What do we know about W-18?

“W18 drug is 10,000 times stronger than morphine: Calgary police warning”

“Police warn against deadly new street drug W-18”

“Alberta health official warns of deadly new street drug”

“W-18, a drug 100 times more potent than fentanyl, is now in B.C.”

“Albertans left in the dark about police seizure of deadly new street drug”

“ER doctors warned about massive seizure of suspected W-18, 100 times more powerful than fentanyl”

“A toxic drug, more powerful than fentanyl, hits the streets in Alberta”

Those are some recent headlines regarding a newly emerged drug named W-18 in North America. The substance is supposedly 10,000 times more potent than morphine or 100 times more potent than fentanyl as a central nervous system depressant.

Counterfeit Oxycodone tablets containing fentanyl

Image taken from CBC News

http://www.cbc.ca/news/canada/saskatoon/w18-overdose-saskatchewan-alberta-1.3549043

W-18 is a compound in a series of 32 substances (named W-1 to W-32) that were first synthesized in academic research by Edward Knaus, Brent Warran, and Theodore Ondrus at the University of Alberta in 1981. These W-series compounds are covered under US patent 4468403A (August 28, 1984). The chemical name for W-18 is 4-chloro-N-[1-[2-(4-nitrophenyl)ethyl]-2-piperidinylidene]-benzenesulfonamide and it has a chemical formula C₁₉H₂₀ClN₃O₄S. Molecular weight is 421.9 g/mol.

Chemical structure of W-18

Image drawn by ForensicToxGuy (2016)

W-18 was detected in counterfeit tablets sold as fentanyl in Calgary, Alberta, Canada in August 2015. W-18 was also identified as the constituent in four kilograms of powder in a drug seizure in Edmonton, Alberta, Canada in December 2015; purity of the powder substance was reported to be 90% by Canadian authorities. In 2016, a Florida man was found to be in possession of 2.5 pounds of a powder containing W-18.

Despite media reports and quotes from law enforcement officials, the pharmacological profile for W-18 is not established at this time.  We have no data on absorption, distribution, metabolism, or excretion of the substance. We do not know on what specific receptors W-18 acts. We know nothing about receptor binding affinities. We know nothing of the acute effects of the substance. The only piece of pharmacological data that exists for W-18 was acquired via the mouse phenylquinone (PQ) writhing assay. In that test, W-18 had an IC₅₀ equal to 3.7 ng/kg and 50% inhibition. In the same test, morphine’s IC₅₀ was equal to 38,000 ng/kg and 50% inhibition. It very important to note that the PQ writhing assay is a general or non-specific test in which many compounds not considered to be analgesics, including sympathomimetics and central nervous system stimulants, protect mice against the PQ-induced writhing. The assay results should not be interpreted in any way that insinuates W-18 is approximately 10,000 times more potent than morphine as a central nervous system depressant.  We currently have no pharmacological data to support that W-18 has any activity at the opioid receptors: mu (µ), kappa (κ), or delta (δ).

W-18 is not considered a controlled substance in the United States, though it may be considered a controlled substance analog under the Analog Enforcement Act. It was made illegal in Sweden in January 2016. In Canada, the government has proposed making W-18 a Schedule I controlled substance, but it currently remains uncontrolled. In clinical and postmortem toxicology, there have been no analytically confirmed W-18 associated presentations to the hospital or fatalities reported.

As with any other newly emerging psychoactive substance, many claims are made about the compound itself. Many of the headlines are meant to grab attention and readership with hysteria about the new “super potent” or “scary” drug of the day. We should guard ourselves against that sort of hyperbole. But, even though we have no data to support the supposed extreme potency of W-18, let’s not fall into the trap that it isn’t potentially dangerous. We do not have data that shows its lack of potency. This extreme lack of knowledge about the compound makes the drug potentially dangerous.

 

References

Knaus, E.E., Warren, B.K., and Ondrus, T.A. (1984) Analgesic substituted piperidylidene-2-sulfon(cyan)amide derivatives. 399,994. http://www.google.com/patents/US4468403

Brittain, R.T., Lehrer, D.N., Spencer, P.S.J. (1963) Phenylquinone Writhing Test: Interpretation of Data. Nature, 200, 895-896.

Lum, Z-A. (2016) W-18 drug is 10,000 times stronger than morphine: Calgary police warning. http://www.huffingtonpost.ca/2016/01/29/w18-calgary-police_n_9114152.html

Desjardins, L. (2016) Police warn against deadly new street drug W-18. http://www.rcinet.ca/en/2016/04/21/police-warn-against-powerful-deadly-new-drug-w-18/

Zakreski, D. (2016) Alberta health official warns of deadly new street drug. http://www.cbc.ca/news/canada/saskatoon/w18-overdose-saskatchewan-alberta-1.3549043

Eagland, N. (2016) W-18, a drug 100 times more potent than fentanyl, is now in B.C. http://vancouversun.com/health/local-health/w-18-a-drug-100-times-more-potent-than-fentanyl-is-now-in-b-c

Howlett, K. (2016) Albertans left in the dark about police seizure of deadly new street drug. http://www.theglobeandmail.com/news/alberta/alberta-police-seize-drug-100-times-more-deadly-than-fentanyl/article29692152/

Southwick, R. (2016) ER doctors warned about massive seizure of suspected W-18, 100 times more powerful than fentanyl. http://calgaryherald.com/news/crime/er-doctors-warned-about-massive-seizure-of-suspected-w-18-100-times-more-powerful-than-fentanyl

Markusoff, J. (2016) A toxic drug, more powerful than fentanyl, hits the streets in Alberta.

http://www.macleans.ca/?dpsfa_article=a-toxic-drug-more-powerful-than-fentanyl-hits-the-streets-in-alberta

Russell, A. (2016) What we know about W-18, a drug ‘100 times more powerful than fentanyl’. http://globalnews.ca/news/2495761/what-we-know-about-w-18-a-drug-100-times-more-powerful-than-fentanyl/

McMahon, P. (2016) Broward man who smuggled synthetic heroin also had new lethanl, but legal, street drug. http://www.sun-sentinel.com/local/broward/fl-fentanyl-broward-sentencing-20160318-story.html

Consultation - Proposal regarding the scheduling of W-18 under the Controlled Drugs and Substances Act and its Regulations". Health Canada. Canadian Government. http://www.hc-sc.gc.ca/hc-ps/consult/w-18-eng.php

Gonçalves, Jacqueline (13 February 2016). "Notice to interested parties — Proposal regarding the scheduling of W-18 under the Controlled Drugs and Substances Act and its regulations". Canada Gazette (Government of Canada) 150 (7). http://gazette.gc.ca/rp-pr/p1/2016/2016-02-13/html/notice-avis-eng.php#nl3