Codeine Potentiators

[darkglobe]

[Drugs-Forum note: Factual errors are contained in this post. Grapefruit juice does not affect CYP2D6 activity. See this thread for more information.]

This post is for those wishing to get the most out of any Codeine available to them. This has no doubt been posted before, and is well-known information, but I'd like to point out the advantages/disadvantages associated with each method of potentiation.

First off, Codeine is - in every sense of the word - a weak opiate. This is determined by a number of factors

1. The Side Effects
Okay, this is probably the most obvious of all. Yes, the use of Codeine at recreational doses brings with it some nasty side effects. Namely:

• The Opiate Itch: Due to Codeine's analgesic qualities, scratching probably won't help.
• Shortness of breath: This is caused by large doses of Codeine slowing down the respiratory process.
• Other side-effects: These vary between individuals. As this is not the focus of this post, I won't go into any further detail.

2. Dosage Issues
The majority of Codeine's recreational properties are noticed due to it being metabolised into Morphine in the body:

• Conversion into Morphine: There appears to be a ceiling to the amount converted. The conversion is approx 100% Codeine = 10% Morphine.
• Availability of the drug: This varies greatly between countries. As an example, in the UK Codeine is available upto 8mg without prescription. With prescription, Codeine is available upto 30mg. The amount of tablets needed to obtain a recreational dosage can run into hundreds.

Anyway, back to the topic in hand... CODEINE POTENTIATION.

Aww, crap. Unfortunately something important has come up and I now have to leave my computer. I shall post this as it is. Don't bother replying I will complete the writing in another post later today. Apologies for a useless post so far.

[darkglobe]

Codeine Potentiators Contd.

[Drugs-Forum note: Factual errors are contained in this post. Grapefruit juice does not affect CYP2D6 activity. See this thread for more information.]
This completes the above unfinished post. I have split my list of substances which can be used to potentiate a recreational dose of Codeine into two sections. The first section is a list of good potentiators (those which work effectively with no known/significant drawbacks. The second is a list of bad potentiators (those which either do not work, or have significant drawbacks). Also included at the end is a list of non-drug potentiators and ingestion methods to increase efficacy. Here we go:

1. Good Potentiators
Some of these substances are known well amongst recreational users of Opiates, while others are lesser known (or indeed very hard to obtain):

• Diazepam (Valium) & Other Benzodiazepines: It is possible, although by no means sensible to mix opiate narcotics (of which group Codeine is obviously a member) with Benzos. According to www.opiods.com, use about 70% of your normal Codeine dose, and a non-recreational (ie therapeutic) dose of benzos. This will make a Codeine nod (if you don't know what a nod is then maybe you should reconsider drug mixes! ) much 'sleepier' and possibly prevent the insomnia that most people experience while on Codeine.
• Diphenhydramine: This can be found as Diphenhydramine Hydrochloride (HCl). It is a sedative antihistamine, found in allergy pills and sleeping aids. If a normal ('what it says on the box') therapeutical dose of say, 25-75mg Diphenhydramine HCl is taken together with your normal Codeine dose, the nod will feel somewhat more intense. I absolutely DO NOT recommend you take large quantities of either: "Those who take larger doses of antihistamines or other anticholinergics for the euphoriant properties should not take opiates along with them; needless to say, the mixing of opiates with the much higher deliriant doses of anticholinergics can be assumed to invariably have catastrophic effects because of the combination of respiratory depression and thickening of bronchial secretions caused by these drugs. It is assumed that any dose of diphenhydramine above 125 mg cannot be safely mixed with any quantity of opiate." (www.opiods.com)
  
• Dextromethorphan Hydrobromide: While not really much of a potentiator to the 'opiate buzz'. DXM HBr will definitely make Codeine use feel much calmer. Don't take more than one and a half times the proper dose, though. I've a friend who's had a lot of experience with this drug, and as a result of a terrifying experience, he will never touch it again. In case you didn't know, DXM HBr is a very potent dissociative drug in its own right.... but SWIM loves it
  
• Cyclobenzaprine: I've included this purely because it is a Codeine potentiator.SWIM has had personal experience with using this as a potentiator when he was almost out of Codeine. SWIM told me in no uncertain terms that this drug is SHIT. SWIM recommends some research into this drug before even considering it. SWIM will point out that it did indeed make for a kick-ass Codeine experience. SWIM reminds readers not to take ANY amount of Cyclobenzaprine when taking any other medication. In fact, SWIM says just don't take it. If you do, BE CAREFUL! NO other drugs! NO ALCOHOL AT ALL. And lower your Codeine dose, too. Okay... rant over. Also, take an antacid and 100mg of Caffeine 30mins before taking Codeine and Cyclobenzaprine. Believe it or not, the antacid will potentiate it further. And help your stomach
  
