Not getting high off ketamine

[copium7777]

The esketamine nasal inhaler (Spravato) contains a measly 28 mg of esketamine HCl (two doses of 14mg) at a per unit MSRP of $295 USD. And you're meant to use wo or three inhalers per treatment session, let's say once every two weeks, that's 52-78 devices at a cost of $15,000-23,000 per year. That's absolutely insane. $23,000 of ketamine is Tony Montana amounts of ketamine. You could sedate a small European country for like 3 months with that. Even the worst drug dealers would think twice before trying to charge $300 for a single key bump of ket.

Yes, spravato is "innovating" by using a less effective entaniomer that can be patented , and thus is making huge amounts of money off this.

However, regular racemic ketamine can be had for reasonable prices if compounded by a compounding pharmacy, and prescribed by a doctor. And you don't have to jump through all. the same hoops as with spravato.

I get a measly 300 mg/month for 60$, in an intranasal spray, but you're really paying for the labor of compounding and I think many people get far bigger doses like 1.5 g/month prescribed. If I wasnt already getting refills while. Not having a pcp and while asking a doctor that I haven't seen in person for awhile to keep refilling one of my only pain meds I'd ask for the dose to be upped as mine is fairly low. But it would probably be just as cheap at a higher dose.

The sad fact of reality is that intranasal ketamine is just not that terribly effective

Not that effective for what? In what context? It has decent bioavailability and onset and works fine for pain, depression, or just mildly tripping out a little. It's true that it's not the best ROA if you want to k hole, but that's not what everyone is going for

 

[X11400]

The esketamine nasal inhaler (Spravato) contains a measly 28 mg of esketamine HCl (two doses of 14mg) at a per unit MSRP of $295 USD. And you're meant to use wo or three inhalers per treatment session, let's say once every two weeks, that's 52-78 devices at a cost of $15,000-23,000 per year. That's absolutely insane. $23,000 of ketamine is Tony Montana amounts of ketamine. You could sedate a small European country for like 3 months with that. Even the worst drug dealers would think twice before trying to charge $300 for a single key bump of ket.

(and people are acting like this is some sort of novel innovation... I guess it's a fun fact that Trump supports people using ketamine. Wonder if he's ever K-holed?)

The sad fact of reality is that intranasal ketamine is just not that terribly effective. It's kind of against typical thinking, but my belief is that in some cases it is less harmful to use ketamine in an IM injection rather than intranasally. Yes, needles are a risk, but ketamine has a very long history of safety when given IM (and is even sold in sterile solution) meaning overall you use much less ketamine (saves you money and reduces the risk of bladder damage - which seems to be related to total dose consumed), the effects are much more profound, and your nasal mucosa don't suffer as much. You may find that you can use as little as 1/5 the dose you were previously taking to get similar effects.

I also have heard of people being prescribed ketamine as its freebase in a multi-component cream meant for topical relief of pain. One recipe was 10% ketamine, 6% gabapentin, 2% baclofen, 2% diclofenac, and 2% lidocaine. I know they are less abusable than ketamine sprays/injections, but I don't know how effective they are, and I think they are a specialty medication you'd need to have compounded. One benefit would be that I am unaware of anyone suffering bladder damage from ketamine used topically (not that it's impossible, it's just very unlikely).

I’m still not understand how DXM and other less toxic dissociatives aren’t being used in the treatment of depression.

 

[copium7777]

I’m still not understand how DXM and other less toxic dissociatives aren’t being used in the treatment of depression.

How is dxm less toxic than ketamine ?

 

[X11400]

How is dxm less toxic than ketamine ?

I haven’t heard of any brain damage or excretory system impairment from dxm as of yet. If these phenomena have been observed, then I would like to see some evidence.

 

[sekio]

Yes, spravato is "innovating" by using a less effective entaniomer

Esketamine is the more effective isomer, isn't it?

Not that effective for what? In what context? It has decent bioavailability

I don't know if I'd say 25-50% BA is "decent". Yeah, it works, but if you can give someone 1/4 the dose and have the same effect, it makes economic sense to me.

I’m still not understand how DXM and other less toxic dissociatives aren’t being used in the treatment of depression.

Of all the dissociatives, there's only been studies showing the unique antidepressant effect of ketamine. I don't know if a similar effect is observed in DXM or PCP users, for instance. We don't even know the causative factor either - other NMDA antagonists don't seem to behave the same way.

