Dose of Product or Product Concentration: A Comparison of Change in Heart Rate by THC Concentration for Participants Using Cannabis Daily and Occasionally.

Introduction: Studies show that acute cannabis use significantly increases heart rate (HR) and mildly raises blood pressure in the minutes following smoked or inhaled use of cannabis. However, less is known about how the THC concentration of the product or an individual's frequency of use (i.e., tolerance) may affect the magnitude of the change in HR. It is also relatively unexamined how the physical effects of increased HR after acute cannabis use relate to self-reported drug effects or blood THC levels. Aims: To describe the relationship between THC concentration of product used, self-reported subjective intoxication, THC blood levels, and frequency of cannabis use with the change in HR after acute cannabis use. Materials and Methods: Participants (n = 140) were given 15 min to smoke self-supplied cannabis ad libitum, HR was measured at baseline and an average of 2 min post-cannabis smoking. The ARCI-Marijuana scale and Visual Analog Scales (VAS) were administered, and blood samples were taken at both time points. Participants were asked about their frequency of use. Information about the product used was recorded from the package. Linear regression was used to analyze the relationship between changes in HR (post-pre cannabis use) and post-cannabis use HR, blood THC concentration, THC product concentration, frequency of use, and self-reported drug effect. Results: There was a significantly higher HR among those who smoked cannabis compared to the controls (p < 0.001), which did not significantly differ by frequency of use (p = 0.18). Higher concentration THC (extract) products did not produce a significantly different HR than lower concentration (flower) products (p = 0.096). VAS score was associated with an increase in HR (p < 0.05). Overall, blood THC levels were not significantly related to the change in HR (p = 0.69); however, when probed, there was a slight positive association among the occasional use group only. Discussion: Cardiovascular effects of cannabis consumption may not be as subject to tolerance with daily cannabis use and do not directly increase with THC concentration of the product. This is a departure from other effects (i.e., cognitive, subjective drug effects) where tolerance is well established. These findings also suggest that, at least among those with daily use, higher concentration THC products (>60%) do not necessarily produce cardiovascular physiological effects that are significantly more robust than lower concentration (<20%) products.

Effects of acute cannabis inhalation on reaction time, decision-making, and memory using a tablet-based application.

BACKGROUND: Acute cannabis use has been demonstrated to slow reaction time and affect decision-making and short-term memory. These effects may have utility in identifying impairment associated with recent use. However, these effects have not been widely investigated among individuals with a pattern of daily use, who may have acquired tolerance. The purpose of this study was to examine the impact of tolerance to cannabis on the acute effects as measured by reaction time, decision-making (gap acceptance), and short-term memory. METHODS: Participants (ages 25-45) completed a tablet-based (iPad) test battery before and approximately 60 min after smoking cannabis flower. The change in performance from before to after cannabis use was compared across three groups of cannabis users: (1) occasional use (n = 23); (2) daily use (n = 31); or (3) no current use (n = 32). Participants in the occasional and daily use group self-administered ad libitum, by smoking or vaping, self-supplied cannabis flower with a high concentration of total THC (15-30%). RESULTS: The occasional use group exhibited decrements in reaction time (slowed) and short-term memory (replicated fewer shapes) from before to after cannabis use, as compared to the no-use group. In the gap acceptance task, daily use participants took more time to complete the task post-smoking cannabis as compared to those with no use or occasional use; however, the level of accuracy did not significantly change. CONCLUSIONS: The findings are consistent with acquired tolerance to certain acute psychomotor effects with daily cannabis use. The finding from the gap acceptance task which showed a decline in speed but not accuracy may indicate a prioritization of accuracy over response time. Cognitive and psychomotor assessments may have utility for identifying impairment associated with recent cannabis use.

Accuracy and replicability of identifying eyelid tremor as an indicator of recent cannabis smoking.

