We all know that drugs like heroin, meth and cocaine have ruined a lot of lives. That isn’t (or shouldn’t) be news. And yet despite their dire effects, the science and the stories behind these drugs is sort of fascinating nonetheless. They’re sort of like a vast unplanned neuroscience experiment that reveals some interesting things about how the human brain works.
So forget about the politics of the drug war and the future of American drug policy for now… we’ll leave that for the pundits and the politicians to debate. Instead, let’s talk about the chemistry and biochemistry of illegal drugs. We’ll find out why people smoke crack and snort cocaine; what LSD does inside the brain, and why it glows under a black light; what chemists and crackheads mean by “freebasing”; why the DEA tracks sales of iodine; and why Bayer used to sell heroin as a cough suppressant. Because this is the interesting stuff.
There’s a scene in the movie Traffic where Catherine Zeta-Jones’ character approaches the head of the Obregon cartel. Her husband, a major distributor for Obregon in the US, is about to go on trial in San Diego and she wants to offer Obregon a deal. Forgive her husband’s debts and kill the lead witness for the prosecution, she tells him, and in exchange she’ll give him…a new way to smuggle cocaine into the states. A doll.
Obregon: “If you want to smuggle narcotics in Senore Espastic Jacobo, that is nothing new, Senora.”
C Z-J: “No, not in. The doll IS cocaine. High-impact, pressure-molded cocaine. It’s odorless. Undetectable by the dogs. Undetectable by anyone…”
Obregon: “I don’t believe you, Senora.”
A wise move on his part, because the solid-pure-cocaine doll that no one can detect isn’t a very plausible plot element. The movie doesn’t bother to explain, although in order to demonstrate her doll is legit C Z-J dissolves some of it in water. Which is interesting, because it comes back to some basic chemistry.
The structure of the cocaine molecule is like this:
–shamelessly borrowed from Wikipedia because their structure is accurate and borrowing is faster than drawing my own in ChemDraw. (Lazy, I know.) One of the first few things you should notice about this structure is the nitrogen or “amine” up on top of that boat-shaped ring. Amines are in general somewhat basic, meaning they can pick up a hydrogen ion. (A base is something that wants to accept a hydrogen ion, whereas an acid is something that wants to give a hydrogen ion away.) Once the nitrogen has a hydrogen or H attached to it in addition to the three bonds it’s formed already, it will have a positive charge.
If I take cocaine, which is a base, and mix it with an acid like HCl, I end up with a salt — positively charged cocaine ions and negatively charged Cl ions. If I take this salt and mix it with a base, I’ll remove the hydrogen ion back from the amine group so we end up back with the structure you see above, the “freebase” structure because the amine is “free” — it doesn’t have a hydrogen ion attached to it. And this is where freebasing comes in.
What most people call cocaine is actually the hydrochloride salt, cocaine HCl. Crack cocaine, by contrast, is the freebase form. When crackheads cook up their
narcotic drug of choice, they’re mixing some cocaine HCl with a weak base in water, and so they end up with pure freebase cocaine (aka crack) which forms an oily slick.
So why are they doing that? is it just ’cause they’re crackheads? No, it’s ’cause they know some science, that’s why. (Well, maybe that’s why. More likely they’re just doing it because somebody told them to do it that way.)
Why do some things play well with water and others don’t? You can mix water and ethanol just fine, for example, but try mixing water and dichloromethane or water and MTBE and you get something that looks like this:
Notice how there are two separate layers — layers that don’t mix. You can force them to mix by picking up the funnel and shaking it, but put it back down and before you know it they’ll separate again.
The reason why some things dissolve in water and others don’t is a little complicated, but there’s an easy general rule of thumb you can use to figure out what dissolves in what. It goes like this:
Like dissolves like.
