Flakka Drug: Symptoms, Side Effects & Complications

The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) was monitoring about 930 NPSs at the end of 2022, with synthetic cathinones representing the second largest group of substances monitored until 2021 5. Results obtained using LDH assay further confirm the impact of the side-chain length on the cytotoxicity of pyrrolidinophenones. PVP and its analogs caused only benign disruption of SH-SY5Y and H9C2(2-1) cell membranes, while PV8 and PV9, and their substituted derivatives, evoked marked damages.

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Alpha-PiHP, as mentioned above, is a α-PHP isomer and therefore is also considered a pyrovalerone derivative from the class of synthetic cathinones 25. Alpha-PiHP hydrochloride, in its pure form, tends to be odourless and can vary from off-white to white 25,34,80,81,82,83,84. This substance has been sold on the streets under its original name and the same name as synthetic cathinones and has already been reported in a branded product called “Insomnia” 25.

• 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.
• Considering all the published cases, it can be concluded that most of these are fatal intoxications, and given the novelty of this type of substance, few cases have been shared with the scientific community.
• It is common to hear reports that it takes multiple people to restrain and sedate these patients.
• This section collects any data citations, data availability statements, or supplementary materials included in this article.
• For 5-HIAA/5-HT ratios, LgA self-administration of both synthetic cathinones lowered 5-HIAA/5-HT compared to ShA groups.
• The combination of a high body temperature and extreme muscle overactivity can cause other metabolic problems to happen in the body.
• It can be consumed through oral, intravenous, rectal, and nasal (insufflation and inhalation) routes.

What are the symptoms of flakka abuse?

In contrast, self-administration of 4MMC during LgA conditions decreased 5-HT in all brain regions except thalamus and decreased 5-HIAA in most brain regions compared to naïve (Table 1 and Fig. 3). Small, but significant changes in DA levels for LgA groups compared to naïve were found in select brain regions where α-PVP decreased DA levels in thalamus, whereas 4MMC increased DA levels in hypothalamus and thalamus. The most striking effects of condition were large elevations of DOPAC and HVA levels in striatum that were noted following LgA self-administration of both α-PVP and 4MMC.

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

• Significant reductions were also seen in H9c2(2-1) cells between 10 and 300 μM, and in SH-SY5Y, Hep G2, and RPMI 2650 cells between 25 and 300 μM after 72-h incubation (Fig. 6b).
• 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.
• 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).
• Flakka is a synthetic cathinone with effects and a chemical makeup similar to bath salts and CNS stimulants.
• Alpha-PHP or PV-7, as mentioned above, is a synthetic stimulant of the cathinones class, which is part of the pyrovalerone derivatives subgroup 19,60.
• Furthermore, it was noteworthy that 4MMC decreased 5-HT and 5-HIAA levels, whereas α-PVP increased 5-HIAA levels.

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. Thus, in 2020, the International Narcotics Control Board (INCB) listed α-PHP as a schedule II drug on the list of Psychotropic Substances under International Control following the Convention on Psychotropic Substances of 1971 36,37. In addition, in 2022, the Drug Enforcement Administration (DEA), part of the Department of Justice of the United States of America (USA), updated the schedules of controlled substances, placing α-PHP in schedule I 38. Furthermore, α-PHP is in class B in the United Kingdom, and it is illegal in China, Sweden, Poland, and Italy 19. In contrast, since it was first time reported in 2016, α-PiHP was placed in schedule II in March 2023 through the Convention of Psychotropic Substances of 1971 by the INCB.

These findings are consistent with a past study showing that ShA 4MMC self-administration did not alter DA, DOPAC, or HVA in striatum (Motbey et al., 2013). Thus, LgA synthetic cathinone self-administration for 21 days models most neurochemical changes predicted by the Koob and Volkow hypothesis for the binge and intoxication stage. 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). Thus, although abuse liability assessment of these individual drugs is now emerging, assessment of the effects and abuse potential of combinations of these drugs will be more difficult yet should be a central focus of future research.

Adverse Effects

Using a discrete trials current intensity threshold intracranial self-stimulation procedure, the present study assessed the effects of 2 common second-generation synthetic cathinones, α‐pyrrolidinopentiophenone (0.1–5mg/kg) and 4-methyl-N-ethcathinone (1–100mg/kg) on brain reward function. Use of synthetic cathinones, which are designer stimulants found in “bath salts,” has increased dramatically in recent years. Following governmental bans of methylenedioxypyrovalerone, mephedrone, and methylone, a second generation of synthetic cathinones with unknown abuse liability has emerged as replacements. Many studies measure the neurochemical effects of stimulants of abuse during direct drug effects (Ahmed et al., 2004; Mantsch et al., 2004), which does not provide information alpha-pyrrolidinopentiophenone function on lasting brain changes.

In contrast, other studies measured neurochemical effects several days after the last drug exposure (Briand et al., 2008; Hadlock et al., 2011; Schwendt et al., 2009), which may be during withdrawal. Brain tissue was collected approximately 24 h after the last drug exposure in this study and the past companion studies (Marusich et al., 2019a; Marusich et al., 2019b). While effects on DA were largely absent in this study, self-administration of either synthetic cathinone altered 5-HT and 5-HIAA levels. The serotonergic effects of 4MMC were expected because it releases 5-HT (Baumann et al., 2012).

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

These patients are a threat to themselves, the people around them, and the first responders (police, EMS) who are there to help them. It is common to hear reports that it takes multiple people to restrain and sedate these patients. Rescue crews and emergency department staff need to give sedatives to these patients to calm them and make them safe. Flakka is a dangerous drug that has many bad side effects, mostly including changes in behavior or mood. Various instances of “Man on Flakka” have been captured in videos on news channels and social media platforms such as YouTube. 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.

Communicating therapeutic indication information in direct-to-consumer television ads for prescription cancer drugs

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. 2016).

The Koob and Volkow hypothesis of drug abuse posits that treatment needs may differ based on the amount of drug consumed over time, and that stimulant-induced neurochemical changes may occur at different times for different brain regions or neurotransmitter systems (Koob and Volkow, 2010). Thus, ShA self-administration does not model the expected changes in neurochemistry for stages of drug abuse based on Koob and Volkow’s hypothesized model (Koob, 2010; Koob and Volkow, 2010; Marusich et al., 2019a). Alpha-PHP and -PiHP, as with many others synthetic cathinones, are currently not only drugs with a high power of abuse and addiction, but also substances with a very high rate of toxicity and mortality. This review aimed to bring together all the information on the two pyrrolidine derivates, α-PHP and α-PiHP, covering legislative, physicochemical, toxicological, and analytical aspects.