CBD is safe and tolerable for short-term use for a maximum of 30 days at a maximum dose of 200 mg/day through oral administration, Health Canada’s scientific committee has decided.
On the 28th of July 2022, the Science Advisory Committee on Health Products Containing Cannabis, asked by Health Canada to provide advice that would help shape regulations for health products containing cannabis in Canada, published their report.
The nine-member Committee co-chaired by Dr. Paula Brown and Dr. Richard Huntsman contains ten recommendations for the safe use of cannabidiol (CBD). The Committee said it believes that their recommendations strike a balance between the desire of Canadians to access health products containing cannabis without practitioner oversight while ensuring public health concerns are addressed.
These recommendations will serve as guidance for a government model for the sale of CBD as an over-the-counter medicine in pharmacies or veterinarian practices. So far, Health Canada was issuing processing licenses for manufacturing products containing CBD for sale, and those could only be sold by a provincially or territorially authorized cannabis retailer or federally licensed seller of cannabis for medical purposes. A license is also needed for import and export unless there is an international agreement intended for scientific or medical purposes.
Worldwide CBD Regulations 2021
Health Canada outlined four objectives for the Committee:
– Assess the evidence regarding the safety, efficacy, and quality of cannabis, including specific phytocannabinoids such as cannabidiol (CBD) or Delta-9-tetrahydrocannabinol (THC), when used for therapeutic purposes for short-term minor ailments and provide advice on the harms, uncertainties and the possible benefits of using cannabis for therapeutic purposes;
– Outline information Health Canada should consider when deciding whether products can be used for self-care without practitioner oversight, and suggest ways to deal with gaps in information for making that decision;
– Explain issues with cannabis that should be considered as Health Canada determines the recommended dosage thresholds and the conditions when cannabinoids can be used without a practitioner’s oversight; and,
– Suggest priority areas and considerations for the research and medical community on potential therapeutic uses of cannabinoids.
The Committee has focused the scope of their investigation by defining CBD preparations where:
-CBD is 98 percent or more of the total cannabinoid content of the preparation.
-Any cannabinoids other than CBD must be only those naturally found in cannabis and together equal no more than two percent of the total cannabinoid content of the preparation.
-THC content must not be more than one percent of the total cannabinoid content.
This definition included purified CBD, CBD isolate, CBD-rich cannabis extracts and synthetic CBD ((-) enantiomer only, meaning the form of CBD produced naturally in the cannabis plant, while the positive (+) enantiomer interacts with the CB1 receptor and could potentially cause intoxication).
The Committee found only these products fully meet the criteria.
The Committee also concluded that it is important to note this definition and the recommendations are meant to inform Health Canada’s decision-making to develop a potential pathway for non-prescription health products containing cannabis and that this definition does not apply to currently available cannabidiol products on the Canadian market.
The committee unanimously agreed it would not be appropriate to give any products containing CBD to individuals who are pregnant or breastfeeding, children, adolescents or youth under the age of majority without practitioner oversight.
All members agreed that safety data on CBD use are missing for key groups of patients who could be at risk, including:
– Young adults (between the ages of 18-25), due to the unknowns regarding the potential impact of CBD on the developing brain;
– Individuals with co-existing psychiatric conditions, because of CBD’s influence on the brain;
– Elderly people, who are more likely to be on several medications, are more susceptible to falls, and who may metabolise CBD differently, which would require different doses;
– Individuals with underlying medical conditions or taking medication;
– People with liver disease or damage, as they may not be able to clear CBD from their body easily;
– Pregnant and lactating individuals, although much remains unknown about the potential effects of CBD on the developing child and impact on milk production/quality, there is emerging evidence that CBD may have a harmful effect on fetal development in animal models;
– Individuals with allergies to cannabis or other non-medicinal components contained in the CBD preparation (such as the carrier oil);
– Certain ethnic groups and Indigenous Peoples, as genetics can play a role on how CBD and other cannabinoids affect the body; and
– People who identify as LGBTQ2+ — because the potential gender-based impact of CBD use has not been assessed.
Recommendations: A to J
A) The committee unanimously agreed CBD is safe and tolerable for short-term use (a maximum of 30 days) at doses from 20 milligrams per day (mg/day) to a maximum dose of 200 mg/day through oral administration (i.e. by mouth via capsules or oils) for healthy adults provided they discuss the use of any other medications with their pharmacist.
According to the committee’s definition of CBD preparations, the committee also noted that if an individual took up to the maximum dose of 200mg/day, the maximum amount of THC that is absorbed into the bloodstream and reaches the brain would potentially be too low to cause appreciable psychotropic effects for most people.
B) The committee strongly recommends that all health products containing CBD should carry statements on potential interactions between CBD and other drugs or alcohol, and should not be used for individuals who are pregnant, lactating, or considering pregnancy, or people with allergies or hypersensitivity to cannabis, cannabinoids, or other components of the manufacturing process.
