Search

In the United States, cocaine use and mortality have surged in the past 5 years. Considering cocaine’s reputation as a fashionable social drug, the rise of cocaine mentions in popular music may provide a signal of epidemiological trends of cocaine use. We characterized the relationship between mentions of cocaine in song lyrics and incidence of cocaine use and mortality in the US. Incidence of cocaine use from 2002 to 2017 was obtained from the National Survey on Drug Use and Health and cocaine overdose mortality rate from 2000 to 2017 was obtained from the Centers for Disease Control. Distributed lag models were fit using ordinary least squares on the first difference to identify associations between changes in cocaine lyric mentions and changes in incidence of cocaine use and mortality. A total of 5955 song lyrics with cocaine mentions were obtained from Lyrics.com. Cocaine mentions in song lyrics were stable from 2000 to 2010 then increased by 190% from 2010 to 2017. The first-order distributed lag model estimated that a 0.01 increase in mentions of cocaine in song lyrics is associated with an 11% increase in incidence of cocaine use within the same year and a 14% increase in cocaine mortality with a 2-year lag. Lag-times were confirmed with cross-correlation analyses and the association remained after accounting for street pricing of cocaine. Mentions of cocaine in song lyrics are associated with the rise of incidence of cocaine use and cocaine overdose mortality. Popular music trends are a potentially valuable tool for understanding cocaine epidemiology trends.

A 35-year-old woman presented to the emergency department in cardiac arrest after ingesting large quantities of powdered cocaine. With an initial rhythm of ventricular fibrillation, emergency medic...

Resumen Introducción. Se han desarrollado nuevas estrategias terapéuticas contra la toxicidad por sobredosis de cocaína basadas en el aumento en la actividad catalítica de enzimas que participan en la destrucción de su molécula, antes de que tenga la oportunidad de penetrar el tejido nervioso. Objetivo. Describir los avances en el efecto del aumento en la actividad catalítica de las enzimas BChE y las hCE, producidas para el tratamiento de pacientes en condiciones de toxicidad por sobredosis de cocaína, así como mencionar sus ventajas y desventajas y su potencial uso futuro en pacientes internados por una sobredosis de cocaína. Método. Se realizó una búsqueda bibliográfica por medio del PubMed, usando como descriptores las palabras “Cocaine”, “hydrolase”, “esterase” y “butyrylcholinesterase”. Se obtuvieron 220 artículos de los cuales se usaron 126 para esta revisión. Resultados. Las enzimas BChE, COCH y CoCe bacteriana disminuyeron significativamente los niveles de cocaína en la sangre y el cerebro y con ello atenuaron los efectos de una sobredosis de cocaína. Discusión y conclusión. Los resultados obtenidos en modelos animales sugieren el potencial terapéutico del uso de estas enzimas en humanos, para inactivar rápidamente a la cocaína y desarrollar tratamientos para evitar las muertes asociadas con la intoxicación por sobredosis. Estas metodologías enzimáticas ofrecen una aplicación terapéutica novedosa para el tratamiento de la sobredosis.

Cocaine use disorders include short-term and acute pathologies (e.g. overdose) and long-term and chronic disorders (e.g. intractable addiction and post-abstinence relapse). There is currently no available treatment that can effectively reduce morbidity and mortality associated with cocaine overdose or that can effectively prevent relapse in recovering addicts. One recently developed approach to treat these problems is the use of enzymes that rapidly break down the active cocaine molecule into inactive metabolites. In particular, rational design and site-directed mutagenesis transformed human serum recombinant butyrylcholinesterase (BChE) into a highly efficient cocaine hydrolase with drastically improved catalytic efficiency toward (-)-cocaine. A current drawback preventing the clinical application of this promising enzyme-based therapy is the lack of a cost-effective production strategy that is also flexible enough to rapidly scale-up in response to continuous improvements in enzyme design. Plant-based expression systems provide a unique solution as this platform is designed for fast scalability, low cost and the advantage of performing eukaryotic protein modifications such as glycosylation. A Plant-derived form of the Cocaine Super Hydrolase (A199S/F227A/S287G/A328W/Y332G) we designate PCocSH protects mice from cocaine overdose, counters the lethal effects of acute cocaine overdose, and prevents reinstatement of extinguished drug-seeking behavior in mice that underwent place conditioning with cocaine. These results demonstrate that the novel PCocSH enzyme may well serve as an effective therapeutic for cocaine use disorders in a clinical setting.