Bear in mind, that doesn’t mean “like” in terms of color or scent. Electron density in a molecule can be evenly distributed (nonpolar) or unevenly distributed (polar). Water is a very polar molecule — so polar, in fact, that water molecules can form weak interactions with each other called hydrogen bonds. So water is very good at dissolving things that are polar and can form lots of hydrogen bonds (like dissolves like). It’s very good at dissolving ionic compounds like table salt, because these are formed from ions that have + and – charges on them (because having a charge is like being extremely super-polar if you want to think about it like that). And it’s very bad at dissolving things that are mostly or completely nonpolar, like the molecules in oils and fats.
If we stick a hydrogen ion onto the cocaine molecule by mixing it with acid, we end up with ions that are much more soluble in water than the original compound. That’s why cocaine HCl dissolves in water and crack cocaine doesn’t. If you wanted to dissolve crack cocaine, you’d just mix it with some acid (e.g. lemon juice), and that would do the trick just fine.
The same thing is true for lots of other big ugly organic (carbon-based) compounds that contain amine groups. Make a salt out of them by mixing them with acid and they dissolve pretty well in water; remove the hydrogen ion by mixing them with base and they dissolve much better in some other more nonpolar solvent like dichloromethane. Next time you go down the OTC drug aisle in the pharmacy or the supermarket, take a look at the ingredient list and see if you spot any compounds with “HCl” on the end. These are hydrochloride salts. The manufacturer used the hydrochloride salt of the drug rather than the freebase form.
So why does anybody want the freebase form of cocaine? The answer has to do with vaporization. At pretty much any temperature above absolute zero, molecules are moving around. In a solid they’re held together by tight bonds, so they’re fidgety but they stay put. In a liquid they’re held together but have some more freedom to move, and in a gas they’re flying around like ping-pong balls. So to turn something from a solid into a liquid or a liquid into a gas, we have to overcome the forces that hold these molecules together, and that takes energy. The stronger those forces, the more energy it takes, and the higher the melting point (or boiling point) of the solid or liquid.
Solid cocaine HCl contains positively charged cocaine ions and negatively charged Cl ions. They’re held together by the attraction between opposite charges, which is very strong, so vaporizing cocaine HCl isn’t easy. In fact, you’d have to heat it high enough you’d kickstart some chemical reactions that would destroy your cocaine, and now you just defeated the whole purpose of the experiment. So that’s why people don’t smoke coke.
In crack cocaine, on the other hand, the molecules don’t have any charge, so the forces that hold the crack cocaine molecules together are much weaker and you can vaporize it at a reasonable temperature. Inhaling the vapor puts it into circulation much more rapidly and the maximum blood concentration or Cmax is generally higher.
Once you have the cocaine in your system, your body will get rid of it by chemically altering (metabolizing) it and by excreting it (filtering it out of the bloodstream into the urine), just like any other drug. The way the body metabolizes it is just about what you’d expect: by breaking down (hydrolyzing) those esters. If you look at the structure again, you have two C-O-C=O groups that look a little like legs on the boat-shaped ring, and these are called esters. When you break them down, you wind up with the junk you see below (depending on what gets hydrolyzed):
These reactions are spontaneous and happen of their own accord in water, but enzymes in your blood and liver catalyze these reactions or speed them up so they happen very rapidly, and cocaine doesn’t actually last very long in your bloodstream. Your liver also converts a small fraction of the cocaine into another metabolite called norocaine by yanking the CH3 group off of the nitrogen in the boat-shaped ring.
Ultimately, the three molecules you see above end up in your urine, together with a tiny amount of unaltered cocaine*. So if you’re a drug testing lab, your best bet is to look not for cocaine itself, which is only going to be present in trace amounts, but for the metabolites; and in fact, drug testing labs look for the second molecule down from the top in urine samples. But cocaine is eliminated so rapidly from your system that labs can only confirm its presence for a fairly limited period of time — unlike THC, which is eliminated much more slowly.
Coming up in the next post: Meth (which gives me an excuse to talk about the awesomeness that is Breaking Bad.) Stay tuned.
Jatlow P (1988). Cocaine: analysis, pharmacokinetics, and metabolic disposition. The Yale journal of biology and medicine, 61 (2), 105-13 PMID: 3043924