It is also strongly recommended that a warning be prominently placed on the product label and insert which states that due to the potentially harmful effects of CBD products on fetal development, this product should not be used by individuals who are pregnant, considering pregnancy, or breastfeeding.
The members were concerned about variations in the bioavailability of CBD depending on its dosage form, outlining that the maximum daily safe dose of CBD would be different depending on how CBD is taken. For instance, inhaled CBD goes directly into the bloodstream through the lungs and takes effect quickly, although this can vary depending on the mechanism of inhalation. Given the risks and additional harmful chemicals associated with smoking and the unclear risks of vaping, the Committee did not recommend these types of products for CBD delivery. When CBD is taken orally, such as a capsule or drop, it is absorbed through the digestive system, which can take more time and impact the amount absorbed. When pure CBD oil is applied to the skin, such as in cream, very little is able to penetrate beyond the most superficial layers of the skin. In order to penetrate deeper tissues, such as the joints or tendons, different transport mediums can be used. Therefore, CBD can be absorbed very differently depending on other ingredients present in the cream such as excipients.
C) The committee recommends that packaging for health products containing CBD should have clear dosing instructions and warnings of potential side effects, emphasizing that side effects can be worse at higher doses.
D) CBD is not habit forming, however, the committee recommends that health products containing cannabis should carry a warning to clarify they are not intended to help reduce the consumption of opioids or alcohol as there are no definitive studies that have validated its use for those indications.
All members of the committee agreed research shows CBD alone is not habit forming, which reflects a similar finding reached in a recent CBD review done by an expert committee of the World Health Organization (WHO).
E) The committee recommends that the approval of health products containing CBD should be accompanied by public education to explain possible benefits and risks, information on safety, and on gaps in research knowledge around the non-prescription use of CBD.
F) The committee recommends that:
– Labels on health products containing CBD should encourage consumers to report adverse reactions that result from using the product by offering multiple, easy-to-use reporting options. All platforms and resources for reporting adverse reactions should be designed to ensure equitable access for the wider Canadian community.
– Health products with CBD should be packaged in boxes, so an insert with key details on the product can be included with every sale.
– Consultation with a pharmacist should be encouraged if taking other medications, therefore health products containing CBD should only be available in pharmacies
The Committee outlined that the evidence requirements maintained under Health Canada’s Food and Drugs Act for health products could also be applied to potential non-prescription CBD products. They agreed that safety, efficacy, and quality requirements developed for potential nonprescription CBD health products could be modeled on those used by Health Canada’s Natural and Non-prescription Health Products Directorate as this provides the best mechanism for Health Canada to assess and regulate non-prescription or natural health products containing CBD.
They observed that different classes of natural health products also require clinical evidence on safety, efficacy, and robust quality standards. As the Natural Health Products Regulations outline requirements for how clinical trials with natural health products must be conducted, that would allow flexibility for these types of products while still requiring consistent evidence standards. The Natural Health Products Regulations standards for setting dosages and outlining uses could also be applied to CBD products as defined within this committee mandate.
The committee recommended the need for consistent quality standards and requirements to ensure Canadians have access to non-prescription drugs containing CBD of consistent quality. Additionally, the committee identified the following product-specific elements to consider when setting quality requirements for health products containing CBD:
– The source of the product, including the cultivar or variety and its country of origin.
– All other phytocannabinoids and terpenoids present in the product and their concentrations.
– The total carboxylated and decarboxylated forms of the CBD (these different forms may have different effects on the body).
– Which solvents were used to extract the cannabinoids from cannabis, how much of them remain in the product, and the type of extraction. This is particularly important as some solvents can be toxic at certain levels.
– Allergens (e.g. some individuals with tree nuts allergies may cross-react to fractionate coconut oil).
The veterinary subcommittee of the Science Advisory Committee on Health Products Containing Cannabis, launched in January 2021, created its own definition of CBD to support deliberations and draw conclusions about the evidence in a consistent manner. It defined CBD where it comprises 98 percent or more of the total cannabinoid content and THC is less than 0.3 percent of the total cannabinoid content. Based on how products were defined within the available studies for animals, the THC limit of less than 0.3 percent was identified to be consistent with the definition of industrial hemp used under the Cannabis Act. Their recommendations show insufficient evidence in present animal studies, especially when it comes to horses as pets.
G) Among the evidence available for CBD use in companion animals, subcommittee members agreed that there was only sufficient safety evidence for CBD use in dogs. Specifically, when administered at very low doses between 0.2-2mg/kg orally twice daily.