Drug addiction is a brain disease characterized by compulsive drug-seeking and taking and a high likelihood of relapse when exposed to drugs or drugassociated cues, even long after abstention [1]. Relapse is the major challenge for the treatment of drug addiction in humans. Cocaine is a widely abused drug that causes significant morbidity and mortality. There are currently no FDA-approved medications for reducing cocaine use or treating relapse in cocaine addicts. Moreover, there are no interventions for the acute emergencies that result from cocaine overdose. A novel skin stem cell-based gene therapy has recently been described to be effective in reducing core features of cocaine abuse in laboratory mice [2], offering hope of producing the first medication for treating cocaine abuse, and adding a new tool for treating drug abuse and co-abuse.

The rapid detection of cocaine has received considerable attention because of the instantaneous and adverse effects of cocaine overdose on human health. Aptamer-based biosensors for cocaine detection have been well established for research and application. However, reducing the analytic duration without deteriorating the sensitivity still remains as a challenge. Here, we proposed an aptamer-based evanescent wave fibre (EWF) biosensor to rapidly detect cocaine in a wide working range. At first, the aptamers were conjugated to complementary DNA with fluorescence tag and such conjugants were then immobilized on magnetic beads. After cocaine was introduced to compete against the aptamer-DNA conjugants, the released DNA in supernatant was detected on the EWF platform. The dynamic curves of EWF signals could be interpreted by the first-order kinetics and saturation model. The semi-log calibration curve covered a working range of 10–5000 µM of cocaine, and the limit of detection was approximately 10.5 µM. The duration of the full procedure was 990 s (16.5 min), and the detection interval was 390 s (6.5 min). The specified detection of cocaine was confirmed from four typical pharmaceutic agents. The analysis was repeated for 50 cycles without significant loss of sensitivity. Therefore, the aptamer-based EWF biosensor is a feasible solution to rapidly detect cocaine.

It is a grand challenge to develop a truly effective medication for treatment of cocaine overdose. The current available, practical emergence treatment for cocaine overdose includes administration of a benzodiazepine anticonvulsant agent (e.g. diazepam) and/or physical cooling with an aim to relieve the symptoms. The inherent difficulties of antagonizing physiological effects of drugs in the central nervous system have led to exploring protein-based pharmacokinetic approaches using biologics like vaccines, monoclonal antibodies, and enzymes. However, none of the pharmacokinetic agents has demonstrated convincing preclinical evidence of clinical potential for drug overdose treatment without a question mark on the timing used in the animal models. Here we report the use of animal models, including locomotor activity, protection, and rescue experiments in rats, of drug toxicity treatment with clinically relevant timing for the first time. It has been demonstrated that an efficient cocaine-metabolizing enzyme developed in our previous studies can rapidly reverse the cocaine toxicity whenever the enzyme is given to a living rat, demonstrating promising clinical potential of an enzyme-based novel therapy for cocaine overdose as a successful example in comparison with the commonly used diazepam.

