners).
Scientific: These methods involve some combination of extraction using a chemical solvent and/or the manipulation of atmospheric pressure. These methods can use homemade or adapted apparatus, using solvents such as butane, propane, isopropyl alcohol, carbon dioxide, liquid nitrogen, as well as homemade or commercial vacuum and heating chambers. The products of this concentration method can be termed “dabs,” “hash oil,” “wax,” and “shatter,” depending on the procedure used and marketing.
Mixtures: Mixtures are of two general types: extracts and dilutions. The difference between dilutions and extracts from concentrates is not one of potency, but that in dilutions and extracts adjuncts are intentionally included in the product besides components of the cannabis plant.
Extracts: The active chemical constituents of a concentrated cannabis product can also be extracted into a carrying media that becomes part of the end product that is consumed, such as fat (“canna-butter”) or alcohol (cannabis tincture). This may be consumed as is or transformed into another product.
Dilutions: Concentrates can be diluted in preparations, such as in edible foodstuffs, as lotions for external or internal application. Dried harvested material can also be diluted with other plant matter, such as tobacco or lobelia, or with non-psychoactive cannabis plant matter, for respiratory ingestion.
Throughout history the cannabis plant has been used for medical, social, and religious purposes. Marijuana, and weed are slang terms for the dried flowers, leaves, stems and seeds of the cannabis plant, all of which can be consumed in a variety of ways.
For decades marijuana use has been associated with smoking, and although this is no longer the only way to enjoy the benefits of the plant, it is still a very popular method. When the flower of the female cannabis plant is heated THCA is converted to THC, the psychoactive component of cannabis. Upon inhalation, the effects are experienced quickly, whether using a pipe, bong, joint, or dugout. New devices can even convert water bottles instantly into single use bongs. Cannabis is traditionally smoked in joints or spliffs (cannabis rolled in cigarette paper) which may or may not be mixed with tobacco. Blunts (partially or entirely hollowed out cigar wrappers filled with cannabis) are another common method for combusting cannabis. Smoking methods can, however, lead to long-term lung problems, including bronchitis. The instant effects and relatively low-cost make smoking a tempting option compared to other delivery methods; however, consumers should bear in mind potential health impacts.
Another inhalation method, vaporizing (or “vaping”), involves heating dried cannabis flower or cannabis oil, by passing heated air across the sample. Often seen as a healthier alternative to traditional smoking, vaping still delivers effects rapidly and is less harsh on the lungs. These products come in various forms, including small vape pens as well as portable and desktop vaporizers. Vaporizing flower minimizes the hazardous effects compared to smoking as only the heated vapor is inhaled without the pyrolytic breakdown products. Potential downsides of vaping cannabis oil are the cutting agents used for the oil cartridges. These could include propylene glycol, polyethylene glycol, substances which may also lead to lung problems with chronic use.
A newer method of cannabis consumption is “dabbing”. This method takes cannabis oils, waxes or shatters and vaporizes them on a dab rig. Unlike a bong which heats flower, the dab rig will heat highly concentrated oils/products for consumption. The rig is often composed of a nail, or banger with product on it that is heated at high temperature with a butane torch, and then the vapors are inhaled. This method is rapid and can lead to a very high state due the highly concentrated THC in these products. Not much is known, to date, about dabbing large amounts of THC over a long period of time. Additionally, the high heat associated with the butane torch can lead to pyrolytic breakdown products such as benzene and acrolein.
Cannabis material that is classified as “live” means it is not produced from the extraction of dried plant material, but rather, from fresh flower that is frozen. This process maintains the terpene profile, including monoterpenes that are often lost during extraction processes. This can enhance the flavor profile of the products. Live rosin is made from a solventless process with an ice wax intermediate step so there is no risk for residues such as butane, pentane, or hexane. It uses heat and a press to create small batch artisanal concentrates. Live rosin can be expensive due to the small quantities produced. Live resin is another concentrate product made by butane extraction following the freezing process.
