In 2018, the UK government announced the rescheduling of cannabis. This milestone allowed the prescription of unlicensed cannabis-based medical products in the UK for the first time in almost 50 years. Medical cannabis can now be prescribed for five indications through the NHS, including various forms of treatment-resistant epilepsy, chemotherapy-induced nausea and vomiting, and spasticity associated with multiple sclerosis (MS).
Furthermore, prescriptions can also be granted by specialist clinicians at private clinics (through which all but a handful of unlicensed medical cannabis prescriptions have been filled since 2018) for a multitude of other conditions. Still, almost exclusively, conditions where medical cannabis is prescribed are either neurological conditions themselves, such as epilepsy, MS, and migraine, or those that require the modulation of neurotransmission in either the central or peripheral nervous system, such as in chronic pain, psychiatric conditions, and insomnia.
As such, a recent article examined some of the existing pre-clinical and clinical rationale underpinning the increase in the prescription of cannabis-based medical products since their rescheduling in November 2018.
What is the Evidence for Medical Cannabis?
The majority of research into medical cannabis in recent years has focused on the plant’s two most abundant cannabinoids: cannabidiol (CBD) and tetrahydrocannabinol (THC). These cannabinoids interact with a receptor system in the human body known as the endocannabinoid system (ECS). Receptors in the ECS (CB1R and CB2R) are expressed predominantly throughout the central nervous system and the immune system, respectively.
The authors of the current article focused on three key areas of medical cannabis research: chronic pain, spasticity, and seizures.
Medical Cannabis and Chronic Pain
Chronic pain is the most common condition for which medical cannabis is prescribed in the UK. Chronic pain may refer to a primary condition or a symptom of other neurological conditions, such as MS. Evidence has shown that CBD and THC affects the transmission of nociceptive (pain) signals through both the peripheral and central nervous systems. Furthermore, medical cannabis has been seen to modulate pathways involved in the emotional and cognitive manifestations of pain.
Recommendations by Busse et al. suggest trialling non-inhaled medical cannabis in cases where conventional treatments have proven ineffective. These findings support the pre-clinical evidence that cannabis-based medicines do not just impact the transmission of nociceptive signals, but also the psychological component of chronic pain pathophysiology.
Medical Cannabis and Spasticity
Spasticity, characterised by an increase in muscle tone due to involuntary contraction, occurs because of a lack of central inhibition of peripheral motor neurons. As CB1Rs regulate the neurotransmission at synapses of glutaminergic and γ-aminobutyric acid (GABA)-ergic neurons, it is thought that they may be important regulators of muscle tone during spasticity.
Furthermore, one licensed medical cannabis product (nabiximols) containing both CBD and THC has been extensively studied in clinical trials for this indication. The results of these studies indicate that nabiximols is associated with an increase in the chance of clinically significant improvements in spasticity by 2.5 times that of a placebo. However, to date, nabiximols has not been evaluated for its potential in spasticity in other settings, such as stroke; therefore, there is limited data on its effectiveness in conditions that cause spasticity secondary to upper motor neuron lesions.
Medical Cannabis and Seizures
CB1R agonism has also been implicated in the effect of cannabinoids during seizures. Activation of CB1R has been shown to reduce neuronal hyperexcitability and increase seizure thresholds, reducing and even terminating seizures.
Current evidence in this area supports the use of CBD products in favour of THC or combined products. Epidyolex, a CBD isolate therapy has been licensed in the UK as an add-on therapy in tuberous sclerosis complex, as well as Dravet and Lennox-Gastaut syndromes. Further clinical trials are awaited in this area to evaluate products which contain other compounds from the cannabis plants, including THC.
Prescribing Medical Cannabis in the UK
Licensed medical cannabis products are only available within the NHS for a small number of indications; however, both licensed and unlicensed products may be prescribed for further indications when there is clinical evidence, as outlined by the Medicines and Healthcare Products Regulatory Agency, of their potential benefit. Under this guidance, medical cannabis may only be prescribed if other conventional therapies have proven ineffective or were associated with adverse events.
An estimated 32,000 patients are now in receipt of a medical cannabis prescription in the UK. These patients represent those who have had conditions or specific symptoms that were otherwise treatment-resistant. The vast majority of these patients access their medication via private clinics, like Sapphire Medical Clinics. The authors of this article note that, with the provision of such clinics, “alongside a developing field of research, it is expected that more patients with neurological conditions will be prescribed medical cannabis in the coming years.”
Finally, the authors conclude that “The regulatory environment helps to protect and safeguard patients, but it can cause certain aspects of care to be inaccessible to patients and healthcare professionals alike.
“An understanding of the current landscape and evidence will be essential in helping patients navigate the potential options available to them.”