Article and case study written in collaboration with Life Science Law – Legal experts in life science industry laws and regulations; providing practical solutions to business challenges and objectives. LS Law provides confidence to businesses that the legal landscape is known, risk has been identified and mitigated in a proportionate manner which supports the attainment of its goals and priorities.
In 2013, Dr. Sanjay Gupta of CNN presented a program called ‘Weed’ (*1), in which he profiled a young girl with Dravet syndrome whose life was turned around and significantly improved after being given a CBD-rich hemp extract. This documentary catapulted a fringe product into the mainstream, and within 10 years, surveys suggest that 60% of US adults (*2) and 15% of consumers across Europe (*3) have tried CBD.
Meanwhile, the regulatory status of cannabidiol (CBD) and cannabis-containing products is playing catch up with consumer demand. Many regulatory agencies across the globe are looking into how to develop a legislative framework fit for purpose. The current routes to market vary widely and are highly complex. Understanding the relevant national and regional status of cannabis products is critical for any company wishing to enter this sector, including manufacturers, distributors, and life sciences companies.
In this article, we will explain the key terms, cover the main routes to market, and provide insights into a case study we undertook for a client of RegAsk who wished to understand the regulatory landscape of Medical Use Cannabis worldwide.
What is Cannabis?
UN Single Convention of Narcotic Drugs
‘Cannabis’ is defined as the “flowering or fruiting tops of the cannabis plant (excluding the seeds and leaves when not accompanied by the tops) from which the resin has not been extracted, by whatever name they may be designated,” as per Article 1, Definitions, UN Single Convention on Narcotic Drugs, 1961 (*4). While ‘’cannabis resin’’ is defined as ‘’the separated resin, whether crude or purified, obtained from the cannabis plant’’. The Single Convention on Narcotic Drugs (SCND) is an international treaty that controls activities (cultivation, production, supply, trade, and transport) of specific narcotic drugs and lays down a system of regulations (licenses, measures for treatment, research, etc). As of 2022, the SCND has been ratified by 186 countries. It is the primary treaty and document from which all signatory countries refer when they translate the content of the SCND into their national Misuse of Drugs Acts and Regulations.
At the adoption of the Convention in 1961, cannabis and cannabis resin were listed in both Schedule I and Schedule IV. Schedule IV is the most tightly restricted category, reserved for drugs that are ‘’particularly liable for abuse and to produce ill effects’’ and whose ‘’liability is not offset by substantial therapeutic advantages.’’ Its initial placement into this category was not based on science, and a scientific assessment had not been undertaken until 2018 when the World Health Organisation (WHO) tasked the Expert Committee on Drug Dependence (ECDD) to prepare a scientific evidence-based assessment of substances. (5*)
The ECDD made several recommendations but only one recommendation was adopted. That is to remove cannabis and cannabis resin from Schedule IV and only list it in Schedule I. Schedule I is less restrictive and lists other drugs for medical and scientific purposes such as natural, semi- and synthetic opiates. Schedule I lists a requirement of a medical prescription for the supply or dispensation of drugs to individuals. Since 2021, cannabis and cannabis resin remain listed in Schedule I of the SCND, alongside extracts and tinctures of cannabis. The reason why the cannabis flowers and tops, rather than a single constituent, was originally declared a narcotic is that the structure of the main psychoactive phytocannabinoid, tetrahydrocannabinol (THC) that causes the ‘high’, was not yet discovered. THC was not determined until three years later (1964) in Israel by Mechoulam (6*).
The WHO also tasked the ECDD to review the compound cannabidiol (CBD). CBD is one of the main cannabinoids naturally abundant in the plant. In December 2018, the ECDD recommended that preparations considered pure CBD not be placed under international drug control as the substance was not found to have psychoactive properties and presents no potential for abuse or dependence. (7*). The ECDD recommendation 5.5 has been rejected meaning that the UN will not add a footnote to read ‘preparation containing predominantly CBD and not more than 0.2% of THC are not under international control’ in the vote in December 2, 2020. Despite the recommendation, CBD was not removed from international control. This means that the SCND considers that all cannabis tinctures and extracts made from the flowers of any plant of the species cannabis is subject to schedule I controls, but the change in legal status could facilitate access and availability of medical cannabis.
