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InvisibleMostly_HarmlessM
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Sheep on ketamine study reveals what happens when you fall into a "K-hole"
    #26748346 - 06/16/20 06:47 AM (3 years, 9 months ago)

https://www.inverse.com/mind-body/ketamine-k-hole-effects-brain

https://doi.org/10.1038/s41598-020-66023-8

Quote:


Humans who descend into a "k-hole" describe an intense state of oblivion that’s not unlike a near-death experience. It's what happens when one takes a high enough dose of ketamine that they feel what's described as a separation of mind and body.

Scientifically speaking, we didn’t know much about why ketamine causes that to happen. But thanks to some sheep in England who accidentally fell into a k-hole, researchers are very close to understanding.

A general anesthetic once popular as a rave drug, ketamine has gained traction as a novel tool for treating depression. It's known for its fast-acting soothing of suicidal thoughts, and the creation of new connections in the brain that might sustain anti-depressant effects — in 2019, a ketamine-based nasal spray became approved to alleviate treatment-resistant depression. It's far from a perfect solution, but new research has also shown it also has the potential for combating alcohol abuse.

A study published Thursday in Scientific Reports shows that ketamine can also substantially change the way brain waves work.

This helps explain the drug's dissociative effects, including the experience of falling into a k-hole. When sheep were given 24mg/kg of ketamine, the electrical activity in the cerebral cortex completely stopped. (The study reports that this is on the high end of the anesthetic use range. Dosages for recreational ketamine vary).

Jenny Morton, the lead study author and a professor of neurobiology at The University of Cambridge, tells Inverse that there probably was some brain activity happening in the deep brain — the sheep were still breathing, after all. But the cerebral cortex, which is “usually very active, had just gone very quiet.”

“The activity in the cortex in some of the sheep stops completely for a short time. But the brain is NOT dead or damaged,” she explained by email.

A few minutes later, the sheep brains were functioning normally again, Morton added. The study suggests that this strange moment — when activity seemed to cease — might represent what happens in the brain after a k-hole fall.

The brain on ketamine – The study was actually never intended to plumb the neurological depths of the k-hole. It was designed to be an investigation of therapeutic drugs, like ketamine, on the brains of those with Huntington’s disease. Sheep are often used as models of Huntington’s disease in research. That drug just happened to be ketamine in this case.


An "EEG hole" or, likely, a K-hole, as seen in one sheep in the experiment.

Over the course of several months, the researchers gave 12 sheep escalating doses of the drug from 0.5 mg/kg to 24 mg/kg. They also took EEG readings of their cerebral cortices to see how the brain's electrical activity matches up with their drug experiences.

At the lower doses, they found that the brain goes through three phases while on ketamine. Sheep entered the first phase “shortly” after receiving ketamine, the paper notes. They lost the ability to move, but their eyes stayed open (they could also blink).

Then, the sheep entered the second phase: They still couldn't move but were able to “respond” to touch or movements in front of them. In the third phase, they were conscious and alert with “awake levels” of EEG activity, though they didn't move around.

However, the crucial patterns of brain activity were seen during the second phase.

When we’re awake, the activity in the cerebral cortex usually covers a wide band of frequencies or “waves” says Morton. You can think of that as a conversation in a busy restaurant. Things seem chaotic while lots of information is being exchanged during conversations at different tables.

During the second phase of a ketamine high, the team observed oscillations between lower frequency theta waves and higher frequency gamma waves. That’s like having groups of tables performing a call-and-response to one another in unison, Morton says. There's a lot of talking, but not a lot of information being exchanged.

This “oscillation of oscillations,” or pattern of brain activity, is probably responsible for the dissociative experiences of ketamine, even before falling into a k-hole. The brain is processing reality and exchanging information, in a uniform but very different way.

In turn, the six sheep who received the highest doses of ketamine had very different patterns of brain activity shortly after getting dosed. In five of the sheep, after two minutes, their brain activity seemed to shut off."

