Use Of Synthetic Cathinones Research Articles

Bath salts and polyconsumption: in search of drug-drug interactions.

Polydrug use is a widespread phenomenon, especially among adolescents and young adults. Synthetic cathinones are frequently consumed in combination with other drugs of abuse. However, there is very little information regarding the consequences of this specific consumption pattern. The aim of this review is to introduce this topic and highlight the gaps in the existing literature. In three different sections, we focus on specific interactions of synthetic cathinones with alcohol, cannabinoids, and the stimulants nicotine and cocaine. We then dedicate a section to the existence of sex and gender differences in the effects of synthetic cathinones and the long-term psychophysiological consequences of adolescent and prenatal exposure to these drugs. Epidemiological studies, case reports, and results obtained in animal models point to the existence of pharmacological and pharmacokinetic interactions between synthetic cathinones and other drugs of abuse. This pattern of polyconsumption can cause the potentiation of negative effects, and the dissociation between objective and subjective effects can increase the combined use of the drugs and the risk of toxicity leading to serious health problems. Certain animal studies indicate a higher vulnerability and effect of cathinones in females. In humans, most of the users are men and case reports show long-term psychotic symptoms after repeated use. The co-use of synthetic cathinones and the other drugs of abuse analyzed indicates potentiation of diverse effects including dependence and addiction, neurotoxicity, and impaired cognition and emotional responses. The motivations for and effects of synthetic cathinone use appear to be influenced by sex/gender. The long-term consequences of their use by adolescents and pregnant women deserve further investigation.

Synthetic Cathinone Use Among Polysubstance Users: Indirect Indicator of Indiscriminate Drug Taking or Preferred Drug of Abuse?

A survey pertaining to synthetic cathinone (SC) use was completed by 499 polysubstance users enrolled in a residential recovery program in the Southeastern United States. Of the final sample, 28% reported ever SC use. SC-users, compared with nonusers, were more often younger (32.7 vs. 36.0, p = .001), White (93.4% vs. 80.8%, p = .001), and on probation/parole since 2010 (80.9% vs. 70.9%, p = .032). SC-users evidenced extensive drug histories and were less likely to be enrolled in an urban-based program, compared to a rural, Appalachian-based program (73.8% vs. 86.6%, p = .001). Use of synthetic cannabinoids (adjusted odds ratio [AOR] = 1.9, p = .044), kratom (AOR = 1.7, p = .045), and inhalants (AOR = 2.3, p = .001) were significantly associated with SC use. Approximately 23% of SC-users preferred SCs to amphetamines or cocaine; however, only 3.6% ranked SC as their most preferred drug. Past-year SC use declined to 6.6%. Among polysubstance users in this sample, SC use may be a potential indicator of versatile and indiscriminate drug-taking.

“Flakka” use among high school seniors in the United States

BackgroundUse of synthetic cathinones, commonly referred to as “bath salts”, has been associated with tens of thousands of emergency department visits in the US; however, few national studies have estimated prevalence of use and we know very little about use among adolescents. In this study we estimate prevalence and correlates of use of “Flakka” (alpha-PVP), a highly-potent “bath salt” associated with at least 80 deaths in the US.Methods: We analyzed data from the 2016/2017 Monitoring the Future study, which surveyed a nationally representative sample of high school seniors in the US (n = 3786). Bivariable and multivariable models were used to determine demographic and drug-related correlates of use. ResultsOverall, 0.8% (95% CI: 0.5–1.2) of high school seniors in 2016/2017 is estimated to have used Flakka in the past year. Students whose parents have less than a high school education were at higher odds for use (aOR = 4.12, 95% CI: 1.00–16.94). Flakka users reported high prevalence of use of other drugs, particularly synthetic cannabinoids (85.6%), ketamine (72.3%), marijuana (59.1%), and GHB (47.5%). Flakka use was also associated with use of a higher number of other drugs and higher frequency of use of other drugs, with 51.7% using 4–12 other drugs and 22.4% using 4–12 other drugs >6 times. ConclusionsStudents who use multiple drugs are elevated risk for Flakka use, suggesting synthetic cathinone use alone is rare and the use of multiple substances may compound adverse effects of these drugs. Socio-economic disparities are concerning given reduced access to prevention and intervention.