• Meprobamate: A therapeutic dose of this (200-600mg) combined with just over half your normal Codeine dose will definitely intensify things. Throw in some Quinine (found in tonic water drinks, incidentally) and you could reach morphine-style experiences. SWIM has tried this, but due to not finding any Quinine-based info out there probably hasn't done it properly.
• Barbiturates: While theoretically good potentiators to opiate highs, Barbs are almost definitely impossible to mix with, well.... anything. If you do it, you'll die. Why on earth did I write about them, then? Meh.

2. Bad Potentiators
These drugs may be written about on the internet as helping out a Codeine nod. They're either too dangerous to use, ridiculously hard to get hold of, or simply too ineffective to bother with:

• Barbs: As mentioned above - combine Barbs with opiates and you'll die. Put it this way, Methyprylon (not a barb, but in fact a non-barbiturate sedative-hypnotic with many of the same charateristics) and 60mg of Codeine gave SWIM such an intense buzz he literally forgot to breathe quite a few times. Poor SWIM laid asleep for nearly 3 hours outdoors in pouring rain after combining his because, back then, he didn't realise that Barbs were such powerful respiratory depressants.
  
• Nutmeg: I honestly do not know where this crazy-ass idea originated, but let me tell you this. Admittedly, Nutmeg is a hallucinogenic (well, one of it's chemicals is, I forget which...) and can indeed give a good 'trip'. But, unlike say DXM HBr, Nutmeg will make you feel VERY sick. Mix it with Codeine and it will make you EXTREMELY sick. SWIM told me about his experience with them. SWIM didn't like it.
• Alcohol: I apologise sincerely if this turns into an opinion-based rant. But seriously, why do people do such stupid things? The same friend I spoke about earlier decided to drink 35cl of Vodka, a shot of apricot brandy and half a glass of port.... then combined it with 100mg of Codeine. SWIM had to call an ambulance for him. He was actually dead for 30 seconds, too. A SMALL quantity of alcohol (say, maximum 2 shots of Vodka or equivalent) and HALF your normal Codeine dose will suffice. Be careful.
• Gluthethimide: This is famous amongst Codeine users online. Theoretically it's a good potentiator, although probably dangerous. It belongs to the same group as Methyprylon (the piperidine-derived drugs). Besides, it's near impossible to get hold of in the UK and US. *(If a Mod reads this, please PM me to tell me if that last sentence is in breach of the sources rule)*

Non-Drug Potentiators
These are mostly common sense, but can be easily overlooked:

• An empty stomach: An empty stomach helps the codeine all get metabolised at once. I won't go into the chemistry of it, but Codeine itself is a Cytochrome P450 inhibitor. Redosing within short periods of time is ok, but redosing say 2 hour later is a waste. Also an empty stomach means your Codeine will hit sooner.
• Good health: Try and maintain good overall health. A good pair of lungs and a nice low pulse rate will most likely counter any bad breathing problems you will experience.

Methods Of Ingestion
Okay, you're probably not gonna like this...

• Rectal: I appreciate that most of you won't want to squirt Codeine water up your ass, but it is a fact worth noting if you're looking to squeeze every bit of potency out of your Codeine supply.
• Oral: The most common method, for obvious reasons. With this, 400mg of Codeine will likely give you one hell of a buzz.
• Insufflation: Snorting crushed pain pills will fuck your nose up. If looking like a 30-years-of-coke addict appeals to you, then go for it. But seriously, it's FAR too dangerous to do. Pure Codeine powder may not be so dangerous. I honestly do not know.
• IV/IM/SC: Injecting Codeine, or anything, is dodgy territory, hence why I recommend strongly against it. Codeine can be injected SC (sub-cutaneously: just under the skin) but unless you know what you are doing, PLEASE avoid. Also, calibrated ACCURATE measuring equipment and STERILISED equipment MUST be used.

So there you go. Above is pretty much everything I know about Codeine use. Apart from one extra fact... no more than 400mg of Codeine can be metabolised at any one time. So if you go over, you're wasting it. Also you'd be reaching the lower end LD50.

So there you go. Above is actually ALL of my knowledge of Codeine. This post was intended to be a quick guide to all things Codeine, but ended up being a long-winded, boring mess of facts.
If anyone notices any incorrect facts, wants something I've quoted removed/credited, wants to tell me anything important about this post, please PM me. Otherwise reply below.

