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    Codeine potentiation and synergy thread 
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    Hey all, over the last couple of months I have been doing much experimenting with codeine and various ways to potentiate it and drugs which synergise well with it. There was a thread recently but I feel it took a turn more towards tripping on DXM and antihistamines.

    Codeine is a pro-drug converted into morphine in the liver by CYP2D6, an enzyme of the CYP450 system. This process is called O-demethylation. Approximately 7% of the Caucasian population are CYP2D6 poor metabolizers, meaning they have few or no copies of this enzyme available to metabolize codeine into morphine. For the rest of us who can metabolize codeine, this thread aims to educate you on how to get the most out of it.

    For those of you unfamiliar with codeine or cold water extraction techniques, these links will be helpful:
    Wiki
    Erowid codeine FAQ
    Mr Blonde's Cold Water Extraction FAQ

    CYP2D6 Inducers:

    Carbamazepine: Anticonvulsant and mood stabilizer. (Schedule 4)

    Dexamethasone: Glucocorticoid steroid. (Schedule 4)

    Ethanol: AKA alcohol, beware drinking too much and experiencing side-effects such as severe nausea or CNS depression. One or two standard drinks 45 minutes before the codeine should work.

    Phenobarbital: Barbiturate, be careful if you try this due to the risk of CNS depression. If used, lower your standard dose of both substances to be safe. (Schedule 4, wasn't in the TGA Posion Standard 2008 document but wikipedia says schedule 4)

    Phenytoin: Antiepileptic, also used in treatment of neuralgia and arrhythmia. (Schedule 4)

    Primidone: Anticonvulsant and pro-drug for phenobarbital. Exercise due caution as with phenobarbital. (Schedule 4)

    Rifampin: Antibiotic. This drug is known for hepatotoxicity and so users combining this with codeine from a CWE should be careful here and those with liver problems should probably avoid. (Couldn't find schedule as yet, will look further, given the rest barring grog and St John's Wort are schedule 4 its probably a safe bet this one is too)

    Ritonavir: Antiretroviral used in treatment of HIV/AIDS. NOTE: DXM is probably best avoided being used in conjunction with Ritonavir. (Schedule 4)

    St John's Wort: Herbal supplement that is sometimes used for depression. NOTE: As St John's Wort is supposed to be an MAOI it is best avoided if you take certain medicines. DXM may interact badly with it, as well as SSRI's. This is one there is a chance I might not experiment with, because I always try avoid MAOI's.

    Taking any of these substances will theoretically increase the amount of codeine that is converted into morphine; a quick cross check with the TGA Poisons Standard 2008 shows that most of these are scheduled aside from ethanol and St John's Wort.


    Other Potentiatiors/Ways to get the most out your Codeine

    General Potentiation- These are a few easy ways to boost what you get out of your codeine, didn't feel like they really fit in another section

    Empty stomach- One of the most important factors, seriously I can have lowish tolerance and take a shitload of other potentiators but if my stomach is full you can bet that I am getting minimal effects. I can't stress enough, leave 4 hours after the last time you ate and eat lightly. Leave more time if you can.

    Antacid/baking soda- Supposed to neutralise some of your stomach acids so less codeine gets destroyed. Baking soda is disgusting but a few mylanta tablets go down easy enough. Definately seems to work to a degree.
    Wiki
    Drugs.com

    Nicotine- Everytime I smoke a cigarette or a cone when on opiates it definately seems to increase the nod, it also causes some nausea but if you smoke regularly it should be manageable. 'Nicotine and Opiates' is a good piece of reading that suggests codeine's action in the brain is similar to opiates. Here is a much more in depth look at nicotine and its interaction with opiates.
    Wiki
    Drugs.com
    Erowid

    Grapefruit Juice (GFJ)- I had toyed with the idea of using grapefruit juice for a long time but have read mixed reports. Recently I read that it doesn't inhibit CYP2D6 but rahter 3A4 which is responsible for conversion of codeine into norcodeine. In theory by inhibiting 3A4 you leave more codeine for 2D6 to turn into morphine. After reading this I decided to bite the bullet and give it a go. I had about 200ml of store bought grapefruit juice and about 100ml of squeezed juice around an hour before drinking my codeine. It definately seemed to increase the effects of both the codeine and the diazepam I took. I would say it potentiates diazepam/valium more than codeine but it does potentiate both. It is not a miracle potentiator and it definately does not potentiate codeine to a large extent, I found it to taste pretty gross personally and it isn't terribly cheap. Some people might not find it worth the mild potentiation it causes, if one is combining valium with their codeine I would say it is more worthwhile. I will be using it again, although the bitter taste is a bit of a deterrant for me, personally I would rather drink CWE! At this stage I have only used the red grapefruit juice and it seemed to work well enough, I have been advised that white grapefruit juice is better for potentiation purposes of both codeine and benzodiazepines.

