Martin Bradley outlines provisional guidance on when medical cannabis can be prescribed, ahead of a forthcoming NICE guideline
On 1 November 2018, the government rescheduled cannabis-based products for medicinal use (CBPMs) from Schedule 1 to Schedule 2 of the Misuse of Drugs Regulations 20011 following a review of medical evidence by the Advisory Council on the Misuse of Drugs.2 The review did not include synthetic cannabinoids and a decision on these has been reserved for future consideration.2 CBPMs, therefore, may now legally be prescribed where there is an unmet clinical need. The government has restricted the prescribing of cannabis-based products to specialist clinicians only, that is, those on the Specialist Register of the General Medical Council (GMC).2
Definition of CBPMs That Can Now Be Prescribed
CBPMs are defined as products containing cannabis, cannabis resin, cannabidiol (CBD), or a CBD derivative, for example, delta-9- tetrahydrocannabinol (THC) produced for medicinal use in humans. They are a medicinal product or an ingredient of a medicinal product.2
Prescribers are expected to prescribe a product only where they are certain of its content and quality. The Medicines and Healthcare products Regulatory Agency (MHRA) has published guidance for the supply, manufacture, importation, and distribution of unlicensed CBPMs (specials) in humans.3
The product being prescribed must be procured from a manufacturer or importer holding a good distribution practice certificate from the MHRA and the cannabis strain and THC/CBD ratio, where relevant, should be detailed.3 Alternatively, patients may have the option of applying to the home office for a personal import licence.
However, there are other CBPMs or synthetic derivatives that were already licensed or under regulatory review for licensing for medicinal use. The legislation has made no change to the status of those substances.
Commissioning Status and Expected Internal Governance Processes
The responsible commissioner for CBPMs depends on the indication. On 31 October 2018, NHS England produced a short summary for providers and commissioners; currently no CBPM is routinely commissioned by NHS England.2 This communication recommends that, as a minimum, approval for prescription by an individual NHS provider should be granted only on a named patient basis by the trust’s drug and therapeutics committee or equivalent, or the trust’s medical director, and that trusts will need to meet the cost of treatment.2 Prescribers should also be aware that any decision to prescribe an unlicensed product must take into account the GMC guidance.4 It is expected that prescribing of a CBPM would only be considered after all other treatment options had been shown to fail or were judged inappropriate.2
In December 2018, NHS England produced supplementary information for providers and commissioners highlighting which CBPMs are affected by the regulations (see box 1), and the CBPMs available before the legislation change that are not affected (see box 2).5
Box 1: Cannabis-based products available for medicinal use after 1 November 2018 (i.e. unlicensed product but manufactured under a GMP certificate and intended for medicinal use)5
Tilray and Bedrocan products
These are a range of preparations containing THC and CBD with differing percentages of the active constituents. These are now legally available on prescription on a named patient basis if supplies are possible. They are now classed as Schedule 2 controlled drugs and commissioning responsibility depends on the indication.
At the time of writing, the choice of products available for prescription in the UK is very limited. Dutch law currently prevents export of Bedrocan cannabis oil products.
GMP=good manufacturing practice; THC=delta-9-tetrahydrocannabinol; CBD=cannabidiol
Box 2: Cannabis-based products or synthetic derivatives already available for medicinal use before 1 November 20185
Nabiximols (extracts from two strains of cannabis with standardised content of THC and CBD)
This is licensed in the UK for spasticity in multiple sclerosis, but not recommended by NICE because it is not cost effective.6 CCGs are the responsible commissioners and it is a Schedule 4 controlled drug.
A synthetic cannabinoid that mimics THC. It is licensed in the UK for nausea and vomiting caused by chemotherapy and is a Schedule 2 controlled drug. NHS England is the responsible commissioner for this indication and it is considered in tariff.
This is a synthetic, structurally identical form of THC. It is not licensed in the UK but is approved for use in the US by the Food and Drug Administration to treat loss of appetite in people with AIDS and severe nausea and vomiting in cancer chemotherapy. It is a Schedule 2 controlled drug and available on a named patient basis as an imported product.
CBD isolated from pure cannabis
This is unlicensed in the UK. It is registered as a medicine and approved for use in the US to treat Lennox-Gastaut Syndrome or Dravet Syndrome in patients aged 2 years and older. The European Medicines Agency is reviewing it for licence in the European Union, but it is available through an early access programme at some specialist centres in the UK. NICE is reviewing this treatment under a technology appraisal that is due in November 2019 and NHS England is the responsible commissioner for this indication. It is pure CBD and is not a controlled drug.
Evidence for Use of CBPMs
NICE is reviewing the use of medicinal cannabis-based products and intends to publish final guidance by October 2019. It will cover their use in chronic pain, intractable nausea and vomiting, spasticity, and severe treatment-resistant epilepsy.7 In the interim, some medical bodies have produced guidance for specialists on the use of CBPMs.
