High doses of dextromethorphan.. produce effects similar to classical hallucinogens

[DotChem]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3652430/

Abstract

Rationale

Although reports of dextromethorphan (DXM) abuse have increased recently, few studies have examined the effects of high doses of DXM.

Objective

This study in humans evaluated the effects of supratherapeutic doses of DXM and triazolam.

Methods

Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg/70kg), and placebo were administered to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Subjective, behavioral, and physiological effects were assessed repeatedly after drug administration for 6 hours.

Results

Triazolam produced dose-related increases in subject-rated sedation, observer-rated sedation, and behavioral impairment. DXM produced a profile of dose-related physiological and subjective effects differing from triazolam. DXM effects included increases in blood pressure, heart rate, and emesis, increases in observer-rated effects typical of classic hallucinogens (e.g. distance from reality, visual effects with eyes open and closed, joy, anxiety), and participant ratings of stimulation (e.g. jittery, nervous), somatic effects (e.g. tingling, headache), perceptual changes, end-of-session drug liking, and mystical-type experience. After 400 mg/70kg DXM, 11 of 12 participants indicated on a pharmacological class questionnaire that they thought they had received a classic hallucinogen (e.g. psilocybin). Drug effects resolved without significant adverse effects by the end of the session. In a 1-month follow up volunteers attributed increased spirituality and positive changes in attitudes, moods, and behavior to the session experiences.

Conclusions

High doses of DXM produced effects distinct from triazolam and had characteristics that were similar to the classic hallucinogen psilocybin.

up to 800mg DXM! ... long term effect after 1time use is similar to that Ibogaine. With opiates..

Studies have suggested that the N-methyl-d-aspartate antagonist dextromethorphan may be useful in the treatment of opioid dependence..." We provide evidence—decreased concomitant heroin use—of low-dose add-on DM’s efficacy for treating opioid-dependent patients undergoing MMT ...": A Placebo-Controlled Trial of Dextromethorphan as an Adjunct in Opioid-Dependent Patients Undergoing Methadone Maintenance Treatment: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540107/

My question is: can mega doses of DXM(>500mg) lead to similar detox that Ibogaine without the need for MMT. The second study used only 60mg DXM as adjunct to MMT and the first up to 800mg. Since it has pretty large TI ie very safe,
Now what's up with increased spiritualty/mystical experience a month following use? is DXM inducing LTP in some parts of the brain associated with religious experience??? or good moods (anti-depressants..)

 

[N0 W4RN1NG]

High doses of DXM, can very efficiently bind to it the serotonin transporter. Binding ki at SERT is actually higher than some SSRIs for the unmetabolized parent.

This, along with the NMDA antagonism of DXO and the potential opioid affinity of 3-methylmorphinan, can lead to elevated serotonin levels, theoretically sufficient enough for 5HT2A/C to be preferentially stimulated.

Evidence for this outcome is weak.

IMHO, many of the users who thought they had received a classical hallucinogen, might not have actually had much real experience with "true" hallucinogens.

I have had experiences with 3-MeO-PCP, another dissociative with some serotonergic activity, that to an inexperienced "psychonaut" could TOTALLY have been perceived as what "LSD must be like".

I want to highlight that taking 800mg DXM on MMT is NOT SAFE, I REPEAT, NOT SAFE. I did not read the entire study, only your brief synopsis, but that bit of advice is absolutely ridiculous, and for the time being I will blame that error on the study.

Large doses of DXO, or any NMDA antagonist, can indeed produce marked future antidepressant qualities.

And it is well known that DXM potentiates all opioid, as well as helps mitigate tolerance. Although it is not to be used with pethidine, especially at the beginning of pethidine treatment.

EDIT: I do not know whether high dose DXM can successfully mimic ibogaine-style treatment for opioid dependence. I suspect that part of Ibogaine's efficacy lies in it's ability to force the user to abstain for quite some time from using the addictive agent, since they are more or less incapacitated for a lengthy period - after which, the worst of their withdrawals may actually already be over. Get a second opinion from someone else here on that last bit.

