Guidance and advice for prescribing decisions
The National Institute for Health and Care Excellence (NICE) has published Technology Appraisals for the use of cannabidiol (Epidyolex®) for severe treatment-resistant epilepsies.
- Cannabidiol with clobazam for treating seizures associated with Dravet syndrome
- Cannabidiol with clobazam for treating seizures associated with Lennox–Gastaut syndrome
- Cannabidiol for treating seizures caused by tuberous sclerosis complex
NICE has also published a guideline on cannabis-based products for medicinal use.
The guideline and technology appraisals include recommendations for people with:
- chronic pain
- intractable nausea and vomiting
- severe treatment-resistant epilepsy.
Guidance and advice produced previously by Professional Organisations has now been superseded by issuing of the NICE guidance as outlined above.
However, the British Paediatric Neurology Association (BPNA) has guidance on the use of cannabis-based products for medical use in paediatric patients with certain forms of severe epilepsy. It recommends that CBD (Epidiolex®) should be the default choice when considering prescription of a cannabis-derived medical product in its licensed indications. It does not recommend prescribing other non-licensed cannabis-derived medical products, which includes all artisanal cannabis oils, whether or not they comply with good manufacturing practice (GMP) or good distribution practice (GDP) standards.
The only robust evidence for efficacy and safety in childhood epilepsies relates to use of pure cannabidiol (Epidyolex®). Currently there is no good evidence that products that contain THC are either safe or efficacious and there is a concern about the harmful effects 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. Therefore, further evidence is required before these products can be routinely commissioned or prescribed.
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 medical 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. These products are unlicensed, and the quality of these products has not been assessed by the regulator.
In 2018, NHS England developed an e-learning information package with Health Education England and the University of Birmingham, on cannabis and cannabis based products for medicinal use which all healthcare professionals can access.
The session includes the pharmacology of cannabis, legislation governing medical use and therapeutic areas and evidence for its use. This module will be updated as more information becomes available.
Indications for use
There is no restriction in law for which indications CBPMs may be prescribed. When prescribing CBPMs, it is a clinical decision to determine the most appropriate treatment option for a patient. Prescribers will need to consider the patient’s values and preferences, their clinical condition, other medicines, the clinical evidence of efficacy and safety for the indication being considered, and the suitability of other licensed medicines.
There is the most evidence of clinical effectiveness in the following areas where licensed products are now available:
- intractable nausea and vomiting
- MS related spasticity
- severe treatment-resistant epilepsy
As the majority of products are currently not licensed, CBPMs will not be considered as first line treatments. Prescribers should always first consider prescribing medicines that are licensed for the specific condition that the patient presents with.
The MHRA has more information about supply unlicensed medicinal products (specials) and off-label or unlicensed use of medicines: prescribers’ responsibilities.
There is also information at:
- General Medical Council Good Practice in Prescribing Medicines
- Health & Care Professions Council
- General Dental Council
Use in Multiple Sclerosis
The National Institute for Health and Care Excellence (NICE) guideline on Chronic pain (primary and secondary) in over 16s: assessment of all chronic pain and management of chronic primary pain covers use of CBPMs in chronic neuropathic pain. This is the predominant type of pain that patients with multiple sclerosis (MS) experience. Use of CBPMs for chronic pain is not recommended as there is insufficient evidence, this is discussed further below.
The NICE guideline on Cannabis-based medicinal products recommends offering a 4-week trial of THC:CBD spray (Sativex®) to treat moderate to severe spasticity in adults with multiple sclerosis, if other pharmacological treatments for spasticity are not effective. If the trial proves effective, then prescribing should be continued. THC: CBD spray is licensed for use in MS spasticity and should be used over any unlicensed cannabis-based products for medical use.
Use in chronic pain
The current evidence for use of cannabis-based products for medicinal use (CBPMs) 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 CBPMs in the long term have also not been studied. Experience with other medicines, show us that, rare or unexpected side effects can develop once prescribing is more widespread and for a longer duration. There are no licensed CBPMs available for use in pain.
A 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.
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.
There are three requirements that a cannabis-based product for medicinal use (CBPM) should satisfy:
- the product is or contains cannabis, cannabis resin, cannabinol or a cannabinol derivative,
- it is produced for medical use in humans, and
- it is a product that is regulated as a medical product, or an ingredient of a medical product.
