Member- Sep 21, 2016
- 1,051
- Tinnitus Since
- 2011 - T, 2016- H, relapsed 2019
- Cause of Tinnitus
- noise-induced
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!
Hough Ear Institute's Hair Cell Regeneration Project
- Thread starter all to gain
- Start date
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.
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?
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.
This may be more of a breakthrough than FX-322.
Someone at the FDA needs to priority review this and get it going.
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.
HootOwl
Member
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...
- Dec 18, 2015
- 618
- 45
- Tinnitus Since
- 03/2015
- Cause of Tinnitus
- Noise induced, loud rock concert
Does anyone know if they plan to run clinical trial phase II also in Europe (EU), or in USA exclusively?
- Aug 28, 2019
- 1,496
- Tinnitus Since
- -
- Cause of Tinnitus
- -
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.
- Dec 18, 2015
- 618
- 45
- Tinnitus Since
- 03/2015
- Cause of Tinnitus
- Noise induced, loud rock concert
- Jun 15, 2019
- 157
- Tinnitus Since
- May 2019
- Cause of Tinnitus
- Likely infection/ear stress after walking pneumonia
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?
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.
This entire situation is FUBAR hence my desire to see us organized and screaming at people with demands.
FounderAre you serious? They owe us absolutely nothing. But more than that, don't you remember how you already wondered why they are waiting to continue the trials, and how you already received a response?
Justin also said:
Finally, JohnAdams...
Do you see many companies joining here and offering to talk to all of us like Justin has?
Do you see many companies wanting to discuss their research and future plans with us on the Tinnitus Talk Podcast?
But if you're not happy with how things are, I want to see you run ONE worthy campaign, ONE real grassroots movement.
Collect a couple hundred people and go scream at the FDA headquarters or whoever. Whatever you feel makes the most difference. That's something tangible for you to do instead of running in circles on this forum.
But for the love of god, do not come here in the threads with that attitude and potentially alienating the few researchers and/or otological companies willing to contribute.
- Oct 24, 2017
- 849
- Tinnitus Since
- 10/2017
- Cause of Tinnitus
- one-sided hearing loss (of unknown origin)
Hi there, Justin just responded to me saying he's doing his best to nail down a recording date a.s.a.p. Stay tuned!
Completely agree with @Markku, we cannot tolerate wild speculation and unfounded allegations against companies or researchers, particularly when they have demonstrated willingness to discuss and engage with the community. Let's first hear what they have to say, hopefully recording soon!
MRItechssuck
Member
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.
Maybe Streisand will remember... the way we were... before tinnitus?
She might have some spare change lost in her couch cushions.
You're a newer member, did you ever see this memorial fundraiser?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.
The idea was sound, only donors could vote what was funded. I loved the democratic nature of that.
Danny Boy did not like the BTA, but his family approved of the fundraiser, and BTA was crucial in helping with the grant call and organizing it. I talked with Danny Boy on Skype several times and I can confidently say he would have been fine with that set up (where donors make the ultimate decision of who the money is given to).
But that whole thing shows you how difficult it is to raise funds for tinnitus research. There's no magic line to celebrities' wallets - most of whom aren't very vocal about the condition to begin with.
Another good example is the Dr. Rauschecker fundraiser, where the goal first was $50K, but then it was lowered to $10K. Unfortunately, even that goal was not met.
It's with heavy heart I have to say this, but we recently lost another Tinnitus Talk member. I'm currently trying to reach out to the family to discuss what they'd like to do (if anything). There might be another fundraiser, but hopefully at least a warm memorial thread.
OK, but let's get back on topic now (we will make any related announcements when and if we can).
With regards to the Hough Ear Institute funding, the cost of phase 2 seems to be $50M-$100M according to Justin. That's a hefty amount. I'm sure we'll also discuss this funding aspect in the interview.
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.
HootOwl
Member
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?
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