    The following links have useful information on grapefruit juice:
    Grapefruit Juice FAQ
    Negative Results
    Erowid
    'Caffeine and Grapefruit to Potentiate Codeine'

    IMPORTANT NOTE: Using grapefruit juice will potentiate benzodiazepines as well as codeine, if you are using benzodiazepines to potentiate as well as grapefruit juice then please take this into consideration when dosing, according to one of the linked documents on GFJ it also potentiates DXM. Furthermore, it is definately worth noting that there are as many negative reports about the use of GFJ as positive ones, it seems to work for me but your results may vary as it may also inhibit 2D6.

    Valerian- Said to add sedation, personally I felt no diference but I wasn't too surprised given my relatively extensive experience with much more powerful sedatives. Perhaps it would work well for people with little to no experience with sedatives, although if one is inexperienced polydrug use/potentiation is probably not a great idea.

    Antihistamines- Antihistamines are very useful in the potentiation of codeine and other opiates, not only do certain antihistamines increase sedation but they help to counteract some negative effects of the opiate like itching and nausea.
    Wiki

    Doxylamine succinate/'Restavit'- Excellent antihistamine, can be taken before codeine unlike diphenhydramine and promethazine. I find it particularly useful for relief of nausea, less so for itching. Funnily enough a friend who favours travalcam finds the opposite, less effective for nausea but more so for the itches. I usually take it 45 minutes to an hour before my codeine, dosing 25-50mg. (1-2 'restavit' tablets)
    Wiki
    Drugs.com

    Promethazine/'Phenergan'- Good antihistamine, I find it more effective at relieving itching than doxy, but as you have to wait a while after drinking your codeine to take it I don't like it so much. I use 25-50mg usually. I find promethazine seems to increase the duration of the warmth, possibly because it inhibits CYP2D6 although since I wait till after dosing and notice no reduction in effects it seems like it might just be synergy.
    Wiki
    Drugs.com
    Erowid

    Diphenhydramine/'Snuzaid'- Inhibits CYP2D6, gets raved about as an opiate potentiator in general. My one and only experience using this was dismal. I waited about 15 minutes after my codeine started to come on to take it, roughly the same I would with promethazine, within 15 minutes my high was dead. Not only did it not escalate but it seemed to kill the buzz I already had going. Somehow even though it is an antihistamine, by half an hour after popping the 50mg of diphenhydramine the only opiate effect I had left was itchiness!
    Wiki
    Drugs.com
    Erowid

    Dimenhydrinate/'Travalcam Original'- This contains 50mg dimenhydrinate, .2mg hyoscine hydrobromide and 20mg caffeine. I have read/heard dimenhydrinate is basically just a pro drug of diphenhydramine yet any time I have used travalcam I take it 45 minutes before dosing codeine and have never had a problem. I would advise anyone unfamiliar with this product to start off with one tablet the first time. It is the only antihistamine that has made me pretty whacky off lowish doses, although that only happened once. I usually take two of thse if I use them, or one of these and one restavit. I have read belladonna alkaloids potentiate opiates too so that could be why these work so well.
    Wiki-Dimenhydrinate
    Wiki-/Scopolamine/Hyoscine
    Wiki-Caffeine
    Drugs.com-Dimenhydrinate
    Drugs.com-Scopolamine/Hyoscine
    Drugs.com-Caffeine
    Erowid-Dimenhydrinate
    Erowid-Scopolamine/Hyoscine
    Erowid-Caffeine

