Morphine-less Opium Poppies and Pain Relief

There is a mutant opium poppy that is causing a lot of excitement amongst scientists looking for new, strong, and non-addictive pain relievers.

Ordinary opium poppies, Papaver somniferum, are the source of morphine and codeine, as well as heroin and opium.

But this particular mutant poppy produces no morphine and codeine, instead producing other alkaloids that can be used to make painkillers.

Australian farmers call the mutant poppy "Norman", from "no morphine".

Opium poppies have been grown in Australia's island state of Tasmania since the 1970s, making up more than 40% of the world's legal opiates. It is one of the few places in the world where growing opium poppies is legal.

The mutant no-morphine poppy, also called top1, has been grown commercially in Tasmania since 1997.

Johnson & Johnson controls the Norman poppy research in Tasmania through its Tasmanian Alkaloids subsidiary. It was the UN (in 1961) that decided to allow Tasmania to produce opium poppies. Tasmania has the right growing conditions, a relatively sparse population, and good security.

Most folks have seen pictures of opium harvesting in places like Afghanistan (where the production is illegal) or India and Turkey, which produce a significant portion of the world's legal opium poppy crop. The poppy seedpods are milked...cut with a knife, allowing a white-to-cream sap (called latex) to ooze, harden into a gum, and be collected. The Norman poppies have pink or red latex when primitively milked.

Tasmanian farmers employ modern agricultural methods, using a harvester which cuts the poppy seed heads off and mashes them. Morphine and thebaine are then efficiently extracted from the mash with solvents. Morphine, a depressant which the Norman poppy lacks, is the precursor to codeine and heroin...all are addictive. With Norman poppies on the rise, 1,455 Tasmanian farmers produce more thebaine than do 159,000 Indian peasants. I'll discuss thebaine in a moment.

The researchers looked at 17,000 poppy genes and identified 10 that were involved in blocking the biochemical pathway that leads to morphine production.

Poppies that overexpressed these genes accumulated precursors of morphine and codeine, called thebaine and oripavine.

These compounds can be made into strong painkillers like buprenorphine, which is used after surgery or to treat addiction, and naltrexone, which is used to treat addiction.

Thebaine and oripavine would normally be made from morphine itself, Larkin told ABC Science Online.

"Rather than creating morphine and destroying it, thebaine and oripavine accumulate in the [mutant] poppy," he said, adding this saved pharmaceutical companies time and money.

Thebaine, a stimulatory drug (provides a rush), is the precursor to oxycodone of OxyContin fame...an effective but addictive pain reliever (related post here).

As noted above, thebain is also the precursor to buprenorphine and naltrexone. These and related drugs are effective for moderate-to-severe pains, like with pancreatitis, cancer surgery, intractable cancers, etc.

Buprenorphine and naltrexone evidently compete for the same receptors in the brain that other opiates and alcohol take advantage of. Under the right circumstances, doctors can prescribe them to addicts, allowing then to stop using the addictive substances, then slowly undergo "medically supervised withdrawal" (detox). Methadone (previous blog here) works better for folks with higher levels of addiction, but it is easier to abuse and overdose on methadone. Buprenorphine is sometimes used to treat methadone addiction.

The researchers are now looking at the pathway to determine which genes could be switched off to produce other poppies with useful pharmaceutical benefits.

For example, poppies could in the future accumulate alkaloids used in anticancer agents or in cardiovascular medicine, Larkin said.

"It's a new philosophy for plant pharmaceuticals; we're working backwards with the [pharmaceutical] companies to identify useful alkaloid compounds and get the poppies to accumulate an alkaloid that would be useful for that compound," Larkin said.

Good thing Norman is a natural mutation...wouldn't want people fearful of GMOs to whine about this progress being made through artificial genetic modification of the opium poppy. But even if man develops an entire arsenal of pain relievers that replaces all the addictive opiates, the opium poppy will still remain popular. Physical pain certainly isn't the only thing people want to escape.