There are a variety of edible cannabis products on the market that present desirable alternatives for those looking beyond inhalation methods, including candies and baked goods, savory crackers, and drinks like tea and soda. Nowadays, the taste of marijuana is barely, if at all, detectable. The downside of edibles is that they can take a long time for effects to kick in depending on the consumer’s metabolism, weight and gender. Further, many edible products on the market can be inconsistent in terms of dosing, and consumers must take care to “start low and go slow” to avoid taking too much, too quickly.
Other oral products that are not eaten include micromist sprays delivered sublingually (under the tongue) that directly enter the bloodstream. They are administered from a fine-mist sprayer and come in a variety of flavors for a vegan, sugar-free, gluten-free experience. Onset of action can be as fast as 15 minutes from consumption. These products offer extremely precise dosing for enhanced consistency and effectiveness.
Another oral alternative is a tincture. Tinctures are made from cannabis flower or extracts steeped in alcohol that are administered through a dropper under the tongue. When delivered this way, the product enters the bloodstream to deliver rapid effects. With an extremely long shelf life, tinctures offer an option for those looking to receive faster relief than edibles, while still avoiding the risks associated with smoking.
Topical salves, transdermal creams and patches are options that apply cannabis-infused products to the skin. Simply massaged into the skin like any other lotion, cannabis topicals are discreet and effective, providing targeted relief for problem areas. Many are infused with essential oils to improve the aroma while allowing the product to permeate skin cells more deeply and maximize effects–with limited psychoactivity. Patches are touted for their pain-relieving ability. Dermal products may be a good entry point for new cannabis consumers.
Cannabis nasal mist administration is one of the most effective delivery methods for cannabis due to the nasal cavity’s large surface area and extensive vascularization. Effects can also be felt quickly. Further, devices currently on the market are designed to administer super fine mists, allowing the product to cover more of the highly permeable nasal membrane with active cannabinoids, taking effect in as little as ten minutes.
Just as no two cannabis consumers are exactly alike, neither are any two cannabis products. Each has its own unique formula and delivery mechanism. What is pleasurable for one individual may be less effective or enjoyable for another. Above all, it is important to speak with local dispensary staff to determine the ideal product type for the specific need. It’s an exciting time to be a part of the cannabis community as we work together to develop healthier, more effective and innovative technologies, all with the consumer’s safety and experience in mind.
From ‘Its all in the Delivery: Cannabis Consumption and emerging Technologies. Dr. Dorothy Colagiovanni
Know Your Dose
Dosing remains highly individualized and relies to a great extent on titration (i.e. finding the right dose where potential therapeutic/desired effects are maximized while adverse or harmful effects are minimized). The most prudent approach to dosing in the absence of evidence-based guidelines is to "start low and go slow."
Other than for products that have received a notice of compliance from Health Canada and a DIN, the dose of cannabis required to achieve therapeutic effects and avoid adverse effects is difficult to estimate and is affected by many variables. However, higher doses of THC (and CBD) are associated with an increased risk of experiencing adverse or harmful effects.
Individuals with no prior experience with cannabis and initiating such therapy for the first time are cautioned to begin at a very low dose (e.g. 1 mg THC) and to immediately stop if unacceptable or undesirable side effects occur (e.g. disorientation, dizziness, and loss of coordination, agitation, anxiety, rapid heartbeat, chest pain, low blood pressure/ feeling faint, depression, hallucinations, or psychosis).
When beginning with cannabis it is best to try to have someone you trust with you in case you experience an adverse effect and require medical attention.
While there have been a few clinical studies of smoked/vapourized dried cannabis for therapeutic purposes, there are no clinical studies of fresh marijuana or cannabis oil for therapeutic purposes. As such, providing precise dosing guidelines for such products is not possible although existing sources of information can be used as a reference (see below).
Onset, Peak, and Duration Effects
With inhalation (smoking, vaporizing), effects may be felt within a few minutes of dosing and will generally peak within 30 mins. Acute effects generally last between 2 and 4 hours but may be longer (e.g. 24 hours).
