Abstract

3,4-methylenedioxypyrovalerone (MDPV) is classified as a Schedule I controlled substance by the DEA. Substances in this category are considered to have no accepted medical use in the United States, exhibit a significant risk of abuse, and lack established safety for use even under medical supervision. MDPV is also recognized as a hallucinogenic substance. This article presents a comprehensive overview of MDPV, including its general information, physico-chemical properties, pharmacology in recreational use, effects and symptoms, toxicity, use street names, prices and approximate dosage, dangerous interactions, legal status, synthesis of MDPV, conclusion, and bibliography.

Numerous samples seized in Treviso, including powders, agglomerated powders, and tablets, are displayed in Figure 0. The contents of these samples include MDPV, 4-FA, cocaine, and either lidocaine or procaine. The seizure was conducted by the Police Department of Treviso.

The Full Ride – An MDPV Trip Report

General Information About MDPV [1-6]

• Other synonyms names of MDPV are: Methylenedioxypyrovalerone; 3,4-methylenedioxypyrovalerone; 1-(1,3-Benzodioxol-5-yl)-2-(1-pyrrolidinyl)-1-pentanone; (RS)-1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-yl)pentan-1-one
• IUPAC Name of MDPV: 1-(1,3-benzodioxol-5-yl)-2-pyrrolidin-1-ylpentan-1-one
• CAS numbers are 687603-66-3 (free base); 24622-62-6 (hydrochloride salt); 1388142-27-5 (R-enantiomer base); 1388142-28-6 (S-enantiomer base)
• Trade names are Ivory Wave; Energy 1; Monkey Dust
• DEA Code Number 7535 (DEA schedule I controlled substance)

Physico-Chemical Properties of MDPV [1-6]

• Molecular Formula C₁₆H₂₁NO₃
• Molar Weight 275.34 g/mol
• Melting Point 238-239°C with decomposition
• Solubility: Soluble in chloroform, methanol, deionized water (3,4-Methylenedioxypyrovalerone hydrochloride)
• Color/Form: White or light tan powder; Fine white or off-white powder; white-tan crystalline hygroscopic powder

Structural formula present on Figure 2.

General Information of MDPV, Recreational Use and Pharmacology [1, 5-10]

MDPV, or 3,4-Methylenedioxypyrovalerone, is a synthetic stimulant belonging to the cathinone and pyrrolidine classes. It is an analog of a-PVP, developed in the 1960s for treating chronic fatigue and as an appetite suppressant, but it led to issues of abuse and dependence.

Despite some structural similarities, MDPV’s effects differ significantly from those of other methylenedioxy phenylalkylamines like MDMA. Instead, MDPV primarily produces classic stimulant effects, with only mild entactogenic properties.

Structurally, MDPV is related to cathinone, an active compound found in the khat plant, as well as to 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine, and other Schedule I phenethylamines. Like several substances in this class, MDPV acts as a central nervous system (CNS) stimulant and has also been reported to induce hallucinogenic effects.

Crystalline solid possible of the MDPV can be seen in the picture provided in Figure 3.

MDPV is believed to function mainly as a powerful norepinephrine-dopamine reuptake inhibitor. By reducing the reuptake of these neurotransmitters, MDPV increases their concentrations in the synaptic cleft—the space between neurons.

This inhibition leads to enhanced and prolonged dopaminergic and noradrenergic signaling at the receptors on the postsynaptic neuron. While serotonin also contributes to MDPV’s effects, its role is significantly less pronounced. The rapid increase in neurotransmitter levels in the brain is thought to be responsible for the euphoric effects associated with MDPV.

Due to its reuptake inhibition rather than releasing properties, MDPV is more similar in action to cocaine or methylphenidate than to amphetamine. In contrast, amphetamine primarily acts as an agonist that promotes the release of dopamine and norepinephrine through the activation of the TAAR1 receptor.