Synthetic cannabinoid and synthetic cathinone use in Hungary: A literature review

Purpose In the past decade, novel psychoactive substances (NPSs) gained a significant role on the contemporary drug scene. Synthetic cathinones and synthetic cannabinoids are the most common NPSs both in Hungary and worldwide. This study aims to provide a literature review on the Hungarian characteristics related to the use of these NPSs. Materials and methods Available literature regarding synthetic cathinone and cannabinoid use in Hungary was overviewed and structured into (a) epidemiological studies, (b) studies on the subjective and somatic effects, and (c) studies on toxicity and adverse consequences. Published papers between 2007 and 2017 were identified using PubMed and MATARKA search engines. Results One hundred twenty-six papers were identified and after exclusion, 54 papers remained for in-depth analysis. Most of the reviewed studies were providing epidemiological information regarding the NPSs of our interest. Hungarian prevalence rates were not higher than the European averages. Identified risks of these NPSs consisted of drug-induced psychosis, further severe psychiatric symptoms, and fatal overdose. Injecting of cathinones was also a commonly reported phenomenon, mostly among clients of needle-exchange programs. Conclusion Based on the reviewed body of research, necessary information is available to plan effective prevention and intervention programs and establishes specific therapeutic guidelines for the treatment of NPS users.

Synthetic cathinone adulteration of illegal drugs.

Current prevalence estimates of synthetic cathinone ("bath salt") use may be underestimates given that traditional metrics (e.g., surveys, urinalysis) often fail to capture the emergent issue of synthetic cathinone adulteration of more common illegal drugs, such as ecstasy (3,4-methylenedioxymethamphetamine). This review examines the evolution of synthetic cathinones and prevalence of use over the past decade in the United States. We also review methods of self-report and biological testing of these compounds as well as adverse outcomes associated with adulterated drug use. Synthetic cathinone use emerged in the United States by 2009 with use associated with tens of thousands of poisonings. Reported poisonings and self-reported use have substantially decreased over the past five years. However, our review suggests that current estimates of use are underestimates due to underreporting stemming primarily from unknown or unintentional use of adulterated formulations of relatively popular illegal drugs, such as ecstasy. While intentional synthetic cathinone use has decreased in recent years, evidence suggests that prevalence of use is underestimated. Testing of drugs and/or biological specimens can improve the accuracy of synthetic cathinone use estimates. Furthermore, we advocate that researchers and clinicians should become better aware that exposure to these potent compounds (e.g., as adulterants) often occurs unknowingly or unintentionally. To improve our understanding of synthetic cathinone adulteration, research utilizing a combinatorial approach (survey and biological testing) will help more accurately estimate the prevalence and impact of this public health issue.

Analysis of neurotransmitter levels in addiction-related brain regions during synthetic cathinone self-administration in male Sprague-Dawley rats.

