Dose - alchol has no effect any more

[mashed]

swim knows this sounds strange but here goes,
swim used to be able to get quite drunk easily lately though no matter how much swim drinks swim feels no effects,nothing at all.
this has all started since swim has been taking differet things.swim has been on
citralopram,mitrazepam from the doctor and has been taking valium 30mg and also a lot of codeine.
and even though swim havnt drunk for about 4 months thus should have no tolerance swim just doesnt feel no effects UNLESS swim combines alchol with another depresssant e.g. valium or codeine then swim gets the effects.last night swim drunk half a bottler of 40% smirnoff vodka,a large bottle of WKD and 3 bottles of 8% wine and i was still sober as could be wtf?
swim finds this really strange,has it happened to any one else?
thanks

[Mile High]

Can't say this has ever happened before. Swim once heard that the more a person drinks the more tolerant they become. Correct swim if she is wrong anyone....
Swim hasnt really had any experience mixing with other drugs...only coedine which just makes Swim pass out if mixed with alcohol.

[cc2792]

Well, swim drinks almost every day and so is quite used to the feeling. I don't think it's that it has no effect anymore, you're just USED to it.

My morning consists of an energy drink or two every morning. Now, three years ago these drinks made me a little loopy and jittery, but now they don't seem to have any effect... unless I DON'T drink one. But the next day, I feel as though I'm acting normal. I don't feel jittery.

So I think you might have just become completely used to being drunk and it might take a lot longer than four months to get rid of your tolerance, especially when you're taking all of these other medicines that have similar effects as alcohol... swim in under the impression that the feelings from your prescription drugs and alcohol are very similar, but that mixing the two would be a different story.

[fnord]

It takles grandma silly amount of booze to get her to her happy place nowadays. Its called tollerence and its a bitch!

[AquafinaOrbit]

Tolerance will go up, and rather quickly to a point. I don't believe alcohol could completely lose its effects however unless another drug in the system is somehow canceling it out.

[Cryptic Concoction]

If SWIY has been taking 30 mg of diazepam (valium) regularly, I do not find it altogether strange that he now experiences attenuated effects from alcohol. Cross-tolerance is seen in GABAergic drugs. Both diazepam and alcohol are GABAergic drugs.

Frequent use of GABA agonists, such as benzodiazepines and alcohol, can result in densitization or downregulation of GABA receptors or other changes in receptors that render post-synaptic neurons less-responsive to the presence of GABA and other substances that act as GABA agonists.

Both alcohol and diazepam are GABA(sub A) receptor agonists (though the precise binding site of alcohol on this receptor remains unknown), and regular use of diazepam could result in compensatory mechanisms in the central nervous system that produce desensization or downregulation of GABA (sub A) receptors to their agonists.

Changes in GABA receptors, induced by regular diazepam use, could easily account for tolerance to alcohol, given that they appear to exert their effects via the same receptor (although alcohol also appears to act as an antagonist at NMDA receptors). Whether it is downregulation or desensitzation, the result of tolerance is reduced responsiveness to GABA and GABA agonists on post-synaptic neurons forming synaptic connections with GABAergic neurons. Thus, regardless of the drug, these neurons will be less responsive to any drug that exerts its effects via GABA (sub A) receptor agonism. If SWIY's nervous system has already compensated for the diazepam use by desensitizing itself to GABA (sub A) receptor agonists, alcohol too (a GABA receptor agonist) will see its effects reduced.

This may be rather confusing, so I will attempt to outline this in a more simplified format:

1. Both diazepam and alcohol activate GABA (sub A) receptors.
2. Diazepam is administered frequently, resulting in desensitization to molecules acting on GABA (sub A) receptors (in order to restore balance).
3. Alcohol is administered, and acts on GABA (sub A) receptors, but the central nervous system is already desensitized to the presence of such molecules. Consequently, its effects are attenuated.

This is, of course, an over-simplification, but I intend to render this as intelligible as possible to those not familiar with neuropharmacology without delving into the various intricacies that may confound the uninitiated.

To further simplify and summarize my post, benzodiazepine tolerance can translate into alcohol tolerance (pharmacodynamic tolerance), because they share similar mechanisms of action.

[stratry]

Nothing unusual. In simplest terms, this may have to do with how the antidepressants are effecting enzymes in SWIY's liver.

SWIM cannot get drunk no matter how much he drinks if he is taking the antidepressant Elavil. SWIM hasn't had the same problem with most of the antidepresants he has tried (Lexapro, Remeron, Wellbutrin, Zoloft, Paxil, Prozac, Effexor). Everyone's different. A different antidepressant might make it possible for SWIY to get drunk.

As for benzodiazepines, they do nothing for SWIM when taken alone, but when mixed with alcohol blackouts occur.