INTRODUCTION: Cannabis intoxication may increase the risk of motor vehicle crashes. However, reliable methods of assessing cannabis intoxication are limited. The presence of eyelid tremors is among the signs of cannabis use identified under the Drug Evaluation and Classification Program of the International Association of Chiefs of Police. Our objectives were to assess the accuracy and replicability of identifying eyelid tremor as an indicator of recent cannabis smoking using a blinded, controlled study design. METHODS: Adult subjects (N = 103) were recruited into three groups based on their cannabis use history: daily, occasional, and no current cannabis use. Participants' closed eyelids were video recorded for 30 seconds by infrared videography goggles before and at a mean ± standard deviation time of 71.4 ± 4.6 minutes after the onset of a 15-minute interval of ad libitum cannabis flower smoking or vaping. Three observers with expertise in neuro-ophthalmology and medical toxicology were trained on exemplar videos of eyelids to reach a consensus on how to grade eyelid tremor. Without knowledge of subjects' cannabis use history or time point (pre- or post-smoking), observers reviewed each video for eyelid tremor graded as absent, slight, moderate, or severe. During subsequent data analysis, this score was further dichotomized as a consensus score of absent (absent/slight) or present (moderate/severe). RESULTS: Kappa and intraclass correlation coefficient statistics demonstrated moderate agreement among the coders, which ranged from 0.44-0.45 and 0.58-0.61, respectively. There was no significant association between recent cannabis use and the observers' consensus assessment that eyelid tremor was present, and cannabis users were less likely to have tremors (odds ratio: 0.75; 95 percent confidence interval: 0.25, 2.40). The assessment of eyelid tremor as an indicator of recent cannabis smoking had a sensitivity of 0.86, specificity of 0.18, and accuracy of 0.64. DISCUSSION: Eyelid tremor has fair sensitivity but poor specificity and accuracy for identification of recent cannabis use. Inter-rater reliability for assessment of eyelid tremor was moderate for the presence and degree of tremor. The weak association between recent cannabis use and eyelid tremor does not support its utility in identifying recent cannabis use. LIMITATIONS: Videos were recorded at only one time point after cannabis use. Adherence to abstinence could not be strictly supervised. Due to regulatory restrictions, we were unable to control the cannabis product used or administer a fixed Δ9-tetrahydrocannabinol dose. Participants were predominately non-Hispanic and White. CONCLUSIONS: In a cohort of participants with a range of cannabis use histories, acute cannabis smoking was not associated with the presence of eyelid tremor, regardless of cannabis use history, at 70 minutes post-smoking. Additional research is needed to identify the presence of eyelid tremor accurately, determine the relationship between cannabis dose and timeline in relation to last cannabis use to eyelid tremor, and determine how it should be, if at all, utilized for cannabis Drug Recognition Evaluator examinations.

Blood cannabinoid molar metabolite ratios are superior to blood THC as an indicator of recent cannabis smoking.

INTRODUCTION: Cannabis use is a growing concern in transportation and workplace incidents. Because Δ9-tetrahydrocannabinol is detectable after acute psychoactive effects have resolved, it has limitations as an indicator of recent usage or potential impairment. METHODS: In an observational study of driving and psychomotor performance, we measured whole blood Δ9-tetrahydrocannabinol plus its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol by liquid chromatography with tandem mass spectrometry at baseline and 30 min after starting a 15-minute interval of smoking cannabis in 24 occasional and 32 daily cannabis smokers. We calculated two blood cannabinoid molar metabolite ratios: 1) [Δ9-tetrahydrocannabinol] to [11-nor-9-carboxy-Δ9-tetrahydrocannabinol] and 2) ([Δ9-tetrahydrocannabinol] + [11-hydroxy-Δ9-tetrahydrocannabinol]) to [11-nor-9-carboxy-Δ9-tetrahydrocannabinol]. We compared these to blood [Δ9-tetrahydrocannabinol] alone as indicators of recent cannabis smoking. RESULTS: Median Δ9-tetrahydrocannabinol concentrations increased from 0 ( 0.38). By comparison, a cut-point for Δ9-tetrahydrocannabinol of 5.3 µg/L yielded 88% specificity, 73% sensitivity, and 80% accuracy. CONCLUSIONS: In occasional and daily users, the blood cannabinoid molar metabolite ratios were superior to whole blood Δ9-tetrahydrocannabinol as indicators of recent cannabis smoking. We recommend measurement and reporting of Δ9-tetrahydrocannabinol, 11-hydroxy-Δ9-tetrahydrocannabinol, and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol, and their molar metabolite ratios in forensic and safety investigations.

