• Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

  • N&PD Moderators: Skorpio | someguyontheinternet

NMDA Antagonist: Tolerance and Withdrawal Concerns

Memantine has been found to not have a withdrawal in healthy subjects, my own anecdotal confirms that even, with doses of up to 60mg (altough only for a few weeks).

I'l post the reference a bit later, need to look it up again.

Ive seen reports of several years with regards to memantine and tolerance to the anti tolerance effects has never reported to be a issue.
 
Memantine HCl is a low to moderate affinity uncompetitive NMDA antagonist that did not produce any evidence of drug-seeking behavior or withdrawal symptoms upon discontinuation in 2,504 patients who participated in clinical trials at therapeutic doses
Click to expand...

On the other hand there is a case report of decline in alzheimer with abrubt cessation:
Two cases of discontinuation syndrome following cessation of memantine.

Although memantine is widely used and generally considered safe, an abrupt cessation of memantine may result in discontinuation syndrome that can be distressing and result in decline of natural course. We report two patients who developed significant behavior disturbance after abrupt cessation of memantine. Although re-trial of memantine improves these symptoms, more additional drugs may be required to achieve previous status. Therefore, abrupt cessation of memantine should be prudent and require cautious follow up.
Click to expand...
 
I can tell you from my own personal experience of using recreational doses of dextromethorphan for the better part of a year at least 2nd plateau 3-5 times a week (sometimes tripping every day, even doing plateau sigmas to continuously trip over 12 hours) I never developed a significant tolerance to DXM. I quit cold turkey and had no withdrawals other than a psychological desire to robo trip and I remained off the DXM for ... at least 3 years. When I tried it again, I found that it had no recreational effects on me however it still worked for reducing tolerance to Valium when I took 60mg of Delsym twice a day for a week or so - it was more effective than memantine, in fact, and the reason I stopped it and waited for my memantine was because of a hypertensive reaction when I took 31.2mg of 4-HO-MET while on my 60mg Delsym dose.

Ketamine ... my tolerance to that went up and never came back down.

Based on my extreme abuse of DXM and no noticeable tolerance developing to its psychoactive effects and no issues discontinuing it when I decided to quit, I would say that developing tolerance to the much lower doses used for NMDA antagonism (usually 30-60mg twice a day in the case of Delsym) is unlikely. Memantine I can't be too sure but since its receptor profile is so clean compared to DXM, I imagine there won't be a discontinuation syndrome unless you were using it to quit something like GABAergics - in this case, I imagine that quitting memantine abruptly after discontinuation of high dose benzos or something would be contraindicated since NMDA would quickly up-regulate as the memantine was eliminated and if GABA wasn't given sufficient time to recover from the benzo effects then there may be some big problems.

I don't know for sure though as far as the benzos go but considering how long it generally takes the brain to heal from benzo discontinuation, I would recommend staying on NMDA antagonists for at least 2 months after discontinuation to make sure that withdrawals don't start. It would massively suck to go into a grand mal seizure about a week after stopping memantine (it has a long half-life) so I won't be the guinea pig on this one. I plan to stay on NMDA antagonists for at least 4-6 months after I get off of my valium and I plan to taper off of the NMDA antagonists as well, albeit quicker than my benzo taper will be.
 
MagickalKat777 said:
I can tell you from my own personal experience of using recreational doses of dextromethorphan for the better part of a year at least 2nd plateau 3-5 times a week (sometimes tripping every day, even doing plateau sigmas to continuously trip over 12 hours) I never developed a significant tolerance to DXM. I quit cold turkey and had no withdrawals other than a psychological desire to robo trip and I remained off the DXM for ... at least 3 years. When I tried it again, I found that it had no recreational effects on me however it still worked for reducing tolerance to Valium when I took 60mg of Delsym twice a day for a week or so - it was more effective than memantine, in fact, and the reason I stopped it and waited for my memantine was because of a hypertensive reaction when I took 31.2mg of 4-HO-MET while on my 60mg Delsym dose.

Ketamine ... my tolerance to that went up and never came back down.

