DXM as a novel antidepressant

[knockout_mice]

An open-label, flexible-dose study of memantine in major depressive disorder.

Memantine demonstrated early-onset efficacy in patients with MDD. The treatment was well tolerated. This study suggests that double-blind, placebo-controlled studies of memantine in depression are merited.

Memantine treatment reverses anhedonia, normalizes corticosterone levels and increases BDNF levels in the prefrontal cortex induced by chronic mild stress in rats.

Our results demonstrated that chronic stressful situations induced anhedonia, hypertrophy of adrenal gland weight, and an increase of corticosterone levels in rats, but did not alter BDNFprotein levels in the rat brain. Memantine treatment reversed anhedonia and the increase of adrenal gland weight, normalized corticosterone levels and increased BDNF protein levels in the prefrontal cortex in stressed rats. Finally, these findings further support the hypothesis that NMDA receptor antagonists such as memantine could be helpful in the pharmacological treatment of depression.

On the contrary:
Mechanisms underlying differential effectiveness of memantine and ketamine in rapid antidepressant responses

These results demonstrate significant differences between the efficacies of ketamine and memantine on NMDAR-mediated neurotransmission that have impacts on downstream intracellular signaling, which we hypothesize is the trigger for rapid antidepressant responses.

 

[dopamimetic]

(indeed, its primary mechanism might not involved the nmda-complex at all)

Do you have a source for this, where potential primary mechanisms are explained (just for it's use in Alzheimer's, or regardless of indication)? It is probably a somewhat potent dopamine agonist of some kind, and antagonizes 5-HT3 as well as some nACh receptors, but thought the main target would still be the NMDA complex- at least it feels like a true dissociative, albeit one that lacks psychotomimetic effects..

 

[knockout_mice]

I don't have studies for his claim, but it's hypothesised that its primary neuroprotective effect is glial cell mediated. By the way it's a 5-HT3 antagonist, not a 5-HT7.

 

[Dresden]

DXM tastes so gross. I just can't take it anymore. Even the pills, I can still taste them. It is SO nasty.

 

[AlphaMethylPhenyl]

^that's ot...but anyways that's probably largely due to guiafenasin or however you spell it. That's good. It can really fuck people up if taken at highish (note:ish) doses for even months. Let's not forget that the best model for schizophrenia is that of the NMDA antagonist.

 

[pharmakos]

still OT i know, but naw, even 99% pure DXM tastes really really gross

 

[dopamimetic]

Let's not forget that the best model for schizophrenia is that of the NMDA antagonist.

While this is true very possibly, I hope they do not repeat what they did with the dopamine model and neuroleptics - e.g. "too much DA is bad -- so let's use D2 antagonists for any psychiatric disorder". Might be rare / atypical, but I definitively have some kind of glutamate overactivity. NMDA antagonists help me function in everyday life much more than anything else, and even in high doses I've never hit any hint of psychosis. The same for DA increasing substances (granted, they get messy when dosed too high). On the other side, high potency neuroleptics (risperdal for example) -made- me repeatedly feel and behave very strange, not to say psychotic. Glutamate positive modulators like the racetams had a different, but also worsening effect, mostly increasing tense, stress etc. and negativity in general.

DXM is another story of course, but I'm quite sure it's its SNRI and possibly release activity, and / or sigma agonism that makes it dirty.

 

[serotonin2A]

Many people here seem to equate activity at sigma receptors with some type of subjective response. But I've never actually seen any conclusive evidence that sigma activation is actually psychoactive in a way that would produce intoxicating effects. Can anyone here cite any specific evidence that sigma activation actually produces any specific mental effects? I don't mean citations showing that psychoactive drugs bind to sigma receptors, because that isn't actually evidence that the sigma receptor is involved (unless the drug is highly selective).

Most of the evidence for sigma receptors having psychoactive effects was derived from the early work with PCP and benzomorphans. It is now recognized that PCP works through a different site (the PCP receptor). For the benzomorphans, it is now recognized that the stereoselectivity is wrong for the hallucinogenic response to be mediated by sigma, and their effects in humans are blocked by naloxone, which does not block sigma receptors. So is there actually any other evidence linking sigma receptor activity to hallucinations or any other effect?