“The cortex is the part of the brain that is essential for thinking and decision making. We speculate that if ketamine causes a cessation of EEG activity in the cortex in humans, that this feeling of insensibility would result,” says Morton.

Sheep brains and human brains are far from perfect parallels, and the team was only imaging the cerebral cortex. There could be far more complex processes that underpin the experience of ketamine.

We already know that ketamine works by inhibiting the action NMDA receptors in the brain, which is one way it causes a dissociative state. That’s one reason it works as anesthesia, but whether that’s the mechanism that causes its fast-acting effects on depression is currently out for debate.

Morton's work suggests that this oscillating behavior between two brain waves continues even after the sheep recovered from sedation (or at least appeared to). That adds yet another layer of complexity, suggesting that the drug's effects could persist in the brain after sheep appear to wake up.

This study is also another demonstration that we still don’t know everything about how ketamine works — especially when it causes the cerebral cortex to go quiet.

Quote:

Abstract: Ketamine is a valuable anesthetic and analgesic that in recent years has gained notoriety as a recreational drug. Recently, ketamine has also been proposed as a novel treatment for depression and post-traumatic stress disorder. Beyond its anesthetic actions, however, the effects of ketamine on brain activity have rarely been probed. Here we examined the cortical electroencephalography (eeG) response to ketamine of 12 sheep. Following ketamine administration EEG changes were immediate and widespread, affecting the full extent of the EEG frequency spectrum measured (0–125 Hz). After recovery from sedation during which low frequency activity dominated, the EEG was characterized by short periods (2–3 s) of alternating low (<14 Hz) and high (>35 Hz) frequency oscillation. This alternating eeG rhythm phase is likely to underlie the dissociative actions of ketamine, since it is during this phase that ketamine users report hallucinations. At the highest intravenous dose used (24 mg/kg), in 5/6 sheep we observed a novel effect of ketamine, namely the complete cessation of cortical eeG activity. this persisted for up to several minutes, after which cortical activity resumed. this phenomenon is likely to explain the ‘k-hole’, a state of oblivion likened to a near death experience and keenly sought by ketamine abusers.








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InvisibleThe Thing
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Re: Sheep on ketamine study reveals what happens when you fall into a "K-hole" [Re: Mostly_Harmless]
    #26748384 - 06/16/20 07:25 AM (3 years, 9 months ago)

😶

Edited by The Thing (08/17/20 07:46 PM)

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Offlinegolden-student
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Re: Sheep on ketamine study reveals what happens when you fall into a "K-hole" [Re: The Thing]
    #26748637 - 06/16/20 09:49 AM (3 years, 9 months ago)

Likely due to the doses used.

Not sure what the LD50 is for ketamine but you'd have a hard time as a researcher obtaining ethics to use very high doses (taken from the abstract - highest intravenous dose used (24 mg/kg)) in human research.

Pretty interesting finding though.

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InvisibleThe Thing
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Re: Sheep on ketamine study reveals what happens when you fall into a "K-hole" [Re: golden-student]
    #26748706 - 06/16/20 10:47 AM (3 years, 9 months ago)

😶

Edited by The Thing (08/17/20 07:46 PM)

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InvisibleKimble
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Re: Sheep on ketamine study reveals what happens when you fall into a "K-hole" [Re: The Thing]
    #26748731 - 06/16/20 11:05 AM (3 years, 9 months ago)

I'm about 75kg and I've had 1.8g doses of ketamine. I mean that is full khole territory but it's pretty safe. 24mg/kg isn't gonna kill anyone.


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Invisibletyrannicalrex
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Re: Sheep on ketamine study reveals what happens when you fall into a "K-hole" [Re: Kimble]
    #26748810 - 06/16/20 12:03 PM (3 years, 9 months ago)

Quote:

Kimble said:
I'm about 75kg and I've had 1.8g doses of ketamine. I mean that is full khole territory but it's pretty safe. 24mg/kg isn't gonna kill anyone.