Synthetic cathinones are used as stimulants of abuse. Different stimulants may induce distinct rates of disease progression, yielding neurochemical changes that may vary across brain regions or neurotransmitter systems. This research sought to behaviorally and chemically differentiate stages of synthetic cathinone abuse through rodent self-administration and measurement of the neurotransmitter profile in multiple brain regions. Male rats were trained to self-administer α-PVP, mephedrone (4MMC), or saline. Half of each drug group stopped self-administering after autoshaping; the other half self-administered for another 21days. Brain tissue from amygdala, hippocampus, hypothalamus, PFC, striatum, and thalamus was profiled with electrochemical detection to assess neurotransmitter levels. During autoshaping, the majority of infusions were delivered noncontingently. In the self-administration phase, rats responded more for α-PVP and 4MMC than for saline, demonstrating that both synthetic cathinones were reinforcing. Longer durations of exposure elevated 5-HIAA in hypothalamus, PFC, and hippocampus, indicating that learning may produce changes in addiction-related brain regions. Both synthetic cathinones decreased norepinephrine in hippocampus, while α-PVP decreased glutamate in hippocampus and PFC, and 4MMC decreased glutamate in thalamus. Furthermore, α-PVP increased dopaminergic metabolites in striatum, whereas 4MMC decreased serotonin in the amygdala, hippocampus, and PFC. Interestingly, neither synthetic cathinone affected dopamine levels despite their functional effects on the dopaminergic system. In summary, the neurotransmitter changes observed here suggest that synthetic cathinone use likely produces sequential neurochemical changes during the transition from use to abuse. Consequently, treatment need may differ depending on the progression of synthetic cathinone abuse.

Is the 3,4-methylendioxypyrovalerone/mephedrone combination responsible for enhanced stimulant effects? A rat study with investigation of the effect/concentration relationships.

The use of synthetic cathinones as recreational drugs frequently sold in combination has been increasing exponentially. However, the consequences of combining cathinones on the resulting stimulant effects and the pharmacokinetics have been poorly investigated. To study 3,4-methylenedioxypyrovalerone (MDPV; 3mg/kg) and mephedrone (4-MMC; 30mg/kg)-induced effects on rat locomotor activity and pharmacokinetics, administered alone or in combination by the intragastric route. The pharmacokinetic parameters were determined using non-compartmental analysis and the relationships between the locomotor activity and drug concentrations using sigmoidal Emax modeling. Locomotor activity significantly increased during the first hour post-administration with the MDPV/4-MMC combination in comparison to MDPV (p < 0.001) and 4-MMC (p < 0.01) alone. The pharmacokinetic profile of MDPV, but not 4-MMC, was significantly modified with the combination resulting in decreases in Cmax (16.4 ± 5.5 versus 62.2 ± 14.2μg/L, p < 0.05) and AUC0 → ∞ (708 ± 91 versus 3316 ± 682μg/L/min, p < 0.01) and increases in V/F (582.6 ± 136.8 versus 115.9 ± 42.7L/kg, p < 0.05) and Cl/F (4.6 ± 0.7 versus 1.2 ± 0.4L/kg/min, p < 0.01) in comparison to MDPV alone. The sigmoidal Emax model fitted the observed data well; MDPV being markedly more potent than 4-MMC (EC50, 0.043 versus 0.7μmol/L). The enhancing factor representing the MDPV contribution to the alteration in the relationships between locomotor activity and 4-MMC concentrations was 0.3. An MDPV/4-MMC combination results in enhanced stimulant effects in the rat, despite significant reduction in MDPV bioavailability. Enhanced effects could be explained by increased MDPV distribution and/or possible complementation at the brain dopaminergic targets. However, the exact consequences of the MDPV/4-MMC combination in humans remain to be clarified.

The Effects of Exposure to Mephedrone During Adolescence on Brain Neurotransmission and Neurotoxicity in Adult Rats

