2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone and Substance-Related-Disorders

An increasing number of novel psychoactive substances are currently available and sold as 'legal highs' or 'research chemicals' accompanied by the indication that they are 'not for human consumption'. Among those that have emerged in the last few years, methoxetamine (MXE) owes its wide popularity to its easy access on the Internet and its reputation of being a 'safe' drug. MXE is an arylcyclohexylamine with a chemical structure analogous to ketamine and phencyclidine, and similar noncompetitive glutamate N-methyl D-aspartate receptor antagonist properties. Yet, very recent preclinical data highlighted a stimulatory effect of MXE on dopamine neurotransmission within the mesolimbic pathway. The aim of this review is to provide an updated review of the behavioral and toxicological effects of MXE as well as the latest findings on its pharmacology that might explain sought effects and frequent occurrence of adverse effects. In light of the growing number of intoxications induced by MXE, knowledge of its short-term and long-term effects is urgently needed. However, the hypothetical rapid antidepressant activity of MXE suggested by its chemical analogy with ketamine and supported by recent preclinical findings deserves further investigation.

Topics: Animals; Cyclohexanones; Cyclohexylamines; Dopamine; Humans; Illicit Drugs; Substance-Related Disorders; Time Factors

Methoxetamine is one of the constantly growing group of novel psychoactive substances that has emerged in recent years. The compound belongs to the arylcyclohexylamine class, which is used for its recreational and psychedelic effects. Methoxetamine is a structural analogue of ketamine, with a much longer duration of action and intensity of effects, and has been extensively advertised as its 'legal' and 'bladder friendly' alternative. This review surveys the current state of knowledge regarding the metabolism, pharmacology, prevalence and pattern of methoxetamine use, and analytical methods of its detection. Consumption of methoxetamine bears a significant health risk and may even lead to fatal intoxication. A significant amount of research is still needed in order to fully quantify the short- and long-term effects of methoxetamine and its interaction with other drugs of abuse.

Topics: Cyclohexanones; Cyclohexylamines; Hallucinogens; Humans; Illicit Drugs; Ketamine; Substance-Related Disorders

Recent years have seen the emergence and proliferation of "legal highs" or "designer drugs," compounds purposefully designed as legal alternatives to controlled substances of abuse. This article describes methoxetamine, a dissociative drug belonging to the arylcyclohexylamine class including phencyclidine and ketamine. Methoxetamine acts principally on the glutamatergic N-methyl-D-aspartate receptor and the serotonin receptor. It is sold as a white or off-white powder. Marketed as a "bladder friendly" alternative to ketamine, preliminary research suggests renal and cystic toxicity similar to ketamine. Methoxetamine is primarily ingested nasally, though also orally, intramuscularly, intravenously, and rectally. Users report dissociative features and, at higher doses, an "m-hole" experience akin to ketamine's "k-hole" described as extreme depersonalization and derealization. The 13 cases of acute methoxetamine toxicity described in the literature are summarized. The toxidrome consists of dissociation/delirium, sympathetic activation, and cerebellar symptoms. Methoxetamine is not detected in standard urine drug tests and there are no reliable laboratory findings. Management of acute methoxetamine toxicity is supportive, consisting of benzodiazepines, antiemetics, intravenous fluids, and respiratory support as indicated. Should methoxetamine conform to the observed 2-year lag of designer drugs migrating from Europe to the United States usage may increase in early 2014.

Topics: Cyclohexanones; Cyclohexylamines; Designer Drugs; Humans; Illicit Drugs; Military Personnel; Substance-Related Disorders; United States

This article reviews the recreational use of ketamine ("Special K"; KET) and explores the recent diffusion of its new derivative methoxetamine ("Special M"; MXE). The literature search on the nonclinical/recreational use of KET and MXE was carried out in a range of medical databases. Considering the limitations of peer-reviewed information, data were integrated with a qualitative assessment of a range of websites, drug fora, and other online resources including e-newsgroups, chat rooms, mailing lists, e-newsletters, and bulletin boards. The recreational use of KET has started since its discovery in 1962. This was due to its rapid onset, short duration of action, and peculiar psychotropic effects ("K-hole"). The latter effect ranges from confusion to dissociation and depersonalization (near-death experience). However, KET abuse is often associated with physical and psychological side effects, of which the worst is urological/bladder toxicity. Recently, MXE has emerged as a legal and "bladder-friendly" KET alternative. MXE presents with the same dissociative effect of KET, but with slower onset and longer duration of action. However, MXE seems to be associated with worse side effects than KET, ranging from mood disturbances/suicidal attempts to acute cerebellar toxicity. After 50 years of its discovery, KET has led to the emergence of MXE. However, this latter derivative does not appear to be a safer alternative to KET itself.

