On Friday several French agencies opened an investigation into a clinical drug trial that has hospitalized six men in the last week, leaving one permanently brain dead and three in critical condition, likely with permanent brain damage.
At a press conference held Friday afternoon at the University Hospital of Rennes, where the six victims are currently being treated, the French Minister of Health, Marisol Touraine, vowed to “get to the bottom of this…tragic incident.” She also denied reports that the experimental drug contained cannabis or cannabis derivatives, as some French media agencies had originally reported.
When the story of the hospitalizations broke, several French media agencies erroneously reported that a “cannabis based product was in question” and i-Télé reported that a cannabis-based pain killing drug was being injected into the trial participants. This assertion was categorically denied by Touraine during her press conference.
“Contrary to what I've heard, this drug does not contain cannabis and is not a cannabis derivative,” said Touraine. “It acts on the endo-cannabinoid system.”
The confusion likely stems from the use of the word ‘cannabinoid,’ the term for a wide variety of compounds which act on the cannabinoid receptors in the brain. These cannabinoid receptors are part of the endocannabinoid system, which is found in a wide variety of mammals and is responsible for helping regulate everything from memory and pain to appetite and mood.
There are three major types of cannabinoids: endocannabinoids (produced naturally in humans and animals), synthetic cannabinoids (manufactured artificially) and phytocannabinoids (which are found naturally in some plants, such as cannabis). Although tetrahydrocannabinol (also known as THC, the main psychoactive compound in cannabis) is perhaps the most well-known cannabinoid, it is not a part of the drug that was being tested in Rennes.
Just which molecule was being tested is not known for sure: a press release from Bial, the Portuguese pharmaceutical company that produced the drug in question, described the molecule as a type of pain medication known as an FAAH enzyme inhibitor. There is a chance the molecule was BIA 10-2474, an experimental drug for “neurological and psychiatric pathologies” and one of two substances listed on Bial’s website as in the first phase of clinical trials.
The clinical trial for the molecule that has left six men, ages 28-49, with varying degrees of neural complications (one brain dead, three in critical condition, one with neurological problems and one under close observation) began last year in July. It has been executed by Biotrial, a research company operating on behalf of Bial.
So far the molecule has been administered to a total 90 participants, although the six hospitalized last week were the first to show such severe adverse effects. The six men began taking the molecule on January 7, and by January 10 the first man was hospitalized and his condition rapidly deteriorated until he was declared to be brain dead by Gilles Edan, the chief neuroscientist at the Rennes hospital. According to Edan, there is no known antidote to the compound.
This calamitous occurrence is a first for France, which maintains strict national and international regulations for carrying out drug testing on humans.
Typically, a drug undergoing a clinical trial goes through three phases. In Phase I, the drug is administered to healthy patients in incremental doses—the first patients will receive a single dose while latter patients will receive multiple doses over several days. In Phase II, experimental drugs are given to patients with relevant conditions to see if the drug helps them. In Phase III, the drug is tested against a placebo and compared with existing treatments to gauge its effectiveness.
The six hospitalized participants were participating in the first phase of the clinical trials for this molecule and were all declared healthy prior to beginning the study. According to Bial’s press release, the company had the clinical trial approved by the French Regulatory Authorities as well as the French Ethics committee in accordance with the guidelines laid out in Good Clinical Practices and Declaration of Helsinki.
The trials related to the Bial drug have been suspended as of January 11 and at her press conference Touraine promised a full scale investigation into the trial spearheaded by the French General Inspectorate of Social Affairs. The Health Minister said she expected a final report on the occurrence by the end of March at the latest.