Wednesday, April 10, 2013

Big Pharma making cannabinoid-like drugs? Been there already, right?

This New York article on the synthetic drug craze was somewhat interesting, if not a bit breathlessly reported.* But here is a statement from a New York-area physician that I felt was wrong:
[Dr. Julie] Holland believes that it’s a foregone conclusion that the next decade will include a new generation of Big Pharma meds based on marijuana. “You’re going to have medicine for inflammation and metabolism tickling the cannabis receptors—they’ll act like cannabinoids, but aren’t going to get you high.” (Harvard Medical School professor John Halpern recently started a company, Entheogen Corp., to develop 2-bromo-LSD, a non-hallucinogenic LSD analog, to treat cluster headaches, one of the most painful conditions in medicine.)
So I'm probably wrong about this, since I'm not a medicinal chemist. But hasn't the ground of CB1/CB2 receptor targeted compounds been plowed pretty thoroughly, with some prominent failures? There are most certainly other receptor systems that haven't yet been investigated, but I suspect that Dr. Holland is incorrect in her prediction that Big Pharma is bringing such things to market.

[Also, Dr. Holland's prediction reminds me of the XKCD column on 'translating researchers.']

Readers, please, prove me wrong.

*I'm so bored with this genre, it's not funny. 


  1. CJ ; CB1/CB2 receptors are interesting TOI. The expression of the former in the brain has been implicated as an obesity target. Many companies worked on an inverse agonist/antagonist based molecules selectively targeting the CB1 receptor. Merck, took its lead compound for phase 3 trial but did a very fast retreat because lot of people during the study also reported of suicidal tendencies. Subsequently, Sanofi, that got its drug approved in the Europe (FDA declined!) had to withdraw its product, Rimanobant for the same reasons (suicidal tendency in people who took it). Recall that doors to getting approval here in the US (the largest market in the Globe !)goes through FDA. Granted that many of these drugs also display psychotic effects (suicide, depression, QT wave prolongation etc.) it is going to be an uphill task to get an approval, even if it displayed smooth efficacy with out any adverse effects.

  2. I don't know about imminently, the Rimonabant incident was damaging to a potential blockbuster area. But it really did work as a weight loss drug, so there is enormous potential there. I've seen work on peripheral CB antagonists (in person, as the guy in my lab has worked on it!) with applications in a variety of areas so the potential for CB based therapies is definitely there, if they can work through the issues.

  3. Merely passing on what I've heard, but CB1/2 are supposedly interesting targets, especially from THC-like derivatives, according to a colleague in the know. I'll stop talking now before I say something silly, as I'm not a med chemist either.

    If big pharma aren't working on these targets right now, I'd have guessed it was due to uphill battles even trying to do initial research on classified drugs, never mind getting similar drugs approved for medical use. It's a big risk, even in pharma terms.

  4. This could actually be an interesting space for legitimate pharmaceutical chemistry in the coming years. In New Zealand, they are currently debating a bill that will allow the sale of novel recreational drugs if the drug can be proven sufficiently safe ( I wouldn't be surprised to see pharmaceutical companies jump on this opportunity. Finding and developing a sufficiently safe drug that gets people high has got to be a lower bar than finding a sufficiently safe drug that reduces illness, and the potential customer base is huge.

  5. CB2 agonists have been studied for relieving pain. CB2 Inverse agonists have been shown to be effective in rodent models of arthritis and MS. My impression is that the compounds haven't progressed because the pharmacology and resulting side effect profile was more complicated than people would tolerate.

  6. GW Pharmaceuticals out of England is going to beat everyone to the punchline. Their product Sativex uses a nebulizer delivery method to administer ratios of cannabinoid/cannibinols for a variety of conditions. Extracted straight from analogues or inverse agonist etc. Currently on the market in up to 10 countries now.In final phases in the US for an FDA indication of cancer pain.

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