Key Learning Points: NICE Cannabis-based Medicinal Products

Dr David Spraggett Outlines Five Key Learning Points to Take Away from the 2019 NICE Guideline on Cannabis-based Medicinal Products

Cannabis sativa has been used for centuries both recreationally and medicinally. It has more than 100 potential active constituents, usually referred to as cannabinoids, the best known being delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD).¹ Many reports of the effects of cannabis consumption are anecdotal; however, there is increasing knowledge of how both THC and CBD affect the human endocannabinoid system in a beneficial way. THC and CBD mimic a number of naturally occurring neurotransmitters and so are able to activate cannabinoid receptors that exist within the body. These receptors are involved in many biological functions and are the mechanism by which cannabis-based products produce their effects.¹

Cannabis-based medicinal products are used in many countries and there is considerable interest in their use in UK practice. Numerous over-the-counter cannabis-derived products are available in the UK but they are not strictly regulated. The consequence is that the content of these products has been found to be extremely variable, with some not even containing any cannabis-derived product at all.² The variability in illegal recreational drugs is almost certainly higher. Healthcare professionals should be aware that people might use cannabis-based products without medical supervision. This has many implications, particularly the potential for unforeseen severe drug interactions should a doctor be unaware a patient is also taking a cannabis-derived product, whether for medicinal or recreational use.

Cannabis-based medicinal products, on the other hand, are highly controlled in content. They are either directly derived from plants or are synthetic compounds with a chemical structure identical to naturally occurring cannabinoids.³ It is, therefore, important to differentiate between cannabis-based medicinal products and the recreational and over-the-counter cannabis-derived products.

NICE Guideline (NG) 144 on Cannabis-based medicinal products,⁴ published in November 2019, provides recommendations for healthcare professionals and patients about which cannabis products can be prescribed and for which conditions. This article highlights five key points for primary care from the NICE guidance.

1. Understand Which Conditions Can be Treated

NG144 looked at cannabis-based products for medicinal use prescribing only for four groups of conditions.⁴

Intractable Nausea and Vomiting

Only limited evidence is available that cannabis-based medicinal products can result in either complete or partial reduction in chemotherapy-induced nausea and vomiting in adults. One cannabis-based product in particular, nabilone, is already licensed for the indication in the UK. NG144 gives a specific positive recommendation that nabilone may be considered as an add-on treatment in the management of chemotherapy-induced nausea and vomiting in adults which persists after using optimised conventional antiemetics.⁴ The evidence of effectiveness in children and young people was so limited, however, that NICE was unable to make any recommendation relating to its use in this age group.⁴

Chronic Pain

NG144 recommends that cannabis-derived products are not offered to manage chronic pain in adults.⁴ The available evidence for their ability to reduce chronic pain is at best modest and the cost of the cannabis-derived products is very high.⁴ NICE concluded that their potential benefits in chronic pain would, therefore, be small compared with high ongoing costs so they would not be a good use of NHS resources.⁴ However, while new NHS prescriptions of cannabis-based medicinal products for chronic pain are not expected, those patients who had previously been prescribed such products for chronic pain should be able to continue treatment. Legally, a doctor on the Specialist Register can still prescribe cannabis-derived products in the private sector.³

Spasticity

There is evidence showing the benefits of THC:CBD spray for treating moderate-to-severe spasticity caused by multiple sclerosis in adults.⁴ Economic evaluation for the use of THC:CBD spray in moderate-to-severe spasticity caused by multiple sclerosis does suggest it is a cost-effective use of NHS resources.⁴

NG144 makes a recommendation specifically for prescribing THC:CBD spray in patients with multiple sclerosis for whom other pharmacological treatments for spasticity have not been effective. The prescription should only be continued when, after a 4-week trial, there has been at least a 20% reduction in spasticity-related symptoms.⁴

However, there is not sufficient evidence available for the use of cannabis-based products for any other cause of spasticity.⁴

Severe Treatment-resistant Epilepsy

NICE was unable to make any recommendations regarding the use of cannabis-based medicinal products for severe treatment-resistant epilepsy because the current published research is very limited. However, there are cases where individual patients have reported having fewer seizures with these medicines when other treatments have not fully controlled the seizures.⁴ NICE did not make a recommendation against the use of cannabis-based medicines in this area because that might restrict further research, as well as preventing those with current benefit from continuing with their treatment.⁴

It is important to note that in NG144,⁴ two specific causes of seizure that are associated with Lennox–Gastaut syndrome and Dravet syndrome were not considered because these are addressed by specific NICE technology appraisal guidance published in December 2019.^5,6

2. Be Aware that More Evidence is Needed

NICE has acknowledged the need for more research in the effectiveness of cannabis-based medicinal products and NG144 outlines five key research recommendations relating to their use:⁴

1. CBD containing no, or traces of, THC in fibromyalgia or persistent treatment-resistant neuropathic pain in adults
2. cannabis-based medicinal products in chronic pain in children and young people
3. CBD for severe treatment-resistant epilepsy
4. THC in combination with CBD for severe treatment-resistant epilepsy
5. cannabis-based medicinal products (other than THC:CBD spray) in spasticity.

In addition, four other recommendations are made for research in intractable nausea and vomiting.