Topics: Cyclohexanones; Cyclohexylamines; Humans; Illicit Drugs; Ketamine; Substance-Related Disorders

On the basis of the material available both in the scientific literature and on the web, this paper aims to provide a pharmacological, chemical and behavioural overview of the novel compound methoxetamine. This is a dissociative drug related to ketamine, with a much longer duration of action and intensity of effects. A critical discussion of the availability of information on the web of methoxetamine as a new recreational trend is here provided. Those methodological limitations, which are intrinsically associated with the analysis of online, non-peer reviewed, material, are here discussed as well. It is concluded that the online availability of information on novel psychoactive drugs, such as methoxethanine, may constitute a pressing public health challenge. Better international collaboration levels and novel forms of intervention are necessary to tackle this fast-growing phenomenon.

Topics: Cyclohexanones; Cyclohexylamines; Designer Drugs; Hallucinogens; Humans; Illicit Drugs; International Cooperation; Internet; Ketamine; Public Health; Substance-Related Disorders; Time Factors

Methoxydine (4-MeO-PCP) and Methoxetamine (3-MeO-2-Oxo-PCE) are both commercially produced designer drugs with structural and biochemical similarities to phencyclidine (PCP). Although phencyclidine toxicity is well documented, its recreational use in present times is rare. With the advent of new designer drugs being available widely through internet sites, Acute Physicians should be aware of the clinical features and management of these potential toxins. We present a case of methoxydine ingestion (which to our knowledge has not been previously documented in any medical journals) and a case of methoxetamine ingestion, and discuss their history, contrasting clinical features and acute management.

Topics: Adult; Cyclohexanones; Cyclohexylamines; Designer Drugs; Drug Overdose; Emergency Service, Hospital; Emergency Treatment; Follow-Up Studies; Humans; Illicit Drugs; Incidence; Male; Middle Aged; Neurotoxicity Syndromes; Phencyclidine; Risk Assessment; Substance-Related Disorders; Treatment Outcome

Hundreds of new psychoactive substances (NPS) have emerged in the drug market over the last decade. Few drug surveys in the USA, however, ask about use of NPS, so prevalence and correlates of use are largely unknown. A large portion of NPS use is unintentional or unknown as NPS are common adulterants in drugs like ecstasy/Molly, and most NPS are rapidly eliminated from the body, limiting efficacy of urine, blood and saliva testing. We utilized a novel method of examining prevalence of NPS use in a high-risk population utilizing hair-testing. Hair samples from high-risk nightclub and dance music attendees were tested for 82 drugs and metabolites (including NPS) using ultra-high performance liquid chromatography-tandem mass spectrometry. Eighty samples collected from different parts of the body were analyzed, 57 of which detected positive for at least one substance-either a traditional or new drug. Among these, 26 samples tested positive for at least one NPS-the most common being butylone (25 samples). Other new drugs detected include methylone, methoxetamine, 5/6-APB, α-PVP and 4-FA. Hair analysis proved a powerful tool to gain objective biological drug-prevalence information, free from possible biases of unintentional or unknown intake and untruthful reporting of use. Such testing can be used actively or retrospectively to validate survey responses and inform research on consumption patterns, including intentional and unknown use, polydrug-use, occasional NPS intake and frequent or heavy use.

