The types of treatments of pain today are rather scarce, as we only have three available types of treatments available, nonsteroidal anti-inflammatory drugs (NSAIDs), peripheral stimulation and physiotherapy, cannabinoids, and opioids, being opioids the most prescribed medications in this category.

This augmentation of prescription of opioids has led to various patients becoming addicted to the opioids post-operation and/or post-treatment, often caused by the lack of information provided by the health system, failing on providing information about the risks and addictive properties of morphine and other opioid pain-killers and most of the time lack of education and overuse of medication by the patient after building tolerance.

These events were the cause of 100,000 deaths in America caused by opioids in a yearlong period ending in April during this pandemic, this causality between many others, have brought distrust upon big pharmaceutical companies as many patients got withdrawal from their medications and end up consuming alternatives such as botanicals like Kratom and unregulated opioids bought from the streets, compounds regularly adulterated with substances such as fentanyl and fentanyl analogs, to create volume to the batch sold making it cheaper, thus more accessible to the masses.

Consequently, chemists have been researching non-Opioid analgesics to fight these happenings.

In recent studies published by Stephanie Aguero, Simon Megy, Valeria V. Eremina, Alexander I. Kalashnikov, Svetlana G. Krylova, Daria A. Kulagina, Ksenia A. Lopatina, Mailys Fournier, Tatyana N. Povetyeva, Alexander B. Vorozhtsov, Sergey V. Sysolyatin, Vadim V. Zhdanov, and Raphael Terreux in the American Chemical Society, an interesting concept of creating an analgesic based on hexaazaisowurtzitane (CL-20) a component found in rocket fuel and explosives has been brought to light. Despite the innovation, several explosives have been used as drugs in medical history, being one of the most used nitroglycerin for vascular dilatation and peripheral vasodilatation, potassium nitrate to treat premenstrual syndrome, and reducing dentin hypersensitivity.

This new component is currently being patented under the name thiowurtzine, despite being directly derived from CL-20 this molecule lacks all the nitro groups responsible for the explosive properties of the molecule.


Synthesis of thiowurtzine

The biological evaluation of the substance to understand and compare it to drugs such as the synthetic opioid Tramadol, the NSAIDs Ketorolac, and Diclofenac, after a single administration of 100mg per kg, Thiowurtzine displayed a great response to relieve acute pain by 56.4% and prolonged the pain response time, with similar results to the opioid Tramadol. To better understand the action of the drug, an injection of the nonselective opioid receptor antagonist Naloxone was given to the test subjects, the results showed that the effect of Thiowurtzine was diminished, presenting us the possibility that the substance targets the Mu, Kappa, and Delta opioid receptors. Upon further investigation, an injection of naloxone methiodide didn’t seem to have an effect when it came to abolishing the analgesic effect showing us that Thiowurtzine doesn’t have an affinity to peripheral opioid receptors. 

With the obtained results we can discuss whether a new movement towards explosive-based analgesics will occur, as the results look promising. On the other hand, results for Tramadol seem not as promising. According to statistics provided by the Addiction Center around 84% of the users have abused the substance for narcotic effects, 60% of the people obtain their medication from friends, relatives, or from street sellers, under the name of Chill Pills or Trammies, increasing the risk of abuse and misusage of the medication, as well as the risk of overdose and adulterated pills.

The renaissance of Explosive-based medication in pharmacology is a portal to ameliorate accidental addiction to opioids caused by medical treatment, consequently lowering the interaction of the patients with opioids, as well as bringing a new type of treatment for underlying medical conditions such as chronic pain caused by trauma.



National Survey on Drug Use and Health. (2013). Summary of National Findings. Retrieved on June 27, 2015

Discovery of a Novel Non-Narcotic Analgesic Derived from the CL-20 Explosive: Synthesis, Pharmacology, and Target Identification of Thiowurtzine, a Potent Inhibitor of the Opioid Receptors and the Ion Channels- Stephanie Aguero, Simon Megy, Valeria V. Eremina, Alexander I. Kalashnikov, Svetlana G. Krylova, Daria A. Kulagina, Ksenia A. Lopatina, Mailys Fournier, Tatyana N. Povetyeva, Alexander B. Vorozhtsov, Sergey V. Sysolyatin, Vadim V. Zhdanov, and Raphael Terreux
DOI: 10.1021/acsomega.1c01786

Piper, B. J.; Shah, D. T.; Simoyan, O. M.; McCall, K. L.; Nichols, S. D. Trends in Medical Use of Opioids in the U.S., 2006–2016. Am. J. Prev. Med. 2018, 54, 652– 660
DOI: 10.1016/j.amepre.2018.01.034

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DOI: 10.1007/s10573-005-0014-2

Lewanowitsch, T.; Irvine, R. J. Naloxone and its quaternary derivative, naloxone methiodide, have differing affinities for μ, δ, and κ opioid receptors in mouse brain homogenates. Brain Res. 2003, 964, 302– 305
DOI: 10.1016/S0006-8993(02)04117-3

Overdose Deaths Reached Record High as the Pandemic Spread by Roni Caryn Rabin:

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