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An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as "bath salts".

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López-Arnau R, Martínez-Clemente J, Carbó ML, Pubill D, Escubedo E, Camarasa J.

Prog Neuropsychopharmacol Biol Psychiatry. 2013 Apr 17.

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AbstractINTRODUCTION:

Methylone (3,4-methylenedioxymethcathinone) is a new psychoactive substance and an active ingredient of "legal highs" or "bath salts". We studied the pharmacokinetics and locomotor activity of methylone in rats at doses equivalent to those used in humans.

MATERIAL AND METHODS:

Methylone was administered to male Sprague-Dawley rats intravenously (10mg/kg) and orally (15 and 30mg/kg). Plasma concentrations and metabolites were characterized by LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240min.

RESULTS:

Oral administration of methylone induced a dose-dependent increase in locomotor activity in rats. The plasma concentrations after i.v. administration were described by a two-compartment model with distribution and terminal elimination phases of α=1.95h-1 and β=0.72h-1. For oral administration, peak methylone concentrations were achieved between 0.5- 1h and fitted to a flip-flop model. Absolute bioavailability was about 80% and the percentage of methylone protein binding was of 30%. A relationship between methylone brain levels and free plasma concentration yielded a ratio of 1.42±0.06, indicating access to the central nervous system. We have identified four Phase I metabolites after oral administration. The major metabolic routes are N-demethylation, aliphatic hydroxylation and O-methylation of a demethylenate intermediate.

DISCUSSION:

Pharmacokinetic and pharmacodynamic analysis of methylone showed a correlation between plasma concentrations and enhancement of the locomotor activity. A contribution of metabolites in the activity of methylone after oral administration is suggested. Present results will be helpful to understand the time course of the effects of this drug of abuse in humans.

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The novel recreational drug 3,4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: self-administration and locomotor activity in rats.

See on Scoop.it - novel psychoactive substances Aarde SM, Huang PK, Creehan KM, Dickerson TJ, Taffe MA. Neuropharmacology. 2013 Apr 15. pii: S0028-3908(13)00140-8

Abstract

Recreational use of the cathinone derivative 3,4-methylenedioxypyrovalerone (MDPV; "bath salts") has increased worldwide in past years, accompanied by accounts of health and legal problems in the popular media and efforts to criminalize possession in numerous jurisdictions. Minimal information exists on the effects of MDPV in laboratory models. This study determined the effects of MDPV, alongside those of the better studied stimulant d-methamphetamine (METH), using rodent models of intravenous self-administration (IVSA), thermoregulation and locomotor activity. Male Wistar rats were trained to self-administer MDPV or METH (0.05 mg/kg/infusion, i.v.) or were prepared with radiotelemetry implants for the assessment of body temperature and activity responses to MDPV or METH (0-5.6 mg/kg s.c.). METH and MDPV were consistently self-administered within 10 training sessions (mg/kg/hour; METH Mean=0.4 and Max = 1.15; MDPV Mean=0.9 and Max = 5.8). Dose-substitution studies demonstrated that behavior was sensitive to dose for both drugs, but MDPV (0.01-0.50 mg/kg/inf) showed greater potency and efficacy than METH (0.1-0.25 mg/kg/inf). In addition, both MDPV and METH increased locomotor activity at lower doses (0.5-1.0 mg/kg, s.c.) and transiently decreased activity at the highest dose (5.6 mg/kg, s.c.). Body temperature increased monotonically with increasing doses of METH but MDPV had a negligible effect on temperature. Stereotypy was associated with relatively high self-administered cumulative doses of MDPV (∼1.5 mg/kg/hr) as well as with non-contingent MDPV administration wherein the intensity and duration of stereotypy increased as MDPV dose increased. Thus, MDPV poses a substantial threat for compulsive use that is potentially greater than that for METH.

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Analysis of MDPV in Blood--Determination and Interpretation.

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Adamowicz P, Gil D, Skulska A,

Abstract

3,4-Methylenedioxypyrovalerone (MDPV) is a cathinone derivative. It has recently been classified as a controlled substance in many countries. This substance is a stimulant that can be snorted, smoked or taken orally. MDPV has been determined in biological material from four cases sent to the Institute of Forensic Research in 2011. In the first case, a passenger car crashed into a truck; the driver of the vehicle suffered severe injuries, resulting in his death. In the second case, biological material was obtained from the decedent male individual, who did not wake up after a party. In the two cases, the material was secured on suspicion of the possession of narcotic drugs or psychotropic substances, in which the suspects admitted to using "legal highs." The MDPV blood concentrations of the deceased driver and deceased man were 38 and 17 ng/mL, respectively. In the two other cases, the determined concentrations were 306 and 124 ng/mL. However, MDPV was not the sole substance detected in these cases: in each, other drugs were also determined. Analyses of blood were conducted using liquid chromatography-tandem mass spectrometry.

