The effects and toxicity of cathinones from the users' perspectives: A qualitative study

Assi, Sulaf; Gulyamova, Nargilya; Kneller, Paul; Osselton, David

doi:10.1002/hup.2610

Cited by 33 publications

(24 citation statements)

References 25 publications

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“…Clinical case studies and poison control center reports indicate cathinone compounds can acutely produce extremely high blood pressure, confusion, psychotic-like and/or aggressive behaviors (John et al, 2014;Penders et al, 2012) as well as more life-threatening effects such as convulsions, myocardial infarction, arrhythmias, and cardiac arrest, metabolic acidosis and prolonged rhabdomyolysis even after few doses (Forrrester 2012;Spiller et al, 2011;Paillet-Loilier 2014;Sivagnanam, 2013). These are very similar to self-reported adverse effects found on user forums, such as anxiety, hallucinations, nervousness, paranoia, angina, myocardial infarction, tachycardia, and difficulty urinating (Assi et al, 2017).…”

Section: Introductionsupporting

confidence: 78%

Locomotor activity and discriminative stimulus effects of five novel synthetic cathinone analogs in mice and rats

Gatch

Dolan

Forster

2019

Drug and Alcohol Dependence

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Background: The development of novel synthetic psychoactive substances continues to accelerate. There are little or no data on the pharmacological mechanisms, behavioral effects, or abuse liability of many of the newer compounds, despite increasing reports of severe adverse effects in recreational users. Methods: The current study investigated the discriminative stimulus and locomotor stimulant effects of a group of synthetic cathinone analogs: N-ethylpentylone, dimethylone, dibutylone, clephedrone, 3',4'-tetramethylene-α-pyrrolidinovalerophenone (TH-PVP). Locomotor activity was assessed in an open-field assay using Swiss-Webster mice. Discriminative stimulus effects were assessed in Sprague-Dawley rats trained to discriminate either cocaine, methamphetamine or MDMA from vehicle. Results: N-ethylpentylone, dimethylone, dibutylone and clephedrone increased locomotor activity. Maximal effects were similar among the test compounds. Relative potencies were: methamphetamine>N-ethylpentylone>clephedrone> dimethylone>MDMA> cocaine>dibutylone. TH-PVP dose-dependently depressed locomotor activity. N-ethylpentylone, dimethylone, dibutylone and clephedrone substituted fully for the discriminative stimulus effects of methamphetamine. N-ethylpentylone, dibutylone and clephedrone fully substituted for cocaine, whereas dimethylone produced a maximum of 67% drug-appropriate responding. Dimethylone, dibutylone and clephedrone fully substituted for MDMA, whereas N-ethylpentylone produced only 50% drug-appropriate responding. TH-PVP produced a maximum of 38% methamphetamine-appropriate responding, 50% cocaine-appropriate responding, and less than 1% MDMA-appropriate responding.

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Section: Introductionsupporting

confidence: 78%

Locomotor activity and discriminative stimulus effects of five novel synthetic cathinone analogs in mice and rats

Gatch

Dolan

Forster

2019

Drug and Alcohol Dependence

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“…The abuse of SCs poses serious public health concerns due to their high addiction potential and increasing number of fatalities [17,18]. Severe intoxications and death cases have been linked to the usage of butylone, pentylone, and MDPV [19][20][21][22][23][24][25], and the majority of cases have been connected to neuropsychiatric and neurological complications associated with SC toxicity [26,27]. In addition to the direct SC neurotoxicity effects, potential interactions, such as hyperthermia, toxic metabolites, excitoxicity, and neuroinflammation, may also contribute to SC-induced neurotoxicity [28].…”

Section: B C Amentioning

confidence: 99%

Synthetic Cathinones Induce Cell Death in Dopaminergic SH-SY5Y Cells via Stimulating Mitochondrial Dysfunction