3. Know who can Initiate Prescriptions

The Misuse of Drugs (Amendments) Regulations 2018,³ state that initial prescription must be made by a specialist medical practitioner. NG144 goes further in saying that prescribing should only be initiated by a specialist with particular expertise in the condition being treated. NICE also recommends that for children and young people the initiating prescriber should be a tertiary paediatric specialist.⁴

All cannabis-based medicinal products became legal to prescribe in the UK in November 2018. The legislation amendment states that a cannabis-based medicinal product can be ordered if it is for use in accordance with a prescription or direction of a specialist medical practitioner.³ The legislation defines a specialist medical practitioner as ‘a doctor included in the register of specialist medical practitioners kept under section 34D of the Medical Act 1983 (the Specialist Register)’.³

The legislation and guidance could potentially lead to all prescribing and monitoring only occurring in secondary or even tertiary care. NICE recognises that this could place an unnecessary burden on patients, who usually prefer to have as much care as possible close to home. Cannabis-based medicinal products are controlled drugs. In its guidance on controlled drugs (NG46),⁷ NICE advises that healthcare professionals should only prescribe enough of a controlled drug to meet a person’s clinical needs for up to 30 days. The need to travel to a tertiary centre on a monthly basis to collect prescriptions would be particularly onerous for patients.

4. Prescribe Under Shared Care Agreements

GPs and independent prescribers are legally entitled to prescribe cannabis-based medicinal products under the direction of a specialist medical practitioner, most likely on the basis of a shared care agreement.⁸

NG144 states that, after the initial prescription, subsequent prescriptions of cannabis-based medicinal products may be issued by another prescriber as part of a shared care agreement, if it is appropriate and in the person’s best interest.⁴ The other prescriber should be confident to make a fully informed prescribing decision about cannabis-based medicinal products.⁴

As with all shared care arrangements, this allows the majority of treatment to be provided closer to the patient’s home; this is particularly relevant with cannabis-based medicinal products, as initial prescribing is from a tertiary centre which is likely to be a long distance from the patient’s home. It would also make some elements of monitoring more convenient for the patient—monitoring arrangements can be included within the shared care agreement, with overall responsibility remaining with the tertiary specialist. Therefore, it is likely that specialist colleagues will ask GPs if they will take on shared care responsibility for continued prescribing of cannabis-based medicinal products.

NG144 highlights key aspects that should be included in any shared care agreement, which are in line with NHS England guidance.⁴ In particular, any shared care agreement should include clearly defined responsibilities of all parties, including the patient and their family and/or carers.⁴ There should be absolute clarity about the division of responsibilities between the initiating specialist prescriber and the prescriber acting under their direction. NG144 also states that any agreement should include details of how communication between the specialist and primary care prescriber would be managed, how funding for the medication is obtained, and the frequency and nature of monitoring.⁴

The funding is highly likely to need agreement with the patient’s local commissioner, usually in the form of an individual funding request. While the initiating specialist should apply for this, the patient’s GP is usually named in the application.

While it is the responsibility of the specialist to take into account all necessary factors before initiating treatment, the patient’s GP does have a role informing the specialist of any known issues that may be relevant. In particular, this means any other prescribed medication, past adverse reactions, any cannabinoid use that the patient has disclosed, or past history of addiction problems.

5. Understand the Implications for Primary Care

Although UK legislation precludes any initiation of cannabis-based medicines in primary care, it is likely that GPs will be involved in the decision-making process as to whether they are prescribed.

Inevitably, patients will turn to their GPs to discuss the use of these medicines now that they can be prescribed legally. As a referral will usually be needed from a primary care professional to the appropriate specialist to be able to initiate a prescription, GPs are likely to come under pressure from patients to make such referrals.

A significant implication for GPs will be in supporting patients whose application for treatment is denied. Some may choose instead to self-medicate with preparations obtained from unregulated sources. It will be important to try to ensure these patients keep their GP informed of this unregulated use,⁹ in order to avoid potentially dangerous unexpected drug interactions.

With the increased media attention relating to cannabis as a medication for a number of chronic conditions, it would be good practice to consider specifically enquiring about its use in patients at risk of adverse interactions. Drug interactions are numerous, principally relating to drugs influenced by cytochrome P450 enzymes. These include many antidepressant and anxiolytic drugs, as well as anticonvulsants (such as baclofen) and antiplatelet or anticoagulant agents (such as warfarin).¹⁰

With better quality research being encouraged, it is very likely that there will be many more indications for the use of cannabis-based medicinal products in the future. GPs should try to be as well informed as possible about these developments; patients will expect them to be sufficiently informed to advise them regarding cannabis-based medicines, even if they do not actually issue the prescription.

Summary

Legislation changed in November 2018 to allow doctors on the Specialist Register to prescribe cannabis-related medicinal products; it also allows for any doctor or independent prescriber to issue prescriptions for cannabis-based medicinal products under the direction of a doctor on the Specialist Register. NG144 addresses the use of cannabis-based medicinal products in four conditions and has given positive recommendations regarding treatment of spasticity in MS and intractable nausea and vomiting. It also gives recommendations for future research to gather more evidence about the effectiveness of cannabis-based medicinal products.

Dr David Spraggett

GP Partner, Kenilworth

Chair, NHS South Warwickshire CCG

Member of the Guideline Development Group for NG144