Effects and symptoms of MDPV Use [5, 7-10]

The primary psychological effects of MDPV last approximately 3 to 4 hours, while aftereffects such as tachycardia, hypertension, and mild stimulation can persist for 6 to 8 hours. High doses may lead to intense, prolonged panic attacks in users who are intolerant to stimulants, and there are anecdotal reports of psychosis related to sleep deprivation and addiction at higher doses or more frequent usage. Users often experience strong cravings to re-dose.

MDPV can be administered through various routes, including oral consumption, insufflation, smoking, rectal use, and intravenous injection. It is reportedly active at doses of 3–5 mg, with typical dosages ranging from 5 to 20 mg.

Research in mice has shown that repeated exposure to MDPV not only induces anxiety but also increases aggressive behavior, a phenomenon also noted in humans. Similar to MDMA, MDPV appears to accelerate adaptation to repeated social isolation.

There is evidence of cross-sensitization between MDPV and cocaine. Both substances can restore drug-seeking behavior for each other, although relapse is more pronounced with the drug initially used. Additionally, memories associated with MDPV take longer to extinguish. In MDPV-treated mice, a priming dose of cocaine triggers significant neuroplastic changes, indicating a heightened vulnerability to abuse.

Chronic use of MDPV is particularly concerning, as it can lead to severe addiction and a high potential for abuse, resulting in psychological dependence for some users. When addiction develops, stopping usage abruptly can trigger cravings and withdrawal symptoms. The risk of addiction is significant, as MDPV often leads to compulsive redosing and can produce highly unpleasant comedown effects.

Drug Zombie ‘Flakka’ (MDPV) Police Full Rare Video 2017

All effects in different categories [5, 7]

Physical effects

• Stimulation
• Stamina enhancement
• Abnormal heartbeat
• Increased heart rate – Higher doses of MDPV can create a significant and often dangerous increase in heart rate and blood pressure.
• Muscle contractions
• Muscle spasms
• Appetite suppression
• Headaches
• Gustatory hallucinations
• Diarrhea – Some users have reported experiencing diarrhea while under the influence of MDPV, although this seems to be a relatively uncommon effect.
• Nausea – Some users have reported experiencing nausea while under the influence of MDPV, although this seems to be a relatively uncommon effect.
• Restless leg syndrome

Auditory effects

• Auditory distortion
• Auditory hallucination

After effects

The effects which occur during the offset of a stimulant experience generally feel negative and uncomfortable in comparison to the effects which occurred during its peak. This is often referred to as a “comedown” and occurs because of neurotransmitter depletion. Its effects commonly include:

• Anxiety
• Cognitive fatigue
• Depression
• Irritability
• Motivation suppression
• Thought deceleration
• Wakefulness

It should be noted that many users consider the after effects of MDPV to be significantly more unpleasant if compulsively redosed.

Cognitive effects

The general cognitive effects of MDPV can be described as being similar to those of other typical stimulants. At common dosages, the MDPV high is described as being euphoric and slightly empatheogenic in its effects, causing increased motivation, sociability, sexual desire and concentration. Higher doses of MDPV, however, can intensify numerous negative effects such as anxiety and disorganized thoughts; at extremely high doses or continued use, delusions and psychosis become likely.

• Anxiety
• Cognitive euphoria
• Compulsive redosing – MDPV is extremely potent in this effect; it has been shown that some users end up redosing, even if the negative effects outweigh the positives.
• Confusion – This effect is prominent at higher doses and after long periods of staying awake on the drug.
• Creativity enhancement
• Delusions – This effect can also manifest at high doses.
• Ego inflation
• Empathy, love, and sociability enhancement – MDPV’s effects in this regard are similar to, but weaker than, those of MDMA.
• Focus enhancement
• Increased libido
• Motivation enhancement
• Paranoia
• Stamina enhancement
• Psychosis – High doses of MDPV have been known to induce states of psychosis at a more frequent rate than most other stimulants.
• Time distortion – This can be described as the experience of time speeding up and passing much quicker than it usually would when sober.
• Thought acceleration
• Thought organization – Mainly observed with low to common doses.
• Thought disorganization – This effect manifests and is also intensified at higher doses.
• Wakefulness – Strong wakefulness is reported at high doses and can last for many hours after long periods of use.

