A set of clinical frequently asked questions (FAQs) to provide further support to prescribers.
There are three broad requirements that a product should satisfy:
- The product is or contains cannabis, cannabis resin, cannabinol or a cannabinol derivative
- It is produced for medicinal use in humans; and
- It is a product that is regulated as a medicinal product, or an ingredient of a medicinal product.
The definition is necessarily broad to take account of the range of preparations which are cannabis-based that have been used for therapeutic purposes and to ensure that raw products/ingredients and intermediate products are captured. This is essential to ensure that where there is a clinical need, a patient will be able to access appropriate cannabis-based medicines and/or products can be made to meet any prescription.
Epidiolex® and other ‘pure’ cannabidiol (CBD) based products (including synthetic versions) are not classified as a cannabis based medicinal product and are not controlled drugs as they contain very small amounts of THC.
Further details on Epidiolex® can be found below. Epidiolex® is currently going through the licensing process in the UK.
There are three main groups of chemical compounds that fall within the broad category of ‘synthetic cannabinoids’:
- Synthetic compounds which are identical in structure to naturally occurring cannabinoids such as delta-9-tetrahydrocannabinol (THC) e.g. Dronabinol.
- Synthetic compounds structurally related to naturally occurring cannabinoids that have been developed to mimic naturally occurring cannabinoids such as THC e.g. Nabilone.
- Synthetic compounds not structurally related to naturally occurring cannabinoids but which bind to cannabinoid receptors in the body.
With respect to group 1 compounds, Dronabinol has been developed as a medicinal product. Dronabinol is not available as a licensed medicine in the UK. In addition, in group 2, Nabilone has also been developed for medicinal use and is available as a licensed medicinal product. Group 3 synthetic compounds not structurally related to naturally- occurring cannabinoids but which bind to cannabinoid receptors in the body are not available as licensed medicinal products. Many of the compounds in group 3 have frequently been found in illicit street products referred to by the street names of Spice and Black Mamba, and are predominantly new psychoactive substances (NPS). There is clear evidence of significant harm and several deaths associated with their illicit use.
The Advisory Council on the Misuse of Drugs (ACMD) has particular concerns with compounds falling within group 3 and others within group 2, with the exception of Nabilone, and is of the view that further research into this complex group of diverse substances is important, given the associated potency and harms.
This group of new psychoactive substances is being considered by the ACMD as part of their longer-term review.
Due to the limited evidence base and their unlicensed nature, prescribing of cannabis-based products for medicinal use is restricted to only those clinicians listed on the Specialist Register of the General Medical Council.
Any decision to prescribe must take into account the relevant GMC guidance and the relevant NHS Trust governance procedures for unlicensed medicines in the normal way. In addition, a Specialist on the General Medical Council Register should only prescribe within their own area of practice and training, and the decision to prescribe should generally be agreed by the multidisciplinary team. Adhering to the normal medicines governance systems not only supports good clinical practice but also offers liability coverage for NHS employees in prescribing an unlicensed medicine and importantly, is safer for patients.
A GP may make a referral to a specialist doctor on the General Medical Council’s ‘Specialist Register’ once the patient reaches the appropriate point in their treatment pathway.
The law requires that these products be supplied under either the prescription or direction of a clinician on the General Medical Council’s Specialist Register. It is important to ensure that clinical specialists with the appropriate expertise are able to make treatment decisions in their patient’s best interest, and that decisions about prescribing are in the hands of expert clinicians led by evidence on quality, safety and effectiveness, balancing the benefits that might be accrued for a particular patient against the products proven harms.
Private Doctors who are on the General Medical Council’s specialist register are now legally able to prescribe cannabis-based products for medicinal use. This is the same for NHS and private providers. In the NHS, decisions to prescribe should generally be the result of multidisciplinary discussion. The Chief Medical Officer expects clinicians in a non-NHS setting to follow equivalent processes for prescribing unlicensed special medicines.
Specialist Doctors, whether working for the NHS or not, will receive support and guidance on the evidence for the use of cannabis-based products for medicinal use, and the circumstances in which they may be prescribed. This is in the form of the interim clinical guidance (from the BPNA and RCP), the MHRA specials guidance and the NICE clinical guideline.
Prescribing by both private and NHS providers will be monitored by local controlled drugs accountable officers.
Specialist doctors wishing to prescribe this privately outside of a hospital environment will need to contact the local lead Controlled Drugs Accountable Officer for a Prescriber Identification Number.
The law requires that these products be supplied under either the prescription or direction of a clinician on the General Medical Council’s Specialist Register.
However, whilst it is possible for a GP to continue prescribing legally, it is advised that all prescriptions will need to be initiated and signed by a specialist doctor. Consideration will be given to how shared care arrangements should or could work, including determining whether it is indeed appropriate to have such arrangements in place. If a doctor prescribes a medicine under shared care arrangements, he or she accepts clinical and professional responsibility for that prescribing decision.
