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Sunifiram?

sunifiram

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#1201 Climactic

  • Location:USA

Posted 07 July 2013 - 08:09 PM


The symptoms experienced by me and Rudy have shown no reduction or improvement whatsoever. Yes, I am experiencing headaches daily, and right now as I'm writing this message. L-theanine 200mg taken several times a day helps me very temporarily. I have lately tried 40-80mg XR propranolol which also helps, but not perfectly, and is probably insufficient to reverse the problem without lowering my vitals too much. I will soon try something else, and remain hopeful. I also haven't been able to fall asleep all of last month without 200mg L-theanine. The relative permanence of the effects is astounding. It goes to show the power of some drug/combinations, whether for good or bad.

Have you thought about simply dropping any kind of supplement/nootropic/medication, you are taking right now and let some time pass?


Yes, I tried dropping most of my supplements, except some basic anti-excitotoxic vitamins, for a whole month. I also discontinued my nootropics for at least three weeks. It was of no use whatsoever. I will now go back to being on all of my supplements. One more thing left for me to try before I start the doctor-prescribed pharmaceutical regimen is intense exercise, although I am skeptical.

Edited by Climactic, 07 July 2013 - 08:13 PM.

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#1202 Isochroma-Reborn Re: Sunifiram?

  • Location:Your Future
  • no

Posted 08 July 2013 - 02:18 AM

Finally, I found it:

The use of NMDA-receptor antagonists in the treatment of chronic pain

"Chronic pain can be maintained by a state of sensitization within the central nervous system that is mediated in part by the excitatory amino acids glutamate and aspartate binding to the N-methyl-D-aspartate (NMDA) receptor. A number of antagonists to the NMDA receptor are antinociceptive in animal models but are associated with significant dose-limiting side effects. Commercially available NMDA-receptor antagonists include ketamine, dextromethorphan, memantine, and amantadine. The opioids methadone, dextropropoxyphene, and ketobemidone are also antagonists at the NMDA receptor. The NMDA-receptor antagonists have a significant impact on the development of tolerance to opioid analgesics. Consequently, NMDA-receptor antagonists may represent a new class of analgesics and may have potential as coanalgesics when used in combination with opioids."

It struck me that the maintained pain which Sunifiram seems to have induced in a few individuals is very similar to phantom-limb pain and I happen to be researching NMDA antagonists of the arylcyclohexylamine variety in recent weeks. The mechanism ought to be the same between them too.

With this information the certainty is above 90%: Sunifiram is capable of - in some individuals - inducing a state of sensitization in NMDA receptors that can cause perpetual pain to be maintained indefinitely past the initial signal. NMDA blockade is virtually guaranteed to eliminate the pain acutely, but I don't know if it would reverse the LTP. Taking Sunifiram together with an NMDA antagonist would be another option. Sunifiram may sensitize to deactivation as well as activation. If it does possess agonist activity this wouldn't work - but in that case just substitute Unifiram.

Dextromethorphan (DXM) is legal and available in cough syrups.

Methoxetamine (MXE) is legal in most jurisdictions, safe, and can be purchased by mail-order.

Edited by Isochroma-Reborn, 08 July 2013 - 02:27 AM.

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#1203 Climactic Re: Sunifiram?

  • Location:USA

Posted 08 July 2013 - 02:25 AM

The use of NMDA-receptor antagonists in the treatment of chronic pain

"Chronic pain can be maintained by a state of sensitization within the central nervous system that is mediated in part by the excitatory amino acids glutamate and aspartate binding to the N-methyl-D-aspartate (NMDA) receptor. A number of antagonists to the NMDA receptor are antinociceptive in animal models but are associated with significant dose-limiting side effects. Commercially available NMDA-receptor antagonists include ketamine, dextromethorphan, memantine, and amantadine. The opioids methadone, dextropropoxyphene, and ketobemidone are also antagonists at the NMDA receptor. The NMDA-receptor antagonists have a significant impact on the development of tolerance to opioid analgesics. Consequently, NMDA-receptor antagonists may represent a new class of analgesics and may have potential as coanalgesics when used in combination with opioids."

With this information the certainty is above 90%: Sunifiram is capable of - in some individuals - inducing a state of sensitization in NMDA receptors that can cause perpetual pain. NMDA blockade is virtually guaranteed to eliminate the pain acutely, but I don't know if it would reverse the LTP. Taking Sunifiram together with an NMDA antagonist would be another option. Sunifiram may sensitize to deactivation as well as activation. If it does possess agonist activity this wouldn't work - but in that case just substitute Unifiram.

Dextromethorphan (DXM) is legal and available in cough syrups.

Methoxetamine (MXE) is legal in most jurisdictions, safe, and can be purchased by mail-order.


Yes, thanks Isochroma-Reborn, but where would I purchase MXE or pure DXM in the U.S.? The DXM I saw in stores is mixed with expectorant or alcohol, neither of which I want. In any case, I'd probably try memantine before I try either of these chronically. My memantine is in the mail.