    Brompheniramine Maleate/'Dimetapp' (liquid solutions)- I was advised 6-8mg of this is about equivalent to 50mg of doxylamine and decided to give it a go. It is available in formulations that contain 10mg of DXM per 2mg of brompheniramine (5mL of actual solution) and I have determined it could be a useful way to kill two birds with one stone so to speak. It turns out brompheniramine has some SNRI properties too. Anyway, I gave this a whack, I decided to take 8mg. I found it to be sedating, although I would say it is probably the least sedating of the antihistamines in this list. It was a very effective antihistamine and I noted very little itching or nausea for the duration of the opiate high. It is worth considering I am tolerant and experienced with all other antihistamines in this list, but it was my first time using brom so this could be a factor in its effectiveness. Brompheniramine seemed to give me quite a mood lift, possibly due to it's SNRI properties, I suppose the phenylephrine could of caused this but I have been lead to believe phenylephrine is totally inactive. Overall I found this to be excellent, and given the availability of a formulation containing DXM it is rather cost effective.
    Wiki
    Drugs.com

    IMPORTANT NOTE: Due to the SNRI properties it is unsafe to mix brompheniramine with MAOI's. St. John's Wort which is named elsewhere in this thread as a CYP2D6 inducer happen's to have MAOI properties and should not be taken in conjunction with brompheniramine.


    Dissociatives Dissociatives are useful for potentiating opiates via NDMA antagonism, it is not fully understood how it works but it seems as though most studies conclude NDMA antagonists when administered with opiates do increase the effects. It is worth noting that both dissociatives mentioned here do bind to some opioid receptors (mu and sigma I think for ketamine) although that possibly is only in doses higher than reccomended in this thread.
    Wiki

    Dextromethorphan hydrobromide(DXM)/'Robitussin DX'- Dose 30-60mg 45-60 minutes before dosing and/or 30mg 15-20 minutes after dosing, obviously one would be more inclined to do the post codeine dose of DXM if they didn't dose beforehand or took only 30mg as opposed to 60mg. Definately adds to the sedation and body high, would say the addition of DXM makes the high a bit less clear headed. If you can still nod off codeine and get the daydreams DXM makes them more intense. Very worthwhile to go buy a 200ml bottle of DX, you get quite a bit of mileage and it is a great potentiator.
    Wiki
    Drugs.com
    Erowid

    IMPORTANT NOTE: According to the drugs.com link you should not combine Ritonavir with DXM, Ritonavir is in the list of CYP2D6 inducers. Thorough research should be done before considering combining these two medicines and it is probably advisable you just don't do it

    Ketamine- I tried snorting about 1 and a half points of ketamine (not pure but definately decent quality) around 40 minutes before dosing a CWE once, it definately seemed to come on hard and was very enjoyable. I can't say it was direct potentiation and not just synergy of the two highs, but I would use this combination again in a heartbeat. I am pretty sure DXM potentiates opiates through it's dissociative activity but not entirely positive it doesn't have to do with liver enzymes. Assuming dissociative effects of DXM cause potentiation it makes sense that ketamine would do it as well. I will try find something definitive on this in the near future.
    Wiki
    Drugs.com
    Erowid


    Benzodiazepines and Barbiturates- Low to medium doses of benzo's can help codeine along rather nicely. They add sedation to the high and I believe make it overall more pleasant. The muscle relaxation caused by some benzo's can add to the body buzz greatly
    Wiki
    Erowid

    IMPORTANT NOTE: The combination of benzodiazepines and/or barbiturates with opiates can be extremely dangerous and should be attempted with extreme caution, when trying for the first time make sure to dose conservatively as you can always take more but you can't take less. Furthermore, several other potentiators outlined in this thread increase the effects of these classes of sedatives and this should be considered, of particular note are alcohol and grapefruit juice.

    Diazepam/'Valium'- Would have to be my personal favourite benzo for potentiation of codeine. I feel out of the benzodiazepines I have tried this one has the greatest muscle relaxant properties which adds to the high greatly. Adds some sedation, but not a great deal. I would advise against taking more than 10mg with codeine unless you have a decent tolerance to benzo's, both because mixing benzo's and opiates is dangerous and because using too much benzo can really overpower the codeine high. 20-100 hour half-life.
    Wiki
    Drugs.com
    Erowid

    Alprazolam/'Xanax'- Goes quite well with codeine, I reccomend .5-1mg unless already tolerant to benzo's. It adds quite a bit more sedation than diazepam does, but seems to lack the muscle relaxant properties that make diazepam synergise with codeine so well. 10-14 hour half life.
    Wiki
    Drugs.com
    Erowid

    Lorazepam/'Ativan'- This one adds quite a bit of sedation, maybe a little less than alprazolam but definately considerably more than diazepam. Has some muscle relaxant properties that go good with codeine, in my experience diazepam was preferable but given further chance to experiment this one could become a favourite. 9-16 hour half life.
    Wiki
    Drugs.com
    Erowid