Background Ecologic data suggest that elevated outdoor temperature is correlated with mortality rates from cocaine overdose. Using non-aggregated death records, we studied the association of hot temperatures with risk of death from cocaine overdose. Methods We carried out a case-crossover study of all deaths from cocaine or other drug overdose between the months of May and September, from 2000 through 2013 in Quebec, Canada. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between maximum outdoor temperature and death from cocaine or other drug overdose. The main outcome measure was death from cocaine overdose as a function of maximum temperature the day of death and the days immediately preceding death. Results There were 316 deaths from cocaine overdose and 446 from other drug overdoses during the study. Elevated temperature the preceding week was associated with the likelihood of death from cocaine but not other drug overdose. Compared with 20 °C, a maximum weekly temperature of 30 °C was associated with an OR of 2.07 for death from cocaine overdose (95% CI 1.15–3.73), but an OR of 1.03 for other drug overdoses (95% CI 0.60–1.75). Associations for cocaine overdose were present with maximum daily temperature the day of and each of the three days preceding death. Conclusions Elevated ambient temperature is associated with the risk of death from cocaine overdose. Public health practitioners and drug users should be aware of the added risk of mortality when cocaine is used during hot days.

Cocaine is highly addictive and there are no pharmacotherapeutic drugs available to treat acute cocaine toxicity or chronic abuse. Antagonizing an inhibitor such as cocaine using a small molecule has proven difficult. The alternative approach is to modify cocaine’s pharmacokinetic properties by sequestering or hydrolyzing it in serum and limiting access to its sites of action. We took advantage of a bacterial esterase (CocE) that has evolved to hydrolyze cocaine and have developed it as a therapeutic that rapidly and specifically clears cocaine from the subject. Native enzyme was unstable at 37°C, thus limiting CocE’s potential. Innovative computational methods based on the protein’s structure helped elucidate its mechanism of destabilization. Novel protein engineering methodologies were applied to substantially improve its stability in vitro and in vivo. These improvements rendered CocE as a powerful and efficacious therapeutic to treat cocaine intoxication and lead the way towards developing a therapy for addiction.

Introduction Capgras syndrome has originally been described as psychiatric syndrome. However, in the last few years reports of patients with this syndrome has significantly increased in patients with neurological, metabolic, and infectious diseases and those who consume alcohol. Different hypotheses have been proposed to explain the neurobiology of this very unusual symptom, such as changes in the dopamine circuit and specific dysfunctions in facial processing. Case In this work we present a new case of Capgras syndrome, associated with an acute cocaine overdose, which was transient and reversible. Discussion The neurobiological bases of this syndrome are analysed, along with their relationship with the changes induced by cocaine use. Thus, Capgras syndrome could be the expression of functional changes at frontal-temporal level, and the paralimbic region secondary to the consumption of psychoactive substances such as cocaine.

Enhancing cocaine metabolism by administration of cocaine esterase (CocE) has been recognized as a promising treatment strategy for cocaine overdose and addiction, because CocE is the most efficient native enzyme for metabolizing the naturally occurring cocaine yet identified. A major obstacle to the clinical application of CocE is the thermoinstability of native CocE with a half-life of only a few minutes at physiological temperature (37 degrees C). Here we report thermostable variants of CocE developed through rational design using a novel computational approach followed by in vitro and in vivo studies. This integrated computational-experimental effort has yielded a CocE variant with a approximately 30-fold increase in plasma half-life both in vitro and in vivo. The novel design strategy can be used to develop thermostable mutants of any protein.

Aim To investigate the frequency of non-fatal cocaine overdose, and responses to overdoses, among injecting and non-injecting cocaine users. Design Cross-sectional study. Setting Sydney, Australia. Participants Two hundred current cocaine users. Measurements Structured interview. Findings Thirteen per cent of the sample had overdosed on cocaine, 7% in the preceding 12 months. Cocaine injectors were more likely to have overdosed, both ever (17 ∨ 6%) and in the preceding 12 months (9 ∨ 3%). The most common symptoms of overdose were palpitations (68%), intense sweating (44%) and seizures (40%). The use of other drugs in combination with cocaine prior to the most recent overdose was prevalent (64%), most commonly opioids (40%), alcohol (24%) and cannabis (24%). Those who had overdosed were more likely to be female, had longer cocaine use careers, had used more cocaine in the preceding month and preceding 6 months, had higher levels of cocaine dependence and more extensive polydrug use. Twenty-four per cent had witnessed a cocaine overdose, 13% in the preceding 12 months. Injectors were more likely to have witnessed overdoses, both ever (35% ∨ 8%) and in the preceding 12 months (20% ∨ 3%). Conclusions Experience of, and exposure to, overdose were not rare events. Cocaine users need to be aware of the possibility and nature of overdose, and that cocaine overdose can occur irrespective of method of use. There is a need to emphasise the potential danger of combining cocaine with other drugs.

