Medical Cannabis: Understanding the Evidence

Cannabis-Based Medicinal Products: Understanding the Current Evidence

Cannabis has been a crop for thousands of years, lending itself to countless uses from the manufacture of clothing and even building materials. In more recent years there has been the development of pharmaceutical products which contain either extracts of the cannabis plant or are parts of the flowering plant itself. Despite the long-lasting and widespread utilisation of cannabis, however, the introduction of global prohibition in the 20th century has seen research and understanding of this plant lag behind. Unfortunately, this has had a significant impact on the development of medical cannabis, with many patients still unable to access cannabis-based medicines in most countries around the world.

In more recent years, a growing number of countries have begun to accelerate their research into cannabis, in addition to introducing significant law reforms. Medical cannabis is now legal through much of Europe, the Americas and further afield. The UK government announced the legalisation of medical cannabis in November 2018, opening the doors to patients appropriately seeking access. Nonetheless, access remains restricted, with only a handful of prescriptions being granted by the National Health Service. The vast majority of medical cannabis prescriptions are fulfilled by private clinics, like Sapphire Medical Clinic.

Continued lack of access is due to the need for more high-quality evidence to support the various uses of the plant and its derivatives. With this in mind, the authors of a recent article aimed to review the current literature on the therapeutic effects and applications of the two main cannabinoids found in the cannabis plant and resulting medicines – CBD and THC.

What are CBD and THC?

The cannabis plant contains over 100 chemical compounds known as cannabinoids – the most common of which are CBD and THC. These two compounds are also the most researched of the many cannabis derivatives, with growing evidence on their clinical effects. As a result, both CBD and THC have been incorporated into a variety of cannabis-based medicinal products. As a non-intoxicating compound, CBD has also become a popular ingredient for wellness products, including food supplements.

CBD and THC are similar in chemical structure, however, they interact with the body in different ways, leading to distinct effects on a number of physiological and cognitive processes. 

How do they interact with the body?

Humans, like many mammals, have an Endocannabinoid System that is expressed throughout the central and peripheral nervous system and the immune system. This consists of cannabinoid receptors, enzymes, and endogenous cannabinoids such as anandamide. These endocannabinoids interact with cannabinoid receptors to trigger various responses. The similar structure of phyto-cannabinoids, like CBD and THC, to those produced in the body allows them to also interact with these receptors. For example, THC is an analog of the endocannabinoid anandamide. 

THC is also responsible for many of the intoxicating, psychoactive, and euphoria-inducing effects of the cannabis plant. When prescribed as part of a medical cannabis regimen the goal is to start at a low dose of THC and increase this slowly to avoid these potential effects. In addition, it also demonstrates a variety of additional properties which are why it is incorporated commonly as part of the regimen medical cannabis patients are prescribed. In comparison, CBD is not intoxicating even at high prescribed doses.

The Existing Evidence

Chronic Pain

Evidence demonstrates the role of the endocannabinoid system in several processes – including pain signalling. As a result, a growing number of human clinical trials are being conducted to further understand the potential of cannabinoids in cases of pain. The authors suggest that the current evidence for cannabis-based medicinal products is more promising for chronic pain rather than acute pain. Furthermore, products that contain both CBD and THC are suggested to have the greater effects in chronic cancer- and neuropathic pain compared to isolated compounds.

A recent article featured in the British Medical Journal recommended that CBMPs be trialled in patients who had not achieved satisfactory improvement in pain outcomes with conventional therapeutics. 

Multiple Sclerosis

Multiple Sclerosis (MS) is a condition that is associated with a number of symptoms – the most common being pain and spasticity. Current evidence, assessed in a recent Cochrane review, demonstrates that CBMPs are associated with a 2.5-times increased chance of clinical improvement in spasticity.

Nabiximols is a synthetic THC analog that has been licensed for use in the UK for spasticity associated with MS in cases where first-line therapies have been ineffective. 

Treatment-Resistant Epilepsy

Epidyolex – a CBD isolate solution – has been approved in the UK as an adjuvant therapy for a number of rare treatment-resistant childhood epilepsies – particularly Lennox-Gastaut and Dravet syndromes. Current evidence supports the potential of Epidyolex in reducing seizure severity and frequency associated with epilepsy. In contrast, the effect of THC on seizures remains unclear, with animal models demonstrating a combination of both anti-convulsant and pro-convulsant effects. THC is still yet to be studied within randomised controlled trials for treatment-resistant epilepsy.

The Prescription of CBMPs

The most suitable cannabis-based medicinal product should be determined on a case-by-case basis, depending on factors such as condition, patient demographic, preferred route of administration, and potential drug-drug interactions. 

While a number of CBMPs have been licensed for use in the UK, a number of other unlicensed products can also be considered for prescription by a member of the General Medical Council Specialist Register. The prescription of these medicines is gaining traction; however, conducting randomised controlled trials for unlicensed CBMPs remains difficult due to current regulations. Nonetheless, real-world evidence collected through patient registries, such as the UK Medical Cannabis Registry is helping to improve clinical understanding of the outcomes associated with unlicensed CBMPs. Promisingly, there is growing clinical evidence on use of cannabinoids and cannabis-based medicinal products in a number of conditions.