 

[fatstep]

MyDoorsAreOpen posted an amazing thread of his daily life building up to him becoming an MD(I believe, I remember him saying he was an amazing candidate at his residency((shitty wording I know my mind isn't working the best right now because im nodding by accident/surprise)) but if he could possibly chime in Id really appreciate it because his thead was simply amazing. It was basically him using low-dose dxm for it's cognitive enhancing effects and possibly as an antidepressant for him, cant quite remember if he was using it as an antidepressant but I seem to recall that was part of it as well.

 

[Abject]

I remember that thread
http://www.bluelight.org/vb/threads...M-every-day-for-a-year-This-is-my-story-(LONG)

There have been a few people on BL who have made threads about using DXM frequently at low doses

 

[Random-dude-from-internet]

Its been known for awhile that NMDA antagonism is a novel approach to antidepressants
Med Hypotheses. 2011 Feb 28. [Epub ahead of print]
Dextromethorphan as a potential rapid-acting antidepressant.
Lauterbach EC.

Department of Psychiatry and Behavioral Sciences, Mercer University School of Medicine, 1550 College Street, Macon, GA 31201, United States; Department of Internal Medicine, Neurology Section, Mercer University School of Medicine, 1550 College Street, Macon, GA 31201, United States.
Abstract
Dextromethorphan shares pharmacological properties in common with antidepressants and, in particular, ketamine, a drug with demonstrated rapid-acting antidepressant activity. Pharmacodynamic similarities include actions on NMDA, μ opiate, sigma-1, calcium channel, serotonin transporter, and muscarinic sites. Additional unique properties potentially contributory to an antidepressant effect include actions at ß, alpha-2, and serotonin1b/d receptors. It is therefore, hypothesized that dextromethorphan may have antidepressant efficacy in bipolar, unipolar, major depression, psychotic, and treatment-resistant depressive disorders, and may display rapid-onset of antidepressant response. An antidepressant response may be associated with a positive family history of alcoholism, prediction of ketamine response, increased AMPA-to-NMDA receptor activity ratio, antidepressant properties in animal models of depression, reward system activation, enhanced erythrocyte magnesium concentration, and correlation with frontal μ receptor binding potential. Clinical trials of dextromethorphan in depressive disorders, especially treatment-resistant depression, now seem warranted.



I was the original poster in this thread

DXM noticeably improved my intelligence

A lengthy read, but worth it… As a little background, I am in college and just completed finals a couple of weeks ago. I am also prescribed 20mg of adderall twice daily which I rarely take due to tolerance issues. I ended up taking slightly more than prescribed during my last two weeks of the...

www.bluelight.org

and have begun trialing 60mg extended release to combat my depression/hypomania. The results last time showed noticeable antidepressant effects withno long term benefit upon cessation. No side effects were noted. I was wondering if anybody else has been using it for this purpose. I am currently on 75mg venlefaxine now, but there have been no side effects at these dosages.

@zenistry
Nice thread thanks for bringing this research to light!

Here you have some more clinical research material:

I was in Spain in the 90ties or early 2000 something, and I had a horrible cough the whole time I was there, like a really proper cough. So I buy this bottle OTC of "Romilar", not thinking much about it I head of to the airport the next day and waiting in line to board the plane I realize that the OTC cough-syrup was loaded with DXM the whole bloody bottle was almost full, and DMX was highly illegal in the country I was traveling to.

I panicked there was no time to run to the toilettes and flush it or even just throw the bottle, so being a "true yolo-bro" at the time I made the mature decision to just chug the whole bottle...

Best flight ever, I was flirting with the cute flight attendants, their eyes looked really big kind of anime style and the colors where really vivid, and I was completely free from depression like at least a couple of weeks almost a month after that, and I was struggling with deep depression after that time... And my cough went away!

Nice memory I would not mind experimenting more with DMX, for pure scientific proposes of course!

Stay safe!