INTRODUCTION — This topic discusses the epidemiology, toxicity, clinical manifestations, and management of acute intoxication with cannabis.
The clinical manifestations and management of toxicity from synthetic cannabinoids, medical uses of cannabinoids, and the manifestations and treatment of cannabis use disorder are provided separately:
●(See "Synthetic cannabinoids: Acute intoxication".)
●(See "Symptom management of multiple sclerosis in adults", section on 'Cannabinoids'.)
●(See "Overview of the management of epilepsy in adults", section on 'Alternative therapies'.)
●(See "Cannabis use: Epidemiology, pharmacology, comorbidities, and adverse effects" and "Cannabis use disorder in adults".)
EPIDEMIOLOGY — According to the World Health Organization (WHO), 147 million people, or 2.5 percent of the world population, use cannabis, making it the world's most widely cultivated, trafficked, and abused illicit substance [1]. Use is high in the adolescent age group. As an example, among surveyed adolescents in the United States, approximately 6 percent of 8th graders, 17 percent of 10th graders, and 21 percent of 12th graders reported cannabis use in the past month [2].
Some countries have legalized cannabis, including Uruguay and Canada [3,4]. At the United States federal level, cannabis products are classified as Schedule I (ie, no currently accepted medical use and a high potential for abuse) [3,5,6]. However, over 30 states have decriminalized medical cannabis or are reviewing legislation to allow low-dose delta-9 tetrahydrocannabinol (THC) products for specific medicinal indications. As of 2021, 18 states have allowed the retail sale and possession of recreational cannabis [7].
The public health impact of decriminalization or legalization of recreational cannabis use includes the following:
●Both decriminalization and legalized recreational use have been associated with increased unintentional pediatric ingestions [8-16]. As an example, after legalization of recreational cannabis use in Colorado, annual calls to the regional poison control center for pediatric cannabis exposure increased 34 percent on average to 6 cases per 100,000 population, which was almost twice the rate for the rest of the United States [10]. Exposure to recreational cannabis accounted for about half of cases. Rates of hospital visits at a large regional children's hospital system also increased significantly during the period of the study, although the total number of presenting patients (81) was small.
●The impact of cannabis legalization on prevalence of use among youth is mixed. In regions with medical cannabis availability, diversion of drug from registered users may encourage adolescent abuse [17]. The National Survey on Drug Use and Health cross-sectional survey reported a small increase in cannabis use disorder in the adolescent and young adult population in the regions of the United States that have legalized recreational cannabis [18]. On the other hand, a separately administered high school survey in Colorado has not demonstrated a significant increase in admitted cannabis use in high school students. However, there was a significant increase in use of alternative forms of cannabis, with dabbing increasing to 10.2 percent and vaporizing to 6.8 percent in 2019 among cannabis users [19].
●Approximately 1 in 20 pregnant women report cannabis use some time during pregnancy. The prevalence of use in this population has continued to increase in the United States, most notable in states that have legalized medical and recreational cannabis. Common reasons for use included self-treatment of stress, anxiety, nausea, vomiting, and pain. (See "Substance use during pregnancy: Overview of selected drugs", section on 'Cannabis (marijuana)'.)
●In other countries where cannabis can be used legally, rates of usage vary. In the European Union, cannabis use in 2020 for those aged 15 to 34 was estimated at 15.4 percent, ranging from 3.4 percent in Hungary to 21.8 percent in France [20]. Thus, the impact of decriminalization or legalization on the subsequent prevalence of cannabis use is not easily predicted and varies depending upon the specifics of enacted regulations [3].
PHARMACOLOGY AND TOXICITY
Site of action — The cannabinoid receptor is a G-protein-coupled receptor, which inhibits adenylyl cyclase and stimulates potassium conductance. There are two known cannabinoid receptors: CB1 and CB2 [21-23]:
●CB1 is found in the central nervous system including the basal ganglia, substantia nigra, cerebellum, hippocampus, and cerebral cortex. It acts presynaptically and inhibits release of several neurotransmitters including acetylcholine, L-glutamate, gamma amino butyric acid (GABA), norepinephrine, dopamine, and 5-hydroxytryptamine.
