Severe poisoning with semi-synthetic cannabinoids.

Recently, semi-synthetic cannabinoids have entered the illegal market and are produced to mimic the psychoactive effects of tetrahydrocannabinol (THC). This is a case report of a 19-year-old man, who was hospitalized due to severe sedation, hypotension and tachy- and bradycardia after ingestion of the semi-synthetic cannabinoids hexahydrocannabinol (HHC) and hexahydrocannabiphorol (HHC-P) mixed in food. HHC-P, HHC and metabolites were identified in blood samples. The amount of semi-synthetic cannabinoids in illegal products can be high, which can explain the described prolonged clinical effects.

Delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate exposures reported to America's Poison Centers.

INTRODUCTION: Since the passage of the Farm Bill in 2018, the availability of synthetic tetrahydrocannabinols has increased, including delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate. The objective of this study is to investigate the characteristics of delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate exposures reported to United States poison centers from 2021 to 2022. METHODS: National Poison Data System data were analyzed, including year, individual demographics, substance category and type, reason for exposure, highest level of health care received, and medical outcome. United States Census Bureau data were used to calculate population-based rates. RESULTS: There were 5,022 reported cases involving delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate as the primary substance reported to United States poison centers from 1 January 2021 to 31 December 2022. The rate of exposure per 100,000 United States population increased by 89.1 percent from 0.55 in 2021 to 1.04 in 2022. Children less than 6 years old accounted for 30.1 percent of cases, with a mode at age 2 years (representing 8.9 percent of cases). Most cases involved delta-8 tetrahydrocannabinol (98.1 percent), were single-substance exposures (94.3 percent), or occurred in a residence (95.9 percent). Ingestions accounted for 94.2 percent of cases, including 95.1 percent among children less than 6 years old. The leading reason for exposure was unintentional-general (40.2 percent), followed by abuse (33.1 percent). The most common related clinical effects were mild central nervous system depression (25.0 percent), tachycardia (23.0 percent), and agitation (15.6 percent). More than one-third (38.4 percent) of cases experienced a serious medical outcome, and 10.3 percent were admitted to a noncritical care unit and 5.3 percent to a critical care unit. DISCUSSION AND LIMITATIONS: The National Poison Data System is limited by its passive surveillance design. Delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate have toxic effects, and reports to United States poison centers increased from 2021 to 2022. Unintentional ingestions by young children are of particular concern. CONCLUSIONS: Opportunities exist to improve regulation, with accompanying enforcement, of these products and to educate the public about their potential toxicity.

Overview of Pathologic Findings of Vaping in the Context of an Autopsy Patient With Chronic Injury.

CONTEXT.­: Electronic cigarettes are handheld devices that heat an inner liquid containing chemicals to be aerosolized and inhaled, and have become a popular alternative to conventional cigarettes. Their use, termed vaping, has been linked to severe injury, with 2711 cases of associated lung injury and 60 deaths reported to the Centers for Disease Control and Prevention at the time of writing. Published case reports and series have emerged detailing clinical and imaging characteristics of vaping-induced lung injury. However, the pathologic characteristics of these induced injuries are still being established, particularly findings occurring over time. OBJECTIVE.­: To illustrate the autopsy findings of an older patient who died of vaping-induced injury after prolonged symptomology and to provide a review of the most recent literature regarding the basic science, epidemiology, clinical presentation, imaging characteristics, and pathology of vaping-induced lung injury. DATA SOURCES.­: Autopsy case and peer-reviewed literature. CONCLUSIONS.­: Vaping-induced lung injury has emerged as a public health issue, and this case represents a rare opportunity to evaluate this issue at autopsy. Most commonly, the injury has been attributed to tetrahydrocannabinol product use as opposed to nicotine. This case demonstrates that as today's young and relatively healthy "vapers" grow older and develop the comorbidities that come with advanced age, there is serious risk of chronic lung damage from vaping that could result in death. Further observations and studies, particularly autopsy evidence, are clearly important to understand the possible outcomes.

Unknown Tetrahydrocannabinol Edible Ingestion Resulting in Acute Stroke Presentation.