Toxicity and harm potential

MDPV has a relatively brief history of human use, with limited documentation prior to 2004. Initially considered a potential alternative to existing stimulants due to a perceived lower risk of toxicity, MDPV has not undergone extensive clinical study for many decades. However, recent research on cases of persistent psychosis linked to chronic MDPV use indicates promising recovery rates for individuals treated with certain antipsychotics and first-line antihistamines. Currently, there is no conclusive evidence regarding the neurotoxicity of MDPV in the human brain.

Anecdotal reports from users suggest that low doses of MDPV, when taken sparingly and alone, may not result in negative health effects, though this cannot be guaranteed.

In vitro and in vivo studies have shown that MDPV shares properties similar to methamphetamine and cocaine, often proving to be more potent than these stimulants in various aspects. The overstimulation of dopamine and norepinephrine caused by MDPV, combined with its potential inability to trigger compensatory serotonergic activity, can lead to hostile and psychotic reactions. Such behaviors have been observed in emergency situations and have garnered significant media attention, particularly following incidents where individuals under the influence of MDPV committed violent acts. It remains unclear whether these individuals had pre-existing mental health conditions or were using other substances concurrently.

Lethal dosage

The precise lethal dosage of MDPV remains unknown, and no formal studies have been conducted on humans. One report suggested a lethal dose of 0.4 micrograms per milliliter for a 39-year-old male based on post-mortem findings; however, this information is highly individual and too variable to draw meaningful conclusions.

MDPV can be detected in blood, plasma, or urine using gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry, which can confirm poisoning in hospitalized patients or serve as evidence in medicolegal death investigations. Typically, blood or plasma concentrations of MDPV in recreational users range from 10 to 50 μg/L, exceed 50 μg/L in intoxicated individuals, and can surpass 300 μg/L in cases of acute overdose.

Street Names, Prices and Approximate Dosage [1, 5, 7-10]

MDPV powder present on Figure 4.

MDPV has been identified in various products marketed as “bath salts,” “plant food/fertilizer,” and sometimes even “ecstasy.” It is known on the street by names such as Ivory Wave, Energy 1, and Monkey Dust.

Dosage Guidelines:

• Threshold: 2 mg
• Light: 4 – 8 mg
• Common: 8 – 14 mg
• Strong: 14 – 25 mg
• Heavy: 25 mg and above

Duration of Effects:

• Total Duration: 2 – 7 hours
• Onset: 15 – 30 minutes
• Peak Effects: 1 – 4 hours
• Offset: 0.5 – 2 hours
• Aftereffects: 2 – 48 hours

Pricing:

Reports from six countries indicate varying prices for MDPV:

• France: EUR 2–15 per gram
• Hungary: EUR 13.5 (quantity unspecified)
• Italy: EUR 14.95 for 0.5 g to EUR 169 for 10 g
• Netherlands: EUR 35 per gram and EUR 160 for 5 g (from forum discussions)
• Romania: EUR 25 (quantity unspecified)
• Spain: EUR 50–60 per gram when sold as cocaine, and EUR 20 per gram when sold as MDPV

Dangerous interactions [5, 7]

Stimulants: Combining MDPV with other stimulants can be particularly hazardous, as it may elevate heart rate and blood pressure to dangerous levels.

25x-NBOMe & 25x-NBOH: These compounds are highly stimulating and can put significant physical strain on the body. Mixing them with MDPV should be strictly avoided due to the risk of excessive stimulation, which could lead to increased blood pressure, vasoconstriction, panic attacks, thought loops, seizures, and even heart failure in extreme cases.

Alcohol: Mixing alcohol with stimulants poses risks due to the potential for accidental over-intoxication. Stimulants can mask alcohol’s depressant effects, making it difficult for users to gauge their level of intoxication. Once the stimulant effect wears off, the unopposed depressant effects can lead to blackouts and severe respiratory depression. If combining, users should strictly limit their alcohol intake to a certain amount per hour.