 

[DotChem]

I want to highlight that taking 800mg DXM on MMT is NOT SAFE, I REPEAT, NOT SAFE. I did not read the entire study, only your brief synopsis, but that bit of advice is absolutely ridiculous, and for the time being I will blame that error on the study.

Take time to read before reacting! It save a lot of times for everybody. larges doses WITHOUT THE NEED FOR MMT!!! the sudy that uses 800mg do not, I repeat do not use methadone whatsover. where did you get that??

I agree with you though: the experience has nothing to do with classical psychedelic. Was discussed in length in some earlier thread dealing with Ibogaine and similiar dissociatives. Which is the reason I ask the question: can large doses of DXM be equivalent (and yes SAFER) than Ibogaine for heroin detox?

 

[N0 W4RN1NG]

Ahh, I see. Keep in mind: I said overtly in my previous post that I had not read the study in full, only your summary - and after quickly rereading that summary, I cannot help but notice that nothing you posted (without actually following the links therein) mentions that the patients receiving "up to 800mg DXM" had actually ceased their MMT therapy; as such, in the nature of harm reduction, I stand by my original comment (mind you, I blamed the study, and not you, for recommending that combination ... I feel the majority of MMT users reading this thread will also not click the links. Therefore, as a friendly suggestion, I ask you to edit your OP to include that information).

I think there is some truth to the idea that high dose DXM for a few days in a row may be similar in efficacy - once already having terminated their opioid use for at least a day - as ibogaine for remission from opioid dependence.

However, I would not recommend it. The idea as a whole holds water - but then, why not use safer NMDA antagonists? Surely a multiple day, carefully dosed regimen of 2-oxo-PCE, or MXE, would have similar benefits to DXM "therapy", and be quite a bit safer in my opinion.

 

[DotChem]

A

However, I would not recommend it. The idea as a whole holds water - but then, why not use safer NMDA antagonists? Surely a multiple day, carefully dosed regimen of 2-oxo-PCE, or MXE, would have similar benefits to DXM "therapy", and be quite a bit safer in my opinion.

Are you kidding me? do you actually know what DXM is? it is the ingredient of the common cold flu medicine Nyquil sold over the counter without any scripts for decades: Over-the-counter! that is as safe as it gets at least according to the United States FDA

Now,2-oxo-PCE and MXE are designers drugs sold after the crackdown ban on PCP-like and ketamine related on the streets. Use at your and mine own perils! There is no science behind either their safety or effectiveness. Now that doesnt mean they are not safe: I just don't want be the first to fiind out the effect of larges doses of MXE!!

 

[N0 W4RN1NG]

Are you kidding me? do you actually know what DXM is?

I hope not to come across as callous, seriously, as although English and German are native languages to me, I often find myself "thinking" in German and then translating the English equivalent...and direct translations of German are often impolite sounding...

But I actually, literally laughed at this line.

Look, I understand where you're coming from. You're right, there is not much science on those specific chemicals, although the science on their close relatives is truly a plethora...

Yes, many thanks, but I am keenly aware of what DXM is - and it is good to have your link in the thread for
Those who might not.

However, you would be really something quite different from the "first person to experience the effects of high dose MXE".

I am in contact with many peoples who take upwards of 1g MXE in a single day, many MANY days in a row, and have been doing so for months if not years. They aren't "at the height of their health" exactly, but more so than a Ketamine user I know who does less than that daily.

Perhaps you should look into some of the more obscure forums out there, there is great info from heavy users, even some CBCs post-use, etc.

I do not in any way reccomend taking either substance in such quantities or frequency. But it is quite clear that a much lower dose, for only a few days in a row, MXE (and therefore, presumably it's 3-hydrogen counterpart (2-oxo-PCE) is not an acutely toxic substance, and despite there not being a direct study comparing toxicity of DXM to MXE, I am of strong conviction in regards to my previous post, and as such, stand by it's contents firmly.

EDIT: Where are you living, that this "crackdown" has occurred? Surely not in Europe or north america, where PCP and Ketamine have been banned for aeons...

