Pharmacology NAC, dopamine, and psychiatric/addiction indications

[Snafu in the Void]

I have heard NAC being indicated in a plethora of applications. So many that I actually started to doubt it as it seemed too good to be true.

I have used NAC in the past, mainly to protect against alcohol induced liver stress and to see if it actually helps prevent hangovers as I have seen anecdotally reported. I concluded that it does not help hangovers, at least not in a noticeable way with the amount I drink, so I stopped using it.

Recently I decided to try it again and I noticed 3 very interesting things this time.

1. NAC blocks the euphoric properties of kratom, but does not put me into withdrawal like a MOR antagonist would. It seems to block both the stimulation and the opioid effects (?). Not sure why it would block opioid effects, but raw analgesia seems to still be present. Physical stimulation is still present, but not mental stimulation.

Apparently NAC lowers dopamine levels, and kratom increases dopamine significantly in the frontal lobe (not acutely, but with repeated administration).

I can see this being very useful as an aid while trying to taper or reduce tolerance.

I'm now reading many anecdotes about NAC also blocking the euphoria from pharma stimulants, as well as protecting against meth neurotoxicity.


2. I've noticed a very significant and immediate reduction in schizophrenia related symptoms. The symptoms I have are minor and generally consist of unusual thoughts and odd internal hallucinations, and they only really present if I am using alcohol or other substances.

NAC seems to eliminate these in a dose dependent manner for 12-20 hours. When the NAC wears off, they come back, and there may actually be a small rebound effect.

This was more effective than any antipsychotic I've ever taken, which can actually make my symptoms worse. My schizophrenia was drug induced and my symptoms are very atypical, a more accurate definition may be "drug induced brain damage".

3. I have also noticed a general reduction in anxiety and improved sleep. I am wondering if these positive reactions may be due to rebalancing my dopamine, or a general reduction in oxidative stress.


I found all of this to be very interesting and will keep experimenting with NAC.

I'm curious if anyone is more familiar with NAC, specifically it's role in the brain and drug interactions.

 

[Snafu in the Void]

I've done a bit more experimenting.

A dose as low as 600mg is enough to block kratom euphoria for over 32 hours. Oral half life is 6.2 hours. Considering it's oral bioavailability is only 4-10%, this suggests it's quite potent in this regard. It blocks the mental stimulation, sedation, and opioid feeling completely. Taking a double dose did not overcome this. The physical feeling of kratom is still there, but is rather dysphoric without the high. Kratom induced anxiety was also present. Basically all the side effects, but no buzz.

I cannot find any anecdotes or studies about kratom blocking typical opioids. It has been shown to be beneficial in mitigating acute opioid withdrawal, as well as other drugs, likely due to its glutaminergic effect.

This is rather curious to me, I can understand why it might blunt kratom stimulation, but not the opioid effect.

 

[entheologian]

I can't comment on kratom but recently I dosed NAC at the start of an apihp 1.5g binge, for the first 10 hours I thought it was shit quality then the expected full effects kicked in.

Could the NAC be responsible? I usually take it on the comedown

 

[Snafu in the Void]

I can't comment on kratom but recently I dosed NAC at the start of an apihp 1.5g binge, for the first 10 hours I thought it was shit quality then the expected full effects kicked in.

Could the NAC be responsible? I usually take it on the comedown

NAC seems to decrease dopamine transporter availability.

Cathinones are dopamine transporter inhibitors (?).

I'm not qualified to speculate on the interaction but there certainly seems to be one. Plenty of anecdotal reports of NAC blocking the euphoria of amphetamines and methylphenidate.

 

[entheologian]

NAC seems to decrease dopamine transporter availability.

Cathinones are dopamine transporter inhibitors (?).

I'm not qualified to speculate on the interaction but there certainly seems to be one. Plenty of anecdotal reports of NAC blocking the euphoria of amphetamines and methylphenidate.

Yes APIHP is a dopamine/norepinephrine reuptake inhibitor

 

[CFC]

I have heard NAC being indicated in a plethora of applications. So many that I actually started to doubt it as it seemed too good to be true.

I have used NAC in the past, mainly to protect against alcohol induced liver stress and to see if it actually helps prevent hangovers as I have seen anecdotally reported. I concluded that it does not help hangovers, at least not in a noticeable way with the amount I drink, so I stopped using it.

Recently I decided to try it again and I noticed 3 very interesting things this time.

1. NAC blocks the euphoric properties of kratom, but does not put me into withdrawal like a MOR antagonist would. It seems to block both the stimulation and the opioid effects (?). Not sure why it would block opioid effects, but raw analgesia seems to still be present. Physical stimulation is still present, but not mental stimulation.