●CB2 is found peripherally in the immune system tissues (eg, splenic macrophages and B lymphocytes), peripheral nerve terminals, and vas deferens. It is postulated that it plays a role in regulation of immune responses and inflammatory reactions. Anandamide and palmitoylethanolamide are known endogenous cannabinoid receptor ligands.
Pharmacokinetics — Delta-9 tetrahydrocannabinol (THC) is the most psychoactive cannabinoid. The pharmacokinetics and pharmacodynamics of THC vary by route of exposure as follows [21,23-31]:
●Inhaled cannabis – After inhalation of cannabis smoke, onset of psychoactive effects occurs rapidly, with peak effects felt at 15 to 30 minutes and lasting up to four hours. These effects mirror plasma THC concentrations. Approximately 2 to 3 mg of inhaled THC is sufficient to produce drug effects in a naïve user. Pulmonary bioavailability varies from 10 to 35 percent of an inhaled dose and is determined by the depth of inhalation along with the duration of puffing and breath holding.
●Ingested cannabis – When compared with inhalation, cannabis ingestion has a delayed onset of psychoactive effects that ranges from 30 minutes to three hours. Clinical effects may last up to 12 hours. Orally administered cannabis has low bioavailability (5 to 20 percent) because of chemical degradation in gastric acid and substantial first-pass metabolism in the liver. In naïve users, psychotropic effects occur with 5 to 20 mg of ingested THC.
THC is lipid soluble, highly protein bound (95 to 99 percent), and has a volume of distribution of 2.5 to 3.5 L/kg [21,27].
THC metabolism occurs via hepatic cytochrome oxidases, CYP2C9 and 3A4. The primary active metabolite is 11-hydroxy THC (11-OH THC), and the inactivated metabolite is THC-carboxylic acid (THC-COOH) [21]. After metabolism, THC is mostly excreted as hydroxylated and carboxylated metabolites via feces (65 percent) and urine (20 percent) [21]. Although difficult to measure, the acute elimination half-life of THC is slow, ranging from 25 to 36 hours [21]. This lengthy half-life is likely due to slow release from lipid storage compartments and enterohepatic circulation. Elimination half-life is longer in regular cannabis users.
THC crosses the placenta with fetal plasma concentrations 10 to 30 percent of maternal concentrations. Limited data demonstrate that THC also accumulates in breast milk, peaking at four hours after maternal smoking, and can be detectable in breast milk at least six days after last maternal use. (See "Infants with prenatal substance use exposure" and "Substance use during pregnancy: Overview of selected drugs", section on 'Cannabis (marijuana)'.)
Cannabis formulations — There are a variety of subspecies and strains of cannabis; Cannabis sativa is one of the most commonly used for recreational purposes. Cannabis sativa contains over 500 different clinical compounds and over 60 known cannabinoids; of these, THC is the most psychoactive and is responsible for most symptoms of intoxication [21,25].
The dried flower of the cannabis plant has a large range of THC content, ranging from 1 to 20 percent of the total weight; however, much variability exists among cannabis samples [32]. In general, cannabis potency has increased over the past 20 years [33]. Common slang terms for cannabis include "pot," "grass," "dope," "MJ," "Mary Jane," "doobie," "hooch," "weed," "hash," "reefer," and "ganja."
Chemical analogues of THC called "synthetic cannabinoids" may have been available in Europe as early as 2004 and were first reported in the United States in December 2008. The clinical effects can be similar to natural cannabis intoxication but may also result in more severe life-threatening symptoms. Acute intoxication from synthetic cannabinoids is discussed separately. (See "Synthetic cannabinoids: Acute intoxication".)
Recreational use — Recreational cannabis use often consists of smoking the dried flower in the form of rolled cigarettes (joints) and water bongs [34]. THC is also extracted using various solvents (butane, ethanol, hexane, isopropanol) to create highly concentrated products (60 to 99 percent of THC by weight) including oils and tinctures called "wax," "dabs," "budder," and "shatters" [35-37]. In addition to being smoked, these highly concentrated products are vaporized (eg, using electronic cigarettes [38,39]) or mixed in food products (such as baked goods, candies, and other food and beverages) and ingested ("edibles").
