Behind the Buzz: How Ketamine Changes the Depressed Patient's Brain | Hacker News Reader

Behind the Buzz: How Ketamine Changes the Depressed Patient's Brain

scientificamerican.com

81 pointslaurex42 comments

I am surprised that the piece does not mention last year's finding that the anti depressive effects may be linked to the opioid system:

https://med.stanford.edu/news/all-news/2018/08/ketamines-ant...

The linked scientific American piece only mentions the glutamate system.

Does anyone know whether the opioid link ended up being valid?

The short answer is that no one knows. It's likely we won't know for a long time.

As for this study, a side-effect of naltrexone is depression. That would seem to me to make it unsuitable to use in a study with ketamine.

Relevant:

Caution Against Overinterpreting Opiate Receptor Stimulation as Mediating Antidepressant Effects of Ketamine

https://www.ncbi.nlm.nih.gov/pubmed/30818991 https://sci-hub.tw/10.1176/appi.ajp.2018.18091061r

Like all complex pathologies, it is multifactorial, there is no single pathway

Ketamine is an NMDA antagonist, and there are other drugs in this class being developed as antidepressants. AXS-05 was granted "breakthrough therapy" status by the FDA and combines the NDRI bupropion with dextromethorphan which has effects similar to ketamine's. We really are in exciting times for antidepressants.

> dextromethorphan

Cough medicine? I'm astonished. I guess kids drinking NyQuil weren't just doing it for the alcohol.

When I was younger, I've done dextromethorphan quite a bit, and while I was mostly doing it for the dissociative effect, it always had the side effect of lifting my mood for a couple of weeks afterwards

Well yeah, DXM is the drug people are drinking cough medicine for. Its called "Robotripping" when you take it. I believe most people just try to drink the cough medicine that is straight dextromethorphan, like robitussin, when taking it. The other ingredients, like the expectorant, in stuff like Nyquil would probably just make you sick drinking a lot of it... and i doubt the amount of alcohol in it is enough to have any noticeable effect.

I wish I could feel what others feel when they try a certain drug. I've taken ketamine recreationally and I mostly just feel a numbing sensation similar to having a couple drinks that wears off fairly quickly. I don't totally get the appeal as a party drug from that perspective.

I never really understood it either, other than mixing it with MDMA which was like launching into outer space.

I did professional ketamine treatments twice. The first session was over four weeks, with weekly injections given for an hour each session.

It helped tremendously for about 4 months. Then my depression kicked in again, and I enrolled again. This second round I cut off after only two sessions. It was too intense. The first one was exciting and psychedelic. The second was psychedelic but... uncomfortable? It’s hard to describe. I didn’t enjoy it, and stopped after only two.

I can see the possibilities for it, and it did help, if only for a while. But that brief respite from the constant “you’re a shit, James, no one loves you and they never will,” that voice was silenced for a while.

And it was heaven.

I know this sounds strange, but recently I ended up with a prescription for Suboxone, and it has completely cured me of lifelong debilitating depression. I really hope more research is being done. Within the span of one year my career has gone from being on the rocks to skyrocketing success, all because the crushing weight of depression has been lifted from my shoulders. YMMV.

Yeah, it didn’t work for my wife :-(. We were hopeful.

Ketamine is among common psychedelics the most likely to lead to "bad trips", unfortunately. My anesthesiologist friends don't have much good to say about it (but of course they're not concerned with the anti-depressive effect).

SWIM always has very pleasant claymation visuals with K, as opposed to the usual soul-shredding ego death from LSD.

However prolonged use can cause bladder damage and (for the extreme mainliners) k-holes seem correlated to suicidal ideation, so as always tread carefully.

I doubt writing SWIM would ever work so I don't think you need to bother with it.

SWIM disagrees on grounds of plausible deniability, but you do you.

(There is the persnickety universe inside one's head, and there is actual experience. Please speak from experience or remain silent.)

You didn't do enough. At the dose I tried I don't see it as a party drug either, I didn't move.

Ketamine is unique in that it is very much a different drug at different doses. Do it again and this time do much more.

I've said this before in regards to other substances on this board.

Please, please, please do your own research or talk to a professional before embarking on such things. Think for yourself and don't take advice from random people on any forum. You're too important.

