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A coca plant's leaves, fruit, and flower.

A closeup of the coca plant relative, Erythroxylum australe.

Photograph by Neil Fletcher and Matthew Ward, Getty Images

Dave Mosher

for National Geographic News

Published June 12, 2012

A mysterious but crucial step that coca plants use to build cocaine has been discovered, according to a group of biochemists.

Despite the drug's infamy, cocaine is chemically similar to a host of anesthetics and stimulants used legally every day. Understanding how cocaine is made in the coca plant might therefore lead to new anesthetic drugs without the addictive qualities, the study authors say.

"Plants can't run away, so they have to be the planet's best chemists to survive," said study co-author John D'Auria, a biochemist at the Max Planck Institute for Chemical Ecology in Germany.

"They make chemicals other organisms simply cannot make, including cocaine."

(Related: "Cocaine Addiction Uses Same Brain Paths as Salt Cravings.")

But to maximize a chemical's benefits to humans, he said, "we need to have some idea how the plants are making it. If you understand the biochemistry, you might take away the bad properties and keep the anesthetic ones."

Ancient Medicine

South Americans have cultivated coca for about 8,000 years.

"Coca is important in terms of a cash crop for South America and the source of an infamous street drug, but it also has a strong medicinal history," D'Auria said.

Indigenous tribes that cultivated coca chewed its leaves for religious rituals as well as for hunger and thirst suppression.

(Related: "Cocaine to Blame for Rain Forest Loss, Study Says.")

Yet today little is known about how the plant actually creates cocaine, in part because of its highly illicit nature—few, if any, U.S. labs are permitted to grow coca or study cocaine, which is part of a group of compounds called tropane alkaloids.

To probe the mysteries of cocaine, D'Auria and his team began by studying a highly similar yet legally grown family of flowering plants called Solanaceae, also known as the potato or nightshade family.

Although cocaine is part of a different family, many Solanaceae plants also produce tropane alkaloids, some of which have been made into medicines that dilate pupils, wrangle motion sickness, and treat peptic ulcers.

(Related: "Cocaine, Spices, Hormones Found in Drinking Water.")

But D'Auria's team eventually realized that coca plants weren't using the same enzymes as Solanaceae plants to build their tropane alkaloid molecules.

That's surprising, he said, because the alkaloids are complex molecules that take many stages to create, and evolution typically conserves the best solutions rather than reinventing them.

"Another thing is that the roots of Solanaceae make tropane alkaloids. Coca does it in the leaves, which is a huge difference," D'Auria said. "That means nature has found two very different ways to make very similar compounds, which I think is extremely impressive."

To pinpoint one of cocaine's production steps, D'Auria and his colleagues ground up the coca leaves and searched for enzyme activity they thought might help prepare molecules of cocaine, which looks like two carbon-based rings bridged by bonds with oxygen.

The team eventually found an enzyme—and the gene that codes for it—that prepares cocaine's main ring to merge with benzoic acid, the plant's second-to-last step in building the drug.

Next Steps

The researchers are now gearing up to publish a study on the final step in the cocaine-building process, and they hope to retrace the earlier steps until the whole pathway is mapped.

Biochemist Toni Kutchan, who studies medicinal compounds at the Donald Danforth Plant Science Center, said the work wasn't a revalation but noted its importance in unraveling cocaine synthesis.

"This is one of many steps, so I'll be interested to see what they reveal in the next study," she said.

Kutchan also said she'd like to know why the coca plant began making such a complex molecule in the first place.

Study co-author D'Auria hinted that cocaine's natural purpose may be to kill bugs.

Previous work found that a high amount of cocaine in cultivated coca plants—as much as 10 percent of young leaves' dry weight—acts as an insecticide. More studies of the crop's wild ancestors, he said, could help solve the riddle.

"We are absolutely interested in this and are working on the question," D'Auria said, adding that his team is now studying six relatives of coca in the lab, and "we are working on obtaining the insect herbivores which are known to feed on them."

The new study about how plants make cocaine was published online last week in the journal Proceedings of the National Academy of Sciences.

2 comments
Mary Wille
Mary Wille

Unless N.G. and this German backed,ie Merke,chemist used absolutely no ethanol and hydrochloric acid in the synthetic extraction method,,which they did use,,all they have done is made the molecule benzoylecgonine,not ,''discovered''anything.Just adding to the propaganda machine to exterminate coca.Coca is never ever touched by western chemists w/out those 2 chemicals,ever.They use ethanol/acid in every single method apply'd to the coca leaf.The reason is they cannot claim ,''cocaine''because w/out those 2 chemicals,there is no molecule of cocaine,or benzoylecgonine.Alone,coca is just coca,just like the poppyseed.Alone a poppyseed is just a poppyseed.Alone,coca is just coca,,,paita

Jerry Wolfe
Jerry Wolfe

@Mary Wille Sounds like you know the ins and outs of how it is really made in South America. I only know what I've seen on TV and I certainly can't take that to the bank. The TV shows villagers stomping these leaves and at some point there is acetone and/or kerosene used in the process.


Can you comment on this in anyway without having to spill all the beans if your not comfortable with the explaining the full process. As far as I've seen, again on TV, is the actually leaves never make it out of the general area where they are harvested.


It seems like I remember that they either something on the underside of the leaves or just mash up the entire leaf in some substance to create a type of paste. I have no idea what happens after that point as I believe they intentionally stop the filming and commentary  as it may show just a little too much relating to the process that gets to the final product.


I certainly don't need anything close to written direction, but I am very curious as the chemicals that actually used in "the field" to get where the need it to be as far as shipping it out?


My suspicion is that cocaine itself is probably not as dangerous as some of the residual chemicals entrapped by the process???


Thanks!

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