With oral ingestion (e.g. oils, foods, capsules), acute effects may begin to be felt as quickly as 30 mins and as late as 3 or 4 hours after administration. This variability in timing depends on a number of factors (e.g. amount of food in stomach). It is prudent to wait a minimum of 2 hours between administration of single doses of oral products to avoid possible overdosing. Acute effects generally peak between 3 and 4 hours after dosing and can last up to 8 hours or longer e.g. 12–24 hours).
With topical application, it is not known how long it takes for potential therapeutic effects to appear, nor how long they last. There have been reports of hypersensitivity reactions (e.g. rashes, itching) when skin has come into contact with cannabis.
Information obtained from a limited number of small and short-term clinical studies of cannabis for medical purposes indicate the daily doses of smoked or vaporized dried cannabis ranged from as little as 75 mg of dried cannabis 9.4% THC by weight) (i.e. 7 mg THC/day) to a maximum of 3.2 grams of dried cannabis (1–8% THC by weight; i.e. 32 to 256 mg THC).
Doses of THC as low as 2.5–3 mg of THC (and even lower) are associated with a therapeutic benefit and minimal psycho-activity.
Various surveys published in the peer-reviewed scientific and medical literature have suggested that the majority of people using smoked or orally ingested cannabis for medical purposes reported using between 10–20 grams of cannabis per week, or approximately 1–3 grams of dried cannabis per day.
One study reported the average daily dose of dried cannabis (of various potencies) used by patients in the Netherlands’ Medical Cannabis program was 0.68 grams per day (range: 0.65 –0.82 grams per day).
Another study suggests that regardless of route of administration (inhalation vs. oral), individuals reporting use of cannabis for medical purposes reported consuming equivalent amounts of cannabis per day and that amount averaged at around 3 grams per day.
- For smoking and vaporizing, the median reported dose was 1.5–2.0 grams per day respectively.
- For edibles, the median reported dose was 1.5 grams per day.
- For teas, the median reported dose was 1.5 grams per day.
There is no information available on dosing amounts for topically applied cannabis products (e.g. ointments, creams, lotions, oils, balms, salves), however one study suggests approximately 5% of individuals who use marijuana for medical purposes use such products.
There is no information available on dosing amounts for fresh marijuana.
In the absence of any clinical studies conducted with cannabis products, such as oils that are ingested orally, the following information has been provided as a reference to give some potential guidance around dosing.
For products such as oils that are ingested orally:
- The available clinical evidence for Marinol®, an orally administered capsule that has received market authorization and that contains synthetic THC dissolved in sesame oil, indicates a dosing range from as low as 2.5 mg THC per day to a maximum dose of 210 mg THC per day. Doses lower than 2.5 mg (e.g. 1 mg) THC may further avoid incidence and risks of adverse effects.
- Average dose of Marinol® is 20 mg THC per day.
- Maximal recommended daily oral dose of Marinol® is 40 mg per day.
- Preliminary information from an open-label clinical trial with Epidiolex® (an orally administered oil extract containing mainly cannabidiol (CBD) for treatment of certain types of childhood epilepsy not responsive to conventional treatment), suggests a daily dosing range between 5 and 20 mg/kg CBD. However, further clinical studies are required to substantiate this information.
Terpenes are chemicals primarily made and stored in the flower portion of the cannabis plant – along with the cannabinoids – and give cannabis its distinctive smell. Terpenes are basically the essential oil component of the cannabis plant, and are generated in highest concentrations by the trichomes.
Different strains of cannabis will have different terpene profile - which are the particular mix of terpenes characteristic of a particular phenotype. The aromas a plant can have are determined by the terpene profiles, or the way terpenes stack against each other. These oils can have effects on our mood in much the same way that an aromatherapy session would.
