Molecule of the Day

GHB stands for gamma-hydroxybutyrate. It has received buckets of terrible press in recent years that would certainly have resulted in lawsuits in both directions if it was a patented pharmaceutical. Let’s take a look at the structure, then we will take a look at the days of yore when GHB was a blameless little molecule you bought at GNC (or you could get from Aldrich for organic synthesis). Then, we’ll take a look at the subsequent demonization and where we stand today.

On the top is GHB. You’ll see that it’s remarkably similar to GABA. Both are endogenous (i.e., in your body). GHB was not thought to be physiologically significant until people started taking grams of the stuff orally; GABA is a well-known neurotransmitter. As you’ll remember from our previous discussions, similar structure tends to beget similar biological activity (To a point. And this is trickier than I make it sound.), and, indeed, GHB binds to the GABA neurotransmitter receptor.

Its status as an endogenous chemical caused it to fall under the auspices of the Dietary Supplement Health and Education Act of 1994, which allows pretty much anything in your body to be sold as a “Dietary Supplement,” which is regulated a lot like food. There are obvious exceptions - testosterone is endogenous, and steroids are regulated. Ethanol occurs naturally - you wouldn’t have evolved enzymes to process it if it didn’t - and it’s regulated. Stuff like vitamins and metabolites (witness the craze for valium (diazepam), as well as fallen heroes like rohypnol (flunitrazepam). Both drugs are members of the controlled substances act. From Wikipedia, this means:

(A) The drug or other substance has a high potential for abuse. (B) The drug or other substance has no currently accepted medical use in treatment in the United States. (C) There is a lack of accepted safety for use of the drug or other substance under medical supervision. (D) The drug is not alcohol (ethanol) due to the failure of prohibition.

This standard is not as simple as the criteria make it seem and involves some politicking. While Schedule I drugs are undeniably dangerous, many don’t satisfy criterion B. For example:

• Heroin: Painkiller, twice as strong as morphine.
• GHB: Used to treat alcoholism, as general hypnotic. Much like other GABAergic drugs (i.e., benzodiazepenes)
• Methaqualone: These are Quaaludes. If you don’t remember them, they’re hypnotics

The “high potential for abuse” is where most of these fail. GHB was also abused much like any other sedative or alcohol. Bodybuilders also used to use it (this was the angle most GNC-type brands used, I believe); the claim was it encouraged human growth hormone release. (Well, sleep does too..). The trouble was, GHB really is more like a drug than anything else, and unsupervised use of anything like benzodiazepenes will surely get some people into trouble eventually. So it went with GHB.

Finally, you’re probably wondering why I didn’t touch on GBL yet. GBL stands for “gamma-butyrolactone.” This is the cyclized version of GHB. The nomenclature works like this:

• GHB: Gamma-hydroxybutyric acid. “Gamma” means the hydroxyl group is on the third carbon from the carboxylic acid group. Count: alpha, beta, gamma.
• GABA: Gamma-aminobutyric acid. As in GHB.
• GBL: Gamma-butyrolactone. “Lactone” means a cyclic ester. An ester is what happens when an acid and an alcohol are linked together, with loss of water. As in the other two, “gamma” specifies that the alcohol is on the third carbon from the carboxylic acid. The “lactone” name implies both the alcohol (hydroxyl group) and acid. Gamma gives the position.

GBL is unique in that it was an ubiquitous industrial solvent for years. (Don’t get me wrong, here. Although I say “industrial solvent,” it’s still about as toxic as GHB - which, again, occurs endogenously. Acetone is an industrial solvent that also occurs naturally in your body. I’m not suggesting you take either internally, but the dose makes the poison, here.) It was banned as a GHB precursor; any lactone (any ester, for that matter) can be converted into its corresponding acid and alcohol by treatment with acid or base. This was, in fact, the primary synthesis route for GHB, since 55-gallon drums of GBL were available. GBL was phenomenally useful stuff for chemistry; its ban threw a wrench in the works of many procedures.

See you tomorrow!