    Temazepam- Very sedating. I have always found temazepam an odd benzo, I require large doses to get a good effect but once I get going there probably isn't a benzo (by itself) I prefer for recreation. Unlike every other benzo I have experience with however, it seems to really lack any appreciable but more subtle effects at lower doses. My one experience using temaz with codeine I took too much and it overpowered the high. It is my belief this isn't a great benzo for synergising with codeine as it is generally the subtle effects of a benzo at lower doses that go well with it. If I was to reccomend a dose I would guess maybe 30-40mg. 3.5-18 hour half life.
    Wiki
    Drugs.com
    Erowid

    Clonazepam- Much like diazepam, clonazepam has strong muscle relaxant properties which seem to synergise well with the codeine, although less muscle relaxation than diazepam. Very anxiolytic with a subtle underlying calmness. Start with 0.5mg with a low or no tolerance. 19-60 hour half-life.
    Wiki
    Drugs.com
    Erowid

    Oxazepam- Quite anxiolytic and a bit more sedating than diazepam or clonazepam, seems to induce depression the next day compared to other benzos, possibly due to short half life. Overall a weak benzo, though that makes it a little safer to mix with codeine before trying stronger benzos. I'd recommend starting with 30mg for potentiation without tolerance. Half-life somewhere between alprazolam and clonazepam. 4-14 hour half-life.
    Wiki
    Drugs.com

    Bromazepam/'Lexotan'- Mediocre benzo to use with codeine really, it does the job but the sedation it adds is minimal compared to certain other benzos, it also lacks muscle relaxant properties which I personally value when using drugs synergisticalyl with codeine. Definately does induce a positive mood life though and some may find the lesser sedation more desirable as not everyone is looking to get stoned as.

    Phenobarbital- This is a relatively weak barbiturate that I believe is mainly used to treat epilepsy and perhaps restless leg syndrome. As noted earlier in this thread, phenobarbital is a CYP inducer which combined with its psychoactivity make it a good candidate for codeine potentiation. I only had the pleasure of trying this once and it seemd to increase the effect of codeine quite a lot, it is worth noting it also potentiates alcohol rather strongly. Phenobarbital is quite a slow acting drug, taking around 3 hours to reach peak plasma concentrations in the blood, bear this in mind when timing your dosing if you want your drugs to peak at the same time. This one should probably only be attempted by those experienced with both codeine and strong GABAergics and should be dosed conservatively on the first attempt regardless of user experience.


    Nonbenzodiazepines- This is a class of sedative drugs that have similar activity to benzodiazepines but are not benzo's. The most common ones would probably be the "Z drugs" which include zolpidem tartrate, zopiclone and eszopiclone. Unfortunately the only one with which I have personal experience is zolpidem.
    Wiki

    Zolpidem tartrate/'Stilnox'- I was unimpressed. Didn't feel the codeine strongly at all, although like anyone familiar with decent doses of this drug will tell you after a few drinks and cones I was well fucked up. I think this drug is best used for sleeping, or to relax with some marijuana and small amounts of alcohol. Overpowers codeine WAY too much to be useful for potentiation/synergy. Maybe ultra low doses could go OK.
    Wiki
    Drugs.com
    Erowid


    Antipsychotics- Antipsychotics are a class of medications typically used to treat psychosis among other things. Some of these are quite sedating and may have some use to add sedation to codeine. Promethazine could be put in this category, I felt it was more fitting in the antihistamine category however because it's antihistamine properties are a lot of what makes it so desirable to use with codeine/opiates.
    Wiki

    Quetiapine/'Seroquel'- An atypical antipsychotic with very sedating properties. From my experience there was no increased euphoria or 'mood lift', perhaps a very slight added body buzz through the extra sedation. But the main reason I sometimes use it for potentiating is the greatly increased sedation which increases the likelihood of entering 'the nod'. Seroquel on its own has zero recreational properties, pretty much only useful for medicating psychotic illnesses or killing amphetamine/other stimulant comedowns and causing heavy sedation.
    Wiki
    Drugs.com
    Erowid


    Antidepressant Drugs- This section covers various antidepressants and their synergistic effect with codeine.

    St John's Wort- This is an OTC supplement used for stress and anxiety and is a mild MAO, it is said to induce CYP2D6. I never found this to make much difference, possibly a mild one but in my mind not worth the risk of consuming MAOI as someone who dabbles in a variety of substances.