> I don't totally get the appeal as a party drug

it's just not a party drug. Best appreciated in a dark quiet room with someone taking care of the body you leave behind.

10-20ml = drinks at a party 20-40ml = clubbing, party drug 40-70ml = in another dimension 70-150ml = khole

You need to do more, triple the dose

Zarate is quoted in the article and is one of the authors of Ketamine for Treatment Resistant Depression. A great book that will give you quite a bit of background.

I take ketamine with a prescription at home. If anyone here knows someone who is going to an IV clinic I can give out my doctor's information. He's taking new patients and is okay with me giving out his e-mail.

When you're depressed it's easy to overlook the financial implications of spending $500 for an IV. And then you end up in financial trouble. I tried to contact Brooke, but I think I may have been too late...

https://www.ketamineadvocacynetwork.org/forums/topic/despera...

What form do you take the drug? IV? Powder?

Could you please describe the process and the dosage?

I take 250mg sublingual. I put it under my tongue at night while listening to music.

Can you describe your experience with it (how resistant your depression was, how effective ket is, what the short and long term effects you’re noticing are)?

I had tried several anti-depressants before ketamine. I feel a lot better and have much more energy.

A side effect while taking the drug in the short term is dissociation. As tolerance builds that eventually goes away.

I'm having some issues with sleep and productivity at night.

Is that a standard dose? Why do you take it sublingually instead of snorting it?

I have taken ketamine recreationally...that is quite a high dose at least from my experience, though I've never though to take it sublingually.

There isn't a standard dose. Far too early for that.

I take it sublingually because that's what my doctor prescribes.

Doc here. Sublingual application bypasses the liver, which removes drugs from the bloodstream. Same reason why nitro is applied here.

That’s interesting. What’s the mechanism for that? Uninformed intuition would lead one to think there would not be a difference.

It's a function of anatomy. The sublingual veins drain into the jugular and then vena cava. For drugs this avoids the first-pass effect, which is exploited when giving nitroglycerin for angina pectoris. Other ways to achieve this are suppositories (rectal veins) and intravenous (i.v.) or intramuscular (i.m.) injection.

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

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

Some of the drug will always be absorbed orally and travel to the liver through the the portal vein.

The liver will eventually remove ketamine from the bloodstream regardless of which route is used.

That's my understanding at least.

I take 50mg weekly, insnuflation, but suddenly considering sublingual. It's rid me of a lifetime of persistent ideation that had become a daily burden. It seems like I need way less than clinics give people

250mg seems exceptionally high (in reference to the OP's response below). The esketamine nasal spray that was just approved contains only 28mg per dose (1-2x/week). I don't know if that's because you need more if you take it sublingually. Snorting/nasal is almost certainly the most efficient/most effective way to take it.

1) The different ROAs have different bioavailability.

2) Ketamine is cheap. Convenience should be prioritized over efficiency.

It's not just about the expense, ketamine can damage liver and kidneys, and reduce iron uptake. Efficiency, in this case, is more about harm reduction than expense

I've read some of the most important papers and books and have never come across this. Please post a source.

Depression is a very serious illness and ketamine is a very safe drug. We need to give people more options.

Are you concerned about potential long term side effects of the drug?

Like MDMA, which has also garnered attention from researchers for potential medical benefits, I was under the impression K had nontrivial neurotoxic potential if abused.

Yes, and that's why I take small doses infrequently. I took a few months off because I was doing that much better, but the intrusive thoughts came back. But overall. No, my brain is fucked and tells me to kill myself every day; I don't need that abuse. Those brain cells deserve to die. More serious take: my quality of life is improved by an order of magnitude. I didn't want to survive another decade in that condition, but now I do. That's worth the risk

That is amazing, I've read quite a bit about this and did not know that anyone was prescribing for home use. Roughly how much does it cost? Did you receive initial treatment in a clinic and then transition to home use?

The prescription costs $80-$100 a month but since I'm out of state and there are other costs like flights, shipping, etc it's more expensive. If you live near Maryland you have an advantage here. I am paying under $3000 a year.

Before I found my doctor I was being mercilessly ripped off by IV clinics. I've been to 3 different clinics around the country. My doctor agrees that IV clinics are spreading pseudoscience.

Any doctor can prescribe ketamine off label. It's one of the safest drugs out there and has a lower addiction potential than Adderall (according to DEA scheduling).

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