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Case Report of Cathinone-Like Designer Drug Intoxication Psychosis and Addiction With Serum Identification
Abstract
The use of designer drugs commonly marketed as "Bath Salts" or "Energy" has dramatically risen in recent years. Fatalities and cases of aggressive behavior, even cannibalism have been recently reported in the media. However, these cases have been poorly documented. In this paper, we report a case of repetitive and similar acute psychotic episodes induced by Energy 3 intake. Comparative Analyses of Energy 3 sample and patient's serum by gas chromatography-mass spectrometry detected the presence of 2 synthetic cathinone derivatives: methylenedioxypyrovalerone and pentylone. Finally, this patient's clinical picture is characterized by the insidious development of dependence to this product. The absence of patient's personal addiction history, the late onset of this dependence, and its high intensity, suggest a high addiction potential of these substances.
... (Diestelmann et al. 2018) reported that two of their cases included patients that were described as psychotic with visual hallucinations, with MDPV plasma concentrations of 68 and 141 μg/L, respectively, and that both tested negative for presence of other substances with urine screening. Similarly, case reports of patients experiencing symptoms of psychosis after reported solo insufflation of SCs include a middle-aged male who experienced persecutory delusions after ingesting MDPV and pentylone-confirmed via mass spectrometry of blood serum (Thornton et al. 2012), and a young male who experienced hallucinations after MPDV and flephedrone ingestion, which was confirmed by blood and urine analysis (Sadeg et al. 2014). In conjunction with the mono-intoxication reported with the included articles, these case reports provide further support that SCs can elicit psychotic symptoms, although polysubstance abuse is more prevalent and often a necessary consideration when determining the extent of adverse events occurring after SC use. ...
Rationale
Synthetic cathinones (SC), commonly referred to as “bath salts”, are stimulants resembling the natural alkaloid cathinone found in the khat plant. These substances have the potential to induce serious health risks such as hallucinations, delusions, paranoia and agitation which can lead to substance-induced psychotic disorders. Despite growing concerns, there is a limited understanding of the association between SC consumption and the devolvement of such psychopathologies.
Methods
We conducted a systematic review to investigate the frequency of substance-induced psychotic disorder (SIPD) and associated conditions in humans following synthetic cathinone consumption. We qualitatively and quantitatively analyzed SC exposure cases.
Results
A total of 32 studies were included, with a diverse range of demographics, synthetic cathinone types, and consumption patterns. The proportion of individuals developing psychotic symptoms was reported at 0.380 (Random-effects model, 95% CI 0.289 – 0.475). Additionally, the significant heterogeneity in diagnostic approaches limited our ability to provide a precise estimate of prevalence.
Conclusions
Synthetic cathinone consumption is associated with the risk of developing psychotic symptoms as indicated by the prevalence of hallucinations and/or delusions. Due to the lack of information on classifying factors, particularly duration of symptoms, we are unable to conclude synthetic cathinone-induced psychosis. Further research is warranted to elucidate the underlying mechanism linking synthetic cathinone consumption and psychosis. This review underscores the urgency of addressing the growing health risks posed by synthetic cathinone use. Additionally, it highlights the necessity of proper quantification of psychotic symptoms through scales and reporting of classification criteria to accurately diagnose SIPD.
... Synthetic cathinones represent a new trend in the recreational drug market and numerous cases of abuse, dependence, intoxication, and deaths related to their consumption were described in the literature [1,5,[11][12][13][14]. As a consequence, forensic and clinical laboratories worldwide are continuously requested to update their analytical procedures for the identification and quantification of these new drugs in various biological matrices. ...