Based on my extreme abuse of DXM and no noticeable tolerance developing to its psychoactive effects and no issues discontinuing it when I decided to quit, I would say that developing tolerance to the much lower doses used for NMDA antagonism (usually 30-60mg twice a day in the case of Delsym) is unlikely. Memantine I can't be too sure but since its receptor profile is so clean compared to DXM, I imagine there won't be a discontinuation syndrome unless you were using it to quit something like GABAergics - in this case, I imagine that quitting memantine abruptly after discontinuation of high dose benzos or something would be contraindicated since NMDA would quickly up-regulate as the memantine was eliminated and if GABA wasn't given sufficient time to recover from the benzo effects then there may be some big problems.

I don't know for sure though as far as the benzos go but considering how long it generally takes the brain to heal from benzo discontinuation, I would recommend staying on NMDA antagonists for at least 2 months after discontinuation to make sure that withdrawals don't start. It would massively suck to go into a grand mal seizure about a week after stopping memantine (it has a long half-life) so I won't be the guinea pig on this one. I plan to stay on NMDA antagonists for at least 4-6 months after I get off of my valium and I plan to taper off of the NMDA antagonists as well, albeit quicker than my benzo taper will be.
Click to expand...

WOW thank you for such anecdotal insight!!!! Much appreciated mate!

Cheers,
-Van
 
Not a problem. Also I am finding that mixing Delsym twice a day with my 40mg of memantine is dropping my tolerance much quicker. I added in the Delsym to my regimen yesterday when I was suffering some nasty benzo withdrawal side effects and about two hours after taking 30mg, I experienced a rather profound sense of relief and ended up having yet another night where I didn't make it to my bed to fall asleep and just passed out right in my chair.
 
MagickalKat777 said:
Not a problem. Also I am finding that mixing Delsym twice a day with my 40mg of memantine is dropping my tolerance much quicker. I added in the Delsym to my regimen yesterday when I was suffering some nasty benzo withdrawal side effects and about two hours after taking 30mg, I experienced a rather profound sense of relief and ended up having yet another night where I didn't make it to my bed to fall asleep and just passed out right in my chair.
Click to expand...

What exactly are you suggesting? That mixing DXM and memantine reduces your tolerance to benzos?
 
DXM reduces tolerance to drugs while you continue to take them. Memantine does as well but at a much slower rate. So I added DXM back in to allow me to taper even faster.
 
I expressed some concerns in the NMDA antagonists and tolerance thread here: http://www.bluelight.ru/vb/showpost.php?p=9131180&postcount=111

Reading these posts I'm becoming more optimistic. Still this should be looked into more thoroughly. I can't say DXM has such a profound effect on tolerance as most folks here describe. I've been using it on and off (cycle of a week or two on it) as an antidepressant at low doses (~30-150mg/d usually) over years and had a few fullblown trips, not many since the side effects are massive. Also been using Ketamine for 6 years, only full blown doses, IN and IM every now and then with an initial 2yr (?) episode of heavier use. Additionally there has been a short (3-4month) episode of pcp abuse.

Now I'm really not sure about the effect DXM has on my amphetamine tolerance. I can't say I feel that tolerance has decreased in any way, but: While subjectively the effects actually felt seem to be about the same, I observed a more profound effect on my behaviour in regards to talkativeness (very annoying actually), appetite suppression and decreased desire to go to sleep on time. So I might just not be noticing the real impact of the DXM with not solely changes in dosage going on, but also in quality of experience. Hard to say really, would be a lot easier if I'd be using a diary and measure a few symptoms of the amphetamine use (bp for a start).
 
Now I'm really not sure about the effect DXM has on my amphetamine tolerance. I can't say I feel that tolerance has decreased in any way
Click to expand...

NMDA antagonists are generally acknowledged as effective for tolerance prevention, as opposed to reversal.
 
So this thread is a bit old but as I am about to start memantine for depression / drug cravings that simply never go away I need some more information.

Is it really true that memantine will not produce withdrawal symptoms after being taken for a prolonged time? The stronger NMDAR antagonists (PCP/Ketamine) causes physical addiction and bad pain/anxiety upon discontinuation of use if used for a prolonged time (for me at least).

