Breaking Bad 2.0: Is it possible to synthesize Oxycodone from Naloxone?

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Or perhaps a conversion to Oxymorphone is plausible.  The answer, NOT LIKELY!  But, this is surely another reason to allow naloxone distribution through the hands of a pharmacist with or without a prescription, after the pharmacist or another healthcare provider assesses the patient for risk of opioid-induced respiratory depression. Allowing naloxone to be purchased from a gas station or variety store for example should never be an option.

Breaking Bad 2.0: Do We Have Another Illegal Drug Synthesis Problem on the Horizon?

Is naloxone the new pseudoephedrine? This question was posed to me by an astute colleague, Dr. David Craig of H. Lee Moffitt Cancer Center.  He inspired our group to formulate this interesting post.

Here to answer the “burning” question is Joseph Gottwald, a PharmD Candidate (aka “4-0h Joe”) headed to medical school in a few short weeks and our very own Dr. Jacqueline Pratt Cleary (aka “Naloxone Queen”) to share their thoughts.  Here’s what they have to share…

At this point most people have seen or at least heard about the methamphetamine (meth) epidemic. Houses blowing up, television drama series’ centered on synthesis of the drug, and monitoring/control of pseudoephedrine sales. Pseudoephedrine does a pretty good job as a decongestant, but we’ve also found out it can be used as a reagent in the synthesis of methamphetamine (crystal meth, meth). Who knew such a widely available OTC medication could result in a highly abusive drug? Well, clearly people in the drug abuse business did. About 1.2 million people reported use of meth in the past year according to the 2012 National Survey on Drug Use and Health (NSDUH).1 Data from the Drug Abuse Warning Network revealed 103,000 ED visits associated with meth in 2011.2 Since cracking down on pseudoephedrine sales, there has been a drop in meth lab incidents/seizures according to data from the DEA. Still, there were 9,338 meth-related lab incidents in 2014.3 The rise and fall of methamphetamine-related lab incidents highlights the very real danger of having medications available without restriction in the OTC marketplace that have chemical structures conducive to manipulation and alteration.

Fast forward to today, with an opioid epidemic that shows no signs of abating. According to the 2014 NSDUH, 4.3 million Americans used prescription opioids for non-medical use in the last month and a whopping 1.4 million Americans joined the ranks of prescription opioid non-medical users in the past year.4 And this is with prescribed “legal” medications. According to the same study, 4.8 million Americans reported using heroin during their lifetime and 212,000 reported first-time heroin use in the past year. But we’re not just talking about abuse here – the CDC revealed that in 2014 opioids were related to 28,647 deaths.5 And overdoses are on the rise, experiencing a quadrupling since 2000.5 The precipitous rise in opioid-overdose related death has underscored the absolute need for widely available reversal agents to prevent death from occurring. Naloxone and naltrexone are opioid antagonists that are able to quickly displace opioids such as heroin from the opiate receptors due to superior binding affinity. These drugs have been used in the emergency department and hospital settings for many years, and have recently seen an increase in prescription use for outpatients that are at high risk of opioid overdose whether from prescribed agents or abused drugs. There has also been a push to get opioid antidotes into the hands of first responders and clinical providers in the community to increase the chance that the antidote is available if an overdose is witnessed. For pharmacists and community members at elevated risk to witness an opioid overdose, it is possible in many states to take a short educational course on the use of naloxone, and be provided with the medication in the event of an emergency.

To see how Good Samaritan laws protecting healthcare providers and laypersons vary from state to state, click HERE

Having these medications available in the community pharmacy setting has been discussed as a possibility. There is very little risk of harm if naloxone is administered when the cause of overdose/respiratory depression is not opioids. The medication is effective at displacing the opioid with relatively no risk other than a precipitated pain crisis; it would seem inappropriate not to make these medications more available. The advent of auto-injector and nasal devices make administration more simple and crisis-friendly compared to previously available products.