Most routine practices for drugs‐of‐abuse testing do not include screening procedures for new psychoactive substances, despite their increasing diffusion, preventing clear knowledge of the real consumption of these drugs in the populations. To make up for this shortcoming, a GC‐MS method was developed for the simultaneous determination of 18 synthetic cathinones and one amphetamine‐like compound in human urine. The sample preparation was based on liquid–liquid extraction under alkaline condition followed by derivatization with trifluoroacetic anhydride. The separation of the 19 analytes was achieved in less than 10 minutes. The whole methodology was validated according to national and international guidelines. Selectivity, linearity range, limit of detection and limit of quantitation, precision and accuracy were evaluated. For all the analytes the calibration curve was linear in the 100–1000 ng/mL concentration range. The limits of detection ranged from 10 to 30 ng/mL and limits of quantitation from 30 to 100 ng/mL. Precisions were in the ranges 0.1–10.4%, and 1.0–12.1% for low (100 ng/mL) and high (1000 ng/mL) concentration, respectively. The accuracy, expressed as bias% was within ±20% for all the analytes. The present method was successfully applied to urine samples originating from autopsies, drug abuse/withdrawal controls, clinical investigations, roadside controls, driving re‐licensing and workplace testing.
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... Butylone was also associated with fatal intoxications [7,13]. A couple of studies have confirmed the presence of pentylone in biological matrices of intoxicated patients, but associated with others substances [14,15]. Until now, benzedrone was not associated with intoxication cases, but was frequently reported in the mixtures of other synthetic cathinones sold on illegal market [16,17]. ...
Purpose
The long-term stability of four synthetic cathinones in dried blood spots (DBS) were tested and compared with those of whole blood samples.
Method
A method to determine four cathinones (pentylone, butylone, mephedrone and benzedrone) in DBS was developed and validated. For comparison, the traditional liquid-liquid extraction for the same analytes in whole blood was also performed.
Results
The calibration curve was found to be linear over 25–1000 ng/mL for DBS samples, with a limit of quantification (LOQ) at 25 ng/mL. The interday imprecision and bias results [up to 7.1% relative standard deviation (RSD) and 5.8%, respectively] were much lower than the maximum data recommended by SWGTOX guidelines. The validation results were similar to those of whole blood samples, which showed interday imprecision and bias results of up to 8.1%RSD and 12.3%, respectively, with a linear calibration curve between 10 and 1000 ng/mL and LOQ of 10 ng/mL. A stability study to compare the degradation rate between both matrices at three storage temperatures [room temperature (25 °C), 4 and − 20 °C] and during 90 days proved the poor stability of cathinones in whole blood, where the methylenedioxy cathinones displayed better stability than those with ring substituents. DBS allowed detection of synthetic cathinones after much longer periods than in whole blood samples.
Conclusions
DBS proved, therefore, to be an useful alternative technique to store blood samples. Extraction of DBS is easy and analytes remain stable for much longer periods.
... In addition, cathinone NPS pose a significant public health hazard, as their use is significantly associated with clinical toxicity of multiple physiological systems [7][8][9][10]. Despite this high risk of adverse effects, cathinone users frequently report a persistent desire to continue using the drugs, and prolonged periods of misuse have been reported [10][11][12][13][14][15][16][17]. Collectively, these observations suggest that some cathinone NPS possess a high potential for abuse and dependence. ...
Since the mid- to late 2000s, there has been a dramatic rise in the use and abuse of synthetic derivatives of cathinone, a stimulant alkaloid found in the African shrub Catha edulis. Cathinone novel psychoactive substances (NPS), also referred to as synthetic cathinones or "bath salt"-type drugs, have gained popularity among drug users due to their potency, low cost, ease of procurement, and diverse array of evolving chemical structures. While the ability of cathinone NPS to produce psychotomimetic effects, multiple organ system toxicity, and death in humans is well documented, there has been limited scientific investigation into the reinforcing effects and abuse liability of these drugs. In this chapter, we will summarize the existing literature on the reinforcing effects of cathinone NPS in rodents using the intravenous self-administration (IVSA) paradigm. We will also compare the ability of cathinone NPS to serve as reinforcers to that of classical psychostimulants such as cocaine, methamphetamine, and methylenedioxymethamphetamine (MDMA). The chapter will conclude with a summary and indications for future avenues of research on cathinone NPS.
... Despite its placement into Schedule I status in the USA in 2012, MDPV continues to appear in drug markets, and recent reports of MDPV addiction have emerged [9]. While MDPV-related toxicity is now well established, the scientific assessment of abuse liability is still in its infancy [10,11]. ...
Background:
In recent years, there has been a dramatic increase in abuse of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV), often in combination with other illicit stimulants.