BACKGROUND: Marijuana is a commonly used substance in the United States for both recreational and medicinal purposes. Detrimental health-related effects of marijuana continue to be a source of controversy. CASE REPORT: We describe a case of a woman who presented to the emergency department with acute right upper and lower extremity weakness and altered speech after accidental unknown ingestion of food containing tetrahydrocannabinol (THC). This is a unique case in that we could find no other published report of focal weakness or motor stroke symptoms occurring in the setting of THC ingestion. We will discuss in detail the patient's medical history and timeline of events leading to her presentation to the emergency department. Marijuana contains the psychoactive substance THC and is becoming more commonly used for medicinal and recreational purposes in the United States and abroad. The use of THC is associated with changes in levels of consciousness, perception, and several other physiologic processes. We hope to increase awareness through this case report of accidental THC use by a female patient that resulted in a stroke code and potentially could have led to the use of tissue plasminogen activator. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: To the best of our knowledge, focal neurologic deficits associated with THC use have not been reported in the published literature. We hope that this knowledge will encourage physicians to consider THC intoxication as a cause of new onset extremity weakness.

Delta-9-tetrahydrocannabinolic acid A (THC-A) in urine of a 15-month-old child: A case report.

INTRODUCTION: The acidic forms of cannabinoids, THC-A and CBD-A are naturally present in cannabis plants and preparations and are generally decarboxylated to the active compounds before the use (e.g. thermally decarboxylated through smoking). Hence, the identification of the acidic compounds in urine could be an evidence of cannabis ingestion rather than a passive exposure to smoke. This case report described a 15-month-old child that suffered an acute intoxication by accidental cannabis ingestion. It is important to assess the ingestion and to discriminate it from a passive exposure to better interpret the clinical findings and to establish the correct therapeutic procedure. METHODS: Urine samples were simply diluted in deionized water and directly injected in the LC-MS/MS system. D3-THCCOOH was used as internal standard. Chromatographic separation of THCCOOH, THC-A and CBD-A was carried out in reversed phase on a c18 column. A triple quad in MRM negative mode was used to monitor the three analytes. RESULTS AND DISCUSSION: The developed LC-MS/MS method was simple and fast. A LOD of 3.0ng/mL and a LOQ of 10.0ng/mL were measured for the three compounds. The analytical procedure was validated accordingly to international guidelines. The two urine samples collected from the 15-month-old child at the hospitalization and after three days provided positive results for THCCOOH (130.0 and 10.0ng/mL respectively). THC-A was found only in the urine sample collected at the hospitalization (concentration: 70.0ng/mL). CONCLUSION: THC-A was detected and quantitated in a urine sample of a 15-month-old child.

Epidemiología de las intoxicaciones agudas por drogas de abuso en las urgencias de un hospital del Centro de España basada en datos de análisis toxicológico de orina / Epidemiology of acute poisonings for drugs of abuse in the emergency room of a hospital from the Center of Spain based on analysis data toxicological urine

Introducción: las intoxicaciones agudas son motivo de consulta cada vez más frecuente en los Servicios de Urgencia hospitalarios (SUH) debido a la mayor disponibilidad y acceso a productos químicos tóxicos. Se observan diferentes patrones en cada área sanitaria según el tipo de población, geografía y perfil epidemiológico de consumo. Material y métodos: el objetivo de nuestro estudio es realizar un perfil epidemiológico y describir el manejo del paciente que acude por clínica compatible con intoxicación aguda por drogas de abuso (IA) basado en la determinación de tóxicos en orina para seis sustancias (cannabis, opiáceos, cocaína, anfetaminas, benzodiazepinas y éxtasis) solicitados en el período de estudio 2010-2012. Resultados: se solicitaron 2755 peticiones, de las cuales fueron positivas 1429, y se estudiaron al azar 661 historias clínicas. El perfil de paciente intoxicado de nuestra área es el de varón de entre 30 y 40 años, consumidor preferentemente de cannabis y cocaína; las benzodiazepinas son el tóxico más frecuente en las mujeres, con clínica mayoritariamente neurológica, sin diferencias en cuanto a la franja horaria o el mes del año en que recibió el alta desde el propio SUH en casi el 60% de los casos. Discusión: las IA en los SUH representan casi el 1% de las consultas y tienen una escasa mortalidad. En algunos casos, el médico de urgencias comienza el tratamiento antes de conocer el resultado toxicológico, lo que nos hace plantearnos la utilidad real y el coste-efectividad de estas determinaciones en todos los pacientes con alteración del nivel de conciencia. (AU)