I'm hoping that chronic NMDA blockade over weeks will reverse the LTP, although I have little basis for such hope.

Edited by Climactic, 08 July 2013 - 02:30 AM.

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#1204 Isochroma-Reborn Re: Sunifiram?

  • Location:Your Future
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Posted 08 July 2013 - 02:29 AM

DXM is available in every drugstore as cough syrup. Of course check the ingredients to be sure.
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#1205 Climactic Re: Sunifiram?

  • Location:USA

Posted 08 July 2013 - 02:31 AM

DXM is available in every drugstore as cough syrup. Of course check the ingredients to be sure.

Cough syrup contains expectorant or alcohol, both of which are unacceptable when it comes to chronic dosing. The expectorant is known to give a headache, and the alcohol causes a rebound glutamatergic effect after it wears off. I guess I can buy pure DXM from an RC seller if I wanted.

Edited by Climactic, 08 July 2013 - 02:33 AM.

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#1206 Isochroma-Reborn Re: Sunifiram?

  • Location:Your Future
  • no

Posted 08 July 2013 - 02:36 AM

Chronic NDMA blockade by itself is less likely than when combined with a sensitizing/desensitizing agent - though it's all theory right now.

As for the other junk in cough syrups - a simple two-phase extraction can be found online - I used to do it all the time and it worked perfectly.

The extraction requires nothing more than solvent (lighter fluid, etc. but NOT alcohol), ziploc, water, pin to poke a hole in the ziploc's corner, household ammonia and citric acid or Vitamin C powder.

dextroverse.org: Agent Lemon Extraction Method
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#1207 Climactic Re: Sunifiram?

  • Location:USA

Posted 08 July 2013 - 02:43 AM

Chronic NDMA blockade by itself is less likely than when combined with a sensitizing/desensitizing agent - though it's all theory right now.

As for the other junk in cough syrups - a simple two-phase extraction can be found online - I used to do it all the time and it worked perfectly.


For what it's worth, aerobic exercise increases NMDAR and LTP, so it should be capable of serving as the speculated agent.

I'd rather just buy 5g dextromethorphan hydrobromide than bother filtering it myself. I don't intend to use it for life.

Edited by Climactic, 08 July 2013 - 02:50 AM.

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#1208 Isochroma-Reborn Re: Sunifiram?

  • Location:Your Future
  • no

Posted 08 July 2013 - 02:46 AM

As for memantine, forget it: it is absolutely useless to reverse NDMA-sensitized pain:

Excerpted from: The Emerging Role of NMDA Antagonists in Pain Management:

"Memantine: Other NMDA receptor antagonists such as memantine, amantadine, and dextromethorphan have shown mixed results in neuropathic pain.20 Memantine has a safe side-effect profile and rapid onset of action; however, in a randomized, double-blind, crossover study where memantine was administered to a group of 19 patients with chronic pain due to nerve injury after surgery, there was no difference in pain reduction with memantine versus placebo.21 In addition, a study with memantine in patients with HIV-associated sensory neuropathy did not show positive results.22"


More specifically - for those with the headache: Memantine for prophylaxis of chronic tension-type headache--a double-blind, randomized, crossover clinical trial:

"Treatment for chronic tension-type headache (CTTH) is unsatisfactory. Our aim was to investigate the efficacy of the N-methyl D-aspartate (NMDA) antagonist memantine in the prophylactic treatment of CTTH. We included 40 patients in a randomized, double-blind, placebo-controlled, crossover trial. Memantine 20-40 mg/day or placebo was each given for 10 weeks separated by a 2-week wash-out period; 29 patients completed the study. The primary efficacy variable, area-under-the-headache curve (duration x intensity), did not differ between memantine (1352 +/- 927) and placebo (1449 +/- 976; P = 0.10). Headache intensity in both sexes was significantly lower on a 0-10 verbal rating scale with memantine (3.8) than with placebo (4.1; P = 0.03). In women, area-under-the-headache curve was significantly lower with memantine (1343 +/- 919) than with placebo (1555 +/- 1019; P = 0.01). The most common side-effects were dizziness and nausea. In conclusion, although no statistically significant effect was seen in the primary end-point, some beneficial effects of memantine were observed in women. Memantine was shown to reduce pain intensity in CTTH patients, albeit to a limited extent. Future NMDA antagonists with higher efficacy could be of major interest as regards the pathophysiology and future treatment of CTTH and other chronic pain disorders."


Your best choices among molecules that have a chance of working in a decent fashion are DXM from cough syrup/gels and MXE.

Pure DXM powder has been legislated against in the USA if you're living there but it's still legal if in syrup/dosed form and still sold at drug stores.

Sigma-Aldrich is in close collaboration with the DEA and tracks all purchases so don't buy from them.

Edited by Isochroma-Reborn, 08 July 2013 - 03:35 AM.

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#1209 xsiv1 Re: Sunifiram?

