Harm Reduction Drug enha(n)cers

[Shitake]

I saw that ketoconazole is a potent CYP3A4 inhibitor, who makes the drug metabolism slower than normal, increasing the concentration and bioavailability.
Does anybody have another ways to give a boost in some substances? Like opioids, benzos, ketamine, LSD etc..?

 

[Jabberwocky]

I saw your post about morphine and methylphenidate and meant to respond but fell asleep.

CYP 3a4/2d6 inhibition is not going to potentiate either morphine or methylphenidate, because neither of those drugs are metabolized by those enzymes. It works for drugs like oxycodone or codeine but not morphine.

Also enzyme inhibition doesn't necessarily make drugs stronger in every case. Usually it just results in a longer duration, but it's different in every case.

Codeine would be a unique example of direct potentiation because it has both an active and non active metabolite (codeine itself is not psychoactive). By inhibiting 3a4 more of it turns into morphine via 2d6.

Anyways... for me the best potentiators are natural. Good sleep, healthy diet, positive state of mind, moderation of tolerance, etc...

 

[psychnauticmage]

CYP 3a4/2d6 inhibition is not going to potentiate either morphine or methylphenidate, because neither of those drugs are metabolized by those enzymes. It works for drugs like oxycodone or codeine but not morphine.

You've got it backwards. CYP2D6 metabolizes codeine, inhibiting it means you get less codeine metabolized into stronger opioids like morphine. What you'd want instead is a CYP2D6 inducer of which there are practically none. The only one I know of is dexamethasone.

Edit: Made a correction. Thank you for that Snafu. 3A4 turns codeine into norcodeine not morphine.

 

[psychnauticmage]

Kava also markedly inhibits some of the Cytochrome P450 family of enzymes, with significant inhibition of the activities of CYP1A2 (56% inhibition), 2C9 (92%), 2C19 (86%), 2D6 (73%), 3A4 (78%), and 4A9/11 (65%). According to this study: https://pubmed.ncbi.nlm.nih.gov/12386118/

Though Kava also is a GABA-A PAM (positive allosteric modulator), monoamine oxidase inhibitor and a calcium channel blocker among other pharmacological properties. In my experience I have used it to extend the duration of certain substances but it's not a great solution.

It's cheap and readily available though. Also bear in mind monoamine oxidase inhibitors increase the potential for drug to drug interactions a fair bit so be careful what you take it with. Although it is not a particularly potent monoamine oxidase inhibitor.

- I'm not a doctor, this is just my 2 cents.

 

[Jabberwocky]

You've got it backwards. CYP3A4 metabolizes codeine into morphine, inhibiting it means you get less codeine turned into morphine making it weaker. What you'd want instead is a CYP3A4 inducer of which there are practically none. The only one I know of is dexamethasone.

No. It's definitely 2d6 that metabolizes it to morphine, but 3a4 is the preferred route which is why codeine is so weak dose comparatively, because most of it is metabolized that route.

 

[psychnauticmage]

No. It's definitely 2d6 that metabolizes it to morphine, but 3a4 is the preferred route which is why codeine is so weak dose comparatively, because most of it is metabolized that route.

You are correct in stating that CYP2D6 and CYP3A4 both metabolize codeine. I was not arguing with you there. However you said that inhibition of said enzymes may increase the effects of the drug. This is not true, with codeine you would not want to inhibit CYP2D6/3A4 but rather induce them so that they metabolize more of the codeine into morphine.

If you inhibited it, less codeine would be converted to morphine.

Edit: I was incorrect in stating CYP3A4 metabolizes it into morphine rather than into norcodeine, but my point about the inhibition of said enzymes still stands.

 

[Jabberwocky]

You are correct in stating that CYP2D6 and CYP3A4 both metabolize codeine. I was not arguing with you there. However you said that inhibition of said enzymes may increase the effects of the drug. This is not true, with codeine you would not want to inhibit CYP2D6/3A4 but rather induce them so that they metabolize more of the codeine into morphine.

If you inhibited it, less codeine would be converted to morphine.

Heh I did list them backwards. My bad.

I should have clarified, for codeine you want to inhibit 3a4 and/or induce 2d6.

You wouldn't want to induce 3a4.

By inhibiting 3a4 more of it is forced through 2d6.

Inhibition at 3a4 would be much more important than inducing either of them.

 

[psychnauticmage]

Heh I did list them backwards. My bad.

I should have clarified, for codeine you want to inhibit 3a4 and/or induce 2d6.

You wouldn't want to induce 3a4.

By inhibiting 3a4 more of it is forced through 2d6.

Inhibition at 3a4 would be much more important than inducing either of them.

Yep that's spot on. Thank you for correcting me. For some reason I thought 3A4 turned it into morphine, I also had it backwards lol