Both Flakka and bath salts are incredibly dangerous when abused, causing harmful side effects, overdose, death, and are addiction-forming. The adverse effects of Flakka abuse, its damaging nature to physical and mental health, and the potential for overdose all make Flakka a highly dangerous drug. NPS drugs like synthetic cathinones began to gain prevalence in the early 2000s and were designed to mimic the effects of other drugs such as cocaine, LSD, and ecstasy. PV8, 4-F-PV8, and 4-MeO-PV8 inflicted significant damage to the membranes of SH-SY5Y and RPMI 2650 cells at 200 and 300 μM, and to H9c2(2-1) cells when applied at 100 to 300 μM. Moreover, 4-F-PV8 and 4-MeO-PV8, but not PV8, disrupted Hep G2 cell membranes at 200 and 300 μM. The most pronounced cytotoxicity was observed after treatment of Hep G2 cells with 4-MeO-PV8 (71% of positive control toxicity) (Fig. 5).

Short-Term Effects Of Flakka Use

Despite the DEA’s efforts to ban flakka, the drug is still being manufactured and sold illegally, often through online vendors. The core chemical compound used to make flakka, alpha-PVP, is still legal in many parts of the world. SH-SY5Y (ATCC® CRL-2266™), Hep G2 (ATCC® HB-8065™), and RPMI 2650 (ATCC® CCL-30™) cell lines were purchased from Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures (DSMZ, Braunschweig, Germany). H9c2(2-1) (ATCC® CRL-1446™) cell line was purchased from the European Collection of Cell Cultures (ECACC, Porton Down, UK). Body weight and rectal temperature were recorded at baseline, immediately prior to each injection, and two hours after the last injection. Temperature was measured by inserting a lubricated probe 1.5 cm into the rectum and recording the readout from a connected TH-8 Thermalert temperature monitor (Physitemp Instruments; Clifton, NJ, USA) after the signal reached steady state.

What are the side effects of Flakka?

Similarly, after 24-h incubation, 4-MeO-PV8 decreased the viability of all tested cell lines (25–300 μM for SH-SY5Y and RPMI 2650 cells, 200 and 300 μM for Hep G2 and H9c2(2-1) cells), with the greatest effect being 59% reduction of the survival for SH-SY5Y, 68% for Hep G2, 87% for RPMI 2650, and 33% for H9c2(2-1). Extending incubation time to 72 h increased the cytotoxicity at 300 μM, leading to the decrease of the viability by 91% for SH-SY5Y, 97% for Hep G2, 98% for RPMI 2650, and 63% for H9c2(2-1). Moreover, a broader concentration range was found to elicit a significant drop in the viability for the Hep G2 (25–300 μM) and H9c2(2-1) (10–300 μM) cell lines, compared to 24-h exposure (Fg. 4c). 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.

Unveiling the Chemistry and Applications of Flakka

The role of serotonin systems in working and recognition memory is an area ripe for additional research. ShA synthetic cathinone self-administration did not alter total DA in any measured brain region. LgA self-administration only affected DA levels in hypothalamus and thalamus compared to naïve, and in striatum and thalamus compared to saline ShA, and these changes were small in magnitude. Surprisingly, only LgA 4MMC affected total DA in striatum when compared to saline ShA, a region in which LgA exposure increased DA metabolites (Fig. 3 and 5).

Effects on Neurochemistry

Each animal had a familiarization (training) session with a pair of identical objects (~ 5 cm long x 5 cm wide x 10 cm high) placed 5 cm away from the walls but adjacent in the open field. 6 hours after familiarization (Leger et al. 2013), each mouse was tested in the same alpha-pyrrolidinopentiophenone function box with a novel object replacing one of the familiar objects.Familiarization and testing sessions lasted 10 minutes, were video recorded, and were assessed offline. Exploration was defined as sniffing the object or orienting the head towards the object while the subject was within 1 cm of distance from the object. The percentage of the total exploration time spent exploring the novel object was calculated to reflect recognition memory.

• This plasticity hijacks normal learning mechanisms to create habits that persist despite adverse consequences and contribute to the deterioration of cognitive performance (Koob and Volkow, 2010).
• In contrast to the minor sex differences in self-administration behavior, sex differences in neurochemical changes were more widespread.
• Future studies are needed to determine why there were vast sex differences in the neurochemistry of ShA groups that seemed to dissipate in the LgA groups.
• Stimulant-induced neurochemical changes may occur at different times for different brain regions or neurotransmitter systems.
• Synthetic cathinones altered DA metabolite levels in a few select locations in the brain compared to saline.
• This will often be part of inpatient or outpatient treatment programs which include a course of behavioral therapy to help manage addiction, identify causes and triggers of addiction, and treat any co-occurring mental health disorders.

It is also possible that Koob and Volkow’s hypothesized neurochemical changes are dependent on drug contingency, dose, or other methodological considerations. Neurotransmitter and metabolite concentrations for all brain regions and all LgA and naïve rat groups are shown in Fig. There were differences between condition (LgA vs naïve), between males and females, and there were interactions between condition and sex.

Figure 2.

• Additionally, an impact of pyrovalerones on the fluidity of the plasma membrane, as the potential mechanism of their cytotoxicity, was examined.
• Despite the DEA’s efforts to ban flakka, the drug is still being manufactured and sold illegally, often through online vendors.
• All self-administration and neurotransmitter data for these three rats were excluded from graphs and analyses.
• Additionally, one male 4MMC ShA and saline ShA rat were exposed to the incorrect infusion volume.
• Sex differences in ShA saline self-administration were noted (Fig. 2) but were only statistically different for two days.

In contrast, it had no significant effect on elevated plus maze performance or object discrimination in the novel object recognition test. The locomotor-stimulant effects of α-PPP were comparable to cocaine (30mg/kg), and α-PPP (80mg/kg) did not induce hyperthermia. ED50 values represent the mean dose leading to 50% maximal response with upper 95% confidence limits (UL) and lower 95% confidence limits (LL). Maximal response values represent the mean maximum intracranial self-stimulation (ICSS) threshold reduction (independent of dose)±95% confidence intervals.

Group two underwent dosing with α-PPP and was assessed in the NOR test four days later and sacrificed for neurochemical analysis the following day. For example, binge-like self-administration of MDPV resulted in neurodegeneration and deficits in the novel object recognition (NOR) test (Sewalia et al. 2018). Likewise, adolescent rats exposed to methylone exhibited persistent depletions of serotonin and deficits in reference memory (Lopez-Arnau et al. 2014). However, mephedrone and methylone have also been reported to not persistently deplete brain monoamine content (Baumann et al. 2012).

A 10-μl aliquot was injected onto a Luna Omega 2.1 x 150 mm column (Phenomenex, Torrance, CA) coupled to a LPG-3400RS pump, WPS-3000TBRS autosampler, and a CoulArray electrochemical detector. The mobile phase consisted of 50 mM sodium phosphate, 47 mM citric acid, 0.14 mM EDTA, 0.64 mM octanesulfonic acid, and 5% methanol, with a flow rate of 0.4 ml/min. The detector was set to sequentially deliver potentials of −150 mV, 150 mV, 400 mV, and 600 mV.