Trends in Ketamine Use, Exposures, and Seizures in the United States up to 2019.

Objectives. To determine whether there have been shifts in nonmedical ketamine use, poisonings ("exposures"), and seizures. Methods. We used generalized additive models to detect trends in past-year use (2006-2019), exposures (1991-2019), and seizures (2000-2019) involving ketamine in the United States. Results. There was a quarterly increase in self-reported past-year nonmedical ketamine use in 2006 to 2014 (Β = 0.21; P = .030) and an increase in 2015 to 2019 (Β = 0.29; P = .036), reaching a peak of 0.9% in late 2019. The rate of exposures increased from 1991 through 2019 (Β = 0.87; P = .006), and there was an increase to 1.1 exposures per 1 000 000 population in 2014, with rates remaining stable through 2019. The rate of ketamine seizures increased from 2000 through 2019 (Β = 2.27; P < .001), with seizures reaching a peak in 2019 at 3.2 per 1000 seizures. Conclusions. Indicators suggest that ketamine use and availability has increased, including before increased medical indications, but nonmedical use is still currently uncommon despite increased acceptance and media coverage. (Am J Public Health. 2021;111(11):2046-2049. https://doi.org/10.2105/AJPH.2021.306486).

Recreational ketamine-related deaths notified to the National Programme on Substance Abuse Deaths, England, 1997-2019.

BACKGROUND: Ketamine is a phencyclidine derivative with dissociative anaesthetic properties. Increasing numbers of individuals in England take ketamine recreationally. Information on deaths arising from such use in England is presented. METHODS: Cases were extracted on 31 January 2020 from the National Programme on Substance Abuse Deaths database, based on text searches of the cause of death, coroner's verdict and positive toxicology results for the terms 'ketamine' or 'norketamine'. FINDINGS: During 1997-2005, there were <5 deaths p.a. in which ketamine was implicated. Numbers increased until 2009 (21), plateauing until 2016; thereafter, deaths have risen to about 30 p.a. Decedents' characteristics (N = 283): male 84.1%, mean age 31.2 (SD 10.0) years, employed 56.5%, drug use history 79.6% and living with others 60.3%. Ketamine was detected with other substances in most cases. Main (74.6%) underlying cause of death was accidental poisoning. Ketamine may have impaired judgement in other cases. CONCLUSIONS: Although controlled, recreational ketamine use and related fatalities continue to increase. Consumers need to be more aware of the potentially fatal risks they face.

Fatal intoxication related to two new arylcyclohexylamine derivatives (2F-DCK and 3-MeO-PCE).

Continuous development and rapid turnover of drug market of new psychoactive substances (NPS) make it difficult to obtain up-to-date analytical methods for efficient detection of intoxication cases with new substances: no analytical data and no previously published concentration values in biological samples are indeed available. In this context, we aim to report the first fatal case involving two newly emerging arylcyclohexylamine derivatives (a group of dissociative ketamine-based substances): 2-fluoro-deschloroketamine (2F-DCK) and 3-methoxyeticyclidine (3-MeO-PCE). A 42-year-old man was found dead at his home with three plastic bags of "research chemicals" powders near him. Comprehensive screenings of drugs and toxic compounds as well as more selective assays (performed using NMR, HS-GC-FID, LC-MS/MS and LC-HRMS methods) allowed (1) to identify the three unknown powders, 2F-DCK, 3-MeO-PCE, and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT, a hallucinogenic tryptamine-related NPS), with purity above 95%, and (2) to determine peripheral blood (1780, 90, and 52 µg/L), urine (6.1, 6.3, and 2.2 mg/L), bile (12, 3.5, and 1.7 mg/L), and vitreous humour (1500, 66 and 155 µg/L) concentrations of 2F-DCK, 3-MeO-PCE and 5-MeO-DMT, respectively. In addition, toxicological results also revealed recent use of cannabis, cocaine, and amphetamine by the victim, and hair analysis draw pathway of addiction (including experiments with various other NPS) for several months before death. This fatality was considered as the consequence of respiratory depression in a poly-drug user due to a "cocktail effect" of concurrent intakes of 2F-DCK (mainly), 3-MeO-PCE, 5-MeO-DMT, amphetamine, and cocaine. In addition, this case report provides analytical data that could support subsequent toxicological result interpretation in forensic cases involving such arylcyclohexylamine derivatives.

Characteristics and circumstances of death related to the self-administration of ketamine.

