Abuse potential of new psychoactive substances: N-ethylhexedrone, 4-Methylethcathinone, 4-Fluoromethcathinone and Buphedrone
New psychoactive substances (NPS) remain a considerable public health challenge worldwide. Synthetic cathinones (SC), one of the most sought classes of NPS among the users, is the second largest group of new drugs monitored by the EMCDDA. As the banning on NPS progresses, emerging new SC, some times with resulting enhance pharmacological activity or even unpredictable responses, are being synthetized. SC are thought to act on the central nervous system (CNS), and according to users, ingestion of these SC usually produces fast-acting but short-lived stimulant effects, hence inducing higher desire of redosing. Therefore, it is expected that these SC will lead to compulsive redosing and addictive behaviours on its users.
As defined by international drug agencies (FDA, EMA, EMCDDA) abuse-related animal behavioural studies should be conducted when a test drug or any of its major metabolites are CNS-active. These in vivo studies evaluate whether a test drug produces behavioural changes in animals that suggest abuse potential in humans. Hence, this study aims to access the abuse-potential of selected SC. Conditioned place preference (CPP) test is a specific abuse-related study used to evaluate whether a drug has rewarding or reinforcing properties, using the paradigm of stimulus association between a specific location and drug taking
For that purpose, popular ring-substitute cathinones such as 4-Methylethcathinone (4-MEC), 4-Fluoromethcathinone (4-FMC), and an emerging SC, N-ethylhexedrone (Hexen), were selected to be studied and compared with another cathinone derivative, Buphedrone, known for its rewarding and reinforcing properties (Oh et al 2018). To access the rewarding properties of each SC under study we used the CPP test. CPP apparatus, consisting on 2 conditioning compartments of equal size connected by a corridor that remained closed during the conditioning sessions, were used. Conditioning sessions were performed on 4 consecutive days, two sessions per day for each mouse: one during mornings with saline (10 mL/kg, i.p.) and the second with 0, 4, 16 mg/kg of tested SC. At D5, animals were allowed to circulate freely between compartments and place preferences registered. All trials were video-recorded to score the time spent by animals in each compartment. The score of the time spent in the drug-associated compartment was computed for each drug. The results show that Hexen and 4-FMC induced significant CPP at 4 and 16 mg/kg doses like Buph does, compared with controls, while 4-MEC displays significant CPP only at doses of 16 mg/kg. In conclusion, all SC studied so far displayed CPP shift in mice for doses as low as 4 mg/kg, which suggests a potential risk of repeated abuse for these NPS, hence their use poses a considerable public health concern.