The definition is broad to account for 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 CBPMs to meet the requirements of any prescription.
CBPM do not include raw/unrefined cannabis or cannabis/hemp oil products that can be purchased online/in health food shops. These products are not produced for medicinal use and cannot be recommended or prescribed.
There is no specific list of suppliers of CBPMs. 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.
Further information is available from regional procurement lead pharmacists.
There are three main groups of synthetic compounds that fall within the broad category of ‘synthetic cannabinoids’, those that are:
- identical in structure to naturally occurring cannabinoids such as THC (delta-9-tetrahydrocannabinol), e.g. Dronabinol (developed as a medicinal product but is not a licensed medicine in the UK).
- structurally related to naturally occurring cannabinoids that have been developed to mimic naturally occurring cannabinoids such as THC e.g. Nabilone (licensed product in the UK).
- not structurally related to naturally occurring cannabinoids but which bind to cannabinoid receptors in the body (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 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.
Cannabidiol oral solution (Epidyolex®) is a licensed medicinal cannabis product that has been through randomised controlled trials for epilepsy syndromes (Dravets syndrome, Lennox-Gastaut syndrome and tuberous sclerosis complex).
‘Pure’ cannabidiol (CBD) only based products (including synthetic versions) are not classified as cannabis-based products for medicinal use and are not controlled drugs as they contain very small amounts of delta-9-tetrahydrocannabinol (THC).
To be exempt from scheduling a product will need to fulfil the three requirements of the ‘Exempt product’ definition as outlined in the law. Epidyolex® is a schedule 5 medicine.
However most CBD oils sold in health food stores are classed as food supplements; these products are not always properly authorised. The food standards agency has issued advice to consumers stating that vulnerable groups (pregnant, breastfeeding and those on medication) should not consume CBD oil, with healthy adults taking a maximum of 70mg/day.
Quality of products
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 (licence), the Medicines and Healthcare Products Regulatory Agency (MHRA) will have assessed the product in line with its normal procedures for safety, quality and efficacy.
Unlicensed medicines are not assessed as above and the MHRA cannot guarantee the quality of the product. However, unlicensed medicines imported into or manufactured in the UK, can only be sourced from 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.
By rescheduling the medicine, 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 issued a Themed Call: Cannabis-based products for medicinal use (2018) | NIHR call for research proposals to increase our knowledge in this area.
In March 2019, the Secretary of State for Health and Social Care commissioned NHS England to review NHS systems and processes to identify and recommend any action necessary to address any barriers to clinically appropriate prescribing of cannabis-based products for medicinal use (CBPMs) on the NHS. The findings and recommendations are available in Barriers to accessing cannabis-based products for medical use on NHS prescription.
The report outlines several recommendations aimed at addressing the potential barriers to clinically appropriate prescribing. These include establishing a UK-wide paediatric network to support discussion of complex cases and assist in evidence generation, establishing a register and development of clinical trials. NHS England has worked with other national organisations to implement the recommendations and ensure that where it is clinically appropriate, clinicians feel supported to prescribe a cannabis-based medicinal products on the NHS.
Due to the limited evidence base and their unlicensed nature, the law requires that these cannabis-based products for medicinal use (CBPM) be supplied under either the prescription or direction of a clinician on the General Medical Council’s (GMC) Specialist Register.
Any decision to prescribe must consider the relevant GMC guidance and the relevant NHS Trust governance procedures for unlicensed medicines in the normal way. Additionally, a Specialist on the GMC specialist 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. In the case of treatment resistant epilepsies in children, we would expect any prescribing to be initiated by tertiary paediatric neurologists as advised by NICE in their guidance.
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 – the specialist carries clinical and medico-legal responsibility for prescribing.
A GP may make a referral to a specialist on the GMC specialist register once the patient reaches the appropriate point in their treatment pathway once all licensed medicines for treating epilepsy have been tried and the patient has not responded.
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.
The GMC requires that the prescriber to be responsible for the prescriptions they sign. It further requires that prescribers only prescribe drugs when they have adequate knowledge of the patient’s health, are competent to prescribe for that clinical condition and must be satisfied that the drugs serve the patient’s need.
