Creating Synthetic Opioids

Fentanyl and its cousins lead to lethal overdose at a staggering rate

Sitting side-by-side in glass vials, heroin and fentanyl look remarkably similar: two unassuming white powders. The latter, however, has a lethal dose 100 times smaller than the former, meaning that just two milligrams of fentanyl, a few crystals or a capsule-sized pill, can kill an adult man. Since distinguishing between the two opioids is so difficult, drug-mixing poses a grave risk to users who accidentally overdose on unsafe drugs. The number of fentanyl overdoses has skyrocketed in the United States, with 36,539 deaths from synthetic opioids in 2019, up from less than 5,000 in 2013. The structure of synthetic opioids and the process through which they are chemically manufactured offer scientists a deeper understanding of their potency, symptoms, and dangerous natures. 

The chemical structure of fentanyl: C21H23NO5

The history of opioids predates labs, pills, and biotechnology. These pleasure-causing drugs come in natural, semi-synthetic, and fully synthetic forms. Natural opioids include morphine, a substance derived from the opium poppy and codeine. To activate a pleasurable response, molecules bind to opioid receptors in the brain called GPCRs, or G protein-coupled receptors, triggering hormone-based reward systems in the brain. GPCRs rest on the surface of nerve cells, and, in some cases, inside neurons. Scientists have identified at least three different types of receptors: mu (µ), delta, and kappa, with mu receptors responsible for both the most pleasurable responses and unwanted side effects, including symptoms like nausea and constipation. One of the most dangerous reactions to opiates is slowed breathing, which can reduce oxygen flow to the brain (hypoxia) and induce a coma or even cause death. 

Since the potency of natural opioids pales in comparison to that of synthetic opioids, the latter substance requires far less quantity for an overdose. Heroin (C22H28N2O), a semi-synthetic opioid, is made from a combination of lab-based compounds and morphine, and has become infamous for its deadly nature. Even more dangerous is fentanyl, a synthetic opioid that is entirely man-made and responsible for 59% of drug overdoses in the U.S. Containing two carbon rings, fentanyl (C21H23NO5) was originally developed for cancer patients’ pain relief, to be applied as a patch or through an injection. Since its initial creation, fentanyl has been manufactured in labs and sold for non-prescription drug use as a powder, pill, or strip. Although many forms of fentanyl are banned for non-medical use, the drug and its component parts are still sold illegally online, particularly from China to the U.S., Mexico, and Europe. Fentanyl is relatively inexpensive and easy to synthesize, making it profitable for drug manufacturers and dealers. 

Drug overdoses related to synthetic opioids have skyrocketed in recent years

Not only is using fentanyl in its basic form extremely dangerous, but variants and drug-mixing exacerbate its risk. For example, the variant Alpha-methylfentanyl adds an extra methyl group to the fentanyl molecule, making it 600 times as potent as morphine, in contrast to plain fentanyl, which is only 470 times as powerful. Its higher potency reduces the amount of alpha-methylfentanyl necessary for an overdose, increasing the risk of death. Another form, Carfentanil, is said to have 10,000 times the strength of morphine, with only a few granules needed for a lethal overdose. Fentanyl also becomes more lethal when mixed with other drugs, such as cocaine, meaning that those who overdose may not even know that they are using the substance.

In order to combat the rise in accidental opioid deaths, America must take measures to reduce the amount of illegal synthetic opioids in circulation. The increasing ease with which drug dealers ‘cut’ their wares creates grave threats for human life. One part of the difficulty stems from our inability to differentiate between different types of illegal substances, another from the manufacturing of non-medical synthetic opioids altogether. By curbing the importation of non-medical synthetic opioids and regulating the production and distribution of medical ones, the United States may be able to flatten the alarmingly steep curve of deaths due to opioid overdose and the tragic statistics which continue to grow.

– Julia Shephard

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