Terpene profiles and levels not only are affected by the genetics of the plant, but also by the plant’s environment while it is alive, and after it has been harvested. For example: Clones (cuttings) grown in different types of soil or fed different nutrients, can produce different quantities and possibly even different types of oils. With environments being equal, combinations of cannabis genetics are potentially endless, so the ranges of terpene profiles, and their related phenotypes are equally vast.
Although there have been a huge number of terpenes reported, there has only been a small minority that have actually been studied. Of the ones that have been studied, scientists have found them to have numerous medicinal properties.
Terpenes in some form are found in nearly all living organisms. Thousands of terpene chemical structures from natural sources have been identified, and they have many functions in nature. Plants produce terpenes and other volatile compounds to interact with the surrounding environment. Terpenes can serve as environmental cues to attract pollinators or a chemical defense against herbivores.
Many products and chemicals you may be familiar with are composed of terpenes. Essential oils used in aromatherapy and perfumes are often terpenes. Everyday products such as turpentine are made from terpenes in pine tree resins. Vitamin A and cholesterol are terpenes. In traditional and modern medicine terpenes are used for their anti-microbial, anti-inflammatory, and anti-cancer properties. The anti-malaria drug artemisinin from sweet wormwood (Artermesia annua) and the anti-cancer drug paclitaxel from the Pacific yew tree (Taxus brevifolia) are both terpenes. The plant pigments carotene found in carrots and lycopene found in tomatoes are also terpenes.
From a chemical perspective terpenes are defined based on the number of 5 carbon building blocks, called isoprene units, they contain. Biosynthetically speaking the 5 carbon chemical precursors isopentenyl-pyrophosphate and dimethylallyl-pyrophosphate are used to manufacture terpenes in living organisms. Terpenes made from 2 isoprene units with 10 carbons are called monoterpenes, 3 units (15 carbons) sesquiterpenes, 4 units (20 carbons) diterpenes, 6 units (30 carbons) triterpenes and 8 units (40 carbons) tetraterpenes (Figure 1).
Figure 1. Terpene building blocks.
In plants, terpenes are often produced in specialized cell types. In pine trees terpenes are secreted into the resin ducts. In citrus fruits terpenes are made in oil glands located below the plants epidermal surface. In many plants including cannabis terpenes are produced in stalk like glandular structures known as trichomes. A cluster of cells which sit at the top of the stalk act as chemical factories for the production of cannabinoids and terpenes in cannabis.
Based on the findings of several studies about 120 terpenes have been identified in cannabis essential oil, mostly monoterpenes and sesquiterpenes. In dried cannabis flowers terpenes are usually present in the range of 0.5% – 3.5%. Of these, 10-30 terpenes tend to be present at levels we can measure accurately in routine analytical testing using gas chromatography. Many terpenes found in cannabis are also common in other plants. The monoterpenes myrcene are found in mango and hops. α-pinene and β-pinene, pine trees. Limonene, citrus fruits. The sesquiterpene, β-caryophyllene is found in cloves and black pepper.
Figure 2. Cannabis monoterpenes (left), sesquiterpenes (right).
The easiest way to begin to understand the patterns of terpenes found within the wide variety of cannabis cultivars out there is to look at the raw data. In this case the data generated by the gas chromatograph, called a chromatogram. Figure 3 shows a chromatogram of the terpenes typically found in an OG Kush sample. A chromatogram is simply the record or result of the chromatographic analysis. In gas chromatography, terpenes are vaporized and pushed with a gas through a small tube, called a capillary column. This process separates the chemical mixture of terpenes over time as they move through the column. Different terpenes will come out of the column and hit the detector at different times which is how analysts identify them. The x-axis represents the time it takes the signal to move through the gas chromatogram. The signals, displayed as peaks along the y-axis, represent a different terpene found in the sample. The bigger the peak the more of that terpene is found in that sample. In figure 3 the biggest peaks come from limonene and myrcene, which is characteristic of many OG Kush cultivars.
Chromatogram showing terpenes found in OG Kush sample.
