Budding opportunities for pharma

With shifting attitudes surrounding cannabis-based drugs, it is essential to explore the array of benefits this may have for patients and the pharmaceutical industry as a whole.

Since Neolithic times, the cannabis genus of plants has been cultivated by humans as a result of its unique physical and pharmacological properties. Dating back to around 500 BC, cannabis was initially grown by ancient Asian civilisations, and over time, spread to Europe, Africa, and eventually the Americas. The cannabis, or ‘hemp’, plant was first produced in Britain around the 10th century AD, where it was mainly used in ropes, fishing nets, and canvases because of its robust natural fibres. The demand for the material became so important in Britain that Henry VIII mandated the cultivation of hemp by landowners.

While working for the British East India Company in Bengal, William Brooke O’Shaughnessy began studying the medical benefits of cannabis. It was this research that kick-started Western medicine’s interest in the cannabis plant in the 19th century. O’Shaughnessy’s research suggested that cannabis had the ability to effectively treat rheumatic pain, convulsions, and muscular spasticity; as a result, it became an extensively used remedy for these conditions. Centuries later, cannabis was used in many applications and was widely accepted across Western society. However, public opinion changed during the 19th century, leading to the current restrictions enforced by most countries across the globe today.

There are hundreds of naturally occurring cannabinoids in the cannabis plant. The most famous of these is tetrahydrocannabinol (THC), which, when ingested by humans, has a psychoactive effect. There is also a relatively high concentration of cannabidiol (CBD) in the plant, which is not psychoactive.

The path to UK prohibition was gradual. Although the drug became banned in many British colonies during the 19th century, it wasn’t until 1928 in mainland Britain that cannabis was criminalised and added to the Dangerous Drugs Act 1920. For decades cannabis use was a minor issue, until the 1960s when a shifting global youth and drug culture caused concerns around cannabis to come to the surface. In 1960, 235 people were arrested in the UK for cannabis-related offences. By 1970, this figure had grown to almost 5,000 annually, rising again to over 11,000 1973. Currently, cannabis is a Class B drug in the UK and is illegal for recreational use. Therefore, unlicensed dealing and production are met with strict penalties.

International law on cannabis followed suit, which further held back genuine efforts to research the numerous medical benefits of cannabinoids. In the Single Convention on Narcotic Drugs, 1961, cannabis was internationally prohibited as a Schedule I substance (considered very addictive with potential for abuse), and a Schedule IV substance (any therapeutic benefit limited or non existent). Ten years later, the Convention on Psychotropic Substances was agreed, and cannabis was denoted as “a substance for which control is recommended because it may be abused and pose a particularly severe risk for public health and because its therapeutic value is very limited or inexistent”. Later, in 1988, various activities including the production, supply, sale, and import of any narcotic drug or psychotropic substance were classified as criminal offences by the United Nations Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances, 1988.

Changing Attitudes to Cannabis

The last 10 years have seen a huge change in attitudes and legal frameworks around cannabis. While the consumption and sale of cannabis for recreational use is only fully legal in Uruguay and Canada, many other countries are loosening their laws, especially around the medicinal use of cannabis-derived products. Indeed, on 24 January 2019, the Director General of WHO wrote to the UN recommending that cannabis and associated substances should be rescheduled at an international level, in particular noting that products containing predominantly CBD and no more than 0.2% Delta-9-THC should be excluded from international control. The reason for this was that there was no sufficient evidence that the substance was any risk to public health.

In the UK, the prescription of cannabis-derived products was rescheduled in November 2018. However, the types of products that can be prescribed are restricted, seemingly to reduce the risk of abuse. This has created some uncertainty among the big players within the medical cannabis sector and led to concerns that patients are not benefitting from changes in the law at all.

Ireland is pushing forward with plans for a five-year medical cannabis access programme for patients suffering with multiple-sclerosis (MS), chemotherapy-related nausea, or severe epilepsy.

The German Federal Government has taken similar steps to the UK, having passed a bill in 2017 to legalise the importation and domestic production and distribution of cannabis for medicinal purposes. The Federal Institute for Drugs and Medical Devices then granted contracts for the growth, subsequent sale, and delivery of cannabis to two manufacturers in the face of stiff competition.

The UK pharmaceutical industry seems to be moving, somewhat slowly, in the same direction. According to the clinicaltrials.gov website, the number of trials involving cannabis derived medicaments has increased considerably in the last five years; with 2019 likely to see even more trials begin. Current trials are examining an array of conditions, including chronic pain, epilepsy, MS, cerebral palsy, bipolar affective disorder, schizophrenia, Parkinson’s disease, irritable bowel syndrome, and a wide range of cancers.

While it is positive to see the number of trials involving medical cannabis increasing, the complex regulatory issues have impeded the progress made by players in this field. So far, only one cannabis based drug is licenced for use in the UK – Nabiximols, developed by the UK based GW Pharmaceuticals and marketed by Bayer as Sativex. It contains THC and CBD and is approved for the treatment of symptoms of MS.

Epidiolex, another GW Pharmaceuticals product containing purified CBD for use in the treatment of rare forms of childhood-onset epilepsy, has been approved by the FDA but is still in the approval process in the UK.

Medical Cannabis at a Crossroads

There are many opportunities for R&D in the medicinal use of cannabis, as indicated by the vast amount of research undertaken in the last century, and investors and innovators are coming to realise the opportunities offered by this budding sector in Europe. The cannabis plant produces hundreds of phytocannabinoids, and many of these may possess therapeutic benefits which are undiscovered as of yet. The development of new synthetic chemical entities based around the cannabinoid core chemical structure in theory presents endless research opportunities. This is not to mention the deluge of medical indications against which CBD itself could be effective, and the possibility of developing further research into new innovative uses of the compound.

In the UK, the National Institute of Health Research has recognised the possibility of cannabis-based products and has issued a call for more evidence and research on the potential drug. The institute has offered funding opportunities for primary clinical research into the safety and clinical efficacy or clinical effectiveness of cannabis-based products for medicinal use in humans.

In any emerging pharma sector, a strong intellectual property portfolio is crucial, not least the medicinal cannabis space and its related industries. This is particularly true of the CBD ‘wellness’ space, where gaining an edge over competitors could be decisive in driving sales. Strong trademark protection in this area will help deter would-be infringers, and solid patents can protect new CBD formulations, industrial processes, such as extraction and purification, uses of CBD compositions, and more.

The broad scope for innovation in this field goes hand in hand with an opportunity to obtain patent protection for the resulting inventions, which can provide an invaluable business tool and attract the investment needed to drive important research forward. Patents can be used to protect not only the use of known or novel cannabinoids to treat specific diseases, but also novel combination therapies, extraction and synthesis processes, dosage regimens, administration routes, and synthetic compositions and chemical entities.

GW Pharmaceuticals, for instance, have filed patent applications directed at a wide range of cannabinoid treatment, such as for epilepsy, brain tumours, mental disorders, inflammatory skin diseases, intestinal inflammation, degenerative skeletal muscle diseases, neuropathic pain, fatty liver disease, nausea, and even snoring.

The medicinal cannabis regulatory framework is at a crossroads in many countries around the world. Although there is an increasing awareness of the positive potential that cannabis-derived products may have in medicine, the enduring social and political stigma unfortunately still prevents general acceptance.

It is not until we collectively move past cannabis’ reputation simply as an illicit substance that we will truly harness its potentially ground-breaking properties.

Article originally published in European Biopharmaceutical Review. View the original article (pages 18 - 21).