Talk:Dextromethorphan

Woah! Woah! Woah! Why the heck dose Dxm follow the normal dosage template here??? Dxm does not come in light, moderate, heavy, etc doses! If one is an experienced Dxm user they know the dose is heavily based off of body weight and the desired plateau! I must fix this, this dosage info is a disgrace to William Whites Dxm FAQ! Just kidding I'm being overly dramatic but seriously I'm gonna change that along with the description of the plateaus. Anyone else agree?

Hey there, thanks for the advice! I encourage you to change it however you wish. :) I agree that plateaus should be listed and have quickly edited the DXM substancebox template to reflect this. https://psychonautwiki.org/wiki/Template:SubstanceBox/DXM --Oskykins (talk) 15:54, 20 January 2016 (UTC)

Changed to the mg/kg system if an admin approves -- Sam (talk) 2:21, 17 July 2019 (UTC)

Perhaps for harm reduction purposes the plateaus of DXM should be mentioned in the main summary at the top. Since, for example I used to weigh ~115 - 125 pounds back in my early 20s; and 391.2mg for me would be a 3rd Plateau. Whereas for an individual who weighs 210 pounds, a 3rd Plateau would be 713.4mg. Which is a 322.2mg difference for reaching the intensity of a 3rd Plateau between different people; and this example could be even more extreme for someone who is rather underweight (I am 5'8 so 115lbs is only underweight by 1bmi) versus someone who is overweight or more so if obese. It would also be noted that these dosages are for DXM HBr which is 2x the potency & 0.5x the duration of DXM Polystyrex, so someone who is used to taking Polystyrex doesn't accidentally take a much larger dose than they want.

--JH556 (talk) 19:55, 13 July 2023 (UTC)

I'll preface this by saying I am not suggesting Wikipedia be cited as a source, but if the sources Wikipedia cites in this case could be verified as accurate and credible and consulted to contain said information, the following could be added under "Drug Interactions" for harm reduction purposes. Apparently, Bupropion (Wellbutrin), which is both dopaminergic and affects norepinephrine, but not serotonergic, is purported to interact with dextromethorphan and thus, lower the seizure threshold because a metabolite of bupropion is a strong inhibitor of the enzyme that metabolizes dextromethorphan.

"...because bupropion is itself a strong inhibitor of CYP2D6 (Ki = 21 μM),[2][30] as is its active metabolite, hydroxybupropion (Ki = 13.3 μM), it can slow the clearance of other drugs metabolized by this enzyme.[2][3][4][67] As an example, the ratio of dextromethorphan (a drug that is mainly metabolized by CYP2D6) to its major metabolite dextrorphan increased approximately 35-fold when it was administered to people being treated with 300 mg/day bupropion, indicative of a major drug interaction with a common over-the-counter medicine.[67]"

Purported sources: [2] "Zyban 150 mg prolonged release film-coated tablets – Summary of Product Characteristics (SPC)". electronic Medicines Compendium. GlaxoSmith

[3] "Prexaton Bupropion hydrochloride PRODUCT INFORMATION". TGA eBusiness Services. Ascent Pharma Pty Ltd. 2 October 2012. Retrieved 22 October 2013.

[4] FDA Buproprion Label Last revised December 16, 2014 as described on the FDA Label Website. See that site for updates. Page accessed April 8, 2016

[30] Dwoskin LP, Rauhut AS, King-Pospisil KA, Bardo MT (2006). "Review of the pharmacology and clinical profile of bupropion, an antidepressant and tobacco use cessation agent". CNS Drug Rev. 12 (3–4): 178–207. doi:10.1111/j.1527-3458.2006.00178.x. PMID 17227286.

[67] Jefferson JW, Pradko JF, Muir KT (November 2005). "Bupropion for major depressive disorder: Pharmacokinetic and formulation considerations". Clin Ther. 27 (11): 1685–95. doi:10.1016/j.clinthera.2005.11.011. PMID 16368442.

Dextromethorphan has now been shown to have antidepressant effects in as little as 3 days. Could someone add this to the cognitive effects? I can't figure out how to edit the effect matrix. It's also been investigated for anti-aggressive effects. Lastly, based on the reports it looks like it can cause sweating, even if there isn't a change in body temperature. May want to add this.

