Thread by @mariliacout

@EaterSouls @PerfumeFlogger @Khanjae4 1/ This is going to be a thread. First, it's been a while that the research community had its eye on ketamine (50% of ketamine is esketamine, one of its racemic forms). Its biological activity went way beyond anesthesia. But lets stick to depression for now.

@EaterSouls @PerfumeFlogger @Khanjae4 2/ Since the first pharmacological treatment for depression was approved (the monoamine oxidase inhibitors MAOI), a theory about the molecular mechanism of altered mood states was adopted: some monoamine deficiency (particularly serotonin).

@EaterSouls @PerfumeFlogger @Khanjae4 3/ The problem is that this is not how the scientific method works. Because a drug that blocks reuptake of serotonin or inhibits its oxidation is *associated* with an anti-depressant effect, it doesn't mean that the cause was a lack of serotonin.

@EaterSouls @PerfumeFlogger @Khanjae4 4/ "Association" and "cause" are two completely different things. Insisting on the wrongly adopted theory to develop new drugs was expected from the pharmaceutical companies: it's their job to do that. The problem is that they also fund research.

@EaterSouls @PerfumeFlogger @Khanjae4 5/ The wrong theory was a nice shortcut and a very profitable one (many, many trillions of dollars). For over 50 years, we've been mis and under-treating patients because of that.

@EaterSouls @PerfumeFlogger @Khanjae4 6/ It's no surprise that it took so long to admit mass funding research into ketamine. It required a paradigm shift.
sciencedirect.com/science/articl…

@EaterSouls @PerfumeFlogger @Khanjae4 7/ To make a (very) long story short, what ketamine does is promote a rewiring of neural connections at the cortical level instead of acting on serotonin, dopamine and norepinephrine reuptake, oxidation or whatever. But that requires a *whole new theory about depression*.

@EaterSouls @PerfumeFlogger @Khanjae4 8/ It gets better. Unless they manage to fool the public opinion, ketamine will force a new perspective on opioids and their receptors (which are many and involved in different things).

@EaterSouls @PerfumeFlogger @Khanjae4 9/ Because ketamine (and esketamine) action does involve opioid receptors.
jamanetwork.com/journals/jamap…

@EaterSouls @PerfumeFlogger @Khanjae4 9/ Of course it involves risks, many of which we don't know yet. I got news for you: no amount of clinical trials will EVER reveal all the risks. It only identifies obvious lethal risks. The rest is up to time and widespread use.

@EaterSouls @PerfumeFlogger @Khanjae4 10/ I'll tell you what else is high-risk: not treating resistant depression, bipolar disorder or PAIN. It causes something called DEATH by suicide. And the good thing about ketamine/esketamine is that it is the ONLY medication with short-term effect.
focus.psychiatryonline.org/doi/abs/10.117…

@EaterSouls @PerfumeFlogger @Khanjae4 11/ (sorry, the double "9": 9/ Because ketamine (and esketamine) action does involve opioid receptors.
jamanetwork.com/journals/jamap…

@EaterSouls @PerfumeFlogger @Khanjae4 12/ So yes, it's a great choice. Why? Because the percentage of depression patients that are either totally resistant to other treatments or partially so is immense (and under-reported). The theory was WRONG.
jamanetwork.com/journals/jama/…

@EaterSouls @PerfumeFlogger @Khanjae4 13/ Another one:
link.springer.com/article/10.100…

@EaterSouls @PerfumeFlogger @Khanjae4 13/ But guess what happens when the USPTO (US patent and trademark office) approves a drug for "new use"? That's right: it gets patent protection. And with it, a many-orders-of-magnitude boost in price. It will need measures to make it affordable.
icer-review.org/wp-content/upl…

@EaterSouls @PerfumeFlogger @Khanjae4 14/ Another one:

link.springer.com/article/10.100…

@EaterSouls @PerfumeFlogger @Khanjae4 15/ As I see it, it will be expensive and complicated to get. I'm sorry about you veterans especially because of the "super tapering" slash zero-prescription policy adopted by the VA.
va.gov/painmanagement…

@EaterSouls @PerfumeFlogger @Khanjae4 16/ As I have profusely argued in several threads and articles, the American "opioid paranoia" is a product of political corruption and Transnational Criminal Organization success in closing the chain of production and supply.
wakelet.com/wake/7020fb92-…

@EaterSouls @PerfumeFlogger @Khanjae4 17/ Once the Triad finally optimized synthetic opioid production to worldwide distribution levels, it makes total sense to push patients to the black market. Oh, wait - did you think it was "big pharma" and dirty physicians, like the Trump administration wants you to believe?

@EaterSouls @PerfumeFlogger @Khanjae4 18/ Nooooooo.... the original American "opioid crisis" was actually caused by your lack of a National Public Health System. So patients were kicked out of hospital beds too soon, with a generous prescription of opioids.

@EaterSouls @PerfumeFlogger @Khanjae4 19/ That has been going on for the past 40-50 years. It CANNOT be solved except by adopting what all other democratic countries have: a National Public Health System. And it's not either/or: it lives beautifully with private providers.

@EaterSouls @PerfumeFlogger @Khanjae4 20/ Now that we put the opioid-lie aside it's time to face the American suicide crisis. And that will take a long time to manage. It starts with the absence of a National Health Care system and social networks.

@EaterSouls @PerfumeFlogger @Khanjae4 21/ And we can't forget your evangelicals. They do a great job at covering up sexual violence and mental suffering. The USA has the highest rate of sexual violence among certain groups that are pretty low risk in EVERY other democratic country. That's a handful, isn't it?

@EaterSouls @PerfumeFlogger @Khanjae4 22/ Well, with esketamine and naltrexone (opioid receptor blocker) sprays, first responders may be able to handle several thousands of suicides. Patients may live lives with less mental suffering. It's something, I think.

@EaterSouls @PerfumeFlogger @Khanjae4 @threadreaderapp unroll