Dissociatives [Interaction Subthread] DXM & Medication / Supplements

EDIT (02/11/2022): 20 years later, we now know that combining DXM with SSRIs, SNRIs, or MAOIs is extremely unsafe and can lead to serotonin syndrome - which is potentially fatal. Serotonin syndrome can cause seizures, long-term cardiovascular and neurological issues, and - in many cases - death. Two of DXM's mechanisms of action are as a serotonin-norepinephrine-reuptake-inhibitor and serotonin releaser, so it should not be combined with serotonergic compounds under any circumstances. These include 5-HTP, MDMA, and similar compounds. Here is a report of a patient admitted to a hospital due to taking Coricidin while on SSRIs.

Combining DXM with Magnesium is also extremely unsafe and has been reported to lead to seizures and even death. Wellbutrin (an NDRI) and other CYP2D6 inhibitors should be avoided, as they can prevent your body from metabolizing DXM and lead to it staying in your system for many days - also potentially causing serotonin syndrome. Wellbutrin is particularly unsafe as its NDRI effects significantly worsen physiological effects of DXM such as high blood pressure and increased heart rate while also worsening anxiety in many cases. Many on Bluelight and Erowid have reported negative side effects from these combinations ranging from highly unpleasant to life-threatening. Please avoid them for your own safety. - @arrall

Do not under any circumstances use DXM with yohimbine or any other alpha-2 adrenergic antagonist. This combination could vastly potentiate the danger of Olney's lesions.
Ok, before I begin no this is not the typical "can i take dxm and ssri's" question. Hopefully this will benefit anyone considering using dxm while on an ssri. To continue...
I've been on an SSRI for quite a while now, and during that time have been doing a lot of experimenting with DXM. Yes, I have been under over and through all of the warnings between the two and have considered them in all my use.
To consolidate what I have learned, I have found that personally an SSRI greatly enhances, lengthens and intensifies a dxm trip. For me it has cut down on nausea, increased my euphoria, and helped with the lingering after effects. Being on an SSRI has solved almost all the problems I've had with DXM and in turn made it a much more powerful drug. (this seems to be contrary to general info)
After *much* searching for the results and experiences of other SSRI + DXM users I have found VERY little, so here I'm reaching for ANYONE who has EVER used DXM while on treatment of an SSRI. What did you notice different about the trip, was it overall better/worse? What about the length of the trip?
I am really looking for any info I can get here, as this seems to be a pretty uncharted (or at least unrecorded) region. Thx for your time
(note: I've already hit erowid, the lycaeum, and every dxm-specific source there is)

For me it lengthened the trip and made it a bit stronger. I was still extremely under the influence when I woke up which was not a good thing in my book.

I haven't necessarily used DXM while on SSRIs but decided to go back on my medication (Celexa) the morning after tripping on DXM. It was not cool to say the least...pounding headaches and feeling sick for 2-3 days. This was not due to DXM alone...I consider myself an experienced DXM tripper and have NEVER experienced those side effects. Hope this helps.

stardreamer... I'd be interested in hearing about your experiments... ie. dosages, what happened, how many times, which SSRI, etc.

PuristLove: Yeah I'd love to share my results. I've dedicated nearly a year to discovering the "truth" of this combo - wheather it is actually harmful or if it can be positive. I think many would find what I've come to interesting and helpful.
I'll pop you an email.

after careful research i decided it would be ok to do dxm... i'm on a very low dose of celexa and i hadn't taken any that day. the trip was probably stronger than usual, but nothing bad happened.
celexa, however, is a special case - unlike most SSRIs it's only a weak inhibitor of the liver enzyme CYP-2D6. CYP-2D6 is responsible for metabolizing DXM into its more psychoactive metabolite, DXO. therefore, a person taking any SSRI except celexa (e.g. prozac, zoloft, or paxil) would be much less able to metabolize DXM into DXO and would experience, most likely, a longer, less pleasant trip. larger doses of celexa might be somewhat riskier as well.

i thought dxo was the less enjoyable part of dxm tripping. cant remember the source but i think it was on erowid experiences. were this guy made some dxo and compared it to regular dxm experiences.
but that would make celexa a good combo as it can enable you to lower ur regular dxm dosage(and avoid nausea etc from dxm)?
anyone?

A large portion of when I've used dxm while on an SSRI has been with celexa.
I am now on zoloft and am still using dxm and notice that the trip is longer, but seems to be much more euphoric. This may be psychosamatic(sp?). Thanks for the heads up

Instead of "popping an email" to purewristlove, why don't you just fucking post it on the board. You started a post about it, follow through or delete your post.