Everything here is for information purposes only and is in no way intended to encourage nor advise anybody into doing anything illegal or dangerous. I will accept no damage or liability arising from problems if people attempt anything described in this text.

~Dark

[Forthesevenlakes]

DXM may not be effective for the reason that codeine MUST be metabolized into morphine to be effective. Blocking or inhibiting one of the enzymes which performs this by taking DXM will lessen this process and render the opiate less effective. One would end up with more of a DXM high.

Also, it is NOT reccomended to combine other downers (benzodiazepines, barbiturates, high doses of antihistamines, etc.) with codeine or any opiate. To do so increases the risk of respiratory depression and even death!

Other than that, this could look to be an informative post. Codeine is unique among the opiates in that it must be metabolized to be active, so many common potentiators (DXM, grapefruit juice, tagamet) will actually decrease it's action.

[darkglobe]

Originally Posted by Forthesevenlakes

DXM may not be effective for the reason that codeine MUST be metabolized into morphine to be effective. Blocking or inhibiting one of the enzymes which performs this by taking DXM will lessen this process and render the opiate less effective. One would end up with more of a DXM high.

I'd overlooked that. If DXM is combined with Codeine, then it definitely does change the experience. While not technically 'potentiating' anything (as you quite rightly said it actually inhibits it) it will make for a better experience for some. But thanks for pointing that out.

Originally Posted by Forthesevenlakes

Also, it is NOT reccomended to combine other downers (benzodiazepines, barbiturates, high doses of antihistamines, etc.) with codeine or any opiate. To do so increases the risk of respiratory depression and even death!

Please don't take this as being argumentative, but taking recreational doses of Codeine os not recommended. If done with enough caution and knowledge, it can be done safely. Barbiturates - as I stated - are one hell of a no-no. I believe I didn't encourage reckless doses of anything. Do you think upto 75mg of say, Diphenhydramine is safe(ish)?

Originally Posted by Forthesevenlakes

Other than that, this could look to be an informative post. Codeine is unique among the opiates in that it must be metabolized to be active, so many common potentiators (DXM, grapefruit juice, tagamet) will actually decrease it's action.

Codeine is my favourite .

[Drugs-Forum note: Factual errors are contained in this post. Grapefruit juice does not affect CYP2D6 activity. See this thread for more information.]

While Grapefruit juice does inhibit the enzyme which slows down metabolism, it's also an inhibitor of Cytochrome P450 (SWIM told me, but his brain is fried from antihistamine OD last night). I'm uncertain as to whether it's a US only substance, but I've never heard of Tagamet.

EDIT: GFJ does NOT inhibit Cytochrome CYP2D6. See here for more details.

In conclusion: Thanks a lot for the extra advice, and I hope readers of this thread will take all advice given into consideration and be safe while they experiment and have fun.

[gotxp]

yea SWIM has heard a lot of mixed things on Codeine & grapefruit juice. Most say although it works for most opiates it inhibits the enzyme needed to convert codeine into morphine, while others say it inhibits a different enzyme responcible for turning codeine into norcodeine (bad), and therefore causes more codeine to be converted into morphine..

can anyone provide SWIM with a definitive answer.. thanks

[darkglobe]

You want the long version or the short version?

I'll give you both...

1. The Short Version
Codeine is metabolised by two things in the liver/small intestine.
The first one turns Codeine into Morphine (gooooood )
The second turns Codeine into Norcodeine (baaaaad )

Grapefruit juice inhibits the one that turns it into Norcodeine (baaaaaad )

2. The Long Version

Codeine, unlike hydrocodone, has little to no intrinsic activity. It is a prodrug. This means, for codeine to work, it must first pass through an enzyme that chops off a methyl group, converting the codeine to morphine. This happens primarily in the liver or small intestine.

This enzyme is known as Cytochrome P450 2D6, or "2D6" for short. AKA the codeine to morphine convertor in your body.
Studies have shown that in population subgroups with a genetically inactive version of 2D6 have little to no response to codeine.

Codeine is also metabolized by another enzyme, called "3A4", which metabolizes it to norcodeine, an undesirable product of little or no activity.

So there are at least two major pathways by which codeine is metabolized.

If one blocks the 3A4 enzyme without blocking the 2D6 enzyme, theoretically, more morphine is produced in your body.

Grapefruit juice, being a specific inhibitor of 3A4, functions by blocking 3A4 and allowing more codeine to be converted to morphine via 2D6. Grapefruit juice is desirable because the active compound is specific to 3A4, with no effect on 2D6.

3. My Opinion
I've never actually tried it. Theoretically, it works.
Problem is, like you, I've heard confliction reports.