The minor cannabinoid cannabigerol (CBG) is a highly specific blood biomarker of recent cannabis smoking.

INTRODUCTION: The determination of recent cannabis use is of forensic interest in the investigation of automotive crashes, workplace incidents and other mishaps. Because Δ9-tetrahydrocannabinol may persist in blood after psychoactive effects of intoxication resolve, particularly in regular users, short-lived minor cannabinoids such as cannabigerol have merited examination as adjunct indicators of recent cannabis inhalation. METHODS: As part of an observational cohort study, whole blood cannabinoids including cannabigerol were measured in whole blood by liquid chromatography with tandem mass spectrometry at baseline, and 30 minutes after initiation of a 15-minute supervised interval of ad libitum cannabis smoking in occasional (1-2 days/week over the past 30 days) (n = 24) and daily cannabis smokers (n = 32). Per protocol, subjects self-reported abstention from inhaling cannabis (>8 h) or ingesting cannabis (>12 h) prior to baseline measurement. RESULTS: At baseline, none of the occasional users had detectable cannabigerol (limit of detection = 0.2 µg/L), whereas cannabigerol was detectable post-smoking in 7 of 24 (29%). Among daily cannabis users, 2 of 32 (6%) had detectable cannabigerol at baseline, increasing to 21 of 32 (66%) post-smoking. The odds ratio for recent cannabis smoking associated with a detectable cannabigerol was 27 (95% confidence interval: 6.6, 110.3). In this mixed cohort of occasional and daily cannabis users, receiver operator characteristic curve analysis indicated that whole blood cannabigerol concentration of ≥ 0.2 µg/L had 96% specificity, 50% sensitivity, and 73% accuracy for identifying a 15-minute interval of ad libitum cannabis smoking initiated 30 minutes earlier. Post smoking blood Δ9-tetrahydrocannabinol (median = 5.6 µg/L in occasional users, 21.3 µg/L in daily users) was significantly correlated with post-smoking cannabigerol (P < 0.0001). CONCLUSION: Whole blood cannabigerol may have forensic utility as a highly specific albeit insensitive biomarker of recent cannabis smoking.

Comparison of Two-Bag Versus Three-Bag N-Acetylcysteine Regimens for Pediatric Acetaminophen Toxicity.

BACKGROUND: Acetaminophen overdose is a leading cause of liver failure, and a leading cause of pediatric poisoning requiring hospital admission. The antidote, N-acetylcysteine (NAC), is traditionally administered as a three-bag intravenous infusion. Despite its efficacy, NAC is associated with high incidence of nonallergic anaphylactoid reactions (NAARs). Adult evidence demonstrates that alternative dosing regimens decrease NAARs and medication errors (MEs). OBJECTIVES: To compare NAARs and MEs associated with two- versus three-bag NAC for acetaminophen overdose in a pediatric population. METHODS: This is a retrospective observational cohort study comparing pediatric patients who received three- versus two-bag NAC for acetaminophen toxicity. The primary outcome was incidence of NAARs. Secondary outcomes were rates of MEs and relevant hospital outcomes (length of stay [LOS], intensive care unit (ICU) admission, liver transplant, death). RESULTS: Two hundred forty-three patients met inclusion criteria (median age of 15 years): 150 (62%) three-bag NAC and 93 (38%) two-bag NAC. There was no difference in overall NAARs (p = 0.54). Fewer cutaneous NAARs were observed in the two-bag group, three-bag: 15 (10%), two-bag: 2 (2%), p = 0.02. MEs were significantly decreased with the two-bag regimen, three-bag: 59 (39%), two-bag: 21 (23%), p = 0.01. No statistical differences were observed in LOS, ICU admissions, transplant, or death. CONCLUSION AND RELEVANCE: A significant decrease in cutaneous NAARs and MEs was observed in pediatric patients by combining the first two bags of the traditional three-bag NAC regimen. In pediatric populations, a two-bag NAC regimen for acetaminophen overdose may improve medication tolerance and safety.