Intractable childhood epilepsy
The British Paediatric Neurology Association has produced guidance on the use of CBPMs in children and young people with epilepsy.8 It details the evidence for pure CBD (Epidiolex®) and criteria for use of this agent as a last resort for children with uncontrolled epilepsy. It advises that CBD should be the default choice of CBPM in children with epilepsy. It does not recommend prescribing other non-licensed CBPMs, whether or not they comply with good manufacturing practice (GMP) and good distribution practice (GDP) standards, as there is no randomised controlled clinical trial evidence of safety or efficacy in children and young people with epilepsy for these products. It recommends that patients who are already taking other cannabis-based products of GMP and GDP standard that contain higher proportions of THC (>0.2%) with apparent benefit are transitioned to CBD (Epidiolex®) until robust evidence emerges of these products’ safety and efficacy.8
Chemotherapy-induced nausea and vomiting (CINV)
The Royal College of Physicians (RCP) states that there is some evidence for the use of cannabinoids to prevent CINV. Evidence from randomised controlled trials suggests nabilone is effective, but it has significant side effects in the form of neurological symptoms.9
The RCP advises that studies show mixed or uncertain results for cannabinoids in the treatment of pain in palliative care. Therefore, their place in therapy is unclear and is not recommended in routine clinical practice.9 The evidence for use in this setting mainly relates to nabiximols. The RCP does not recommend the use of CBPMs in chronic pain because there is no robust evidence.9
Spasticity in multiple sclerosis
NHS England has asked the Association of British Neurologists to provide interim guidance on the use of CBPMs in adult neurological conditions, including multiple sclerosis.5 The evidence specifically relates to nabiximols, which is licensed for this indication, however, NICE does not recommend this treatment on cost-effectiveness grounds.6
Implications of the Change in Legislation
There is significant disparity between public expectations of the implications of the legislation change and the actual effects. Certain reports in the media appear to have accepted medical cannabis to be effective in a lengthy list of conditions, whereas the current view of the majority of expert clinicians is that the evidence as a whole is weak.8-10 Importantly, the key evidence supporting the indications which NICE is reviewing, is generally for CBPMs or synthetic derivatives that are not the subject of current interest and are not impacted by the recent legislative changes. The current lack of a source of UK-manufactured CBPM and the challenges of sourcing products made outside of the UK which meet the regulatory requirements for importation, continue to severely constrain supply of products for UK patients.
1. Home Office. The Misuse of Drugs Regulations 2001. SI No. 3998. London: The Home Office, 2001. Available at: www.legislation.gov.uk/uksi/2001/3998/pdfs/uksi_20013998_en.pdf
2. Department of Health and Social Care. Cannabis-based products for medicinal use. London: DHSC, 2018. Available at: assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/753444/letter-with-guidance-oncannabis-based-products-for-medicinal-use.pdf
3. Medicines and Healthcare products Regulatory Agency. The supply, manufacture, importation and distribution of unlicensed cannabis-based products for medicinal use in humans ‘specials’. London: MHRA, 2018. Available at: assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/752796/Cannabis_Guidance__unlicensed_CBPMs__-_Final_311018.pdf
4. General Medical Council. Prescribing unlicensed medicines. www.gmc-uk.org/ethical-guidance/ethical-guidancefor-doctors/prescribing-and-managingmedicines-and-devices/prescribingunlicensed-medicines (accessed 10 January 2019).
5. NHS England. Supplementary information on cannabis-based products for medicinal use. London, 2018. Available at: www.england.nhs.uk/wp-content/uploads/2018/11/letter-additional-guidance-on-cannabisbased-products-for-medicinal-use.pdf
6. NICE. Multiple sclerosis in adults: management. NICE Guideline 186. London: NICE, 2014. Available at: www.nice.org.uk/guidance/cg186
7. NICE. Cannabis-based products for medicinal use. www.nice.org.uk/guidance/indevelopment/gid-ng10124 (accessed 10 January 2019).
8. British Paediatric Neurology Association. Guidance on the use of cannabis-based products for medicinal use in children and young people with epilepsy. Bolton: BPNA, 2018. Available at: www.bpna.org.uk/userfiles/BPNA_CBPM_Guidance_Oct2018.pdf
9. Royal College of Physicians. Recommendations on cannabis-based products for medicinal use. October 2018. Available at: www.rcplondon.ac.uk/projects/outputs/recommendations-cannabis-basedproducts-medicinal-use
10. Bar-Lev Schleider L, Abuhasira R, Novack V. Medical cannabis: aligning use to evidence-based medicine approach. Br J Clin Pharmacol. 2018; 84 (11): 2458–2462.