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Introduction Alpha-pyrrolidinohexanophenone (α-PHP) is a synthetic cathinone with uneven distribution throughout the world. Its use is not uniformly regulated and its distribution is legal in some European countries. Easily accessible and available through different websites. Synthetic cathinones inhibit monoamine transporters which include dopamine, norepinephrine, and serotonin, resulting in increased neurotransmitter synaptic concentration. Ways of administration show wide range regarding latency period. Onset and appearance of symptoms as well as their duration and intensity may fluctuate. A decreasing order of latency (oral, inhaled, sublingual and intravenous) has been reported. α-PHP can result in the appearance of psychiatric symptoms, include among others, intoxication with sensory perception disturbances and α-PHP -induced psychotic episodes. Objectives The aim of our study was to assess the epidemiology, clinical and legal features regarding Alpha-pyrrolidinohexanophenone (α-PHP). Methods Review the current bibliography to upgrade the existing knowledge. -Present assorted cases with diverse clinical features. All cases include variability through psychopathological interview, symptoms assessment and treatment response according to rating scales (PANSS, YMRS). -Evaluate different treatment administration ways during acute phase and after hospital discharge. Results Differences were observed after hospitalization in the response using diverse rating scales. We used antipsychotics to treat intoxication with sensory perception disturbances and α-PHP -induced psychotic episodes. α-PHP had a negative impact on the quality of life of the patients. Conclusions α-PHP is a synthetic cathinone with potential risk to mental health and life of users. It is mandatory to implement common legislation all through the European Union to prevent its use and possible implications on population’s mental health. Disclosure No significant relationships.

Novel psychoactive substances (NPS) threaten public health and safety while also straining the limited resources of forensic laboratories. To efficiently allocate the finite resources available, we propose a new strategy for prioritizing NPS with abuse liability testing using a preclinical behavioral procedure in rats known as intracranial self-stimulation (ICSS). To validate this assay, the recently-scheduled synthetic cathinone α-PHP was compared to cocaine, a mechanistically similar drug of abuse, as a positive control and saline as a negative control. Male Sprague-Dawley rats (n=6) were implanted with electrodes targeting the medial forebrain bundle and trained to respond by lever-press for electrical brain stimulation. The rats were tested with doses of 0.32, 1.0, and 3.2 mg/kg α-PHP as well as 10 mg/kg of cocaine and saline administered by intraperitoneal injection. Neither saline nor 0.32 mg/kg α-PHP altered ICSS response rates compared to baseline levels of responding; however, doses of 1.0 and 3.2 mg/kg α-PHP and 10 mg/kg cocaine facilitated ICSS responding. This ICSS profile suggests that α-PHP has high abuse potential, with a rapid onset of effects and a long duration of action, and supports the decision to schedule this compound. This study demonstrates the ability of ICSS to distinguish between compounds of low and high potential for abuse. A strategy is proposed here to screen NPS using ICSS and classify emerging drugs into four priority categories for further analysis.

Novel psychoactive substances (NPS) threaten public health and safety while also straining the limited resources of forensic laboratories. To efficiently allocate the finite resources available, we propose a new strategy for prioritizing NPS with abuse liability testing using a preclinical behavioral procedure in rats known as intracranial self-stimulation (ICSS). To validate this assay, the recently-scheduled synthetic cathinone α-PHP was compared to cocaine, a mechanistically similar drug of abuse, as a positive control and saline as a negative control. Male Sprague-Dawley rats (n=6) were implanted with electrodes targeting the medial forebrain bundle and trained to respond by lever-press for electrical brain stimulation. The rats were tested with doses of 0.32, 1.0, and 3.2 mg/kg α-PHP as well as 10 mg/kg of cocaine and saline administered by intraperitoneal injection. Neither saline nor 0.32 mg/kg α-PHP altered ICSS response rates compared to baseline levels of responding; however, doses of 1.0 and 3.2 mg/kg α-PHP and 10 mg/kg cocaine facilitated ICSS responding. This ICSS profile suggests that α-PHP has high abuse potential, with a rapid onset of effects and a long duration of action, and supports the decision to schedule this compound. This study demonstrates the ability of ICSS to distinguish between compounds of low and high potential for abuse. A strategy is proposed here to screen NPS using ICSS and classify emerging drugs into four priority categories for further analysis.