    Amitriptyline- A tricyclic antidepressant used as a sleep aid sometimes, I find this does increase the sedation from codeine and seems to work OK as an antihistamine. I tend to find it makes the high a bit more dopey and less euphoric and would only really reccomend it if you are trying to get best effects from a lower dose than you would usually take.

    Recreational Drugs- This section covers illicit and otherwise recreational substances I have used with codeine that don't particularly fit into any other section.

    Alcohol- Alcohol is an inducer of CYP2D6 so I always have 1 or 2 shots of whisky/bourbon in the half hour to 45 minute lead up to consuming my CWE. I usually have another shot or two half an hour after drinking my CWE give or take. This gets a mention in the list of CYP2D6 inhibitors too, but felt it had a place here because it is a sedative in its own right.
    Wiki
    Drugs.com
    Erowid

    GHB/GBL/1.4B- A small dose of 1,4b (presumably similar applied to GHB and GBL, but I can not attest to this from personal experience) works quite well at potentiating codeine, while it does probably slightly diminish some of the opioid effects it adds a more relaxed body high as well as a slightly more upbeat euphoria. Be careful with this combo as dosing G can be dicey at the best of times and is known to greatly increase the effects of other CNS depressants when used in conjunction with them.

    Cannabis- I find small amounts of smoked cannabis synergise extremely well with codeine. Don't smoke too much or it will overpower your high. Definately worth trying if Mary Jane is your thing.
    Wiki
    Drugs.com
    Erowid

    Methamphetamine- I found dosing codeine on the tail end of a meth comedown quite pleasant. There does seem to be some synergy with the lingering meth body high and it definately takes the edge off the comedown. Although if you dose too early I wager you would not get much from your codeine at all.
    Wiki
    Drugs.com
    Erowid

    Dexamphetamine- Pretty much the same as for methamphetamine, as it is a weaker amphetamine it probably has less of a tendency to overpower the codeine if you dose it early.
    Wiki
    Drugs.com
    Wiki-Amphetamine


    Other Opiates/Opioids- If you are reading this thread chances are you are a fan of opiates. I have found that since illicit opiates are often either limited in supply or rather expensive, using codeine in conjunction is a cost effective and reliable way of spreading them out further and in some cases the synergy actually provides a superior buzz
    Wiki

    Dihydrocodeine/'Rikodeine'- Have tried everywhere from 50ml to 200ml with various doses of codeine. I did not find it very impressive. DHC seems to be less sedating than codeine and it definately overpowers it when you use the two together. Combining this cough syrup with CWE is rather nauseating as well I should add, and the sorbitol content gives many the runs.
    Wiki
    Erowid

    Tramadol- Used to crush and eat 200mg about an hour before dosing codeine, always found it highly effective. Some of the best nods I ever had were from this combo, the tramadol seems to increase the sedation and duration of the high quite a bit for me. Do keep in mind that tramadol has SNRI properties.
    Wiki
    Drugs.com
    Erowid

    Heroin- Obviously this went down well, I predominantly felt the heroin but the codeine made it itchier than prior experiences with heroin despite the fact it was the only time I used an antihistamine with heroin. If you use codeine with heroin expect to use less heroin, but not much less.
    Wiki
    Erowid

    Morphine- Goes well with codeine, feels like it is more sedating without increasing the itch and stuff. Good combo, although can be costly given morphine has poor bioavailability unless it is injected, as the majority of codeine users are probably not intraveinous drug users this is definately something to consider.
    Wiki
    Drugs.com
    Erowid

    Loperamide/'Imodium'- It is an opiate that has difficulty crossing BBB, some people report recreational effects. It is said there are a few ways to get it to cross BBB, and GFJ is one of them so there could be something there. When I used this I did not look too much into reported ways to make it cross the BBB and can't report if some of these may work. On its own I noticed no synergistic or potentiating effect with codeine but it made opioid constipation much worse (as to be expected really). I would note that in my experience this is a very bad drug to take with Rikodeine, the abdominal pains and discomfort as a result are far worse than the effect of too much sorbitol.

    There are a number of other things I intend to try in the near future so I will update as I try them, anyone with experience in any of these is highly encouraged to contribute.

    On my to do list I have:

    Tonic Water- Quinine is in tonic water and is said to potentiate opiates.
    NOTE: I have had this article pointed out to me - LINK - and it seems to suggest quinine actually inhibits the effects of codeine. I am still likely to give this a go at some point, but it seems there is a high chance of disappointment.