Introduction: acute intoxications are a rising and common query demand on the emergency rooms because of the easy access and disponibility to toxic substances, where we can observe different patterns attending to type of population, geography and epidemiologic consume profile. Material and methods: our objective is to analyze the epidemiology and patient handling coming to the Emergency Room (ER) with compatible symptoms of street drugs abuse, based on the determination of cannabis, cocaine, amphetamine, benzodiazepine, opiates and ectasy urine levels in the period 2010-2012. Results: the ER requested 2755 determinations being positive 1429 and randomly examined 661 clinical histories. The profile of intoxicated patient was male, 30 to 40 years old, preferently cannabis and cocaine consumer (benzodiazepine in women), mostly with neurological symptoms when arrive, without differences between months or day time and, almost 60% of them, discharged directly from the ER. Conclusions: acute intoxications barely represent 1% of ER demands and produce poor or scarce mortality. Sometimes, doctors in charge start with therapeutic measures before knowing the results of toxicology, what leads us to ask about actual usefulness and cost-efficiency of the toxicology assay to every patient with low conscious level. (AU)

Marijuana Misadventures in Children: Exploration of a Dose-Response Relationship and Summary of Clinical Effects and Outcomes.

OBJECTIVES: This study aimed to explore a dose-response relationship of delta-9-tetrahydrocannabinol (THC) in THC-naïve children after unintentional acute exposure and compare clinical outcomes with non-naïve children. METHODS: A retrospective review was performed on children aged 31 days to 20 years who presented to Children's Hospital Colorado for care related to acute THC toxicity. The children were divided into groups based on exposure: group 1 (THC naïve) and group 2 (THC non-naïve). RESULTS: A total of 38 children (age, 3.5 [3] years) met inclusion for group 1 and an equal number of children (age, 15.1 [3.9] years) met the criteria for comparison in group 2. Eight naïve patients had documentation of estimated THC dose ingested (mean [SD], 7.13 [5.8] mg/kg; range, 2.9-19.5 mg/kg). A direct relationship between estimated oral THC dose, level of medical intervention required, and hospital disposition was observed. Lethargy/somnolence was more common in the naïve group (84% vs. 26%, P < 0.0001) whereas problems in cognition, perception, and behavior were more common in the non-naïve group (4% vs 11%, P = 0.01). The duration of clinical effect and length of hospital stay were longer in the naïve group (19.3 vs 5.0 hours, P < 0.0001) and (0.73 vs 0.19 days, P < 0.0001) respectively. CONCLUSIONS: There seems to be a direct relationship between the estimated oral THC dose (mg/kg), hospital disposition, and level of medical intervention required. Symptoms and duration of effects after THC exposure varied based on the route of exposure, age of patient, and history of previous THC experience.

Characterization of edible marijuana product exposures reported to United States poison centers.

