Flakka Drug: Symptoms, Side Effects & Complications

These videos often depict alarming scenes of erratic behavior, such as individuals running naked through streets, attempting to break into homes, jumping from heights, exhibiting extreme aggression towards others, or displaying bizarre and dangerous acts. These instances highlight the profound and often alarming effects that flakka can have on behavior and mental state, emphasizing its dangers to both users and the community at large. Α-Pyrrolidinopentiothiophenone (also known as α-PVT) is a synthetic stimulant of the cathinone and thiopropamine (thiophenylpropylamine) families that has been sold online as a designer drug.123 It is an analogue of α-PVP where the phenyl ring has been replaced by thiophene. The NOR test has been proposed to measure recognition memory by allowing mice to explore novel and familiar objects (Antunes and Biala 2012).

Treatment for Flakka abuse

Thus, future research should extend the duration of self-administration past 21 sessions to examine what neurochemical changes transpire and if increasing neurochemical dysregulation occurs with continued drug use as hypothesized. Flakka is a synthetic cathinone with effects and a chemical makeup similar to bath salts and CNS stimulants. The adverse side effects of the drug include volatile psychosis, leading it to be dubbed “the zombie drug”. The term “man on flakka” does not refer to a specific individual but rather describes the behavior typically exhibited by individuals under the influence of flakka (alpha-PVP), a synthetic cathinone known for inducing extreme and unpredictable actions. Exposure to α-PPP significantly impaired performance in the Y-maze, decreased overall exploratory activity in the novel object recognition test, and resulted in regionally specific depletions in monoamine neurochemistry.

Drugs and Chemicals

Drug concentrations used in this in vitro study, reaching 300 μM, exceed those normally found in the blood obtained from intoxicated patients and during autopsies (Kudo et al. 2015; Marinetti and Antonides 2013). However, as discussed in our previous work (Wojcieszak et al. 2016), organs such as the liver, brain, and upper airway epithelium can be exposed to significantly higher local drug concentrations than those measured in blood. 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. alpha-pyrrolidinopentiophenone function 2016).

• Likewise, norepinephrine levels in the hippocampus are elevated during spontaneous alternations (Men et al. 1999) and depletion of norepinephrine from forebrain projections results in impaired spontaneous alternation (Pisa and Fibiger 1983).
• 4-Methylmethcathinone (4MMC; mephedrone) releases dopamine (DA), norepinephrine (NE), and serotonin (5-HT) (Baumann et al., 2012; Cameron et al., 2013; Simmler et al., 2013).
• There were differences between condition (LgA vs naïve), between males and females, and there were interactions between condition and sex.
• This trips the brain’s reward pathway, causing a euphoric high and priming a person to feel cravings to repeat the experience in the future.
• Females had lower NE levels than males in amygdala and thalamus for ShA rats, the latter of which only occurred for 4MMC groups, and higher NE levels than ShA males in hippocampus, PFC, and striatum.
• 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.

ICSS Apparatus

Although spontaneous alternation behavior has been closely linked to brain cholinergic systems (Lalonde 2002), previous studies have documented a role for catecholamines, as dopamine depletions in the striatum or septum result in impaired spontaneous alternations (Taghzouti et al. 1985). Likewise, norepinephrine levels in the hippocampus are elevated during spontaneous alternations (Men et al. 1999) and depletion of norepinephrine from forebrain projections results in impaired spontaneous alternation (Pisa and Fibiger 1983). Relating specific neurochemical depletions to specific behavior impairments presents rich research opportunities. In this study, we document persistent effects of the second-generation pyrrolidine synthetic cathinone α-PPP on behavior and neurochemistry. We document that, consistent with previous studies of amphetamine derivatives (Murnane et al. 2012), α-PPP acutely decreases body weight over the course of a standard 6-hour dosing regimen.

What are the symptoms of flakka abuse?

• The present study suggests that 21 days of LgA self-administration models the neurochemistry of the beginning stages of the Koob and Volkow model of dysregulated drug intake (Koob and Le Moal, 2005, 2008; Koob and Volkow, 2010).
• 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.
• This study confirms that pyrovalerone cathinones are endowed with the prominent cytotoxicity.
• Researchers have not thoroughly clinically studied the long-term effects of flakka, but renal failure can occur that is irreversible.
• These patients are a threat to themselves, the people around them, and the first responders (police, EMS) who are there to help them.
• The following day, we performed an extensive neurochemical profiling across the striatum and prefrontal cortex for monoamine neurochemistry.
• 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.

Long incubation times were applied in order to show whether the cytotoxicity of studied compounds increase with time, which is relevant since the common abuse pattern of synthetic cathinones includes long sessions during which multiple doses are administered (Zawilska and Wojcieszak 2013). The effects of α-PPP on serotonin levels are somewhat surprising, as it has reported selectivity for the dopamine and norepinephrine transporters over the serotonin transporter (Eshleman et al. 2017). However, we used a relatively high dose regimen to ensure near maximal levels of toxicity, and α-PPP likely loses some selectivity at such doses.

Effects of PV9, 4-F-PV9, and 4-MeO-PV9 on the Survival of SH-SY5Y, Hep G2, RPMI 2650, and H9c2(2- Cells

On the other hand, the incubation of cells with PV8 and its analogs, containing an additional two carbon atoms, reduced cell viability by a maximum of 70–80% after 24 h, and by more than 90% after 72 h. Further elongation of the side-chain increased the cytotoxic activity, as observed in the tests on PV9 and its substituted analogs. Incubation for 72 h with the highest tested doses (200 and 300 μM) resulted in almost complete extinction of cell viability in all but the H9C2(2-1) cell lines. Finally, it is also important to mention that both first- and second-generation synthetic cathinones are often sold as mixtures. 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).

Treating Flakka Abuse

Pyrovalerone derivatives (α-pyrrolidinophenones) form a branch of synthetic cathinones, a second most prominent group of novel psychoactive substances. Although the toxicity of 3,4-MDPV, a progenitor of the α-pyrrolidinophenones, is well described, little is known of the potential cytotoxicity of the new members of this group entering the recreational drug market each year. Additionally, an impact of pyrovalerones on the fluidity of the plasma membrane, as the potential mechanism of their cytotoxicity, was examined. The longer side-chain α-pyrrolidinophenones and their fluoro- and methoxy-analogs produce more pronounced maximal cytotoxicity, with regard to mitochondrial activity and cell membrane integrity, than the five-carbon α-PVP and its substituted derivatives.