In regions where cannabis use is legal, concentrated forms are popular and may pose a risk of unintentional ingestion by young children or excessive use by adolescents and adults [40-42]. As an example, in Colorado, some companies have produced packaging for cannabis products that mimic popular candy, although state law prohibits packaging and advertising that targets children [43]. Furthermore, many of these products contain up to four times the suggested adult serving size dose of 5 to 10 mg. Cannabis edible product ingestions have significantly increased in young children, with a greater proportion of calls due to edible product ingestion in states that have legalized cannabis [15].
Medicinal use — Medicinal cannabis is supplied as dried flowers of the Cannabis sativa plant that are smoked as described for recreational cannabis use (see 'Recreational use' above). Derivatives of cannabinoids are also available as pharmaceuticals in some countries including oral preparations (dronabinol and nabilone) and a spray for buccal use (nabiximols).
Cannabis and its components have been proposed for various medicinal purposes, such as chronic severe pain (eg, due to cancer), refractory nausea and vomiting, anorexia and cachexia, glaucoma, and seizures [22,44]. However, none have been proven to have greater efficacy than other currently available medications.
Of these indications, medical cannabis is most frequently prescribed for severe or chronic pain. An oromucosal spray containing THC and cannabidiol (CBD; Sativex, also called nabiximols) has been shown to have some efficacy as a multipurpose analgesic in combination with traditional therapy and is approved for use in Canada and elsewhere but not in the United States. No controlled studies demonstrate the efficacy of inhaled cannabis as an adjunct to traditional pain medications for patients with cancer-related pain (see "Cancer pain management: Role of adjuvant analgesics (coanalgesics)", section on 'Cannabis and cannabinoids'). Trials in patients with multiple sclerosis have failed to show consistent pain reduction. (See "Symptom management of multiple sclerosis in adults", section on 'Cannabinoids'.)
Although inhaled, buccal, or ingested cannabis has shown some efficacy for refractory nausea and vomiting or glaucoma [45,46], consensus expert guidelines do not support its use. (See "Cancer pain management: Role of adjuvant analgesics (coanalgesics)", section on 'Cannabis and cannabinoids' and "Assessment and management of nausea and vomiting in palliative care", section on 'Cannabinoids and cannabis'.)
In addition, cannabinoids, specifically CBD, have been studied for the treatment of refractory epilepsy in children as discussed separately. (See "Lennox-Gastaut syndrome" and "Dravet syndrome: Management and prognosis", section on 'Cannabidiol'.)
Toxic effects — Recreational cannabis intake to achieve psychoactive effects can often result in adverse effects because there is no clear demarcation between doses that achieve symptoms desired by a cannabis user and noxious effects.
In adolescents and adults, inhaled doses of 2 to 3 mg of THC and ingested doses of 5 to 20 mg of THC impair attention, concentration, short-term memory, and executive functioning [21,23-31,47-53]. More severe adverse effects may occur at doses >7.5 mg/m2 of THC, including nausea, postural hypotension, delirium, panic attacks, anxiety, and myoclonic jerking [48,49]. Acute psychosis has also been associated with use of higher potency/concentrated cannabis products [54,55].
Toxicity in children is most often reported after ingestion of a highly concentrated food product [8,9,15,56-61] or hashish resin [62]. Estimated oral doses from 5 to 300 mg in pediatrics have caused a range of symptoms such as mild sleepiness, ataxia, behavior changes, excessive and purposeless motor activity of the extremities (hyperkinesis), coma, and respiratory depression with more severe intoxication correlated with higher estimated doses. For example, in a small cohort of 38 children presenting to an emergency department for acute cannabis intoxication after ingestion, degree of symptoms corresponded to an estimated dose as follows: 3.2 mg/kg of THC led to observation and minimal medical intervention, 7.2 mg/kg of THC led to admission to an inpatient floor and moderate medical intervention, and 13 mg/kg of THC led to admission to an intensive care unit and major medical interventions [63]. Patients without prior THC exposure more commonly had lethargy or somnolence and had a longer duration of clinical symptoms. Similarly, as concentrated hashish resin has become more available in France, a corresponding increase in the number of annual admissions and severity of symptoms has occurred among infants and young children [62,64].
