If I take dextromethorphan (NyQuil) then four or so hours later I’m back to feeling like I did before I took it.
Just to be clear, I’m asking about taking ketamine under the supervision of a doctor. Not recreationally.
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I was told by a psychiatrist that the ketamine treatment is ongoing. You need to keep going back to maintain the effects so I don’t know how long term the effects are. Psilocybin and even LSD have been known to have long term effects.
It may or may not be BS, but the way i understood it is that the ketemine has a temporary side effect that makes your brain a bit more malliable(easier to change) .
I was told a weekly supervised ketemine session would be immidietly followed by a therapy session. The ketemine is supposed to make it easier to permanently change how your brain processes input in a more healthy way, by not taking nearly as many repetitions to rewrite old pathways.
So the effects of the drug is temporary, but any changes you make to your brain while under the effects of the drug may be longer lasting.
Think of it like preworkout supplements but for therapy. NMDAR antagonists induce a dissociative state that gives you that kind of trippy, hallucinogenic feeling. That state (also possible through other drugs, notably recreational mushrooms) is associated with increased neuroplasticity, the ability of your brain to change existing neural pathways and form new ones.
Now you can take a drug like that, sit in on your couch until it wears off, and you’ll be the same as you were before. *But* if you take that drug and then go into a therapy session where you’re actively trying to train yourself out of harmful thought patterns, it makes it much easier to build up new pathways and people see faster, lasting progress in treating things like PTSD and depression. The drugs don’t do anything to fix you on their own, they just create more potential for change should you choose to use it.
The other important distinction is that while there are lots of drugs that induce neuroplasticity to some degree, not all of them are gonna be a good fit for a therapy setting – you need something that will give you the goldilocks level of neuroplasticity to be helpful but not enough other side-effects like nausea, drowsiness, confusion, seizure risk. NyQuil specifically won’t produce ketamine’s dissociative effects unless you take crazy high doses and that comes with a risk of psychotic breaks and a bunch of other kinda terrifying side effects.
The brain is an incredible organ that can literally delete or hide memories because they are so traumatic. Most people also have a warped sense of self (ego) and ignore, distract from, refuse to accept or overlook the root causes for trauma/depression.
Ketamine is a dissociative that melts your ego away leaving nothing but facts and the truth. Biases and defense mechanisms are temporarily blocked. Most pyschadelics also have the same affect – you hear alot of people “giving in” to a trip when on acid/mushrooms/dmt.
So let’s take a normal person who was sexually abused as a child. And let’s say this person refuses to accept it, refuses to think about it or process it. This will likely result in negative behaviour, that could result in something like a drug addiction.
That person then refuses to accept they have a drug problem so overconsume drugs leading to health issues. The health issues get worse over time resulting in decreased energy or chronic fatigue. The chronic fatigue results in being withdrawn and losing friends and performing worse at work.
That person will likely blame others or bad luck for everything because that is easier to accept. They’ve created a warped sense of reality that will likely remain unchallenged forever.
See how a single event can cause a chain reaction?
Ketamine breaks the chain at the first link of trauma. You are forced to see the event, or think about it whilst being incapable of deflecting from the truth. That realisation will remain forever even after the effects of the drug have worn off.
Combine this with therapy and now the person can unpack the chain of events that got them to clinical depression or drug addiction.
Think of Ketamine like a truth serum for your brain.
Ketamine is a very interesting drug. There are a number of different effects induced by ketamine that may (or may not) be related.
First, you have the sedative effects that are mediated through NMDA.Then you have the so called “dissociative” effects. Dissociation is usually mediated through the serotonin system (think LSD, ecstasy, ayahuasca, etc), but ketamine doesn’t interact with the serotonin system. This effect is likely related to the sedative mechanism but is achieved at lower doses.
You also have analgesic (painkilling) effects, which could be mediated through the NMDA receptor, mu opioid receptor, the sigma receptor, or all/any/none of the above.
Then you have the rapid acting and long term antidepressant effects. This is the one we know least about because we generally have a poor understanding of how antidepressants work beyond their pharmacological binding profile. It’s weird too because we typically think of serotonin, norepinephrine, and occasionally dopamine as the mediators of depression and subsequent treatment. There are antidepressants that work through NMDA (i.e. gabapentin), but we don’t typically think of NMDA as being the main player in depression.
So what makes the effects of ketamine different than dextromethorphan? Well, the first one is potency. Ketamine is about 10,000 times more potent at NMDA than DXM is. But beyond that, ketamine is a “dirty” drug. That doesn’t necessarily mean that it’s bad, it just means that it binds at many receptors and isn’t super specific to just one. It interacts with at least 20 different receptors, and it’s metabolites could also interact with other receptors as well. (Of note, this is true for DXM as well, but for different receptors and at different potencies.) Because of this, it’s really difficult to pin down exactly what’s going on with ketamine. There is a lot of research looking into ketamine right now, including whether the analgesic and dissociative properties are related (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572586/), whether the dissociative and antidepressant effects are related (https://www.nature.com/articles/s41467-020-20190-4), and so on.
So, in brief, we don’t really know what makes ketamine different than other NMDA antagonists with respect to depression, but we’re trying to find out.
From what I’ve seen the effects of keta one treatment for depression does seem to be time limited and repeat treatments after the initial round are often necessary. If there’s a remission of depression then it’s discontinued until symptoms recur which is true of most antidepressants except for ECT (due to the more medically intensive care needed for ECT).
To the second point of your question, Dextromethorphan is [hypothesized the have antidepressant properties like ketamine](https://www.sciencedirect.com/science/article/abs/pii/S0306987711000545). The hypothesis is preliminary and needs confirmation though.
Edit: Also, just a heads up for anyone coming in to this thread, there’s commenters talking about *how* ketamine works and it’s all wildly speculative bullshit with no foundation in any theory of the mechanisms I’m aware.
One commenter is talking about ketamine as a primer for therapy but therapy is rarely done in immediate conjunction with ketamine treatments and the efficacy of ketamine for depression is independent of psychotherapeutic counseling.
Another commenter posits ketamine efficacy comes from egoic alteration which just isn’t supported or theorized in anything I’ve seen concerning the treatment.
I went through a Ketamine injection treatment for about a year when I was battling chronic depression as I was treatment resistant to all other forms of treatments. It was the only treatment that actually worked and helped me to permanently cure my depression; and for ultimately being the only treatment that saved my life.
It essentially allows you to reboot your brain and build new neural pathways that aren’t rooted in the deep seated negative thinking. There’s a lot of studies done around it, but I wouldn’t say that any of them are heavily peer-reviewed or conclusive enough to make a scientific conclusion on. However, from my own anecdotal experience with it, it truly is an amazing treatment if other forms of treatment have already been exhausted.
The proposed effect is not unique to ketamine at all? Other nmda antagonists including pcp and dxm have been examined, ketamine just seems to have a preferable safety, tolerability and efficacy profile
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