Trends of prescription psychotropic medication exposures in pediatric patients, 2009-2018.

BACKGROUND: Mental health disorders and related suicide attempts are increasing in both the adult and pediatric patient populations. Because of the increasing prevalence of mental health disorders, there is increased use of psychotropic medications in adult and pediatric patients, which can pose a risk for potentially adverse pediatric ingestions. The objective was to determine trends and outcomes for pediatric psychotropic medication ingestions reported to the American Association of Poison Control Centers (AAPCC) National Poison Data System (NPDS). METHODS: This was a retrospective review of pediatric (≤18 years of age) exposures reported to AAPCC NPDS between January 1, 2009 and December 31, 2018. Single psychotropic medication ingestions of atypical antipsychotics, bupropion, buspirone, clonidine, lithium, methylphenidate, mirtazapine, monoamine oxidase inhibitors (MAOIs), selective norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), trazodone, and tricyclic antidepressants (TCAs) were examined. RESULTS: Over the 10-year study period, 356,548 pediatric psychotropic medication ingestions were reported to NPDS. SSRI ingestions were the most frequently reported (34%), followed by atypical antipsychotics (17%), and methylphenidate (15%). Unintentional ingestions were most prominent in patients 0-12 years of age (79%), whereas, in patients age 13-18 years, 76% were intentional. SSRI ingestions were asymptomatic in 68% of cases. Clonidine and bupropion ingestions had the highest proportion of moderate and major clinical effects (29 and 25%, respectively). There were 29 deaths: atypical antipsychotics (n = 4), bupropion (n = 10), lithium (n = 1), SNRI (n = 1), SSRIs (n = 7), and TCAs (n = 6); 19 (65%) were in adolescent patients. CONCLUSIONS: SSRIs were the most frequently reported ingestion, while bupropion and clonidine were associated with a high percentage of moderate and major clinical effects. This study demonstrates opportunities for targeted prevention strategies to prevent potentially adverse pediatric ingestions to psychotropic medications.

Prescribing Patterns of Oral Opioid Analgesic for Acute Pain at a Tertiary Care Children's Hospital Emergency Departments and Urgent Cares.

OBJECTIVES: Despite Centers for Disease Control and Prevention guidelines on adult opioid prescribing, there is a paucity of evidence and no guidelines to inform opioid prescribing in pediatrics. To develop guidelines on pediatric prescribing, it is imperative to evaluate current practice on opioid use. The objectives were to describe prescribing patterns of opioids for acute pain at a children's hospital and to compare clinical characteristics of patients who received less or greater than 3 days. METHODS: A retrospective review of oral opioid analgesics prescribed for acute pain at a tertiary care children's hospital emergency department and urgent care from January 1, 2017, to December 31, 2017. Patients younger than 22 years who received an opioid prescription upon discharge were included. Patients with hematology/oncology or chronic pain diagnosis were excluded. RESULTS: Opioids were prescribed for a median of 2.2 days (interquartile range, 1.4-3.0 days). Most opioids were prescribed for ≤3 days (1326; 79.3%), and there were 44 (2.6%) prescriptions for >7 days. Twenty-two opioid formulations were prescribed. Single-ingredient oxycodone was the most commonly prescribed (877; 52.5%); there were 724 (43.3%) acetaminophen combination products. Common diagnoses were orthopedic (973; 58.2%), surgery/burn/trauma (195; 11.7%), and ear/nose/throat (143; 8.6%). Patients who received >3 days of opioids were younger (P < 0.001), and there was no differences in sex, ethnicity, insurance, or provider qualifications. CONCLUSIONS: Overall, prescribing patterns for the duration of opioid analgesics were ≤3 days, with a median of 2 days. There was a large range of days prescribed, with variations in prescribing characteristics among patients and providers.