Topics: Cyclohexanones; Cyclohexylamines; Hair; Humans; Illicit Drugs; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Pentanones; Prevalence; Psychotropic Drugs; Pyrrolidines; Substance Abuse Detection; Substance-Related Disorders

To assess the prevalence of use and subjective effect profile of methoxetamine among a group of polydrug users.. Cross-sectional, anonymous, online survey of UK-based polydrug users was conducted. Prevalence of lifetime, last year and last month use, sourcing of the drugs, motivations for use, and subjective effect and risk profile compared with that of ketamine were measured.. There were 7700 UK-based polydrug users, of whom 326 reported recent use of methoxetamine. Of the whole sample, 4.2% reported last 12 month use of methoxetamine compared with 24.5% for ketamine. The most common route of use was intranasal and the predominate effect described as psychedelic. Of the 15.5% of last year users of ketamine reporting last year use of methoxetamine, only 18.7% reported that they thought methoxetamine was less damaging to their kidneys or bladder than ketamine. Its broad effect profile, based on participants' first experience of use, was very similar to that of ketamine. Almost one-third of users reported that they did not intend to try the drug again.. Methoxetamine appears to have a broadly similar effect profile to that of ketamine. Only a minority of participants were motivated to use it because they believed it was less damaging to their kidneys or bladder than ketamine. The impact of the recent temporary banning order on availability and use of both methoxetamine and ketamine should be monitored carefully.

Topics: Adult; Cross-Sectional Studies; Cyclohexanones; Cyclohexylamines; Female; Hallucinogens; Humans; Illicit Drugs; Ketamine; Male; Motivation; Prevalence; Substance-Related Disorders; Surveys and Questionnaires; United Kingdom; Young Adult

Methoxetamine (MXE) is a ketamine analog sold online that has been subject to widespread abuse for its dissociative and hallucinogenic effects. Previous studies have shown that MXE has high affinity for the phencyclidine (PCP) binding site located within the channel pore of the NMDA receptor (NMDAR), but little is known about its behavioral effects. Dissociative anesthetics such as ketamine and PCP produce a characteristic behavioral profile in rats that includes locomotor hyperactivity and disruption of prepulse inhibition (PPI) of acoustic startle.. The goal of the present investigation was to determine whether MXE produces PCP-like effects in Sprague-Dawley rats using the PPI paradigm and the behavioral pattern monitor (BPM), which enables analyses of patterns of locomotor activity and investigatory behavior. PPI studies were conducted with several other uncompetitive NMDAR antagonists that produce dissociative effects in humans, including PCP, the S-(+) and R-(-) isomers of ketamine, and N-allylnormetazocine (NANM; SKF-10,047).. MXE disrupted PPI when administered at 3 and 10 mg/kg SC. The rank order of potency of MXE and the other test compounds in the PPI paradigm (PCP > MXE > S-(+)-ketamine > NANM > R-(-)-ketamine) parallels their affinities for the PCP binding site reported in the literature. When tested in the BPM, 10 mg/kg MXE induced locomotor hyperactivity, reduced the number of rearings, increased the roughness of locomotor paths, and produced perseverative patterns of locomotion. Administration of PCP (2.25 and 6.75 mg/kg, SC) produced a similar profile of effects in the BPM.. These results indicate that MXE produces a behavioral profile similar to that of other psychotomimetic uncompetitive NMDAR antagonists. Our findings support the classification of MXE as a dissociative drug and suggest that it likely has effects and abuse potential similar to that of PCP and ketamine.

Topics: Acoustic Stimulation; Animals; Cyclohexanones; Cyclohexylamines; Exploratory Behavior; Male; Motor Activity; Prepulse Inhibition; Rats; Rats, Sprague-Dawley; Reflex, Startle; Substance-Related Disorders

The intoxication caused by "kiken" drugs (law-evading drugs), such as synthetic cannabinoids, cathinones, and methoxetamine, has recently increased in Japan. We retrospectively examined the characteristics of patients poisoned with the "kiken" drugs. We included patients who presented at the emergency department at the Tokyo Metropolitan Bokutoh Hospital from January 2011 to December 2014. Eighteen patients admitted between January 2011 and December 2013 were included in the early period group and 10 patients admitted between January and December 2014 were categorized into the late period group. The number of the patients transported to our emergency department between 2011 and 2014 increased annually. Patients were mainly admitted between May and October 2014; no patients were admitted after November 2014. The patients' age, history of previous mental disease, habitual use, Triage DOA results, serum creatinine values on admission, and respiratory management differed significantly between the groups. However, the median serum creatinine values of both groups on admission were within the normal level. Patients poisoned with the "kiken" drugs showed more severe symptoms, higher rate of habitual use, and higher average age. The annual increase in the number of the patients observed thus far is expected to decrease in the future. Maintenance of the law and expansion of medical institutions that treat patients addicted to the "kiken" drugs are warranted.

