Toxicity, Marijuana

Introduction

The term “marijuana” typically refers to the tobacco-like preparations of the leaves and flowers of the plant Cannabis sativa. The active ingredient is believed to be tetrahydrocannabinol, which is also responsible for intoxication. Different preparations of marijuana vary in strength, with THC concentration in cannabis varying with climate, soil, and cultivation techniques. Also, the amount absorbed by the body varies with route of administration. The effects of cannabis depend on various things: the dose, mode of administration, user’s prior experience with the drug, user’s expectations/attitudes towards the drugs, and social environment when using the drug.

Etiology

Marijuana intoxication is dose-related and has multiple names depending on the preparation: grass, ganja, hashish, etc. The amount absorbed by the body varies by the route of administration. Marijuana is commonly smoked due to the rapid onset of symptoms, but marijuana can also be eaten, (i.e., “grass” brownies), or drank, (i.e., marijuana tea). Smoked marijuana has an increased potency, quoted as high as 2.6 times by some sources. Marijuana is used for both recreational and therapeutic purposes. Although some people promote the “harmless” nature of marijuana, acute and chronic intoxication can occur.

Epidemiology

According to the World Health Organization (WHO), marijuana is the world’s most widely cultivated, trafficked, and abused illicit substance. Approximately 2.5% of the world’s population (147 million people) uses it. Its use is more prevalent among men than women—a gender gap that widened in the years 2007 to 2014.  Use is widespread in the adolescent and young adult population.  According to the Monitoring the Future survey, an annual survey of drug use in America’s middle and high school students, rates of use within one year ranged from approximately 9% in 8 graders to 35% in 12 graders.  In the United States, cannabis is still a Schedule 1, meaning it is not scheduled for federal medical use and has a high potential for abuse.

History and Physical

The initial state of acute intoxication formulates the symptoms that recreational users enjoy: euphoria, perception alterations such as time and spatial distortion, intensification of ordinary sensory experiences, and motor impairment. Not all effects of cannabis intoxication are welcomed by users, as some experience unpleasant psychological reactions such as panic, fear, or depression. Acute intoxication also affects the heart and vascular system, resulting in cannabis-induced tachycardia and postural hypotension. CNS and respiratory depression have been noted with high doses in animal models. Studies show that inhaled doses of 2 to 3 mg of THC and ingested doses of 5 to 20 mg THC can cause impairment of attention, memory, executive functioning, and short-term memory. Doses > 7.5 mg/m2 inhaled in adults and oral doses from 5 to 300 mg in pediatrics can produce more severe symptoms such as hypotension, panic, anxiety, myoclonic jerking/hyperkinesis, delirium, respiratory depression, and ataxia. Conjunctivitis is a consistent physical exam finding regardless of the route of administration. In children, neurological abnormalities such as lethargy and hyperkinesis can be signs of life-threatening toxicity. Although acute toxicity is uncommon in non-pediatric patients, those who come to medical attention are more likely to have hyperemesis, behavioral problems or a medical emergency such as bronchospasm due to inhalation. There is disagreement about how long these impairments persist after taking cannabis, ranging from hours to days. Chronic use may lead to long-term effects on cognitive performance, “Amotivational syndrome” (loss of energy and a will to work), and respiratory disorders. There have also been various reports of patients presenting with cyclic vomiting syndrome/cannabinoid hyperemesis.  Cannabis intoxication can lead to acute psychosis in many individuals and can produce short-term exacerbations of pre-existing psychotic diseases such as schizophrenia.  Psychiatric symptoms observed in some studies include depersonalization, fear of dying, irrational panic, and paranoid ideas.

Evaluation

The standard urine drug screen can be used to detect THC metabolites, primarily THC carboxylase. The lower limits range from 20 to 100 ng/mL. Second-hand exposure causing positive results is tough to achieve in adolescents and adults, although this has not been studied in children. Reported false positives for THC include dronabinol, efavirenz, PPIs, hemp seed oil, NSAIDs, and baby wash products in infants. Positive results for THC have been reported up to 10 days after weekly use and up to 25 days for after daily use, making the timeline of exposure different and severity of intoxication difficult to correlate. Breathalyzer tests have been proposed, but since small amounts of cannabis continue to be released from fat into the blood long after short-term impairment wears off, this method has not been promoted.

Treatment / Management

Most adolescents and adults do not warrant testing for diagnosis or treatment of cannabis intoxication.  If chest pain is present, it is reasonable to obtain a 12-lead electrocardiogram and possibly cardiac markers to assess for myocardial ischemia or infarction, as there is thought to be an elevated risk up to 4.8 times for MI within 1 hour of marijuana use.  Patients with toxic ingestion should also be screened for co-ingestion, especially if electrolyte abnormalities or OTc or QRS prolongation is noted on EKG. Some patients, particularly children, may require further testing if exposure is unknown, including rapid blood glucose, electrolytes, blood gas analysis, and neuroimaging (e.g., computed tomography of the head). Neuroimaging should be avoided in known cannabis exposures unless focal neurologic findings are also present or concerns for other etiologies such as head trauma exist.
The treatment for marijuana intoxication is symptomatic management. The extent of management has numerous factors, including an age of individual and amount of cannabis ingested.  There have been several cases of accidental cannabis poisoning in a geriatric patient resulting in intensive care admissions due to central nervous system depression. Unintentional ingestion by children has also resulted in similar admissions. In cannabis-induced psychotic disorders, safe cannabis detoxication typically requires 24 hours, but sometimes longer if persistent psychosis or unstable vital signs occur.

Other Issues

For obvious ethical reasons, there is no experimental evidence to determine the lethal dose in humans; but the dose that kills animals range from 40 mg/kg to 130 mg/kg intravenously. Well-controlled studies have not implicated in utero marijuana exposure in any major fetal growth or physical abnormalities, but it may have may have long-term emotional and behavioral consequences. Marijuana has an affinity for lipids and accumulates in human milk, so its use is contraindicated during breastfeeding.

Questions

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