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Review
. 2025 Aug 1;13(8):659.
doi: 10.3390/toxics13080659.

The Blurred Lines Between New Psychoactive Substances and Potential Chemical Weapons

Loreto N Valenzuela-Tapia  1 , Cristóbal A Quintul  1 , Nataly D Rubio-Concha  1 , Luis Toledo-Ríos  2   3 , Catalina Salas-Kuscevic  2   3 , Andrea V Leisewitz  4 , Pamela Cámpora-Oñate  5 , Javier Campanini-Salinas  1
Affiliations
Review

The Blurred Lines Between New Psychoactive Substances and Potential Chemical Weapons

Loreto N Valenzuela-Tapia et al. Toxics. .

Abstract

The historical use of toxic chemicals to cause intentional harm has evolved from blister agents in World War I to highly lethal organophosphates and emerging families of chemicals, such as Novichok. In turn, medical or recreational substances like fentanyl, lysergamides, and phencyclidine pose a growing risk of hostile use, particularly related to the rapid proliferation of new psychoactive substances (NPSs). A narrative literature review was conducted covering specialized databases (PubMed, ScienceDirect, SciELO, Google Scholar) and sources from international organizations (OPCW, UNODC, ONU), analyzing historical and recent cases of the use of nerve agents in conflicts and the use of NPSs for hostile purposes. The main families of conventional agents (G, V, A series, and Novichok) and NPSs (lysergamides, PCP, fentanyl derivatives) were identified, highlighting their ease of synthesis, high toxicity profiles, and the regulatory gaps that facilitate their illicit production. In this scenario, it is essential to strengthen regulatory frameworks, surveillance systems, and ethical protocols in chemical research, as well as to promote international cooperation to prevent these substances from becoming chemical threats.

Keywords: chemical warfare agents; chemical weapons; cognitive warfare; neurotoxic agents; new psychoactive substances; non-lethal chemical weapons.

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Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Structural evolution of chemical weapons and their modifications over the years [13,33,34,35].
Figure 2
Figure 2
Chemical structure of LSD. Position 6 is marked because of its relevance to the structure-activity relationship of the molecule.
Figure 3
Figure 3
Chemical structure of ketamine.
Figure 4
Figure 4
Chemical structure of fentanyl. Position 3 and 4 is marked because of its relevance to the structure-activity relationship of the molecule.
Figure 5
Figure 5
Chemical structure of diazepam. Position 5 is marked because of its relevance to the structure-activity relationship of the molecule.
Figure 6
Figure 6
Chemical structure of tetrahydrocannabinol (THC) (A) and dimethylheptylpyran (DMHP) (B), which forms the chemical basis for EA-2233. EA-2233 is the O-acetate ester of DMHP and possesses three stereogenic centers, resulting in eight possible stereoisomers (EA-2233-1 to EA-2233-8), with varying R/S configurations.
See this image and copyright information in PMC

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