The UNSC is the primary treaty, and the National Drug Acts and Regulations could be likened to second tier legislation interpreting the UNSC and translating it into their national laws. The interpretation varies widely which makes cannabis such a complex legal topic. There is no harmonised approach, and every country has a unique programme with specific requirements placed on manufacturers, distributors and how patients can access medicinal cannabis.
Terms to Know
The terminology of cannabis and its constituents can be confusing. For clarity we apply the following meaning:
- ‘Cannabis plant’ means any plant of the genus Cannabis.
- ‘Medical Cannabis’ means any type of cannabis product prescribed by an authorised practitioner to prevent, treat or cure a medical condition.
- ‘Cannabis-based medicines’ are produced for medicinal use in humans; it is a product that is regulated as a medicinal product, or an ingredient of a medicinal product.
- ‘Licenced medicinal cannabis product’ is a medication that has been through randomised controlled trials and received marketing authorisation.
- ‘Cannabinoids’ are ligands that have affinity for an activity at cannabinoid receptors. Over 100 cannabinoids have been isolated from cannabis so far.
- ‘Major cannabinoids’ or the big six are the main cannabinoid types that are usually detected in each breeding strain of cannabis. There is no strict definition but widely acknowledged as major cannabinoids are trans-Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromine (CBC) and Δ9-tetrahydrocannabivarin (THCV).
- ‘Minor cannabinoids’ means other phytocannabinoids that are present in smaller amounts in the plant. (11*) Examples include cannabidioloic acid (CBDA), cannabigerolic acid (CBGA), tetrahydrocannabinolic acid (THCA), cannabidivarin (CBDV) and cannabichromevarin (CBCV) amongst many others.
- ‘Cannabidiol (CBD)’ is one of the major cannabinoids, abundantly present in certain strains of cannabis that are generally called hemp, or industrial hemp. CBD is non-psychoactive and used both in medication and in food supplements.
- ‘Hemp’ is cannabis Sativa L. A strain of cannabis that contains predominantly the cannabinoid CBD, is non-psychoactive and the seeds are used in human and animal foods.
- ‘CBD rich extract’ means that the extract contains primarily CBD but also other major and minor cannabinoids that are present in small or trace amounts.
- THC (Δ9-tetrahydrocannabinol/Δ9-THC)– the most prevalent psychoactive compound in the cannabis plant.
The History of medical cannabis
According to the Chinese historic records and archaeological data, the history of Chinese cannabis cultivation and use spans approx. 5,000-6,000 years. The first documented case of its alleged healing properties dates back to 2,800BC, when it was listed in the Emperor Shen Nung’s (regarded as the father of Chinese medicine) pharmacopoeia. (*8). In Europe, the world’s oldest cookbook, ‘De Honesta voluptate Et Valetudine’ included a cannabis recipe, a ‘nectar of health’ in the first ever cookbook printed in Latin in 1475. In the 19th century cannabis was widely used in Europe for a variety of ailments, including muscle spasms, rheumatism, epilepsy, to aid childbirth and for many other health conditions. Medicinal cannabis emerged as a mainstream medicine in the West, it was added to the US Pharmacopeia in 1851.
The 20th century heralded the age of cannabis prohibition and with it the loss of its use for medical applications. The entire 20th Century is a sequence of Countries banning cannabis, until 1996, when California became the first jurisdiction in the United States to legalise cannabis for medicinal use (*9), followed in 2001 by Canada. The tide has been swinging in the other direction once again since the beginning of the 21st Century. The list of Countries legalising medicinal cannabis is constantly expanding with North America, South America and Europe in the lead, followed by African nations. A slower progress is observed in Asia and there is still stringent prohibition with severe penalties in almost all Muslim Countries.
In 2020, the UN Commission on Narcotic Drugs (CND), based on WHO recommendations, recognised the medical value of cannabis and removed it from Schedule IV of the 1961 Convention, but left it in Schedule I (*10). Finally, the medicinal usefulness of cannabis has been officially acknowledged and a number of governments mentioned the withdrawal from Schedule IV in their rationale for recently established national medical cannabis reforms, such as Morocco, Spain, Japan and Peru.