The subcommittee looked at safety evidence for health products with CBD by species of animal and unanimously agreed that there was not enough evidence to consider the non-prescription use of CBD in horses. Members also discussed concerns with the use of CBD in food-producing animals, because so little is known about the extent to which residues would impact the human food chain. They pointed out that there are no guidelines on acceptable maximum residue limits (MRLs) for CBD and other phytocannabinoids in animals, which may end up within the food chain or be exported internationally. The residue limit is the length of time required for food-producing animals to clear their system of any cannabis residue to a level considered safe for human consumption. Due to this factor, the use of CBD or cannabis in food-producing animals was not considered within the subcommittee’s scope of work. Should there be an inadvertent administration of cannabis products to animals destined for the food chain, the subcommittee suggested the need to establish MRLs. This would also add clarity to the potential development of such products intended for food animals.
Members agreed that while there is some evidence regarding the safety of CBD use in cats, the available evidence is insufficient to draw any reliable conclusions or provide any specific recommendations.
Members agreed that there are significantly more studies done on dogs than on other companion animals. Based on the available information, members agreed that CBD is considered safe for dogs when administered at very low doses between 0.2-2 mg/kg and taken orally twice a day.
However, the Subcommittee unanimously agreed that the only health issue for which there is sufficient evidence regarding the efficacy of CBD for the treatment of pain associated with osteoarthritis in dogs. There is some promising early evidence for dogs, that CBD might work to promote calmness, treat nervousness, rashes and limit aggression, but the data was not strong enough to support recommendations for use.
H) Subcommittee members agreed there was sufficient evidence regarding the efficacy of CBD for the treatment of pain associated with osteoarthritis in dogs, however insufficient information to recommend a specific dose.
The subcommittee suggested CBD products be sold only in veterinary clinics, for specific conditions diagnosed by a veterinarian.
I) The subcommittee recommends that any CBD product that is intended only for dogs should have a confirmed diagnosis of osteoarthritis from a veterinarian.
Until more safety and efficacy information becomes available, pet owners should consult a veterinarian prior to administering CBD to their pets.
J) The committee recommends that high-quality clinical research into the safety and efficacy of cannabis, CBD and other phytocannabinoids, should be further supported by governments and funding agencies.
Priority areas for the CBD research
When addressing the priority areas and considerations for the research, the Committee found that most of what is known about CBD safety and efficacy is drawn from studies focused on serious conditions that would require practitioner oversight, such as for epilepsy or severe psychiatric illnesses. The data available on how CBD may promote sleep, or help with symptoms associated with nervousness or mild pain, tends to be secondary in nature and were not what the studies were designed to investigate. These outcomes are identified as observations from studies where a severe condition is a primary focus. As they point out, that makes it difficult to draw conclusions on how the results would apply to a healthy adult population. Also, most of the pain studies combined CBD and THC or added CBD to opioid treatment for severe chronic pain, which made it difficult to distinguish the effects of CBD.
Also, the Committee found that the studies used CBD products of different quality and product types, and the doses tested varied. Further information is needed on different routes of administration such as for CBD creams and ointments, which are administered topically. In many instances, the cannabis product being investigated in a study was not defined which made it difficult to draw conclusions regarding the committee’s definition of CBD and made comparisons between studies challenging. There were limited randomized placebo-controlled trials, and among the information available, many of the studies were comprised of a small number of participants. This lack of consistent quality data limits the ability to draw clear conclusions. Furthermore, committee members also discussed the barriers currently in place in Canada to conduct this type of research and agreed that implementing a less complex regulatory framework and providing easier access to quality products to conduct studies would support the research community.
The committee’s review and discussions revealed numerous gaps in research evidence on CBD and cannabis in general. These gaps, which should be made priorities for research, include:
– Long-term safety data, including from studies of people using cannabis products over time;
– Potential interactions between cannabis health products and other medications (including for use in animals);
– Bioavailability and safety data for delivery formats other than by mouth;
– Safety and efficacy data for people with unique risks and understudied populations, including the elderly, individuals with liver damage, ethnic populations, Indigenous peoples, pregnant and lactating individuals, children and young adults (particularly between 18-25 years of age), people who identify as LGBTQ2+ or two-spirited, and individuals with certain mental and psychiatric conditions;
– Appropriate dosing; and
– Studies focused on effective treatment of minor health problems
The Subcommittee on animal health noted that more scientific evidence is needed on specific indications for CBD use in companion animals, such as dogs, horses, and cats. The overall absence of research meant there was little information on possible side effects of cannabidiol or cannabis use in these species. Most of the available safety and efficacy information came from scientific studies and surveys of owners and veterinarians where the most commonly reported side-effect was sedation. No serious side effects were reported, however further scientific information is needed.
With regards to food-producing animals, more information is needed to support the establishment of maximum residue limits for cannabis in food-producing animals. This information would inform potential risks for humans that consume animals who have ingested CBD.
The recommendations are based on the information available as of March 2022 and should be revisited as further scientific and clinical evidence develops.
The full report can be found here.
Reviewed by Sasha Bajilo, founder of ILESOL Pharmaceuticals, an industrial scale producer of CBD products and formulations. Expert on Hemp/Cannabis policy, member of the Croatian Ministry of Health regulatory commission for medical cannabis.