EDIT2: To assume a substance is safe purely because the FDA has deemed it O.K. for OTC sale, and approved only at 13x lower dosage than OP suggested, is the height of folly. By this logic, 6,500mg acetaminophen is a great dose.

 

[Solipsis]

To assume a substance is safe purely because the FDA has deemed it O.K. for OTC sale, and approved only at 13x lower dosage than OP suggested, is the height of folly. By this logic, 6,500mg acetaminophen is a great dose.

QFT

and much agreed: I don't think very high doses of DXM aren't that safe at all, the promiscuous pharmacology and the fact that it plays notoriously bad with other psychoactives don't exactly bode well either.

As for potential for addicts: it doesn't seem like it's understood, theorized strongly or agreed on what is the key to iboga alkaloid therapy, and whether kappa or sigma are important. Seems like we'd have to know more about which one (or two) are important and how these are best and most selectively found in one drug or a mix of say two selective ones.

Dissociative trips of nearly any kind seem to have the potential to be transformative, so they can help with problems / changes in a person's life or crucial insights... but despite that, those experiences are far less reliable than iboga effects apparently... I don't think we are collectively so foolish that we overlook that it is just NMDA antagonism.

 

[DotChem]

OP detox .. serendipity DXM 30 mg single dose + diphenydramine .. BL thread
(anecdotal evidence)

Hi, this is my first post here. I never really felt the need to create an account as I never really had anything to say. This all changed earlier today.

First a little about me. I'm legitimately prescribed 150 10mg/325mg norco each month for a back injury that I simply haven't had the time to get operated on. This happened roughly 3 years and all was well for the first year. Then I'd have a bad day and take a few extra to relax... and... well... I'm sure you all know how it goes from here.

The last year and half the following pattern has persisted. Get prescription filled (this time I'm going to be strong and only use 4-5 a day so I don't run out early). The first 3 days are great. Then I start chasing that high and within a week I'm back to using 15 a day. 10-15 days later... wtf happened? This was supposed to be it. That's it, I'm never touching this shit again.

I know what I have coming. A seven day all expenses paid trip to hell. I take my last dose even though I know I won't enjoy it. All I can think about is what's to come. 6-8 hours later my nose starts to run. The profuse sweating begins. Next I start to feel that growing inferno in my stomach. As if Hades has taken residence in my abdomen. I'm freezing cold and burning hot at the same time. Put a blanket on it just exacerbates the putrid heat. Take the blanket off and I feel naked outside on a cold winters day. The vomiting and diarrhea are as relentless as an addict looking for his next fix. The mental anguish... knowing that the worst is still to come. I lay down to get some sleep. It is difficult to describe the horror that is opiate RLS. I am exhausted as if I had not eaten in 10 days yet my body constantly taunts me to move. "Move your arms, legs, get up and stretch, jog in place" it says. "I am so completely exhausted, I just want to rest." But it shows no mercy. The depression... oh the depression. My little brother was killed by a drunk driver a few years ago and every time I go through withdrawal the depression reminds of how I felt after my parents told me what happened. An all encompassing feeling of utter doom. As if your life as you know it is completely over.

Sure enough though, these symptoms begin to vanish. The first week after the symptoms subside I have an optimistic attitude toward life. I feel like I can beat this. I start hanging out with friends again. Exercising and playing sports. I feel like I'm in the clear. Then without fail, an indescribable urge to use overcomes me. As a wild boar instinctively runs for its life when chased by a lion, I call in my prescription as if my very existence depended on it. Nothing else matters. The vicious cycle repeats.

Fast forward to last night. In an attempt to get the most out of my last few pills I decided I'd try to potentiate them with DXM and diphenhydramine. About 1 hour before using I took therapeutic doses of both (30mg of DXM and 50mg diphenhydramine). I took my pills and waited. 30min went by and I didn't feel much. "That's odd" I thought. "I'm usually feeling something by now". It took about an hour before I started feeling anything and it went away fairly quickly. "Fuck it" I thought and I took the remainder of my pills (a dose that would normally have my flying high). I sat there and waited... and waited... nothing. "Potentiates my ass, what a fucking waste of pills" I thought. At this point I figure I'll try to get as much sleep as possible because I know I won't sleep 5 minutes in the next week. To my surprise I sleep for a full 10 hours. "That's odd" I'm thinking. Normally I'd be in pretty bad withdrawal right now. I feel a little sweaty and warm but that's about it. "The DXM must have slowed my metabolism of the opiates, guess it's just gonna hit me a bit later". As the day goes on things aren't getting worse but slightly better. Here as I type it's been 24 hours since my last dose and the only symptom I have is mild discomfort due to light sweating.

