Hough Ear Institute's Hair Cell Regeneration Project

Thanks for the heads up - am excited to hear the podcast! Thanks so much for organising this and all the hard work you put in!

 

Will you please ask about the dosage? I just did a rough calculation on their test data:

For a 160 lbs human that's like 20 grams per dose twice per day. Are we going to be swallowing ~40+ big pills of this stuff per day?

 

Would like an answer to this too but I doubt it will be 300mg/kg. You typically don't use the rodent intraperitoneal dose and just extrapolate to humans. Medications have wildly different doses between species.

Case in point: a 25lb dog needs the same amount of Benadryl as an adult human man to be effective and a cat sized dose of LSD famously killed an elephant once.

 

LSD is non-toxic from what I've read. I can easily see it giving the elephant a heart attack though.

Have you ever done LSD? Asking for a friend.

 

Yeah. I have. Twice. A long time ago.

I looked up the Tusko (the elephant) story again and my undergrad physiology professor had described it as a "cat dose" when actually reading the Wikipedia, it was a massive dose. So that probably wasn't the best example.

But my larger point (elephant story aside) was that toxicity and dosing varies wildly between species. To use a more common example: think of chocolate and dogs.

 

Right. That's a Paracelsus teaching, that the dose makes the poison. Irregardless, I think the elephant died from mental shock, and not the LSD itself.

Paracelsus, the "father of toxicology".

https://en.wikipedia.org/wiki/Paracelsus

 

Wrong. LSD did not kill the elephant. Most likely an overdose of 2 other drugs that are sedatives did. Although we won't know, because the experiment was messed up and the scientists did not record the exact amount used.

First of all, the dose was HUGE. "About 100-200 micrograms (.1 – .2 milligrams or about .02 mg/kg) is enough to produce major mental disturbances in people that resemble psychosis and delirium. The authors argued animals require an even higher dose to induce similar disturbances in an elephant, so they chose to inject Tusko with 297 mg of LSD, or .1 mg/kg. To summarize, this dose per kilogram is 25 times the dose needed to induce hallucinations in humans. The authors even acknowledged that this concentration of LSD in the human body would definitely cause an overdose, but based on previous research with other animals, they hypothesized that the elephant would be less sensitive to the drug."

Animals do not need a higher dose of LSD to feel effects. Just as I, with a lower dose of LSD, felt effects weighing 3x as much as a female friend.. it's all dependent on many factors. This is similar to most psychedelic substances, unlike opiates or alcohol. But the researchers didn't know about this back then. Or they had an idea but wanted to do the messed up experiment just to see what happens.

"As you may have guessed, shortly after they injected the elephant, it keeled over and started seizing. As any scientist in their right mind would predict, Tusko had overdosed on LSD. In attempt to counteract the overdose, the researchers quickly injected the animal with promazine, an antipsychotic drug. This stopped the seizures. But Tusko wasn’t recovering, so they injected him with pentobarbital, a common, short-acting barbiturate."

Both of these drugs led to the actual death, not the LSD. No one has ever died directly as of LSD by itself. Plenty of people, many famous celebrities died from barbiturates.. that's why they're not common drugs anymore. Pentobarbital is used in Missouri for inmates on death row for executions.

"This experiment was fraught with unjustified protocols and major assumptions that would not pass muster today. First, the researchers should never have started with such a high dose of LSD. Today, when researchers are testing a new drug in a new species, they start with a low dose and work their way up until they either induce the effects they are looking for or until they find that they are causing undue harm to the animal. This minimizes the risk of accidental overdose. By starting with a dose that would cause an overdose in a human, the researchers were taking a major, unnecessary risk with Tusko."

"Next, these scientists may have not taken the best approach to treating the overdose, although it is difficult to assess the validity of their protocol, because they did not explain it all that well. This brings up another important point: scientists need to record every detail of their experiments. The researchers did not explain why they used promazine, an experimental antipsychotic drug, and they did not even specify what dose of pentobarbital they used. When scientists are running experiments, they are supposed to write down everything they do so that future scientist not only can replicate their experiments, but also so that if something goes wrong, they can avoid making the same mistake again."