Topics: Adult; Age Factors; Alkaloids; Cannabinoids; Creatinine; Cyclohexanones; Cyclohexylamines; Emergency Service, Hospital; Female; Humans; Illicit Drugs; Male; Respiration, Artificial; Retrospective Studies; Severity of Illness Index; Substance-Related Disorders; Time Factors; Tokyo; Triage; Young Adult

Methoxetamine (MXE) is an N-methyl-d-aspartate (NMDA) receptor antagonist that is chemically and pharmacologically similar to ketamine. Recently, there have been many reports regarding its use/misuse in humans which have resulted in serious or even fatal outcomes. Despite these reports, MXE is not controlled or regulated in many countries which may be partly due to the lack of scientific evidence regarding its abuse potential. Thus, in the present study we evaluated the abuse potential (rewarding and reinforcing effects) of MXE through the conditioned place preference (CPP) and self-administration (SA) tests in Sprague-Dawley rats. In addition, locomotor activity during the conditioning phase of the CPP was also analyzed. Ketamine was used as a reference drug. MXE (2.5 and 5mg/kg) induced significant CPP in rats, an effect comparable to that of ketamine (5mg/kg). Interestingly, MXE did not produce any locomotor alterations while ketamine decreased the locomotor activity of rats. In the SA test, rats showed modest self-administration of MXE (0.25, 0.5, 1.0mg/kg/infusion), while ketamine (0.5mg/kg/infusion) was robustly self-administered. These results demonstrate that MXE, similar to ketamine, has rewarding and reinforcing effects in rats. The present study strongly suggests that MXE has a potential for human abuse. In addition, the discrepant effects of MXE and ketamine on locomotor activity and rate of self-administration propose that the psychopharmacological effects of these drugs may diverge in some aspects. More importantly, this study advocates the careful monitoring and prompt regulation of MXE and its related substances.

Topics: Animals; Conditioning, Psychological; Cyclohexanones; Cyclohexylamines; Dose-Response Relationship, Drug; Ketamine; Male; Motor Activity; Rats; Self Administration; Substance-Related Disorders

The goal of this study is to provide an update on the data given on methoxetamine (MXE)-related fatalities that occurred in 2011-2013, presented at the Second International Conference on Novel Psychoactive Substances.. Fatalities involving MXE were extracted from the database of the National Programme on Substance Abuse Deaths, which receives information on drug-related deaths from Coroners in the UK and Islands (Isle of Man, Jersey, Guernsey) and other data suppliers.. Eight cases, received by 3 September 2013, in which MXE was found at post-mortem and/or directly implicated in the death and/or mentioned in the Coroner's verdict are described. The median age at death was 27 years, with the majority of White ethnicity (6/8) and male (7/8). MXE was used together with other substances in 7/8 cases. MXE was found at post-mortem in all cases, directly implicated in the deaths of four and likely to have had an influence in two.. More research needs to be conducted into its health effects and toxicity potential. Health care professionals should be made aware of the potential health harms of MXE, in order to develop early intervention measures and minimise the number of MXE-related poisonings and fatalities.

Topics: Adolescent; Adult; Cyclohexanones; Cyclohexylamines; Diagnosis; Female; Humans; Illicit Drugs; Male; Retrospective Studies; Substance-Related Disorders; United Kingdom; Young Adult

