Cannabis-based products for medicinal use

In November 2018 the Home Office released a draft Guideline scope for Cannabis-based products for medicinal use in which they announced that specialist doctors (like consultant neurologists) on the Special Register of the General Medical Council will be able to prescribe cannabis-based medicinal products to some patients. Before this, the only cannabis-based medicines licensed for use in the UK were nabiximols (Sativex), used as a treatment for spasticity (where muscles are continuously contracted, causing stiffness or tightness of the muscles, interfering with normal movement and speech), in multiple sclerosis (MS).

What is cannabis?

Cannabis plants produce a group of chemicals called cannabinoids. Although there are over 100 identified cannabinoids, the two most well-known are tetrahydrocannabinol (THC) and cannabidiol (CBD).

THC is the main psychoactive part of cannabis. It is responsible for producing the ‘high’ associated with cannabis use. It is the main active ingredient in nabiximols.

CBD does not appear to have any psychoactive properties and therefore does not produce a ‘high’. Its use as a possible treatment for anxiety, cognition, movement disorders and pain has previously been studied but the way in which it produces its pharmacological and therapeutic effect remains unclear.

In general, cannabinoids act on cannabinoid receptors in the cells that alter neurotransmitter release in the brain. A neurotransmitter is a substance that transmits nerve impulses across a synapse.

Illustration of motor neurone showing neurotransmitters moving across a synapse

What’s legal and what’s not?

Recreational cannabis

In the UK, the possession, distribution and cultivation of cannabis for recreational use (that is, when it is not prescribed for a medical condition) is illegal. Many countries have decriminalised possession, and some have fully legalised the consumption and sale of recreational cannabis.

Medical cannabis

Medical cannabis is a broad term for any sort of cannabis-based medicine used to relieve symptoms and refers to the use of cannabis as a physician-recommended form of medicine or herbal therapy. This includes the constituents of cannabis, THC and other cannabinoids. Medical cannabis is prescribed legally in several countries, including the UK. However, it is not legal to obtain it in another country and bring it into the UK without a Home Office drug import licence.

CBD (sold as a food supplement, marketed as CBD oil)

CBD with THC content not exceeding 0.2% is legally and widely available in the UK in liquid and capsule form. Although it can have some side effects such as drowsiness, decreased appetite and weakness it is not thought to have psychoactive effects as the THC component has been removed. CBD is not licensed as a medicine but the products can still be sold providing no claims are made about any medical benefits.

Possessing cannabis products (unless they contain less than 0.2% THC) is illegal in the UK, unless they have been prescribed for you. The use of medical cannabis by anyone other than the person it has been prescribed for is also illegal in the UK.

Looking at the evidence of efficacy

Can a cannabis-based medicine be effective in treating MND? Although THC/CBD is known to be used by some people with MND, few systematic investigations have been reported.

In 2012, ALS Untangled, a group of MND clinicians and researchers who collect and assess evidence on various unproven treatments, reviewed the available literature on cannabis as a potential treatment for MND. At the time of their review, there had been no human trials. Results from animal studies suggested it could potentially slow progression and there is plenty of anecdotal evidence claiming that it helps to relieve troubling MND symptoms. They concluded that cannabis has biological properties that suggest it could be useful but further studies are needed to confirm any reported benefits.

In 2016, Italian researchers Giacoppo and Mozzan published an overview of evidence from studies using SOD1 mouse models. They found that THC, administered before or after symptom onset, improved motor symptoms and increased survival by 5%. They also reported that treatment with cannabinoids may reduce elevated glutamate levels. It is believed that excessive exposure to glutamate might be one of the reasons that motor neurons die in MND. Preventing the rise of glutamate levels could protect motor neurones and slow disease progression. Another study found that, in the SOD1 mouse model Sativex was found to be effective in delaying MND progression in the early stages of the disease although this was decreased as the disease progressed. In another investigation, oral THC was found to be safe and well-tolerated by people with MND but had no effect on symptoms.

Fast forward to 2018-19. Animal studies continue and results from human trials are now being published.

In Spain, researchers discovered that CB2, a receptor in the cannabinoid system, together with activation of another receptor, provided neuroprotection in a mouse model of MND. Based on this, the researchers investigated the neuroprotective effects of EHP-102, a new non-psychoactive cannabinoid-derived medicine. EHP-102 reduced weight loss, preserved motor neurons of the spinal cord and displayed an anti-inflammatory effect in the mice. These results would have to be replicated in other animal models before the drug could be taken into clinical trials.

At the International Symposium on ALS/MND, held in December 2018 and organised by the MND Association, this subject was covered by several presentations.

