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

We did not find previous reports of ischemic strokes caused by α-PVP, although cardiovascular events such as myocardial infarction had been previously reported 3. Structurally and pharmacologically synthetic cathinones are similar to amphetamine, and physiological changes include hypertension, arrythmia, and vasoconstriction, which are known to cause strokes 5. Α-PVP poisoning was notably detected in Scandinavian countries, Denmark, and Iceland in 2012. In Finland, there were 162 cases of using various illegal drugs in 2012, confirmed by positive test results. In Sweden, there were 255 cases using various illegal drugs, confirmed by positive test results. From April 2013 to November 2015, there were 31 patients with α-PVP poisoning, of which 73% were known drug users 64.

• However, due to legal gaps, underground chemists started to exploit them in designer drugs 13,14,15.
• “Flakka” related cases, published or reported, including fatalities or intoxications, as well as seizures are reviewed.
• The results showed that α-PVP was in the same class and that α-PVP had the strongest selectivity for DAT and the lowest selectivity for SERT among the above-mentioned similar drugs.
• In a study with rodents, the acute administration of α-PVP at doses of 1–10 mg/kg by vapor or injection evoked a robust dose-dependent hyperlocomotion, likely involving enhanced signaling at dopamine D1 and D2 receptors 51.

Future research should focus on the development of analytical methods for rapid identification in both live and dead specimens. Flakka has emerged as a significant substance of abuse, yet research on its addictive properties is still limited due to its relatively recent appearance on the drug scene. Despite this, there is a strong consensus among experts that Flakka has a high potential for abuse, dependence, and addiction.

LgA self-administration of α-PVP increased 5-HIAA levels in all brain regions, compared to control. In contrast, both LgA and ShA 4MMC self-administration decreased 5-HT and 5-HIAA levels in most brain regions. LgA exposure to both synthetic cathinones increased DOPAC levels in hypothalamus and striatum, and increased HVA levels in striatum compared to control. LgA self-administration of either synthetic cathinone produced region-specific increases in NE levels, whereas ShA self-administration lowered NE levels in select locations compared to control. Kolesnikova and coworkers characterized the behavioral effects of α-PVP in adult zebrafish following acute (1, 5, 25, and 50 mg/L for 20 min) and chronic (1, 5, and 10 mg/L for seven days) treatments 43. Overall, acute exposure to α-PVP evoked psychostimulant (but not anxiolytic-like) effects in this novel zebrafish tank test, with characteristic and stereotypic ‘side-to-side’ bottom swimming at 5, 25, and 50 mg/L.

6. Clinical Course and Health Risks

The range of chemical structures of these compounds is very broad and constantly changing. The initial effects of taking Flakka are similar to those of bath salts and methamphetamines. This includes feelings of euphoria, heightened focus, increased sex drive, and being sociable. When Flakka is abused in high amounts it can cause users to have paranoid, violent, and bizarre behavior, again similar to bath salt abuse. Nelson et al. 53 studied the stereoselective effects of α-PVP, and the results showed that the adverse effects of racemic α-PVP were mediated primarily by the S isomer.

Alpha-pyrrolidinovalerophenone (α-PVP), or “flakka” by its street name, is a synthetic stimulant used recreationally. Α-PVP is related to other cathinone derivates often commonly referred alpha-pyrrolidinopentiophenone to as “bath salts,” and the mechanism of action resembles that of cocaine and amphetamine by inhibiting dopamine and norepinephrine reuptake 1. Unlike older drugs, the adverse effects of newer designer drugs are not as well known.

For Immediate Treatment Help Call 800-526-5053

Once a person who has misused Flakka is in a state where they are not a danger to themselves and others, a full diagnosis and course of treatment can be prescribed by a clinician or doctor. 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. In a study with rodents, the acute administration of α-PVP at doses of 1–10 mg/kg by vapor or injection evoked a robust dose-dependent hyperlocomotion, likely involving enhanced signaling at dopamine D1 and D2 receptors 51. Human psychopharmacological effects of α-PVP occur 10 min after a single dose (typically between 15 and 300 mg), peaking within 10–40 min and lasting for 2–3 h.

Illegal Drug Addiction

The normal urine drug screen used at the emergency departments in Finland does not demonstrate the use of synthetic drugs. As this case demonstrates, patients seeking medical aid sometimes willingly share information about illicit drug use, if only they are asked. Law enforcement agencies and health care providers have expressed significant concerns about the widespread use of flakka, particularly among younger demographics and in clubbing scenes where synthetic drugs are more prevalent.

Treatment Options for Flakka Addiction

In contrast, Flakka is primarily composed of alpha-Pyrrolidinopentiophenone (alpha-PVP). This difference in chemical structure contributes to variations in their effects and potential for addiction. Alpha-PVP is known for producing intense stimulation and can lead to extreme behavioral changes, including agitation and violent outbursts. 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. Flakka also has a high potential for overdose, especially when vaporized as the exact amount being taken is hard to quantify. The onset of a Flakka overdose is often rapid and can cause heart problems, aggressive behavior, and psychosis.