BACKGROUND AND AIMS: Ketamine is used for anaesthesia, sedation and the treatment of mood disorders, but is also widely used for non-medical purposes. This study aimed to: (1) determine the characteristics and circumstances of all recorded cases of self-administered ketamine-related death in Australia, 2000-19 and (2) determine the toxicology and major organ pathology of cases. DESIGN: Retrospective study of all Australian cases in which self-administered ketamine was a mechanism contributory to death, retrieved from the National Coronial Information System. SETTING: Australia-wide. CASES: Sixty-eight cases, with a mean age of 35.2 years (standard deviation = 11.5, range = 16-63), 76.5% male. MEASUREMENTS: Information was collected on cause of death, demographics, circumstances of death, toxicology and major organ pathology. FINDINGS: Death was attributed to toxicity in 82.3% of cases (accidental, 58.8%; deliberate, 23.5%), suicide by violent means (8.8%) and traumatic accident (8.8%). In six cases the decedent had been prescribed ketamine. In 32.4% the final route of ketamine administration was by injection. The fatal incident predominantly occurred in a private environment (72.1%). Ketamine was present in the blood of 90.1% and other biomarkers in the remainder. The median blood ketamine concentration was 0.2 mg/l (0.02-6.9 mg/l). Other drugs were detected in 95.5% of cases: opioids (59.1%), hypnosedatives (57.6%), psychostimulants (50.0%), alcohol (27.3%), Δ-9-tetrahydrocannabinol (18.2%), antidepressants (28.8%) and antipsychotics (9.1%). Pulmonary oedema was present in 82.2% of cases that underwent autopsy and pneumonia in 26.7%. CONCLUSIONS: The typical case of self-administered ketamine-related death in Australia, 2000-19, was a male in his mid-30s who had used multiple drugs, with the fatal incident most commonly occurring in a private setting. Death due to accidental drug toxicity was the most common manner of death, but suicide was highly prevalent.

Violence against women and drug-facilitated sexual assault (DFSA): A review of the main drugs.

Sexual violence is a universal phenomenon without restriction to sex, age, ethnicity or social class that causes devastating effects in the physical and mental health spheres, in the short-term and long-term, such as pregnancy, sexually transmitted infections (STI) and greater susceptibility to psychiatric symptoms, especially depression. Some cases of sexual assault and rape are based on the use of so-called drug-facilitated sexual assault (DFSA), which cause victims' loss of consciousness and inability to defend, making them vulnerable to violence. Thus, this article aimed to review the literature on gender violence and the drugs used to facilitate sexual assault, addressing their mechanism of action and pharmacokinetics, as well as drug detection times in human body and types of forensic identification. It is understood that the knowledge of these drugs and their pharmacological and diagnostic mechanisms should be widely disseminated, especially about sensitivity tests and the time the drug remains in the body, which would validate the promotion of evidence to prove abuse, and, thus, being able to give a promising outcome to cases of aggression, which is extremely beneficial for women.

Mortalities of methamphetamine, opioid, and ketamine abusers in Shanghai and Wuhan, China.

Studies on the mortalities of drug abusers in China are scarce. This study explores the deaths of methamphetamine, opioid, and ketamine abusers in Shanghai (2004-2017) and Wuhan (2005-2017). Chi-square/Fisher's exact tests were used to compare the differences in terms of region, gender, age, cause of death, and the method used in the last drug abuse. Poisson regression models were used to estimate the rate ratios ("RRs") and annual percentage changes ("APCs"). 314 heroin, 43 methamphetamine, and 4 ketamine abusers were included. Furthermore, simultaneously, 6 abusers used heroin and methamphetamine, and 7 abusers used methamphetamine and ketamine. Heroin-related deaths have declined in Shanghai (APC, -16.1; 95 % CI, -18.4 to -11.3) and Wuhan (APC, -16.0; 95 % CI, -18.9 to -10.6), whereas methamphetamine-related deaths have increased in Wuhan (APC, 12.8; 95 % CI, 0.0 to 29.2). On the whole, in the two cities, males were more frequently observed than females in heroin-related deaths (4.4, 230/52). However, the gender ratios for methamphetamine- (1.8, 34/19) and ketamine-related deaths (1.2, 6/5) were close to one. In view of the mortality rates of the drug abusers in most Chinese cities were still unclear, it is thus important to improve mortality surveillance of the drug abusers at the national level.

A Fatal Case Involving N-Ethyldeschloroketamine (2-Oxo-PCE) and Venlafaxine.