CLINICAL MANIFESTATIONS — The clinical manifestations of acute cannabis intoxication vary according to age.
Neurologic abnormalities are more prominent in children and include ataxia, excessive and purposeless motor activity of the extremities (hyperkinesis), seizures, lethargy, and prolonged coma, which may be life threatening [8,9,56-62].
Acute cannabis intoxication is an unusual primary complaint in adolescents and adults. Patients who come to medical attention are more likely to have hyperemesis or behavioral problems (eg, dysphoria or agitation) caused by adverse cannabis effects or medical emergencies (eg, bronchospasm or pneumothorax) associated with the method of inhalation. Although rare, chest pain with myocardial infarction in young adults without any prior history of coronary artery abnormalities has been described [65-69]. The issue of causation is unclear, however, in light of the frequency of cannabis use in the general population and the presence of unsuspected atherosclerosis or other cardiac conditions in some of these patients.
Children — In children, acute cannabis intoxication typically occurs after exploratory ingestion of cannabis intended for adult use [8-10,57-61,70,71]. Less commonly, intentional exposure of children by caretakers, including encouragement of cannabis inhalation to promote sleepiness and to decrease activity, has been reported [72]. Pediatric ingestions of cannabis products happen more frequently in regions with decriminalization or legalization of cannabis use [8-15,73]. (See 'Epidemiology' above.)
After limited exposures, children may display sleepiness, euphoria, irritability, and other changes in behavior [8,9,57-61,70,72-74]. Vital signs may show sympathomimetic effects (eg, tachycardia and hypertension) or, in patients with depressed mental status, bradycardia. Nausea, vomiting, conjunctival injection, nystagmus, ataxia, and (in verbal children) slurred speech may also be present. Dilated pupils have frequently been reported, although miosis has also been described [74-77].
In large overdoses (eg, ingestion of edible products, concentrated oils, or hashish), coma with apnea or depressed respirations can occur [8-10,57-62,71,74].
Although not typical of pediatric cannabis intoxication, seizures have also been reported [58,70,71,76]. In one instance, cocaine was also found on urine screening [76]. In one retrospective series of 29 children under age three admitted with documented cannabis exposure, seizures occurred in four patients, all of whom had ingested hashish resin [70].
Adolescents and adults — The physiologic signs of cannabis intoxication in adolescents and adults can include [21,23,24]:
●Tachycardia
●Increased blood pressure or, especially in older adults, orthostatic hypotension
●Increased respiratory rate
●Conjunctival injection (red eye)
●Dry mouth
●Increased appetite
●Nystagmus
●Ataxia
●Slurred speech
Complications associated with inhalation use include:
●Acute exacerbations and poor symptom control in patients with asthma [78]. (See "Acute exacerbations of asthma in adults: Emergency department and inpatient management".)
●Pneumomediastinum and pneumothorax suggested by tachypnea, chest pain, and subcutaneous emphysemas caused by deep inhalation with breath-holding [79]. (See "Spontaneous pneumomediastinum in children and adolescents" and "Pneumothorax: Definitive management and prevention of recurrence".)
●Rarely, angina, myocardial infarction, and cardiac dysrhythmias [80-83]. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department".)
The risk for myocardial infarction among regular cannabis users has been found to be significantly elevated over baseline risk in nonusers [69,80].
Cannabis intoxication in adolescents and adults also results in the following neuropsychiatric effects:
●Mood, perception, thought content – Ingestion typically leads to feeling "high," marked by a euphoric, pleasurable feeling and a decrease in anxiety, alertness, depression, and tension. However, first-time cannabis users, as well as anxious or psychologically vulnerable individuals, may experience anxiety, dysphoria, and panic [24]. Increased sociability usually occurs during intoxication, although dysphoric reactions may be accompanied by social withdrawal. Inexperienced users who ingest cannabis products may not be aware that effects may not be felt for up to three hours, which may cause them to continue to consume high-potency products with an increased likelihood of dysphoria. (See 'Pharmacokinetics' above.)
