Cannabis, or marijuana, has been used for medicinal purposes for many years. Several types of cannabinoid medicines are available in the United States and Canada. Dronabinol (schedule III), nabilone (schedule II), and nabiximols (not U.S. Food and Drug Administration approved) are cannabis-derived pharmaceuticals. Medical cannabis or medical marijuana, a leafy plant cultivated for the production of its leaves and flowering tops, is a schedule I drug, but patients obtain it through cannabis dispensaries and statewide programs. The effect that cannabinoid compounds have on the cannabinoid receptors (CB(1) and CB(2) ) found in the brain can create varying pharmacologic responses based on formulation and patient characteristics. The cannabinoid Δ(9) -tetrahydrocannabinol has been determined to have the primary psychoactive effects; the effects of several other key cannabinoid compounds have yet to be fully elucidated. Dronabinol and nabilone are indicated for the treatment of nausea and vomiting associated with cancer chemotherapy and of anorexia associated with weight loss in patients with acquired immune deficiency syndrome. However, pain and muscle spasms are the most common reasons that medical cannabis is being recommended. Studies of medical cannabis show significant improvement in various types of pain and muscle spasticity. Reported adverse effects are typically not serious, with the most common being dizziness. Safety concerns regarding cannabis include the increased risk of developing schizophrenia with adolescent use, impairments in memory and cognition, accidental pediatric ingestions, and lack of safety packaging for medical cannabis formulations. This article will describe the pharmacology of cannabis, effects of various dosage formulations, therapeutics benefits and risks of cannabis for pain and muscle spasm, and safety concerns of medical cannabis use.

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Background Although, especially in the United States, there has been a recent surge of legalized cannabis for either recreational or medicinal purposes, surprisingly little is known about clinical dose-response relationships, pharmaco- and toxicodynamic effects of cannabinoids such as Δ9-tetrahydrocannabinol (THC). Even less is known about other active cannabinoids. Methods To address this knowledge gap, an online extraction, high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of 11 cannabinoids and metabolites including THC, 11-hydroxy-Δ9-tetrahydrocannabinol (11OH-THC), 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide (THC-C-gluc), cannabinol (CBN), cannabidiol (CBD), cannabigerol (CBG), cannabidivarin (CBDV), Δ9-tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-Δ9-tetrahydrocannabivarin (THCV-COOH) was developed and validated in human urine and plasma. Results In contrast to atmospheric pressure chemical ionization (APCI), electrospray ionization (ESI) was associated with extensive ion suppression in plasma and urine samples. Thus, the APCI assay was validated showing a lower limit of quantification (LLOQ) ranging from 0.39 to 3.91 ng/mL depending on study compound and matrix. The upper limit of quantitation (ULOQ) was 400 ng/mL except for THC-C-gluc with a ULOQ of 2000 ng/mL. The linearity was r> 0.99 for all analyzed calibration curves. Acceptance criteria for intra- and inter-batch accuracy (85%-115%) and imprecision (<15%) were met for all compounds. In plasma, the only exceptions were THCV (75.3%-121.2% inter-batch accuracy) and CBDV (inter-batch imprecision, 15.7%-17.2%). In urine, THCV did not meet predefined acceptance criteria for intra-batch accuracy. Conclusions This assay allows not only for monitoring THC and its major metabolites, but also of major cannabinoids that are of interest for marijuana research and clinical practice.

Author Contributions: Drs Ghiggeri and Ravani had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Ravani, Ghiggeri.

We describe the case of a patient with massive acetaminophen-diphenhydramine overdose and a 4-hour serum acetaminophen concentration of 653 μg/mL. The patient was treated with acetylcysteine 5 hours after ingestion. Because of a persistently elevated serum acetaminophen level of 413 μg/mL 45 hours after ingestion, a medical toxicologist recommended that the patient be treated with a second bolus of acetylcysteine (150 mg/kg followed by 12.5 mg/kg per hour for 4 hours, then 6.25 mg/kg per hour). On hospital day 3, she developed hepatic failure despite early treatment. Her transaminase levels and hepatic synthetic function began to improve on hospital day 6, and acetylcysteine was discontinued on hospital day 10. In cases of massive acetaminophen overdose, standard acetylcysteine dosing may not be adequate. We suggest that elevated serum acetaminophen concentrations at the end of a standard 20-hour acetylcysteine infusion should be discussed with the local poison center.

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.

Background and Objective: Poisoning is the leading cause of injury death in pediatric patients. Hospital and provider readiness, including pharmacy stocking, depends on reliable surveillance data describing local patterns of age-specific clinically significant exposures and the therapeutic modalities employed in their treatment. We aimed to characterize trends in clinically significant toxic exposures and their management.Methods: We performed a retrospective review of patients 18 years or younger in the American College of Medical Toxicology's Toxicology Investigators Consortium (ToxIC) Registry, a self-reporting database completed by bedside consulting medical toxicologists. We reviewed cases from January 1, 2010, through December 31, 2015. In 2015, ToxIC included 101 health care facilities. Data collected included demographics, geographic region, encounter and exposure details, survival, and therapeutic modalities employed, including antidotes, antivenoms, gastric decontamination, enhanced elimination, hyperbaric oxygen therapy, and extracorporeal membrane oxygenation.Results: From 2010 to 2015, 11,616 consults were recorded in ToxIC. Pediatric consultations increased from 934 (23.7%) in 2010 to 2425 (29.9%) in 2015 ( P < 0.001). Exposures were most commonly reported in females (57.8%) and adolescents (59.4%). Intentional ingestions (55.5%) comprised the majority of cases. The most frequent agents of exposure were analgesics (21.0%). There were 38 deaths reported (0.9%). The antidote used most commonly was N-acetylcysteine (11.0%). Geographic variation was demonstrated in prevalence of envenomations and heavy metal exposures, their respective treatments, and overall use of decontamination.Conclusions: Toxicology consultations for pediatric exposures increased from 2010 to 2015. Understanding which pediatric exposures require toxicologist management, the therapies most frequently employed, and geographical patterns is paramount to facility-level planning, pharmacy stocking, and provider education.

State-level all-payer claims databases (APCDs) are a possible new public health surveillance tool, but their reliability is unclear. We compared Colorado’s APCD with other state-level databases for use in monitoring the opioid epidemic (Colorado Hospital Association and Colorado’s Prescription Drug Monitoring Program database for 2010–2017), using descriptive analyses comparing quarterly counts/rates of opioid-involved inpatient and emergency department visits and counts/rates of 30-day opioid fills between databases. Utilization is lower in the Colorado APCD than the other databases for all outcomes but trends are parallel and consistent between databases. State APCDs hold promise for researchers, but they may be better suited to individual-level analyses or comparisons of providers than for surveillance of public health trends related to addiction.