"There is widespready speculation that it was the Promazine which directly killed Tusko. Making the same error in dose calculation that he did with the LSD, Dr West is said to have adminitered a huge dose of promazine to the elephant, although the amount is not documented in the paper. Richard Mesco wrote to the MAPS-Forum:"As for most major tranquilizers, a well known side-effect of thorazine is orthostatic hypotension. This represents the body's inability to mount a sufficient blood pressure when standing upright to adequately perfuse the brain, and possibly even the heart. When this happens, the blood pressure drops precipitously and the person or animal may experience a syncopal episode (sudden loss of consciousness accompanied by a fall to the ground), and a cardiac tachyarrhythmia (rapid heart beat). In any case there occurs what is termed 'hemodynamic compromise.'"
MAPS-Forum, 2/22/2000"

- https://www.erowid.org/chemicals/lsd/lsd_history4.shtml
- https://www.illinoisscience.org/2016/06/lsd-and-the-elephant/

 

Woah. That's *really* interesting and way more than I was taught in (undergrad physiology) class about this case.

 

The active ingredient to the Hough Ear pill is HPN-07. It is also called NXY-059.


Why is the FDA making all of these researchers test the safety over and over again? If one trial shows it is safe why can't they use that safety data and proceed with a phase 2 trial?

 

Good question, but aren't they done with phase 1, though? I believe phase 2 is what they are aiming for next.

 

I'm pretty sure that the Hough Ear pill is going to treat all kinds of nervous system problems.

This may be more of a breakthrough than FX-322.

Someone at the FDA needs to priority review this and get it going.

 

What's going on with that stroke trial with this drug under a different name?

 

Failed.
"CONCLUSIONS:
NXY-059 is ineffective for the treatment of acute ischemic stroke within 6 hours after the onset of symptoms."
https://www.ncbi.nlm.nih.gov/pubmed/17687131

Which makes sense. Once the tissue is dead it's not going to undergo neuritogenesis.

 

https://en.wikipedia.org/wiki/Marsh_Chapel_Experiment

 

Hopefully they’ll announce phase 2 in the next couple of months (please don’t be a full year). Now that @JohnAdams has explained that this could have therapeutic value well outside the acute window I’m itching to get into the trial. And also hoping I don’t get placeboed...

 

Does anyone know if they plan to run clinical trial phase II also in Europe (EU), or in USA exclusively?

 

Can they even do that if they haven't done a phase I in Europe first?

I think a lot will depend on where they are going to get their funding from.

 

@Hazel was the podcast already recorded and if so when do you plan to publish it?

 

I don't speak for Hazel or Tinnitus Talk, but as I recall there was a scheduling issue that prevented the initial recording from taking place. I think the new goal was February or possibly March.

 

Whose fault is it that the Hough Ear pill is not being tested right now? The government? Hough Ear? What is the deal? What is the reason this isn't being tested at all right now?

 

Wouldn't their biotech partner partially be in charge of testing?

http://otologicpharma.com/

 

So then my question becomes what in the world are they doing?

 

Phase I completed in 2015... Man that sucks to read everytime.

 

These people owe us answers. They have come out and declared that they have a potential remedy for us and then radio silence for years. That's f-ed up. It's not like they are making this stuff to give to us for free. It is we whom are going to be buying it from them. We are going to be making them money.

This entire situation is FUBAR hence my desire to see us organized and screaming at people with demands.

 

GoFundMe for tinnitus research?
Maybe Streisand will remember... the way we were... before tinnitus?

She might have some spare change lost in her couch cushions.

 

To take a group of people with NIHL and give some of them the drug and some of them a sugar pill and then see what happens. Makes sense.

 

Wait I’m confused. Is it $7 million or $50-100 million for a phase 2 study? Both figures have been quoted by Justin so one is obviously a mistake, but which?