Apparently NAC lowers dopamine levels, and kratom increases dopamine significantly in the frontal lobe (not acutely, but with repeated administration).

I can see this being very useful as an aid while trying to taper or reduce tolerance.

I'm now reading many anecdotes about NAC also blocking the euphoria from pharma stimulants, as well as protecting against meth neurotoxicity.


2. I've noticed a very significant and immediate reduction in schizophrenia related symptoms. The symptoms I have are minor and generally consist of unusual thoughts and odd internal hallucinations, and they only really present if I am using alcohol or other substances.

NAC seems to eliminate these in a dose dependent manner for 12-20 hours. When the NAC wears off, they come back, and there may actually be a small rebound effect.

This was more effective than any antipsychotic I've ever taken, which can actually make my symptoms worse. My schizophrenia was drug induced and my symptoms are very atypical, a more accurate definition may be "drug induced brain damage".

3. I have also noticed a general reduction in anxiety and improved sleep. I am wondering if these positive reactions may be due to rebalancing my dopamine, or a general reduction in oxidative stress.


I found all of this to be very interesting and will keep experimenting with NAC.

I'm curious if anyone is more familiar with NAC, specifically it's role in the brain and drug interactions.

It's a while since I did a lot of research on NAC and its interactions with various DOCs. But certainly in terms of schizophrenia I remember the mechanism being postulated was at least partly related to attenuation of oxidative stress and inflammation in certain parts of the brain, and the reversal of downstream effects that typically causes.

WRT to alcohol, you may find a reduction in negative/liver/hangover effects, but only if you take the NAC several hours beforehand. Taken afterwards, NAC actually appears to make things worse and cause more liver damage. Mechanism of damage (iirc) has not been properly elucidated.

Also bear in mind that most people supplementing with (larger doses of - say 3-6g/day) NAC may require additional glycine at the same time for some of the beneficial effects (ie GlyNAC). This is because it's been noted that glycine appears to be a rate limiting step in the conversion of NAC to glutathione. In research circles, the normal ratio of glycine to NAC in a GlyNAC preparation is 4:3 (eg 4g glycine with 3g NAC).

 

[CFC]

I'm not qualified to speculate on the interaction but there certainly seems to be one. Plenty of anecdotal reports of NAC blocking the euphoria of amphetamines and methylphenidate.

Don't quote me, but I think it may have been partly attributed to a role of glutathione in stabilization/permeability of various relevant cell membranes. So on the plus side, less cellular inflammation and neuronal damage/loss. But from a stim user's POV, probably less of a subjective high as well.

I have felt like I noticed a very modest effect from NAC when I use stims, but not always an attenuation. Sometimes it can cause quite a boost during the latter stages of a binge, which I just assumed was related to the capacity of NAC (via glutathione) to help recover and enhance mitochondrial energy function/production.

 

[Neuroprotection]

it’s funny seeing this thread knowing that just a few years ago, my perspective would have been completely different, my answer being warped by my deluded belief that antioxidants could cure everything and free radicals were solely the evil mastermind behind all Brain diseases. thankfully, I’ve grown out of that and though I’m not an expert, this is what I’ve got from my research so far.
NAC is a precursor to the amino acid cysteine and it is taken up by neuronal transporters called the cysteine- glutamate antiporter. this transporter pulls cysteine into the neuron and exchanges it for glutamate which is dumped out. The neuron can then use the cysteine to make the powerful antioxidant glutathione, for protein synthesis and modification amongst many other functions. Meanwhile, the glutamate that is released goes on to stimulate either presynaptic or postsynaptic Mglu2/3 receptors which diminish glutamate release and glutamate response to ionoTropic Receptor activation respectively. Mglu2 also have some direct anti-apoptotic effects on neurons through increasing pro survival BCL2 proteins in mitochondria. This is according to a recent study I read, I’ll try and post the link when I find it. Mglur2 through the above-mentioned actions on glutamate release and receptors, produces a range of interesting tranquilliser like effects. for example, potent agonists of this receptor produce anxiolytic, antipsychotic, analgesic, sedative and amnesic effects in a dose-dependent manner. such agonists also produce an anti-reward effect which at high doses can apparently suppress motivation for natural rewards. this could occur through simultaneous suppression of dopamine release and suppression of glutamatergic signalling downstream of postsynaptic dopamine receptors. I wonder if this explains the suppression of Psychostimulant and opioid euphoria by NAC.