I've also heard that djremix. And I put that shit to the test...
I know it sounds crazy, but I'm sure that everyone had heard about the grapefruit juice thing. I drank about 3/4 gallon of grapefruit juice after dosing ~10mg/kg of pure DXM HCl. From what I have read this was to help turn more of the DXM into DXO. I understand that the body does this also, but not enough to fully change all the DXM. My trip was rather uncomfortable to say the least, and I have much experience with DXM in the form and amount I was taking. I had less euphoric effects and the trip had much more physical discomfort.
I realize that this was only one experience, but I tried to control set and setting - taking the DXM/grapefruit combo whilst alone and in a good frame of mind - something I had done many times before on the plain DXM. But something was different and I am not really willing to dismiss it as a placebo effect (although that might have effected my expectations a bit I will admit).
I would be interested if an SSRI's ability to somehow block DXO being produced might be responsible for stardreamer's positive experiences. I realize the dangers, but it is interesting nonetheless.

Maybe I should somehow turn this into a FAQ, but here goes
NOTE: These results may or may not be individual, and trying anything here is not in the true spirit of harm reduction.
<b>One man's experiences with dxm + ssri's
[ 12 July 2002: Message edited by: stardreamer ]

ssri potentiates dxm via metabolism?

I thought of this the other day apon just waking up
I recall someone saying that (certain?) ssri's compete for the same liver enzyme which metabolizes dxm into dxo. As I understand it, dxo is the less pleasant of the two, and often attempts are made to avoid it.
As I wrote a month or two ago, my use of an ssri (zoloft and celexa) has made dxm 10x better. Could this be related to the slower metabolism of dxm?
Just looking for opinions or info I missed. Also please correct me if I'm wrong on any part of this, as im not 100% solid.

good question... let me go research the specific isoenzymes involved in the cytochrome P450 with each agent and get back to you. I believe the 3A4 or the 2C9 might play a significant role. If they are monopololized by the specific SSR your on, and are needed to break down DXM, then your answer is YES - they would influence the DXM trip... it's then a matter of discerning to what magnitude.
I'll follow up in a bit.
SG

dextromethorphan undergoes O-demethylation to form dextrorphan via the same route CYP2D6 enzyme system that converts codeine to morphine.
Knowing this SSRI's like paxil and some other effect the CYP2D6 enzyme maybe making it weaker in creating dextrorphan, at least that is the most in cases when codeine undergoes transfermation to morphine.

^^^
That sounds right, as I recall. So Purist and stardreamer would also be correct.

Cool, good to come to some reasonable conjecture.
Also, for safety's sake, no one reading this go out and take a few ssri's and some dxm hoping to get high, you'll probably get entirely sick and vomit, or worse.
So far Celexa has been my ssri of choice to potentiate dxm. I find the euphoria is far more intense and the comedown is actually satisfying! It's not like normal where I slowly drop into feeling shitty and then fall asleep, I actually come down into a pleasant state which remains for much of the day.
Somewhere back in time I posted a long thread about my results with dxm+ssri's, and I'm glad to finally have an answer for it.

In one pilot study CYP2D6 deficient subjects (whose liver does not form DXO) barely tolerated 3 mg/kg dose of DXM. This suggest that DXM is responsible for sedation, dysphoria, and motor impairment, whereas the positive subjective effects may be mediated by the active metabolite dextrorphan (DXO). Though, there seems to be some contradicting reposrts about the psychoactivity of DXO (see: http://www.erowid.org/experiences/exp.php3?ID=7559 )
Reference:
Zawertailo LA et al. Psychotropic Effects of Dextromethorphan Are Altered by the CYP2D6 Polymorphism: A Pilot Study. J Clin Psychopharmacology, 1998, 18(4):332-337

^^^
the dxm was barely tolerated, how does this suggest that it is dysphoric?
I've been searching around for about six months, and it seems that most people prefer to avoid dxo in any way they can, and I've seen some pretty strange methods of doing this, whether or not they worked is another story.
It seems to me that dxm appears more euphoric, although I'm sure cases vary tremendously, and that dxo is more responsible for physical aspects (possibly explaining why some get "robo itch" and others dont)
Interesting, to say the least.

DXM Combination Interactions

Beware of mixing DXM and other drugs, legal or not. Any time you do, you risk an adverse reaction with your own physiology that cannot be predicted. Nonetheless, people have asked about it and here are the results from people who have combined DXM and other drugs.

ALCOHOL

Some users report that a small amount of alcohol (a beer or two) before the DXM can both enhance the trip and prevent some nausea. Alcohol following the DXM trip seems to be reduced in some, but not all, of its effects. Note that large doses of alcohol combined with DXM often cause prolonged vomiting (up to 2 hours!) Alcohol after the end of a high dosage DXM trip has been reported to temporarily bring back many of the dissociative effects (cannabis and nitrous oxide also do this). This seems possible up to five days after the DXM trip, depending on your metabolism and brain chemistry.

Barbiturates and Benzodiazpines

Barbiturates ("downers") include drugs like seconal and nembutal; benzodiazepines include drugs like diazepam (ValiumTM), LibriumTM, and other antianxiety drugs. Generally speaking most but not all prescribed sedatives, antianxiety drugs, and recreational "downers" fall into this category.