Leong

Philp

Simone

et al. 2020

IJMS

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Increasing reports of neurological and psychiatric complications due to psychostimulant synthetic cathinones (SCs) have recently raised public concern. However, the precise mechanism of SC toxicity is unclear. This paucity of understanding highlights the need to investigate the in-vitro toxicity and mechanistic pathways of three SCs: butylone, pentylone, and 3,4-Methylenedioxypyrovalerone (MDPV). Human neuronal cells of SH-SY5Y were cultured in supplemented DMEM/F12 media and differentiated to a neuronal phenotype using retinoic acid (10 μM) and 12-O-tetradecanoylphorbol-13-acetate (81 nM). Trypan blue and lactate dehydrogenase assays were utilized to assess the neurotoxicity potential and potency of these three SCs. To investigate the underlying neurotoxicity mechanisms, measurements included markers of oxidative stress, mitochondrial bioenergetics, and intracellular calcium (Ca2+), and cell death pathways were evaluated at two doses (EC15 and EC40), for each drug tested. Following 24 h of treatment, all three SCs exhibited a dose-dependent neurotoxicity, characterized by a significant (p < 0.0001 vs. control) production of reactive oxygen species, decreased mitochondrial bioenergetics, and increased intracellular Ca2+ concentrations. The activation of caspases 3 and 7 implicated the orchestration of mitochondrial-mediated neurotoxicity mechanisms for these SCs. Identifying novel therapeutic agents to enhance an altered mitochondrial function may help in the treatment of acute-neurological complications arising from the illicit use of these SCs.

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“…In 2010, MEPH was classified as a controlled substance in some European countries, and 2 years later in the USA ( 7 ). Despite its ban, it has remained a popular recreational drug to this day ( 18 , 19 ).…”

Section: Introductionmentioning

confidence: 99%

Mephedrone (4-Methylmethcathinone): Acute Behavioral Effects, Hyperthermic, and Pharmacokinetic Profile in Rats

et al. 2018

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Mephedrone (MEPH) is a synthetic cathinone derivative with effects that mimic MDMA and/or cocaine. Our study in male Wistar rats provides detailed investigations of MEPH’s and its primary metabolite nor-mephedrone’s (nor-MEPH) pharmacokinetics and bio-distribution to four different substrates (serum, brain, lungs, and liver), as well as comparative analysis of their effects on locomotion [open field test (OFT)] and sensorimotor gating [prepulse inhibition of acoustic startle reaction (PPI ASR)]. Furthermore, in order to mimic the crowded condition where MEPH is typically taken (e.g., clubs), the acute effect of MEPH on thermoregulation in singly- and group-housed rats was evaluated. Pharmacokinetics of MEPH and nor-MEPH after MEPH (5 mg/kg, sc.) were analyzed over 8 h using liquid chromatography with mass spectrometry. MEPH (2.5, 5, or 20 mg/kg, sc.) and nor-MEPH (5 mg/kg, sc.) were administered 5 or 40 min before the behavioral testing in the OFT and PPI ASR; locomotion and its spatial distribution, ASR, habituation and PPI itself were quantified. The effect of MEPH on rectal temperature was measured after 5 and 20 mg/kg, sc. Both MEPH and nor-MEPH were detected in all substrates, with the highest levels detected in lungs. Mean brain: serum ratios were 1:1.19 (MEPH) and 1:1.91 (nor-MEPH), maximum concentrations were observed at 30 min; at 2 and 4 h after administration, nor-MEPH concentrations were higher compared to the parent drug. While neither of the drugs disrupted PPI, both increased locomotion and affected its spatial distribution. The effects of MEPH were dose dependent, rapid, and short-lasting, and the intensity of locomotor stimulant effects was comparable between MEPH and nor-MEPH. Despite the disappearance of behavioral effects within 40 min after administration, MEPH induced rectal temperature elevations that persisted for 3 h even in singly housed rats. To conclude, we observed a robust, short-lasting, and most likely synergistic stimulatory effect of both drugs which corresponded to brain pharmacokinetics. The dissociation between the duration of behavioral and hyperthermic effects is indicative of the possible contribution of nor-MEPH or other biologically active metabolites. This temporal dissociation may be related to the risk of prolonged somatic toxicity when stimulatory effects are no longer present.

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The effects and toxicity of cathinones from the users' perspectives: A qualitative study

Abstract: The Internet discussion forums provide useful sources of information regarding the effects and toxicity of cathinones, which can be taken into account when assessing the safety of drugs.

Cited by 33 publications

References 25 publications

Locomotor activity and discriminative stimulus effects of five novel synthetic cathinone analogs in mice and rats

Locomotor activity and discriminative stimulus effects of five novel synthetic cathinone analogs in mice and rats

Synthetic Cathinones Induce Cell Death in Dopaminergic SH-SY5Y Cells via Stimulating Mitochondrial Dysfunction

Mephedrone (4-Methylmethcathinone): Acute Behavioral Effects, Hyperthermic, and Pharmacokinetic Profile in Rats

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