Ways to increase the half life of Methadone? (Elimination)

[OpiateKiller]

Hello all,

I’m wondering if there are any effective ways to make my dose last longer.

I have a fast metabolism, drink coffee and alcohol... which are all reasons my dose isn’t holding.

i might cut out coffee and switch to an energy drink which I believe would be less acidic?

I’ve read baking soda can hell just like it does with amps or meth to reduce stomach acid causing better or slower absorption..

Thoughts?

 

[Deru]

I’ve read baking soda can hell just like it does with amps or meth to reduce stomach acid causing better or slower absorption..

The absorption speed through the stomach and intestinal walls into the bloodstream would really only affect onset. With methadone, who's half-life is so long, that all happens in the bloodstream and tissues. I'm not sure if I would want to increase the half-life of methadone, honestly - it's so long to begin with. If it's something you would really want to proceed with, I would think you would need to target metabolic process speeds on a systematic level - targeting gastrointestinal would be the wrong system. Also, and possibly, I wonder if altering the pH of blood plasma could play a role here - although I'd imagine there could be many negative side effects to doing so.

Side note: alcohol is fantastic to increase absorption time of other drugs, so alcohol would actually be beneficial to what you're trying to do.

 

[dopamimetic]

For substances with long half life and enzymatic metabolism like methadone is one, usually the best bet is to inhibit whatever enzyme(s) are primarily responsible for breakdown. I'm this case it appears to be cyp 2b6, for which drugbank found 59 inhibitors. What caught my attention is curcumine, it is available as a supplement but don't know about the potency. Among the other inhibitors some antidepressants like sertralin or venlafaxine are found but mostly lesser used drugs. Memantine is listed too, this one would then have two benefits at once - slower tolerance development and increased duration. Might need high doses of it though.

Another paper says that methadone has differing kinetics in cyp2d6 slow vs extensive metabolizers, indicating that inhibiting that might slightly extend the duration too.

But depending on whether some metabolites are active, influencing the enzymes will lead to changed levels of these and potentially more side effects but would guess with metha its less of a problem.

 

[OpiateKiller]

The absorption speed through the stomach and intestinal walls into the bloodstream would really only affect onset. With methadone, who's half-life is so long, that all happens in the bloodstream and tissues. I'm not sure if I would want to increase the half-life of methadone, honestly - it's so long to begin with. If it's something you would really want to proceed with, I would think you would need to target metabolic process speeds on a systematic level - targeting gastrointestinal would be the wrong system. Also, and possibly, I wonder if altering the pH of blood plasma could play a role here - although I'd imagine there could be many negative side effects to doing so.

Side note: alcohol is fantastic to increase absorption time of other drugs, so alcohol would actually be beneficial to what you're trying to do.

I want to increase these things because despite methadone long half life, I find myself already entering withdrawal 20 hours later, by the time I get to the clinic to get my dose I’m already beginning the stages of withdrawal. I have an incredibly fast metabolism. I could eat cakes and McDonald’s every meal and not go a pound past 160.

 

[OpiateKiller]

For substances with long half life and enzymatic metabolism like methadone is one, usually the best bet is to inhibit whatever enzyme(s) are primarily responsible for breakdown. I'm this case it appears to be cyp 2b6, for which drugbank found 59 inhibitors. What caught my attention is curcumine, it is available as a supplement but don't know about the potency. Among the other inhibitors some antidepressants like sertralin or venlafaxine are found but mostly lesser used drugs. Memantine is listed too, this one would then have two benefits at once - slower tolerance development and increased duration. Might need high doses of it though.

Another paper says that methadone has differing kinetics in cyp2d6 slow vs extensive metabolizers, indicating that inhibiting that might slightly extend the duration too.

But depending on whether some metabolites are active, influencing the enzymes will lead to changed levels of these and potentially more side effects but would guess with metha its less of a problem.

Thank you I have circumin in my cabinet!! Appreciate it

 

[OpiateKiller]

Grapefruit juice inhibits the metabolism of methadone, thus raising it’s serum level. But this could prove dangerous, because of how individuals metabolize methadone and unpredictability raise serum levels to unpredictable levels. Like @Deru correctly states, methadone already has an incredible half-life. This might also be dangerous if you are taking other medications on top of methadone, ie diazepam and some blood pressure medications. It might be smart to talk to a pharmacist and get their opinion. They love talking drugs, and they don’t even ask your name!

—Wizard

I have actually found grapefruit juice to help and do this, but the days I’ve drank it it’s actually made me feel weird or off, not so much more high or a pleasant feeling. Strange

 

[evo4ever]

Diphenhydramine (Benadryl) is an effective CPY2D6 inhibitor. I normally co-administer Grapefruit juice and Diphenhydramine for enhanced/dual inhibition before I take my Oxycodone which produces much more potent and longer lasting effects than taking just one inhibitor alone.

 

[dopamimetic]

Diphenhydramine (Benadryl) is an effective CPY2D6 inhibitor. I normally co-administer Grapefruit juice and Diphenhydramine for enhanced/dual inhibition before I take my Oxycodone which produces much more potent and longer lasting effects than taking just one inhibitor alone.

Yeah this might indeed be more effective than each one alone because they block different enzymes, afaik grapefruit juice the 3A4 one.

But feeling weird might indicate that by blocking 3A4 some other enzyme does metabolize metha into something causing adverse effects. An infamous example is paracetamol which competes with alcohol for one enzyme and if that's busy with ethanol, a toxic intermediate builds up. Usually it's not that bad (and would probably be known with something as old and widely used as methadone).

With some luck these both inhibitors are synergistic and inhibiting 2d6 would cause less of that other product.

 

[evo4ever]

Yeah this might indeed be more effective than each one alone because they block different enzymes, afaik grapefruit juice the 3A4 one.

But feeling weird might indicate that by blocking 3A4 some other enzyme does metabolize metha into something causing adverse effects. An infamous example is paracetamol which competes with alcohol for one enzyme and if that's busy with ethanol, a toxic intermediate builds up. Usually it's not that bad (and would probably be known with something as old and widely used as methadone).

With some luck these both inhibitors are synergistic and inhibiting 2d6 would cause less of that other product.

The only problem with using multiple inhibitors is a marked increase in Histamine response which is quite paradoxical as Diphenhydramine is meant to block Histamine.

 

[F.U.B.A.R.]

Usually if your dose isn't holding you it means you need an increase. Is that an option?

 

[OpiateKiller]

Usually if your dose isn't holding you it means you need an increase. Is that an option?

Yes I am on 120 mg now but I could convince my counselor I want to go higher. She told me my dose was pretty low compared to most others, which kind of shocked me. My clinic average must be like 180 mg which is nuts. I’m hoping I can quit this fall**

 

[F.U.B.A.R.]

Yes I am on 120 mg now but I could convince my counselor I want to go higher. She told me my dose was pretty low compared to most others, which kind of shocked me. My clinic average must be like 180 mg which is nuts. I’m hoping I can quit this felsk

Yeh, you need to find a dose that holds you properly then stabilise on that dose for several months with no 'treats' before you can even think of reducing. My sweet spot was 120mg and I stayed on that for about 2 years before dropping. It's a long road and the slower you travel the easier it is.

 

[OpiateKiller]

Yeh, you need to find a dose that holds you properly then stabilise on that dose for several months with no 'treats' before you can even think of reducing. My sweet spot was 120mg and I stayed on that for about 2 years before dropping. It's a long road and the slower you travel the easier it is.

Thanks Fubar, I actually just increased to 120 yesterday so we’ll see if this does the trick(y)