  • Location:Canada

Posted 08 July 2013 - 02:59 AM

Robitussin Cough gels contain DXM (15mgs/per cap) and should be available anywhere. I don't think that these ones contain anything else in them like guafenisin or whatever it's called.
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#1210 Isochroma-Reborn Re: Sunifiram?

  • Location:Your Future
  • no

Posted 08 July 2013 - 03:15 AM

And good news as of now!

My 5g MXE was just posted by Express Mail direct from the Chinese manufacturer - expected transit is 7-10 days.

It's not regulated in my country but Customs might still seize it - they seized 100g Oxiracetam just last month from China.

Nevertheless, I plan to re-buy until it penetrates.

This agent may be the only option or one of only two for those unlucky enough to have gotten locked into NMDA-potentiated pain.

Edited by Isochroma-Reborn, 08 July 2013 - 03:15 AM.

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#1211 Climactic Re: Sunifiram?

  • Location:USA

Posted 08 July 2013 - 03:27 AM

This agent may be the only option or one of only two for those unlucky enough to have gotten locked into NMDA-potentiated pain.


There is also acamprosate, although like memantine, I expect it to be weak. The NMDA receptor has various binding sites, and different antagonists may have different affinities for these sites.
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#1212 Isochroma-Reborn Re: Sunifiram?

  • Location:Your Future
  • no

Posted 08 July 2013 - 03:38 AM

Can't find a single study of Acamprosate on pain so it's likely those in the know have already decided it would be too weak.

Memantine seems to show some effects in some studies but I agree that it's very weak.

And yes, NDMA blockers are each very different and the channel itself - like many other receptors - behaves very differently with different ligands.

Edited by Isochroma-Reborn, 08 July 2013 - 03:40 AM.

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#1213 Climactic Re: Sunifiram?

  • Location:USA

Posted 08 July 2013 - 04:53 AM

Can't find a single study of Acamprosate on pain so it's likely those in the know have already decided it would be too weak.


Acamprosate is comparatively newer than memantine and others. This can explain the presence of limited studies. Unless studies explicitly show that it doesn't work, there is a possibility that it can work by its NMDA antagonist effect.

Edited by Climactic, 08 July 2013 - 05:19 AM.

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#1214 Isochroma-Reborn Re: Sunifiram?

  • Location:Your Future
  • no

Posted 08 July 2013 - 05:02 AM

Indeed. However,

"Certain serious side effects include diarrhea, allergic reactions, irregular heartbeats, and low or high blood pressure"


Not that DXM and MXE don't have any side effects - irregular heart beats are noted on forums by DXM users - but at much higher 'recreational' doses - ones that would not be needed for pain relief.
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#1215 deeptrance Re: Sunifiram?

  • Location:Austin, TX

Posted 08 July 2013 - 05:31 AM

This new agent is very safe, does not suppress breathing, there are no withdrawals, it can be used orally and it has a long duration of action - up to all day - and also includes up to a week of antidepressant action from a single small dose.

This agent is called Methoxetamine


Wow, this is such a bad idea to be recommending MXE as though it were as safe as exercising and getting more fresh air. See http://jesusgreen.tu...amine-mxe-my-2c for a different perspective. No individual with addictive history or tendencies should use MXE on a regular basis, to be sure, but beyond that I would just caution everyone not to take MXE on a regular basis.

I used MXE daily, in very small doses, for about a week, but flushed it when I realized I was taking it in spite of feeling dysphoric, confused, and detached from life. Not caring about anything can feel "good" to a person who hates life, and being detached from the notion of "self" is pretty alluring especially to those who are afflicted with painful self-awareness. But there are healthier ways to deal with these things. And as far as pain relief is concerned, this is about the last thing anyone should be trying as a daily prophylactic.

As for the claim of "no withdrawals", this may be true as far as physiological symptoms are concerned, but I recommend doing a search on "MXE addiction" and reading some user experiences before jumping to conclusions about its long term safety with respect to addiction. I have been in direct contact with 2 individuals whose lives spun out of control on MXE, and they went through plenty of hell when they stopped using.
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#1216 Isochroma-Reborn Re: Sunifiram?

  • Location:Your Future
  • no

Posted 08 July 2013 - 01:34 PM

"Not caring about anything can feel "good" to a person who hates life, and being detached from the notion of "self" is pretty alluring especially to those who are afflicted with painful self-awareness."

What's with the psychologisms? We're dealing with NMDA-potentiation induced chronic headaches not 'painful self-awareness'. Repeat: on-topic please.

MXE is perfectly safe as a low-dose daily NMDA antagonist.

As for your own case - you just didn't like the slight dissociative effect - your preference, not a hazard.

Others found they could use low doses without said effect and still others found that these side-effects were tolerable.

PS. Most medicines have side effects and at low doses MXE's side-effect profile is better than many approved prescription drugs.