According to the European Drug Report (2016), the use of synthetic cathinones, such as mephedrone, among young people has rapidly increased in the last years. Studies in humans indicate that psychostimulant drug use in adolescence increases risk of drug abuse in adulthood. Mephedrone by its interaction with transporters for dopamine (DAT) and serotonin (SERT) stimulates their release to the synaptic cleft. In animal studies, high repeated doses of mephedrone given to adolescent but not adult mice or rats induced toxic changes in 5-hydroxytryptamine (5-HT) neurons. The aim of our study was to investigate the effects of mephedrone given in adolescence on brain neurotransmission and possible neuronal injury in adult rats. Adolescent male rats were given mephedrone (5 mg/kg) for 8 days. In vivo microdialysis in adult rats showed an increase in dopamine (DA), 5-HT, and glutamate release in the nucleus accumbens and frontal cortex but not in the striatum in response to challenge dose in animals pretreated with mephedrone in adolescence. The 5-HT and 5-hydroxyindoleacetic acid contents decreased in the striatum and nucleus accumbens while DA turnover rates were decreased in the striatum and nucleus accumbens. The oxidative damage of DNA assessed with the alkaline comet assay was found in the cortex of adult rats. Therefore, the administration of repeated low doses of mephedrone during adolescence does not seem to induce injury to 5-HT and DA neurons. The oxidative stress seems to be responsible for possible damage of cortical cell bodies which causes maladaptive changes in serotonergic and dopaminergic neurons.

Synthetic Cannabis Use in Israel: “Nice or Bad Guy—Spice”

An alarming increase in the use/abuse of synthetic psychoactive substances known as “designer drugs” or “legal highs” (“Nice Guy” in Israel) has caused the governments of many countries including the USA to pass legislation banning the sale, possession, and use of specific synthetic cathinones and cannabinoids. “New psychoactive substances” (NPS) pose a public health risk. Early research on synthetic cannabinoids done in the 1980s and 1990s describes benign outcomes. Research in vivo in animals supported the positive influence of synthetic cannabinoids as an antiemetic used to prevent vomiting and nausea. However, reports of emergency departments evidence the toxicity and side effects of synthetic cannabinoids. This situation calls for policy, law enforcement, and medical intervention to address this growing problem.

Abuse‐Related Discriminative Stimulus Effects of Synthetic Cathinones

The use of synthetic cathinones, or “bath salts,” has become more widespread in recent years. “Bath salts” share many chemical properties with psychostimulants like methamphetamine or with entactogens like 3,4‐methylenedioxymethamphetamine (MDMA or “Ecstasy”), presumably reflecting structural differences that lead to differing neurochemical actions. Yet, currently available synthetic cathinones have not been well‐characterized in primate species, and it is unclear which pharmacological activity mediates their abuse‐related behavioral effects. The present study was initiated to address this question, using drug discrimination procedures to evaluate several synthetic cathinones in two groups of squirrel monkeys. Each subject was trained to respond on either of two levers under a FR10 schedule of reinforcement and, during training sessions, responding on one lever was reinforced after pretreatment with vehicle whereas responding on the second lever was reinforced after pretreatment with the training drug. Under terminal conditions, one group of monkeys discriminated 0.1 mg/kg methamphetamine from saline; the other group discriminated 0.6 mg/kg MDMA from saline. Drug or saline lever assignments were counter balanced across the left and right levers within each group. Training sessions comprised multiple components, and a component consisted of a ten‐minute timeout period followed by ten presentations of the FR10 schedule, each followed by a brief 50‐second timeout. After criterion performance was met (≥ 90% correct), test days interspersed training days, with at least two training days between each test day. The effects of five different synthetic cathinones ‐ α‐pyrrolidinovalerophenone (α‐PVP), methylenedioxypyrovalerone (MDPV), mephedrone, methylone, and methcathinone) were tested in both groups. A full range of doses of each drug was administered using cumulative dosing procedures. Results show that doses of 0.1 mg/kg – 0.32 mg/kg of MDPV, α‐PVP, and methcathinone were identified as methamphetamine in subjects trained to discriminate 0.1 mg/kg methamphetamine from vehicle, whereas doses mephedrone and methylone up to those that decreased overall response rates did not generalize to MA. Preliminary results suggest an opposite profile of substitution in MDMA‐trained animals. Thus, mephedrone and methylone, but not MDPV, α‐PVP, and methcathinone did appear to generalize to MDMA. These results demonstrate that synthetic cathinones have differing substitution profiles in animals trained to discriminate methamphetamine or MDMA, which may reflect differing subjective effects and, perhaps, differing abuse liability in man.Support or Funding InformationSupported by NIH Grants: DA002519. GM113117, DA039306, GM111385This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Synthetic Cathinone and Cannabinoid Designer Drugs Pose a Major Risk for Public Health.