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Analysis of new classes of recreational drugs in sewage: Synthetic cannabinoids and amphetamine-like substances.

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Compartment Syndrome After "Bath Salts" Use: A Case Series.

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Levine M, Levitan R, Skolnik A. (2013) Compartment Syndrome After "Bath Salts" Use: A Case Series. Ann Emerg Med.

Abstract

In recent years, synthetic cathinones, often labeled as "bath salts" in an attempt to evade drug laws, have emerged as substances of abuse. Sympathomimetic drugs are well known to cause rhabdomyolysis but are rarely associated with acute compartment syndrome. In this case series, we describe 3 patients who presented with sympathomimetic signs or symptoms including hyperthermia and agitation and had confirmed synthetic cathinone use. All 3 patients had severe rhabdomyolysis with delayed development of an acute compartment syndrome. Two patients developed paraspinal compartment syndromes, whereas 1 developed bilateral forearm compartment syndromes. Management included fasciotomy in 2 patients and medical management in the third. Two of the 3 patients made a complete recovery before hospital discharge; the third patient was hemodialysis dependent at 5-month follow-up.

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Kronic hysteria: Exploring the intersection between Australian synthetic cannabis legislation, the media, and drug-related harm.

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Stephen J. Bright, Brian Bishop, Robert Kane, Ali Marsh, Monica J. Barratt, Kronic hysteria: Exploring the intersection between Australian synthetic cannabis legislation, the media, and drug-related harm, International Journal of Drug Policy, Available online 17 January 2013AbstractBackground

Having first appeared in Europe, synthetic cannabis emerged as a drug of concern in Australia during 2011. Kronic is the most well-known brand of synthetic cannabis in Australia and received significant media attention. Policy responses were reactive and piecemeal between state and federal governments. In this paper we explore the relationship between media reports, policy responses, and drug-related harm.

Methods

Google search engine applications were used to produce time–trend graphs detailing the volume of media stories being published online about synthetic cannabis and Kronic, and also the amount of traffic searching for these terms. A discursive analysis was then conducted on those media reports that were identified byGoogle as ‘key stories’. The timing of related media stories was also compared with self-reported awareness and month of first use, using previously unpublished data from a purposive sample of Australian synthetic cannabis users.

Results

Between April and June 2011, mentions of Kronic in the media increased. The number of media stories published online connected strongly with Google searches for the term Kronic. These stories were necessarily framed within dominant discourses that served to construct synthetic cannabis as pathogenic and created a ‘moral panic’. Australian state and federal governments reacted to this moral panic by banning individual synthetic cannabinoid agonists. Manufacturers subsequently released new synthetic blends that they claimed contained new unscheduled chemicals.

Conclusion

Policies implemented within in the context of ‘moral panic’, while well-intended, can result in increased awareness of the banned product and the use of new yet-to-be-scheduled drugs with unknown potential for harm. Consideration of regulatory models should be based on careful examination of the likely intended and unintended consequences. Such deliberation might be limited by the discursive landscape.

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Kronic hysteria: Exploring the intersection between Australian synthetic cannabis legislation, the media, and drug-related harm.

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Stephen J. Bright, Brian Bishop, Robert Kane, Ali Marsh, Monica J. Barratt, Kronic hysteria: Exploring the intersection between Australian synthetic cannabis legislation, the media, and drug-related harm, International Journal of Drug Policy, Available online 17 January 2013AbstractBackground

Having first appeared in Europe, synthetic cannabis emerged as a drug of concern in Australia during 2011. Kronic is the most well-known brand of synthetic cannabis in Australia and received significant media attention. Policy responses were reactive and piecemeal between state and federal governments. In this paper we explore the relationship between media reports, policy responses, and drug-related harm.

Methods

Google search engine applications were used to produce time–trend graphs detailing the volume of media stories being published online about synthetic cannabis and Kronic, and also the amount of traffic searching for these terms. A discursive analysis was then conducted on those media reports that were identified byGoogle as ‘key stories’. The timing of related media stories was also compared with self-reported awareness and month of first use, using previously unpublished data from a purposive sample of Australian synthetic cannabis users.