The law has been drafted such that a specialist needs to be responsible for the decision to prescribe. However, the law does allow other prescribers to continue prescribing once the decision to prescribe has been made by a specialist.
There are existing arrangements permitting doctors not on the specialist register but working under the direction of a specialist within a hospital setting (e.g. speciality registrars, supplementary prescribers, non-medical independent prescribers etc.) to continue prescribing, once patients have become established on a particular treatment with no problems.
In general, however it is expected that patients receiving these products to remain under the direct care of a specialist doctor (i.e. initiation and continued prescribing) in the first instance.
Private prescriptions from outside the UK will not be permissible as the law indicates that prescribing of cannabis-based products for medicinal use is restricted to only those clinicians listed on the Specialist Register of the General Medical Council.
UK Regulations mean that Schedule 2 and/or 3 controlled drugs and unlicensed medicines may not be supplied on a prescription authorised by an EEA practitioner. This is not unique to cannabis. In addition any prescription that does not comply with the UK requirements cannot be used to lawfully import a product for personal use from another jurisdiction.
As with prescribing any other unlicensed medicine, it is a clinical decision to determine the most appropriate medication or course of treatment to prescribe for a patient, having taken into account the patient, the clinical condition, the clinical evidence of efficacy and safety and the suitability of licensed medicines.
The National Institute for Health and Care Excellence (NICE) has been commissioned to produce a clinical guideline on the prescribing of cannabis-based products for medicinal use in humans. This guidance is expected in October 2019.
The draft scope of NICE guidance includes use in:
- people with chronic pain
- people with intractable nausea and vomiting
- people with spasticity
- people with severe treatment-resistant epilepsy.
In the interim, the British Paediatric Neurology Association (BPNA) has developed clinical advice on the use of cannabis-based medicinal products in paediatric patients with certain forms of severe epilepsy, and the Royal College of Physicians (RCP) has developed additional advice around prescribing of cannabis-based products for medicinal use in intractable chemotherapy induced nausea and vomiting, and chronic cancer pain.
The Association of British Neurologists (ABN) has developed guidance on the use of cannabis-based products for medicinal use in adult patents with neurological conditions. This guidance is now available and covers use in rare epilepsies and MS related spasticity.
Advice produced by the Professional Organisations does not remove the clinical discretion of the prescriber in accordance with their professional duties as is the case for all other guidance.
No. Doctors should always first consider prescribing medicines that are licensed for the specific condition that the patient presents with. This is because these products have been tested for quality, safety and efficacy by the regulators for the indication they are prescribed for, and are subject to the quality assurance arrangements that apply to all licensed medicines when they are manufactured. If this is not possible then the next option would be an off-label use of a licensed medicine, again because these will have been subject to those quality assurance arrangements, but the doctor has to be confident that the medicine would be appropriate for the specific indication and the patient, that it is being prescribed for.
Prescribing an unlicensed product should be considered third and only if an individual patient has exceptional clinical needs that cannot be met by a licensed or off-label medicine.
The BPNA guidance recommends that pure CBD (Epidiolex®) should be the default choice when considering prescription of a cannabis-derived medicinal product in intractable epilepsy in children. They do not recommend prescribing other non-licensed cannabis-derived medicinal products, which includes all artisanal cannabis oils, whether or not they comply with good manufacturing practice (GMP) or good distribution practice (GDP) standards.
Epidiolex® is a pure CBD product that has been through randomised controlled trials for two epilepsy syndromes (Dravets syndrome and Lennox-Gastaut syndrome). Epidiolex® is not a controlled drug and does not fall under the group of products that have been subject to re-scheduling. However, it is currently unlicensed in the UK, although we expect it to be licensed in early 2019.
Because the only evidence for efficacy and safety in childhood epilepsies relates to use of pure cannabidiol (Epidiolex®). Currently there is no good evidence that products that contain THC are either safe or efficacious and there is a concern about the effect of THC on the developing brain. There is evidence that chronic high exposure to THC during recreational cannabis use can affect brain development, structure and mental health.
Cannabis has many active chemical constituents and two of these constituents, tetrahydrocannabinol (THC) and cannabidiol (CBD) have been investigated the most in respect of their medicinal value. THC is the major psychoactive constituent of cannabis and is considered responsible for giving so called “highs” to users of cannabis. CBD on the other hand, is not psychoactive. “Pure CBD” is not a controlled drug for the purposes of the 1971 Misuse of Drugs Act.
Products falling within Schedule 2 will contain varying quantities and ratios of THC and CBD and may be available in a range of pharmaceutical forms.