Perceptual changes include the sensation that colors are brighter and music is more vivid [24]. Time perception is distorted in that perceived time is faster than clock time. Spatial perception can also be distorted, and high doses of potent cannabis products may cause hallucinations. Mystical thinking, increased self-consciousness, and depersonalization may occur, as well as transient grandiosity, paranoia, and other signs of psychosis [24,84]. Acute intoxication from THC can also lead to acute psychotic symptoms, which are worsened with higher doses of THC [55,85].
●Cognition, psychomotor performance – Cannabis use slows reaction time and impairs attention, concentration, short-term memory, and risk assessment. These effects are additive when cannabis is used in conjunction with other central nervous system depressants [24]. Acute cannabis use also impairs motor coordination and interferes with the ability to complete complex tasks that require divided attention [86].
Impairment of cognition, coordination, and judgment lasts much longer than the subjective mood change of feeling "high." Psychomotor impairment lasts for 12 to 24 hours due to accumulation of cannabis in adipose tissue, slow release of THC from fatty tissue stores, and enterohepatic recirculation. However, a cannabis user may think that they are no longer impaired until several hours after the acute mood-altering effects have resolved. As an example, a placebo-controlled trial with licensed pilots found that smoking cannabis impaired performance on a flight simulator for up to 24 hours, although only one of the nine subjects recognized this impairment [87].
Acute psychomotor impairments interfere with the ability to operate other heavy machinery, such as automobiles, trains, and motorcycles. A meta-analysis of nine studies found an association between cannabis intoxication and an increased risk of a motor vehicle collision involving serious injury or death [24,52,88,89]. Drivers using cannabis are two to seven times more likely to be responsible for accidents compared with drivers not using any drugs or alcohol [90]. Furthermore, the probability of causing an accident increases with plasma levels of THC [52].
DIAGNOSIS
Children — Diagnosis of cannabis intoxication in young children based solely on clinical criteria can be difficult because a history of exposure is often lacking, and the symptoms of cannabis exposure are nonspecific. Thus, ancillary studies are often needed to exclude other causes of altered mental status (see 'Other ancillary studies' below). Urine drug screens help confirm the diagnosis because any positive result in a symptomatic child likely represents an acute exposure. (See 'Drug testing for cannabinoids' below.)
Adolescents and adults — Acute cannabis intoxication is a clinical diagnosis in adolescents and adults. Urine drug screens are less helpful in adolescents and adults for the diagnosis of acute intoxication. Although testing is usually positive several hours after acute exposure, it can also be positive well after symptoms have resolved. As an example, positive results for THC metabolites have been reported up to 10 days after weekly use and up to 25 days after daily use [91]. Thus, cannabis testing does not provide any specific information on the timeline of exposure or correlate with severity of intoxication.
Pure cannabidiol (CBD) should not result in a positive THC urine drug screen. However, CBD products may contain THC, which will result in a positive urine drug screen [92]. Confirmatory testing evaluating individual cannabinoids and respective metabolites can help determine the specific exposure.
Selected adolescents and adults with chest pain may warrant an electrocardiogram (ECG), cardiac biomarkers, or chest radiograph to identify associated myocardial ischemia or pneumomediastinum. (See 'Other ancillary studies' below.)
Drug testing for cannabinoids — Hospital testing for cannabis typically consists of a urine drug screen. (See 'Diagnosis' above.)
Standard urine drug screens that are available in most health care facilities consist of immunoassays that detect THC metabolites, primarily the main metabolite THC-COOH. The lower limits of detection range from 20 to 100 ng/mL, depending upon the specific assay [93]. The Substance Abuse and Mental Health Services Administration (SAMHSA) standard is 50 ng/mL, with confirmatory testing using 15 ng/mL, as the lower limit of detection [94]. Immunoassays for THC do not detect synthetic cannabinoids, which are structurally distinct from THC.
In situations where a positive screen for cannabis has legal implications or may impact school attendance or sports participation, individuals may claim that the test results from passive inhalation of cannabis smoked by others. In adolescents and adults, it is difficult to achieve sufficient concentrations from secondhand smoke from typical cannabis cigarettes to detect metabolite concentrations above most urine drug screen limits [95-99]. However, studies using products with higher THC content (typical of what is more commonly used since 2005) have not been performed. There has been a case report of an infant becoming symptomatic after passive cannabis smoke exposure [100]. Metabolites of THC have been detectable in a cohort of children hospitalized for bronchiolitis exposed to passive cannabis smoke, although below the limits of detection of standard immunoassays [101].