You don't know that for sure.


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OfflinePizzaN8thegr8
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Re: Sheep on ketamine study reveals what happens when you fall into a "K-hole" [Re: tyrannicalrex]
    #26749056 - 06/16/20 01:49 PM (3 years, 9 months ago)

I actually am gonna test this sheep study out on myself for "human testing" 😂😂 Ive messed with it here and there and i handle a lot of things in my line of work... I acquired some extra K and its very high quality, i have a triple decimal 'jewelry' weighing scale that i use for measuring DMT doses that ill use to take precise doses with, this post had inspired me to keep it for myself, I will reply with results when able to lol

Edited by PizzaN8thegr8 (06/16/20 01:51 PM)

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Offlinegolden-student
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Re: Sheep on ketamine study reveals what happens when you fall into a "K-hole" [Re: Kimble]
    #26749808 - 06/16/20 06:36 PM (3 years, 9 months ago)

I should have clarified; in order to obtain ethics you would need to convince the review board that there is little risk to the research participants.

While I can definitely accept that humans could tolerate that dose and not die, I think you would probably have a hard time convincing the ethics squad that it'll be fine to send it without having a decent body of evidence to suggest otherwise.

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InvisibleHolybullshit
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Re: Sheep on ketamine study reveals what happens when you fall into a "K-hole" [Re: Mostly_Harmless] * 1
    #26750805 - 06/17/20 06:22 AM (3 years, 9 months ago)

They are using sheep because they are investigating Huntington's Disease, which sheep are a model for. This presented information has little to do with the original goal of the researchers, they wouldn't use it on humans because they aren't investigating ketamine.

But even if they were, ethical concerns would keep them from dosing humans at such high levels IV. This goes beyond the risk of death, of which there is almost none as the LD50 of ketamine is something like 600mg/kg...there are concerns about toxicity, effects on ones neurology, and even the load such a dose would put on ones psyche. It might not be such a leap if they were using IM doses, but thats just too high for IV to be easily justified by the data gained.

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InvisibleKimble
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Re: Sheep on ketamine study reveals what happens when you fall into a "K-hole" [Re: tyrannicalrex]
    #26750814 - 06/17/20 06:30 AM (3 years, 9 months ago)

Quote:

tyrannicalrex said:
Quote:

Kimble said:
I'm about 75kg and I've had 1.8g doses of ketamine. I mean that is full khole territory but it's pretty safe. 24mg/kg isn't gonna kill anyone.



You don't know that for sure.





No, you are absolutely right. I really don't know what I'm talking about and i should not pretend to. All of my experiences are anecdotal and i should leave it to the experts. See this is my issue with spouting off opinions online.


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OfflineFractal420
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Re: Sheep on ketamine study reveals what happens when you fall into a "K-hole" [Re: Kimble]
    #26762269 - 06/21/20 05:09 AM (3 years, 9 months ago)

Man, that is some nothingness (brain activity)

As for lethal dosage, I have heard something like several grams at a time, if I recall correctly

But apparently 5g+ daily will give almost anyone bladder damage relatively quickly (if they keep using 5g a day, that seems to be the event horizon)

From an article I was checking out.
But low-moderate doses seem to be safe as far as organs


--------------------
Dreaming of That face again.
It's bright and blue and shimmering.
Grinning wide
And comforting me with it's three warm and wild eyes.

Prying open MY third eye


Edited by Fractal420 (06/21/20 05:15 AM)

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InvisibleHolybullshit
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Re: Sheep on ketamine study reveals what happens when you fall into a "K-hole" [Re: Fractal420]
    #26762684 - 06/21/20 10:29 AM (3 years, 9 months ago)

~600mg/kg from what I've read, but I don't know if that applies to IV. Either way, IV or not, dying from ketamine isn't easy to due...but imagine the emotional damage that someone drug naive not seeking such an experience could suffer at such dosages, I wouldn't worry about bladder damage from acute dosing but at those levels neurotoxicity would be a concern I imagine.