CONTEXT: Edible marijuana products are sold as brownies, cookies, and candies, which may be indistinguishable from counterparts without marijuana and are palatable to children and adults. The consumption of an entire product containing multiple dose-units may result in overdose. OBJECTIVE: To characterize edible marijuana exposures reported to US poison centers with subgroup analysis by age. METHODS: We analyzed single substance, human exposure calls coded to marijuana brownies, candies, cookies, beverages, or other foods reported to the National Poison Data System from January 2013 to December 2015. Calls were analyzed by state, age, gender, exposure route, clinical effect, therapies, and level of healthcare facility utilization. RESULTS: Four-hundred and thirty calls were reported: Colorado (N = 166, 1.05/100,000 population/year) and Washington (96, 0.46) yielded the highest number of exposures. Three hundred and eighty-one (91%) calls occurred in states with decriminalized medical/recreational marijuana. The number of calls increased every year of the study. The most common age groups were: ≤5 years (N = 109, 0.15/100,000 population/year) and 13-19 (78, 0.09). The most frequent clinical effects were drowsiness/lethargy (N = 118, percentage = 43%), tachycardia (84, 31%), agitated/irritable (37, 14%), and confusion (37, 14%). Children ≤5 years have more drowsiness/lethargy, ataxia, and red eye/conjunctivitis. No deaths were reported. The most common therapies administered were intravenous fluids (85, 20%), dilute/irrigate/wash (48, 11 %), and benzodiazepines (47, 11%). Three patients (ages 4, 10, and 57 years) received intubation. 97 (23%), 217 (50%), and 12 (3%) calls were managed at home, treated/released, admitted to a critical care unit, respectively. DISCUSSION: Although most clinical effects are minor, ventilatory support may be necessary for children and adults. We speculate the increasing exposures may be related to a combination of delayed absorption kinetics of Δ9-tetrahydrocannablnol, lagging packaging regulations, increased accessibility in decriminalized states, and increased familiarity of poison center specialists with edible product codes. CONCLUSIONS: Edible marijuana exposures are increasing and may lead to severe respiratory depression.

Marijuana poisoning.

The plant Cannabis sativa has been used for centuries for the effects of its psychoactive resins. The term "marijuana" typically refers to tobacco-like preparations of the leaves and flowers. The plant contains more than 400 chemicals but the cannabinoid δ-9-tetrahydrocannabinol (THC) is the major psychoactive constituent. "Hashish" is the resin extracted from the tops of flowering plants and generally has a much higher THC concentration. Marijuana is the most commonly used illicit drug in the United States. Currently, several states have passed legislation to decriminalize possession of small amounts of marijuana for both medical and personal use and several other states have similar legislation under consideration. The most common form of marijuana use in humans is inhalation of the smoke of marijuana cigarettes, followed by ingestion. In animals, although secondhand smoke inhalation is possible, the most common source of exposure is through ingestion of the owner's marijuana supply. The minimum lethal oral dose for dogs for THC is more than 3 g/kg. Although the drug has a high margin of safety, deaths have been seen after ingestion of food products containing the more concentrated medical-grade THC butter. There are two specific cannabinoid receptors in humans and dogs, CB1 (primarily in central nervous system) and CB2 (peripheral tissues). In animals, following oral ingestion, clinical effects begin within 60 minutes. All of the neuropharmacologic mechanisms by which cannabinoids produce psychoactive effects have not been identified. However, CB1 activity is believed to be responsible for the majority of cannabinoid clinical effects. Highly lipid soluble, THC is distributed in fat, liver, brain, and renal tissue. Fifteen percent of THC is excreted into the urine and the rest is eliminated in the feces through biliary excretion. Clinical signs of canine intoxication include depression, hypersalivation, mydriasis, hypermetria, vomiting, urinary incontinence, tremors, hypothermia, and bradycardia. Higher dosages may additionally cause nystagmus, agitation, tachypnea, tachycardia, ataxia, hyperexcitability, and seizures. Treatment of marijuana ingestion in animals is largely supportive. Vital signs including temperature and heart rate and rhythm must be continually monitored. Stomach content and urine can be tested for cannabinoids. Gas chromatography and mass spectrometry can be utilized for THC detection but usually may take several days and are not practical for initiation of therapy. Human urine drug-screening tests can be unreliable for confirmation of marijuana toxicosis in dogs owing to the interference of a large number of the metabolites in canine urine. False negatives may also arise if testing occurs too recently following THC ingestion. Thus, the use of human urine drug-screening tests in dogs remains controversial. No specific antidote presently exists for THC poisoning. Sedation with benzodiazepines may be necessary if dogs are severely agitated. Intravenous fluids may be employed to counter prolonged vomiting and to help control body temperature. Recently, the use of intralipid therapy to bind the highly lipophilic THC has been utilized to help reduce clinical signs. The majority of dogs experiencing intoxication after marijuana ingestion recover completely without sequellae. Differential diagnoses of canine THC toxicosis include human pharmaceuticals with central nervous system stimulatory effects, drugs with central nervous system depressant effects, macrolide parasiticides, xylitol, and hallucinogenic mushrooms.