Here’s the catch: take a look at the chemical structures of naloxone compared to oxymorphone, a full-agonist opioid.

naloxone oxycodone compare

Notice the similarity? The only structural difference between the two is one substituent on the tertiary amine (nitrogen) on the bottom right. Would it really be that hard to set up a lab and convert a widely available naloxone into oxymorphone with an abuse and misuse potential? We investigated this concept and here’s what we have found.

First, it is very reasonable to conceptualize a potential reaction mechanism for this to occur. The mechanism is very similar to the reverse process used to synthesize naloxone from more natural opioid products or their synthetic derivatives. Here’s a potential mechanism below which doesn’t require that many steps:

To see the reaction scheme for conversion of Naloxone to Oxymorphone, click HERE.

Of course with all great (and really dangerous) ideas, it’s not as easy as it looks. We consulted with a professor who conducts organic synthesis research and gathered much of the following information.

To accomplish this reaction, you would need lab glassware, stirrers, ice, vessels for storing and adding the reagents and ideally a fume hood since the chloroformate proposed in the first step will generate hydrochloric acid gas which would need to be trapped. Methyl iodide is considered to be carcinogenic since it is a powerful alkylating agent and should be handled with precaution. There would also need to be a way to analyze and purify the intermediates and final product, so chromatography equipment (i.e. flash columns, silica gel) and access to an NMR and mass spectroscopy would be necessary.  The analysis could be sent out to a lab for analysis, so the majority of this would be do-able in an “at-home” lab.  One of the other things to consider is that reagents like chloroformates are not readily available on the street or in a drug store.  This and the other reagents would have to be ordered from a chemical supplier like Sigma-Aldrich or obtained through illegal means.  Legitimate chemical suppliers are generally very cautious about where things get shipped (i.e. a residential address versus a legitimate business or academic institution), and in some cases are required by law to not ship to residential addresses. Someone thinking of doing this would have to be clever about how they would get access to these reagents.

So it appears the reaction would not be impossible in a makeshift lab built in someone’s basement, but gaining access to some of the other materials as well as assessing for purity of a product would cause some issues. In the case of this reaction, having leftover unreacted naloxone would result in blocking any of the oxymorphone that may be produced. So there are some roadblocks that would inhibit illegal manipulation of naloxone if it were to become even more available to the public. However, the realistic possibility of synthesizing a potent opioid from an OTC medication should cause a bit of pause. So how do we rectify this potential problem? One potential solution is to empower community pharmacists with the ability to issue prescriptions for naloxone devices after proper counseling and training on their use. This would allow for tracking of naloxone sales as well as ensure there is a reasonable need for the device prior to dispensing. We can’t prevent illegal use of naloxone with 100% certainty, but we also need to recognize the benefit of an opioid antidote for preventing the drastic increase in opioid-related deaths. The most recent auto-injector device, Evzio, has reportedly been used to treat more than 600 suspected opioid overdoses from 10/1/14-12/31/15 through the Kaléo Cares Product Donation Program – and this is only reported uses. Greater than 1/3 of the donated auto-injectors (>1000 as of 12/31/15) have been successfully used to reverse an opioid overdose during this timeframe, which has proved to be a lifesaving intervention for almost 10 patients/week.6

We can’t prevent every illegal manipulation of naloxone if it is distributed more widely throughout the community, but given the lifesaving potential of prescription naloxone products for take-home use we also can’t ignore the apparent need for increased availability of an easy-to-use opioid antidote. By smartly introducing a product like this to the community accompanied with appropriate training, we can reduce the risk of harm while providing a much needed service to the public.

As usual, comments are welcome!

Joseph Gottwald is a 2016 PharmD candidate at the Albany College of Pharmacy and Health Sciences and will begin medical school after graduation. He has experience as a research assistant in organic synthesis and interest in neuropharmacology. He is currently under the mentorship of Dr. Fudin subsequent to completion of an advanced practice rotation in pain management.