We describe the management and recovery of a 28-year-old man following a history of overdose by nasal inhalation of cocaine. The patient was presented in a comatose state suffering from seizures and marked cardiovascularly instability. Intravenous lipid emulsion was administered following initial resuscitation and tracheal intubation, as a means of treating persistent cardiac arrhythmias and profound hypotension. Following lipid emulsion therapy, the patient's life-threatening cardiovascular parameters rapidly improved and he recovered well without any side effects, thus being discharged within 2 days.

Objective: To describe fulminant hepatic failure in a man following cocaine overdose as a result of an acquired mitochondrial defect.Design: Case report.Patients: One patient admitted to the emergency room following cocaine abuse. The patient deteriorated into multi-organ failure requiring inotropic, ventilatory and renal support.Intervention: Multi-organ support and liver transplantation.Conclusions: Hepatotoxicity was initially thought to be hyperthermic or due to direct cocaine hepatotoxicity; post mortem results demonstrate significant evidence to support an acquired mitochondrial defect.

We describe the management of a young patient who had experienced a cocaine overdose. The patient presented with altered mental status and seizures and subsequently developed a wide complex arrhythmia with a rare alternating bundle branch block pattern. Intravenous lipid emulsion was administered following initial resuscitation and endotracheal intubation, because conservative methods of treating the persistent cardiac arrhythmias failed.

Laboratory rats injected daily with a moderate dose of cocaine hydrochloride (30 mg/kg, i.p.) showed increased fatalities when cocaine injections were followed by 30 min of restraint stress. The 5-day mortality rate was 58% for the cocaine-plus-stress group, while 17% of the animals receiving cocaine without restraint stress died. This finding suggests that stress can augment the toxic effect of cocaine and that minimizing stress may be an important consideration in the clinical management of cocaine overdose.

Since patients with cocaine overdose were reported to develop rhabdomyolysis involving skeletal muscle damage leading to elevated levels of serum creatine kinase (CK), we determined whether cocaine can directly act on isolated rat skeletal muscles and increase the leakage of CK. In the fast-twitch muscle such as the extensor digitorum longus (EDL), following exposure to normal physiological solution for 1, 2, 3, and 4 hr, the mean leakage of CK was 0.6, 0.7, 0.9, and 1.2 units/mg of muscle respectively. On exposure of EDL to 0.1, 0.5, and 1.0 mM cocaine, there was no significant change in CK leakage. In the slow-twitch muscle such as the soleus, following exposure to normal physiological solution for 1, 2, 3, and 4 hr, the mean leakage of CK was 1.5, 2.2, 2.7, and 3.1 units/mg, which was significantly greater (P < 0.001) than in EDL at each time interval. On exposure of soleus to 0.1 mM cocaine, the CK leakage did not increase significantly, but on exposure to 0.5 mM cocaine, it significantly increased to 2.4, 3.4, 4.4, and 5.7 units/mg, and on exposure to 1.0 mM cocaine, it further increased to 2.7, 4.9, 6.5, and 7.6 units/mg. The CK activity of fresh muscle homogenate was 115.5 units/mg in EDL and 51.9 units/mg in soleus. These results indicate that cocaine can directly act on skeletal muscle and increase the leakage of CK especially from slow-twitch muscle like soleus, but not from fast-twitch muscle like EDL.