 

[X11400]

How is dxm less toxic than ketamine ?

How is dxm less toxic than ketamine ?

And with regards to ketamine and brain damage, I’m not sure that there’s any evidence with that regard to brain damage.

 

[copium7777]

I haven’t heard of any brain damage or excretory system impairment from dxm as of yet. If these phenomena have been observed, then I would like to see some evidence.

There are no in vivo studies on olneys lesions in humans in any dissociative anesthetic, including dxm and ketamine, at least at therapeutically relevant doses.

But both heavy dxm addicts and heavy ketamine addicts have damage to all sorts of bodily systems including brain.

It seems like dxm has more toxicity potential bc of how it interacts with serotonin and raises blood pressure. It can cause serotonin syndrome which is not true of ketamine. And just anecdotally sounds like the users tend to have more issues with brain damage and stuff. But I don't think there's hard evidence either way

 

[X11400]

Esketamine is the more effective isomer, isn't it?



I don't know if I'd say 25-50% BA is "decent". Yeah, it works, but if you can give someone 1/4 the dose and have the same effect, it makes economic sense to me.



Of all the dissociatives, there's only been studies showing the unique antidepressant effect of ketamine. I don't know if a similar effect is observed in DXM or PCP users, for instance. We don't even know the causative factor either - other NMDA antagonists don't seem to behave the same way.

Numerous anecdotes as well as studies have been done on the anti-depressive effects of MXE and DXM, so I’m confused as to how you don’t know about that.

 

[X11400]

There are no in vivo studies on olneys lesions in humans in any dissociative anesthetic, including dxm and ketamine, at least at therapeutically relevant doses.

But both heavy dxm addicts and heavy ketamine addicts have damage to all sorts of bodily systems including brain.

It seems like dxm has more toxicity potential bc of how it interacts with serotonin and raises blood pressure. It can cause serotonin syndrome which is not true of ketamine. And just anecdotally sounds like the users tend to have more issues with brain damage and stuff. But I don't think there's hard evidence either way

Well, ketamine is seratonergic. Maybe you mean dxm might be more seratonergic?

 

[copium7777]

I don't know if I'd say 25-50% BA is "decent". Yeah, it works, but if you can give someone 1/4 the dose and have the same effect, it makes economic sense to me.

Ketamine is fairly cheap as an end product before you price in issues like paying for specialty compounded formulations, so I really think maxing out the bioavailability and efficiency isn't the biggest deal. By decent bioavailability I basically mean you can quite easily get enough absorbed to treat pain, and depression , and certainly can get enough to get pretty high, via the intranasal route. It's also easy to use, and quick onset , and many people aren't comfortable with needles, so it makes obvious sense why this route would be preferred by doctors. Its pleasant and easy for me, using a ketamine spray intranasal.

 

[copium7777]

Esketamine is the more effective isomer, isn't it?

I think the evidence for it is weaker than the evidence for racemic ketamine. Will find some links

 

[copium7777]

I think the evidence for it is weaker than the evidence for racemic ketamine. Will find some links

This study. Published in nature which is the best journal, says r isomer is more effective in many ways, has biomarkers for its efficacy too not just subjective cognitive effects, but on the other hand they say that esketamine has more crazy psychedelic effects so maybe I would prefer that.

R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects - Translational Psychiatry

Although the efficacy of racemate ketamine, a rapid onset and sustained antidepressant, for patients with treatment-resistant depression was a serendipitous finding, clinical use of ketamine is limited, due to psychotomimetic side effects and abuse liability. Behavioral and side-effect...

www.nature.com

Either way I thought I'd read, and this confirmed that, that most of the studies for depression used the other isomer, as an example of the company behind spravato rushing this to market with not very good evidence

 

[sekio]

This study. Published in nature which is the best journal, says r isomer is more effective in many ways,

Interesting. The S-isomer is more tolerable as an anesthetic, the R-isomer is more of a recreational drug? I have only ever had racemic K, so I wouldn't know.

Numerous anecdotes as well as studies have been done on the anti-depressive effects of MXE and DXM, so I’m confused as to how you don’t know about that.

Can you provide some study references? I know there's been anecdotal reports, but I've never seen a peer-reviewed study show a similar effect to ketamine.