However NMDAR antagonists have everything I need (anxiety reduction, neuropathic pain reduction and mood stabilizing effects) so I would really like to try memantine. Low dose PCP or ketamine always used to completely abolish depression however the comedown after using even low amounts at this point is so terrible it's not worth it at all.

I need an NMDAR antagonist I can take daily, memantine seems to be the only option. However if it doesn't work I don't want to be stuck with a comedown that lasts over a year like I got from PCP. I also realize memantine is an uncompetitive antagonist and may not cause the same problems at all upon discontinuation, as it should not have messed with normal functioning of the receptors.
 
Last edited:
@Toz
Naltrexone works pretty well for cravings. It is however not a good idea to start using it before your opioid system has recovered. Side effects can be crazy unpleasant, obviously.
 
Toz, I am taking memantine for general stabilization / alleviating neuronal hyper/overexcitation which is much the same why anti epileptics are used as mood stabilizers (and while it's not approved for that, mem. seems to be seizure-preventing and possibly, for some, antipychotic). Just that I'd rather stay on memantine for the rest of my life than touching things like carbamazepine or (even atypical) neuroleptics again. There are some side effects noted that could be stoppers, but the list is short for this kind of drug and for me it was just some slight dissociative feeling for the first week or so (started straight with 20mg/d).

By the way, I too found it coincidentally after I realized how dissociatives (DXM in my youth, later methoxetamine) are able to control my mood when all usual meds have failed. It helps greatly in alleviating constant inner tension / stress / anxiety and impulsivity. For cravings it has real potential and it's synergetic with methylphenidate (if you find yourself to feel sedated / unmotivated on it).

Concerning discontinuation, memantine has a low affinity to the NMDA receptor and doesn't completely block it at therapeutic dosages. As I accidentally ran into some rebound excitation and anxiety after stopping suddenly at 60mg/d (but I was using some other drugs in that time too, so I don't know)- I definitely recommend a slow taper. It's long half life of up to 100h helps too (and causes a huge buildup when dosed daily, much like fluoxetine). When tapering over some weeks it should go almost unnoticeable (besides of course that the effects go away, and if it shows to be an effective anxiolytic for you, discontinuing will afford some strength of will independent of any tolerance/withdrawal).

--

cr00k, have you personally used naltrexone successfully to manage cravings (to opioids, or other substances too)? How does the naltrexone feel, is it really unnoticeable when enough time has passed since the last opioid use / w/d…? Would you say it affects non-drug related pleasure or overall feelings in any way due to blocking endorphins?
 
Last edited:
I've used it and the cravings were gone, but I couldn't handle the side effects. Maybe I should've waited longer after last using opioids.

I know others who have been using it for years to stay sober. I'm also treated by one of Germany's leading psychiatrists specialized in addiction treatment and he tells me it's pretty much hit or miss. It works wonders for some people and for others it doesn't do shit. Some patients even use it successfully on-demand whenever they feel the thoughts creeping up (usually there's a delay of 1-7 days before I would actually use and it's the same way for most of us I suppose).

It's received a bad name it seems, probably due to some drug users condemning this type of treatment, based on nothing but naivety or their own lack of success in trying the substance. This former is often paired with unwillingness to accept their own addiction as an illness that they cannot break free of without help.

My psychiatrist also mentioned that some patients are successful with microdoses. Most start at 25mg and later increase to 50mg. Be warned that this is a lot and the effects are comparable to opioid withdrawls, the half-life being quite long.


Something funny for you since you mentioned anticonvulsants: Lamotrigine causes massive cravings in me! When I'm off it I have a really easy time staying sober, but my mood will fluctuate daily between -5 and 7 on a scale of -10 to 10. It's fucking hellish. However, I decided to get back on it since it gives me 100% relief of affective instabilities without a single (!) side effect other than cravings. Lithium on the other hand caused a shit ton of sides and never did anything for my mood. Godamn, fucking drug addiction!!!!
 
You must log in or register to reply here.
Top