Comments

[Jeremy Pierce]

I guess it's also important to know if it gives a high or if it muddles thought processes. If it's a negative on both, this is great. People have been working for a while to synthesize chemicals in marijuana that have the medical effect but not the high or the other undesirable effects (well, some find them desirable, but I don't understand that at all). This may be a natural way around that problem.

[Tim Worstall]

I'm extremely sceptical about all of this. I'm not sure I even subscribe to the idea that there is a difference between "addictive" and "pain relief". People get addicted to things, whether opiates, alcohol, sex or barbiturates, becasue they like the way they make them feel. "Chemical dependency" is rare. I am reminded of the reason why heroin was first refined: what if we could have the pain relief of morphine without the addictive part?

[RoguePundit]

Pain relievers can be addictive on several levels. I think it would be a significant accomplishment if man could develop strong pain relievers that weren't addictive purely on a physical basis. Some of these newer strong pain relievers don't seem to give much of a high, which is better than heroin or Oxy, but it's still a somewhat altered state.

We know that some folks who take some of the newer pain drugs don't detect much if any rush, but find that their body adjusts to the drug and becomes physically addicted. If they come off the drug, they feel tremendous physical pain. I've seen stories that show in some cases, the brain is actually sensing pain from the body (indicated a physical/chemical change in the body), while in other cases the brain chemistry seems to have changed. Probably sometimes it's both.

Pain is a tremendously complicated subject...it would certainly be nice if scientists could figure out what it was in smoking marijuana that relieves pain for some folks that taking THC pills doesn't. I suspect there are a plethora of answers, because there are so many differences in brain and body chemistry, the ability of bodies to adjust to different chemicals, etc.

It would be good if in newer strong pain drugs, we only had to worry about the "mental addiction" (for lack of a better term)...no physical addiction, no increasing tolerance, no altered mental state from things like rushes, etc. But, I agree that pain relievers will probably always involve the risk of some sort of addiction in many folks.

[Jackie Knott]

I'm hunting info and stumbled on your site. I am almost finished writing a biography about a reclusive inventor. My guy held 39 industrial patents and was a bit strange. He had Asperger's Syndrome (high functioning autism) and refused to be touched by another human being, including doctors. When S got old he extracted his own teeth and made himself dentures out of metal - I'm not kidding. I know he used some natural narcotic because he was a botanist as well. I have good reason to believe it was from poppies. He lived in southern FL during WWII and this is where most his experimentation with plants occured.
Questions: Does the poppy grow wild in southern FL?
I have reason to believe he used the poppy as a tranquilzer also - how would he have controlled the 'dosage' so as not to overdose himself.
Any response, either email or by post would be appreciated.

[RoguePundit]

Opium poppies aren't native to the Americas, but they used to grown legally in the U.S. (until just before WWI), for the opium, edible seeds, a type of oil, and decoration. They are annuals that do reseed readily and stay established in various locations in the U.S., especially here in the NW. I know that they've reseeded and stayed in N. Florida (see www.floridata.com/ref/p/papa_som.cfm), but I don't know about South Florida...it's certainly possible though. There are a number of decorative opium poppy hybrids (sold under the species name Papaver somniferum without the opium label attached), and they are sold in Canada, England, and I'm sure other countries.

The government has been trying to develop fungus that kills the opium poppy, and it at least planned to test it in controlled fields of opium poppies near Gainesville FL.

That still doesn't help for you for South Florida. Sorry.

As far as dosing, if he didn't know of or wasn't up to extracting morphine, codeine, etc., or even know about how to score the immature seed pods to get the latex, he could have readily experimented with simpler means. If he mashed the immature seed heads and wiped some of the liquid on his gums, he should have been able to feel some numbing. It dissolves in alcohol (google for laudanum)...could dab it on that way or drink it...with some sugar for flavor.

Hope that helps some.

[Jackie Knott]

Okay, that helps but I have more questions. In some of the material I have read about poppies, some refer to opium, some to cocaine, and now I have laudanum to add to it. All these derivatives come from poppies so what distinguishes one from the other? Laudanum is the milk of the poppy mixed with alchohol and sugar, right? What would be some other ways to prepare the milk of the poppy for a medicine? My inventor was a chemist and a botanist and extremely well read. The particular area of FL (Okeechobee) has a large Indian population. It is possible he could have learned some techniques from the Seminoles. You said he could have rubbed this on his gums to produce numbness but I don't see how that could control the pain of extracting molars. Surely he would have had to ingest the painkiller to be effective enough.