As part of an increasing worldwide use of designer drugs, recent use of compounds containing cathinones and synthetic cannabinoids is especially prevalent. Here, we reviewed current literature on the prevalence, epidemiology, bio-behavioral effects, and detection of these compounds. Gender differences and clinical effects will also be examined. Chronic use of synthetic cathinone compounds can have major effects on the central nervous system and can induce acute psychosis, hypomania, paranoid ideation, and delusions, similar to the effects of other better-known amphetamine-type stimulants. Synthetic cannabinoid products have effects that are somewhat similar to those of natural cannabis but more potent and long-lasting than THC. Some of these compounds are potent and dangerous, having been linked to psychosis, mania, and suicidal ideation. Novel compounds are developed rapidly and new screening techniques are needed to detect them as well as a rigorous regulation and legislation reinforcement to prevent their distribution and use. Given the rapid increase in the use of synthetic cathinones and cannabinoid designer drugs, their potential for dependence and abuse, and harmful medical and psychiatric effects, there is a need for research and education in the areas of prevention and treatment.

Examination of Synthetic Cannabinoid and Cathinone Use among a Drug-Using Offender Sample, 2013–2015

ABSTRACTUse of novel psychoactive substances (NPS) such as synthetic cannabinoids (e.g., “Spice,” “Serenity”) and cathinones (e.g., “bath salts”) has proliferated in recent years; however, there is a gap in research examining prevalence among offender samples. This study examined demographics, drug use, mental health characteristics, and criminal histories of NPS users compared to non-NPS users within an offender sample entering drug treatment. Using logistic regression analysis, combined 2013–2015 assessment data were examined (N = 8,791). NPS users offended more often (x̄ = 10.3), were more likely to have experienced homelessness (12.2%), and to have lived in a metro area (59.0%). NPS users reported significantly more past-year drug use, including substances not readily detected by standard urine analysis (e.g., hallucinogens, alcohol, and inhalants). Individuals with higher anxiety symptom counts (OR = 1.07; p < .001) and those who reported drinking to intoxication (OR = 1.30; p < .001) had an increased likelihood of NPS use. Older individuals (OR = 0.95; p < .001) and those who began using drugs at an older age (OR = 0.95; p < .001) were less likely to report NPS use. NPS use may be a marker of more severe using patterns in an offender sample. Future investigation should focus on NPS use as a possible method for bypassing drug testing measures.

Abuse‐Related Effects of “Bath Salts” Mixtures: Studies with MDPV, Methylone, and Caffeine in Rats.