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OfflineFractal420
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Re: Sheep on ketamine study reveals what happens when you fall into a "K-hole" [Re: Holybullshit]
    #26773265 - 06/22/20 04:44 AM (3 years, 9 months ago)

I’d imagine so. I consider all dissociatives to “probably be neurotoxic”

But also I think when someone truly hits anesthesia, I’m not sure if they even remember anything

But perhaps just at high doses. It’s hard to say whether lower doses may even be good or whether they do some minimal damage too. I believe most/all dissos have “plateaus” and depending on where you’re aiming, I feel like the lower ones may not be all that bad (and even can lead to enlightenment and creativity, and positive personality changes) whereas high doses prolly fry you

I can’t imagine it being safe to K-hole. you are literally anesthesizing yourself, not just a sedative

ALSO: I think dissociatives are quite literally reverse opioids (like dxm vs levomethorphan) and they are two sides to the same coin. Tho obv effects are very different. But also as far as Ket and stuff as psychedelics, I feel they can never be as safe as serotonin tryps/phens but they provide this sort of numbness like an opioid on top of their hallucinogenic effects, which I feel people do get addicted to. An acid trip sometimes you just want to get through it, but dissos provide some sort of comfort (perhaps for me, anyway)

And I’ve never tried 3hopcp or anything with proven opi effects except maybe dxm


--------------------
Dreaming of That face again.
It's bright and blue and shimmering.
Grinning wide
And comforting me with it's three warm and wild eyes.

Prying open MY third eye


Edited by Fractal420 (06/22/20 05:00 AM)

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InvisibleHolybullshit
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Re: Sheep on ketamine study reveals what happens when you fall into a "K-hole" [Re: Fractal420]
    #26773755 - 06/22/20 08:20 AM (3 years, 9 months ago)

I don't know what one would experience at those levels, but obviously people can remember holing and what happens after that...there's a reason anesthesiologists administer benzo's along with ketamine, and its got nothing to do with keeping one under.

But yeah, I think we are largely in agreement that you'd have a hard time providing enough evidence to get approval for human experiments at such ridiculous dosages.

I mean, safe means different things to different people, some level of risk of doing a small amount of reversible harm is generally acceptable in human expirements...the problem is proving that's all there is.

And I don't see a lot of societal benefit coming from such experiments, so only a small level of risk is acceptable.

But just to be clear, I didn't say probably neurotoxic, I said it would probably become a concern. Obviously some risk is acceptable, and the risk grows smaller when talking about acute dosing...but at those levels, it'd be harder to provide evidence to make the argument that it isn't a concern.

I'm of the frame of mind that ketamine(I won't extend this to all disso's) is relatively safe at in large amounts if dosed infrequently, and still relatively safe(although a little less so) in moderate amounts dosed far more often. You might not agree if you're an organic eating, vegetarian, gym rat, who spends a lot of time on longecity and the only drugs you'd ever consider taking are nootropics...but compared to most recreational drugs, ketamine is about as "safe"(if not harm free) as it gets...but that doesn't mean I would feel good about the ethics of scientists conducting human experiments where they dose individuals with enough ketamine to knock out a bus full of people.

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OfflineFractal420
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Re: Sheep on ketamine study reveals what happens when you fall into a "K-hole" [Re: Holybullshit]
    #26777145 - 06/23/20 03:53 PM (3 years, 9 months ago)

I am def not that health obsessed but the cystitis thing I think is worrying, I say this all the time. If it wasn’t for that, Ket would be the safest dissociative and as safe as I thought it was back in like 2000ish

Btw, that bladder stuff applies to vet/pharm Ket also


--------------------
Dreaming of That face again.
It's bright and blue and shimmering.
Grinning wide
And comforting me with it's three warm and wild eyes.

Prying open MY third eye


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