Some people have reported that combining DXM with a low dose of a benzodiazepine can prevent some of the more annoying side effects (mostly related to overstimulation, high blood pressure, and tachycardia). Clonazepam (Klonopin) in particular has been reported to have specific effects in combination with DXM, different from other benzodiazepines. These effects include enhanced CEV's (closed-eye visuals) and, of course, limiting or preventing sympathomimetic effects (high blood pressure and heart rate, sweating, etc.). I can't recommend this, and these drugs are of course prescription-only, but it doesn't seem to me that a low dose would be harmful. Just don't do it regularly.

Avoid barbiturates, and be careful with benzodiazpeines; both barbiturates and benzodiazepines tend to be dangerous enough by themselves and are frequently fatal when combined with other depressants (such as alcohol).

Amphetamines

This is probably asking for high blood pressure problems, strokes, brain hemorrhages, and the like. While a few people enjoy this combination, most find it unpleasantly speedy anyway. Most who've tried it reported that DXM will potentiate other stimulants. Since DXM inhibits dopamine reuptake, combining it with a dopamine releasing agent (amphetamine or methamphetamine) will naturally produce a combined, synergistic effect. I'd suggesting avoiding this at all costs.

Combining DXM, a psychostimulant, and a monoamine oxidase inhibitor is a sure way to make your blood pressure skyrocket and will probably kill you (if you're lucky) or leave you with severe brain damage (if you aren't lucky).

Cannibas

DXM and cannabis is a frequent combination, which most people seem to enjoy, at least at lower doses of DXM. High doses of DXM (third plateau and up) mixed with cannabis can be very, very dissociative and sometimes unpleasant. A few people have reported that cannabis with DXM makes them feel very stupid.

Some users reported that 360mg DXM followed 3.5h later by "a bowl or two" produced a very profound, and unique, intoxication. Severe flanging of all sensory input was present, and there was an overall "vibration" feeling present in the muscles. With eyes closed, some claim that they can think fairly clearly, and solve simple and complex tasks much easier than on DXM or cannabis alone; however, with eyes open (or other sensory distraction) cognitive abilities deteriorated rapidly. Motor skills were possible only when performed automatically; any attempt to focus on them led to difficulties.

Several users have reported that cannabis and DXM generally "go well" together. Note that cannabis after the DXM trip is over seems to bring back some of the dissociative effects, much like alcohol and nitrous oxide.

DXM probably interacts with marijuana at a pharmacological level. Dissociatives decrease the analgesic response to THC and downregulate THC receptors.

LSD, Psilocybin (Shrooms), and Other 5HT Hallucinogens

Limited numbers of reports of mixing DXM with 5HT hallucinogens, primarily LSD and mushrooms. While some say this combination was "not recommended", most have had incredibly profound experiences. On the other hand, very few of these have said they would ever repeat the combination, as it was simply far too powerful and terrifying. Some have reported that DXM helped avoid unpleasant cognitive effects and "bad trips" might otherwise get from LSD alone. Regular use of DXM may alter the effects of LSD due to overall increase in 5HT binding and decreased 5HT2 receptor binding

Opiates

Some say that small amounts of opiates tend to "mellow out" the DXM trip, and reduce the possibility for panic attacks or anxiety. Other users said opiates should only be taken after the peak of the DXM trip, because otherwise they would cancel each other out to some degree.

On the other hand, this may be a dangerous combination, and I'd recommend against it. Both DXM and opiates can depress respiration and high enough doses, and there might be a synergistic effect.

Recently, a new product has appeared on the streets containing heroin, scopolamine, dextromethorphan, cocaine, and thiamine. Called "Homicide" or "Super Buick", it presents extraordinary problems due to its high toxicity. Even worse, when naloxone is given for overdose, the toxicity of the other drugs can become apparent

PCP and Ketamine

The few reports have indicated that ketamine plus DXM was not much different from ketamine. Some have said that a small dose of ketamine can boost the DXM experience by one plateau. I expect that most of DXM's particular effects on sigma receptors are overshadowed by ketamine's NMDA antagonism. Ketamine is a much more potent NMDA antagonist than DXM, and since they both compete for the same site, DXM isn't going to affect this much.

Nicotine

This is a combination which evidently is fairly interesting. Nicotine seems to vastly potentiate DXM's effects for some people, enough so that one user reported that one cigarette could floor him on a second plateau trip. Another user reported that nicotine helped him overcome some of the memory problems with higher doses of DXM, but tended to induce nausea.

On the other hand, several people report that DXM should be avoided if one smokes cigarettes regularly (even if you don't smoke during the trip), because of nausea, hot flashes, and other unpleasant interactions. This might be due to inhibition of MAO by cigarettes and if so, cigarettes should be avoided.

Do not under any circumstances use DXM with yohimbine or any other alpha-2 adrenergic antagonist. This combination could vastly potentiate the danger of Olney's lesions

nice one!