By: S. Passalaqua and J. Fischedick
The most researched cannabinoid is delta-9-tetrahydrocannabinol (THC). THC is the main psychoactive component of the Cannabis plant and is found in highest concentrations in the Trichomes. In the plant, it occurs in the form of THCA, an acid that requires decarboxylation – which is a function of heat and time - to denature into the mind and body altering compound THC. Immediate effects reported are feelings of euphoria, heightened sensory perception, and an increase in heart rate.
THC is a partial agonist at both the CB1 and the CB2 receptors. The binding to the CB1R is primarily responsible for the psychotomimetic effects of cannabis, while the interaction with the CB2R may have other immunologic or other anti-inflammatory properties. Other effects of THC have been used for clinical benefit, and include antiemetic, appetite stimulation, analgesic properties, and possibly some immunologic-modulating actions.
Studies have shown that THC can have negative effects on the cognition in young people, but interestingly new research suggests the opposite for aging adults. In a study out of the University of Bonn, in Germany, adult rats given daily doses of THC were shown to have ‘a dramatic improvement in cognitive functions’, suggesting the potentially neuroplastic qualities of THC.
The potency (concentration or strength) of THC in cannabis is often shown as a percentage of THC by weight (or by volume of an oil). THC potency in dried cannabis has increased from an average of 3% in the 1980s to around 15% today. Some strains can have an average as high as 30% THC, while certain concentrates such as isolates, have percentages as high as 99%.
The Figure below depicts the THC molecule:
Cannabidiol (CBD) is the second most researched cannabinoid. Unlike THC, CBD does not produce a high or intoxication. There is some evidence that CBD may attenuate some of the psychoactive, and deleterious effects of THC. This may occur when the amount of CBD in the cannabis is the same or higher than the amount of THC, expressed in a 1:1 ratio.
CBD is also being studied for its possible therapeutic uses. In general CBD has been found to be well tolerated and have few to no psychoactive effects, with the most common side effect being sedation. The pharmacology of CBD is complex, because more than 20 different mechanisms of action have been described to inhibit the activity of fatty acid amide hydrolase, thus increasing AEA concentrations in the body.
Clinical effects of CBD are being explored in a variety of illnesses, including epilepsy, anxiety disorders, cancer, anti-inflammatory effects, and schizophrenia. The rise of CBD to cannabinoid stardom, and its foothold in the Wellness industry has propelled an entire movement of research and development, with an aim to breed plants with specific and reliable levels of CBD to satisfy consumer demand.
CBD has several molecular targets, and new ones are currently being uncovered. CBD antagonizes the action of CB1 and CB2 receptors agonists and is suggested to act as an inverse agonist of these receptors. Moreover, recent evidence points to CBD as a non-competitive negative allosteric modulator of CB1 and CB2. It has been shown to inhibit the activity of fatty acid amide hydrolase, which increases the concentration of AEA in the body. CBD is also an agonist of the vanilloid receptor TRPV1, and has been shown to facilitate the neurotransmission mediated by the serotonin receptor 5-HT1A.
In a rat model of Alzheimer's disease, CBD, through interaction with PPARγ, stimulates hippocampal neurogenesis, inhibits reactive gliosis, induces a decline in pro-inflammatory molecules, and consequently inhibits neurodegeneration.
CBD's mechanisms of action. CBD acts as agonist of the receptors TRPV1, PPARγ, and 5-HT1A, and as antagonist of the receptor GPR55. CBD is an inverse agonist of the receptors GPR3, GPR6, and GPR12. Moreover, CBD antagonizes the action of CB1 and CB2 receptors agonists, and is suggested to act as an inverse agonist and a negative allosteric modulator of these receptors. CBD also inhibits FAAH, which results in increased anandamide levels. Anandamide activates CB1, CB2, and TRPV1 receptors. By acting on mitochondria, CBD increases the activity of mitochondrial complexes. In addition, CBD displays antioxidant and anti-inflammatory effects—that are partially mediated by CBD's actions on TRPV1, mitochondria and PPARγ. 5-HT1A, serotonin receptor 1A; CB1, cannabinoid receptor type 1; CB2, cannabinoid receptor type 2; FAAH, fatty acid amide hydrolase; GPR3, G-protein-coupled receptor 3; GPR6, G-protein-coupled receptor 6; GPR12, G-protein-coupled receptor 12; GPR55, G-protein-coupled receptor 55; PPARγ, peroxisome proliferator-activated receptor gamma; ROS, reactive oxygen species; TRPV1, transient receptor potential vanilloid type 1.