The recreational use of synthetic cathinones has become a serious public health problem worldwide. In the US, “bath salts” products often contain MDPV (a monoamine transporter inhibitor) or methylone (a monoamine transporter substrate); however, preparations often contain mixtures of multiple synthetic cathinones, or mixtures of a synthetic cathinone and caffeine. In order to determine if the reinforcing effects of mixtures of “bath salts” constituents differed from the reinforcing effects of the constituents alone, adult male Sprague Dawley rats were trained to self‐administer either 0.032 mg/kg/inf MDPV or 0.32 mg/kg/inf methylone under a progressive ratio (PR) schedule of reinforcement. Drug mixtures were based on the concept of dose equivalence, with each pair of drugs evaluated at three ratios (3:1, 1:1, and 1:3) relative to the mean ED50 for each drug. Dose addition analyses were used to calculate predicted effect levels for an additive interaction at each dose pair of each combination of drugs using the Emax, ED50, and slope parameters derived from dose‐response curves obtained in individual rats. Although high levels of responding were maintained by each of the “bath salts” mixtures, the nature of the interaction varied depending upon the constituent drugs. For combinations containing a cathinone and caffeine (MDPV+caffeine and methylone+caffeine), the interactions were generally additive, however, when mixed at a 3:1 ratio of their ED50s the reinforcing effects of both sets of mixtures were found to be supra‐additive. Interestingly, although combining caffeine with MDPV appeared to only increase the potency of the mixture, combining caffeine and methylone significantly increased the reinforcing effectiveness of the a “bath salts” mixture beyond that which would be predicted for an additive interaction. Unlike with combinations of cathinones and caffeine, when MDPV was combined with methylone departures from additivity tended to occur in the sub‐additive direction, with the onset of toxicity observed with larger dose pairs of the MDPV+methylone mixtures. Together, these studies suggest that the reinforcing effects of binary mixtures containing common bath salts constituents (i.e., MDPV, methylone, and caffeine) are generally additive in nature; however, both supra‐additive (MDPV+caffeine and methylone+caffeine) and sub‐additive interactions (MDPV+methylone) can be observed. Although such interactions could account for the high rates of bath salts abuse, further study will be needed to determine if similar interactions exist between these and other bath salts constituents with regard to other abuse‐related and toxic effects.Support or Funding InformationThis study was supported by a National Institutes of Health (NIH) research grant (R01 DA039146) from the National Institute on Drug Abuse (NIDA), as well as the NIH Intramural Research Programs of NIDA and National Institute on Alcohol Abuse and Alcoholism (NIAAA).

Motivations for new psychoactive substance use among regular psychostimulant users in Australia

BackgroundExamine the motivations for new psychoactive substance (NPS) use amongst a sample of regular psychostimulant users (RPU) in Australia, and determine whether motivations differ across substances. MethodData were obtained from 419 RPU interviewed for the 2014 Ecstasy and related Drugs Reporting System who reported lifetime NPS use. Based on the most recent NPS used, motivations for use were rated on an 11-point scale (0 ‘no influence’–10 ‘maximum influence’). ResultsFor NPS overall, value for money was found to be the most highly endorsed motivation for use, scoring a median of five out of ten. However, there was substantial variation in motivations for use across substance types. Availability (i.e. no other drug was available to me at the time; 6/10) was the most highly endorsed motivation for the use of synthetic cathinones, which was significantly higher than reported for DMT. Perceived legality and availability were the most highly endorsed motivations for synthetic cannabinoids (5/10); perceived legality scored higher for synthetic cannabinoids than for all the other NPS, whilst in regards to availability synthetic cannabinoids scored significantly higher than DMT only. Value for money was the most highly endorsed motivation for NBOMe (8/10) and 2C-family substances (5/10); in regards to NBOMe this scored significantly higher than all other NPS. Short effect duration was the most highly endorsed motivation for DMT (7/10), which was significantly higher than for all other NPS. ConclusionSynthetic cathinones and cannabinoids appear to be largely motivated by ‘opportunistic’ reasons (i.e. availability, legality), while NBOMe, 2C-family substances and DMT appear to be motivated by particular desirable qualities of a substance (i.e. value for money, short effect duration). Providing a nuanced understanding of why individuals use particular NPS improves our ability to understand the NPS phenomenon and to tailor harm reduction messages to the appropriate target groups.

Poisoning by synthetic cathinones: Consumption behaviour and clinical description from 11 cases recorded by the Addictovigilance Centre of Bordeaux

Synthetic cathinones represent a large class of new popular drugs of abuse in France and in Europe, commonly called new psychoactive substances (NPS). We describe 11 cases of synthetic cathinone abuse reported to the Bordeaux Addictovigilance Centre between January 2014 and December 2015. Cases were described according to the type of substance used, patient's age and gender, type of complications, context of use and year of the event, and, when a toxicological analyse was available, the analytical method of detection and the samples of analyse (blood, urine, powder). All patients were male, with a mean age of 35.9 years old. The synthetic cathinone most frequently reported by users was methylenedioxypyrovalerone ( n = 8). There was analytical confirmation of synthetic cathinone use in 6 cases. Nine cases were serious, with neurologic and/or psychiatric complications in most cases. The outcome was favourable in 10 cases but one patient died. Questioning patients about use of NPS is essential, as well as NPS analytical identification when an intake is suspected.