Purpose:
We sought to determine if repeated exposure to MDPV would produce sensitization to the motor stimulant effects of the drug, and whether cross-sensitization would develop with the stimulant effects of methamphetamine (METH).
Study design:
Male Sprague-Dawley rats were administered MDPV (1 or 5 mg/kg) or saline once daily for 5 days at 24 hour intervals, or were administered MDPV (1 mg/kg) or saline once daily for 5 days at 48 hour intervals. For cross-sensitization experiments, rats were administered METH (1 mg/kg) or MDPV (1 or 5 mg/kg) once daily for 5 days at 48 hour intervals, and following a 5 day incubation period, were given an acute challenge injection of either MDPV (0.5 mg/kg) or METH (0.5 mg/kg), respectively.
Results:
Rats repeatedly administered MDPV (1 mg/kg) every 48 hours, but not every 24 hours, demonstrated increased motor activity when given either a subsequent challenge of MDPV (0.5 mg/kg i.p.) or METH (0.5 mg/kg), indicating the development of behavioral sensitization and cross-sensitization, respectively. Moreover, rats repeatedly administered METH (1 mg/kg) every 48 hours did not exhibit cross-sensitization to the motor stimulating effects of a subsequent challenge with MDPV (0.5 mg/kg).
Conclusion:
These results suggest that specific patterns of MDPV administration may lead to lasting changes in behavioral responses to subsequent METH exposure.
... Synthetic cathinone use is also associated with toxicity of multiple organ systems, sometimes referred to as the "sympathomimetic toxidrome" [7], including chest pain, nausea, vomiting, seizures, hypertension, tachycardia, hyperthermia, cardiac arrest, and death. Despite the high risk of these adverse effects, users of synthetic cathinones frequently report a persistent desire to continue use of these drugs, and prolonged periods of synthetic cathinone use have been reported [2,3,6,8,12,[21][22][23][24][25][26][27], suggesting a high potential for addiction and dependence. ...
Synthetic cathinones, colloquially referred to as "bath salts", are derivatives of the psychoactive alkaloid cathinone found in Catha edulis (Khat). Since the mid-to-late 2000's, these amphetamine-like psychostimulants have gained popularity amongst drug users due to their potency, low cost, ease of procurement, and constantly evolving chemical structures. Concomitant with their increased use is the emergence of a growing collection of case reports of bizarre and dangerous behaviors, toxicity to numerous organ systems, and death. However, scientific information regarding the abuse liability of these drugs has been relatively slower to materialize. Recently we have published several studies demonstrating that laboratory rodents will readily self-administer the "first generation" synthetic cathinones methylenedioxypyrovalerone (MDPV) and methylone via the intravenous route, in patterns similar to those of methamphetamine. Under progressive ratio schedules of reinforcement, the rank order of reinforcing efficacy of these compounds are MDPV ≥ methamphetamine > methylone. MDPV and methylone, as well as the "second generation" synthetic cathinones α-pyrrolidinovalerophenone (α-PVP) and 4-methylethcathinone (4-MEC), also dose-dependently increase brain reward function. Collectively, these findings indicate that synthetic cathinones have a high abuse and addiction potential and underscore the need for future assessment of the extent and duration of neurotoxicity induced by these emerging drugs of abuse.
... Most recently, severe intoxications and fatalities have been encountered with new and emerging designer drugs, presenting analytical challenges for detection and identification of such novel compounds. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Clinical and forensic toxicology laboratories utilize screening methods such as immunoassays for a quick, cost-efficient approach to gaining basic information about the drug content of a biological specimen such as blood or urine. Immunoassays are designed to indicate the presence (above a certain cut-off concentration) of a particular class or type of substance, such as amphetamines. ...