Jacqueline pratt cleary
Dr. Pratt Cleary is a PGY2 Pain and Palliative Care Resident at the Stratton VA Medical Center in Albany, New York, under the mentorship of Dr. Jeffrey Fudin. Her research interests include risk stratification prior to and following opioid therapy with emphasis on requisite naloxone qualification for in-home use. She has been a leader in the expansion of the risk index for overdose or serious opioid induced respiratory depression (RIOSORD) tool presenting and educating providers and patients on a national scale.  Prior to completion of a PGY1 General Practice Residency at Sentara Healthcare System in Norfolk, Virginia, she earned her BS in Biochemistry at Furman University and her Doctor of Pharmacy at South Carolina College of Pharmacy, MUSC Campus.  Dr. Pratt hopes to pursue a career in pharmacy academia upon completion of her PGY2 residency training


  1. Substance Abuse and Mental Health Services Administration, Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-46 (HHS Publication No. SMA 13-4795). Rockville, MD: Substance Abuse and Mental Health Services Administration, 2013.
  2. Substance Abuse and Mental Health Services Administration, Drug Abuse Warning Network, 2011: National Estimates of Drug-Related Emergency Department Visits. HHS Publication No. (SMA) 13-4760, DAWN Series D-39. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2013.
  3. US Drug Enforcement Administration. Methamphetamine lab incidents, 2004-2014 [Internet]. 2014[cited 2016 Mar 22]. Available from:
  4. Center for Behavioral Health Statistics and Quality. (2015). Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health (HHS Publication No. SMA 15-4927, NSDUH Series H-50). Retrieved from
  5. Centers for Disease Control and Prevention. Increases in drug and opioid overdose deaths – United States, 2000 to 2014. MMWR 2015.

**Chemical Structures obtained from**

18 thoughts on “Breaking Bad 2.0: Is it possible to synthesize Oxycodone from Naloxone?

  1. *cough* *wheezzz wheeezzz* by way of N-deallylation of naloxone “theoretically ;] one can access controlled intermediates with noroxymorphone using uncontrolled reagants and pre-cursors. Maybe if addicts had access to endless amounts of their desired molecule we would have less fatalities as a result of impure or laced dope, also it takes the fun out of it you know?

    PS the hardest part of this process is the deprotection following the chloroformate N-deallylation involves an HCl gas, this problem can easily be overcome using salt and sulphuric acid in a closed system it can be vented through a tube out a window or however you wish to do it. but the gas needs to be bubbled through the solution

  2. Using naloxone to make active opioids is definitely talked about on the web, but seems quite impractical.. As of now, most people would be trying to stock up on Narcan which would be economically unfathomable. You would need 4 nasal sprayers (2 boxes) to make a 10-15 mg dose of oxymorphone. Maybe if you had an insider source for bulk naloxone powder it could be feasible. Also, the above mentioned point of naloxone impurity in the final product would be an additional challenge to overcome, I don’t think that a legitimate concern should exist unless naloxone becomes easily available in bulk quantities for cheap. I believe naloxone cost would have to be under $0.50/mg (at least) for it to begin to look like an idea worth undertaking.

