What differentiates cannabis-based medicinal products from other medicines?

Cannabis-based medicinal products (CBMPs) such as Sativex and Epidyolex have been authorised in many countries due to their unique pharmacological properties and potential to treat symptoms associated with various neurological conditions such as spasticity in Multiple Sclerosis and seizures in pediatric syndromes such as Dravet, Lennox-Gastaut and Tuberous Sclerosis.

However, their off-label use is rare and very limited to refractory cases of neuropathic pain.

Beyond these two medications, unlicensed CBMP are garnering significant interest in other clinical fields relevant to neurorehabilitation such as unspecified chronic pain, often resistant to conventional treatments, or Parkinson's disease, where cannabis-based therapies can alleviate non-motor symptoms and improve patients' quality of life.

Since their legalisation in 2018, unlicensed CBMPs of different presentations and composition can be prescribed by any registered medical specialist in the UK.

Thousands of patients are already benefiting from their medicinal use, contributing to a growing body of real-world, post-commercialization evidence on CBMP safety and effectiveness.

Real-World Evidence and Clinical Use of unlicensed CBMP

Real-world evidence from countries with established access programs suggests that CBMPs can significantly improve the management of chronic illnesses.

Patients report reductions in symptoms, enhanced quality of life, better sleep patterns, and improved mood, with minimal serious side effects.

The therapeutic use of cannabis is not a new concept; historical records indicate its use in various cultures for centuries. Modern science is now providing empirical support for many traditional claims.

The renewed interest in CBMPs has led to more rigorously designed clinical studies and a better understanding of their mechanisms of action and potential outcomes.

CBMPs are particularly valuable in managing conditions that are resistant to conventional treatments. Chronic pain, multiple sclerosis, and certain forms of epilepsy are among the conditions where patients have found relief with cannabis-based treatments.

The use of CBMPs can reduce dependence on opioids, which are associated with significant risks of addiction and overdose. This aspect is crucial, considering the ongoing opioid crisis in many parts of the world.

Moreover, the holistic effects of CBMPs, such as improved sleep and mood, contribute to overall patient well-being. These benefits extend beyond mere symptom relief, offering a more comprehensive approach to healthcare. The integration of CBMPs into standard medical practice represents a shift towards more personalized and patient-centered care.

Unique Active Compounds which a Unique Pharmacological Target

The cannabis plant contains a multitude of active molecules, including common plant compounds like terpenes and flavonoids. However, its remarkable pharmacological profile is primarily due to delta-9-tetrahydrocannabinol, or THC.

THC is unique in its ability to bind to specific proteins in our cells, eliciting notable physiological responses. These proteins, known as type-1 cannabinoid receptors (CB1), are part of the larger G-protein-coupled receptor (GPCR) family. GPCRs are crucial for cellular communication and have been extensively studied for drug development. Notably, CB1 is the most abundant GPCR in the human brain, underscoring its significant role in human physiology.

The structure of THC was identified in the 1960s, sparking a wave of medicinal chemistry research aimed at developing drugs with similar effects. By the 1990s, researchers had synthesised more selective and potent THC-like molecules, leading to the discovery of the endocannabinoid system (ECS).

The ECS is a crucial physiological system involved in cellular communication, present in various organs and tissues, including the nervous, vascular, musculoskeletal, and digestive systems. Its primary function is to maintain homeostasis, helping the body adapt and respond to environmental changes.

The other active ingredient, cannabidiol or “CBD”, does not activate but may rather act as a negative modulator of CB1. However, its main pharmacological action in epilepsy and other channelopathies seems to be mediated by non-classical cannabinoid targets, such as GPR55, a different member of the GPCR family of receptors.

Alternative clinical indications for which CBD could be of value are currently under investigation in trials performed mainly with Epidyolex.

Challenges for the Traditional Development of Cannabinoid Medications

The potential for designing drugs targeting the ECS is remarkable. However, the clinical development of cannabinoid drugs has faced numerous challenges. Despite the promise, THC remains the only CB1 agonist approved for medical use in various forms, such as Marinol®, Syndros®, Sativex®, and medicinal cannabis products.

Other compounds like nabilone (Cesamet®) have not gained widespread acceptance, and drugs like ajulemic acid are still under clinical development.

Alternative strategies, such as endocannabinoid reuptake inhibitors and degradation inhibitors, initially attracted significant interest from the pharmaceutical industry. These strategies aimed to enhance the body's natural endocannabinoid levels, offering a novel approach to pain management and other conditions.

However, clinical trials have not yielded the expected results, leading to a decline in research efforts in this area.

Future Directions and Research Needs

Despite the promising real-world evidence available, there is still a need for more extensive and rigorous observational studies to fully understand the long-term effects of CBMPs when included as an adjuvant to the standard of care.

Researchers are exploring various aspects, including optimal dosing, the development of new cannabinoid compounds, and the potential for treating a broader range of conditions.

However, deepening our understanding of the cost-benefit ratio of these treatments is also critical for their integration into healthcare systems. The regulatory landscape for CBMPs is evolving, with more countries recognising their therapeutic potential and adjusting their laws accordingly.

This trend is likely to help more real-world evidence emerge from better designed studies, supporting the safe and effective use of cannabis-based treatments.

Cannabis-based medicinal products stand out from other medicines due to their unique interaction with the ECS and their potential to address a wide range of medical conditions. While challenges remain in their development and acceptance, the growing body of evidence supports their use as a valuable tool in modern medicine.

Continued research and regulatory advancements will be key to a wider acceptance of their full therapeutical potential and their integration into comprehensive healthcare strategies.

Dr Guillermo Moreno-Sanz is Scientific Advisor at Zerenia. Learn more about Zerenia here