The primary psychological effects have a duration of roughly 3 to 4 hours, with aftereffects such astachycardia,hypertension, and mild stimulation lasting from 6 to 8 hours.[7] High doses have been observed to cause intense, prolongedpanic attacks in stimulant-intolerant users,[7] and there are anecdotal reports ofpsychosis from sleep withdrawal and addiction at higher doses or more frequent dosing intervals.[7] It has also been repeatedly noted to induce irresistiblecravings to re-administer.[7][8]
Reported modalities of intake include oral consumption,insufflation,smoking,rectal andintravenous use. It is supposedly active at doses of 3 to 5mg, with typical doses ranging between 5 and 20mg.[7]
The long-term effects of MDPV on humans have not been studied, but it has been reported that mice treated with MDPV during adolescence show reinforcing behavior patterns to cocaine that are higher than the control groups. These behavioural changes are related to alterations of factor expression directly related to addiction. All this suggests an increased vulnerability to cocaine abuse.[9]
In April 2011, two weeks after being reported missing, two men in northwestern Pennsylvania were found dead in a remote location on government land. The official cause of death of both men washypothermia, but toxicology reports later confirmed that both Troy Johnson, 29, and Terry Sumrow, 28, had ingested MDPV shortly before their deaths. "It wasn't anything to kill them, but enough to get them messed up," the county coroner said. MDPV containers were found in their vehicle along with spoons, hypodermic syringes and marijuana paraphernalia. In April 2011, anAlton, Illinois, woman apparently died from an MDPV overdose.[10]In May 2011, the CDC reported a hospitalemergency department (ED) visit after the use of "bath salts" in Michigan. One person was reported dead on arrival at the ED. Associates of the dead person reported that he had used bath salts. His toxicology results revealed high levels of MDPV in addition to marijuana and prescription drugs. The primary factor contributing to death was cited as MDPV toxicity after autopsy was performed.[11] An incident ofhemiplegia has been reported.[12]
A total of 107 non-fatal intoxications and 99 analytically confirmed deaths related to MDPV between September 2009 and August 2013 were reported by nine European countries.[2]
Treatment in theemergency department forhypertensive emergency,tachycardia,agitation, orseizures consists of large doses oflorazepam in 2–4 mg increments every 10–15 minutes intravenously or intramuscularly. If this is not effective,haloperidol is an alternative treatment. It is suggested that the use ofbeta blockers to treat hypertension in these patients can cause an unopposed peripheral alpha-adrenergic effect with a dangerous paradoxical rise in blood pressure.[15]Electroconvulsive therapy (ECT) has been shown to improve persistent psychotic symptoms associated with repeated MDPV use.[16][17]
MDPV is much more potent thanamphetamine as an NDRI, with 23-fold higher potency fordopamine reuptake inhibition and 2.6-fold greater potency fornorepinephrine reuptake inhibition in rat brain synaptosomes.[3] With HEK293 cells expressing the monoamine transporters, MDPV was 568-fold more potent as a dopamine reuptake inhibitor and 12.5-fold more potent as a norepinephrine reuptake inhibitor than amphetamine.[6] The drug is also far more potent as an NDRI thancocaine andmephedrone in both rat brain synaptosomes and HEK293 cells.[3][6] MDPV is one of the most potent dopamine reuptake inhibitorsin vitro orin vivo known.[19] The only others that were more potentin vivo weredesoxypipradrol (2-DPMP) and3,4-dichloromethylphenidate (3-DCMP) andin vitro wasα-PVP.[19]
In addition to its monoamine reuptake inhibition, MDPV acts as a weaklyefficaciouspartialnorepinephrine–dopamine releasing agent (NDRA), withEmaxTooltip maximal efficacy values of 24% for bothnorepinephrine anddopamine in rat brain synaptosomes.[5][18] However, MDPV failed to produce any dopamine, norepinephrine, or serotonin release at a concentration of 100,000nM in HEK293 cells.[6][20]
MDPV has no record of FDA approvedmedical use.[21] It has been shown to produce robust reinforcing effects and compulsive self-administration in rats, though this had already been provisionally established by a number of documented cases of misuse and addiction in humans before the animal tests were carried out.[22][23] When assayed in mice, repeated exposure to MDPV causes not only ananxiogenic effect but also increasedaggressive behaviour, a feature that has already been observed in humans. As with MDMA, MDPV also caused a faster adaptation to repeatedsocial isolation in rodents.[24] A cross-sensitization between MDPV and cocaine has been evidenced.[25] Furthermore, both psychostimulants, MDPV and cocaine, restore drug-seeking behavior with respect to each other, although relapse into drug-taking is always more pronounced with the conditioning drug. Moreover, memories associated with MDPV require more time to be extinguished. Also, in MDPV-treated mice, a priming-dose of cocaine triggers significant neuroplasticity, implying a high vulnerability to its abuse.[26]