We conducted a multicenter retrospective survey of patients poisoned by synthetic chemicals (SCs) in Japan.. Letters were sent to 467 emergency facilities requesting participation in the study, and questionnaires were mailed to facilities that agreed to participate. Patients The study participants were patients who were transported to emergency facilities between January 2006 and December 2012 after consuming SC-containing products.. We surveyed 518 patients from 60 (12.8%) facilities. Most patients were male (82.0%), in their 20s or 30s (80.5%), and had inhaled SCs (87.5%) contained in herbal products (86.0%). Harmful behavior was observed at the scene of poisoning for 56 patients (10.8%), including violence to others or things in 32, traffic accidents in seven, and self-injury or suicide attempts in four. Other than physical and neuropsychiatric symptoms, some patients also had physical complications, such as rhabdomyolysis (10.0%). Of the 182 patients (35.1%) admitted to hospitals, including 29 (5.6%) who needed respirators, all of the 21 (4.1%) hospitalized for at least seven days were male, and 20 had physical complications (rhabdomyolysis, 12; liver dysfunction, 5; renal dysfunction, 11; and physical injuries, 3). Most patients (95.6%) completely recovered, although 10 (1.9%) were transferred to a psychiatric department or hospital, and three (0.6%) were handed over to the police due to combative or violent behavior. SCs such as synthetic cannabinoids, synthetic cathinones, or methoxetamine were detected in 20 product samples.. Consuming products containing SCs can result in physical complications, including rhabdomyolysis, injuries, and physical or neuropsychiatric symptoms, which may require active interventions, such as respirator use or prolonged hospitalization.

Topics: Adult; Aged; Alkaloids; Cannabinoids; Child; Cyclohexanones; Cyclohexylamines; Data Collection; Designer Drugs; Emergency Service, Hospital; Female; Hospitalization; Humans; Illicit Drugs; Infant; Japan; Male; Middle Aged; Outcome Assessment, Health Care; Psychotropic Drugs; Retrospective Studies; Substance-Related Disorders; Young Adult

To report the demographic and clinical characteristics of cases of methoxetamine toxicity reported to The National Poisons Information Service (NPIS) by healthcare professionals. To assess the pattern of enquiries from health professionals to the UK NPIS related to methoxetamine, including the period of the making of the UK first Temporary Class Drug Order (TCDO).. All telephone enquiries to and user sessions for TOXBASE, the NPIS on-line information resource, related to methoxetamine (and synonyms 'MXE', 'mket' and '2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone') were reviewed from 1 April 2010 to 1 August 2012. Data were compared for the 3 months before and after the TCDO.. There were 47 telephone enquiries and 298 TOXBASE sessions regarding methoxetamine during the period of study. Comparing the 3 months before and after the TCDO, TOXBASE sessions for methoxetamine fell by 79% (from 151 to 32) and telephone enquiries by 80% (from 15 to 3). Clinical features reported by enquirers were consistent with case reports of analytically confirmed methoxetamine toxicity and typical toxidromes were of stimulant (36%), reduced consciousness (17%), dissociative (11%) and cerebellar (6.4%) types, but also particularly featured acute disturbances in mental heath (43%).. Structured NPIS data may reveal trends in drugs of abuse use and toxicity when interpreted within their limitations. Since April 2012, there have been fewer enquiries to NPIS from clinicians, indicating reduced presentations with suspected methoxetamine toxicity to healthcare services. It is unclear if this is related to the TCDO made on 5 April 2012.

Topics: Cyclohexanones; Cyclohexylamines; Databases, Factual; Drug Information Services; Substance-Related Disorders; Telephone; United Kingdom

Topics: Alkaloids; Cyclohexanones; Cyclohexylamines; Designer Drugs; Humans; Illicit Drugs; Legislation, Drug; Poison Control Centers; Psychotropic Drugs; Substance-Related Disorders; United Kingdom; United States

Topics: Cyclohexanones; Cyclohexylamines; Humans; Illicit Drugs; Substance-Related Disorders

Methoxetamine (MXE) is an analogue of ketamine.. We present a 25-year-old male who, after getting an information from the Internet, started to use MXE to avoid the excitement connected with recreational codeine abuse. For about 8 - 10 months he injected about 100 mg of MXE intramuscularly. On the day of admission the patient decided to take much higher dose of 750 mg of MXE. For the first 3-4 hours of hospitalization the profound agitation, which demanded the usage of high doses of benzodiazepines, was observed every several minutes. After 6-7 hours of supportive treatment the patient returned to his baseline mental status.. MXE presents the new healthcare threat because of easy accessibility via Internet, and lack of legal restrictions in many countries. The low dose of MXE can cause "peace and serenity", however, higher dose may act opposite.

Topics: Adult; Akathisia, Drug-Induced; Codeine; Cyclohexanones; Cyclohexylamines; Humans; Illicit Drugs; Injections, Intramuscular; Internet; Male; Substance-Related Disorders