No matter the number of pre-clinical studies conducted, putting a new drug inside a human for the first time carries inherent risks. In a tragic reminder of that fact, a man has died during the first stage of a clinical trial in France, and three others may have permanent brain damage.
Reports of the trial taking a turn for the worst first surfaced three days ago, on January 15, when six people were said to be in a critical condition after receiving an experimental pain-relief drug. Details were scant at the time, and although rumours in the French media initially suggested that the trial involved a cannabis-based painkiller, this was quickly denied by the French health minister, Marisol Touraine.
Now, the pharmaceutical company behind the trial, Portuguese firm Bial, has revealed that the novel drug was an inhibitor of an enzyme called FAAH. In the body, FAAH acts on our so-called endocannabinoid system – a group of receptors and molecules involved in a range of physiological functions, such as pain and appetite – by degrading said molecules and thus preventing them from functioning at the site of action. Inhibiting FAAH therefore helps boost the levels of these chemicals, such as the “bliss molecule” anandamide, a natural pain-suppressor.
Although there’s evidence that cannabis and cannabis-like molecules can also activate this system and reduce pain, because these also have unwanted side-effects, namely getting people high, scientists are keen to look for other ways to achieve the same goal.
While Bial stated the drug was designed for the “area of pain,” an email from the company has surfaced from an applicant who was turned down for the trial, which states the experimental treatment was “developed for different medical afflictions from anxiety to motor troubles caused by Parkinson’s disease and also in the treatment of chronic pain, multiple sclerosis, cancer, high blood pressure and even the treatment of obesity.”
The trial, which began last June, was in phase 1, a stage involving a small number of healthy participants – in this case 108 – in order to test safety and evaluate dose ranges. Although no adverse reactions occurred in any of the 84 other volunteers given the drug (18 received only a placebo), the six men who fell seriously ill were all among the group receiving the highest amount, the Guardian reports.
Administration of this particular dose began on January 7, and within three days one participant was admitted to hospital in the city of Rennes. Within the next few days, five others followed suit. Although these five are now reported to be in a stable condition, the other volunteer was said to have slipped into a coma before being left brain-dead and dying shortly afterward. The trial has consequently been suspended and numerous investigations are underway.
As with any clinical trial, vigorous tests on both cells in the lab and animals have to be conducted before the drug is given to humans in order to evaluate safety. While this reminds us that these studies are not necessarily translatable, it’s important to note that, though tragic, instances such as this are extremely rare in the field.
