The Reason France’s Bial Painkiller Experiment Went Horribly Wrong Wasn’t Cannabis

Touraine said the drug was a so-called FAAH inhibitor meant to act on the body’s endocannabinoid system, which deals with pain. Earlier reports suggested that the drug contained cannabinoids, an active ingredient found in cannabis plants, but the minister said it did not contain the drug or any derivatives of it…

(2011) The Discovery and Development of Inhibitors of Fatty Acid Amide Hydrolase (FAAH)

(2009) Discovery and Characterization of a Highly Selective FAAH Inhibitor that Reduces Inflammatory Pain (by Pfizer)

(2012) An efficient randomised, placebo-controlled clinical trial with the irreversible fatty acid amide hydrolase-1 inhibitor PF-04457845, which modulates endocannabinoids but fails to induce effective analgesia in patients with pain due to osteoarthritis of the knee.

Achieving analgesia without cognitive and behavioral side effects has been a holy grail for companies developing pain therapeutics, but separating the desirable and undesirable effects of analgesics has been a challenge for compounds that act in the CNS. Now, a team of Italian and American researchers may have sidestepped the problem with a molecule, URB937, that works entirely in the periphery.

URB937, a p-hydroxyphenyl-O-arylcarbamate, targets fatty acid amide hydrolase (FAAH), an enzyme that degrades the lipid molecule anandamide, which in turn activates cannabinoid receptors on sensory neurons in the periphery and on a range of other neurons in the brain. Inhibiting FAAH raises natural anandamide levels and leads to long-term cannabinoid receptor activation and pain relief…

“There is an undercurrent of controversy in the pain field about whether pain is better controlled peripherally or centrally,” said Daniele Piomelli, director of the Italian Institute of Technology (IIT)’s Drug Discovery and Development (D3) research unit. Piomelli also is a professor of pharmacology at the University of California, Irvine.

To resolve the question, Piomelli said his team screened for “a compound that inhibited anandamide degradation in the periphery without at all affecting anandamide degradation in the brain. We were lucky to find URB937, which doesn’t enter the brain at all.” …

Altogether, the findings support the hypothesis that stimulating cannabinoid signaling in the periphery is effective at relieving pain and that targeting the pathway in the brain may not be necessary.

“We now know that anandamide in the periphery works as a gate that prevents entry of pain signals into the brain,” said Piomelli…

Earlier this year, Pfizer Inc. discontinued development of its FAAH inhibitor PF-04457845, which failed a Phase II trial for pain in osteoarthritis of the knee. Ironwood Pharmaceuticals Inc.’s IW-6118 has completed Phase II testing for molar extraction pain. Vernalis plc’s V158866 FAAH inhibitor is in preclinical development for pain.


3 thoughts on “The Reason France’s Bial Painkiller Experiment Went Horribly Wrong Wasn’t Cannabis

  1. It went horribly wrong because it wasn’t cannabis. Nature got it right. The cognitive-behavioral side effects lessen with usage, don’t they? Most people go through an adaptation period of feeling whacked out when starting antidepressants or any drug that messes with the body’s chemistry (f-u-a-whole-lot-gabapentin!), and by most people, my study group consists of me, myself, I, and one other person. We’re self-proclaimed experts of nothing. 🙂

    Liked by 1 person

    • When they say “cognitive and behavioral side effects,” they really mean the “high” effect, which to them, always means a potential for abuse and/or addiction. (Can you get high from antidepressants? I never did.)

      They don’t look at drugs according to how hard it is to stop taking them. If they did, the drug war would look a lot different.

      What they look at as a bad thing, I look at as the thing that brings pain relief. One of the reasons that cannabis is rarely addicting is because the CBDs act to minimize the effect of the THC. Yeah, Mother Nature knows what she’s doing. Big Pharma? Not so much. 🙂

      Liked by 2 people

  2. Reblogged this on EDS Info (Ehlers-Danlos Syndrome) and commented:
    The most important thing to know is that these drugs had zero cannabis or cannabinoids in them. The connection is that they were trying to target the same receptors cannabinoids affect, without using cannabinoids.

    Apparently, it’s better (and certainly far, far more profitable) to harm and even kill the occasional guinea pigs than to just give people medicine that’s cheap, effective, and has been used for thousands of years: opioids.

    Liked by 1 person

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