Dextromethorphan (DXM) can reduce the risk of dementia and hearing loss

[CosmicExplorer]

DXM is a very interesting substance. In a lot of countries, you can buy it (even the pure version with the only ingredient being DXM) in the form of cough syrup or gel pills OTC. It's a dissociative, with somewhat similar effects to ketamine. I've tried it a few times and the biggest problem for me is very strong nausea and vomiting, and the only solution is to take it together with Diphenhydramine (DPH) but it makes the effects worse and DPH is generally a very unhealthy deliriant drug which use is associated with dementia. Many people don't experience nausea/vomiting from DXM or only mild.

Chronic DXM use is associated with a reduced risk of dementia: https://journals.sagepub.com/doi/full/10.1177/15333175221124952

Quote

Dextromethorphan (DXM) has been reported to reduce neuronal damage and neurodegeneration in animal and human models
We used a Cox regression hazard model to identify risk factors of dementia during 16 years of follow-up, and the results indicate that a significantly lower percentage of subjects with DXM use (P < .001) developed dementia compared with those without DXM use (11.38%, 4541/39 895 vs 18.66%, 29 785/159 580). After adjustment for age and other variables [adjusted hazard ratio: .567 (95% confidence interval: .413-.678, P < .001)], this study also demonstrated that DXM use appeared to reduce the risk of developing dementia. DXM use may potentially provide a protective effect against dementia.

Furthermore, there is a dose dependent pattern, where higher dosage of DXM relates with a lower risk of dementia.

Hazard ratio for no DXM use 1 (reference)

Hazard ratio for 1-30mg a day 0.754

Hazard ratio for 31-90mg a day 0.563

Hazard ratio for ≥91mg a day 0.442

DXM use is associated with a reduced risk of hearing loss: https://pubmed.ncbi.nlm.nih.gov/32878128/

Quote

In human study, we used a Cox regression hazard model to indicate that a significantly lower percentage individuals developed SNHL compared with and without DXM use (0.44%, 175/39,895 vs. 1.05%, 1675/159,580, p < 0.001). After adjustment for age and other variables [adjusted hazard ratio: 0.725 (95% confidence interval: 0.624-0.803, p < 0.001)], this study also demonstrated that DXM use appeared to reduce the risk of developing SNHL. This animal study demonstrated that DXM significantly attenuated noise-induced hearing loss. In human study, DXM use may have a protective effect against SNHL.

It has profound anti-inflammatory, anti-arthritic, and Immunomodulatory effects:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595833/

Edited April 15 by CosmicExplorer

[Schizophonia]

I would be wary, Ketamine induces serious neurological deficits, and has a very similar pharmacology.

[CosmicExplorer]

@Schizophonia Only in extremely high doses for ketamine. No evidence of DXM causing Olney’s lesions even at lethal doses

https://www.researchgate.net/publication/6264286_Oral_administration_of_dextromethorphan_does_not_produce_neuronal_vacuolation_in_the_rat_brain

Quote

To determine whether dextromethorphan produces these characteristic lesions, dextromethorphan was administered orally either as a single dose of 120mg/kg to female rats, or daily for 30 days at doses of 5-400 mg/(kg day) to male rats and 5-120mg/(kg day) to female rats. Brains were examined microscopically for evidence of neuronal vacuolation (4-6h postdose) and neurodegeneration ( approximately 24 or 48h postdose). Administration of dextromethorphan at 120mg/(kg day) in females, and at > or =150mg/(kg day) in males produced marked behavioral changes, indicative of neurologic effects. Mortality occurred at the highest doses administered. There were no detectable neuropathologic changes following single or repeated oral administration of dextromethorphan at any dose.

 

 

[vibv]

Tread lightly. DXM is very powerful and can be addictive. If used too often it is harmful for sure. I'd say no more than once in 1-3 months. The effects also may linger for many days after, which can be positive but also negative.

That being said, it's one of my favourite dissociatives. It also has a way more "warm" and dreamy feeling to it. I experience Ketamin as very cold and clinical in contrast.

[Schizophonia]

40 minutes ago, CosmicExplorer said:

@Schizophonia Only in extremely high doses for ketamine. No evidence of DXM causing Olney’s lesions even at lethal doses

https://www.researchgate.net/publication/6264286_Oral_administration_of_dextromethorphan_does_not_produce_neuronal_vacuolation_in_the_rat_brain

 

Supposedly, but I posted a study somewhere here that showed regular ketamine users had HOLES in the neo cortex.
In fact, NMDA agonists can be used as a powerful means of increasing neurogenesis and long-term brain health.
The neuroprotective properties of DXM may be linked to other pharmacological properties like Sigma-1/2 agonism or something like that.

 

Edited April 15 by Schizophonia

[Shodburrito]

DXM is also an active ingredient in an anti-depressant. I don't remember what it is called though.

[Leo Gura]

DXM can't be good for you long-term.

Be careful with narrow studies.

[Schizophonia]

On 16/04/2024 at 7:42 AM, Leo Gura said:

DXM can't be good for you long-term.

Be careful with narrow studies.

In fact the sample of people is particularly large, and there is a strong dose-dependent correlation.
This is more interesting than I thought, maybe DXM can be good in the long run.

Memantine is already used as a treatment for demencia.

[Schizophonia]

I looked at the study and they don't really know the reason.
They assume by default a reduction in exitoxicity but that's really weird because normal glutamate levels aren't supposed to be neurotoxic.
NMDA receptor agonists can also be used as antidepressants such as dissociatives, so perhaps in fact NMDA antagonism increases overall glutaminergic neurotransmition (by AMPA and glutamate-1), this is the proposed mechanism for the therapeutic qualities Ketamine.
Dissociatives also often have a direct effect on monoamines (by blocking DAR and SERT) and DXM has a particular effect on Sigma-1/2 like DMT which is widely suspected of being neuroprotective.
There are also effects on acetylcholine and histamine receptors, depending on the dissociative.

Increased glutaminergic and/or dopaminergic neurotransmition increases OXPHOS and strongly upregulates neurogenesis and neuroplasticity.
Ketamine is known to potently increase neurotrophins.

[Leo Gura]

35 minutes ago, Schizophonia said:

In fact the sample of people is particularly large, and there is a strong dose-dependent correlation.
This is more interesting than I thought, maybe DXM can be good in the long run.

Memantine is already used as a treatment for demencia.

Narrowness of study is not about the sample size.

[Carl-Richard]

The problem is that taking DXM produces a state reminiscent of dementia, so that defeats the purpose 😂

[CosmicExplorer]

17 hours ago, Carl-Richard said:

DXM produces a state reminiscent of dementia

DPH is more like dementia to me

[tuku747]

On 4/20/2024 at 10:27 AM, CosmicExplorer said:

DPH is more like dementia to me

Any studies on DPH abuse causing dementia long-term?

[CosmicExplorer]

On 4/21/2024 at 10:58 PM, tuku747 said:

Any studies on DPH abuse causing dementia long-term?

https://www.health.harvard.edu/blog/common-anticholinergic-drugs-like-benadryl-linked-increased-dementia-risk-201501287667

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592307/

https://jamanetwork.com/journals/jamaneurology/fullarticle/2514553