α-Pyrrolidinohexanophenone (α-PHP) and α-Pyrrolidinoisohexanophenone (α-PiHP): A Review

Area of Science:

• Forensic Toxicology
• Medicinal Chemistry
• Public Health

Background:

• New Psychoactive Substances (NPS) represent a growing global public health concern, with 1184 identified by 2022.
• α-pyrrolidinohexanophenone (α-PHP) and α-pyrrolidinoisohexanophenone (α-PiHP) are synthetic cathinones and positional isomers, emerging in 2014 and 2016 respectively.
• Both substances are internationally controlled psychotropic substances with no medical use, primarily abused for recreational purposes, leading to severe health consequences.

Purpose of the Study:

• To comprehensively review the legislative, physicochemical, toxicological, and analytical characteristics of α-PHP and α-PiHP.
• To highlight the challenges these New Psychoactive Substances present to forensic toxicology.
• To inform the development of enhanced detection methods and legislation.

Main Methods:

• Literature review of legislative status, chemical properties, toxicological data, and analytical detection methods for α-PHP and α-PiHP.
• Analysis of reported adverse effects and fatalities associated with these synthetic cathinones.
• Examination of geographical prevalence, particularly in Portugal.

Main Results:

• α-PHP and α-PiHP are easily synthesized and modified, posing challenges for regulatory control.
• Frequent adverse effects include cardiac, psychiatric, and neurological issues, with documented fatal intoxications.
• Consumption and seizures are notably prevalent in Portuguese archipelagos, exacerbating local health crises.

Conclusions:

• α-PHP and α-PiHP are significant threats in forensic toxicology due to their accessibility and abuse potential.
• There is a critical need for advanced analytical techniques for their detection and robust legislative frameworks.
• Continued research is essential to mitigate the public health impact of these and similar emerging substances.