If you think MXE ought to be the 'last' choice in pain-relievers then I suggest you look at the hazard, legal and addictive and withdrawal properties of the only alternative for severe pain - opiates.

At the doses required to alleviate severe pain - which won't work with NMDA-sensitized pain anyway - opiates shut the brain down and put the body in a bad place.

I know due to having been given them after surgery for a burst appendix.

In this case the only alternatives are other NMDA antagonists but the ones like memantine with lower side-effect profiles are too weak to reverse the problem.

Edited by Isochroma-Reborn, 08 July 2013 - 01:43 PM.

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#1217 deeptrance Re: Sunifiram?

  • Location:Austin, TX

Posted 08 July 2013 - 07:19 PM

What's with the psychologisms? We're dealing with NMDA-potentiation induced chronic headaches not 'painful self-awareness'. Repeat: on-topic please.


As a strictly on-topic matter for the specific purpose you've identified, I don't object to the bulk of what you've said, but this -

MXE is perfectly safe as a low-dose daily NMDA antagonist.


- is where I disagree. You're basing your statement on limited scientific research. This research conflicts with the experience of many regular users who felt fine for a few weeks or months, but I have yet to read a report of anyone taking MXE for longer than a few months without experiencing serious repercussions that were (according to my reading of their reports) less tolerable than what a sufferer from chronic pain would endure as a result of a comparable period of taking opiates.

Opiates have centuries of widespread use, and millions of people are able to take opiates on a daily basis without side effects that outweigh benefits. Are they ideal? of course not. And this is where I agree with you about methoxetamine --- it might be preferable to opiates as a means of handling the glutamate cascade that we've hypothesized to be the cause of suffering for a few sunifiram users. It's not ideal to be taking a dissociative every day, but if it makes life bearable and there aren't better alternatives then go for it. In this specific instance, it's possible that there aren't better alternatives.

Ketamine, according to my research, shows stronger antinociceptive effects, but I presume you chose MXE for legal reasons...?

As for your own case - you just didn't like the slight dissociative effect - your preference, not a hazard.


Somewhat true. The point I was trying (and failing) to make is that I compulsively took it in spite of not enjoying it. This is classic addiction behavior. I'm not triggered to take anything compulsively unless it has some kind of reinforcing quality that compels me. I've had amphetamines that I was able to control better than MXE, for instance. But this is "case study" single-user anecdotal stuff so of course I'm not trying to generalize, just warning that others MAY have similar issues.

Others found they could use low doses without said effect and still others found that these side-effects were tolerable.


True dat. Lots of glowing reports all over the drug forums. Like I said, I've not seen any such reports that extend beyond a few months that don't also include a discussion about addiction, but I'm sure they exist.

If what you're advocating is a reasonably finite course of MXE then please accept my apologies, as I'm mostly addressing the problems of using that can obtain from longer-term usage. Perhaps the results people seek could be realized within a matter of weeks, not months, in which case I'm in full agreement with you!
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#1218 Isochroma-Reborn Re: Sunifiram?

  • Location:Your Future
  • no

Posted 08 July 2013 - 08:02 PM

As for how long an NMDA antagonist - MXE, Ketamine, etc. needs to be administered to reverse the process - I don't know.

It might only be one dose but that dose might have to be in the hole range, or maybe not.

It might be a short course like it was for the 12-year old boy whose phantom-limb pain was successfully treated before it kindled into lifetime permanance - it's the case on the "Methoxetamine for Pain Relief" page.

There's something interesting about these reports - the boy and a forum post. There are a few cases of sustained pain decrease or elimination after discontinuation of dosing - indicating long-term NMDA depotentiation:


RUSHDAFUNK: I have pretty bad lower back pain from a herniated disk. Now nerve pain may be acted upon in a diff. way than muscle pain, but all I know is that 20mg MXE (2x10mg about 1.5 hours apart) 2 days in a row resulted in near zero nerve pain from my bulging disk for those days (from the time i dose till the rest of the day).


To add to that, as I speak, its the 3rd day since the initial dose. I have taken nothing today and my back pain is maybe only 20-30% as bad as it was 4 days ago.


I'm pretty f'ing impressed to say the least. Also I dosed orally (not sublingual or nasally).


Impressive: A seventy to eighty percent permanent pain reduction three days after discontinuation - since MXE won't be present the only explanation is NMDA depotentiation or some other long-term therapeutic effect.

Opiates can't do that. GABA agonists can't either. Withdrawal of those agents causes the opposite: rebound pain worse than the original.

Nothing is perfect but comparisons are between alternatives: effective NMDA antagonists or ineffective, hazardous opiates and GABA agonists.

Edited by Isochroma-Reborn, 08 July 2013 - 08:03 PM.

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#1219 Climactic Re: Sunifiram?

  • Location:USA

Posted 08 July 2013 - 08:19 PM

In my case and Rudy's case, the pain in the temples is presumably due to increased ICP, which presumably is caused by excess glutamate in this case. I presume that NMDAR downregulation will help because sunifiram activates NMDAR. At least a pharmaceutical GABA-A agonist was consistently observed to help me temporarily for 8h, but I won't be taking it as a treatment approach for obvious reasons.

