Synthetic cathinones in Belgium: a cluster of poly-drug intoxications involving alpha-pyrrolidinoisohexiophenone (alpha-PiHP) (2025)

BACKGROUND: Synthetic cathinones, known as 'gravel' or 'bath salts', include α-pyrrolidinoisohexiophenone and its analogues α-pyrrolidinovalerophenone and α-pyrrolidinohexanophenone; often referred to as 'flakka' on the street or 'zombie drug' in media reports. Documented motivation for use includes libido enhancement and appetite suppression. Since its international scheduling, α-pyrrolidinoisohexiophenone has gained prevalence in European Union countries where α-pyrrolidinovalerophenone previously dominated.
METHODS: Three Belgian hospitals in adjacent regions reported intoxications involving α-pyrrolidinoisohexiophenone to the national early warning system. This triggered a retrospective analysis of a convenience cluster of 39 cases. Toxicological screening was performed using standardised laboratory protocols. Patient data, encompassing demographics, drug use patterns, and clinical symptoms, were obtained from routine hospital records.
RESULTS: α-Pyrrolidinoisohexiophenone was analytically confirmed in 37 urine samples. The distinction between α-pyrrolidinoisohexiophenone and α-pyrrolidinohexanophenone was not possible for two blood samples. Urine samples quantification, (n = 16), revealed α-pyrrolidinoisohexiophenone concentrations ranging from 1.0 µg/L to 1,366.0 µg/L. A variety of clinical symptoms were recorded, including anxiety, aggression, suicidal thoughts, psychosis, babbling, and decreased consciousness.
DISCUSSION: Symptoms in this cluster matched those from previous synthetic cathinone intoxications. No correlation was found between α-pyrrolidinoisohexiophenone presence and intoxication severity. Synthetic cathinones remain popular due to their availability, low cost, and potency at doses as low as 5-10 mg, likely fuelling continued development of new analogues.
CONCLUSION: The cluster of patients with poly-drug intoxications involving α-pyrrolidinoisohexiophenone in Belgium highlights the challenges posed by synthetic cathinones. Symptoms such as agitation, hallucinations and aggression align with those seen in prior cases of bath salts, although they cannot be solely attributed to α-pyrrolidinoisohexiophenone due to the presence of multiple other substances. We provide insight into α-pyrrolidinoisohexiophenone poisoning and emphasize the need for active information sharing to improve healthcare responses and awareness of the risks associated with synthetic drugs. [Author's abstract]