3 replies to this topic

[Bockemossen]

Why don't I feel stimulants anymore but get drunk/happy on alcohol?

If tolerance to stimulants is created by upregulated kappa opioid receptors, wich counters the pleasure effects of mu opioid receptors, shouldn't that be the case with alcohol as well? And the pleasure effects of all other drugs?

First I got all the positive effects of amphetamine but now I just get dysphoric and feel like shit. When I drink alcohol I don't' feel like in the beginning but still get some pleasure effects.

I know amphetamine is more dopamine and alcohol gaba, but all pleasure is regulated through mu receptors so should there be any difference between amphetamine and alcohols "feel good" effects?

[FW900]

The ineffectiveness of stimulants is largely attributed to downregulation. Using amphetamine repeatedly, will lead to a net decrease in dopamine receptors (viz, downregulation). More of the drug will be required, to have the effect of taking it at a lower dosage early on. If your theory was correct (the upregulation of Kappa opioid receptors) , people would be using opioid receptor antagonists like naltrexone to counter stimulant tolerance.

[nelly33]

I wonder if cycling between alchol could balance the effect?

[Bockemossen]

The ineffectiveness of stimulants is largely attributed to downregulation. Using amphetamine repeatedly, will lead to a net decrease in dopamine receptors (viz, downregulation). More of the drug will be required, to have the effect of taking it at a lower dosage early on. If your theory was correct (the upregulation of Kappa opioid receptors) , people would be using opioid receptor antagonists like naltrexone to counter stimulant tolerance.

From what I read, too much dopamine in the nucleus accumbens upregulates kappa opioid receptors wich counters the dopamine overflow. Maybe the dopamine downregulation is regluated through the kappa system.

I don't know if kappa antagonists downregulate the receptor. But people use kappa agonists like ibogaine and salvia to reverse tolerance to all drugs.