    Poppy seed tea- Recently read someones report that they got a good buzz off this. Figure it could add some good element to codeine maybe, will probably try it on its own first to be safe.

    Chlorpheniramine maleate/'Demazin'- Recently saw this available OTC in 'Demazin', I believe it is 1.5mg chlorpheniramine and 5mg phenylephrine per 5mL. I am considering trying this, but don't see any great benefit as it is pretty much the same as brompheniramine but even less sedating. Factor in that I can get brom forumlations also containing DXM and this isn't a particularly attractive option, but I may do some investigating.


    Hope someone finds this useful, and that some people can add to it. I am sure there are some things I have forgotten, if I remember I will add them.

    Gotta give Mr Blonde special mention and thanks for his contribution to this thread, all the stuff on CYP2D6 inducers and some of the info on codeine came from him. Also would like to mention Puckboy for contributing the sections on seroquel, clonazepam, oxazepam and dexamphetamine. Cheers guys, much appreciated!

    Some links of interest:
    'Opiate Potentiation and Side Effects'
    'Opiate Potentiating Guide'
    'Codeine Potentiators'
    'Caffeine and Grapefruit to Potentiate Codeine'
    'Nicotine and Opiates'
    'Nicotine and Opiates (long)'
    Last edited by drug_mentor; 03-09-2011 at 05:42.
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    #2
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    Also, if anyone has experience with other methods of taking codeine that would be sweet. I was going to try plugging not long ago but decided it was just too much liquid to get up there. I have read it can be used subcutaneously, although I imagine one would want to evaporate the majority of their CWE away and be damn sure there was no inert shit in there or NSAIDS.
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    #3
    Good thread man. Come into possesion of oxys recently so codeines of the radar for the time being.
    My experience of combos has been the following
    alcohol- never too much as I get paranoid bout mixing paracetamol but a couple beers mixes well with codeine
    grapefruit juice - worked at a bar couple years ago and used to bring codeine to work in a water bottle and drink the white grape fruit juice in the cool room. Always drank after dosing, found it increased the buzz but possible it was a placebo

    benzos- only couple times just felt two seperate effects really.

    Stims- always like having the mild opiate buzz when amped up and nice on any come down.

    Never used antihistimines as I've always liked the itch and never mixed dxm with codeine either
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    #4
    Bluelighter Sameria's Avatar
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    Nice thread d_m

    Thanks skatkid for reminding me of the dangers of mixing Paracetemol and alcohol. I've been potentiating codeine with a few beers of late.

    Does anyone know if the dangers (ala increased liver damge) of mixing alcohol and Paracetemol apply to Ibuprofen as well?
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    #5
    My understanding is it increases the risk of stomach ulcers as opposed to the liver. As long as ur not getting smashed and paracetamol intake isn't to high or regular the p over should be ok. Better to be weary tho especially if ur using other recreational drugs. I had to go easy for a while due to months of abusing codeine, alcohol, speed, pills and steroids (which probs did the most damage)
    went to the doc and he said whilst th damage was bad for a 20 yr old a couple months off alcohol would allow the liver to regenerate and as good as new
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    #6
    Bluelighter mav3rick's Avatar
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    Awesome thread D_M!

    I'd say grapefruit juice too! When I use codeine, I always have a big glass full!
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    Prometazine potentiate 
    #7
    This was taken from a post in a tread on www.drugs-forum.com by Suboxer:
    http://www.drugs-forum.com/forum/sho...d.php?t=130315

    Promethazine is not used, like cyclizine and diphenhydramine, to synergize with codeine, however horrible a term that may be when applied to anti-histamines, with anti-histamines.

    Promethazine, like glutethimide, is a true potentiator of codeine, as well as having what some view - spuriously (at least in the case of anti-histamines) - synergistic effects.

    Promethazine is a moderately strong CYP450 IIDVI enzyme inducer. CYP450 IIDVI is the enzyme that converts inactive codeine - methylmorphine, a prodrug for morphine - in to morphine by demethylation. In most people about 10% of the oral dose of codeine is converted in to morphine, so: 90mg codeine = 9mg morphine. Promethazine increases the amount of codeine converted to morphine in vivo by a factor of two, so the same 90mg of codeine is now equal to roughly 18mg of morphine, and, in addition, is made more sedative, less itchy (the itch is the best part of an opioid high besides the nod), and a slightly more effective painkiller (some anti-histaminics have what is called "analgesic sparing" properties, meaning, combined with an opioid, they increase the analgesia it provides synergistically) by the anti-histaminic and mild anti-psychotic effects of promethazine (promethazine is roughly 1/10 the potency of chlorpromazine [Thorazine, Largactil]).