Molecularly, this is seen as demethylenation of methylenedioxypyrovalerone (CYP2D6), followed bymethylation of the aromatic ring viacatechol-O-methyl transferase.Hydroxylation of both the aromatic ring and side chain then takes place, followed by an oxidation of the pyrrolidine ring to the correspondinglactam, with subsequent detachment and ring opening to the correspondingcarboxylic acid.[31]
The hydrochloride salt exists as a very fine crystalline powder; it ishygroscopic and thus tends to form clumps, resembling something like powdered sugar. Its color can range from pure white to a yellowish-tan and has a slight odor that strengthens as it colors. Impurities are likely to consist of eitherpyrrolidine or alpha-dibrominated alkylphenones—respectively, from either excess pyrrolidine or incomplete amination during synthesis. These impurities likely account for its discoloration and fishy (pyrrolidine) orbromine-like odor, which worsens upon exposure to air, moisture, or bases.[32]
MDPV may be quantified in blood, plasma or urine by gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalized patients or to provide evidence in a medicolegal death investigation. Blood or plasma MDPV concentrations are expected to be in a range of 10–50 μg/L in persons using the drug recreationally, >50 μg/L in intoxicated patients, and >300 μg/L in victims of acute overdose.[33]
MDPV was first developed in the 1960s by a team atBoehringer Ingelheim.[35] It remained an obscure stimulant until around 2004 when it was reportedly sold as adesigner drug. In the US, products containing MDPV and labeled asbath salts were sold as recreational drugs in gas stations, similar to the marketing forSpice andK2 as incense, until it was banned in 2011.[36]
In 2010, a 33-year-old Swedish man was sentenced to six years in prison by anappellate court,Hovrätt, for possession of 250 grams of MDPV that had been acquired prior tocriminalization.[37]
In Western Australia, MDPV has been banned under the Poisons Act 1964, having been included in Appendix A Schedule 9 of the Poisons Act 1964 as from February 11, 2012. TheDirector of Public Prosecutions forWestern Australia announced that anyone intending to sell or supply MDPV faces a maximum $100,000 fine or 25 years in jail. Users face a $2000 fine or two years' jail. Therefore, anyone caught with MDPV can be charged with possession, selling, supplying or intent to sell or supply.[38]
Canadian Health Minister Leona Aglukkaq announced on June 5, 2012, that MDPV would be listed on Schedule I of the Controlled Drugs and Substances Act, which was realized on September 26, 2012.[39]
In the United States, MDPV is aDEA federally scheduled drug. On October 21, 2011, the DEA issued a temporary one-year ban on MDPV, classifying it as a schedule I substance. Schedule I status is reserved for substances with a high potential for abuse, no currently accepted use for treatment in the United States and a lack of accepted safety standards for use under medical supervision.[43]
Before the federal ban was announced, MDPV was already banned in Louisiana and Florida.[44] On March 24, 2011, Kentucky passed bill HB 121, which makes MDPV, as well as three other cathinones, controlled substances in the state. It also makes it a Class A misdemeanor to sell the drug, and a Class B misdemeanor to possess it.[45]
MDPV is banned inNew Jersey underPamela's Law. The law is named after Pamela Schmidt, aRutgers University student who was murdered in March 2011 by an alleged user of MDPV.[46] A toxicology report later found no "bath salts" in his system.[47]
On May 5, 2011,Tennessee GovernorBill Haslam signed a law making it a crime "to knowingly produce, manufacture, distribute, sell, offer for sale or possess with intent to produce, manufacture, distribute, sell, or offer for sale" any product containing MDPV.[48]
On July 6, 2011, the governor ofMaine signed a bill establishing fines for possession and penalties for trafficking of MDPV.[49]
On October 17, 2011, anOhio law banning synthetic drugs took effect barring selling and/or possession of "any material, compound, mixture, or preparation that contains any quantity of the following substances having a stimulant effect on the central nervous system, including their salts, isomers, and salts of isomers", listing ephedrine and pyrovalerone. It also specifically includes MDPV.[50] Four days after this Ohio law was passed, the DEA's national emergency ban was implemented.[43]
On December 8, 2011, under the Synthetic Drug Control Act, theUS House of Representatives voted to ban MDPV and a variety of other synthetic drugs that had been legally sold in stores.[51]
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