Cannabis: what's new for the 6000 year old medicine?

Recent changes to the rules in the UK have raised some interesting possibilities and questions. Paul England explores.

A clear(er) definition needed

Given the number of different varieties of cannabis plant that exist, the Medicines and Healthcare products Regulatory Agency (MHRA) needs to be clear in its definition of cannabis-derived products what exactly is being moved from Schedule 1 to Schedule 2. Cannabis plant varieties don't contain just one compound affecting to their properties, but over one hundred. These are called cannabinoids and most are also controlled under the Misuse of Drugs Regulations (MDR) 2001. The best known cannabinoids are tetrahydrocannabinol (THC) and cannabinol (CBN). It is THC that gives cannabis its psychoactive effect and is controlled. CBN, by contrast, has no such effect and is not controlled.

From hemp to skunk

At one end of the scale, there is cannabis with most of the THC removed (hemp), and at the other, cannabis containing high proportions of THC (skunk). Once defined by the MHRA, it is expected that it will be possible to prescribe cannabis-derived products containing certain proportions of THC and other currently controlled cannabinoids. Indeed, there is one example of a cannabis derived medicine containing both CBD and THC in approximately a 1:1 ratio that is already licensed in the UK. This is Sativex, which is an oral spray containing cannabis extracts and was exceptionally licensed by the MHRA for prescription use in treating some of the symptoms of multiple sclerosis in adults. Sativex was exempted from the MDA 1971 and placed in Part I, Schedule 4 of the MDR 2001 in March 2013, on the basis that it has recognised medicinal or legitimate use.

Pain not currently included

Current guidance states that the re-scheduled products should only be made available to children with rare and severe forms of epilepsy, adults with vomiting or nausea caused by chemotherapy, and adults with muscle symptoms caused by multiple sclerosis. The list doesn’t include chronic pain, which is thought to be one of the main uses of medicinal cannabis.

Specialists

The decision to prescribe under Schedule 2 must be made by a specialist doctor – not a GP.

Authorisation – could it take years?

MHRA has already advised manufacturers and retailers of CBD products that they should be regulated as medicines. This means obtaining marketing authorization under the procedures of Directive 2001/83. If so, it could take many years to authorise the many complex combinations of cannabinoids present in the different cannabis varieties.

Exclusivity protection tricky

The market in generic versions of traditional small molecule drugs already provides a thriving business model that relies on the absence (or expiry) of protection (specifically, patent protection). However, as with other new, innovative drugs, if investment is to be attracted to the research and development of entirely new cannabis-derived products, investors will want to see exclusivity protection so that their investment costs can be recouped with premium prices. This is more of a challenge for cannabis-derived products because:

• cannabis-derived products are, as the name suggests, derived from cannabis plants. Distinct, uniform and stable new varieties of plant can be protected by plant variety rights, which protect against reproduction and sale by third parties of the plant variety for 25 years. But, whilst a plant variety right provides protection for a specific, new variety of plant, it does not protect the cannabinoids that are the active ingredients. Therefore, any product derived from a protected variety of cannabis remains open to competition from products derived from other plants and the cannabinoids that confer their properties.
• So patents are not available for plant varieties. But what about patent protection for cannabinoids? The fundamental issue here is that the right of 20 years exclusivity that is afforded by patent protection requires the product to be new and inventive. However, records of cannabis use as a medicine go back as early as 4000 BC and it was still being used as recently as the 19^th and early 20^th centuries to treat various forms of pain. Many cannabinoids are not, therefore, 'new and inventive'. To be patentable, it is essential that the technical subject matter in question must be new ('novel' in patent language) and inventive, that is, contain an 'inventive step' beyond what has been done before.