Since the introduction of synthetic heroin, designer drugs have been increasing in prevalence in the United States drug market over the past few decades. Recently, 'legal highs' sold as 'bath salts' have become a household term for one such class of designer drugs. While a number of federal and state bans have been enacted, the abuse of these designer drugs still continues. Few assays have been developed for the comprehensive detection of such compounds, so it is important to investigate how they may or may not react in presumptive screens, i.e. pre-existing commercial immunoassays. In this experiment, 16 different ELISA reagents were evaluated to determine the cross-reactivity of 30 designer drugs, including 24 phenylethylamines (including 8 cathinone derivatives), 3 piperazines, and 3 tryptamines. Cross-reactivity towards most drugs was <4% in assays targeting amphetamine or methamphetamine. Compounds such as MDA, MDMA, ethylamphetamine, and α-methyltryptamine demonstrated cross-reactivities in the range of 30-250%, but data were consistent with both manufacturer's inserts and published literature. When tested against the Randox Mephedrone/Methcathinone kit, cathinone derivatives demonstrated cross-reactivity at concentrations as low as 150 ng/ml. Since this same reagent did not cross-react with other amphetamine-like compounds, it opens the possibility to screen post-mortem specimens without the interference of putrefactive amines. All other assays demonstrated essentially no cross-reactivity towards any of the analytes evaluated. Given these results, a great need exists for more broad-range screening techniques to be applied when analyzing biological specimens by immunoassays for drugs of abuse, specifically the more recent designer drugs. Copyright © 2013 John Wiley & Sons, Ltd.
Background
Although illegal drug use has largely been declining in the UK over the past decade, this period has witnessed the emergence of a range of novel psychoactive substances (NPS) (‘legal highs’). These are new, mostly synthetic, substances that mimic the effects of existing drugs). Despite there being many causes for concern in relation to NPS, there has been little prior study of the burden associated with their use in public health terms. Clarity is lacking on research priorities in this rapidly developing literature.
Objectives
To inform the development of public health intervention research on NPS by reviewing existing data on their use, associated problems and potential responses to such problems.
Design
A scoping review and narrative synthesis of selected bodies of evidence was undertaken to summarise and evaluate what is known about NPS use and the related harms of, and responses to, such use. Relevant literature was identified from electronic databases (covering January 2006 to June 2016 inclusive), Google (Google Inc., Mountain View, CA, USA), relevant websites and online drug forums and by contacting experts. Articles were included if they were primary studies, secondary studies involving the analysis and interpretation of primary research or discussion papers. A conceptual framework postulating an evidence-informed public health approach to NPS use in the UK was developed through a pragmatic literature review, the iterative development of concepts and finalisation in light of the results from the empirical review work. The process also involved feedback from various stakeholders. Research recommendations were developed from both strands of work.
Results
A total of 995 articles were included in the scoping review, the majority of which related to individual-level health-related adverse effects attributable to NPS use. The prevalence of lifetime NPS use varied widely between (e.g. with higher prevalence in young males) and within population subgroups. The most commonly reported adverse effects were psychiatric/other neurological, cardiovascular, renal and gastrointestinal manifestations, and there is limited evidence available on responses. In these and other respects, available evidence is at an early stage of development. Initial evidence challenges the view that NPS should be treated differently from other illicit drugs. The conceptual framework indicated that much of the evidence that would be useful to inform public health responses does not yet exist. We propose a systems-based prevention approach that develops existing responses, is multilevel and life course informed in character, and emphasises commonalities between NPS and other legal and illegal drug use. We make 20 recommendations for research, including nine key recommendations.
Limitations
Scoping reviews do not interrogate evidence in depth, and the disjunction between the scoping review and the conceptual framework findings is worthy of careful attention.
Conclusions
Key research recommendations build on those that have previously been made and offer more evidence-based justification and detail, as previous recommendations have not yet been acted on. The case for decision-making on commissioning new research based on these recommendations is both strong and urgent.
Future work
The validity of recommendations generated through this project could be enhanced via further work with research commissioners, policy-makers, researchers and the public.
Study registration
The systematic review element of this study is registered as PROSPERO CRD42016026415.
Funding
The National Institute for Health Research Public Health Research programme.
The use of designer drugs commonly marketed as bath salts or plant food has risen dramatically in recent years. Several different synthetic cathinones have been indentified in these products, including mephedrone, 3,4-methylenedioxypyrovalerone (MDPV), and 4-fluoromethcathinone (flephedrone). We report a case of bath salt intoxication with quantitative MDPV and flephedrone levels in a patient's serum and urine, and from the bath salt product.