    The drug, codeine, has no effects. It is converted to morphine by first-pass metabolism in the liver after it has been absorbed by CYPIIDVI. Taking the drug AFTER you've ingested the codeine does nothing but add an anti-histaminic effect on top of the codeine - it acts synergistically.

    If you take the promethazine one to two hours before you take the codeine, it is a true potentiator in addition to whatever "synergistic" effects it might have - it increases the maximum plasma concentration and area under the curve of morphine itself, increasing the actual height and duration of the opioid high - not just adding the effects of a sedative anti-histamine to it. So, for Christ's sake, take the promethazine BEFORE you take ANY of the codeine, and you'll get more of an opioid effect - if you take it after the codeine, YOU WONT! - you'll just have the effects of a sedating anti-histamine/anti-psychotic added to it.

    Now, the above information will get you more opioid bang for your buck - any one who says to take the promethazine after the codeine will not increase the opioid concentration in your blood one bit, but will just add promethazine "buzz" on top of it. Taking the promethazine with the first dose will work, albeit less well than taking it an hour before. For maximum effect, you should always take all your doses together (but be wary of risk of overdose) - all you're getting by taking one-half a dose every thirty minutes is about 55% of the high you would taking it all at once, and 200% the tolerance per "unit of high."

    Note: Promethazine effectively doubles the limit of codeine a person can metabolize, and thus benefits users of low to low-midrange tolerance as well. Normally 300mg of codeine can be metabolized in to only 30mg of morphine, and the liver enzymes are "saturated" in a sense - they can convert no more. This becomes 60mg while taking promethazine around one to two hours before use of the codeine.

    Note 2: Caution: I am unsure of the metabolism of tramadol, but tramadol itself is an extremely weak opioid, that, like codeine, must be demethylated, in the case of tramadol, in to o-desmethyltramadol (the "M1 metabolite" of tramadol) before it is active at the mu-opioid receptors (900x increased affinity compared to tramadol). Tramadol, before being metabolized, is merely a norepinephrine reuptake inhibitor and serotonin releasing agent. If the metabolism of tramadol to o-desmethyltramadol is also catalyzed by CYPIIDVI, you may be putting yourself at risk of opioid overdose by taking promethazine before the codeine and tramadol, because, in essence, you could be effectively doubling your active dosages.
    So I'm still confused wheather the promethazine is used before or after dosing the Codeine. It states in this post that Promethazine doubles the conversion of Codeine to Morphine used 1-2 hrs before dosing the Codeine making it a true potentiator.
    I'd also like to know what people recommend as being the most effective antihistamine. Doxy, Prometh, or DPH?
    Last edited by Anon54; 14-06-2010 at 04:31.
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    I thought prometh inhibited 2D6, that is certainly the first I have read of it doubling the amount of codeine converted to morphine. Maybe someone with more knowledge on the subject than me can chime in?

    I guess I might have to try it, think I may have about 30mg lying around but not sure.

    In regards to the grapefruit juice, what kind are people using? I am definately going to buy a few litres before dosing on Thursday. Thinking about getting some tonic water as well, but it seems wiser to try them seperately to guage their individual effect. I forgot to say that when reading about the loperamide quinine is meant to help it cross the BBB, if GFJ and tonic water really help that as well as potentiating codeine then it could mean loperamide could add significantly to the high. I definately have a lot of detective work to do.

    http://www.drugs-forum.com/forum/showthread.php?t=32404 this is an interesting read for those interested in how GFJ potentiates codeine.

    I am interested in peoples experience using antihistamines I don't have listed, particularly sedating ones which actually add to the effect. A brand name would also be helpful, as that is half the trouble finding shit in the pharmacy, if you ask for the chemical name they are immediately suss. Brompheniramine Maleate could be interesting.
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    This is a very informative thread Mentor. I havnt been able to experiment much with potentiation lately but i find that adding half a bar benzo potentiates it quite nicely. If one wants to increase the desired effects then theyd need to dose a bit more, obviously it comes with side effects. I have been experimenting with travel sickness pills called Travelcalm original and i take it an hour or 2 after i have a big dose of codeine and oxy.