The reason I bring this up is because I've been through this exact withdrawal at least 15 times. Every single time by the 24 hour mark I'm in full blown, crawling out of my skin, hot/cold, debilitating depression, nausea/vomiting/diarrhea. The mild discomfort I'm feeling now is so far from what I was expecting that it's simply mind boggling. Now perhaps the DXM is only delaying the inevitable. If this is the case I'll be paying the piper in the next day or two. However, I don't see how this could be the case considering the different mechanisms of action between opiates and DXM. There should be no cross tolerance between the two drugs. Regardless of what happens, I feel there is something to this. It might also be worth a mention that DXM has a much greater effect on me than most people due to an enzyme deficiency. 90mg of DXM has me pretty out of it which is the reason I only took 30mg to potentiate.

 

[white55]

High doses of DXM, can very efficiently bind to it the serotonin transporter. Binding ki at SERT is actually higher than some SSRIs for the unmetabolized parent.

This, along with the NMDA antagonism of DXO and the potential opioid affinity of 3-methylmorphinan, can lead to elevated serotonin levels, theoretically sufficient enough for 5HT2A/C to be preferentially stimulated.

Evidence for this outcome is weak.

IMHO, many of the users who thought they had received a classical hallucinogen, might not have actually had much real experience with "true" hallucinogens.

I have had experiences with 3-MeO-PCP, another dissociative with some serotonergic activity, that to an inexperienced "psychonaut" could TOTALLY have been perceived as what "LSD must be like".

I want to highlight that taking 800mg DXM on MMT is NOT SAFE, I REPEAT, NOT SAFE. I did not read the entire study, only your brief synopsis, but that bit of advice is absolutely ridiculous, and for the time being I will blame that error on the study.

Large doses of DXO, or any NMDA antagonist, can indeed produce marked future antidepressant qualities.

And it is well known that DXM potentiates all opioid, as well as helps mitigate tolerance. Although it is not to be used with pethidine, especially at the beginning of pethidine treatment.

EDIT: I do not know whether high dose DXM can successfully mimic ibogaine-style treatment for opioid dependence. I suspect that part of Ibogaine's efficacy lies in it's ability to force the user to abstain for quite some time from using the addictive agent, since they are more or less incapacitated for a lengthy period - after which, the worst of their withdrawals may actually already be over. Get a second opinion from someone else here on that last bit.

visuals from dissos? how? choppy vision sure, delusional beliefs to

but psy visuals?

only happened once, i vaped some o-pce and had some slight psy morphing for 20 min or something

can you do it on purpose or is it random?

 

[theGirlWithBlueHair]

I've gotten visuals the first time I did DXM, but this was after everything wore off. I was seeing lights, and plants and environments on the walls. I think they can have cognitive and some visual similarities because of the way they increase glutamate transmission in the prefrontal cortex. A lot of the psychedelics share similar pathways. Such as cannabinoid receptors being coupled to 5ht2a receptors in parts of the brain,etc.

> "High doses of DXM, can very efficiently bind to it the serotonin transporter. Binding ki at SERT is actually higher than some SSRIs for the unmetabolized parent.

This, along with the NMDA antagonism of DXO and the potential opioid affinity of 3-methylmorphinan, can lead to elevated serotonin levels, theoretically sufficient enough for 5HT2A/C to be preferentially stimulated."

Serotonin itself does not cause psychedelic effects though because it doesn't affect phospholipase C activity after receptor activation.

Ibogaine works via mechanisms as a serotonergic hallucinogen, a NMDA antogonist, a mu opioid agonist, and a kappa opioid agonist. That's a combination of three psychedelic mechanisms in one drug. It helps with addiction via spiritual methods and introspection.

