What is Flakka Alpha-PVP: Risks, addiction & treatment

When heated up, it gives off a foul-smelling smoke characterized as smelling like dirty socks. After 24-h incubation PVP caused significant reductions in the survival of SH-SY5Y (25–300 μM), Hep G2 (10–300 μM), RPMI 2650 (50–300 μM), and H9c2(2-1) (10–300 μM) cell lines. At a concentration of 300 μM, PVP produced a decrease in the viability of SH-SY5Y, Hep G2, RPMI 2650, and H9c2(2-1) cells by, respectively, 25, 51, alpha-pyrrolidinopentiophenone function 44, and 21% of control values.

Treatment Options for Flakka Addiction

Slope and ED50 values from previously published data (Watterson et al., 2012, 2014) were also calculated (Table 1) but were not compared statistically because of the possibility of cohort effects. In contrast to the minor sex differences in self-administration behavior, sex differences in neurochemical changes were more widespread. Notably, sex differences in neurochemistry were more abundant for ShA than LgA groups, and the cause of this is unknown.

• Thus, α-PiHP proves to be a potent DAT inhibitor due to its isomer α-PHP and other synthetic cathinones 25,86.
• Cell viability was reduced to below 30% of the control group values by 200 and 300 μM PV9 in Hep G2 (max. reduction by 91%) and RPMI 2650 cells (max. reduction by 96%), and by 300 μM PV9 in SH-SY5Y (max. reduction by 81%) and H9c2(2-1) cells (max. reduction by 89%) (Fig. 6a).
• Notably, the mechanism of synthetic cathinone action had little effect on neurochemistry.
• The additional 21 days of self-administration were also analyzed with separate mixed factors ANOVAs (day x lever x sex), which compared responses on the active and inactive levers.
• Moreover, it is noteworthy that immortalized cancer cell lines, which are a convenient model for in vitro studies, can be more resistant to cytotoxicity, and therefore, cell damage can be observed in concentrations higher than in normal cells in vivo (den Hollander et al. 2014; Wojcieszak et al. 2016).

Figure 6.

Supernatant was then transferred to a 96 well plate for analysis by electrochemical detection (ECD). Some bath salts may be more potent than Flakka, others less, and there is really no way of telling beforehand. Flakka, a street name for the inexpensive and dangerous “designer drug” Alpha-PVP, is one such newcomer. In accordance with each route of administration, the latency and action time are different. Thus, in Table 2 is described the effect duration considering the various routes of α-PHP consumption 19.

Is Weed a Depressant, Stimulant, or Hallucinogen?

Cell viability and mitochondrial function were measured by assessment of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) reduction by mitochondrial dehydrogenases after 24- and 72-h exposure to the drugs. A solution of MTT (0.5 mg/ml) was added to the cells, and the culture was incubated for a further 3-h at 37 °C. After aspiration of culture medium, formazan crystals were dissolved in DMSO, and its absorbance was measured at 570 nm using Bio-Rad microplate reader model 680; this value being proportional to the number of cells with intact mitochondria. The mean values for each group were obtained by subtracting the mean OD of the positive control (1% (v/v) Triton-X100, added 30 min before MTT) from the value.

Cell Lines

Muscle tissue begins to break down, releasing proteins and other cellular products into the bloodstream, in a process called rhabdomyolysis. The result of the cellular products and proteins released during rhabdomyolysis and dehydration can impair the filtering function of the kidneys, leading to renal failure and death. In addition, such agitation may trigger Taser use or other methods that have the potential to harm the individual when law enforcement personnel have to intervene. Our findings are in line with those published by Matsunaga et al. (2017), demonstrating that cytotoxicity of pyrovalerones increases with the elongation of the α-carbon side-chain. Importantly, our results suggest that the risk of intoxication with pyrovalerones, resulting from their cytotoxic properties, could be positively related to the length of their aliphatic side-chain.

Neurotransmitter data from groups that self-administered under ShA or LgA conditions are compared in Fig. Changes in DA levels in striatum and thalamus are hypothesized to occur during the binge and intoxication stage because activation of the mesolimbic DA system produces acute reinforcing properties of psychostimulants (Koob and Volkow, 2010). Furthermore, the dorsal striatum is involved in escalation of drug taking and compulsive behaviors (Clark et al., 2013; Willuhn et al., 2012). LgA, but not ShA, synthetic cathinone self-administration elevated DOPAC and HVA levels in striatum compared to saline and synthetic cathinone ShA levels (Fig. 5), encompassing the binge and intoxication stage of Koob and Volkow’s model. Interestingly, while the metabolites were altered, DA levels only changed in striatum and thalamus for 4MMC and α-PVP LgA groups, respectively, compared to saline ShA.

• Given that the present study primarily observed early-stage neurochemical changes, experimental paradigms using greater than 21 sessions of self-administration may be necessary to reach the negative reinforcement and withdrawal stage of the Koob and Volkow model.
• Neurotransmitter data from groups that self-administered under ShA or LgA conditions are compared in Fig.
• Both α-PHP and α-PiHP have no medical use in therapeutics, and they are abused as novel designer drugs for recreational habits, leading to fatalities 19,25.
• ED50 values represent the mean dose leading to 50% maximal response with upper 95% confidence limits (UL) and lower 95% confidence limits (LL).
• Law enforcement agencies and health care providers have expressed significant concerns about the widespread use of flakka, particularly among younger demographics and in clubbing scenes where synthetic drugs are more prevalent.
• Concerning global regulations, substances, certain chemicals, and drugs are classified into five schedules depending on their medical use and their dependence and abuse potential 35.

Each experiment included a positive control of 1% (v/v) Triton-X100, as recommended by the manufacturer. Results are expressed as a percentage value of the positive control group, considered as 100% cytotoxicity. These NPS drugs are generally classified as Schedule I controlled substances with no accepted medical use and a high potential for abuse and addiction.