Lacosamide Overdose: A Case of QRS Prolongation and Seizure.

BACKGROUND: Lacosamide is a third-generation antiepileptic drug. Its likely mechanism of action is via neuronal sodium channel blockade, via a unique manner compared with other antiepileptic drugs that block sodium channels. A paucity of information exists regarding lacosamide overdosage. Lacosamide overdosage is thought to cause QRS prolongation and seizures, due to its effect of sodium channel blockade. The potential efficacy of sodium bicarbonate to reverse the effects of lacosamide has not been well studied. Furthermore, prior reports of lacosamide toxicity have occurred in the setting of concomitant polypharmacy. Thus, the isolated toxic effects of the drug have not been well elucidated. CASE REPORT: We report a case of a suspected, single-ingestion overdose on lacosamide. The patient developed signs of cardiotoxicity and seizure. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: After lacosamide overdosage, the emergency physician must be capable of acute management of subsequent lacosamide toxicity. Understanding the mechanisms of action causing toxicity due to this drug can help the clinician to anticipate the interventions that may be needed or useful to treat this potentially toxic ingestion.

Brief report: Characterization of marijuana use in us college students by state marijuana legalization status as reported to an online survey.

BACKGROUND AND OBJECTIVE: US college student marijuana use is the highest since 1980. The objective was to investigate use characteristics among college students. METHODS: The RADARS® System College Survey Program surveyed individuals in a university, technical or online school. This was a secondary analysis of existing data. RESULTS: Seven thousand one hundred five students were enrolled, <30% of students' perceived marijuana use a health risk. Students in medical states were more likely to use marijuana compared to non-legal states. (p < .001) Smoking and edibles were common methods of use. CONCLUSIONS: Higher reports of college student use were observed in medical states without differences in risk perception. SCIENTIFIC SIGNIFICANCE: This study further demonstrates the public health impact of marijuana legalization by comparing college study use of marijuana by state legalization status, and demonstrating high rates of use of concentrated products. These findings should be factored when determining regulations and preventative measures when legalizing marijuana. (Am J Addict 2019;28:266-269).

Review of Biguanide (Metformin) Toxicity.

In the 1920s, guanidine, the active component of Galega officinalis, was shown to lower glucose levels and used to synthesize several antidiabetic compounds. Metformin (1,1 dimethylbiguanide) is the most well-known and currently the only marketed biguanide in the United States, United Kingdom, Canada, and Australia for the treatment of non-insulin-dependent diabetes mellitus. Although phenformin was removed from the US market in the 1970s, it is still available around the world and can be found in unregulated herbal supplements. Adverse events associated with therapeutic use of biguanides include gastrointestinal upset, vitamin B12 deficiency, and hemolytic anemia. Although the incidence is low, metformin toxicity can lead to hyperlactatemia and metabolic acidosis. Since metformin is predominantly eliminated from the body by the kidneys, toxicity can occur when metformin accumulates due to poor clearance from renal insufficiency or in the overdose setting. The dominant source of metabolic acidosis associated with hyperlactatemia in metformin toxicity is the rapid cytosolic adenosine triphosphate (ATP) turnover when complex I is inhibited and oxidative phosphorylation cannot adequately recycle the vast quantity of H+ from ATP hydrolysis. Although metabolic acidosis and hyperlactatemia are markers of metformin toxicity, the degree of hyperlactatemia and severity of acidemia have not been shown to be of prognostic value. Regardless of the etiology of toxicity, treatment should include supportive care and consideration for adjunct therapies such as gastrointestinal decontamination, glucose and insulin, alkalinization, extracorporeal techniques to reduce metformin body burden, and metabolic rescue.

Common Substances of Abuse.