I don't really want to suppress the pain without addressing the underlying cause.

If I were to hypothetically take MXE, I would only do it in a way that makes it stay active 24x7 for a few weeks, otherwise I don't see the point.

As for lower back pain and joint pain, I'd first max out on natural and pharmaceutical anti-inflammatories before considering NMDAR antagonists. I've had a lower back herniation in the past, and nothing helped me like a little Physical Therapy.

Edited by Climactic, 08 July 2013 - 09:08 PM.

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#1220 deeptrance Re: Sunifiram?

  • Location:Austin, TX

Posted 09 July 2013 - 04:23 PM

It might be a short course like it was for the 12-year old boy whose phantom-limb pain was successfully treated before it kindled into lifetime permanance - it's the case on the "Methoxetamine for Pain Relief" page.

There's something interesting about these reports - the boy and a forum post. There are a few cases of sustained pain decrease or elimination after discontinuation of dosing - indicating long-term NMDA depotentiation


Color me intrigued. I can feel my skepticism melting away. My prior experience with MXE was of the tip-toe variety, as I'm fairly wary of dissociatives and paranoid about losing my grip even though I got a decent taste of how relaxing it can be to be divorced from self. It's hard to feel anxious without a "self" to worry about.

If I were to hypothetically take MXE, I would only do it in a way that makes it stay active 24x7 for a few weeks, otherwise I don't see the point.



Look at what Iso is saying again --- you could potentially see a substantial benefit from a single experience or a very brief course of treatment. I doubt you'd be one to want to go into the M-hole, but maybe somewhere shy of that intensity you could still see significant improvement. Given the severity of what you're going through, it might be worth a shot.

There are other medications that can have lasting benefits after a single usage, psychedelics being the most prominent category to exhibit this tendency. A study of alcoholism and peyote on a New Mexico Indian reservation showed a remarkable success rate of a single peyote ceremony on curbing alcoholism, beyond what any other treatment had obtained. I have friends who have been able to overcome depression after a single experience with ayahuasca or LSD, and I can personally testify to the latter. These effects are generally temporary but the benefit lasts for months, just from a single dose.

I know you have other things to try first, but if you don't find relief from any of them then maybe MXE would be worth a shot.
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#1221 xsiv1 Re: Sunifiram?

  • Location:Canada

Posted 09 July 2013 - 09:40 PM

There's a reason BigPharma is looking into all variants of Ketamine and methods to nullify it's abuse/dependence characteristics (like they really care) for everything from chronic pain management to major depressive disorders and more. Personally, I couldn't tolerate 15mgs of straight DXM once a day for over a week. It must either metabolize into some other longer acting compound or it has a cumulative effect for me. I was using it to help with glutamate excitotoxicity for a period. This was for a Gaba agonist though and found that various other Gaba agonists, mimetics and analogs along with a very slow taper did the trick. I realize this is a different beast and it's best to simply drop use immediately. I'm unsure how you'll react to an NMDA antagonist but my instinct tells me this cannot be solely overly sensitized NMDAR receptors and massive ongoing cascades of glutamate. If, in fact, Gaba agonists (which carry their own negative profiles) help relieve symptoms, you might want to need to consider Baclofen. If your hunch is correct, Baclofen will ensure you're minimizing any kind of apoptosis. There are scores of people taking baclofen daily and on it for life. You can check it out at my way out forums and find a doctor who will legally prescribe it to you if you live in the US. As a Gaba A agonist with significant affinity to this receptor (moreso than phenibut) but less action at the dopamine pathway (unlike Phenibut), it's side effect profile is also not horrific and tapering off of Baclofen is known to be easier than phenibut and most benzos. I couldn't function daily at work and at home on benzos (eventually just wanted sleep) but many do on some of the Gaba analogs & mimetics. Of course these have dangers of tolerance and dependence but will tip the glutamate/Gaba scale. I only bring this up if the NMDA antagonist idea doesn't work out for you. I'm still not convinced that this is a result of solely what we're looking at. Glutamate should slowly return ever so slightly back into balance with time unless there's some sort of permanent changes that have occurred. I just can't see that either. There's something missing here.
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#1222 Climactic Re: Sunifiram?

