I see that it is possible to purchase the enzyme CYP2D6 from chemical supply companies for a moderate sum of money (more than a few beers, less than a bottle of fancy Scotch) for 5 micrograms. CYP2D6 is the enzyme that converts codeine into morphine in the body. Would it be possible for a totally unskilled home chemist to perform a similar conversion in vitro. How much CYP2D6 would be needed per mg of codeine? This idea may be quite stupid, but I don't know enough to know, so please advise!
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Would purchasing 5 micrograms of CYP2D6 and trying to convert codeine to morphine at home work?
- Thread starter smenkhare
- Start date
BadBoy377
Bluelighter
- Joined
- Apr 9, 2023
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Would be better trying to get some of that genetically engineered yeast that makes morphine from sugar...
www.pbs.org
If you do, can I have some, please?
This genetically modified yeast can now brew morphine
Biologists have created strains of yeast that can brew morphine from sugar, opening the door for cheaper medicine but also easy-to-make illicit drugs.
www.pbs.org
If you do, can I have some, please?
4meSM
Bluelighter
It's not as simple as you think, P450 are complex enzymes which require specific conditions to work : buffer, pH, cofactors, etc...
Are they even selling it as a functional enzyme? AFAIK they aren't very stable so when you use them as biocatalysts you typically use them inside whole cells instead of the purified enzyme. Plus another enzyme called cytochrome p450 reductase (CPR) is usually needed as a source of electrons, and that enzyme uses NADP(H) as a cofactor, so you'd need that as well.
So no.
Are they even selling it as a functional enzyme? AFAIK they aren't very stable so when you use them as biocatalysts you typically use them inside whole cells instead of the purified enzyme. Plus another enzyme called cytochrome p450 reductase (CPR) is usually needed as a source of electrons, and that enzyme uses NADP(H) as a cofactor, so you'd need that as well.
So no.
If you were trying to do this at home, your best bet would be to express the reductase and the cyp in hepatocytes, and then make microsomes.
Enzymes that need to be in complex generally work best in at least a facsimilie of the cellular milleu.
Enzymes that need to be in complex generally work best in at least a facsimilie of the cellular milleu.
Jabberwocky
Frumious Bandersnatch
I need some morphine beer in my lifeWould be better trying to get some of that genetically engineered yeast that makes morphine from sugar...
This genetically modified yeast can now brew morphine
Biologists have created strains of yeast that can brew morphine from sugar, opening the door for cheaper medicine but also easy-to-make illicit drugs.
If you do, can I have some, please?
Grapefruit juice they say potentiates codeine. Why not just buy more codeine? Or synergise it with a good joint? Codeine is the weakest opiate, so don't expect to get much euphoria from it in return.
BadBoy377
Bluelighter
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- Apr 9, 2023
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Could make some Krokodile but just don't...
AlsoTapered
Bluelighter
Making glutethimide is the sure way. Not glutethamide has an ethyl moiety but the n-propyl, 2-fluoroethyl and isopopyl all work BETTER,
BadBoy377
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Very interesting. Thankyou.
sekio
Bluelight Crew
It's perhaps more serious chemistry than most people are capable or interested in, but there is a simple, two step process for making a mixture of dihydroheroin and 6-monoacetyldihydromorphine (its main metabolite and equally active) as HBr salts suitable for injection or smoking.
1. Codeine freebase converted to dihydrocodeine base with hydrogenation. Gaseous H2 is so last century and is an unnecessary risk. Rather, catalytic transfer hydrogenation can be used quite nicely. Dissolve base in methanol, carefully add to catalyst in a flask (any sort of Pt or Pd will work, on any support, at any loading), add anywhere from 5 to 7 mol ammonium formate (1 -1.5g per g codeine, does not have to all dissolve), stir at room temperature for an hour or two, filter the catalyst over celite (scrape the top layer off and save it for next time). Evaporate the methanol and partition the residue between water and DCM/chloroform, give it a cursory drying with MgSO4, evaporate DCM. Boom, almost 100% yield of dihydrocodeine base. Marquis can be used to validate the reaction: DHC is more purple and codeine more violet but they should be distinguishable. Also, I believe codeine will decolorize a dilute solution of iodine via the double bond in e.g. hexane but DHC will not (though I have not tried this). (I usually found that 500mg of 10% Pd/C would do 10 or 20g codeine in 100-200mL methanol, in 2 hours tops, usually an hour or less). I never had any fires either, I think the ammonium formate helps there.
