The chemistry of cocaine

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While we are surrounded by constant conversations about drugs and their dangers, we rarely consider how they have come about and what effect they have on us. Consider the class A drug cocaine - holding second place on the list of the most commonly used illegal drugs in the world. Whilst you may know about its white powder appearance and possibly a little about its effects - do you know what it actually is, or why it even holds that amount of power upon such a large number of humans?

The beauty about chemistry is that it is all around us, and in everything. So, by taking such a commonly known yet confusing concept of illegal drugs and actually learning about the science behind it, we can clear up some misconceptions about it, what it does to you, and how we test for it. Hopefully, this will make you never want to go near it!

Cocaine, or its IUPAC name: methyl (1R,2R,3S,5S)-3-(benzoyloxy)-8methyl-8-azabicyclo[3.2.1] octane-2carboxylate, is a strong stimulant made from coca leaves from one of the four species of plant in the Erythroxylaceae family. Its chemical formula is C17H21NO4 and it is what is known as a tropane alkaloid. This sounds complicated, but it is just explaining that it belongs to a class of alkaloids and secondary metabolites and has a tropane ring in its chemical structure. To understand this, we need to break it down - alkaloids are naturally occurring organic compounds containing at least one nitrogen atom, secondary metabolites are organic compounds produced by bacteria, fungi or plants that are not used in their normal processes and a tropane ring just refers to the bonding of the compounds! See, not complicated, just unfamiliar.

As you now know, cocaine is actually naturally occurring. So, how was it found? Three thousand years BC, ancient Incas in the Andes chewed coca leaves, because the coca bush grows wild there. The bush makes cocaine from the amino acid Lglutamine as a protection mechanism to stop insect predators from eating it, and studies show that its leaves contain around 0.3-0.7% cocaine. The ancient Incas chewed coca leaves in order to get their hearts racing and to make their breathing faster, getting more oxygen into their bodies, in order to counter the effect of living in the mountains. Nowadays, cocaine users don’t actually chew leaves 'thanks' to the work of a few chemists, starting with Heinrich Wackenroder, who was a German pharmaceutical chemist that was able to produce an extract of the active ingredient in the coca leaves. He did this by creating a solution with 84% ethanol and 14% water producing a solution that reacted with isinglass (purified gelatin) solution and iron (III) chloride - so we weren’t quite there yet. Two years later, Friedrich Gaedecke was able to evaporate an aqueous extract of the leaves, and

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with its dry residue he obtained white crystals. However, these crystals were coated in an oily residue, so still not there yet, and he named them “Erythroxyla coca”. Finally, Albert Niemann came along and used the ethanol and water mixture with a dash of dilute sulfuric acid at 40 degrees to produce the final product, giving it the name cocaine.

So, now we know about how cocaine was found and synthesised - let's try and understand why so many people are addicted to it and the answer lies in its chemical structure. To understand the difference it makes, we need to understand the normal brain activity to see the contrast, and in order to do this we can look at the neurotransmitter - dopamine. Neurotransmitters are made by the body and used by the nervous system in order to send messages between nerve cells - they act as a sort of ‘chemical messenger.’ The chemical formula for dopamine is C8H11NO2. Usually, neurons release dopamine into the synapses (gaps between neurons) where it binds to dopamine receptors (special proteins) on the adjacent neuron. This movement is why dopamine is a chemical messenger, as it is able to carry a signal from one neuron to the other. Once this movement happens, the dopamine can be recycled so another special protein, a transporter, removes the dopamine from the synapse to take it elsewhere. However, this is the process in which cocaine gets involved. Once a person has cocaine in their system, it blocks the so-called ‘recycling step’ I previously mentioned. The chemical structure of cocaine allows it to bind to the transporter as it is on its way to pick up the dopamine, prohibiting it from doing so as the space is taken up. Therefore, the dopamine is stuck in the synapse, meaning that over time, the lack of transporters picking the dopamine up creates a build-up of dopamine in the synapse, essentially amplifying the signal to the receiving neurons. This amplified signal results in the ‘euphoric’ feeling users get when they take the drug. This process is a reason why cocaine is known as a SNDRI, a serotonin–norepinephrine–dopamine reuptake inhibitor.

While cocaine can ruin a user’s life very easily, it can surprisingly also be used in different ways to do good. While the medicinal use of cocaine has decreased due to the uprising of other local aesthetics, no other drug is able to combine the anaesthetic and vasoconstricting properties in the same way as cocaine. Cocaine is a good anaesthetic because of its ability to block nerve impulses, especially norepinephrine which allows it to be an anaesthetic and a vasoconstricting agent. Cocaine hydrochloride is an ester local anaesthetic and has been approved for use in the United States for adults. Additionally, it can be used in the form of a topical solution as a numbing agent. While these are a few good uses of cocaine to help people, these positive characteristics exist only in medical settings - any cocaine

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distributed elsewhere will always be dangerous.

It is also quite interesting to observe the chemical reactions that take place when the body deals with cocaine, occurring in the liver. This human organ uses carboxylesterase enzymes hCE1 and hCE2 in order to metabolise cocaine and after these processes only 1% of the cocaine leaves our body unchanged. The liver metabolises cocaine by hydrolysis, and the reaction is catalysed by carboxylesterases and excreted in the urine, and this allow us to detect cocaine use because only a mere four hours after the intake of cocaine, the cocaine metabolites for example, benzoylecgonine, are detectable in urine. Furthermore, if cocaine is taken with alcohol (ethanol), the hCE1 enzyme can turn the cocaine into coca ethylene which is an ethyl ester. This is why the combination of both is more toxic than taking cocaine or ethanol separately.

Finally, due to the way that cocaine is sometimes ‘snorted’ with bank notes, a 2007 study showed that the majority of euro notes had detectable levels of cocaine on them! How did they work this out? They used the technique of mass spectrometry. Essentially, if the note is heated up to 285 degrees for one second, the cocaine molecules are released and carried on a stream of air into the spectrometer. If the spectrometer is looking for cocaine, it is programmed to pick out the peaks with the m/z values of 182 and 105 - the two main fragments of the molecular ion.

Now you know the history behind cocaine - the effects it has on the body, how harmful it can be, and how we test for it. After all, it's just chemistry!

By Nadia Baghai

References and further reading: https://pubchem.ncbi.nlm.nih.gov/ compound/Cocaine

https://sites.duke.edu/thepepproject/ module-1-acids-bases-and-cocaineaddicts/content-background-chemicalcharacteristics-of-cocaine/

https://www.reagent.co.uk/what-iscocaine-made-of/

https://edu.rsc.org/feature/cocaine-ashort-trip-in-time/2020119.article

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