    The thing i am trying to get with this is that if u feel ur tolerance is high (like mine for example) then u need to take a break once u have reached plateau. Id rather increase teh dosage and stick with one or 2 things then taking a whole bunch of other things which can be potentially dangerous. Just make sure u guys are fully aware of the dangers.
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    Promethazine is a CYP2D6 inhibitor, it's listed on my CYP chart as inhibiting it.

    I always dosed it with the codeine and never noticed any real loss in effects, maybe because of how I metabolize codeine or due to the effects of the promethazine balancing out the inhibition and then some.
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    I may have to try dosing prometh first, but after my diphen experience I am rather wary to do so. Assuming it does inhibit CYP2D6 I am assuming that means the quote posted by Anon54 is inaccurate, as I don't see how inhibiting the enzyme which converts codeine to morphine would somehow double the amount turned into morphine.
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    For what it's worth I've always dosed promethazine before codeine, never noticed it to reduce the potency one bit, but never noticed a drastic increase either, mostly just a reduction in nausea and itching.

    I've also found alcohol to have the opposite effect, even a drink or two before codeine seems to kill the codeine buzz completely.
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    Hey guys been doing oxy recently and every time I dose I get strong nausea and vomit a few times. This happens regardless of dose. What are some ways of combating the nausea? Antihistamines? If so which ones? I tried Ginger beer and that did shit all
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    ^ Diphenhydramine is good for nausea, so is promethazine, dose before the codeine though for maximum anti-nausea effect.

    As for alcohol; I have used a drink an hour or so before the codeine and it does boost it a little bit, drinking whilst on the codeine though and it gets messy and I don't like it that much.
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    Quote Originally Posted by skatkid View Post
    Hey guys been doing oxy recently and every time I dose I get strong nausea and vomit a few times. This happens regardless of dose. What are some ways of combating the nausea? Antihistamines? If so which ones? I tried Ginger beer and that did shit all
    I use travelcalm original OTC at the chemist. I use it with a large dose of oxys. I used to get nausea and throw up the next day. Now i can have a half an 80 with no sickness. Works like a charm.
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    ^^ travacalm works best for me too, I used to get terrible nausea from opiates and that kills it completely.
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    Tried using grapefruit juice last night and added a little bit on it in my original post. Definately works to potentiate both valium and codeine, I would say it works better for valium though. It isn't amazing but it definately seems to work for me. I have to say I did find the taste rather unpleasant.
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    good write up DM.... Yeah i also find that grapefruit juice increases the intensity of the codeine euphoria quite a bit... i haven't had a great deal of experience using potentiators in general, but this is a great resource to experiment with, so thanks for taking the time.

    Wednesday i had 160mg of codeine on an empty stomach with grapefruit juice, and last night i did the same, but i had just eaten. I hadn't had codeine for a while so 160mg hit me quite nice.... but the day after it hardly did anything and i know that tolerance wouldn't factor very much at all.... so I agree that dosing on an empty stomach is very relative to the codeine high
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    I love white grapefruit juice. U get used to it. Better then codeine anyway haha.
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    Haha on the grapefruit D_M.. I get 'Black Label' grapefruit juice.. Usually will have a small glass first about 10mins before I drink the CWE then smash down heaps of juice straight afterwards, it eliminates the awful taste of the codeine haha and is pretty tasty too! A bit bitter but good.. I haven't had any other brands though..

    Mav
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    Gonna try dxm in the comming weeks. Anti histamines have been great thanks to ur guys advice. No more sickness and itchiness milder.
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    Regarding St Johns Wort, I never noticed much of a speedy effect from it and it's exact mechanism of action isn't known but I would say it's probably safest not to use it if you are on other meds, particularly SSRIs and it may interact badly with DXM depending on doses being used.
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    Good point man, I should probably add that in, I mentioned it was an MAOI but I probably should elaborate a little.
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    xanax + cannabis w/ 160-200mg codeine go well
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    OK so I tried brompheniramine tonight, so far I am liking it alot. I used 8mg and haven't felt too itchy yet, it is less sedating than say doxylamine but it seems to have a bit of a mood lift, maybe thats just the xanax but I think I could tell. It has SNRI properties so maybe thats why.

    The really awesome thing is dosing 20ml equates to 8mg brom and 40mg DXM, that makes up 2/3 of the dose I use to potentiate, so it works out rather cost effective. I will do a write up on it in the original post tommorrow.
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