EU Clinical Trials Register
The EU Clinical Trials Register lists a number of cannabis-based clinical trials, covering a wide variety of conditions such as PTSD and anxiety disorders, osteoarthritis, neuropathic pain, anti-tumoral effect of cannabis oil. Cannabinoids investigated are for example; Cannabinol (CBN) for the treatment of peripheral neuropathic pain and another trial for patients with epidermolysis bullosa. Tetrahydrocannabivarin (THCV) as an add on to metformin in the treatment of patients with type-2 diabetes. Cannabidivarin (CBDV) for the treatment of HIV-associated neuropathic pain.
The European Medicines Agency (EMA) has provided a number of cannabis products with orphan designation, permitting to supply medicinal products with the active substance lenabasum (containing Δ8-THC) to treat a number of rare conditions including cystic fibrosis, dermatomyositis and systemic sclerosis in the EU.
Licenced Medicinal Cannabis Products
There are a number of Cannabis based products now which have been authorised for medical use across the globe:
Dronabinol is a generic name for the molecule of Δ9-THC in the pharmaceutical context. It is marketed as Marinol® and Syndros ®, a registered trademark of Solvay Pharmaceuticals. Dronabinol is available as a prescription drug in several countries including the United States, Germany, South Africa and Australia.
GW Pharma, founded in 1998, received marketing authorisation in 2018 by both the US FDA and UK FSA for their lead product, Epidyolex®. The medication is made using highly purified cannabidiol (CBD) and can be used to treat two rare forms of epilepsy.
Another GW Pharma medicine is Sativex®. It holds a marketing authorisation in the UK and in almost all EU member states. Sativex contains both Δ9-THC and CBD at roughly equal levels. It has also been approved by Health Canada for the treatment of multiple sclerosis spasticity.
Jazz Pharmaceuticals acquired GW Pharma, a highly innovative global biopharma leader in 2021 for $7.2 billion. A new age for cannabis-based medicines is commencing offering a plethora of commercial opportunities.
Regulatory Status of Medical Cannabis
It is impossible to summarise the regulatory status of medicinal cannabis in a simple way. The reason being that each country translated the UNSC into their National Misuse of Drugs Act and Regulations with variations. More pertinently, only a few Countries so far have developed a medicinal cannabis programme and the licence requirements set out for all parties in the supply and distribution chain are unique in each jurisdiction. There is also no harmonised approach in Europe nor in the US yet either. It is strongly recommended to seek regulatory advice for the type of product and jurisdiction a company wishes to enter.
How to bring a cannabis-based product to market
In countries, where it is legal to bring cannabis-based products to market, the options may include:
- A medicine with full marketing authorisation
- A cannabis-based medicine licensed as part of a medical cannabis programme
- As a food supplement
Where a product is to be used for a medical purpose, the traditional route is to carry out clinical trials in order to confirm the safety and efficacy of a product for the treatment of a specific indication. In the event the primary end point of a phase III trial is successful, it is then permissible to to the Regulatory Authorities for a marketing authorisation within the jurisdiction in which you wish to place the medicine on the market. The Regulatory Authorities will assess the data, and if a marketing authorisation is granted, the product can then be placed on the market for use in relation to the specific indication for which the product has been assessed.
National Medical Cannabis Programmes
Almost 50 Countries have now legalised medical use of cannabis and every year additional Countries introduce access programmes. Navigating the Regulatory landscape is highly complex and can be challenging as each Country has a unique approach and different procedures in place both for how patients can access cannabis-based medicines and what stringent processes need to be followed to import, handle and distribute the products. There is no unified approach and country programmes can vary widely. In 2019, Europe commenced deliberations to create an EU-wide Regulation for medicinal cannabis. Meanwhile several member states have their own, unique national programmes.
Most Countries select a pharmacy-only approach. Often a special license regime permits licensed compounding pharmacies to prepare the cannabis-based medicinal product in accordance with the doctor’s prescription for an individual patient. A doctor may prescribe flowers, capsules, resin, eye drops, suppositories, creams, transdermal gels, edibles and syrups and the pharmacist will prepare and dispense the prescribed cannabis-based medicine.
CBD as a Food Supplements
Some Countries permit or tolerate the sale of food supplements that contain primarily the non-psychoactive compound cannabidiol (CBD). It is important to note, that a food supplement cannot be marketed or claim to treat a medical condition. If medical claims are made, it is likely to fall foul of the legislation and be deemed to be a medicinal product, for which a full marketing authorisation is required.