Results

Between April and June 2011, mentions of Kronic in the media increased. The number of media stories published online connected strongly with Google searches for the term Kronic. These stories were necessarily framed within dominant discourses that served to construct synthetic cannabis as pathogenic and created a ‘moral panic’. Australian state and federal governments reacted to this moral panic by banning individual synthetic cannabinoid agonists. Manufacturers subsequently released new synthetic blends that they claimed contained new unscheduled chemicals.

Conclusion

Policies implemented within in the context of ‘moral panic’, while well-intended, can result in increased awareness of the banned product and the use of new yet-to-be-scheduled drugs with unknown potential for harm. Consideration of regulatory models should be based on careful examination of the likely intended and unintended consequences. Such deliberation might be limited by the discursive landscape.

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Increased brain metabolism after acute administration of the synthetic cannabinoid HU210: a small animal PET imaging study with 18F-FDG.

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» Digital Narcotics May Be the Future of Drugs

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Technologists will become the next drug dealers, administering narcotics through brain stimulation, according to one researcher.

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Scientists finding new uses for hallucinogens and street drugs

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Janeen Delany describes herself as an "old hippie" who's smoked plenty of marijuana. But she never really dabbled in hallucinogens -- until two years ago, at the age of 59.A diagnosis of incurable...

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Behavioral Responses to Acute and Sub-chronic A... [Neurotox Res. 2013] - PubMed - NCBI

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PubMed comprises more than 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Legal Highs- What You Need to Know (UK)

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Overall drug deaths are going down, but latest figures reveal ‘Legal High’ related deaths are going up (from just five in 2009 to 43 in a year). We talk to the newest breed of users and dealers

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Identification and structural characterization of the synthetic cannabinoid 3-(1-adamantoyl)-1-pentylindole as an additive in 'herbal incense'.

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Kneisel S, Westphal F, Bisel P, Brecht V, Broecker S, Auwärter V. J Mass Spectrom. 2012 Feb;47(2):195-200.

Abstract

Since the end of 2010, more than 20 synthetic cannabimimetics have been identified in 'Spice' products, demonstrating the enormous dynamic in this field. In an effort to cope with the problem, many countries have already undertaken legal measures by putting some of these compounds under control. Nevertheless, once a number of compounds were scheduled, they were soon replaced by other synthetic cannabinoids. In this article, we report the identification of a new--and due to its substitution pattern rather uncommon--cannabimimetic found in several 'herbal incense' products. The GC-EI mass spectrum first led to misidentification as the alpha-methyl-derivative of JWH-250. However, since both substances show different retention indices, thin-layer chromatography was used to isolate the unknown compound. After application of nuclear magnetic resonance spectroscopy, high-resolution MS and GC-MS/MS techniques, the compound was identified as 3-(1-adamantoyl)-1-pentylindole, a derivative of JWH-018 carrying an adamantoyl moiety instead of a naphthoyl group. This finding supports that the listing of synthetic cannabinoids as prohibited substances triggers the appearance of compounds with uncommon substituents. Moreover, it emphasizes the necessity of being aware of the risk of misidentification when using techniques sometimes providing only limited structural information like GC-MS.

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Legal Highs- What You Need to Know (UK)

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Overall drug deaths are going down, but latest figures reveal ‘Legal High’ related deaths are going up (from just five in 2009 to 43 in a year). We talk to the newest breed of users and dealers

See on live-magazine.co.uk

Party pill safety move due today - National - NZ Herald News

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The Government is expected to announce a new regime for party pills and fake cannabis which will require makers to prove their products are safe before they can be put on the market...

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Phenomenon of new drugs on the Internet: the case of ketamine derivative methoxetamine.

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Corazza O, Schifano F, Simonato P, Fergus S, Assi S, Stair J, Corkery J, Trincas G, Deluca P, Davey Z, Blaszko U, Demetrovics Z, Moskalewicz J, Enea A, di Melchiorre G, Mervo B, di Furia L, Farre M, Flesland L, Pasinetti M, Pezzolesi C, Pisarska A, Shapiro H, Siemann H, Skutle A, Enea A, di Melchiorre G, Sferrazza E, Torrens M, van der Kreeft P, Zummo D, Scherbaum N. Phenomenon of new drugs on the Internet: the case of ketamine derivative methoxetamine. Hum Psychopharmacol. 2012 Mar;27(2):145-9.

Abstract 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.

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Cannabis use doubles chances of vehicle crash

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Drivers who consume cannabis within three hours of driving are nearly twice as likely to cause a vehicle collision as those who are not under the influence of drugs or alcohol claims a paper published today on bmj.com.

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New psychotropic substances abstracts