 

[Beings]

Based on my brief personal encounter with cough syrup I disagree. Tried from 50 all the way to 700+ mg of dxm at which point there was extreme dissociation from the body (could not tell if I am breathing even if I tried). All vision on the come up turned to a shade of green, like seeing through a green filter, but never went psychedelic. Was not really introspective or enlightening at all. More like being paralyzed where you do not have ego death, but no longer have any stimuli aside from blurred loopy vision and hearing. So you are confined alone with your thoughts. I guess you can use this state to think introspectively. It was fun as a first encounter with mind altering substances, but it is fundamentally different from classical psychedelics. Classicals boost the sensation of all the inputs, even if you lose a sense of external stimuli and are overpowered with the internal stimuli. DXM imo does the opposite, blocks everything where you are left with limited input, so you can parse it easier as nothing else is occupying your brain.

 

[theGirlWithBlueHair]

Dissociatives are classified as a separate class of psychedelics. The visuals aren't psychedelic in a classical sense, but it's definitely hallucinogenic. different types of hallucinogens share similar pathways and affect similar chemicals in the brain, though. DXM isn't a good way to qualify dissociatives because it's a very dirty drug with prominent pharmacological mechanisms other than its NMDA antagonism. I always found dxm very introspective, until hitting a certain dose and getting sucked into a hole, of course.

 

[serotonin2A]

My recollection of the study is that there are several confounds that call into question the conclusion that DXM produces hallucinogen-like effects. It was performed by a laboratory that is well-known for testing psilocybin, so most of the subjects probably expected to receive psilocybin. The weird thing about the study is that they asked the subjects to classify the pharmacology of the test substance and most answered hallucinogen not dissociative anesthetic. Right there, that shows that there is an issue with the study. In other words, there were two problems with the results -- they misidentified DXM as a psilocybin-like hallucinogen, but they also failed to correctly classify DXM.

 

[CNSninja]

What an interesting read. I don't know how many other people have experienced this chemical the way I have, but when I was 17 I was heavily into DXM for about a year, using it at least twice a month, I'd say, and I wouldn't ever take a dose below around 500mg, but a more typical dose for me was closer to a gram (950-1050mg,) and at those doses, every single time, I would always tell my tripping buddy that "forget what I said last time, THIS time I'm tripping an 'unprecedented' amount of balls!" and I would, without fail, have absolute, full-on open-eye visuals (at night.) The visuals from high-dose DXM weren't like tryptamine visuals to me- they weren't all geometric and colorful, but they were definitely extremely interesting, and some of the things I saw would be similarly themed to mushroom visuals (always, always sea life, particularly octopodes and seahorses.) I remember sitting on my friend's porch when we peaked, unable to walk properly anymore (we used to trip and go walk these trails in the woods and trip out at how we didn't fall into any of the foot-wide, several-mile-deep holes we'd both hallucinate on the trail in front of us,) and across the street from us when we sat on this porch were these giant bushes, and one night I stared at them for a good 40 minutes watching this crazy, strange, creepy carnival unfold in the greenery of the bush, and it pulsed and spin and it was so wild. I stood up at one point to point out to him where I saw the various things I was describing to him, and as I looked down the dead-end road he lived on I saw what I can only ever describe as a massive, 30-foot-tall, mechanical, stick-figure deer with a couple smaller baby mechanical, stick-figure deers, the big one up on its hind legs, the rest just chilling, all of them perfectly motionless in front of the woods at the end of the road.
One way the experience was totally different from tryptamine psychedelics is that the closed-eye visuals were the most stable visuals I've ever experienced. By that I mean I could close my eyes and imagine something I wanted to see, open my eyes, close them again and it would still be the exact same image in my visual field. I used to be able to sit and (poorly) draw the CEV images I was seeing because they'd remain perfectly unchanged for as long as I wanted. That was one of the most interesting things about the CEV's I got from high doses of DXM.
For me DXM was definitely highly hallucinogenic, highly psychedelic, more controllable than tryptamines, far less colorful than tryptamines, far more dirty and chemical-esque than tryptamines, and overall more 'stupid-feeling.'

