Frequently asked questions
Cannabis, medicinal cannabis, cannabis-based medicine, cannabinoids, cannabinoid-based medicine,… terminology may lead to confusion. Cannovex aims to bring more clarity on this matter and has developed concise answers to a number of frequently asked questions.Cannovex has made an exhaustive inventory and an in-depth analysis of scientific articles published in international journals on the subject of cannabinoids. These efforts establish Cannovex as the designated conversation partner, sounding board and source of information on cannabinoid-based medicines for all stakeholders.
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Cannabis and hemp both refer to different cultivars of plants of the genus Cannabis sativa L. and to the main botanical products (i.e. dried flowers) derived from this plant. Nowadays the different cultivars of cannabis are cultivated for many uses, such as fiber, seed, oil and indeed, for its pharmacological properties that are attributed to a specific class of molecules: the cannabinoids.
Plants of the genus Cannabis sativa L. that are cultivated for industrial purposes (fiber, seed, oil,etc.) are collectively named ‘hemp’. A specific attribute these hemp varieties have is that they must contain a limited quantity of ð9-Tetrahydrocannabinol (THC the main psychotropic cannabinoid found in cannabis plant genus, usually less than 0.2-0.3%). In Europe,only registered and certified varieties of hemp may be cultivated for industrial purposes by farmers, often after governmental regulatory bodies’ approval. For more information see the EU Plant Variety Database.
Cannabis cultivars that contain more than the limited quantity of THC are not categorised as ‘hemp’ but are known as ‘cannabis’ or ‘drug cultivars’. They are placed under international control by the 1961 Single Convention on Narcotic Drugs of the United Nations (Full text available @ https://www.unodc.org/unodc/en/treaties/single-convention.html). In Europe, these cultivars can only be cultivated to serve medical or scientific purposes and a national regulatory body must provide licenses to cultivate and a form of controlled oversight (i.e. “Bureau Medicinal Cannabis”). An example of this regulation can be found in the Netherlands where the Bureau of Medicinal Cannabis regulates the cultivation and supply chain of cannabis flowers to pharmacies (for more information visit: https://www.cannabisbureau.nl/). In Belgium, the Federal Government has unanimously approved the creation of a Bureau of Medicinal Cannabis (26/02/2019, click here for more information) under the guidance of the Federal Agency for medicines and health products (FAMHP). As of April 2020, FAMHP is still working on Royal Decrees (“Koninklijke Besluiten”) to delineate the necessary guidelines and provisions for the Bureau of Medicinal Cannabis.
In the last couple of years, some countries (most notably Canada) have withdrawn from the international conventions to allow for a government-controlled scheme for the cultivation of cannabis plants for non-medical and non-industrial use known as recreational, adult-use or consumer cannabis.
Cannovex is not involved in the cannabis business for non-medical purposes and has no such future intention. Our mission is to develop cannabinoid-based medicines that improve patients’ lives.
Cannabinoids refer to a group of chemical substances, regardless of their origin or structure, that bind to specific cannabinoid receptors (CB receptors) in the human body. They are a large and varied group of molecules that can be classified in several different ways, but the most useful way to understand the cannabinoid diversity is the following:
Phytocannabinoids, or exogenous cannabinoids, are plant-derived cannabinoids produced by glandular trichomes covering the surface of the cannabis flowers (and sometimes the leaves). They are found exclusively in cannabis plants although some other plants also produce very small amounts of cannabinoid(-like) compounds, such as the Echinacea species, Helichrysum umbraculigerum and Spilanthes oleracea. By 2020, more than 100 different phytocannabinoids have been identified, of which cannabidiol (CBD) and Δ⁹-Tetrahydrocannabinol (THC) are the best known and studied. However, the pharmacological potential of other lesser-known cannabinoids (e.g. Cannabigerol (CBG), Tetrahydrocannabivarin (THCV), etc.) is starting to attract more attention from the scientific community.
Endogenous cannabinoids, or endocannabinoids, are cannabinoids produced inside the mammalian body which function as lipid-based retrograde neurotransmitters. These compounds were discovered in the mid ‘90s along with the specific cannabinoid receptors: (a) CB1R primarily located in the brain and central nervous system; (b) CB2R, mainly localized in the peripheral organs and the immune system. The discovery of these elements also led to the development of the term “the Endocannabinoid System (ECS)”. The two best known and studied endocannabinoids are anandamide (N-arachidonoylethanolamine) and 2-arachidonoylglycerol (2-AG). Endocannabinoids and by extension the endocannabinoid system are involved in a wide variety of processes, including pain, memory, mood, appetite, stress, sleep, metabolism, immune function, and reproductive function. Endocannabinoids are arguably one of the most widespread and versatile signalling molecules known to man.
