Chronic Pain, the First Indication for the Prescription of Medical Cannabis

At least 12 million French people suffer from chronic pain, in other words, permanent pain, suffered for at least three consecutive months, with significant physical, moral, and social consequences.

In such conditions, pain becomes a disease in its own right, affecting the quality of life of patients in a lasting way. And this, especially since in the latter pain treatments are often insufficiently effective: in France, it is estimated that more than 70% of chronic pain patients do not receive appropriate treatment.

This pathology induces a high consumption of care and significant professional absenteeism. It is therefore also a major economic and social issue.

In this context, medical cannabis enriches the range of therapeutic products available, while being part of the overall support of the pain patient. Indeed, in countries that have legalized access to medical cannabis, the relief of chronic pain is the first indication of these products manufactured according to pharmaceutical standards.

Cannabis and pain: how does it work?

Humans have a so-called “endocannabinoid” system, which plays an important role in the regulation of vital processes (homeostasis). Composed of a set of receptors as well as endogenous substances (that is to say, synthesized by the body itself) that attach themselves to it, this signaling system is very old in the animal kingdom. It has been well preserved during evolution, being found in all vertebrates.

The characterization of this neurotransmission system during the 1970s and 1980s initiated research into the value of modulating it in diseases such as chronic pain.

Several molecules produced by the Cannabis sativa L plant affect the human endocannabinoid system. This is particularly the case with delta-9-tetrahydrocannabinol (more commonly known as THC), capable of activating the cannabinoid receptors CB1 and CB2 as well as other proteins involved in the transmission of pain messages to the brain.

Cannabidiol (CBD), the other molecule found in cannabis, is said to have less affinity for cannabinoid receptors. However, it modulates the effect of THC on its receptors and limits its adverse effects, especially neuropsychiatric (drowsiness, anxiety, etc.).

CBD also enhances the activation of the system by inhibiting the breakdown of an endocannabinoid, anandamide. Its activating action on serotonin receptors would explain its anxiolytic effect. Finally, CBD is thought to bind to many other receptors involved in inflammation and the perception of pain.

The beginning of scientific validation

The evaluation of the benefit of medical cannabis in a large number of painful clinical situations has been the subject of scientific publications, however, the levels of evidence often remain modest, even low, in conventional clinical trials that compare it to a placebo.

Many clinical studies have focused on the use of medical cannabis to treat musculoskeletal pain, particularly spasticity, a painful muscle contraction. This disorder affects not only up to 25% of 100,000 French people suffering from multiple sclerosis, but also those with a spinal cord injury or sequelae following a stroke.

Sativex, a drug based on cannabis extract, obtained marketing authorization in 2014 for this indication but is still not marketed, due to a lack of agreement on its selling price between the authorities and the laboratory. Who markets it.

The health benefit of cannabis-derived products has also been demonstrated in neuropathic pain. This type of pain, which affects 7% of French people (or a quarter of people suffering from chronic pain), results from an injury or disease of the somatosensory system.

It appears in the form of a set of painful symptoms (intense tingling, electric shocks, feeling of crushing, burning, or stabbing …) for which the recommended drug treatments, antidepressants or antiepileptics, are only very partially effective and sometimes poorly tolerated.

These two conditions are the main indications of chronic pain retained in the French experiment which will be piloted by the National Agency for the Safety of Medicines and Health Products (ANSM), from 2021 to 2023: 1,500 of the 3,000 people who will be treated during the experiment will be concerned.

French patients prone to very frequent pain will also experiment with medical cannabis. This is particularly the case for those affected by indications for palliative care (500 patients to be recruited) and cancer-related complications (500 patients to be recruited).

Other chronic pain is the subject of research all over the world, with sometimes encouraging results, but which still need to be scientifically confirmed by methodologically more rigorous studies.

This is the case with the therapeutic use of cannabis in fibromyalgia, certain chronic headaches, endometriosis, sickle cell anemia, or osteoarticular pain.

Neither the alpha nor the omega of pain treatment

Cannabis-based drugs are by no means the promise of a pain-free life; they must be part of the overall care of the pain patient. The therapeutic goal of their use to treat chronic pain goes beyond reducing the pain intensity alone, although this is often considered the primary goal in clinical trials.

Medical cannabis could also positively impact pain-related disorders such as mental distress or sleep disorders. The end goal is to improve the quality of life of a patient suffering from a chronic condition, to allow him to no longer devote his vital energy to fighting this pain. It is also to help him to better work on accepting this “pain disease” and to regain more regular physical activity, as well as more positive thoughts.

The French experiment will provide an opportunity to determine the potential place of these drugs and their prescription methods in the therapeutic strategies proposed to counter chronic pain. With this in mind, the choice of products according to their composition, in particular THC and CBD, and the adjustment of dosages still need to be clarified.

Go towards personalized medicine

Treating a patient with chronic pain should not focus on prescribing drugs, which are only part of the solution. On the contrary, research on medical cannabis and pain must be part of precision medicine.

It must aim at relevant therapeutic objectives, centered more on the painful patient than on the mere disappearance of his pain.

For this, complementary approaches combining real-life studies and conventional clinical trials against placebo or against reference drugs must be implemented.

Moreover, the entourage effect, according to which the combination of several compounds contained in the plant would be more effective than if the cannabinoids (THC, CBD …) were administered in isolation, should be better studied.

It is often invoked to justify the administration of the whole plant (whole plant or part of the plant used as it is, and therefore containing many molecules). Cannabis-based medicines are therefore complex mixtures of several dozen or even hundreds of substances. The possible role of other cannabinoids and certain terpenes in their effectiveness should be evaluated, in order to optimize their final composition.

Ultimately, it will be a question of determining more precisely which thc vape oil can be prescribed to which patient in order to have the maximum chance of achieving the therapeutic goal. This will improve the cost/effectiveness ratio of these drugs and avoid prescribing too risky, or even too many, as we sometimes see in painful patients overmedicated and yet not relieved.

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