Susannah Davies

Case series of individuals with analytically confirmed acute mephedrone toxicity.

Context. Previous reports of acute toxicity/harm associated with mephedrone use have been based on self-reported mephedrone use; toxicological screening has not been undertaken in these cases to determine whether mephedrone has been used. Objective. To report the first case series of analytically confirmed mephedrone-related acute toxicity. Materials and methods. Serum samples were collected from individuals presenting to an emergency department (ED) with acute toxicity related to self-reported mephedrone use. Toxicological analysis, by gas-chromatography coupled with mass-spectrometry and liquid chromatography with tandem mass-spectrometry was performed to qualitatively confirm mephedrone use. Symptoms/signs of acute mephedrone toxicity and basic physiological parameters were extracted from the routine ED records. Results. Acute mephedrone-related toxicity was analytically confirmed in seven male patients; the mean ± SD age was 24.6 ± 6.5 years (range 16–36 years). Agitation (four patients) was the most common symptom/sign reported; other common symptoms/signs included: palpitations (two patients); chest pain (two patients); self-limiting pre-hospital seizures (one patient) and headaches (one patient). The mean heart rate was 109.1 ± 21.8 (range 80–140) beats per minute; one patient had a “severe” tachycardia (heart rate of ≥140 bpm). The mean systolic blood pressure was 153.0 ± 39.6 (range 110–210) mmHg; three patients had clinically significant hypertension (systolic blood pressure ≥160 mmHg). Discussion. These analytically confirmed acute mephedrone toxicity presentations had clinical features of toxicity consistent with an acute sympathomimetic toxidrome (e.g. hypertension, tachycardia and agitation). These findings are similar to the pattern of toxicity seen with other sympathomimetic recreational drugs such as 3,4-Methylenedioxymethamphetamine (MDMA) and cocaine. Conclusion. The process for determining whether a novel psychoactive substance should be controlled often relies on demonstrated/proven acute harm associated with its use. It is important that clinical toxicologists undertake appropriate biological sampling and toxicological analyses in suspected cases of “novel psychoactive drug” toxicity. This will ensure that both clinicians and legislative authorities are informed of the confirmed pattern of toxicity associated with these drugs.

Methoxetamine associated reversible cerebellar toxicity: three cases with analytical confirmation.

Abstract Context. There have been recent concerns about increasing use and accessibility of methoxetamine, a ketamine derivative. Few data are available to describe the clinical features associated with methoxetamine exposure. We report three cases that presented to hospital with acute neurological toxicity associated with analytically confirmed methoxetamine exposure. Case details. A 19-year-old male presented with severe truncal ataxia, nystagmus, incoordination and reduced conscious level several hours after nasal insufflation of what was initially thought to be ketamine. Features of cerebellar toxicity persisted for 3–4 days before gradual recovery. Two more patients aged 17 and 18 years presented with severe cerebellar ataxia, imbalance and reduced conscious level 40 minutes after nasal insufflation of methoxetamine (MXE). Both had slurred speech, incoordination and cerebellar ataxia that resolved within 24 hours. Serum methoxetamine concentrations were 0.24 mg/L, 0.45 mg/L and 0.16 mg/L, respectively, and no other drugs were identified on an extended toxicological screen. Discussion. Methoxetamine may cause rapid onset of neurological impairment, characterised by acute cerebellar toxicity. Spontaneous recovery was observed, but the duration of recovery may extend to several days. Presentation with an acute cerebellar toxidrome should alert clinicians to the possibility of methoxetamine exposure.

Delayed Onset of Seizures and Toxicity Associated with Recreational Use of Bromo-dragonFLY

IntroductionMany countries have specific legislation, such as the Controlled Substances Act (1970) in the United States and the Misuse of Drugs Act (1971) in the United Kingdom to control recreational drugs. There is a growing market and supply of “novel” recreational drugs, which include the misuse of pharmaceutical compounds and research chemicals. These are often not covered under current legislation, despite the fact that they often have both similar chemical structures and/or clinical effects to controlled recreational drugs.Case ReportA male patient presented to an emergency department with delayed of severe agitation, hallucinations, and tonic-clonic seizures following the use of Bromo-dragonFLY and an unknown white powder. He settled following IV benzodiazepines and supportive care, and was discharged with no evidence to long-term sequelae: Analysis of the white powder by gas chromatography/mass spectrometry (GC/MS), ultraviolet/visible spectrophotometry (UV/VIS) and thin layer chromatography (TLC) showed the presence of Bromo-dragonFLY (1-(8-bromobenzol[1,2-b;4,5-b’]difuran-4-yl)-2-aminopropane); serum analysis by GC/MS and liquid chromatography with tandem mass spectrometry (LC/MS/MS)_confirmed that a combination of Bromo-dragonFLY (0.95 ng/mL). ketamine (20 ng/mL) and canabis had been used by the patient. No other recreational drugs were detected in an extensive toxicological screen of serum and urine samples.DiscussionThis is the first confirmed case to be reported of toxicity with delayed onset of severe agitation, hallucinations and tonic-clonic seizures associated with recreational use of Bromo-dragonFLY (1-(8-bromobenzol[1,2-b;4,5-b’]difuran-4-yl)-2-aminopropane) in combination with ketamine and cannabis. In our view, this case provides further support for the need for a systematic approach to toxicological screening of patients with recreational drug toxicity, to identify emerging drugs and provide evidence for legislative authorities to assist in revising the legal status of emerging recreational drugs.