  3. I think that the idea of someone successfully doing this on a commercial scale is extremely asinine, there are much more fruitful ways for skilled clandestine chemist to produce opioids that would seem worthwhile to a street level opioid user. (That being said )
    I do not want to see Naloxone become harder for the average person to obtain, instead I think it should be just the opposite and they should make obtaining Naloxone very easy and affordable (If not free).
    I personally have used Naloxone to save the lives of many opioid users. I can tell you that is not something that many of them appreciated at the time because of the horrific pain and side effects of the precipitated withdrawls that follow the application of the Naloxone. Over time I learned how to administrate a dosage that is just strong enough to bring them back safely without the patients experiencing such painful precipitated withdrawls. I cannot see ANYONE wanting to use Naloxone for recreation. Also, something that I haven’t ever heard anyone doing that I have tried is using Buprenorphine and Buprenorphine + Naloxone meds (such as Zubsolv and Suboxone) to reverse opioid overdoses, it works as well and from what Ive been told is that it is not as painful. I am not recommending anyone to use this as a “Go to” method as these medications are not meant for use IM/IV , but I have also used Zubsolv to reverse a opioid overdose by liquifying part of a tablet and using a needleless syringe to spray the liduid intranasally and the patient came back slowly, I would like to add that the patient I used the Zubsolv intranasally on was still just barely breathing(Very shallow and short breaths at maybe once a minute. Almost not breathing at all). I have also (Due to having any “Regular” Naloxone a hand from having to treat multiple patients in one incident and running out of .4mg viails of the medicine) Suboxone by cutting 8-2mg strip into 1/4s mixing it with tap water and injecting into the leg of someone who had stopped brreathing after using Acrylo-Fentanyl and within 5mins the patient began breathing again. I would only recommend having to use such a method if nothing else is available and you need to save someone’s live. But I think using Buprenorphine alongside of Naloxone could prevent another overdose from rapidly occurring after the patient is released from care “Which happens very often” and many times the Naloxone is not nearly effective due to tolerance and the 2nd overdose is the one that kills. But with Buprenorphine also being in one’s system they are not as likely to have as strong of cravings for opioids as someone who has been experiencing precipitated withdrawls from Naloxone after an overdose. Because I’ve personally seen addicts leave the ER/ED only to return to using the exact drug that put them there to begin with. But with Buprenorphine also being in the patient’s system they are less likely to use and if they do use they are much, much less likely to be able to get high or more importantly overdose and that’s why I think giving Buprenorphine to a patient that’s just experience a overdose would be an idea worth exploring.

    (Btw) I think Dr. Pratt Cleary’s photo is very attractive “Not to come off as a complete pig”

  4. My god what a waste of time this article was. I kept waiting for you to say “Sike” and then you reveal his asinine you think it would be to limit availability of the drug. But nope. You just kept on gaslighting yourself (a rarely seen tactic, I admit) until you were confident to say that you think a life saving med with next to zero adverse effeffects (including accidents), ought not be available freely because someone might spend a fortune setting up a lab after they figure out how to turn it into Opana. Jesus Christ that sounds even more stupid when I type it. Ugh.

  5. The proverbial match referred to by Doc Brennan here is, plainly put, nothing more than some relatively obscure chemicalese discussion of the possibility of converting naloxone into oxycodone … or let’s even expand that greatly by saying into any mu agonist … and as such, it fails quite soundly at being much of a fire starter at many points – far more points than it succeeds at. A fire non-starter, maybe? Even if we followed this generally unsustainable logic, surely anyone could see that scrubbing, or even pre-emptive proscription, aimed at the dissemination of this information would serve as far more of a catalyst for potential chemical shenanigans than the availability of the actual information would in the first place. The handful of persons among any random 500 people who can carry out this sort of clandestine conversion would need no prompt to consider the potential of such a venture, or even if it’s worth investing much of their time into researching. That said, let such a person catch a whiff of the suppression of this information, and it’s on. As Eddie Murphy’s if not downright lovable, then let’s say at least crusty but benign, “Uncle Gus” might say, “Now, THAT’S A FIRE!!”.

    I’m not saying that Bubba may not think that sounds like a really great idea…right on up there with that loooo-o-o-ngstanding alchemical stumper of gold from lead (or even a Ronco Combomatic Beer Cooler/Fishin’ Rod Holder/Scrotum Scratcher/Flashlight/Honey Bun Warmer/Penis Stretcherizerer!!), in fact … but of course, Bubba has yet to consider that the conversion of naloxone to (insert your favorite full on mu agonist here) may be a bit more complicated than merely adding an “H” or changing one line into two here and there on one uh them chemical drawing thingamajiggies, even considering that his grandpa’s brother-in-law’s nephew’s cousin, one Festus Fodderwing Grignard Kekule, Esq., was an old school crank cook of some local notoriety. Of course, Bubba also thinks that getting out of the bathtub to piss is a useless waste of valuable time (not to mention the senseless squandering of a ready and renewable source of warm water, too, so go figure…).