The main difference between phytocannabinoids, endocannabinoids and synthetic cannabinoids is that the latter are fully synthetic and created in the laboratory. These synthetic cannabinoids can be (a) completely structurally analogous with phytocannabinoids, for example dronabinol (Δ9-THC synthetic), which is the active compound of MARINOL®, a medicine that comes in capsules and has been consumed in the US since 1985 to prevent nausea, vomiting, loss of appetite and loss of weight or (b) new chemical entities such as nabilone, that is the active substance of CESAMET®, a medicine approved for the nausea and vomiting control caused by cancer chemotherapy.
Our mission is to develop cannabinoid medicines that improve patients’ lives. To this end, Cannovex will continue to investigate the therapeutic potential of various types of cannabinoids.
The human body contains several types of receptors to which different cannabinoids (endogenous and exogenous cannabinoids) can bind to cause a pharmacological effect. These receptors are called ‘Cannabinoid Binding receptors’ and are found in the bodies of mammals on various cell types, organs and tissues. They are G-protein coupled receptors and are activated or inhibited by a class of endogenous molecules (ligands) called endocannabinoids. Endocannabinoids act as a form of retrograde signalling molecules to modulate neurotransmission and communication between cells, organs and tissues. This complex bodily system is called the EndoCannabinoidSystem (ECS) and is the reason why mammalian bodies and the human mind reacts to cannabinoids from the cannabis plant.
The ECS is associated with pain modulation, memory, motoric skills, nausea and vomiting, but also with the immune system.
Cannabinoid receptors are classified as CB1 or CB2 receptors. CB1 receptors are found in the brain and the central nervous system, and their activation stimulates sedation, euphoria, dizziness and an increased appetite. CB2 receptors are mainly found in the peripheral nervous system and the immune system. While the effects of activating CB2 receptors on the human body have not yet been studied in detail, it is generally accepted that activating CB2 receptors would generate immune-modulating and some antinociceptive (pain relieving) effects.
THC is known to be a partial agonist for CB1 and CB2 receptors in the human body.while CBD does not have a stimulating effect on these receptors and is assumed to have an effect on the endocannabinoid system in a different way, which has not yet been fully elucidated, but involves TRPV-class receptors and serotonin receptors.
Our mission is to investigate the therapeutic potential of various types of cannabinoids with the aim to develop medicines for various diseases and/or disorders for which the currently available therapeutic options are often suboptimal. To this end, Cannovex will further investigate the role and functioning of CB1 and CB2 receptors, in order to understand the mode of action for potential new medicines.
First, the endocannabinoid system is associated with pain modulation, memory, motoric skills, nausea and vomiting, but also with the immune system. Hence, it is rational reasoning that this system can be modulated (i.e. stimulated or inhibited) by administering cannabinoids that bind to the targeted cannabinoid receptors in this system.
Furthermore, preclinical and limited clinical research has indicated that cannabinoids show huge pharmacological potential in a wide variety of indications mostly as alleviation for several secondary symptoms (improving quality of life). Although, at this point, it often concerns observational studies, studies involving a relatively limited number of patients and non-randomized and/or non-double blind studies, the findings of many of these studies are so encouraging that they justify further in-depth research.
Moreover, there are already cannabinoid-containing products that have been granted FDA and/or EMA market authorisation for medical use, after having successfully passed scientifically designed clinical trials. They include:
- Sativex® (containing phytocannabinoids THC/CBD) has been granted market authorisation by the European Medicines Agency (EMA) in 2012, and is also available on medical prescription in Belgium
- Epidiolex® (containing phytocannabinoid CBD) has been approved for marketing in the US by the Federal Drug Agency (FDA) as well as by the EMA, but is today (March 2020) not (yet?) available on the Belgian market.
- Dronabinol (synthetic cannabinoid, tradenames Marinol® and Syndros®) is approved by the FDA and is available on medical prescription in the USA and a number of other countries, including Canada, Australia and New Zealand.
Our mission is to investigate the therapeutic potential of cannabinoids with the aim to develop medicines for various diseases and/or disorders for which the currently available therapeutic options are often suboptimal. Cannovex will contribute to build scientific evidence for the therapeutic effect of cannabinoid-based medicines.
First, we refer to the indications of the FDA and/or EMA-authorised medicines:
- Symptom relief in patients with spasticity caused by multiple sclerosis
- Certain types of epilepsy
- Anorexia in AIDS patients
- Nausea and vomiting in chemotherapy patients
Second come the additional indications for which initial research studies have suggested that cannabinoids may have symptomatic events:
- chronic neuropathic pain,
- Lennox-Gastaut syndrome.
Ultimately, further research may be considered for all indications related to body functions associated with the endocannabinoid system: pain modulation, memory, motoric skills, nausea and vomiting in other types of patients, disorders associated with the immune system.
