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

Pyrrolidinophenones are a class of stimulant recreational designer drugs including many substituted cathinones. Brains were sliced into 1 mm thick coronal sections, and these slices were placed flat on a cold plate over ice. Using a 1.5 mm diameter tissue biopsy-punch, regions of interest were taken from individual slices, as we have described previously (Murnane et al. 2012). Synthetic cathinones (“bath salts”) are β-ketone analogs of amphetamines, yet few studies have examined their potential neurotoxic effects. Rats were given 7 days to recover from surgery before commencement of ICSS procedures, alpha-pyrrolidinopentiophenone function during which they received daily injections of 2.5mg/mL meloxicam (0.15mL volume) to minimize postsurgical discomfort.

Effects of Flakka abuse

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).

Prescription Drug Abuse

Substituted analogs differ from native PV8 as they affect H9c2(2-1) cell viability even after 24 h. 4-F-PV8 applied for 24 h markedly reduced the viability of SH-SY5Y (100–300 μM), Hep G2 (50–300 μM), RPMI 2650 (10–300 μM), and H9c2(2-1) (200 and 300 μM) cell lines, with the greatest reduction by 42% (SH-SY5Y), 77% (Hep G2), 79% (RPMI 2650), and 72% (H9c2(2-1)) (Fig. 4b). Cell viability was significantly decreased in SH-SY5Y (25–300 μM; maximal reduction by 83%), Hep G2 (50–300 μM; maximal reduction by 97%), RPMI 2650 (10–300 μM; maximal reduction by 97%), and H9c2(2-1) cells (10–300 μM; maximal reduction by 79%) (Fig. 4b).

Flakka (Alpha-PVP) Overview, Effects, Abuse, Addiction, & Treatment

• Unfortunately, Flakka abuse and addiction are difficult to treat because the lingering effects can take an uncertain period of time to recover from, if at all.
• Additional experiments assessed the time courses of the effects of α-PPP on locomotor activity and core temperature using telemetry.
• 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).
• For the first time in history, the number of unregulated novel psychoactive substances on international drug markets now exceeds those under international control (United Nations, 2013).
• All other data comparing saline versus α-PPP were analyzed by unpaired t-test, and corrected for multiple comparisons by the Bonferroni method to maintain the probability of making a type 1 error at 5%.

Despite this, few studies have examined the effects of synthetic cathinones on neurochemistry. As noted previously, when methylone is administered to adolescent rats in a warm ambient environment, it induces an acute hyperthermic response and persistent depletions of serotonin and deficits in reference memory. These decrements were also selective, as there were no changes in dopamine levels or spatial memory (Lopez-Arnau et al. 2014). An interesting recent study reported the effects of exposure to MDPV, methylone, or mephedrone, using the same dosing regimen that we used in the present study (30–40 mg/kg, QID, q2h, IP), in female C57BL/6 mice, housed at five per cage. There was no significant change in striatal dopamine levels, dopamine transporter density, tyrosine hydroxylase immunoreactivity, or glial fibrillary acidic protein immunoreactivity two days after treatment (Anneken et al. 2015).

5. Drug Self-Administration

• Statistical analyses were conducted using NCSS (Number Cruncher Statistical Systems, Kaysville, Utah, USA).
• Incubation of cells with 4-F-PVP for 72 h resulted in a marked, concentration-dependent decline in the survival of all cell lines, with the maximal effect at the similar level in SH-SY5Y (reduction by 60%), Hep G2 (reduction by 54%), RPMI 2650 (reduction by 59%), and H9c2(2-1) (reduction by 46%) (Fig. 2b).
• Specifically, synthetic cathinone products have been shown to often contain more than one cathinone, as well as other adulterants, including illicit amphetamines, piperazines, cutting/binding agents, caffeine, and topical anesthetics (Brandt et al., 2010; German et al., 2014).
• Results obtained using LDH assay further confirm the impact of the side-chain length on the cytotoxicity of pyrrolidinophenones.
• Thus, while α-PVP and 4MMC are known to elevate DA (Baumann et al., 2012; Baumann et al., 2017; Kehr et al., 2011; Marusich et al., 2014), this affect is fleeting, and was not present one day after final drug exposure when brain samples were collected.

Alpha-PVP is known for producing intense stimulation and can lead to extreme behavioral changes, including agitation and violent outbursts. Both substances can induce euphoria, heightened sex drive, increased sociability, and hallucinations. When used in excessive amounts, they can lead to severe negative effects, including high blood pressure, elevated heart rate, paranoia, aggression, panic attacks, and psychosis. Both drugs can be consumed in various ways—such as smoking, injecting, or snorting—and carry a significant risk of overdose and death. The initial effects of taking Flakka are similar to those of bath salts and methamphetamines.

Interestingly, ShA drug self-administration also led to escalation of intake, particularly for 4MMC. This finding suggests that dysregulated drug intake is not limited to LgA conditions for α-PVP and 4MMC, similar to a past study showing that LgA and ShA cocaine self-administration both led to escalation of intake (Beckmann et al., 2012). To our knowledge, this is the first study to statistically compare male and female rodents for 4MMC and α-PVP self-administration, and the resulting neurochemical changes.

What is Flakka?

The dosing regimen was administered on day 1, and its persistent effects on anxiety, memory, and tissue monoamine neurochemistry were assessed as presented. Group two underwent dosing with α-PPP (80 mg/kg, QID, q2h, IP) and was assessed in the NOR test four days later and sacrificed for neurochemical analysis the following day. All statistically significant effects of drug (synthetic cathinone vs saline) on neurotransmitters in ShA groups, and interactions between drug and sex are shown in Table 2 and Fig. Self-administration of 4MMC produced widespread decreases in 5-HT and 5-HIAA levels compared to saline self-administration, whereas self-administration of α-PVP had little effect on serotonergic levels compared to saline.