    Suppression of information is a difficult task at best, seldom worthwhile even when that info is an arguably valid, and needed consideration. It’s one hell of a slippery slope, too….

  6. To push to restrict access to a life saving drug just to prevent an unlikely and even if so extremely uncommon and small occurrence seems unethical at best. I couldn’t personally live with myself, banning Naloxone would kill tens of thousands. Contributing to that would be like working for the Manhattan project.

    1. John; I think you missed the point. Nobody is suggesting to ban naloxone. To the contrary, it’s just the opposite. This article was in part intended to point out how rediculous PROP folks are when they say that oxycodone is synthetic heroin. Usually my rag logic, so is naloxone and dextromethotphan if you consider their chemistry. I have been a very strong supporter of naloxone access. See the tool I’m developing at

  7. This kind of shows how stupid the drug laws are. A natural product like opium, that just needs sunlight water and soil continues to be “regulated” to the point where people may theoretically be able to synthesise a synthetic form of it (at least in regards to effects on opioid receptors) by mixing the most unnatural and dangerous chemicals with a reversed compound. Aren’t we humans so clever !

  8. With the incredible volume of heroin and other opioids available in our communities and on streets in every community in the US and across the globe, I doubt many will find any, especially an economic incentive, to synthesize oxymorphone from naloxone.

    This is certainly not the case with methamphetamine so that is where the comparison breaks down.

    This would be illogical to consider further restricting naloxone because of the unlikely pssibility of converting naloxone to an active opioid agonist when naloxone access is helping (if only by bringing more awareness to the myriad of opioid problems). In addition to naloxone, we need a very comprehensive approach that balances the need to relieve suffering while avoiding the dangers opioids pose to so many people.

  9. This is at best a theoretical question inasmuch as there are very few reported cases of persons manipulating controlled substances to isolate and recover a specific API. Is it possible? Probably. Just about anything made in a lab can be unmade in a lab. To be sure, there are occasional reports of persons removing APAP from hydrocodone combination products and we know some cooks have discovered ways to remove pseudoephedrine from combination cold and allergy medications to make meth. For good measure, there are reports that in New Zealand, opiate addicts occasionally use an OTC codeine cough medicine to make heroin. The process is complex and costly and would not pay, economically, to do on a large basis. The root for all these opiates, including naloxone and naltrexone, is opium, or, more precisely, thebaine. Rearranging the molecular structure produces the different alkaloids. A more exciting issue involves what is being done in the private sector through selective breeding (not GMO, although this, too, is a possibility) of opium poppies that produce gum with a high concentration of codeine rather than morphine. The codeine can be used as starting material for all the other medicinal opiates while greatly limiting its conversion to heroin. Releasing the pollen of the codeine poppies in regions now being used to cultivate morphine poppies would hasten the collapse of the illicit morphine base and heroin trade. When the morphine content by weight in opium gum slips below 10%, the world price for heroin increases because of the greater volume of raw material needed. In economic terms, the Price Elasticity of Demand = % Change in Quantity Demanded / % Change in Price. By influencing the percent of change in the denominator, i.e., by causing an increase in raw cost of morphine base, you can affect the price sensitivity or PED in a way that reduces the quantity demanded. Right now, this is just a pet theory but one that may be worth thinking about, especially since it can be undertaken with little or no appreciable effect on legitimate markets or the patients served by them.

  10. Jeff – I understand Mike’s concern, but I applaud you for doing this. I am incredibly concerned about too much naloxone on the street – making it altogether too easy for those who wish to overdose, just to have a friend bring them back. I have already heard of parties where this is the plan. It’s a shame there is no other way to help. Perhaps we should look for a deeper and more community based plan.