Exposure to bath salts and synthetic tetrahydrocannabinol from 2009 to 2012 in the United States.

OBJECTIVE: To describe bath salts and synthetic tetrahydrocannabinol (THC) exposures in the US from 2009 to 2012, hypothesizing a yearly increase. STUDY DESIGN: All exposures reported to American Association of Poison Control Centers between January 1, 2009, and April 30, 2012, were extracted from the National Poison Data System using generic and product codes. RESULTS: Bath salts and synthetic THC exposures totaled 7467 and 11,561, respectively. Bath salts exposures were 0 in 2009, 298 in 2010, and 6062 in 2011. Synthetic THC exposures were 14 in 2009, 2821 in 2010, and 6255 in 2011. First-tertile bath salts exposures were lower in 2012 (n = 1007) than in 2011 (n = 2027), and synthetic THC exposures were higher in 2012 (n = 2389) than in 2011 (n = 1888). Most exposures occurred in the midwest and southeast regions (64.8% of bath salts and 58% of synthetic THC exposures). Male subjects comprised 69% (n = 5153) of bath salts users and 74% (n = 8505) of synthetic THC users. Exposure to bath salts were highest in subjects 20-29 years of age (n = 2943), and exposure to synthetic THC was highest for subjects 13-19 years of age (n = 5349). Intentional abuse and inhalation were most common reason for and mode of exposure, respectively. CONCLUSIONS: Bath salts and synthetic THC abuse increased from 2009 to 2011. Synthetic THC emerged first and has more reported exposures than bath salts. In 2012, bath salts abuse declined and synthetic marijuana abuse increased. Young men intentionally abusing the drug via inhalation make up the majority of users.

A characterization of synthetic cannabinoid exposures reported to the National Poison Data System in 2010.

STUDY OBJECTIVE: Δ-9-Tetrahydrocannabinol homologs have been increasingly abused since their introduction in 2004. Such products were used as a "legal high" for those wishing to experience cannabinoid effects while evading basic drugs-of-abuse testing. We describe a series of exposures to products marketed as synthetic cannabinoids to better characterize the clinical effects in these patients. METHODS: All Δ-9-tetrahydrocannabinol homolog exposures reported to the National Poison Data System between January 1, 2010, and October 1, 2010, were extracted with National Poison Data System generic codes and product codes for Δ-9-tetrahydrocannabinol homologs. Only cases involving a single-agent exposure to Δ-9-tetrahydrocannabinol homologs as the major category were analyzed. Descriptive statistics were generated for demographic data, management site, products involved, symptoms, duration of effects, treatments, and severity of clinical effects. RESULTS: During the 9-month study period, there were 1,898 exposures to Δ-9-tetrahydrocannabinol homologs; 1,353 of these cases were single-agent exposures. The mean age was 22.5 years (SD 8.86 years). Most cases were reported in men (n=1,005; 74.3%). The majority of exposures were acute (88.2%; n=1,193). The most common clinical effect was tachycardia (37.7%; n=510). Seizures were reported in 52 patients (3.8%). The majority of clinical effects lasted for fewer than 8 hours (n=711; 78.4%) and resulted in 1,011 non-life-threatening clinical effects (92.9%). The most common therapeutic intervention was intravenous fluids (n=343; 25.3%). There was 1 death (0.1%). CONCLUSION: The majority of cases were in young men intentionally abusing spice. Most exposures resulted in non-life-threatening effects not requiring treatment, although a minority of exposures resulted in more severe effects, including seizures.

What is the mechanism whereby cannabis use increases risk of psychosis?