Dextromethorphan now can be obtained in a combination medication known as Auvelity in the US. It is perscription only, however, the interaction between dextromethorphan and bupropion seems to potentiate the antidepressant effects of dextromethorphan and bupropion together. Just a thought though, maybe include it at the bottom, near interactions? -- (unsigned by User:Rosesareblue at 2023-01-09T14:07:37‎ UTC)

This combination of DXM and Bupropion surprises me, given Bupropion has deliriant-like effects through antagonism of the nicotinic acetylcholine receptors. If a page about it is made, for harm reduction purposes there needs to be significant warning about the dysphoric, nauseating, and especially seizure inducing properties which become an extreme danger at high dosages; since Auvelity contains 45mg of DXM & 105mg of Bupropion per tablet, if someone took 3 tablets they would be at 315mg of Bupropion which is just 10mg away from the danger-threshold of Bupropion @325mg. Taking more than three tablets of Auvelity would be extremely dangerous, and three tablets would be rather dangerous. If a page about Auvelity is made, then this needs to be mentioned for safety reasons. --JH556 (talk) 20:24, 13 July 2023 (UTC)

User:Mnbvcxz removed the bupropion line at https://psychonautwiki.org/w/index.php?title=Dextromethorphan&diff=158985&oldid=158931. I don't think the change is a good idea: while we know that the combination in extended-release form is safe enough to be taken twice a day, spaced 8 hours apart,^[1] the approval does not cover an instant-release combination like what would likely be done when "hacking things together". My preferred wording, which I wrote into Bupropion, is:

On the other hand, dextromethorphan/bupropion is an approved combination drug; each extended-release tablet contains 45 mg DXM and 105 mg bupropion. The maximum dose for depression is set at 2 tablets per day, spaced at least 8 hours apart.^[1] Although this combination drug is safe enough to be approved, the safety of an instant-release combination and of higher doses remains a concern.

I fixed the error. I don't think User:Mnbvcxz meant to do that, their description is a minor edit that only fixes bolding and he reversed two different edits in one. Uzi (talk) 03:32, 8 June 2024 (UTC)

So JH556, I guess the relative safety has something to do with it being extended-release. I don't know how much safety margin goes into the "space doses at least 8hrs apart" disclaimer, but it has to be... decent enough?

The existing source https://sci-hub.se/10.1097/01.jcp.0000162805.46453.e3 speculates at a risk, but it (and the deleted line about Bupropion) does not go into the psychoactive consequences of having less DXM convert to dextrorphan. This should produce a very significant change in the subjective effect, as dextrorphan is much more potent at the hallucinogenic NMDAR than DXM.

• Cafermed (https://www.cafermed.com/post/auvelity) agrees that kicking away CYP2D6 probably prevents the drug from being dissociative.
• https://pubmed.ncbi.nlm.nih.gov/9690700/ shows that people with less functional CYP2D6 has less fun subjective experiences. They also "tolerated" lower doses, lending some credence to the idea that weak CYP2D6 makes DXM less safe. I cannot see the full text, so the important part, a description of adverse effects in non-tolerators, isn't available to me.
• I've taken 180 mg DXM with a different allegedly "strong" CYP2D6 inhibitor, 40 mg fluoxetine (both instant release), as a sort of poor man's Auvelity. It's... not trippy at all. I stopped feeling depressed about 0.8 hour in, and was feeling quite well about 1.5 hours in; but I really could not balance my body while it lasted. Heh.

We also need a source about seizure threshold, I think. --Artoria2e5 (talk) 14:50, 2 June 2024 (UTC)

I'll work on attaching a source for the seizure threshold of DXM and Bupropion. Uzi (talk) 02:05, 8 June 2024 (UTC)

I feel like Plateau Sigma shouldn't be called "Fifth Plateau" and should instead be called as its own distinct plateau. By this distinction I think it'll help drive the point that it does not match with the linear dose-effect relationship of the first to fourth plateaus because it involves a certain hepatic phenomenon from redosing that can create a different subjective effect (by dosage tolerability and ↑DXM:↓DXO blood concentration). On a more off-topic note, I think we should talk about warning against redosing DXM too much throughout the day because of this certain effect (e.g. Redosing after CYP2D6 is being pre-occupied by initial dosages). What do you guys think of this? Uzi (talk) 04:07, 8 June 2024 (UTC)