Nevertheless, CBD is a hugely popular food supplement and is sold widely, particularly in the US, Europe, the UK, South Africa and Japan. However, the sale of food supplements of CBD is more aptly described as tolerated, rather than meets a current regulatory framework. In Europe, there is a public register, called the Novel Food Catalogue, which lists products of animal and plant origin and other substances subject to Novel Food Regulation. A novel food is defined as a food that had not been consumed to a significant degree by humans in the EU before 15 May 1997, when the first Regulation on novel food came into force.
In January 2019 a new entry was added to the EU novel food catalogue for ‘’cannabinoids’’. It states that the Hemp plant (Cannabis sativa L.) contains a number of cannabinoids and the most common ones are as follows’’… it proceeds to list a number of individual cannabinoids such as ‘’THC, THCA, CBD, CBDA, CBG, CBN, CBC and THCV’’ and states that ‘’extracts of Cannabis sativa L and derived products containing cannabinoids are considered novel foods as a history of consumption has not been demonstrated. This applies to both the extracts themselves and any products to which they are added as ingredient. Synthetically obtained cannabinoids are considered as novel’’.
In Europe, novel foods are subject to the novel foods directive, Regulation (EU) 2015/2283 (12*) which requires that a company submits a novel food application to the European Food Standards Agency (EFSA) which needs authorisation prior to placing the product on the market. Several applications for CBD have been submitted but no authorisations have been granted yet. Under the Brexit Transition Agreement, the UK adopted the novel food catalogue and it’s corresponding entries but companies had to submit a separate novel food application to the UK Food Standards Agency (FSA), in addition to their EFSA submission. The UK has taken a more pragmatic approach and permits CBD products that were on the market prior to 13 February 2020, subject to having submitted a novel food application, pending the outcome of the assessment process. (13*) A public list of permitted for sale products has been published by the FSA.
However, there have been regulatory actions against the free access of citizens to purchase CBD products as a food. Hong Kong banned CBD as a dangerous drug in February 2023, following China’s lead having banned CBD in 2022. The US FDA also grapples with how to categorise CBD food products. In January the FDA announced that it concluded that existing regulatory frameworks for foods and supplements are not appropriate for CBD and that they will work with Congress to find a new way forward. (14*) Japan permits only products that are made from the seed and stalk of the plant, and not the flower. The list of countries permitting CBD products to be sold as a food is currently less than countries permitting it as part of a medicinal cannabis programme.
A client of RegAsk wished to obtain a global assessment of the Regulatory and Legal landscape of the medical use and consumer well-being use of a cannabis-based products for a manufacturer who wanted to understand in which jurisdictions it would be more favourable to target. We provided an assessment of and the steps which are required to place it on the market in a number of jurisdictions, including Europe, Asia, US, South America, UEA, and Africa to enable the client to assess commercial viability to launch manufacturing sites to produce raw material for medical use Cannabis products.
For each of the jurisdictions we:
- Identified countries in which the legal and regulatory status of cannabinoids could provide market entry opportunities.
- Differentiated between medicinal and wellbeing markets and provided relevant licensing information.
- Provided expert opinion as to how the Regulatory Landscape is likely to develop in each of those jurisdictions.
5 Tips and Reminders for Market Entries
- Determine which products of your product portfolio you want to export.
- Select regions of interest.
- Asking the right questions is essential – define precise questions in collaboration with a regulatory expert (a service we provide) you need to know in order to make informed decisions.
- Explore the regulatory overview report – based on the outcome of the regulatory overview report, select preferred options to obtain a more detailed report covering legal and regulatory compliance in detail and type of market entry opportunities for the selected portfolio of cannabinoid products, establishment of a processing facility or other commercial activity.
- Action the outcome.
Understanding the relevant national and regional status of cannabis products is critical for any company wishing to enter this sector, including manufacturers, distributors and life sciences companies. The terminology confusing, different regulators apply different parameters, and so there is no harmonised approach.
In this Article, we have provided a snapshot into the main routes to market and some clarity into the terminology and some insights into the different approaches taken to cannabis products in various jurisdictions. What is clear, is that the regulatory and legal landscape is far from straightforward, and it is imperative that at detailed analysis is carried out in terms of the indication, which is proposed, and what are the options available in terms of placing it on the market before embarking on the journey.
We have industry experts who can help you to navigate the landscape and to provide you with a clear path. For an initial consultation, please do contact us, and we will assign one of our cannabinoid regulatory experts to help you.
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