Methoxetamine, 3-methoxyphencyclidine or 3-methoxyeticyclidine are arylcyclohexylamines which have been abused in the past. However, the market for new psychoactive substances, in particular for research chemicals, is rapidly growing and new compounds are being regularly explored by users. Abuse can lead to clinical case and in the worst-case scenario to fatalities. We present the fatal case of a 52-year-old man, who was found dead in the bedroom by his fiancé. He had abused N-ethyldeschloroketamine and venlafaxine prior to his death. These compounds were retrieved from a non-targeted gas chromatography/mass spectrometry-based screening approach of a purified urine sample. In addition, deschloroketamine, bisoprolol and ramiprilate were found in the urine sample, but were either absent or only present at low level in femoral blood. During autopsy a number of tablets were found in the duodenum and identified as venlafaxine. Furthermore, N-ethyldeschloroketamine was quantified in various specimens taken during autopsy and the highest concentration was observed in liver (6,137 ng/g) followed by urine (3,468 µg/L), bile fluid (3,290 µg/L), gastric contents (3,086 µg/L), heart blood (2,159 µg/L) and liquor (1,564 µg/L). The smallest amount was found in femoral blood (375 µg/L). N-ethyldeschloroketamine was also found in the disposable syringes, in a beaker and on the spatula along with deschloroketamine, morphine, metamizole, oxycodone, flupirtin or ibuprofen. The concentrations presented-in particular for femoral blood-are a good starting point for evaluating N-ethyldeschloroketamine intoxications in the future. The other values are helpful for evaluating the post-mortem concentration distribution of this research chemical.

Intoxicación por el cannabinoide sintético 5-fluoro-ABD, adquirido como ketamina / Intoxication by the synthetic cannabinoid 5-fluoro-ABD, acquired as ketamine

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Ketamine exposure demographics and outcomes over 16 years as reported to US poison centers.

BACKGROUND: This study sought to examine ketamine exposures reported to US poison centers over the past 16 years and identify trends in exposures and outcomes. METHODS: A retrospective review was performed of all cases involving ketamine exposures reported to US poison centers and entered into the National Poison Data System from 2000 to 2015. Cases were divided into those involving ketamine alone and those involving ketamine and other agents. Data collected included: age, sex, form of ketamine used, reason for exposure, and outcome. RESULTS: A total of 3109 cases were evaluated. 1595 (51%) reported ketamine to be the only substance exposure, while 1514 (49%) involved multiple substances with ketamine. For single agent exposures, more involved males (67%) between the ages of 16-25 years (49%). Single agent ketamine exposures peaked between 2000 and 2002, fell consistently until 2008; then rebounded to previous peak levels through 2015. Intentional exposures (65% of all cases) were the most common reason for single agent ketamine exposures. 53% of ketamine-only cases resulted in minor effects, with two deaths. In contrast, ketamine exposures with multiple agents resulted in outcomes judged as moderate or worse in 62% of cases, including 20 deaths. CONCLUSION: Single-agent ketamine exposures reported to US poison centers have rebounded to historical peaks in recent years. More deaths and serious outcomes were reported in ketamine exposures involving multiple substances.

Ambient mass spectrometry for rapid diagnosis of psychoactive drugs overdose in an unstable patient.

A 25-year-old man suffered from consciousness change was sent to our emergency department by friends who reported that they were not sure what had happened to him. Physical examination revealed bilateral pupils dilatation, lethargy, slurred speech, and ataxia. Computer-aided tomographic scan of the brain revealed no definite evidence of intracranial lesions. Routine laboratory tests revealed total physiological turmoil. Despite immediate commencement of aggressive treatment, the patient's condition deteriorated long before the traditional drug screen provided an answer for the identities of the multiple drugs overdose. It ended up with the need for cardiopulmonary resuscitation, but in vain. At the end of the tragic event, under the suggestion of a colleague, a portion of the patient's urine specimen was sent to our university esoteric laboratory for rapid analysis by means of a newly-developed thermal desorption-electrospray ionization-mass spectrometry. Ketamine, 3,4-methylenedioxymethamphetamine, and 3,4-methylenedioxyamphetamine were identified in the urine sample within 30s. Conventional toxicological testing techniques like gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry are currently used for identifying abused drugs. One concern is their time-consuming sample pretreatment which leads to relatively low efficiency in terms of turnaround time for revealing the identity of the consumed drugs particularly when the patients are severely overdosed. We learned a lesson from this case that a more efficient toxicological identification technique is essential to expedite the process of emergency care when the patients are so heavily overdosed that they are under critical life-threatening conditions.

Ketamine-related cholangiopathy: a retrospective study on clinical and imaging findings.

PURPOSE: Ketamine is a commonly abused recreational drug in Southeast Asia. There are emerging reports on ketamine abuse causing liver injury and biliary dilatation. This retrospective study aims to investigate the clinical and radiological features of this condition. METHODS: A retrospective search in the database of our institute was performed from January 2008 to February 2014 for patients who were ketamine abusers, with deranged liver function and/or epigastric pain, and had computed tomography of the abdomen or magnetic resonance cholangiopancreatography. Patient demographics, clinical data, and radiological findings were reviewed. RESULTS: Twenty-six patients (11 male and 15 female) were included in this study. Eighteen (69 %) patients had fusiform dilatation of the common bile ducts (CBDs) without evidence of intrinsic or extrinsic obstruction, and non-dilated intrahepatic ducts. The degree of CBD dilatation correlated with duration of abuse. In five patients who achieved abstinence, the CBD dilatation showed improvement. CONCLUSIONS: Ketamine-related cholangiopathy manifested as fusiform dilatation of the CBD without evidence of obstructive lesions. Severity of CBD dilatation appears to be correlated with the duration of ketamine, and the condition is potentially reversible in abstinent patients.