2. Dissolve the DHC base in glacial acetic acid, 1g / 2.5 mL. Then add 2 mL per gram DHC base of 33% w/w (45% w/v) hydrogen bromide in acetic acid, or its equivalent - the 'secret sauce' for this transformation which can be made by constructing a generator for dry HBr and bubbling it into dry acetic slowly, and is stable if sealed in a brown glass bottle. (note: 2ml/g works out to be 3.33 equivalents of HBr per DHC, i.e. a 50% excess, you can probably use less, 1eq is needed to form a salt, and at least 1 eq to rip the methyl ether off. 2.1 equivs would be 1.25mL/g and would be the lowest amount that could work on paper. The original paper said 5mL/g which was 8.36eq: massive overkill. The less HBr you have to pump off the better) Now, put this all in a thick walled glass pressure vessel or other means to prevent escape of gas, and immerse it in a boiling water bath for two to three hours. Nothing should boil or vaporize, and it should remain quiescent. After it's done cooking, take it out of the bath, cool it with running water, carefully open the lid (fumes of HBr and acetic) and slowly add cold methanol. Then evaporate the mixture down as far as you can. Add more methanol. Repeat until you have a dry crusty powder. (The methanol will react with some of the HBr and the acetic acid to make more volatile and slightly safer products, namely methyl bromide and methyl acetate, plus some trace water.) Finally, use a minimum amount of methanol to rinse it out of the flask and into an evaporation dish, where excess methanol is removed with gentle heat, vacuum, or both.
Avoid using water in this process; you may end up hydrolysing it to dihydromorphine, and drying out aqueous solutions is much harder than alcohol.
By virtue of not discarding anything significant at any step, yields are as close to perfect as you can get. Back of the napkin math says about 1.4-1.5 grams of effectively pure dihydroheroin (without cutting, and with generous portions, minimum $300 on the street, more if you cut it or short your portions) per gram of codeine ($8.99 per gram at a pharmacy near me) plus labour (12 hours, adding the extraction of codeine from AC&C tablets - hint: codeine base is moderately soluble in ether and can be selectively extracted with it) and reagents (probably no more than $200 for several batches). The real kicker is the equipment but even then it can be improvised if you know what you doing.
It's not kitchen chemistry but it's the closest you'll get to heroin-from-codeine. You can thank Kenneth Rice and the Naval Institutes of Health for this banger. It got snuck into a footnote in a paper about a suspiciously similar looking compound. The US government looking out for the little guy, y'know?
Also, effects wise, it's basically indistinguishible from the classic unsaturated parent compound, at least as independently verified by some local habitual users. In fact, given that the purity of street heroin (pre-fentanyl crisis) was perhaps 40-60% at best it was a pleasant surprise to some.
It also has a pretty wide therapeutic index, as verified by yours truly. One time while cleaning up after a batch I asked my opioid-using lab associate how much he would like to do, he told me "three points" (as in 3 x 0.1g), so foolishly I weighed out 300mg of the product and gave it to him. Couple of minutes later, light switch comes on in my head, I run to check on my buddy, he's sitting on the shitter barely conscious, still breathing (thank fuck) but also swollen up like a blimp from the histamine release. I didn't have to naloxone him (and, in deference to how awful he was feeling, felt it kinder to not throw him into withdrawals) but did spend the next while helping him get his bearings. He felt awful for the next hour or so but was able to walk it off. I had forgotten a few facts: local dealers always shorted "points" to sometimes 0.06g or less, it was never pure, and he was the sort to do all the drugs at once, and save none. Thank goodness for the safety index of classic opioids, and also his preexisting tolerance. (He found much smaller doses to be far more pleasurable.)
In terms of duration, it's pretty long lasting, and reportedly addicts will take 18-24h before withdrawal really sets in since their last dose, rather than an hour or two with fentanyl. It was preferred to fent by most people who got their hands on it...
Anyway enough incriminating myself.
Not that I'd actually advise doing anything as liberating illegal as making Schedule 1 narcotics. But then again. if I can promote a cottage industry of artisanal dihydroheroin cooks displacing some of the fentanyl from the streets, I will not feel guilty.