Adolescent substance abuse remains common, with almost a third of adolescents admitting to ethanol use, and a quarter admitting to illicit drug use. It is essential for pediatricians to regularly screen adolescent patients for substance use, because early initiation of drug use has been associated with physical, behavioral, and social health risks. Adolescents abuse what is common and readily available; this includes ethanol, over-the-counter products, marijuana, and inhalants. The most common and effective clinical treatments for significant toxicity from substances of abuse is symptomatic and supportive care including hemodynamic support, respiratory support, and sedation to control psychomotor agitation.

Capsaicin Cream for Treatment of Cannabinoid Hyperemesis Syndrome in Adolescents: A Case Series.

Cannabinoid hyperemesis syndrome (CHS) is an underrecognized diagnosis among adolescents. In the adult literature, it is characterized as nausea, vomiting, and abdominal pain in patients with chronic marijuana use. CHS is often refractory to the standard treatment of nausea and vomiting. Unconventional antiemetics, such as haloperidol, have been successful in alleviating symptoms; however, even 1 dose of haloperidol can lead to grave adverse effects, such as dystonia, extrapyramidal reactions, and neuroleptic malignant syndrome. The use of topical capsaicin cream to treat CHS has been well described in the adult literature. This treatment is cost-effective and is associated with few serious side effects. Here, we describe 2 adolescent patients with nausea, vomiting, and abdominal pain in the setting of chronic cannabis use whose symptoms were not relieved by standard antiemetic therapies, but who responded well to topical capsaicin administration in our pediatric emergency department. We also discuss the pathophysiology behind capsaicin's efficacy. These are the first reported cases in which capsaicin was successfully used to treat CHS in pediatric patients.

Medication organizers (pill minders) increase the risk for unintentional pediatric ingestions.

OBJECTIVE: Medication organizers may help improve medication compliance; however, they may increase the risk of having an unintentional pediatric exposure. The objective of this study was to measure the association between a pediatric emergency department (ED) visit for an unintentional pharmaceutical ingestion and the use of a medication organizer in the household. METHODS: This was a cross-sectional case control study at a tertiary care children's hospital ED. Cases included subjects <6 years of age who were evaluated in the ED for an unintentional pharmaceutical ingestion. The control group presented to the ED for a non-injury complaint and was matched using age and sex. RESULTS: The unadjusted odds ratio (OR) of risk for unintentional pharmaceutical ingestion with use of a medication organizer was 2.0 (95% CI, 1.3, 2.9). After adjusting for the presence of prescription medications in the home, the OR of risk for ingestion remained statistically significant at 1.8 (95% CI, 1.1, 2.7). The child obtained the exposure medication from the medication organizer in 63% of cases where a medication organizer was present in the home. Cases were more likely to have knowledge of, and previous contact with poison control centers (PCC) than non-injury controls. Overall, a large number of caregivers (36%) did not have any knowledge of PCC. There were also differences in smoking and use of seat belts between cases and controls. CONCLUSIONS: The use of medication organizers may be a risk factor for unintentional pediatric pharmaceutical ingestions, even when controlling for the use of prescription medications in the home. Further research is needed to evaluate the specific role of medication organizers, and subsequently, improve prevention strategies.

Pediatric Concerns Due to Expanded Cannabis Use: Unintended Consequences of Legalization.

An "unintended consequence" of marijuana legalization is the impact on the pediatric population. From prenatal exposure to unintentional childhood exposures, through concerns of adolescence abuse and marijuana use for medicinal indications in children, marijuana exposure can affect pediatric patients at every stage in childhood. Regardless of the stage or reason of exposure, concerns exist about short-term and long-term consequences in a child's physical and mental health. The use of cannabidiol (CBD) may have some benefit for the treatment of epilepsy, but emphasis needs to be on rigorous clinical trials to evaluate efficacy and safety. As more states allow both medical and recreational marijuana, availability and prevalence of use will likely increase and more surveillance and research is needed to evaluate the consequences on the pediatric population.