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 once further clinical data on medicinal cannabis is available. If a doctor prescribes a medicine under shared care arrangements, he or she accepts clinical and professional responsibility for that prescribing decision. The NHS will not take on shared care from a private prescriber for a treatment not commissioned on the NHS, unless there are exceptional circumstances and approval from commissioners has been sought and agreed.
Medicinal Cannabis Patient Registry
On 1 April 2022 NHS England launched a patient registry to capture information on the prescribing of cannabis-based products for medicinal use. The registry is to be completed by NHS clinicians working within NHS Trusts, when they see a patient who has been prescribed medicinal cannabis – either as a licensed or unlicensed product. The clinician will complete the relevant section of the data collection template. Data will be collected on an on-going basis at each point of clinical interaction. The data can be used to provide summary statistics of the patient population within the registry. Health status data (EQ-5D) linked to the treatment received can be used, potentially to measure the health impact over time on patients.
Data can be accessed by the clinician, Trusts, NHS England and other relevant central organisations, subject to data sharing protocols and general data protection regulations. Clinicians can access patient identifiable data but for all others the data is patient anonymised.
The Refractory Epilepsy Specialist Clinical Advisory Service (RESCAS)
The Refractory Epilepsy Specialist Clinical Advisory Service (RESCAS) is an independent specialist clinical network that provides evidence-based advice to clinicians treating patients with refractory epilepsy. This UK-wide network can provide advice impartially on a range of treatment options for individuals with refractory epilepsy, based on clinical evidence, knowledge and experience.
This clinician-to-clinician support and advice is available to tertiary paediatric neurology consultants, who jointly care for patients with other clinicians, as part of a multi-disciplinary team. The network is independent and is hosted by Great Ormond Street Hospital for Children NHS Foundation Trust.
Private doctors 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 be based on a multidisciplinary team 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 medical use, and the circumstances in which they may be prescribed.
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 clinicians on the General Medical Council’s Specialist Register.
UK Regulations mean that Schedule 2 and/or 3 controlled drugs and unlicensed medicines may not be supplied on a prescription authorised by an European Economic Area practitioner. This is not unique to cannabis. Any prescription that does not comply with the UK requirements cannot be used to lawfully import a product for personal use from another jurisdiction.
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 their local lead Controlled Drugs Accountable Officer for a Prescriber Identification Number.
Specialist clinicians can prescribe unlicensed medicines where there is an exceptional clinical need and where the benefits outweigh any potential risks as determined by the specialist doctor.
However, many doctors and their professional bodies remain concerned about the limited evidence on the long-term safety and efficacy of these products, which are mainly unlicensed. Experience with other medicines, show us that, rare or unexpected side effects can develop once prescribing is more widespread and for a longer duration. Therefore, further evidence of benefits and harms are required before prescribing can become more widespread.
It is also important to recognise that by prescribing an unlicensed product, or product off licence, the prescriber must be willing to accept increased medico-legal responsibilities. In the case of an unlicensed product, there is no input or oversight at all from regulators, such as the Medicines and Healthcare products Regulatory Agency (MHRA), so the prescriber accepts responsibility for the quality of the unlicensed product too.
The law was changed, in part, to support the undertaking of clinical trials, so that robust evidence can be gathered and potentially leading to a marketing authorisation and license.
Prescribing by non-specialists
The law states that a specialist is responsible for prescribing decisions. However, the law does allow other prescribers to continue prescribing once the decision to prescribe initially has been made by a specialist who has asked another prescriber to do so.
There are existing arrangements permitting doctors not on the GMC specialist register but working under the direction of a specialist within a hospital setting (e.g. speciality registrars, non-medical independent prescribers etc.) to continue prescribing, once patients are established on a particular treatment with no problems.
It is expected that patients receiving these products to remain under the direct care of a specialist doctor (i.e. initiation and continued prescribing and monitoring) in the first instance.
In the case of unlicensed cannabis-based medicinal products, these are not routinely commissioned in the NHS. Treatment decisions for all unlicensed medicines are determined on a case by case basis by a specialist doctor considering individual patient clinical need and safety.
If a clinical decision to prescribe is made and supported, trusts meet the costs within the services they are commissioned to provide, taking account of the local procedures for supporting prescribing and funding decisions for unlicensed medicines.
Individual funding requests
Further information on individual funding requests, exceptionality and what it means for patients can be found in Individual funding requests for specialised services a guide for patients.
Publication reference: PRN00111