[RoguePundit]

One can extract morphine (and codeine) from opium, and make morphine into heroin or codeine...the chemistry isn't hard for anyone with some education in the subject. This DEA site explains how to process the opium poppy resin into morphine (http://www.usdoj.gov/dea/pubs/intel/20026/20026.html) and then into heroin. Being an environmental engineer myself, I've certainly had some chemistry...but my high school class gave me enough knowledge to do the processes listed. The chemicals required are common and readily available. Heroin takes more chemical steps, but still isn't difficult for someone with an affinity for chemisty.

Morphine has a long history and list of legitimate medical uses, so he should have been able to readily find ways to make it and learn how to dose it in text books. So, I suppose the question is what form he might have used. Note that with repeated use, opium, morphine, codeine, and heroin are all addictive. They all give a rush, with more chemical refinement bringing a greater high and sturdier addiction. Keeping the rush in mind, did he take it beforehand--sacrificing some mental and physical dexterity to do so, or cause the pain and then quickly treat it? I'm guessing mostly the latter.

- He could have smoked the cooked opium. Easy but not very effective...would treat the pain some and probably mellow him out as well.

- He could have used the morphine by ingesting or injecting it or using it topically...injecting is way more effective (only about 10 percent survives digestion). Ingesting gives both the topical on the way by for teeth and is easier to do. Dosing is by body weight (http://www.a1b2c3.com/drugs/opi005.htm). If he wasn't getting enough relief, he'd just drink more...it's supposed to be bitter, thus people sometimes sweeten it (like laudanum with sugar). Laudanum is morphine mixed with alcohol. It can be used as a tincture for topical uses or prepared for drinking.

- Heroin can be smoked or injected, and it would have worked against the pain. But heroin is mostly for getting stoned...not just sure why he'd have gone to the work for that unless he had a debilitating habit.

- Not sure why he'd have bothered with codeine if he'd made morphine.

I don't know of any connection with Seminoles. With Native Americans sometimes having addiction issues and the U.S. having had morphine addiction issues--especially in the 19th century, maybe they got involved from that perspective. But with opium poppies not being native to the U.S., it would have been an acquired trait after the Europeans arrived.

Again, hope this helps.

[Jackie Knott]

Thanks, that should do it. I can't imagine my inventor injecting himself. He was real peculiar about his body. Neither did he smoke or drink but he had enough anxiety I can see him making some concoction as a tranquilizer, either as a liquid or in his food. I know you've relayed the standard practices using this drug but he was such a talented chemist I can also see him finding an alternate method to medicate himself. He would not have been after a rush so much as a pain reliever and a means to cope with life in general. Really a brilliant but troubled soul. He was observed a few rare times slurring his words and had white saliva around his mouth. Look for a biography in bookstores next summmer or fall, on "Smokey." Thanks again.

[poppies]

we have dried poppy pods for sale a poppies.ws

[Mark Vane]

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[rob]

It is true of THEBAINE that it is a stimulant but it DOES NOT PROVIDE A RUSH.It has an electronegativity SIMULAR tu STRYCHNINE and causes increased blud calcium.It isn't a narcotic but meny persons believ it is and is listed as a narcotic according tu U.S. Federal Law but it causes withdraw symptoms and acts like a narcotic antidote but it is a precursor of numerous narcotics.

[rob]

I believ codeine producing mutants and hybrids must exist alredy in papaver somniferum fields but which plant of millions.A codeine producing plant would be easier tu make codeine frum.Perhaps some partial somniferum garden hybrids produce only codeine and the gardens could be found by asking police agencies that hav(or will test) tested garden poppys.

[can u please send me a few opium poppy seeds they are so hard 2 get in sa]

hey ive been looking for seeds evey were can you please send some at 44 gosfield cres hampstead gardens adelaide 5086