[I couldn't post links to studies. I might have put them without tags but would that have been against the forum's principles?]

This has been interesting thread, thanx!

I apologize if my writing has errors as english isn't my native language.

Despite I don't have PD I decided to register and post my experiences with DXM because I have been interested about it and have been suspecting it might have had positive effect on my dopamine system and mental health. I have used it a lot but for different purpose what has been discussed here. I'm 29 years old male from Europe.

Original reason for my DXM use was to assist with my drug withdrawal and tolerance issues (benzodiazepine etc.) and to help with depression and anxiety associated with that process. I explored DXM and believed it would do more good than harm for the situation I had. I had had previous experience with benzodiazepine addiction and withdrawal at 2008 and after that process I was about 2 years very depressed, anxious and kind of disabled mentally to do anything which only led me to using benzos again. So I wanted to avoid that happening.

My thoughts of its dopaminergic effects:

First is that after 2008 withdrawal I had lot of 'extrapyramidal symptoms' with drugs like amitriptyline or even small doses of antipsychotis like quetiapine (25-50mg).

In case if it isn't familiar..

" Extrapyramidal syndrome (EPS) is due to the blockade of dopamine receptors in the basal ganglia, leading to Parkinson-like symptoms such as slow movement (bradykinesia), stiffness, and tremor." - Wikipedia

Second is that even with small doses of those kind of drugs my depression, apathetic and unmotivated feeling, social isolation all got worse. That implied to me that I had insufficient dopamine levels many years after benzodiazepine withdrawal. Maybe because of long and continuous stress and pain, inflammation and their negative effects on gaba- and opioidergic systems. I wanted to avoid that and so from different drugs I had studied and dealt with DXM with its dopamine boosting, SNRI, NMDA- and Voltage Gated Calcium Channel antagonist properties fitted perfectly to that situation.

Now, when over year has passed I'm quite positive DXM has indeed had a positive effect on my condition. Reasons:

1) No EPS of any kind even with large doses of antipsychotics (using sometimes to get sleep) or trisyclic antidepressants.

2) No anxiety, depression or other ill feelings after withdrawals - which were very present at 2008.

3) I don't have any PAWS symptoms after withdrawals.

And it seems that my dopamine is now going pretty good without DXM because I haven't use it over two weeks and I don't still have signs of dopamine deficiency.

My DXM doses were much larger than has been here discussed. At first I used medium doses (60-120mg/d) and progressed to bigger amounts at max. about 600-800mg/d with grapefruit juice which supposedly improves it absorption and extends half-life.

What I found also was that DXM indeed seems to inhibit tolerance to at least benzodiazepines. It was easier for me to taper benzo dose with DXM than without it.

But few points has come to my mind about DXM supposed opioid antagonist properties. I must say that at least it feels it has rather opioid agonist than antagonist properties. Its hard for me to believe that its immediate 'opioid like effects' comes from endogenous opioids through antagonism because opioid effect can be felt under its influence but not after it wears of. With naltrexone its different. If you use it enough (equivalent doses like 500mg) you get bad feelings, nausea, insomnia etc. from blocking opioid receptors and a positive rebound or "withdrawals" after it wears off or with stable dose after few days when body compensates.

Also, differences are according to studies I've read that:

1) Naltrexone attenuates opioids effects if used simoultaneously
2) DXM enchances opioid effects when used simoultaneously

Both even have positive correlation with dose but to different directions. How do you explain that difference if both are antagonist to opioid receptors? I admit that DXM's NMDA - and Voltage gated calcium channel antagonism definately and possible Sigma agonism plays a role there but hard to believe they could alone cause those differences.

So that is some kind of puzzle to me.

Sorry if I have missed something but at least these studies indicate it might affect through different mechanism or are these effects maybe secondary from its opioidergic effects?:

[B]Dextromethorphan protects dopaminergic neurons against inflammation-mediated degeneration through inhibition of microglial activation.[B]

"Pretreatment (30 min) of rat mesencephalic neuron-glia cultures with DM (1-10 micro M) reduced, in a dose-dependent manner, the microglia-mediated degeneration of dopaminergic neurons induced by lipopolysaccharide (LPS, 10 ng/ml)."