False positives for cannabinoids are rare because the chemical structure is unique and immunoassays are targeted toward metabolites of THC. Reported false positives for THC include: dronabinol, efavirenz, proton pump inhibitors, hemp seed oil, nonsteroidal antiinflammatory drugs (NSAIDs), and baby wash products in infants [102-107]. Most package inserts for commercially available immunoassays will list possible false positives for their cannabinoid assay. If required for clinical or social indications, confirmatory testing of urine, blood, or serum can be sent to reference labs by gas chromatography and mass spectrophotometry. However, results of confirmatory testing do not return quickly enough to affect clinical care.
Other ancillary studies — Most adolescents and adults do not warrant any testing for the diagnosis or treatment of uncomplicated acute cannabis intoxication. Patients with chest pain suggestive of myocardial ischemia or infarction warrant a 12-lead ECG and possibly cardiac biomarkers (eg, troponin T or I). (See "Troponin testing: Clinical use", section on 'Diagnosis of acute MI'.)
Chest radiograph may assist in the diagnosis of stable patients with chest pain indicative of a spontaneous pneumothorax. However, patients with signs of a tension pneumothorax should undergo decompression prior to chest radiography. Bedside ultrasound may assist with rapid diagnosis of pneumothorax in these unstable patients. (See "Bedside pleural ultrasonography: Equipment, technique, and the identification of pleural effusion and pneumothorax".)
Children may warrant testing for other potential causes of altered mental status depending upon whether the exposure is known and based upon specific physical findings including rapid blood glucose, electrolytes, blood gas analysis, lumbar puncture, and neuroimaging (eg, computed tomography [CT] 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. (See 'Differential diagnosis' below.)
DIFFERENTIAL DIAGNOSIS
Children — The differential diagnosis for cannabis exposure in children is broad because toxicity most commonly presents as altered behavior, lethargy, or coma. When history of exposure is lacking, a positive rapid urine drug screen for cannabinoids is helpful for identifying cannabis as the likely culprit in children too young to be using cannabis recreationally. (See 'Drug testing for cannabinoids' above.)
Some common medical causes of lethargy and coma are listed here with features that distinguish them from cannabis intoxication (see "Evaluation of stupor and coma in children", section on 'Etiologies'):
●Hypoglycemia – Low rapid blood sugar (see "Causes of hypoglycemia in infants and children")
●Electrolyte imbalance (eg, hyponatremia or hypocalcemia) – Low serum sodium or calcium (see "Hyponatremia in children: Etiology and clinical manifestations" and "Etiology of hypocalcemia in infants and children")
●Central nervous system infection (eg, meningitis or encephalitis) – Fever and/or meningismus
●Traumatic brain injury, especially abusive head trauma – Child abuse may present with intracranial injury (eg, subdural hematoma) without an appropriate mechanism by history, retinal hemorrhages, skin bruising, and/or fractures (see "Child abuse: Evaluation and diagnosis of abusive head trauma in infants and children", section on 'Clinical features')
A positive urine drug screen for metabolites of cannabis also helps differentiate cannabis intoxication from poisoning with other agents but is not immediately available in most facilities. Toxicologic causes of lethargy and coma in children are extensive (table 1). The following agents and important clinical features that distinguish them from cannabis intoxication include:
●Opioids – Lethargy and coma following cannabis ingestion does not respond to naloxone, which differentiates it from toxicity caused by opioid analgesics. (See "Opioid intoxication in children and adolescents", section on 'Clinical manifestations'.)
●Sedative/hypnotic agents – Cannabis toxicity typically causes more tachycardia or seizure-like activity than sedatives/hypnotics. (See "Benzodiazepine poisoning and withdrawal", section on 'Clinical features of overdose' and "Meprobamate poisoning", section on 'Clinical features of overdose'.)
