Keynote presentation at the 3rd International Conference on Novel Psychoactive Agents

Summary of Dr. Benjamin’s keynote presentation at the 3rd International Conference on Novel Psychoactive Agents in Rome, Italy, May 2014.

Designer Drugs, Synthetic Cannabinoids, “Bath Salts” and the US Federal Analog Act

Historical Overview

The current use of the term “designer drug” evolved from the 1980s, when drug dealers attempted to synthesize or design opioids which were not listed in the Controlled Substances Act (CSA) of 1970, thus interfering with the ability of the US federal government to prosecute distributors and users of such drugs because these “designer drugs” were not listed in the CSA. According to some, during the early 1980s, much of the redesign work focused on the fentanyl or meperidine (pethidine) molecules, resulting in the synthesis of desmethylprodine or 1- methyl-4-phenyl-4-propionoxypiperidine (MPPP), a meperidine analog possessing about 70% of the activity of morphine. Unfortunately, errors in the manufacturing of MPPP led to the formation of a major impurity, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or, MPTP, which was metabolized in vivo to 1-methyl-4-phenylpyridinium , (MPP+), a potent neurotoxin that selectively destroyed the substantia nigra and produced permanent Parkinsonian-like symptoms.  Similar errors in synthetic organic chemistry related to the fentanyl molecule produced potent fentanyl analogues such as China White, that were responsible for many accidental overdoses and deaths.

When Ecstasy (MDMA, 3, 4-methylenedioxymethamphetamine) became popular in the mid-1980s, Ecstasy also was heralded as a designer drug since it was not listed in the CSA, and federal laws were rapidly passed to give the Drug Enforcement Agency (DEA) the power to emergency schedule non-listed chemicals like Ecstasy under the CSA for a year, with an option to extend the designation for 6 months. Emergency-Scheduling power was used for the first time to schedule MDMA as a Schedule I drug, despite a federal judge’s opinion that Ecstasy actually should be classified as a schedule III drug, based on an accepted medical use.

During the late 1980s and early 1990s the United States saw the re-emergence of methamphetamine or “crystal meth” emerge as a widespread public health problem. The government enacted laws to track the sale of precursor chemicals like P-2-P and pseudoephedrine in an attempt to cut down on domestic manufacturing and distribution of the drug, as portrayed in the well-known American TV show, “Breaking Bad.” As a result alternative stimulant drugs emerged, with methcathinone, an analog of amphetamine, and similar to cathinone, the active ingredient in “khat,” also being offered in the black market, but methamphetamine continued to be the most sought after synthetic stimulant on the streets.

During the 1990s and early 2000s, designer drugs were sold over the internet. Some distributors tried to pass the drugs off as “research chemicals” and sold bulk forms rather than tablets of tryptamines and phenethylamines as chemicals as for “scientific research” in an attempt to avoid a claim that the drugs were intended for human consumption. But the DEA raided multiple suppliers, and this approach failed. Shortly thereafter, vendors began selling designer drugs over the internet, using search engines like Google, but this didn’t fool the DEA either.

Soon anabolic steroids joined the list of drugs available over the internet, for use in human and veterinary athletic competitions, and new analytical procedures had to be developed to distinguish endogenously formed androgens from exogenously administered ones.

Since 2005, great attention was focused on a mixed group of drugs called “Synthetic Cannabinoids” sold in Europe which included several products that were sold over the counter as “Spice,” or “K-2” and promoted as “legal marijuana.” In fact, these compounds bore little resemblance to the chemical structure of tetrahydrocannabinol (THC) and are most commonly indole derivatives, more closely related to LSD and DMT in chemical structure, as the THC molecule contains no N atom.

In 2009, a new group of compounds, the cathinones, migrated to the US where they were sold as “Bath Salts” in “head shops” and at “truck stops.” In fact, the most common cathinones in “Bath Salts” were 3, 4-methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (4-MMC or mephedrone), and 4-methylephedrone (methylone) all possible principal active ingredients, with MDPV found most commonly in the US and mephedrone found more commonly in Europe. Physiological effects include CNS stimulation, hypertension, agitation, anxiety, sweating, tachycardia, and vasoconstriction, and psychiatric symptoms include psychoses, self-injury, suicidal ideation, hallucinations, confusion, panic attacks and paranoia, all reminiscent of amphetamine-like effects.

If you look at the chemical structure of methylone, you will see part of the Ecstasy molecule on the left, and part of the amphetamine molecule on the right. Certainly a combination of two stimulant drugs almost guaranteed to cause a toxic reaction.

bath salts