[B]Pubmed: 12649371[B]

This is also interesting new study from 2013:

[B]Dextromethorphan Protects Cells in the Oligodendroglial Lineage and Stimulates Glial Proliferation (P05.164)[B]

"DM at 100 nM-20 microM was not toxic to OL at 1 day, with increasing toxic
ity at 50-100 microM. Glutamate (100 microM) killed 70% of OL; DM protected, reducing OL death to 55% at 100 nM DM and 30% at 20 microM DM, a concentration similar to that found in rat brain after oral administration of 30 mg/kg DM + quinidin"

This study was on this side but I didn't see much comments about it:

[B]Thomas, D.M., and Kuhn, D.M. MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity.*Brain Research*1050(1-2):190-198, 2005.

This is also interesting study:

[B]Effects of*dextromethorphan*on glial cell function: Proliferation, maturation, and protection from cytotoxic molecules.[B]

"These agents and DM were not toxic to AS or MG at the concentrations used. Thus, DM stimulates proliferation of OPC, and protects both OL and OPC against excitotoxic and inflammatory insults. GLIA 2014."

[B]Pubmed:24526455[B]

What is really the main positive action of DXM regarding dopaminergic system? I list here positive actions I think of and would be glad if someone can correct them if they are wrong:

1) Direct increase in dopamine
2) Dopamine receptor density increasing effect
3) Inflammation reducing effect
4) Exitotoxicity preventing effect

[B]Is it possible DXM and LDN affect through different mechanisms to improving brain health?[B]

Would naltrexone have had same kind of positive effects as DXM in ex. those [U]in vitro[U] studies I posted?

Also that methamphetamine study if thinking LDN. If LDN stimulates immune function through OGF and opioidergic system would it then have lead to rather worse outcome by increasing microglial function..? Or would it have stabilazed and inhibit their function like DXM? With different or same mechanism?

Also I'm thinking about those doses. I believe that femtomolar doses could also help but at least usually studies have used larger doses and one pubmed review stated that when there isn't positive results with DXM its usually because of too small doses and they suggested quinine for preventing first pass metabolism. On the other hand, they have usually studied some protective effects from excitotoxicity like in ischemic strokes or something.

Correct if I'm wrong but when looking ex. these studies I referred here it seems doses are bigger than < 10mg. That methamphetamine study has a little vague statement about amount but if it was 5mg/kg (which was only number I found) it is kind of large amount to man.

Other study used molars but stated 30mg/kg + quinine which is extremely large dose.

That dopaminergic degeneration preventing study stated 1-10 micro M which might equal to 1.5-15mg/kg if comparing to that other studys comparison. So very big doses compared to 10mg or under.

What I'm going to try is using DXM and LDN together. I can report here what it does. I was thinking 60-120mg DXM and maybe 4.5mg naltrexone.

My reasons are mental (and overal) health and addiction prevention. There has been studies indicating DXM could be good antidepressant (it actually is best I have ever tried) and especially to people who have a family history of alcoholism/addiction. That has probably something to do with its NMDA antagonism. It has been previously noted that Ketamine causes rapid improvement in depression and it is a strong NMDA antagonist.

So one reason for that medium large dxm dose is depression treatment as I can same time reduce my tricyclic antidepressant allmost zero as they have some effects so similar (SNRI). I would maybe use even larger amount and drop off other AD:s completely but there comes too much side effects mainly NMDA antagonism which starts to affect memory a little bit. Also it is reasonable to think what long term causes could extensive NMDA antagonism have even though it has been noted that DXM doesn't cause any lesions to primates or even to rats (MK-801 is what Olney used). Also that is the good dose for me to optimum sleep quality as I have had deep and refreshing sleep with that dose of DXM and don't need to use GABAergics anymore.

Thanx