Cannabidiol and THC seem to have an important interaction in both negation of detrimental effects and potentiation of positive effects.
In one of the earliest animal studies by Karniol and Carlini, CBD was found to decrease many negative effects related to anxiety but potentiated the analgesic effects of THC. Another rodent study found that CBD actually prolonged the effects of THC in mice, and therefore potentiates the effects of THC. A series of subsequent studies in humans found CBD had few effects in healthy adults, but when combined with THC participants reported less anxiety and psychotic symptoms. Interestingly, one of the early studies, similar to the rodent study showed that smoked cannabis with higher concentrations of CBD prolonged the effects of THC.
Although there have been some contradictive studies, most evidence suggests CBD diminishes many of the psychoactive effects of THC. An epidemiologic study investigated this by taking hair samples from 120 current cannabis smokers. In the study they found individuals with CBD in hair samples reported fewer psychiatric affects than those with higher THC concentrations. This gives further credence that the laboratory findings are valid that CBD decreases psychotomimetic effects of cannabis by decreasing THC effects.
Below is a chart listing Human studies involving CBD, and their results:
Whether CBD could affect other clinical effects of THC has still been questioned. A study in 46 adults found oral CBD 600 mg given 3.5 hours before intravenous THC (1.5 mg) reduced verbal memory deficits to a greater extent than placebo when administered with THC. Furthermore, CBD reduced psychotic symptoms from THC as measured by the Positive and Negative Symptom Scale (PANSS). Emotional perception is altered in many people with cannabis use disorder. The study conducted a randomized, crossover, double-blinded study over the course of 4 days to examine the effects of oral THC (8 mg) and oral CBD (16 mg) and placebo in 48 participants, regarding the ability of participants to recognize emotional facial affect from pictures. Although the test participants reported no difference of feeling “stoned” with THC or THC + CBD, the THC test day resulted in more errors in emotion facial recognition that were corrected when CBD was given concurrently. The authors concluded that CBD reverses the deficits in emotional processing caused by THC.
It is unclear if the attenuation of effects is due to only pharmacodynamic effects or if pharmacokinetic effects are also involved. THC concentrations in the blood do not seem to be altered by CBD, but CBD may prevent THC from being converted into a more psychoactive metabolite, 11-hydroxy-THC. Another study performed a functional magnetic resonance imaging (fMRI) study in which 15 individuals performed a series of cognitive tasks after given oral THC, CBD, or placebo during 3 different study days. They found THC and CBD had opposing neurobiologic effects on blood oxygen level–dependent responses, with CBD generally showing an increase in activation relative to placebo, and THC showing a decrease. In a second phase of the study they gave 6 individuals oral CBD or placebo before intravenous THC on 2 different test days and found that, similarly to previous studies, CBD diminished the psychotomimetic effects of THC. Several subsequent imaging studies from this group have consistently shown that CBD has opposing biologic effects in the brain, suggesting many of the effects are pharmacodynamic.From <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007535/>
The Endocannabinoid System (ECS) is a homeostatic biological system found in all animals. It is because of this system and its constituents, the CB1, CB2, Vanilloid receptors, and its endogenous ligands Anandamide and 2-AG that we are able to feel the effects of cannabis at all.
The successful identification and cloning of the CB1R prompted the discovery of its first endogenous agonist, AEA, in 1992. The fact that AEA cannot fully reproduce the effects induced by THC led to the discovery of another important endocannabinoid, 2-AG. Most studies on the endocannabinoid system focus on these two endocannabinoids, despite the existence of the recently identified CB1R-interacting peptides and a series of arachidonic acid derivatives that generate endocannabinoid-like effects.