(−)-Cocaine is a widely abused drug and there is currently no available anti-cocaine therapeutic. Promising agents, such as anti-cocaine catalytic antibodies and high-activity mutants of human butyrylcholinesterase (BChE), for therapeutic treatment of cocaine overdose have been developed through structure-and-mechanism-based design and discovery. In particular, a unique computational design strategy based on the modeling and simulation of the rate-determining transition state has been developed and used to design and discover desirable high-activity mutants of BChE. One of the discovered high-activity mutants of BChE has a ∼456-fold improved catalytic efficiency against (−)-cocaine. The encouraging outcome of the structure-and-mechanism-based design and discovery effort demonstrates that the unique computational design approach based on transition state modeling and simulation is promising for rational enzyme redesign and drug discovery. The general approach of the structure-and-mechanism-based design and discovery may be used to design high-activity mutants of any enzyme or catalytic antibody.

(-)-Cocaine is a widely abused drug and there is currently no available anti-cocaine therapeutic. Promising agents, such as anti-cocaine catalytic antibodies and high-activity mutants of human butyrylcholinesterase (BChE), for therapeutic treatment of cocaine overdose have been developed through structure-and-mechanism-based design and discovery. In particular, a unique computational design strategy based on the modeling and simulation of the rate-determining transition state has been developed and used to design and discover desirable high-activity mutants of BChE. One of the discovered high-activity mutants of BChE has a approximately 456-fold improved catalytic efficiency against (-)-cocaine. The encouraging outcome of the structure-and-mechanism-based design and discovery effort demonstrates that the unique computational design approach based on transition state modeling and simulation is promising for rational enzyme redesign and drug discovery. The general approach of the structure-and-mechanism-based design and discovery may be used to design high-activity mutants of any enzyme or catalytic antibody.

Previous research indicates that progesterone (PROG) decreased cocaine-seeking behavior in female rats. This effect of PROG may be in part due to its metabolite allopregnanolone (ALLO), which has been shown to decrease the sensitizing effects of cocaine and reduce lethality associated with cocaine overdose in mice.The purpose of the present study was to examine the effects of ALLO on the reinstatement of cocaine-seeking behavior in female and male rats.Rats were trained to lever press for i.v. infusions of cocaine (0.4 mg/kg per infusion) during 2-h sessions, and once acquisition criteria were met, cocaine self-administration continued for 14 days. Cocaine was then replaced with saline, and lever pressing was allowed to extinguish over 21 days. After the extinction phase, rats received s.c. ALLO (15 or 30 mg/kg), PROG (0.5 mg/kg), PROG (0.5 mg/kg) plus the 5-alpha reductase inhibitor finasteride (25 mg/kg), or vehicle pretreatment for 3 days. Rats were then tested during reinstatement with three doses of cocaine (5, 10, and 15 mg/kg, i.p. in mixed order).PROG, and to a greater extent ALLO, decreased cocaine-primed reinstatement in females, while finasteride blocked the attenuating effects of PROG on reinstatement. ALLO had no effect on cocaine-primed reinstatement in males.These findings suggest that ALLO may explain part of PROG's inhibitory effect on cocaine-primed reinstatement, and it may serve as a novel approach for preventing relapse in female cocaine abusers.

Disclosed are catalytic antibodies and polypeptides capable of degrading cocaine. Said catalytic antibodies and polypeptides are characterized by the amino acid sequence of their complementarity determining regions and framework regions. The present invention also discloses a pharmaceutical composition and a method for decreasing the concentration of cocaine in a subject. Finally, the invention discloses pharmaceutical compositions and methods for treating cocaine overdose and addiction in subjects.