“Just another drug” for marginalized users: The risks of using synthetic cathinones among NSP clients in the Czech Republic

ABSTRACTBackground: In several EU countries, synthetic cathinone (SC) use has spread among injecting drug users (IDUs); it has been linked to risk of dependence and HIV/HCV transmission. Aims: To analyze the association between dependence and risky injecting practice with experimental and repeated SC use in the past 12 months among the clients of needle-syringe programs in the Czech Republic. Methods: IDUs in six locations in the Czech Republic were surveyed in 2013 and 2014 (n = 463). Single-predictor multinomial logit models were run to determine SC use upon the Severity of Dependence Scale (SDS) and risky injecting practice; the same predictors were included in the multivariate model with confounders. Findings: SDS score and risky injecting practice were significantly associated with repeated SC use in single-predictor models but not in the multivariate model; SC experimentation was linked to young and male respondents and those who lived in a larger city (>50,000); predictors of repeated SC use were homelessness (AOR = 3.2), co-occurring use of stimulants and opioids (AOR = 4.3), and use of cannabis (AOR = 2.4) in the past month. Conclusions: Repeated SC use was associated with poly-drug use and homelessness; given the rather inferior status of SCs among IDUs, their users face a risk of stigmatization and further marginalization.

The abuse potential of two novel synthetic cathinones with modification on the alpha-carbon position, 2-cyclohexyl-2-(methylamino)-1-phenylethanone (MACHP) and 2-(methylamino)-1-phenyloctan-1-one (MAOP), and their effects on dopaminergic activity

The recreational use of synthetic cathinones has dramatically increased in recent years, which is partly due to easy accessibility and ability of synthetic cathinones to exert rewarding effects similar to cocaine and methamphetamine. Many synthetic cathinones have already been scheduled in several countries; however, novel and diverse synthetic cathinones are emerging at an unprecedented rate, often outpacing regulatory processes. Recently, designer modifications of the basic cathinone molecule are usually performed on the alpha-carbon position. In this study, we designed and synthesized two novel synthetic cathinones with substituents on alpha-carbon position, [1] 2-cyclohexyl-2-(methylamino)-1-phenylethanone (MACHP), and [2] 2-(methylamino)-1-phenyloctan-1-one (MAOP). Then, we evaluated their rewarding and reinforcing effects through the conditioned place preference (CPP) in mice and self-administration (SA) test in rats. Locomotor activity was also assessed in mice during daily MACHP or MAOP treatment for 7days and drug challenge. qRT-PCR analyses were conducted to determine their effects on dopamine-related genes in the striatum. MACHP and MAOP produced CPP at 10 and 30mg/kg. In the SA test, MACHP (1mg/kg/infusion), but not MAOP, was self-administered. Both MACHP and MAOP induced locomotor sensitization in mice. qRT-PCR analyses showed that MACHP and MAOP reduced dopamine transporter gene expression in the striatum. These data indicate that MACHP and MAOP may have rewarding properties, which might be attributed to their ability to affect the dopaminergic activity. These findings may be useful in predicting the abuse potential and hasten the regulation of future cathinone entities with similar modifications.