These two well-documented endocannabinoids, as pharmacologically characterized, possess distinct properties. AEA turns out to be a high-affinity, partial agonist of CB1R, and almost inactive at CB2R; whereas 2-AG acts as a full agonist at both CBRs with moderate-to-low affinity. Interestingly, both AEA and 2-AG have been reported to interact with various receptors. Among those, the transient receptor potential cation channel subfamily V member 1 (TRPV1), which is activated by AEA, is the best-documented for its significant role in synaptic transmission and pain regulation, whereas the interaction of 2-AG and non-CBRs has emerged only recently
Figure 1. The Endocannabinoid System in the Nervous System
- Endocannabinoids are manufactured "on-demand" in the post-synaptic terminals: anandamide (AEA) is generated from phospholipase-D (PLD)-mediated hydrolysis of the membrane lipid N-arachidonoylphosphatidylethanolamine (NAPE); 2-AG from the diacylglycerol lipase (DAGL)-mediated hydrolysis of the membrane lipid diacylglycerol (DAG);
- These endocannabinoids (AEA and 2-AG) diffuse retrogradely towards the pre-synaptic terminals and like exogenous cannabinoids such as THC (from cannabis), dronabinol, and nabilone, they bind and activate the pre-synaptic G-protein-coupled CB1 receptors;
- Binding of phytocannabinoids and endocannabinoids to the CB1 receptors triggers the activation and release of the Gi/Go proteins from the CB receptors and inhibits adenylyl cyclase, thus decreasing the formation of cyclic AMP and the activity of protein kinase A;
- Release of the Gi/Go proteins also results in the opening of inwardly-rectifying K+ channels (depicted with a "+") causing a hyperpolarization of the pre-synaptic terminals, and the closing of Ca2+ channels (depicted with a "-"), arresting the release of stored excitatory and inhibitory neurotransmitters (e.g. glutamate, GABA, 5-hydroxytryptamine (5-HT), acetylcholine, noradrenaline, dopamine, D-aspartate and cholecystokinin) which once released, diffuse and bind to post-synaptic receptors;
- Anandamide and 2-AG re-enter the post- or pre-synaptic nerve terminals (possibly through the actions of a specialized transporter depicted by a "dashed" line) where they are respectively catabolized by fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL) to yield either arachidonic acid (AA) and ethanolamine (ETA), or arachidonic acid and glycerol.
Each province and territory will have the ability to set its own rules for cannabis, including:
- legal minimum age
- where you can buy it
- where you can use it
- how much you can possess
You must respect the laws of the province, territory or Indigenous community you are in, whether you are a visitor or live there. Individual municipalities may also pass bylaws to regulate the use of cannabis locally. Check your municipality for local information.
Once in effect, the Cannabis Act will allow adults, subject to provincial or territorial restrictions, to:
- purchase fresh cannabis, dried cannabis, cannabis oil, cannabis seeds, or cannabis plants from retailers authorized by the provinces and territories;
- consume cannabis in locations authorized by local jurisdictions;
- possess up to 30 grams of dried legal cannabis or equivalent in non-dried form in public;
- share up to 30 grams of dried legal cannabis with other adults;
- grow up to four cannabis plants per household (not per person) for personal use, from licensed seeds or seedlings from a licensed supplier; and make legal cannabis-containing products at home, such as food and drinks, provided that dangerous organic solvents are not used in making them.
IMPORTANT NOTE ABOUT BORDERS
It is illegal now and will remain illegal to take any amount of cannabis across Canada's international borders.
The legalization and regulation of cannabis in Canada will not change Canada's border rules. It is illegal to take cannabis across Canada's international borders.
If you try to travel to other countries with any amount of cannabis in your possession, you could be subject to criminal charges. You could also be denied entry in any country, if you have:
- involvement in the legal cannabis industry in Canada
- previously used cannabis or any substance prohibited by local laws.