Vaporizing drugs in e-cigarettes is becoming a common method of administration for synthetic cathinones and classical stimulants. This latter route of administration leads to a rapid introduction into the blood stream, resulting in a high risk of overdose. The drug has been reported to cause depression, panic attacks, chest pains, paranoia, hallucinations, aggressive behavior, self-injury behaviors (including suicide), and prolonged psychosis 31. New structures have new properties and thus create unique behavioral characteristics during intoxication. It can be assumed that the tendency towards the use of new drugs will grow and that there will be an increasing number of cases in clinical practice.

But like “bath salts,” a group of related synthetic drugs that were banned in 2012, flakka has the potential to be much more dangerous than cocaine. Alpha-pyrrolidinovalerophenone (α-PVP) is a designer drug, the mechanism of action of which resembles that of cocaine and amphetamine. We present a case report of an acute ischemic stroke following the recreational use of α-PVP.

What are the Long-Term Effects of Flakka?

• Data are only available from users who experience these possible hazardous consequences 10.
• 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.
• Flakka was added to the Schedule I list in 2014 by the Drug Enforcement Administration (DEA).
• A synthetic drug known on the streets as “Flakka” (α-pyrrolidinovalerophenone, α-PVP) has become popular in the United States.

Prescriptions of aspirin 100 mg and atorvastatin 10 mg once per day were given, and the patient was advised to continue occupational therapy at the local healthcare center to rehabilitate right arm functions. CT angiography of the head and neck arteries showed no dissection or other signs of trauma of the carotid or vertebral arteries, and no critical stenosis. In the distal part of the basilar artery, either vasospasm or stenosis due to atherosclerosis was suspected. In 2015, the European Monitoring Center for Drugs and Drug Addiction (EMCDDA) conducted a risk assessment for α-PVP. According to the results, on June 27, 2016, the European Council decided to enact control measures for α-PVP that applied to all member states.

This information revealed a interindividual dissimilarity in the main human metabolism of α-PVP, via a decrease of the ketone set or oxidation on position 2’’ of the pyrrolidine ring. There have been no experimental studies on the chronic health impact of α-PVP and/or its metabolites in humans. Similarly, Schindler et al. 54 investigated the neurochemical, behavioral, and cardiovascular effects of racemic α-PVP and its enantiomers in male rats. The results showed that S-α-PVP is slightly more potent than racemic α-PVP, while R-α PVP is 10 to 20 times less effective in blocking dopamine and norepinephrine uptake. When tested at the same dose, S-α-PVP produced a greater effect than racemic α-PVP. Racemic and S-α-PVP were self-administered by rats at a 0.03 mg/kg injection, whereas R-α-PVP was self-administered at a 10-fold higher dose.

The ischemic lesions were located in the middle cerebral artery and deep watershed areas of the left cerebral hemisphere. Occupational therapy and physiotherapy were initiated, and the patient was discharged with only a mild right hemiparesis. In order to explore whether synthetic cathinones have a direct myotoxicity, Zhou et al. 50 investigated the potential toxicological effects of synthetic cathinones on C2C12 myoblasts (a mouse skeletal muscle cell line). After exposing C2C12 myoblasts to α-PVP and other drugs for 1 h or 24 h, the cell membrane integrity, ATP content, mitochondrial oxygen consumption, and mitochondrial superoxide radical anion production were measured. The results showed that α-PVP consumes ATP, causes a loss of cell membrane integrity, and increases superoxide radical anion levels in C2C12 myoblasts in a concentration-dependent manner. In addition, as a pyrrolidone derivative, α-PVP also impairs basic and maximum cellular respiration, suggesting an abnormal mitochondrial function.

High-performance liquid chromatography/high-resolution mass spectrometry (HPLC/HRMS) analyses of zebrafish brains showed detectable levels of α-PVP following its acute administration, likely underlying the observed behavioral effects. The signal peaks for α-PVP in the brain were consistent with the systemic concentrations of the drug that were given. Collectively, these findings support zebrafish sensitivity to α-PVP and show some parallels with its effects in mammals. This study also suggests that aquatic models based on zebrafish can help to further examine the CNS effects evoked by α-PVP and to screen for related new synthetic psychoactive drugs. However, no experimental studies have been conducted to investigate the chronic impact of α-PVP on human health. In fact, knowledge on the long-term effects of α-PVP use in humans is lacking.

Alpha-PVP has been available in the European Union since at least February 2011 and has been detected in 28 Member States, Turkey and Norway. In most cases it has been seized as a powder, but other forms including tablets have been detected. If you or someone you know is suffering from Flakka dependence or addiction, then contact a treatment provider today to discuss what options are available.

Therefore, in addition to the effects on the sympathetic nervous system and vigorous muscle exercise, the direct effects of α-PVP on skeletal muscle mitochondria may lead to myotoxicity in susceptible cathinone users. There is increasing evidence that α-PVP has a cocaine-like stimulating effect. In fact, it is more effective than common psychostimulants such as cocaine and amphetamine 48,49. The results showed that α-PVP was in the same class and that α-PVP had the strongest selectivity for DAT and the lowest selectivity for SERT among the above-mentioned similar drugs. Collins and coworkers 49 used four adult male rhesus monkeys to study the self-administration of MDPV and α-PVP and directly compared the results with the effects of cocaine and methamphetamine.