DXM (Dextromethorphan): Combining MDPV with DXM should be avoided due to DXM’s effects on serotonin and norepinephrine reuptake. This combination increases the risk of panic attacks and hypertensive crises, as well as serotonin syndrome, especially with other serotonin releasers like MDMA, methylone, or mephedrone. It’s important to monitor blood pressure carefully and avoid strenuous activities.

MDMA: The neurotoxic effects of MDMA are likely to be amplified in the presence of other stimulants. There is also an increased risk of excessive blood pressure and heart strain, leading to cardiotoxicity.

MXE (Methoxetamine): Reports suggest that combining MDPV with MXE may dangerously raise blood pressure and heighten the risk of mania and psychosis.

Dissociatives: Both MDPV and dissociatives carry risks of delusions, mania, and psychosis, and these risks may be magnified when used together.

Tramadol: Tramadol is known to lower the seizure threshold, and combining it with stimulants may further increase this risk.

MAOIs (Monoamine Oxidase Inhibitors): Mixing MDPV with MAOIs can lead to dangerously elevated levels of neurotransmitters like dopamine, which may result in fatal consequences. Examples include Syrian rue, Banisteriopsis caapi, and certain antidepressants.

Cocaine: Combining MDPV with cocaine may significantly increase the strain on the heart, raising the risk of cardiovascular complications.

Legal Status [1, 5]

• European Union: In September 2014, the European Council mandated that MDPV be subjected to control measures and criminal penalties by October 2, 2015.
• Australia: In Western Australia, MDPV has been banned under the Poisons Act 1964, added to Appendix A Schedule 9 as of February 11, 2012. The maximum penalty for selling or supplying MDPV is a $100,000 fine or 25 years in prison, while users can face fines of $2,000 or up to two years in jail.
• Austria: MDPV has been illegal to possess, produce, or sell since June 26, 2019, under the Suchtmittelgesetz (SMG).
• Belgium: MDPV was classified as a controlled substance on March 20, 2013.
• Brazil: MDPV is illegal to produce, sell, or possess, as it is listed on Portaria SVS/MS nº 344.
• Bulgaria: Controlled under the Narcotic Substances Control Law since February 2011.
• Canada: On June 5, 2012, MDPV was added to Schedule I of the Controlled Drugs and Substances Act, becoming law on September 26, 2012.
• Croatia: MDPV is classified as a controlled substance.
• Cyprus: MDPV is categorized as a Class B controlled substance under the cathinones catch-all clause.
• Czech Republic: MDPV is recognized as a controlled substance.
• Denmark: Classified as a controlled substance.
• Estonia: MDPV has been a controlled substance since November 29, 2010.
• Finland: Listed as a controlled substance in Appendix IV since June 28, 2010.
• France: MDPV became a controlled substance on August 2, 2012.
• Germany: Controlled under Anlage II BtMG (Narcotics Act, Schedule II) since July 26, 2012. Manufacturing, possessing, or distributing MDPV without a license is illegal.
• Hungary: MDPV is categorized as a Schedule A controlled psychotropic substance.
• Ireland: Covered under the Misuse of Drugs Acts since May 11, 2010.
• Italy: MDPV was classified as a controlled substance on December 29, 2011.
• Latvia: MDPV is a controlled substance.
• Luxembourg: Classified as a controlled substance since July 30, 2012.
• Norway: MDPV became a controlled substance on February 14, 2013.
• Poland: MDPV is recognized as a controlled substance.
• Slovakia: Classified as a Schedule I controlled psychotropic substance since March 1, 2011.
• Slovenia: MDPV is classified as a controlled substance.
• Sweden: MDPV is a controlled substance. A notable case involved a 33-year-old man sentenced to six years in prison for possessing 250 grams prior to its criminalization.
• Switzerland: MDPV is specifically named under Verzeichnis D as a controlled substance.
• Turkey: Classified as a controlled substance.
• United Kingdom: MDPV is categorized as a Class B drug due to the cathinone catch-all clause.
• United States: MDPV became a DEA-scheduled drug on October 21, 2011, following a temporary one-year ban. On December 8, 2011, the US House of Representatives voted to ban MDPV along with other synthetic drugs under the Synthetic Drug Control Act.

