Doctors have to take this into consideration in order to provide appropriate treatments and minimize undesirable damage. Stimulant-induced neurochemical changes may occur at different times for different brain regions or neurotransmitter systems. This study sought to examine the behavioral and neurochemical effects of extended access to α-pyrrolidinopentiophenone (α-PVP) and 4-methylmethcathinone (4MMC). Amygdala, hippocampus, hypothalamus, prefrontal cortex (PFC), striatum, and thalamus were extracted, and tissue was analyzed with electrochemical detection and liquid chromatography mass spectrometry. Rats acquired self-administration of α-PVP and 4MMC, and LgA rats showed more escalation of self-administration than ShA rats. Synthetic cathinone administration produced several effects on neurotransmitters.

• Head MRI showed multiple new ischemic lesions in the left cerebral hemisphere (Fig. 1).
• In the course of the last four years, Flakka (α-PVP) has penetrated markets all over the world, especially the US, European states, Australia, and Japan.
• 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.
• The aim of this review is to summarize the current knowledge of this drug concerning its chemistry, synthesis, metabolism, pharmacology, and toxicology.
• The belief that Flakka or other “bath salt” use can turn you into a zombie or cannibal appears to have been a somewhat effective deterrent against use.

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.

An increasing number of people are being admitted to emergency wards due to the consequences of their use. This work mainly summarizes the history, synthesis, pharmacology, toxicology, structure–activity relationship, metabolism, clinical process and health risks, poisoning and death, forensic toxicology, and legal status of α-PVP. We hope this review will help bring more attention to the exploration of this substance in order to raise awareness of its negative impacts on humans. Α-PVP can be orally ingested, smoked, snorted, used parenterally, and also vaporized in e-cigarette devices.

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.

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.

The patient used a clean needle with a microfilter, which lowers the risk of embolic adulterants to be the direct cause of the ischemic stroke. The comprehensive evaluation ruled out other major causes of stroke, and the onset of the stroke was immediately after the α-PVP injection. The urine drug screen was only positive for benzodiazepines, which rules out other confounding substances. In some of the documented delusions, individuals’ experiences are of a typical paranoia, where the drug users feel they are being chased by a large group of people trying to kill them. 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.

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.

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.

Bath Salts (Synthetic Cathinones)

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.

Flakka: New Dangerous Synthetic Cathinone on the Drug Scene

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.

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.

MeSH terms

Internationally, the legal status of flakka varies by country, but many countries have taken steps to control its use due to its dangerous effects. Ark Behavioral Health offers 100% confidential substance abuse assessment and treatment placement tailored to your individual needs. It may, however, cause an excited delirium resulting in wild, unpredictable, and severely violent behavior in those under this drug’s influence.

• The patient used a clean needle with a microfilter, which lowers the risk of embolic adulterants to be the direct cause of the ischemic stroke.
• In the excited delirium state, restrained patients struggle to free themselves, scream, flail, and can even have seizures.
• Considered a new psychoactive substance (NPS), Flakka is part of a collection of black-market, lab-made drugs imported to the United States from China.
• In addition, national governments should take relevant measures in order to control the use of this novel dangerous drug.
• Flakka and other synthetic cathinones are known as New Psychoactive Substances (NPS).

Is Flakka illegal?

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.

Synthetic Cathinones History

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.

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 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.

“Flakka” related cases, published or reported, including fatalities or intoxications, as well as seizures are reviewed. The existing analytical methodologies for the determination of α-PVP in biological and postmortem samples are summarized, and its current legal status is reported. A synthetic drug known on the alpha-pyrrolidinopentiophenone streets as “Flakka” (α-pyrrolidinovalerophenone, α-PVP) has become popular in the United States. It is chemically similar to MDPV, also known as a bath salt, which was responsible for the increase in bizarre cases of intoxication and agitation in the United States several years ago 30.

In other words, Flakka is a type of bath salt, but not all bath salts are Flakka. Some bath salts may be more potent than Flakka, others less, and there is really no way of telling beforehand. Flakka, a street name for the inexpensive and dangerous “designer drug” Alpha-PVP, is one such newcomer. Manufacturers frequently mix α-PVP with cheap fillers such as caffeine or sugar to alter appearance and maximize profit. These additives rarely affect the psychoactive strength of the drug but can further complicate health risks. We are dedicated to transforming the despair of addiction into a purposeful life of confidence, self-respect and happiness.