Man, I wish it didn't have such a long and anti-functional afterglow. I'd love to revisit it but I just don't want to be stumbling around uncoordinated for a full day afterwords. I never knew what a "hole" was back then, but now that I look back I clearly remember holing on DXM several times, almost exclusively after having taken a long break. Fuck- watching movies on hole-doses of DXM was so crazy. I'd get so absurdly lost and not one single iota of the story or the lines would make any sense, it'd seem like all the characters in the movie were talking 'at' me from the screen, literally looking straight into the camera, right into my eyes, and saying their lines or just random shit directly to me instead of their co-stars lmao. Looking back I realize I probably fought the hole every time. What a shame. I'll have to revisit someday when I've got a few days days and responsibilities to fulfil.
Cheers!

 

[Limpet_Chicken]

Yes! a fascinating bit of eye candy this thread. And btw how important is sigma agonism w/ respect to DXM contribution.

 

[serotonin2A]

Yes! a fascinating bit of eye candy this thread. And btw how important is sigma agonism w/ respect to DXM contribution.

Sigma-1 interactions almost certainly do not contribute to the subjective response. If you look at a wide-range of sigma-1 ligands-- haloperidol, fluvoxamine, citalopram, cocaine, progesterone, phencyclidine, methamphetamine, N-allylnormetazocine, dimethyltryptamine, DXM, clorgyline, harmaline, pregnenolone, sertraline -- it is obvious that there are no commonalities in their subjective effects. I'm not saying that sigma-1 binding is without effect, but it doesn't seem to result in specific subjective effects.

 

[Skorpio]

Sigma binding may very well add to the effects of DXM. The sigma receptor is quite unique as receptors go, and one of its functions is co localizing gcprs such as the cb1 receptor to the nmda receptor. This could cause additive behavioral effects and be part of the reason that DXM has the unique feel (other nmda antagonists are sris too you know).
https://www.ncbi.nlm.nih.gov/pubmed/26461475

Also in a more subjective manner, selective sigma agonists (which are indicated for antitussive activity) such as noscapine have reported effects that seem near the nmda antagonist signature.

 

[serotonin2A]

Sigma binding may very well add to the effects of DXM. The sigma receptor is quite unique as receptors go, and one of its functions is co localizing gcprs such as the cb1 receptor to the nmda receptor. This could cause additive behavioral effects and be part of the reason that DXM has the unique feel (other nmda antagonists are sris too you know).
https://www.ncbi.nlm.nih.gov/pubmed/26461475

Also in a more subjective manner, selective sigma agonists (which are indicated for antitussive activity) such as noscapine have reported effects that seem near the nmda antagonist signature.

I understand why you are making these assumptions, but there is a major problem with your argument for sigma-1 involvement. It is true that the antitussive effects of dextromethorphan and noscapine are thought to be mediated by sigma-1 binding. But those interactions happen at doses that are at least an order of magnitude lower than the doses required to produce behavioral effects. If sigma-1 receptors mediate the effects of noscapine on cough and its dissociative effects, than there should be some overlap in terms of their dose-responses, but that doesn't seem to be the case. When DXM is administered at high doses that produce dissociative effects, it (and its metabolites) interact with a variety of sites that are known to produce dissociative and psychoactive effects.

With noscapine, the therapeutic (presumably sigma-1 mediated) antitussive effects occur at around 30-90 mg. Much higher doses have to be administered to get dissociative effects. Cancer patients have been prescribed 3000 mg/day, resulting in only mild sedation in some patients. At those doses, noscapine interacts with many targets other than sigma-1. Those secondary interactions are why noscapine has been investigated as a cancer treatment. And while it is true that noscapine is not an NMDA-R antagonist, that doesn't eliminate the possibility that one of its metabolites is an NMDA-R antagonist.

 

[Cotcha Yankinov]

Hallucinogenic effects aside, it's possible Sigma 1 receptors are playing a role in DXM's antidepressant effects https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938562/

 

[Limpet_Chicken]

And what is the importance of sigma-2 receptors?