Codeine + Grape Fruit Juice.

[Mr. Squiggle!]

ingesting some grapefruit?

Seems feasible:
http://www.nejm.org/doi/full/10.1056/NEJMoa041888

Although this doesn't list the exact case of grapefruit juice, but rather kidney failure:
CYP2D6 catalyzes hydroxylation or demethylation of more than 20 percent of drugs, including codeine.

O-demethylation of codeine into morphine by CYP2D6 represents a minor pathway of codeine metabolism (accounting for less than 10 percent of codeine clearance)8 but is essential for its opioid activity (Figure 1Figure 1Metabolic Pathways of Codeine Biotransformation.). N-demethylation of codeine into norcodeine by CYP3A4 and the glucuronidation of codeine are the main pathways (accounting for more than 80 percent of codeine clearance) for converting the molecule into inactive compounds.

We describe a patient who presented with life-threatening codeine intoxication despite having received only modest doses of the medication. Analysis of the patient's cytochrome P-450–dependent monooxygenase genotype (CYP2D6) and phenotype (CYP2D6 and CYP3A4) indicated that his unusual response to codeine might be explained by ultrarapid CYP2D6 metabolism, combined with the inhibition of CYP3A4 by other medications and the accumulation of active metabolites because of renal failure.

It still leads on to the question of whether or not grapefruit really does enhance the opioid activity of codeine?

 

[Mr Blonde]

Man, this topic has been done to death.

It doesn't really enhance it but prevents it's metabolism into inactive components somewhat. So the duration will be somewhat longer.

 

[Mr. Squiggle!]

K Dude. I know that GFC was covered extensively with respect to benzos, but during my absence from visiting this site, i was unaware.

It's just that a Wikipedia entry got me by a surprise:
# The benzodiazepines triazolam, midazolam, diazepam, alprazolam and quazepam[2]
Blah, blah, been covered, done and dusted but check this shit out Blondy.


Codeine and Tramadol.[9] It reduces the amount of codeine converted by CYP3A4 into norcodeine thus increasing the amount metabolised into morphine.[citation needed] Morphine itself, however, is not affected by grapefruit juice, as it is not metabolised by the cytochrome P450 system.

 

[Divine Moments]

Yeah CYP2D6 normally converts about 10% of codeine to morphine, so if you block the other pathway/s of metabolism then the codeine lasts longer and more is converted to morphine. As Mr Blonde said there are heaps of threads on bl about it.

 

[Mr Blonde]

^ Theoretically though, if you are a normal metabolizer of codeine then your CYP2D6 enzyme is already going to be inhibited by codeine itself and GFJ will have minimal effect.

GFJ never did anything for me.

 

[titstypedthis]

try eating 10g of black pepper aswell


no i'm not kidding, do it for science cunt

 

[Mr Blonde]

^ It would work just the same way as GFJ, and so is dubious in my book as well.

 

[Divine Moments]

^ Theoretically though, if you are a normal metabolizer of codeine

I am not

 

[Mr Blonde]

^ Poor or extensive CYP2D6 metabolizer?

I'm an extensive metabolizer. :D

 

[Sustanon]

Just a tip. Use dxm about 80-120mg before u take the codeine. Works like a charm regards to potentiation.

 

[titstypedthis]

^ It would work just the same way as GFJ, and so is dubious in my book as well.

yeah but, do it for science cunt

 

[Mr Blonde]

^ I am science.

 

[Divine Moments]

^ Poor or extensive CYP2D6 metabolizer?

I'm an extensive metabolizer. :D

Poor. No DXM, codeine, etc for me

Buuut at least all the best drugs still work normally

 

[BodyHereMindGone]

diltiazem works well..

 

[Mr Blonde]

^ But it inhibits CYP2D6...?

 

[titstypedthis]

^ But it inhibits CYP2D6...?

it's not proven that morphine is the main cause of codienes effects.

significant contributor, yeah, but theres other metabolites that are definitely doing something.

thats about the extent of what i know

 

[Divine Moments]

^ The lack of effects I (and other CYP2D6 poor metabolisers) get from codeine is enough proof for me

I thought the contention was the role played by codeine itself rather than the metabolites, I didn't think codeine had other active metabolites but I may be wrong.

 

[BodyHereMindGone]

i have tested with and without it...

With is always a "better buzz", My brother agrees...

As do many other people i have given this pill to...

By itself, the drug gives me really bad headaches. taken with codeine, i find myself floating on a cloud...

I tested by doing CWE and dosing 150mg of codeine with and without the pill, leaving a one week gap between testing times.

Edit~ In the taste of science, i have repeated it several times.. It was not coincidence.

 

[Mr Blonde]

it's not proven that morphine is the main cause of codienes effects.

significant contributor, yeah, but theres other metabolites that are definitely doing something.

thats about the extent of what i know

I am not of the train of thought that codeine-6-glucuronide contributes much to analgesia and euphoria in humans.

Mainly because the only studies have been done in rats, and from what I have gathered our blood-brain-barrier is a lot more restrictive in what it lets through then the rat BBB. Adding to this is that in an analogous study in rats of morphine-6-glucuronide, the substance when given by normal IV took quite a while to achieve similar distribution in the brain to morphine and had a delayed analgesic effect. The effect is significant enough that I expect in people it would be somewhat noticeable.

Also, the section on Wikipedia's 'Codeine' dealing with this topic is badly written and makes statements without any cites and there is only one really related cite that is to that rat study of C-6-G and the other major cite is to an article abstract that seems to only deal with analysis of metabolites of codeine, dihydrocodeine, hydromorphone and a couple of other opioids.

Those other metabolites may play a role, but if they really contributed much then I would expect my equipotent dose of morphine to be higher then it is in reality.

I thought the contention was the role played by codeine itself rather than the metabolites, I didn't think codeine had other active metabolites but I may be wrong.

It is theorized that it has active metabolites but nothing has been proven in humans. In rats there was analgesic activity of C-6-G that was two thirds that of codeine. The codeine molecule itself, without being metabolized to anything useful, does nothing but provoke a histamine response.

i have tested with and without it...

With is always a "better buzz", My brother agrees...

As do many other people i have given this pill to...

By itself, the drug gives me really bad headaches. taken with codeine, i find myself floating on a cloud...

I tested by doing CWE and dosing 150mg of codeine with and without the pill, leaving a one week gap between testing times.

Edit~ In the taste of science, i have repeated it several times.. It was not coincidence.

How does it make it a better buzz? It may add sedation but I can't see any other mechanism for a calcium channel blocker potentiating an opioid, especially when it inhibits the enzyme that makes that opioid work.

Note to anyone considering trying the combo: it will lead to a more decreased blood pressure, such that it could lead to hypotensive problems and make you feel very dizzy when standing up.

 

[lynnie]

I am pretty certain nobody has questioned sultana's mixed with benzo or codeine. Anyone here has tried the combination?