Yasadışı ilaç ve uyuşturucu maddeleri vücutlarının içinde paket halinde saklamak suretiyle gümrüklerden ve kontrol noktalarından kaçıran kişilere vücut paketçisi denmektedir. Yabancı uyruklu 24 yaşında erkek olgu, fenalaşması üzerine getirildiği hastanede konvülsiyonlar geçirerek ölmüştür. Dış muayenesinde herhangi bir özellik yoktur. İç organ incelemelerinde; organlarda yaygın ödem ve konjesyon görülmüştür. Midesinde ve bağırsaklarında iki adet kokain paketi mevcut olduğu tespit edilmiştir. Olgu; vücudundaki paketlerden birinin patlaması sonucunda akut kokain intoksikasyonu sonucu öldüğüne karar verilmiş bir paket vücuttur. Olgu; şüpheli ölümlerde “Paket Vücut Sendromu”na dikkat çekmek ve konunun tartışılması amacıyla sunulmuştur.Anahtar kelimeler: Kokain, paket vücut sendromu, şüpheli ölüm, otopsi, adli tıp

The process of swallowing or inserting illegal packets of drugs for the purpose of evading law enforcement officers carries risks other than criminal charges. It can be fatal. Individuals engaged in such activities are called "Body Packers" or "Mules". The most frequent cause of the death among body packers is acute drug intoxication due to rupture of the package(s) within the gastrointestinal tract. We present the first documented case of a body packer that died from cocaine intoxication following the rupture of packets of cocaine in Western Pennsylvania.

The illicit use of cocaine continues in epidemic proportions and treatment for cocaine overdose remains elusive. Current protein-based technology offers a new therapeutic venue by which antibodies bind the drug in the blood stream, inactivating its toxic effects. The therapeutic potential of the anticocaine antibody GNC92H2 was examined using a model of cocaine overdose. Swiss albino mice prepared with intrajugular catheters were tested in photocell cages after administration of 93 mg/kg (LD50) of cocaine and GNC92H2 infusions ranging from 30 to 190 mg/kg. GNC92H2 was delivered 30 min before, concomitantly or 3 min after cocaine treatment. Significant blockade of cocaine toxicity was observed with the higher dose of GNC92H2 (190 mg/kg), where premorbid behaviors were reduced up to 40%, seizures up to 77% and death by 72%. Importantly, GNC92H2 prevented death even post-cocaine injection. The results support the important potential of GNC92H2 as a therapeutic tool against cocaine overdose.

Hair analysis for cocaine was used in the investigation of a case of accidental cocaine poisoning. A 25-year-old man consumed an entire bottle of Pony Malta, an imported Colombian soft drink. Unbeknownst to him, the 6.2-oz bottle contained a large quantity of cocaine. It was subsequently discovered that this bottle was one of 45 recovered that contained cocaine as part of a smuggling scheme. The subject was hospitalized for acute cocaine intoxication but died 24 days later. The admission blood contained 2.3 mg/L of cocaine and 4.5 mg/L of benzoylecgonine. Subsequent segmental analysis by MS/MS of hair samples taken at the autopsy revealed a peak cocaine concentration in the segment corresponding to the time he ingested the tainted beverage. The use of hair analysis as an adjunct to traditional analytical techniques may help document drug use history and is especially useful in situations have blood and urine specimens have not been collected in a timely fashion.

The increasing abuse of cocaine by young adults and the many deaths attributed to cocaine overdose have prompted questions concerning the public health risk of abusing the drug. These deaths result from a combination of drug effects on both the central and sympathetic nervous systems (1). In addition to the lethal toxic effects of cocaine, previous reports demonstrated that cocaine has various influences, both suppression and enhancement, on the immune function of humans and experimental animals (2, 3, 4, 5). However, the mechanisms of immunomodulation in vivo are unclear, because cocaine can act either as a local anesthetic or systemically through the central nervous system.