  • Location:USA

Posted 09 July 2013 - 10:04 PM

There's a reason BigPharma is looking into all variants of Ketamine and methods to nullify it's abuse/dependence characteristics (like they really care) for everything from chronic pain management to major depressive disorders and more. Personally, I couldn't tolerate 15mgs of straight DXM once a day for over a week. It must either metabolize into some other longer acting compound or it has a cumulative effect for me. I was using it to help with glutamate excitotoxicity for a period. This was for a Gaba agonist though and found that various other Gaba agonists, mimetics and analogs along with a very slow taper did the trick. I realize this is a different beast and it's best to simply drop use immediately. I'm unsure how you'll react to an NMDA antagonist but my instinct tells me this cannot be solely overly sensitized NMDAR receptors and massive ongoing cascades of glutamate. If, in fact, Gaba agonists (which carry their own negative profiles) help relieve symptoms, you might want to need to consider Baclofen. If your hunch is correct, Baclofen will ensure you're minimizing any kind of apoptosis. There are scores of people taking baclofen daily and on it for life. You can check it out at my way out forums and find a doctor who will legally prescribe it to you if you live in the US. As a Gaba A agonist with significant affinity to this receptor (moreso than phenibut) but less action at the dopamine pathway (unlike Phenibut), it's side effect profile is also not horrific and tapering off of Baclofen is known to be easier than phenibut and most benzos. I couldn't function daily at work and at home on benzos (eventually just wanted sleep) but many do on some of the Gaba analogs & mimetics. Of course these have dangers of tolerance and dependence but will tip the glutamate/Gaba scale. I only bring this up if the NMDA antagonist idea doesn't work out for you. I'm still not convinced that this is a result of solely what we're looking at. Glutamate should slowly return ever so slightly back into balance with time unless there's some sort of permanent changes that have occurred. I just can't see that either. There's something missing here.


Considering that I think my ICP is increased, this by CSF is presumably caused by ependymocytes, which are a type of glial cells. Astrocytes, which are another type of glial cells, are also known to signal to neurons, in addition to releasing neurotransmitters including glutamate.

If you believe that a drug like coluracetam can induce relatively permanent changes with a single dose, there is no reason to believe that other drugs or their combinations might not be capable of inducing relatively long-lasting changes too, whether good or bad. We also already know that a single dose of ketamine or MXE can have long-lasting effects.

I believe excess glutamate would slowly naturally return to normal except if NMDARs (or other glutamate receptors) have been concomitantly overactivated, in which case there may be insufficient negative feedback for the glutamate to return back to normal. I think an ideal treatment plan should therefore probably target both NMDARs by chronic antagonism -- and also glutamate perhaps by a gabaergic.

Anyhow, speaking of pain, http://en.wikipedia....ki/Hyperalgesia is not a bad read, although strictly speaking it does not apply to me right now.

Edited by Climactic, 09 July 2013 - 10:13 PM.

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#1223 Isochroma-Reborn Re: Sunifiram?

  • Location:Your Future
  • no

Posted 10 July 2013 - 12:11 AM

Fascinating discussion.

Arrived home from the food bank to find that a miracle of unbelievable proportions occurred: Customs clearance.

By some crazy permutation of chance - I never believed it would happen - the 5g MXE cleared Customs today and will be in my hands in 1-2 days - unless (1) it was mis-addressed or (2) it's the wrong material (mistake). The combined likelyhood of these two failure modes is about 10% by my calculations.

I am considering distributing tiny amounts to the victims of Sunifiram headaches for testing.

The material is currently unregulated in most of the world.

However, it has not had many years of safety testing and so should be a later resort after better-tested NMDA antagonists are tried - ie. DXM which is cheaply available in local pharmacies.

Edited by Isochroma-Reborn, 10 July 2013 - 12:28 AM.

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#1224 xsiv1 Re: Sunifiram?

  • Location:Canada

Posted 10 July 2013 - 02:53 AM


There's a reason BigPharma is looking into all variants of Ketamine and methods to nullify it's abuse/dependence characteristics (like they really care) for everything from chronic pain management to major depressive disorders and more. Personally, I couldn't tolerate 15mgs of straight DXM once a day for over a week. It must either metabolize into some other longer acting compound or it has a cumulative effect for me. I was using it to help with glutamate excitotoxicity for a period. This was for a Gaba agonist though and found that various other Gaba agonists, mimetics and analogs along with a very slow taper did the trick. I realize this is a different beast and it's best to simply drop use immediately. I'm unsure how you'll react to an NMDA antagonist but my instinct tells me this cannot be solely overly sensitized NMDAR receptors and massive ongoing cascades of glutamate. If, in fact, Gaba agonists (which carry their own negative profiles) help relieve symptoms, you might want to need to consider Baclofen. If your hunch is correct, Baclofen will ensure you're minimizing any kind of apoptosis. There are scores of people taking baclofen daily and on it for life. You can check it out at my way out forums and find a doctor who will legally prescribe it to you if you live in the US. As a Gaba A agonist with significant affinity to this receptor (moreso than phenibut) but less action at the dopamine pathway (unlike Phenibut), it's side effect profile is also not horrific and tapering off of Baclofen is known to be easier than phenibut and most benzos. I couldn't function daily at work and at home on benzos (eventually just wanted sleep) but many do on some of the Gaba analogs & mimetics. Of course these have dangers of tolerance and dependence but will tip the glutamate/Gaba scale. I only bring this up if the NMDA antagonist idea doesn't work out for you. I'm still not convinced that this is a result of solely what we're looking at. Glutamate should slowly return ever so slightly back into balance with time unless there's some sort of permanent changes that have occurred. I just can't see that either. There's something missing here.