Urbi and colleagues reviewed eight pre-clinical studies in their poster ‘Effects of cannabinoid in ALS or MND: a pre-clinical systematic review and meta-analysis’. They looked at studies that used SOD1 mouse models to assess survival time. Analysis showed that early intervention with cannabinoids in high doses significantly delayed disease progression and slowed motor function decline and weight loss.

A team of researchers from Germany looked at the usability and satisfaction of Sativex in people with MND who are experiencing spasticity. Sativex is already licensed in the UK for people with MS and is a potential off-label treatment (the use of a drug for an unapproved condition) for people with MND with resistant spasticity. The majority of the 32 participants reported high treatment satisfaction after two months of using Sativex, although some found the applicator difficult to use (the drug was sprayed into the cheek). This suggests that this may be an important complementary treatment of spasticity in MND, but comparative studies with other oral anti-spasticity medications, such as baclofen and tizanidine, are needed to assess the effectiveness of THC/CBD in relieving MND-related symptoms.

Sabet and colleagues reported on the EMERALD trial which will soon begin recruiting 30 participants with MND in Australia for a randomised, placebo-controlled Phase 2 clinical trial looking at the effectiveness of CannTrust CBD Oil capsules. A medicinal cannabis extract with high CBD and low THC concentration will be used. At the end of 24 weeks treatment, they will be looking for an improvement in ALSFRS-R scores and Forced Vital Capacity (FVC), together with other standard measures of MND progression. The study is expected to finish in January 2021, and it is hoped that it will fill the gap between anecdotal reports and pre-clinical studies, demonstrating the effectiveness of cannabinoids in extending survival and slowing MND progression. You can find out more about the trial at clinicaltrials.gov.

In a paper published in The Lancet in 2019, Italian researchers reported their findings from a Phase 2 clinical trial which investigated the safety and effectiveness of nabiximols on spasticity symptoms in people with MND. They were looking for an improvement in the Modified Ashworth Scale (a measure of muscle spasticity) after six weeks of treatment. Fifty-nine people with MND took part – 29 were given the trial drug and 30 a placebo. In the group that received the drug, Modified Ashworth Scale scores improved, on average, by 0.11 compared to a deterioration of 0.16 in the placebo group. The drug was also well-tolerated. This suggests that nabiximols have a positive effect on spasticity in people with MND and the researchers recommended that larger clinical trials be carried out to investigate these findings further.

It is encouraging that research into the effects of cannabis-based medicines on MND is now moving into human trials and we look forward to reporting the results in due course.

What are the risks?

The risks of using cannabis products containing THC are not clear. This is why clinical trials are needed before they can be widely used.

It is believed that the main risks of THC cannabis products are:

• Psychosis – there is evidence that regular cannabis use increases the risk of developing a psychotic illness such as schizophrenia.
• Dependency on the medicine – although this risk is probably small when its use is controlled and monitored by a specialist doctor.

Illegally obtained cannabis (off the street/internet) is the most dangerous form to use as the quality, ingredients and strength are not known.

Products that contain only CBD are not thought to carry the risks associated with THC.

What does the new legislation mean for people with MND?

Research into the use of cannabinoids in MND is currently ongoing, mostly focusing on using cannabis to help relieve symptoms of muscle spasticity. There are currently no completed human studies that have looked at cannabis as a treatment for delaying progression and prolonging survival. Therefore, it is unlikely that cannabis-based medicines will be available on the NHS to people living with MND until there is evidence of its effectiveness.

Although classification of cannabis has been changed, its use is still tightly governed.

• You cannot get cannabis-based medicines from a GP.
• Cannabis-based medicines cannot be considered as a first-line treatment if they do not have full MHRA marketing authorisation.
• It is likely to only be prescribed for a small number of patients, for example for rare forms of childhood epilepsy, spasticity in MS and nausea/vomiting following chemotherapy. It will only be available for those patients when all other treatments have failed and only if it is believed to be in their best interests.
• Cannabis-based medicines may still be prescribed on a named-patient basis if a clinician feels that the drug is safe and would improve their patient’s condition. You can read more about accessing unapproved drugs in our information sheet.

Although this may seem discouraging for people living with MND, research into using cannabis as a treatment for the disease is ongoing. The reclassification of cannabis-based medicines allowing them to be prescribed in the UK by a registered clinician will hopefully mean that, if evidence establishing a beneficial use of cannabis to treat MND is forthcoming in the future, it will be more easily accessible to those wishing to use it.

Edit: On 11th November 2019, the National Institute for Health and Care Excellence (NICE) recommended that two cannabis based products – Epidyolex (used to treat a rare form of childhood epilepsy) and Sativex (used to treat spasticity in multiple sclerosis) should be made available on the NHS.