Cannabis use has increased greatly over the last three decades. The various types of cannabis differ in their concentration of the main psychoactive component, Delta-9-tetrahydrocannabinol (THC), and the other major ingredient, cannabidiol (CBD). Plant engineering has maximized levels of THC, thus increasing the potency of street cannabis. It is well known that cannabis intoxication can cause brief psychotic symptoms like paranoia, whilst recent evidence demonstrates that heavy use of cannabis increases the risk of chronic psychoses like schizophrenia; genetic vulnerability seems to predispose some people to a higher risk. This paper starts to consider the neurochemical mechanisms whereby cannabis use increases the risk of psychosis.

[Practice of toxicology screening in an emergency department].

UNLABELLED: The present study examines standards of toxicology screening in the Emergency Department. METHODS: A retrospective analysis was performed on 583 patients for whom 713 different toxicology assays were conducted. RESULTS: The most commonly used test was the urine toxicology assay which was found positive in 10% of the subjects. Most of the patients in this group were treated with respective antidotes before the results of the tests became available. One out of 13 subjects who denied acetaminophen ingestion showed toxic blood levels. High carboxyhemoglobin saturation was found only in subjects with symptoms of intoxication. CONCLUSIONS: The medical utility of urine toxicology assay is not clear, as patients reviewed were treated according to their clinical conditions. Acetaminophen blood levels should be examined more frequently, as symptoms are vague and appropriate treatment is very effective. Carboxyhemoglobin saturation should be examined whenever exposure is suspected and symptoms and or signs are compatible with intoxication.

Fatal poisoning in Nordic drug addicts in 2002.

The present study from 2002 includes medicolegally examined fatal poisonings among drug addicts in the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. A common definition "drug addict" is applied by the participating countries. The number of deaths, age, sex, place of death, main intoxicant and other drugs present in the blood are recorded in order to obtain national data, as well as comparable Nordic data and data comparable to earlier studies from 1997 and 1991. The Icelandic results are commented on separately due to the low number of cases. The most fatal overdoses are seen in Norway, in both the death rate (number per 100,000 inhabitants=8.44) and in absolute number (n=232). The comparable figures for the other four countries are Denmark 5.43 (n=175), Iceland 3.6 (n=6), Finland 2.93 (n=94) and Sweden 2.56 (n=136). In earlier studies from 1991 and 1997, the highest death rate is seen in Denmark, with Norway as number two. Denmark is the only country where the death rate decreases from 1997 to 2002. A relatively large increase in deaths in the younger age groups (<30 years) is noted from 1997 to 2002, except in Denmark, where only a small increase in overdose deaths in very young people (15-19 years) is observed. Females account for 12-20% of the overdoses (three out of six deaths in Iceland). Relatively fewer deaths are recorded in the capital areas in 2002 than in 1997 and 1991, suggesting more geographically widespread drug use in the Nordic countries. Heroin/morphine is the single most frequently encountered main intoxicant, varying from 10% of the cases in Finland to 72% of the cases in Norway. Finland differs from the other countries in that a high percentage of the fatal overdoses in Finland are not caused by an illicit drug; buprenorphine overdoses are seen, and relatively few deaths resulting from heroin are seen. Methadone is the main intoxicant in 41% of the Danish overdose cases, 15% of the Norwegian cases, 4% of the Swedish cases and none of the Finnish overdose cases, an observation probably linked to different national prescription rules for methadone. The analytical screening reveals extended polydrug use. Frequently seen substances, in addition to the main intoxicant are amphetamine, tetrahydrocannabinol (THC), benzodiazepines and ethanol.

[Accidental narcotic and buprenorphine poisoning in children notified at the Marseille Poison Center between 1993 and 1999]. / Intoxications accidentelles par stupéfiants et buprénorphine chez les enfants notifiées au Centre Antipoison de Marseille de 1993 à 1999.

To evaluate the frequency and severity of accidental poisoning in children by narcotics or buprenorphine, a retrospective study was carried out: 75 cases were collected by the Marseille Poison Centre between 1993 and 1999. Most of the patients were between 1 and 3 years old and the drugs involved were cannabis and, more recently, Subutex (buprenorphine). These two drugs were responsible for the most severe cases of poisoning, most of which occurred at home.