Now, I know it inhibits Cytochrome 3A4, because every source says so. The only doubt I have is whether or not it also inhibits 2D6. I've also read on numerous occasions that taking an Antacid 30 minutes before taking Codeine works to potentiate it. Then again, I've read that it doesn't.

What we need to find out for sure is whether Grapefruit Juice/Antacids inhibit both enzymes. If they do, then it may result in a net negative effect.

[gotxp]

thanks man!, I will have to give the grapefruit trick a few more trials, and I will report back with my own experience on the situation. I tried it before; however, from what I read I became very sceptic on it working, so I may have had a reversePlacebo effect.

as for the antacid, from what I have read it potentiates codeine by simply increasing absorption rates by making your stomach more basic.

[darkglobe]

Below is more documentation discussing the potentiation of opiates with Grapefruit Juice.


The enzyme found in grapefruit juice is also found in Seville oranges.

http://www.nytimes.com/2006/03/21/he...2a71&ei=5 070

The grapefruit juice interaction with numerous medications, including certain benzodiazepines, is well documented.

http://www.fhma.com/grapefruit.htm

http://www.druginteractioncenter.org...ry=9&detail=61

So maybe there IS a chance tha chugging 16oz of grapefruit juice WILL make your Tylenol's into superpills.

Also....

I'm currently working on some research into the potentiation of benzos/antihistamines with grapefruit juice. When I say research, I mean googling.

A few people are under the impression that I'm a chemist (or even a professional at anything) for some reason. To clarify, I'm an unemployed school-leaver with a passion for drugs and how they do the things they do. All of the advice I present on this website belongs to other people. I do not claim that ANY of it is my own. I just research a lot harder than others. With my googling I am slowly teaching myself some basic Biology/Chemistry/Biochemistry and neuroscience.

It's amazing what one can learn by merely reading stuff on a screen....

~dark

[darkglobe]

My (really rushed) Codeine recipe.

Apologies about spelling/general crappyness of this post. I'm in a rush gonna miss my bus.

1. Drink 8-16Oz of Grapefruit Juce. (Don't go overboard on this, it'a acidic)
2. Take an antacid or two 30 mins later
3. Take Codeine, but drop your dosage slightly. Say, 50mg less.

There ya go. Don't mix with any other drugs. I suppose 25-50mg Diphenhydramine will be ok to soothe the itchies.

Will sort this out soon. I fancy a little project.... compiling all information I can geton Codeine potentiation in general. Maybe others could have their input and help me out? I'm no expert after all. I love a challenge, but think it's best not to do it myself as I would not be aware of any errors.

Post ideas here, don't PM me my inbox keeps getting full.

Back online tomorrow.


~dark

[gotxp]

SWIM looks forward to trying your recipe... perhaps tonight

[mickenator]

Swim has used the grapefruit and tums method quite a few times now and find that it works a treat, but if one has no opiate tollerence then they should decrease the dose to avoid OD.

[darkglobe]

Originally Posted by mickenator

Swim has used the grapefruit and tums method quite a few times now and find that it works a treat, but if one has no opiate tollerence then they should decrease the dose to avoid OD.

Yes, I agree. I probably forgot to include that important advice. It does get hard to remember those who are new to opiates.

A hypothetical person's hypothetical dose of a hypothetical opiate (which I'll call Codeine) is currently 330mg. The hypothetical person combines the hypothetical 330mg with a hypothetical 50mg of Diphenhydramine. Mr Hypothetical still hasn't attempted the Grapefruit juice 'trick' because he simply can't stomach the stuff.

[Tortoise]

Here's my spin on the whole codeine and grapefruit combo discussion;

It seems to me that some people think grapefruit potentialtes codeine, some people who think it does nothing and some people who think it inhibits codeine. The bottome line is when a drug is potentiaited by grapefruit juice, it is generally such an obvious potentiation that nobody disputes it (eg, DXM). If the jury is still out over codeine after all this time (I keep reading both sides of the story all over the net), I think it is safe to say that even if grapefruit juice does add to the experience, it clearly doesn't make a particularly significant difference.

The other thing is, codeine is generally cheap. In fact it is cheaper to use a few extra pills in a CWE than it is to buy a bottle of grapefruit juice. Long story short; if you want a stronger codeine experience, then wouldn't it just be easier to take more codeine?

[darkglobe]

Tortoise: yes yes it would.

Not too much though. Safe upper limit for new users would be 150mg. swims currently on 330mg. and he cant stop. its really affecting him.

im sure he'll tell you more when his head feels better.

~dark

ps: hello again drugs-forum. not beeon on in a while.