In order to protect its intellectual property, Cannovex has filed for patent protection. Awaiting the outcome of this process, Cannovex cannot disclose, for the timing being, the therapeutic areas in which it intends to direct is drug development strategy.
In fact, ‘medicinal cannabis’ is incorrect terminology.
From a linguistic point of view, it would be better to talk about ‘cannabis for medicinal use’ or ‘cannabis-based medicine’.
‘Cannabis for medicinal use’ then refers to an identical type of cannabis that is used for recreational purposes, but then used for a different purpose.
‘Cannabis-based medicine’, on the other hand, refers to a product that contains cannabis, which has a legal status as medicine. The latter implies that such products should meet specific standards, including product purity, adequate formulation, exact dosing, safety and efficacy as confirmed in clinical trials, quality assurance, etcetera. Today, only Sativex® and Epidiolex® qualify for the latter definition.
Cannovex holds the position that most of the so-called ‘medicinal cannabis’ is not suited for medical use since there is no guarantee that these products clinically work or are free of pesticide residues, nor that there is an exact and consistent dosing of the various cannabinoids (THS, CBD,…) in the product. Instead, Cannovex believes that cannabinoid-based products can and should be developed into medicines that can safely and effectively impact quality of life and the health of many patients.
Cannabinoid-based medicines are products containing specific types of cannabinoids in predefined dosages, that are:
- recognised as medicines by the authorities – e.g. the US FDA and the EMA – based on the clinical evidence results from regulated clinical trials
- manufactured according to GMP standards
- marketed in compliance with all relevant legislation pertaining to medicines
- prescribed by a physician, if applicable
- distributed in pharmacies only
- subject to post-marketing monitoring
The mission of Cannovex is to investigate the therapeutic potential of cannabinoids with the aim to develop medicines for various diseases and/or disorders for which the currently available therapeutic options are often suboptimal. Cannovex believes that cannabinoid-based medicines should be subject to the same approval procedures as any other regulated medicinal product.
CBD oil, or cannabidiol oil, is an unofficial name for a variety of products in the form of an oil that contains cannabidiol.
Most so-called CBD oils are manufactured by processing cannabis plants. This implies that, in addition to cannabidiol, they also contain other phytocannabinoids, including ð9-Tetrahydrocannabinol. In many cases, the content of each phytocannabinoid in the product is either unknown, inconsistent or both. Therefore, the vast majority of plant-based CBD oils are not suited to be used for medical purposes – not even in countries where CBD-oil is legally available on medical prescription.
Having said that, CBD oils are marketed under various regulatory statuses in different countries: medicine, food supplement, medical device, but most often with no regulatory status at all.
Over the various countries where CBD oil is available on the market, it is sometimes distributed in pharmacies, general retail outlets, specialised CBD shops… or even in unauthorised distribution channels.
Cannovex urges authorities to issue clear regulations for the distribution of CBD oil in order to protect and stop misleading the patient/consumer, as well as to avoid any product abuse. Cannovex understands that regulatory bodies wish to meet unmet patients’ needs by authorising pharmacy-compounded CBD oil. However, Cannovex believes that this situation should only be maintained while awaiting the availability of cannabinoid-based products that have successfully passed all steps to be granted marketing authorisation as a medicine. In the interim period, Cannovex pleads to restrict the authorisation of CBD oil to pharmacy-compounded products, based on ingredients that meet the required purity standards, upon medical prescription and exclusively distributed in the pharmacy channel.
Cannabinoid-based medicines should be precisely dosed and contain no impurities. At this moment, these requirements can be met with synthetically produced analogous of phytocannabinoids or by combining the use of selected cannabis varieties in which only one specific type of cannabinoid occurs, with innovative techniques for isolating the cannabinoid from the plant.
The so-called ‘medicinal cannabis’ often does not meet the purity and dosing requirements. They may contain pesticide residues and/or the degree of the various cannabinoids and other components is inconsistent and sometimes even not exactly defined. Therefore, these products should not be used for medical purposes.
Cannovex is committed to exclusively apply cannabinoids of the highest purity that enable a precisely dosed formulation.
The legislation concerning cannabis and cannabis-based medicines differs widely in the different EU Member States and by extension the rest of the world and is constantly evolving.
As of April 2020, in most (if not all) EU Member States, cannabis for non-medical purposes is not authorised to be traded on the market. Some countries have instituted a Bureau of Medicinal Cannabis and authorize cannabis and cannabis-derived products for medical use with or without restrictions concerning specific indications (e.g. The Netherlands). Others have authorized pharmacy compounded cannabinoid-based products when medically prescribed and distributed exclusively in the pharmacy channel. A number of EU Member States have granted market authorisation to a number of cannabinoid-based products (e.g. Sativex® and Epidiolex®) as medicinal product for specific indications.