The BPNA advise that any child who is already taking a cannabis-based product for medicinal use containing THC that is having an apparently beneficial effect should transition to pure cannabidiol (Epidiolex®) as there is stronger evidence of effectiveness and a lower risk of long term side effects than for products containing THC. However as with all treatment decisions, it is ultimately the responsibility of the patients’ Paediatric Neurologist, in discussion with the patient and their family, to determine the best treatment options, taking into account the emerging evidence and the patients’ individual clinical circumstances.
The recommendations have been jointly produced by the Royal College of Physicians (RCP), the Royal College of Radiologists (RCR) and in liaison with the Faculty of Pain Medicine of the Royal College of Anaesthetists. The guidance covers cannabis-based products for medicinal use for chemotherapy induced nausea and vomiting and chronic pain (cancer pain and chronic neuropathic pain).
They recommend that for chemotherapy induced nausea and vomiting, cannabis-based products for medicinal use should remain an option for those who have failed standard therapies. They should not be used as a first-line treatment. They do not recommend use of cannabis-based medicinal products for chronic pain as there is no robust evidence supporting this.
The current evidence base for use of cannabis based products for pain is not sufficiently developed yet; whilst individual patients may perceive benefit; this hasn’t been fully tested in comparative randomised controlled trials in large numbers of patients. Potential harms of using cannabis based treatments for medicinal use in the long term have also not been studied. There are currently no licensed cannabis based products available for use in pain.
A recent Cochrane review for neuropathic pain states that ‘there is a lack of good evidence that any cannabis-derived product works for any chronic neuropathic pain’
Rescheduling of these products makes it easier for clinical trials to take place to support furthering our understanding, as the evidence base develops following more research being carried out and as products become licensed, this position will be reviewed.
The ABN guidance recommends that for both Dravets syndrome and Lennox-Gastaut syndrome the BPNA guidance is consulted and they recommend that cannabidiol should be prescribed in these cases.
For other types of epilepsies, they recommend that at present that there is either no or very little evidence for benefit in other forms of epilepsies. Until there is more evidence the ABN guidance advises extreme caution if these products are being considered for any other form of epilepsy.
The RCP guidance covers use in chronic neuropathic pain which is the predominant type of pain that MS patients experience. Use for chronic pain is currently not recommended as there is insufficient evidence.
There is also some evidence for use of cannabis based products for MS related spasticity, as outlined in the CMO report. There is a licensed product available in the UK for use in MS related spasticity – Sativex®. This has been through the licensing process and should be used over any unlicensed cannabis based products for medicinal use; however, to note that NICE have already reviewed the use of Sativex® in MS patients and do not recommend use on the NHS in England as it is not cost effective. In Scotland, the manufacturer has never made a submission to the Scottish Medicines Consortium and so Sativex® is not routinely available. In Wales Sativex® is available for use for MS related spasticity.
The ABN guidance suggests that cannabis based products for medicinal use are used only in people who have had an unsatisfactory response to conventional spasticity drugs e.g. Sativex® – noting NICE and equivalent guidelines on use.
In line with routine clinical practice patients may wish to seek a second opinion and should be supported to do so. Clinicians should refer patients for a second opinion using their established protocols. Further information for patients on second or further opinions is available via the NHS website.
If it is not possible to obtain a second or further opinion using established protocols then please contact your NHS England Regional Medical Director who will be able to offer further advice around a referral route.
No medicine is completely risk free. In the case of products supplied as part of a clinical trial or which is the subject of a Marketing Authorisation, the Medicines and Healthcare Products Regulatory Agency (MHRA) will have assessed the product in line with its normal procedures for safety, quality and efficacy.
Like all other unlicensed medicines imported into or manufactured in the UK, products can only be sourced from reputable suppliers and manufacturers licensed by the MHRA or equivalent organisations of the country from where the product is being sourced. Licence holders in the UK are inspected for compliance with good manufacturing practice standards.
No. These are special medicines and any supplier that has the appropriate MHRA and HO licences and meets the conditions set out in the MHRA guidance can supply. MHRA and DHSC have provided information to Procurement Lead Pharmacists in the NHS. DHSC will keep this information updated until supply becomes established.
Further information will be available from local Procurement Lead Pharmacists.
By rescheduling, we are making it easier to conduct clinical trials on these products. The evidence base for these products is still developing and these changes to the law will encourage further research. The National Institute for Health Research has now issued a call for research proposals to increase our knowledge in this area. The call covers proposals for primary clinical research to evaluate the safety and clinical efficacy or clinical effectiveness of cannabis-based products for medicinal use in humans and it is open until 19th March 2019.
We are discussing workforce education with Health Education England and a training package will be commissioned and developed to support clinicians in prescribing these products. Similar discussions are taking place in the devolved administrations.