The question of how cocaine overdoses are related to preferred routes of cocaine administration and other aspects of cocaine use patterns is sufficiently complex that very little information is available on it. Even the most extensive information on cocaine overdoses, that of the Drug Abuse Warning Network, is severely limited for purposes of examining this topic. Findings are presented from a 1988-1990 study of a purposive but demographically diverse sample of 699 crack and other cocaine users in Miami, 349 of them interviewed in residential treatment and 350 interviewed on the street. Among these respondents: a history of cocaine overdose is extremely common; overdose episodes do not commonly motivate treatment entry and in some populations are relatively unlikely to result in an emergency room visit; cocaine overdose is less associated with crack smoking than with snorting or intravenous (IV) use, whereas IV use is especially likely to result in overdose; and the street and treatment samples are strikingly different in regard to drug use patterns, overdose history, changes some users made to use patterns as a result of overdose experiences, and reasons given by other users for not making such changes.

BY TWEAKING a naturally occurring enzyme, chemists have created a molecule that could flush a cocaine overdose out of the body before it can cause irreparable damage

Cocaine exposure elevates D3 receptor densities over limbic sectors of the striatum in accidental cocaine overdose.

Effective medication for the treatment of cocaine overdose and addiction is a major unmet need of worldwide importance. In contrast to heroin, for which there are effective medications to treat both overdose (naloxone) and addiction (methadone), there are no pharmacologic treatments for any aspect of cocaine addiction. Recent discoveries indicating that an anti-cocaine medication is actually within reach are cause for great optimism. This work is defining specific molecular targets against which such a medication might be directed. A recent study by Giros et al.1 affirms the central importance of the dopamine-reuptake transporter in the behavioral and biochemical action of . . .

The cocaine epidemic which started in the USA in the 1970s has become a pandemic. Cocaine is at present snorted among affluent people in the capitals in the Nordic countries. In this paper clinical signs and symptoms following cocaine abuse are presented. Psychiatric symptoms from anxiety states to paranoid psychoses may follow the abuse. The symptoms mimic traditional mental disorders An overview of treatment aspects is given. The clinician may have to handle cases of cocaine overdose among experimental users. The cocaine abusers may need detoxification from cocaine and from secondary polydrug abuse. Long-term outpatient treatment programs seem to be necessary to help the cocaine abusers abstain and avoid dramatic relapses.

Since cocaine in blood rapidly hydrolyzes to benzoylecgonine, cocaine concentrations determined in postmortem blood may not reflect the presence or concentration of cocaine in the body at the time of death. The interpretative value of the determination of cocaine and benzoylecgonine in brain tissue was investigated. Cocaine and benzoylecgonine were quantitated by coextraction and formation of the propyl derivative of benzoylecgonine followed by selected ion monitoring gas chromatography/mass spectrometry (GC/MS) using electron ion impact ionization. Cocaine and benzoylecgonine were found to be evenly distributed throughout the brain. Cocaine and benzoylecgonine concentrations were stable in frozen brain tissue (-4 degrees C) on reanalysis after 1 to 3 months of storage, and in refrigerated tissue (10 degrees C) after 30 days of storage. Blood, brain, and liver concentrations of cocaine and benzoylecgonine in 37 cocaine overdose cases and 46 cases in which cocaine was incidental to the cause of death were reviewed. The ratios of cocaine/benzoylecgonine in the toxic cases (brain mean 14.7 and blood mean 0.64) were clearly different from those found in the incidental cases (brain mean 0.87 and blood mean 0.27). The brain/blood ratios of cocaine and benzoylecgonine concentrations generally were characteristic of the time elapsed since cocaine dosing. In cocaine overdose cases, the mean ratio was 9.6 for cocaine and 0.36 for benzoylecgonine. These are within the range found in animal studies for brain/blood ratios of cocaine and benzoylecgonine 0.5 to 2 h after cocaine administration. In incidental cases, the brain/blood ratios were mean 2.5 for cocaine and 1.4 for benzoylecgonine.(ABSTRACT TRUNCATED AT 250 WORDS)