Flakka Drug: Symptoms, Side Effects & Complications

Alpha-PHP is known as a recreational drug of abuse and has no pharmacological therapeutic purpose. Thus, it can be abused through oral, nasal, sublingual, rectal, or intravenous application. The following table shows the relationship between the consumed dose and the proportion of the effect triggered through the various routes of administration (Table 1) 19. Nowadays, the number of NPSs on the global market is increasing, after several years of stabilization, due to traffickers who continue to sustain their production. Consequently, the prevalence of their use is higher, especially in younger age groups 4,5. Synthetic cathinones are also labeled as ‘not for human consumption.’ These labels help hide the real reason for the product’s existence, so the drugs distribute easily.

• The strongest effect was observed at 300 μM of 4-F-PVP and 4-MeO-PVP, being 43 and 45% of positive control cytotoxicity, respectively (Fig. 3).
• Prominent sex differences emerged for NE levels in amygdala, hippocampus, PFC, and striatum for ShA groups (Fig. 4).
• Maximal response values represent the mean maximum intracranial self-stimulation (ICSS) threshold reduction (independent of dose)±95% confidence intervals.
• Amygdala, hippocampus, hypothalamus, prefrontal cortex (PFC), striatum, and thalamus were extracted, and tissue was analyzed with electrochemical detection and liquid chromatography mass spectrometry.
• In December of the same year, α-PiHP was formally submitted to the Early Warning System of EMCDDA, and in 2019, its concentration in biological specimens was determined for the first time in an intoxication case 24.
• As well as inducing psychotic episodes, Flakka may also cause hyperthermia, liver and renal failure, hypertension, narrowing of the blood vessels, irregular heartbeat, stroke, heart attack, suicidal ideation, coma, and death.
• In SH-SY5Y neuroblasts, only 4-F-PVP and 4-MeO-PVP used at 300 μM caused a slight elevation of extracellular LDH activity.

Materials and Methods

As flakka is a new drug, there is still a lot to learn about the treatment of the substance. Users have reported that the drug use of flakka can trigger intense and uncontrollable urges to ingest the drug again. As cathinones are hydrophobic alpha-pyrrolidinopentiophenone function molecules, they can cross cell membranes and the blood-brain barrier. This allows them to interact with the monoamine transporters in the synaptic cleft between neurons.

Is Weed a Depressant, Stimulant, or Hallucinogen?

In SH-SY5Y neuroblasts, only 4-F-PVP and 4-MeO-PVP used at 300 μM caused a slight elevation of extracellular LDH activity. In H9c2(2-1) cells the effect was more pronounced and significant at 200 and 300 μM for PVP and 100–300 μM for 4-F-PVP and 4-MeO-PVP. The strongest effect was observed at 300 μM of 4-F-PVP and 4-MeO-PVP, being 43 and 45% of positive control cytotoxicity, respectively (Fig. 3). PVP and its fluoro- and methoxy-substituted derivatives produced moderate and concentration- and time-dependent decline in the viability of SH-SY5Y, Hep G2, RPMI 2650, and H9c2(2-1) cells measured as mitochondrial activity. The observed effects varied among the studied cell lines and the tested compounds (Fig. 2).

In the concentration range of 10–300 μM, significant cytotoxic effects were observed in SH-SY5Y, Hep G2, and RPMI 2650 cells after 24-h incubation, and in SH-SY5Y and RPMI 2650 cells after 72-h incubation. However, at 25–300 μM, the viability of Hep G2 cells was affected only after 72-h incubation. In H9c2(2-1) cells, significant effects were observed at 100–300 μM, irrespective of the incubation time (Fig. 6c). 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).

Treatment Options for Flakka Addiction

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.

Fig. 1.

• 4MMC shows escalation of self-administration during LgA conditions (Nguyen et al., 2017b; Watterson et al., 2014).
• PV9 and its substituted analogs caused profound disruption of cell membranes in all assessed cell lines (Fig. 7).
• Flakka is a highly potent drug that can be snorted, injected, eaten, smoked, or vaporized in e-cigarettes.
• Synthetic cathinones are widely available throughout the U.S. (Baumann, 2014; DEA, 2017; Madras, 2017), and unintentional ingestion of synthetic cathinones is rising (Oliver et al., 2019).
• Both Flakka and bath salts are incredibly dangerous when abused, causing harmful side effects, overdose, death, and are addiction-forming.
• The most remarkable examples of α-pyrrolidinophenones include 3,4-methylenedioxypyrovalerone (3,4-MDPV) and α-pyrrolidinopentiophenone (α-PVP).

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).

Although many synthetic cathinone derivatives exist, 3,4-methylenedioxypyrovalerone (MDPV), mephedrone, or methylone, initially comprised approximately 98% of all synthetic cathinones encountered in US drug seizures (United States Department of Justice, 2011a). As of 2013, these first-generation synthetic cathinones are now permanently classified as Schedule I substances in the United States (United States of America, 2012; United States Department of Justice, 2013a). All statistically significant effects of sex on neurotransmitters are shown in Table 3 and Fig. ShA groups showed considerably more instances of sex differences than LgA and naïve groups. There were sex differences in 5-HT levels for ShA rats, with both synthetic cathinones producing greater 5-HT levels for females than males in amygdala and PFC (Table 4 and Fig. 4).

Α-PHP dose ranges and the respective intensity of the effect produced through the various routes of consumption 19. Received 2024 Mar 1; Revised 2024 Mar 20; Accepted 2024 Mar 20; Collection date 2024 Apr. As little is known about flakka, detoxing in the care of medical professionals is essential. The drug can also raise body temperature dangerously high, leading to kidney damage or failure. The cathinones also inhibit the reuptake of epinephrine, norepinephrine, and serotonin in the central nervous system. This is because the “comedown” after drug ingestion causes feelings of depression and being down.