1. Codeine freebase converted to dihydrocodeine base with hydrogenation. Gaseous H2 is so last century and is an unnecessary risk. Rather, catalytic transfer hydrogenation can be used quite nicely. Dissolve base in methanol, carefully add to catalyst in a flask (any sort of Pt or Pd will work, on any support, at any loading), add anywhere from 5 to 7 mol ammonium formate (1 -1.5g per g codeine, does not have to all dissolve), stir at room temperature for an hour or two, filter the catalyst over celite (scrape the top layer off and save it for next time). Evaporate the methanol and partition the residue between water and DCM/chloroform, give it a cursory drying with MgSO4, evaporate DCM. Boom, almost 100% yield of dihydrocodeine base. Marquis can be used to validate the reaction: DHC is more purple and codeine more violet but they should be distinguishable. Also, I believe codeine will decolorize a dilute solution of iodine via the double bond in e.g. hexane but DHC will not (though I have not tried this). (I usually found that 500mg of 10% Pd/C would do 10 or 20g codeine in 100-200mL methanol, in 2 hours tops, usually an hour or less). I never had any fires either, I think the ammonium formate helps there.
2. Dissolve the DHC base in glacial acetic acid, 1g / 2.5 mL. Then add 2 mL per gram DHC base of 33% w/w (45% w/v) hydrogen bromide in acetic acid, or its equivalent - the 'secret sauce' for this transformation which can be made by constructing a generator for dry HBr and bubbling it into dry acetic slowly, and is stable if sealed in a brown glass bottle. (note: 2ml/g works out to be 3.33 equivalents of HBr per DHC, i.e. a 50% excess, you can probably use less, 1eq is needed to form a salt, and at least 1 eq to rip the methyl ether off. 2.1 equivs would be 1.25mL/g and would be the lowest amount that could work on paper. The original paper said 5mL/g which was 8.36eq: massive overkill. The less HBr you have to pump off the better) Now, put this all in a thick walled glass pressure vessel or other means to prevent escape of gas, and immerse it in a boiling water bath for two to three hours. Nothing should boil or vaporize, and it should remain quiescent. After it's done cooking, take it out of the bath, cool it with running water, carefully open the lid (fumes of HBr and acetic) and slowly add cold methanol. Then evaporate the mixture down as far as you can. Add more methanol. Repeat until you have a dry crusty powder. (The methanol will react with some of the HBr and the acetic acid to make more volatile and slightly safer products, namely methyl bromide and methyl acetate, plus some trace water.) Finally, use a minimum amount of methanol to rinse it out of the flask and into an evaporation dish, where excess methanol is removed with gentle heat, vacuum, or both.
Avoid using water in this process; you may end up hydrolysing it to dihydromorphine, and drying out aqueous solutions is much harder than alcohol.
By virtue of not discarding anything significant at any step, yields are as close to perfect as you can get. Back of the napkin math says about 1.4-1.5 grams of effectively pure dihydroheroin (without cutting, and with generous portions, minimum $300 on the street, more if you cut it or short your portions) per gram of codeine ($8.99 per gram at a pharmacy near me) plus labour (12 hours, adding the extraction of codeine from AC&C tablets - hint: codeine base is moderately soluble in ether and can be selectively extracted with it) and reagents (probably no more than $200 for several batches). The real kicker is the equipment but even then it can be improvised if you know what you doing.
It's not kitchen chemistry but it's the closest you'll get to heroin-from-codeine. You can thank Kenneth Rice and the Naval Institutes of Health for this banger. It got snuck into a footnote in a paper about a suspiciously similar looking compound. The US government looking out for the little guy, y'know?
Also, effects wise, it's basically indistinguishible from the classic unsaturated parent compound, at least as independently verified by some local habitual users. In fact, given that the purity of street heroin (pre-fentanyl crisis) was perhaps 40-60% at best it was a pleasant surprise to some.
It also has a pretty wide therapeutic index, as verified by yours truly. One time while cleaning up after a batch I asked my opioid-using lab associate how much he would like to do, he told me "three points" (as in 3 x 0.1g), so foolishly I weighed out 300mg of the product and gave it to him. Couple of minutes later, light switch comes on in my head, I run to check on my buddy, he's sitting on the shitter barely conscious, still breathing (thank fuck) but also swollen up like a blimp from the histamine release. I didn't have to naloxone him (and, in deference to how awful he was feeling, felt it kinder to not throw him into withdrawals) but did spend the next while helping him get his bearings. He felt awful for the next hour or so but was able to walk it off. I had forgotten a few facts: local dealers always shorted "points" to sometimes 0.06g or less, it was never pure, and he was the sort to do all the drugs at once, and save none. Thank goodness for the safety index of classic opioids, and also his preexisting tolerance. (He found much smaller doses to be far more pleasurable.)
In terms of duration, it's pretty long lasting, and reportedly addicts will take 18-24h before withdrawal really sets in since their last dose, rather than an hour or two with fentanyl. It was preferred to fent by most people who got their hands on it...
Anyway enough incriminating myself.
Not that I'd actually advise doing anything as
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