What happens if FAAH is inhibited?
What happens if FAAH is inhibited?
A major observation was that FAAH inhibitors do not apparently induce those adverse effects commonly associated with exogenous cannabinoids, such as impairment in cognition, motor coordination, and psychoses. However, it must be noted that the effects of chronic treatment are still largely unknown.
What was the end result of the trial for BIA 10 2474?
In BIA 10–2474 Phase I trial, all six subjects were simultaneously administered to multiple higher doses of FAAH inhibitor under investigation. This led to the death of one and serious adverse events in four other volunteers.
What are FAAH inhibitors?
FAAH inhibitors enhance the action of the endocannabinoid AEA and other fatty acid amides indirectly through blocking their metabolism and could serve as potential therapeutic agents for the treatment of diseases where the endocannabinoid activation is beneficial.
What is the FAAH out gene?
FAAH gene. With regard to the FAAH gene, researchers know this gene encodes for the FAAH enzyme involved in endocannabinoid signaling. In essence, FAAH normally degrades anandamide (a fatty acid neurotransmitter) into free arachidonic acid and ethanolamine.
What is FAAH inhibitor?
How bad are clinical trials?
What are the Potential Risks of a Clinical Trial? The new treatment may cause serious side effects or be uncomfortable. The new treatment may not work, or it may not be better than the standard treatment.
What does FAAH mean?
Fatty acid amide hydrolase (FAAH) is a mammalian membrane protein responsible for the hydrolysis and inactivation of biologically active amides (Piomelli, 2003), including the endocannabinoid anandamide and agonists of the peroxisome proliferator-activated receptors, such as oleoylethanolamide and palmitoylethanolamide …
Why do most clinical trials fail?
Failures can arise from a lack of efficacy, issues with safety, or a lack of funding to complete a trial, as well as other factors such as failing to maintain good manufacturing protocols, failing to follow FDA guidance, or problems with patient recruitment, enrollment, and retention.
What percentage of drug trials fail?
(39% failure rate), whereas 67% of all drug trials moved to the application phase (33% failure rate). The high failure rate of Phase II trials reported in that analysis (62% and 67%, respec- tively) is not unexpected for exploratory trials.
Can a fatty acid hydrolase ( FAAH ) inhibitor cause death?
A recent phase 1 trial of the fatty acid amide hydrolase (FAAH) inhibitor BIA 10-2474 led to the death of one volunteer and produced mild-to-severe neurological symptoms in four others. Although the cause of the clinical neurotoxicity is unknown, it has been postulated, given the clinical safety pro …
Are there any FAAH inhibitors that are safe to take?
Although other drug developers, including Pfizer, had already dropped FAAH inhibitors because of disappointing efficacy studies, most of the molecules were shown to be safe, as the U.S. Food and Drug Administration confirmed in August 2016 . But that was not true for BIA 10-2474.
When did Bial start work on FAAH inhibitors?
According to a company statement, a project to develop FAAH inhibitors was initiated by Bial in 2005, and studies with this compound began in 2009 with pre-clinical in vitro and in vivo pharmacological and toxicological evaluation.
Are there any FAAH inhibitors for anxiety disorders?
FAAH inhibitors have been proposed for a range of nervous system disorders including anxiety disorders, alcoholism, pain and nausea. The Portuguese pharmaceutical company Bial holds several patents on FAAH enzyme inhibitors.