- dizziness, drowsiness, feeling faint or lightheaded, fatigue, headache;
- impaired memory and disturbances in attention, concentration and ability to think and make decisions;
- disorientation, confusion, feeling drunk, feeling abnormal or having abnormal thoughts, feeling "too high", feelings of unreality, feeling an extreme slowing of time;
- suspiciousness, nervousness, episodes of anxiety resembling a panic attack, paranoia (loss of contact with reality), hallucinations (seeing or hearing things that do not exist);
- impairments in motor skills and perception, altered bodily perceptions, loss of full control of bodily movements, falls;
- dry mouth, throat irritation, coughing;
- worsening of seizures;
- hypersensitivity reactions (contact dermatitis/hives);
- higher or lower blood levels of certain medications;
- nausea, vomiting;
- fast heartbeat.
- increase the risk of triggering or aggravating psychiatric and/or mood disorders (schizophrenia, psychosis, anxiety, depression, bipolar disorder);
- increase the risk of developing respiratory infections or chronic cough (when smoking);
- decrease sperm count, concentration and motility, and increase abnormal sperm morphology;
- negatively impact the behavioural and cognitive development of children born to mothers who used cannabis during pregnancy;
- negatively affect cognitive functions (ability to think and make decisions);
- lead to a decrease in one or more of the effects of cannabis (tolerance);
- lead to withdrawal-type symptoms when use is abruptly halted or discontinued. Withdrawal symptoms may include anger or aggression, irritability, anxiety, nightmares/strange dreams, insomnia/sleep difficulties, craving, headache, restlessness, and decreased appetite or weight loss, depressed mood, chills, stomach pain, shakiness and sweating; and result in psychological dependence (addiction) which is characterized by impaired control over drug use, compulsive use, continued use despite harm, and craving.
Cannabis should not be used if you:
- are under the age of 25
- are allergic to any cannabinoid or to smoke
- have serious liver, kidney, heart or lung disease
- have a personal or family history of serious mental disorders such as schizophrenia, psychosis, depression, or bipolar disorder
- are pregnant, are planning to get pregnant, or are breast-feeding
- are a man who wishes to start a family
- have a history of alcohol or drug abuse or substance dependence
Talk to your health care practitioner if you have any of these conditions. There may be other conditions where this product should not be used, but which are unknown due to limited scientific information.
- a standardized cannabis symbol that would need to appear on every label, including specific requirements with respect to its size, placement and appearance;
- mandatory health warning messages that would need to appear on every label, including specific requirements with respect to their size, placement and appearance. The warnings, covering six topics, are listed in Annex C of this document. A warning (comprised of a primary and secondary message) would need to appear on every label, and the different warnings would need to be rotated on package labels; and
- requirements with respect to information on THC and CBD content, as well as other information that would be required on each label, including specific requirements with respect to the size, placement and appearance of this information.
- only one other brand element (in addition to the brand name) could be displayed. This element could include, for example, a slogan or logo. If it is a text element, the font must be no larger than the font of the health warning message, and must be a single, uniform colour. If the brand element is a graphic, image or logo, it would be required to be no larger than the standardized cannabis symbol;
- it would be prohibited to display any other image or graphic;
- label and package backgrounds would need to be a single, uniform colour (inside and outside);
- it would be prohibited to use any fluorescent or metallic colours;
- colours must contrast with the colours of the standardized cannabis symbol and the background of the health warning messages (see Annex B for details);
- labels and packaging could not have any coating (e.g. could not be glossy), embossing (raised or recessed relief images), texture, foil, cut-outs or peel-away labels;
- any over-wrap must be clear; and
- it would be prohibited to include any insert in a package.
- minimize its appeal to children and youth
- protect against accidental consumption
- provide consumers with information they need to make informed decisions before using cannabis
- Alberta: 37 locations
- British Columbia: 8 locations