We advise patients to closely evaluate the respective legislation of their EU Member State before purchasing and/or consuming cannabis and cannabis-derived products for medicinal use.
Our mission is to develop cannabinoid-based medicines that are subject to the same approval procedures as any other regulated medicinal product. Cannovex believes that authorisation of pharmacy compounded cannabinoid-based products on medical prescription is a justifiable practice, awaiting the availability of fully-registered cannabinoid-based medicines for a wider indication area. Cannovex does not endorse ‘recreational cannabis’ nor ‘medicinal cannabis’, since the difference between the two implies only the use, not the quality or product consistency.
The potential side-effects depend on the formulation of the product (i.e. the content of the various types of cannabinoids – THC in particular), the dosing, as well as on the way of administration and on individual characteristics of the patient. We advise patients to always closely evaluate the accompanying drug label mandatory for every registered medicines which will indicate the relevant side-effects associated with the respective medicine.
Generally speaking, all side-effects of cannabinoid-based medicines are of a temporary nature and are mainly related to THC.
The main short-term side-effects are: dizziness, weight loss (and an increased risk of falling), dry mouth, disorientation, nausea, sleepiness and euphoria. Severe side effects rarely occur and include: confusion, hallucinations, paranoia and psychosis. Little scientific evidence is available about the chronic medical use of cannabinoids and the related long-term side effects. In general, they are comparable to the short-term side-effects. Long-term side effects associated to THC include: dependency, apathy, reduced concentration and judgement capacity, as well as psychotic symptoms.
Little information is available about side-effects related to cannabidiol. Clinical trials with Epidiolex® refer to: rise in lever enzyme levels , sleepiness, sedation, lethargy, fatigue, reduced appetite, diarrhoea, weight loss, sleeping problems, increased risk for infections, suicidal thoughts or behaviour, and convulsions.
As for all pharmaceutical therapies, the risk of side-effects should be considered in comparison to the benefits of the therapy.
Our mission is to develop cannabinoid-based medicines that are subject to the same approval procedures as any other regulated medicinal product. This implies that the responsible medicines agency would also take the side-effects into account that have been reported in clinical trials when assessing the risk/benefit ration to decide on the market authorisation of a cannabinoid-based medicine candidate.
The mentioned side-effects – mainly those associated with THC – suggest that medical use of cannabinoids can impact driving ability and performance.
As of April 2020, the use of pharmacy-compounded CBD oil and licensed drugs based on cannabis (such as Sativex®) is prohibited in traffic in Belgium (Law of July 31, 2009). Although only trace amounts of THC may be present in the currently available pharmacy-compounded CBD oils there is still a chance that a saliva test is positive. The legally provided limit value for THC in saliva is 10 ng/ml and 1ng/ml in the blood. Exceeding this limit value is in principle possible with the currently available raw material cannabidiol.
It is generally recommended not to drive a car during the first two weeks following the initiation of any daily cannabinoid-containing therapy. For occasional use, it is advised not to drive before 15 hours since the intake of the medicine. Please note that specific regulation applies in several countries.
Cannovex pleads to restrict the authorisation of CBD oil to pharmacy-compounded products, based on ingredients, that meet the required purity standards, are available only on medical prescription and are exclusively distributed in the pharmacy channel. Only this kind of products can provide the guarantee that the THC-level in the product is identified ànd sufficiently low to have no negative impact on the patient’s driving capability.
Contraindications are: a history of psychotic disorders, cardiac disorders (QT interval prolongation, coronary disorders), dependency problems, increased risk of falling, pregnancy and breastfeeding/nursing. Intake of cannabinoids is discouraged for adolescents.
Cannovex’s mission is to develop cannabinoid-based medicines that are subject to the same approval procedures as any other regulated medicinal product. This implies that the responsible medicines agency would also take the contraindications into account that emerge from the clinical trials when assessing their decision to grant market authorisation for a cannabinoid-based medicine candidate.
In general, cannabinoids are usually well tolerated, but bidirectional effects may be expected with concomitant administered agents via affected membrane transporters (Glycoprotein p, breastcancer resistance proteins, and multidrug resistance proteins) and metabolizing enzymes (Cytochrome P450 and UDP-glucuronosyltransferases).
Caution should be undertaken to closely monitor the responses of patients using cannabinoid-based medicines with certain drugs to guard their safety, especially for the elderly and people with chronic diseases or kidney and liver conditions.
Cannovex’s mission is to develop cannabinoid-based medicines that are subject to the same approval procedures as any other regulated medicinal product. This implies that the responsible medicines agency would also take the drug interactions into account that have been reported in the clinical trials when assessing their decision to grant market authorisation for a cannabinoid-based medicine candidate.
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