    1. From my personal experience, while Naloxone is a life-saving drug, and having an antidote may make it possible for addicts to O.D. without death, the act of injecting Naloxone to reverse O.D. a) feels like a nightmare and b) in an addict’s mentality, is technically a waste of a drug, only to be thought about if someone suspects or finds themselves or someone else O’Ding.

      I understand some people’s concern about Naloxone being “too” available, but from my experience, I can’t think of any addict trying to “OD”, unless they were at the end of their rope or contemplating suicide/ “a call for help”

      Thankfully Naloxone is freely available at drug stores here in Montreal, Quebec (Canada)
      This is a great step forward because with heroin & illicit opiates like fentanyl, overdose is more common due to lack of communication between producer/supplier/consumer, lack of regulation [specifically unknown and ever-changing drug concentration (mg/ml or mg/g)] and difficulty in choosing the appropriate amount of pill/powder/liquid to consume.

      Those at highest risk of O.D may benefit the most, such as those who mix opiates w/ alcohol and/or benzodiazepines (xanax, klonopin), illicit opiate drug users, methadone users (if the pharmacist makes a mathematical/measurement error) first-time drug users, and accidental drug users (children, elderly, sober people).

      Even if someone acting really dumb found out that they enjoyed the feeling of overdosing and took advantage of the Naloxone antidote, I bet that person’s family and friends would be happy that such antidote would be the only thing keeping that addict alive, because most of the time the consumption habits of addicts are stronger than their willpower to stop (even though they logically understand the consequences of said habits).

  11. Nice post and love the comments it has generated.

    Just an FYI to readers, this information is easily found on the internet just Google “convert naloxone to oxymorphone”

    Also, don’t forget that naloxone won’t fully reverse all opioids such as those with overdose from Buprenorphine or Tramadol.

  12. I concur with the above thread… This type of news is exactly how people find out about it. It’s like kids inhaling fumes from Whip Cream canisters. Didn’t know about it until the news reports about this new way kids are getting high.

    You’re publishing the road map and then wondering how people found the place.

  13. I am such a great fan and this is my favorite blog. But I have a grave concern.

    Being a philosophy major before med school and wrestling with organic and inorganic chem, I appreciate the fluidity of your wonderful minds. But, ethically I am going to ask to pull this before it is too widely read.

    In 2001 0r 02 in a NYT article reported on the burgeoning Oxycontin epidemic. In it an addict was asked why it took so long for people to start to abuse oxy-5 years or so till the snowball really took off. His quote astounded me. It went something like this: Oxy being around wasn’t enough to make people want to get high. It was the thought you could get high that made people start to abuse it.

    The wood was there, but a match was needed to start the fire.

    Just because it is there does not mean it will occur. Even though it may seem inevitable, must we point the way, including identifying what is a small stumbling block? (IE retained naloxone?)

    Put this away and mail it to the members of the list serve please. Wouldn’t you all hate being identified as the ‘source code’ for the hijacking of what is currently our best immediate hope to save lives?

    1. Dr. Brennan; Thank you so very much for stating this! I was thinking the exact same thing just before hitting the “upload” button. I think though that there’s another important side to this. That is, making sure that appropriate persons have access to naloxone by qualified healthcare providers in the first place so that people are appropriately identified and counseled. Also, it’s sort of already out there – street chemists have considered this, see

      But I take your comments VERY seriously! I’m going to ask other coleagues to chime in either here or via email directly to me. If the consensus is to take it down, I promise to do that immediately!

      Please know Mike that I respect you and this important concern!

      1. Did you google that yourself? The illicit use of naloxone is practically impossible, especially for a ‘street chemist’.

        I see no problem with putting single-use packages of naloxone for sale in gas stations.

        Also, the synthesis scheme in this article wont work. In the first step, the free alcohols will react preferentially with the chloroformate.

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