Synthesis of MDPV [11]

To a solution 1-(benzo[d][1,3]dioxol-5-yl)-2-bromopentan-1-one in diethyl ether was added pyrollidine dropwise over 5 min. The reaction was stirred for 3h at room temperature then quenched with water. The organic layer was separated and washed with bicarbonate solution, dried and solvent evaporated to give the racemic MDPV.

Synthesis of starting from 1-(benzo[d][1,3]dioxol-5-yl)-2-bromopentan-1-one and according to the scheme Figure 5.

MDPV – Mecke Reagent – Normal Test Kit -Bunk Police

Conclusion

MDPV, or 3,4-methylenedioxypyrovalerone, presents significant challenges in terms of its legal status, health effects, and potential for abuse. As a potent stimulant belonging to the cathinone class, MDPV has been associated with a range of dangerous physiological and psychological effects, particularly when used in combination with other substances. Its presence in products marketed as “bath salts” and other legal highs has led to increased scrutiny and regulation worldwide.

The global response to MDPV’s emergence has varied, with many countries implementing strict controls to mitigate its risks. These measures reflect growing concerns over the substance’s potential for addiction, psychosis, and severe cardiovascular complications. Despite some anecdotal claims of safety at low doses, the lack of comprehensive clinical research underscores the need for caution among users.

As regulatory bodies continue to adapt to the evolving landscape of psychoactive substances, it is crucial for users to remain informed about the risks associated with MDPV and similar compounds. Ongoing education, harm reduction strategies, and research into the long-term effects of MDPV are essential in addressing the public health challenges posed by this and other synthetic drugs. The complexities surrounding MDPV highlight the need for a balanced approach that prioritizes both individual safety and informed policy development.

Bibliography

1. https://en.wikipedia.org/wiki/Methylenedioxypyrovalerone
2. https://pubchem.ncbi.nlm.nih.gov/compound/20111961
3. https://www.chemspider.com/Chemical-Structure.32800898.html
4. https://www.chemspider.com/Chemical-Structure.32800897.html
5. https://psychonautwiki.org/wiki/MDPV
6. Joshua C. Yohannan and Joseph S. Bozenko The Characterization of 3,4-Methylenedioxypyrovalerone (MDPV). Microgram Journal, 2010, Volume 7, Number 1, pp. 12-15. https://www.dea.gov/documents/2010/2010-01/2010-01-01/characterization-34-methylenedioxypyrovalerone-mdpv-microgram
7. https://erowid.org/experiences/subs/exp_MDPV.shtml
8. https://www.euda.europa.eu/publications/joint-report/MDPV_en
9. https://erowid.org/chemicals/mdpv/mdpv.shtml
10. C. Michael White Mephedrone and 3,4-Methylenedioxypyrovalerone (MDPV): Synthetic Cathinones With Serious Health Implications. The Journal of Clinical Pharmacology, 2016, Volume 56, Issue 11, pp. 1319-1325. https://doi.org/10.1002/jcph.742 https://accp1.onlinelibrary.wiley.com/doi/epdf/10.1002/jcph.742
11. Masaki Suzuki, Jeffrey R. Deschamps, Arthur E. Jacobson, Kenner C. Rice Chiral Resolution and Absolute Configuration of the Enantiomers of the Psychoactive “Designer Drug” 3,4-Methylenedioxypyrovalerone. CHIRALITY, 2015, vol. 27 (4), pp. 287–293. https://doi.org/10.1002/chir.22423 https://onlinelibrary.wiley.com/doi/abs/10.1002/chir.22423