Variability in the 3,4-methylenedioxymethamphetamine content of ‘ecstasy’ tablets in the UK

Background Toxicity, such as hyperpyrexia, associated with the use of 3,4-methylenedioxymethamphetamine (MDMA; ‘ecstasy’) appears to be related to serum MDMA concentrations. However, there does not appear to be a similar association with the number of tablets ingested, suggesting variation in the tablet content of MDMA. Although work has shown this variation in other areas of the world, no studies have reported on the variation of MDMA content in UK ecstasy tablets. Methods Ecstasy tablets seized from individuals attending nightclubs were analysed qualitatively to determine if they contained MDMA and quantitatively to determine the MDMA content per tablet. Results The mean amount of MDMA hydrochloride in 101 seized ecstasy tablets was 58.7±22.9 mg per tablet, with a range of 20 mg to 131 mg per tablet. The majority (96.0%) of tablets contained less than 100 mg MDMA per tablet. There appeared to be a bimodal distribution of MDMA content at approximately 20–40 mg per tablet and 60–80 mg per tablet. Conclusion There is variability in the MDMA content of ecstasy tablets in the UK. This variability could potentially put users at increased risk of acute harm due to inadvertent excess ingestion of MDMA, as they are unaware of the differences in the MDMA content. Repeat sampling and quantification of MDMA content of ecstasy tablets in the UK will allow better education of users about the potential harms associated with the variability in the MDMA content. In addition, it will provide information to allow the monitoring of changes in not only the MDMA content, but also other adulterants, in ecstasy tablets.

Taking the Pissoir – a novel and reliable way of knowing what drugs are being used in nightclubs

Background: The epidemiology on recreational drug use is based on self-reported user surveys. The scope of this is limited as users are often not aware of exactly what drug(s) they are using. Waste water (sewage plant) analysis has been used to identify “regional” recreational drug use but is limited by a lack of understanding of the metabolism and stability of novel recreational drugs. Aims: The feasibility of collecting pooled urine samples from a sub-population attending a night-club using a portal urinal to confirm the classical and novel recreational drugs being used. Design and Methods: Urine samples were collected from a nightclub over one weekend for analysis by various chromatographic techniques involving mass spectrometry. Results: Classical recreational drugs and novel psychoactive substance, including mephedrone, 3-trifluoromethylphenylpiperazine and 2-aminoindane were found. Parent drug/metabolites were also detected for amphetamine, cocaine, ketamine, MDMA, mephedrone and 3-trifluoromethylphenylpiperazine. Conclusion: Anonymous pooled urine samples from within a nightclub can be used to confirm the actual drugs being used by some individuals within this sub-population. Metabolite detection indicates drugs were being used and not simply discarded into the urinal. This methodology could be used to monitor recreational drug trend in other environments, e.g. schools, geographical regions/areas and compare drug use over time.

Novel drugs—novel branding

There has been increasing use of a number of different novel psychoactive substances (often referred to as ‘legal highs’) over the last few years. The drug that has received the most publicity is mephedrone.1 However, there were 41 new substances detected in Europe in 2010.2 These novel psychoactive substances are often purchased from Internet-based suppliers and are commonly marketed under broad categories such as ‘plant food’, ‘bath salts’ and ‘research chemicals’.2 They are also often sold under brand names such as ‘Ivory Wave’, ‘Head Candy’ and ‘Neuroblast’. Neither the broad categories or these brand names are representative of the actual contents of the products.3–5 There is often little information on …

Energy-1 (‘NRG-1’): don't believe what the newspapers say about it being legal

A 31-year-old man purchased the legal high Energy-1 (NRG-1) over the internet; this was advertised as containing the compound naphthylpyrovalerone (NPV), which at the time was currently legally available in the UK. He ingested 1 g of this substance and developed a prolonged high associated with palpitations, sweating and insomnia. Analysis of both the powder and serum samples from the patient demonstrated that he ingested two classified recreational drugs β-keto-N-methylbenzodioxolylpropylamine (butylone) and methylenedioxypyrovalerone (MDPV) rather than the legal substance NPV. Users of legal highs need to be aware that legal highs purchased over the internet may contain illegal substances and therefore they may be liable for prosecution if found in possession of these substances. Future educational campaigns aimed at recreational drug and legal high users should include reference to the potential legal implications of buying these substances.