Considering that I think my ICP is increased, this by CSF is presumably caused by ependymocytes, which are a type of glial cells. Astrocytes, which are another type of glial cells, are also known to signal to neurons, in addition to releasing neurotransmitters including glutamate.

If you believe that a drug like coluracetam can induce relatively permanent changes with a single dose, there is no reason to believe that other drugs or their combinations might not be capable of inducing relatively long-lasting changes too, whether good or bad. We also already know that a single dose of ketamine or MXE can have long-lasting effects.

I believe excess glutamate would slowly naturally return to normal except if NMDARs (or other glutamate receptors) have been concomitantly overactivated, in which case there may be insufficient negative feedback for the glutamate to return back to normal. I think an ideal treatment plan should therefore probably target both NMDARs by chronic antagonism -- and also glutamate perhaps by a gabaergic.

Anyhow, speaking of pain, http://en.wikipedia....ki/Hyperalgesia is not a bad read, although strictly speaking it does not apply to me right now.


Very interesting but I'm hoping this isn't the case. If it is, I'd definitely try a low dose NMDA antagonist (if you can tolerate it. People have laughed when I told them that 15mgs of DXM used daily was unsettling. You had people like Midevil (or whatever his username was) utilizing 130mgs of DXM per day). Anyways, the other option which I believe is entirely viable is Gabapentin. It's dosing/bioavailability schematic is stupid and Lyrica is said to have corrected this thus becoming it's successor in a lower dose but increased potency form. Personally, I've tried both and Lyrica seems too sedating when I compare it to Gabapentin. They've nicknamed Gabapentin (Neurontin) as Morontin but I've found that using nootropics entirely corrects the situation. At first, you're a bit forgetful and words don't pop up into your head when you need them..but with some time, these side effects diminish. Problem with these Gaba mimetics is that tolerance and even dependence can develop. Of course, a slow tapering protocol must be strictly adhered to and it works. In fact, Lyrica is said to not even affect the Gaba receptors, instead acting as a calcium channel blocker that also acts to block glutamate as well. I've found Gabapentin to actually be kind of enjoyable for chillin' out and have used it sporadically for these very purposes. I was on it years and years ago but they both help will neuropathic pain. I've read the link from Wiki that you've provided and found this part particularly revealing:

Chronic hyperstimulation of opioid receptors results in altered homeostasis of pain signalling pathways in the body with several mechanisms of action involved, one major pathway being through stimulation of the nociceptin receptor,[7][8][9] and blocking this receptor may therefore be a means of preventing the development of hyperalgesia.[10]

So yes, I'm in agreement that various compounds can cause issues that seemingly do not resolve themselves for long periods of time. As Iso said earlier, there's evidence to suggest psychedelic compounds can permanently cause changes in brain activity simply from single use. Anyways, there is a doctor I know of in the Chicago area who will prescribe Baclofen for you legally and actually take you on as a patient..over the phone. If I were in your situation, I'd utilize a cyclical regimen of compounds (all that can address what you're thinking the root cause is) and go through them in a fashion where tolerance and perhaps dependence is mitigated.

MXE should be able to be imported into Canada as well, but custom here can technically do whatever they want. They could hold on to the product despite it's non-scheduled status and ask what you want it for and what it does and what ingredients said compound contains. Kind of sucks for that person caught in their game.

Your lack of other symptoms most common in NMDAR over sensitivity and glutamate excitotoxicity is what is making me scratch my head. You should be overly excitable, extremely anxious, and suffering from chronic insomnia as well. It's not unlike the alcoholic but I suppose it could be affecting different NMDA receptors. Either way, wouldn't a neurologist perhaps consider a spinal tap to determine what's going on in the cerebrospinal fluid? I'm just guessing here and I know it's an extreme diagnostic tool but, I'm at a loss aside from using medications until your symptoms subside. Has the magnitude of the headaches remained at the same level of pain today?
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#1225 Climactic Re: Sunifiram?

  • Location:USA

Posted 10 July 2013 - 04:00 AM

Your lack of other symptoms most common in NMDAR over sensitivity and glutamate excitotoxicity is what is making me scratch my head. You should be overly excitable, extremely anxious, and suffering from chronic insomnia as well. It's not unlike the alcoholic but I suppose it could be affecting different NMDA receptors. Either way, wouldn't a neurologist perhaps consider a spinal tap to determine what's going on in the cerebrospinal fluid? I'm just guessing here and I know it's an extreme diagnostic tool but, I'm at a loss aside from using medications until your symptoms subside. Has the magnitude of the headaches remained at the same level of pain today?


I do have chronic insomnia since this incident. I can't sleep adequately without a good dose of L-theanine along with melatonin. The L-theanine, however, seems like it has stopped working for me altogether now at reasonable doses.