 

[TripSitterNZ]

S isomer is for full on tripping psychedelic zoning out. S isomer is alot more potent dose by dose than racemic and you will k hole alot faster. Racemic is the best for getting totally fucked up in the club all night long and s isomer for heavy zoning out solo trips.

 

[tacodude]

R isomer has more of the physical load and hangover essentially while S isomer effect is considered "cleaner" that doesn't linger in the body the same way giving a clean onset that doesn't really leave the physical hangover that could be considered detrimental for functioning needs yet desirable for recreational... At least thatbbn is my understanding and experience

 

[nznity]

IT IS WAY BETTER for your body to shoot ketamine.

You still get the same toxicity at the same dose, why waste most of your high up your nose omg...

Save a bladder, use a needle IMO.

hahahaha that's some nice HR right there CH XD

 

[sekio]

I know this is a minor complaint (and shows my soft hippy dippy liberal underbelly) but does it concern anyone else the sheer amount of plastic waste the Spravato inhalers must produce when used on any scale? Between the two or three inhalers per person per session and the packaging they are shipped in, how wasteful can they get?

And to top it all off I'm sure that the inhaler, once used, must be disposed of as medical waste containing controlled substance residues. They won't even consider recycling them, despite presumably being made entirely of recyclables. Because sterility. (Juice cans and liquor bottles are OK to have human saliva in though)

I wonder if there will be reports of people gathering a few hundred used Spravato units, autoclaving them, and recovering the residual esketamine? Something to aspire to as a hobby.

 

[tacodude]

Total fucking waste... They could provide vials with leur lock rigs and atomizer nasal spray attachments if they didn't feel the need to measure the doses out for us and actually could trust us to measures our own dose

 

[sekio]

I gues it's bad PR to have a white-coat straight-laced psychiatrist hand you a Chemical Brothers CD case with a couple lines racked up on it and a rolled $20 bill...

 

[Vastness]

Also, check that maximum dose again. I think around 500mg is for IM pre-surgery anesthesia.

I don't think that's necessarily the case - from my reading it seems such doses are prescribed for pain in palliative care, although for sure, it's not common, definitely not via nasal spray, I agree the prescribing of such a huge dose via nasal spray in this case is very unusual. Here's another source that quotes 500mg/day as a max daily dose - https://www.palliativedrugs.com/download/08_09_ketamineguidelines.pdf - although of course in most cases like this, ie, palliative care, presumable the dose would be administered by injection, by a doctor, with constant monitoring, as the patient would be an inpatient in a hospital. In these situations probably other considerations as far as potential harm would be simply outweighed by the short term relief of suffering that ketamine might provide.

Numerous anecdotes as well as studies have been done on the anti-depressive effects of MXE and DXM, so I’m confused as to how you don’t know about that.

Can you provide some study references? I know there's been anecdotal reports, but I've never seen a peer-reviewed study show a similar effect to ketamine.

I had a look and found a couple of studies - although only 1 on DXM that was conducted in humans, and no human studies for MXE. Hardly a convincing body of evidence of course, but somewhat interesting.

Evaluation of dextromethorphan with select antidepressant therapy for the treatment of depression in the acute care psychiatric setting

In this first retrospective chart review of DXM in depression in an acute care psychiatric setting, there was no difference in time to improvement of depressive symptoms in patients receiving DXM and those receiving standard antidepressant therapy. However, due to the aforementioned limitations, future studies should be conducted. Due to pharmacologic similarities between DXM and ketamine and results from a proof-of-concept trial, DXM may still offer promising benefits to patients with depression.

Methoxetamine produces rapid and sustained antidepressant effects probably via glutamatergic and serotonergic mechanisms.

MXE produced antidepressant effects [in mice] 30 min after treatment that persisted for 24 h. Both NBQX and ketanserin blocked the antidepressant effects of MXE in the FST. MXE also altered hippocampal glutamatergic- and serotonergic gene expressions. These results suggest that MXE has rapid and sustained antidepressant effects, possibly mediated by the glutamatergic and serotonergic system.

DXM despite the fact that there is one study in humans seems less promising, on the whole, since it is obviously well known to have a much larger potential for harm than ketamine. MXE I wouldn't be too surprised if it had some antidepressant benefits in humans - obviously many people do report this anecdotally and it is a very similar compound to ketamine pharmacologically. As it stands though, unsurprisingly, again, ketamine is the only such compound to have a truly significant body of research behind it.