A novel synthetic cathinone, 2-(methylamino)-1-(naphthalen-2-yl) propan-1-one (BMAPN), produced rewarding effects and altered striatal dopamine-related gene expression in mice

The recreational use of synthetic cathinones has grown rapidly which prompted concerns from legal authorities and health care providers. However, in response to legislative regulations, synthesis of novel synthetic cathinones by introducing substituents in cathinone molecule has dramatically increased the diversity of these substances. Based on current trends, the aromatic ring is one of the popular sites in cathinone molecule being explored by designer-type modifications. In this study, we designed and synthesized a novel synthetic cathinone, 2-(methylamino)-1-(naphthalen-2-yl) propan-1-one (BMAPN), which has a naphthalene substituent on the aromatic ring. Thereafter, we determined whether BMAPN has rewarding and reinforcing effects through the conditioned place preference (CPP) test in mice and self-administration (SA) paradigm in rats. Locomotor sensitization was also assessed in mice during daily BMAPN treatment for 7days and drug challenge. Furthermore, we investigated the effects on BMAPN on dopamine-related genes in the striatum of mice using quantitative real-time polymerase chain reaction (qRT-PCR). BMAPN induced CPP at 10 and 30mg/kg and was modestly self-administered at 0.3mg/kg/infusion. Repeated BMAPN (30mg/kg) administration also produced locomotor sensitization. qRT-PCR analyses revealed decreased dopamine transporter and increased dopamine receptor D2 gene expression in the striatum of the BMAPN-treated mice. These data indicate that BMAPN has rewarding and reinforcing properties, which might be due to its effects on dopamine-related genes. The present study suggests that these findings may be useful in predicting abuse potential of future cathinone entities with aromatic ring substitutions.

Patterns of Use, Acute Subjective Experiences, and Motivations for Using Synthetic Cathinones (“Bath Salts”) in Recreational Users

ABSTRACTGiven the variety and potential toxicity of synthetic cathinones, clinicians and educators would benefit from information about patterns of and motivations for use, frequency of psychosocial consequences, and experience of acute subjective effects. We administered a comprehensive, web-based survey to 104 recreational users of synthetic cathinones. Sixty percent of respondents consumed synthetic cathinones once or more per month, usually snorting or swallowing these drugs, typically at home, usually with others, customarily during the evening and nighttime hours, and often in combination with another drug such as alcohol or marijuana. Acute subjective effects attributed to synthetic cathinones were similar to those of other psychostimulants, including increased energy, rapid heartbeat, racing thoughts, difficulty sleeping, euphoria, decreased appetite, open-mindedness, and increased sex drive. Reported reasons for using synthetic cathinones included its stimulating effects, curiosity, substitution for another drug, and being at a party/music event. Respondents had experienced an average of six negative consequences of using synthetic cathinones during the previous year (e.g., tolerance, neglecting responsibilities, personality change). In combination with previously published investigations, these findings increase our understanding of the reported rationales and outcomes of recreational use of synthetic cathinones.

Twenty-One Cases Involving Alpha-Pyrrolidinovalerophenone (α-PVP).

Twenty-one cases involving alpha-pyrrolidinovalerophenone (α-PVP) were submitted between 2012 and 2015 to the Western Department of Forensic Science Laboratory. Eighteen suspected impaired driving cases were determined to have α-PVP concentrations <0.005-0.09 mg/L. Three fatalities during this period were determined to have α-PVP concentrations ranging from 0.03 to >20 mg/L. Human use of synthetic cathinones like α-PVP has been reported to induce psychological effects such as delusions, paranoia, hallucinations and deleterious cardiovascular effects. Quantitation was performed using a liquid-liquid extraction with detection by liquid chromatography triple quadrupole mass spectrometry using electrospray ionization in a multiple reaction monitoring mode. The reported behaviors in the 18 suspected impaired driving cases ranged from central nervous system depression to eluding officers in a high speed chase. The mean and median DUID α-PVP concentrations were both 0.030 mg/L. The α-PVP concentrations in the three fatalities were determined to be 0.033, 0.054 and present >20 mg/L. In 18 DUID cases, only 4 cases reported side effects consistent with synthetic cathinones. Two of the three fatalities indicated histories of bath salt and/or recreational drug use. At this time, no correlation can be determined between side effects and α-PVP concentrations.