What differentiates cannabis-based medications from other medications?
Cannabis-based medications have sparked growing interest due to their unique pharmacological properties. But what truly sets these medications apart from others? The cannabis plant contains many active molecules, some of which are common to other plan species, such as terpenes or flavonoids. However, the remarkable pharmacological profile of cannabis is primarily based on its main active compound, delta-9-tetrahydrocannabinol, or THC. THC is a unique molecule in nature as it can bind to proteins present in our cells, eliciting a characteristic physiological response. These proteins, called type 1 cannabinoid receptors (CB1), belong to a family known as “G protein-coupled receptors” or GPCRs, which play a crucial role in cellular communication and have been extensively studied for drug development. Interestingly, CB1 is the most abundant GPCR in the human brain, underscoring the significance of its activity!
The discovery of the THC structure in the 1960s initiated a medicinal chemistry campaign to obtain drugs with similar effects. In the 1990s, molecules similar to THC but more selective and potent were identified, and the endocannabinoid system (ECS) was discovered. The ECS is present in various organs and tissues, including the nervous, vascular, musculoskeletal, and digestive systems, among others. Its general function is to maintain homeostasis, in other words, to help the body adapt and provide a satisfactory response to environmental changes.
The tremendous potential for the rational design of drugs targeting the ECS sharply contrasts with the failure of various strategies pursued so far for the clinical development of cannabinoid drugs. THC remains the only agonist (a molecule capable of directly activating a receptor) of CB1 that can be prescribed by a doctor in various formats: Marinol®, Syndros®, Sativex®, or medicinal cannabis products. Alternatives like nabilone (Cesamet®) have not gained widespread acceptance among the medical community, and compounds like ajulemic acid have not completed their clinical development. Alternative strategies, such as inhibitors of endocannabinoid reuptake or degradation, generated significant interest from the pharmaceutical industry for drug development in the first decade of the century. However, due to various failures in clinical trials, research on cannabinoids for clinical pain management has largely been abandoned.
In this scenario, cannabis-based medications stand as the only pharmaceutical tool clinicians currently have to harness the endocannabinoid system (ECS) for therapeutic purposes. Real-world evidence collected in various countries with existing access programs for these pharmaceutical specialties suggests that their use is associated with robust improvement in managing populations with chronic diseases. Patients report a reduction in symptoms linked to an improvement in quality of life, sleep architecture, rest, and mood, without the emergence of serious side effects. In summary, cannabis-based medications represent an important tool for the management of chronic diseases, but further studies are still needed to fully understand their long-term effects and cost-benefit relationship within the healthcare system.