Chronic hematuria and abdominal pain.

An 18-year-old Asian woman with a history of substance abuse presented to the Emergency Department with right-sided abdominal pain and hematuria of several months duration. Physical examination revealed right upper quadrant and suprapubic tenderness. Liver function tests were normal. Urinalysis showed: large blood, 30-50 red blood cells/high-powered field, and no bacteria. She underwent a CT of the abdomen and pelvis following oral and intravenous contrast.

Ketamine: an update on its abuse.

Ketamine is a dissociative anesthetic and substance of abuse. Numerous effects can result from the abuse of ketamine. Death from acute direct toxicity is rare. Ketamine can alter numerous functions in the brain including color perception, memory, attention, cognition, reaction time, and sense of time and can produce psychological addiction. Chronic ketamine abuse can produce toxicity to the gastrointestinal and urinary tract. Gastrointestinal changes include epigastric pain, hepatic dysfunction, and impaired gallbladder activity. The most common urological condition from ketamine is cystitis but renal failure has been reported.

One-stop clinic for ketamine-associated uropathy: report on service delivery model, patients' characteristics and non-invasive investigations at baseline by a cross-sectional study in a prospective cohort of 318 teenagers and young adults.

OBJECTIVE: To describe a service delivery model and report the baseline characteristics of patients investigated by a non-invasive approach for ketamine-associated uropathy. PATIENTS AND METHODS: This was a cross-sectional study in a prospective cohort of patients who attended their first visit and underwent non-invasive investigations at a dedicated centre to treat ketamine-associated uropathy in Hong Kong from December 2011 to July 2013. Data on demographics, illicit ketamine use, symptoms scores and voiding function parameters at baseline were prospectively collected. Differences between active abusers and ex-abusers, and risk factors for the most symptomatic group were investigated by univariate and multivariate analysis. RESULTS: In all, 318 patients completed the non-invasive assessment at their first visit and were eligible for inclusion. In all, 174 were female and the mean (sd) age of the entire cohort was 24.4 (3.1) years. Patients had used ketamine for a mean (sd) period of 81 (36) months. The mean (sd) ketamine use per week was 18.5 (15.8) g. In all, 214 patients were active abusers while 104 were ex-abusers but had persistent lower urinary tract symptoms. The mean (sd) voided volume, bladder capacity, and bladder emptying efficiency were 111.5 (110) mL, 152.5 (126) mL and 73.3 (26.9)%, respectively. The ex-abusers had a lower symptom score (19.3 vs 24.1; P < 0.001), a larger voided volume (126 vs 85 mL; P < 0.001), and a larger bladder capacity (204.8 vs 126.7 mL; P < 0.001) compared with active abusers. Multivariate analysis found female gender was associated with a higher symptom score (odds ratio [OR] 2.39; 95% confidence interval [CI] 1.35-4.23; P = 0.003) and a smaller voided volume (OR 1.9; 95% CI 1.1-3.3; P = 0.02). Ketamine taken (g/week) was another risk factor for a higher symptom score (OR 1.03; 95% CI 1.01-1.05; P = 0.002). Status of ex-abuser was the only protective factor associated with fewer symptoms, larger voided volume and bladder capacity. CONCLUSIONS: An effective service model for recruiting patients with ketamine-associated uropathy is possible. With such a service model as a platform, further prospective studies are warranted to investigate the appropriate choice of treatment for this new clinical entity.

[Apoptosis in adult mouse brain after chronic poisoning of ketamine].

OBJECTIVE: To study the effect of chronic poisoning of ketamine on brain cell apoptosis in adult mouse under different duration and doses. METHODS: The mouse model of chronic poisoning of ketamine was established on adult mouse by tail vein injection of ketamine twice every week with different doses (4, 10, 20 and 30 mg/kg). The mice were sacrificed after continuous injection of ketamine of 1, 2, 4, 8 and 12 weeks. The qualitative assessment of apoptosis was made by transmission electron microscope and the quantitative assessment was made by Caspase-3 immumofluorescence staining method and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) to estimate the time point of apoptosis. All the experimental results were statistically analyzed. RESULTS: The neuron apoptosis was observed in hippocampus and corpus striatum by transmission electron microscope one week after administration, and continued for eight weeks. High level of Caspase-3 expression was observed one week after administration, but with a low level expression after 4 weeks. The number of TUNEL positive cells obviously increased one week after administration and maintained in a high number at 4 weeks. CONCLUSION: Ketamine by tail vein injection could induce neuron apoptosis in adult mouse.