I am not overly excitable or anxious, but then I have been taking 5mg elemental lithium (as orotate) since the past month, along with 600mg+ L-theanine. I now finally got me some Lemon Balm to try.

I read that a spinal tap is dangerous when ICP is elevated, and is not to be performed.

Yes, the magnitude of the pain has remained the same. One observation is that it is mostly absent in the morning, and gets worse later in the day.

Edited by Climactic, 10 July 2013 - 04:01 AM.

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#1226 jeftrit Re: Sunifiram?

  • Location:USA Harrisburg, PA
  • yes

Posted 10 July 2013 - 10:36 AM

This is an off-label solution now generic but you still need a Doc to write the Rx Donepezil>
www.ncbi.nlm.nih.gov/pmc/articles/PMC2962822/ neuroprotection against glutamate toxicity from British journal of Pharmacology Nov. 2010 the charts reveal substantil proof. I am on my way to acquire 30 tablets hoping to reduce my own suni induced headache. This med can cause nausea so is best with food. I will keep you apprised with results. &$15. USD is not too high for generic when compared to Bigpharma price Aricept >$350.00 for 30 tabs. Also found it interesting that the prices for all Donepezil at any given pharmacy are the same for 5 or 10 mg tablets. Might as well buy the 10mg and take1/2 that way your supply lasts twice as long. 5 mg/day is standard dose for starters.

Edited by jeftrit, 10 July 2013 - 10:51 AM.

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#1227 3AlarmLampscooter Re: Sunifiram?

  • Location:Every nook and cranny... of our little town.
  • yes

Posted 10 July 2013 - 11:57 AM

This is an off-label solution now generic but you still need a Doc to write the Rx Donepezil>
www.ncbi.nlm.nih.gov/pmc/articles/PMC2962822/ neuroprotection against glutamate toxicity from British journal of Pharmacology Nov. 2010 the charts reveal substantil proof. I am on my way to acquire 30 tablets hoping to reduce my own suni induced headache. This med can cause nausea so is best with food. I will keep you apprised with results. &$15. USD is not too high for generic when compared to Bigpharma price Aricept >$350.00 for 30 tabs. Also found it interesting that the prices for all Donepezil at any given pharmacy are the same for 5 or 10 mg tablets. Might as well buy the 10mg and take1/2 that way your supply lasts twice as long. 5 mg/day is standard dose for starters.


Unitedpharmacies sells it also, no prescription required. I've been very impressed with them, thus far I've gotten propranolol and oxytocin both of which were delivered fairly fast, and at pretty great prices.

They are definitely my favorite online pharmacy at the moment.

http://www.unitedpha...tring=Donepezil
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#1228 Climactic Re: Sunifiram?

  • Location:USA

Posted 10 July 2013 - 01:28 PM

This is an off-label solution now generic but you still need a Doc to write the Rx Donepezil>
www.ncbi.nlm.nih.gov/pmc/articles/PMC2962822/ neuroprotection against glutamate toxicity from British journal of Pharmacology Nov. 2010 the charts reveal substantil proof. I am on my way to acquire 30 tablets hoping to reduce my own suni induced headache. This med can cause nausea so is best with food. I will keep you apprised with results. &$15. USD is not too high for generic when compared to Bigpharma price Aricept >$350.00 for 30 tabs. Also found it interesting that the prices for all Donepezil at any given pharmacy are the same for 5 or 10 mg tablets. Might as well buy the 10mg and take1/2 that way your supply lasts twice as long. 5 mg/day is standard dose for starters.


Donepezil seems like a good drug that I previously overlooked. The study you linked states exactly what I wanted to hear, i.e. that it lowers the NR1 subunit (which is activated by sunifiram) and also glutamate mediated calcium entry.

Wait, what did you say about you having sunifiram induced headache? Is this a prolonged headache? If so, we need to hear more about it.
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#1229 rikelme Re: Sunifiram?

  • Location:San Jose

Posted 10 July 2013 - 05:42 PM

Hey guys,

If anyone wants my 988mg (what's left after I took 2x 6mg) of sunifiram, PM me. I get skin itching and increased body temperature without any noticeable cognitive improvements whatsoever and I my intuition tells me that I should not take it anymore.

I bought it from NSN.

Cheers

Edited by rikelme, 10 July 2013 - 05:42 PM.

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#1230 Sunwind Re: Sunifiram?

  • Location:England

Posted 10 July 2013 - 07:54 PM

Hey guys,

If anyone wants my 988mg (what's left after I took 2x 6mg) of sunifiram, PM me. I get skin itching and increased body temperature without any noticeable cognitive improvements whatsoever and I my intuition tells me that I should not take it anymore.

I bought it from NSN.

Cheers


Skin itching? I had that but I assumed it was histamine release from modafinil, are you sure it's the Sunifiram? I haven't taken either of them since I got the itching, but it would be nice to find out it wasn't the Moda, because that was useful for me.
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