A 23-year-old male with a prior psychiatric history arrived via EMS for bizarre behavior, suicidality, and hallucinations after reportedly insufflating a bath salt. He was found to have MDPV levels of 186 and 136 ng/mL in his serum and urine, respectively, and flephedrone levels of 346 and 257 ng/mL in the serum and urine, respectively. The white powder in question was found to contain 143 μg MDPV and 142 μg flephedrone per milligram powder. His psychosis and agitation resolved with lorazepam, droperidol, and observation in the emergency department.
Agitation, psychosis, movement disorders, tachycardia, and hypertension have all been attributed to the use of MDPV; there are no prior reports detailing clinical experience with flephedrone. Considering that our patient's serum flephedrone levels were twofold higher than his MDPV level, it is likely flephedrone contributed to his clinical toxicity. This case suggests the possibility that fluorinated cathinones, such as flephedrone, may have altered metabolism and/or elimination which may affect their course of clinical toxicity. This case highlights the evolving composition of synthetic cathinones found in bath salt products.
A large number of cathinone derivatives have shown a wide range of bioactive properties, attracting great interest from communities associated with pharmaceutical research. Some of these derivatives have gained popularity as so-called recreational 'legal highs' due to their availability on the Internet and high street shops. A previous study described the qualitative analysis of 24 'legal high' Energy-1 (NRG-1) and NRG-2 products obtained from 18 websites following the ban on mephedrone and derivatives in April 2010. The majority of these products contained a mixture of cathinones just carrying a new label. Here, three additional cathinone products have been detected; two from an NRG-1 sample and one from an NRG-3 sample. This report describes their identification. NRG-1 sample 1 consisted of a mixture of 4 cathinones namely 4-fluoromethcathinone (1), 1-(3,4-methylenedioxyphenyl)-2-(methylamino)pentan-1-one (pentylone, 2), 3,4-methylenedioxy-α-pyrrolidinobutyrophenone (MDPBP, 3) and 3,4-methylenedioxypyrovalerone (MDPV, 4). The sample labelled as NRG-3 (mislabelled with the chemical structure of mephedrone) consisted of a mixture of 4-methyl-α-pyrrolidinopropiophenone (MPPP, 5) and (2), whereas the remaining NRG-1 sample 2 (also mislabelled with the chemical structure of mephedrone) consisted of a mixture of (2) and (3). Qualitative analyses were carried out by GC-(EI/CI)-MS, NMR spectroscopy and confirmation by preparation of standards. The preparation of brominated precursors carrying the 3,4-methylenedioxyphenyl nucleus revealed extensive α,α-dibromination: the mass spectral and NMR data of these intermediates are also presented and discussed.
Recreational use of designer substances containing synthetic cathinones such as mephedrone, commonly sold as "bath salts," has recently been increasing in the United States (National Institute on Drug Abuse. Available at: http://www.nida.nih.gov/about/welcome/MessageBathSalts211.html. Accessed March 25, 2011; The Washington Post. Available at: http://www.washingtonpost.com/national/officials-fear-bath-salts-becoming-the-next-big-drug-menace/2011/01/22/ABybyRJ_story.html. Accessed March 25, 2011). "Bath salt" ingestion can generate an intense stimulant toxidrome and has been associated with significant morbidity.
The authors seek to alert clinicians to the potential for profound delirium, psychosis, and other medical and behavioral sequelae of "bath salt" use.
Case series.
We describe our recent experience with two highly agitated and delirious patients following "bath salt" ingestion and offer a brief review of the emergence of this phenomenon.
Challenges and strategies surrounding diagnosis and treatment are described, which may be useful as "bath salt" use becomes more widespread.
As an emerging trend, bath salt intoxication delirium appears to cause intense psychosis that can be managed with antipsychotic medications. Clinicians should be aware of this phenomenon until more precise detection methods are available.
Mephedrone (4-methylmethcathinone) is a synthetic cathinone that is used as a recreational drug. It has been available since 2007 but its availability and use increased significantly during 2009 and 2010. In this review article we will summarize the available literature on the sources, availability, and prevalence of the use of mephedrone. We will also discuss the pharmacology of mephedrone, the patterns of acute toxicity associated with its use, the reports of fatalities associated with its use, and the potential for mephedrone dependence.