●Ethanol – A sickly sweet breath odor, hypoglycemia (when present), and an elevated blood alcohol concentration are important findings of ethanol intoxication. (See "Ethanol intoxication in children: Clinical features, evaluation, and management", section on 'Clinical features'.)
●Oral hypoglycemic agents – Patients typically have a normal mental status and examination unless hypoglycemia is present. Cannabis intoxication is not associated with hypoglycemia. (See "Sulfonylurea agent poisoning", section on 'History and physical examination'.)
●Clonidine – Some patients with coma from clonidine poisoning will respond to naloxone administration. Patients will also show more signs of hemodynamic instability such as bradycardia and hypotension. (See "Clonidine and related imidazoline poisoning", section on 'Clinical features and diagnosis'.)
●Antihistamines – Significant toxicity is often associated with anticholinergic findings (dilated pupils, flushing, dry skin and mouth, decreased breath sounds, and delirium with seizures). (See "Anticholinergic poisoning" and "Anticholinergic poisoning", section on 'Clinical features of overdose'.)
●Carbon monoxide – Other members of the household may have flu-like symptoms in patients with carbon monoxide poisoning, and carboxyhemoglobin will be elevated. (See "Carbon monoxide poisoning", section on 'Clinical findings'.)
●Psychotropic agents (eg, antipsychotic or antidepressant agents) – These agents often are associated with anticholinergic findings as described above and may be associated with arrhythmias or electrocardiographic (ECG) abnormalities (eg, prolonged QRS or QT intervals). (See "First-generation (typical) antipsychotic medication poisoning", section on 'Clinical features of overdose' and "Second-generation (atypical) antipsychotic medication poisoning", section on 'Clinical features of overdose'.)
Adolescents and adults — Several other commonly used recreational drugs have some overlapping clinical features with cannabis intoxication in adolescents and adults, including:
●Cocaine (see "Cocaine: Acute intoxication", section on 'Clinical manifestations')
●Amphetamines and methcathinones (bath salts) (see "Acute amphetamine and synthetic cathinone ("bath salt") intoxication", section on 'Clinical features of overdose' and "Methamphetamine: Acute intoxication", section on 'Clinical features')
●Lysergic acid diethylamide (LSD) and other hallucinogens (eg, phencyclidine [PCP], dextromethorphan, or psilocybin) (see "Intoxication from LSD and other common hallucinogens", section on 'General clinical features of intoxication')
●MDMA (ecstasy) (see "MDMA (ecstasy) intoxication", section on 'Clinical features')
●Synthetic cannabinoids (see "Synthetic cannabinoids: Acute intoxication", section on 'Clinical manifestations')
Cannabis is frequently used recreationally with these drugs or may serve as a vehicle for use (eg, lacing cannabis cigarettes with PCP). Thus, investigation for other intoxicants is indicated if symptoms are prolonged beyond a few hours or if other marked physiologic abnormalities exist such as hyperthermia, acidosis, significant rhabdomyolysis, or end-organ toxicity.
Synthetic cannabinoids (eg, Spice or K2) cause findings that are very similar to cannabis intoxication but are more frequently associated with more pronounced sympathomimetic effects, aggressive behavior and agitation, dystonia, and seizures. A urine drug screen for cannabinoids will be negative after synthetic cannabinoid use. (See "Synthetic cannabinoids: Acute intoxication", section on 'Clinical manifestations'.)
Cannabis use may exacerbate pre-existing mental illness (eg, psychosis, anxiety, or depression). Thus, clinicians should ask about cannabis use in patients who display new onset or worsening of known psychiatric disease.
MANAGEMENT — The management of cannabis intoxication consists of supportive care. Because of the differences in toxic manifestations, the management differs significantly by age.
Children — Children with cannabis exposure are much more likely to demonstrate severe or life-threatening toxicity consisting of excessive and purposeless motor activity (hyperkinesis), seizures, or deep coma. Consultation with a regional poison control center and a medical toxicologist is encouraged for all symptomatic exposures. (See 'Additional resources' below.)
Central nervous system depression — Severe central nervous system depression from cannabis exposure is unique to the pediatric population and can present with profound depression, lethargy, and coma.
Treatment is supportive and consists of the following measures:
●Maintain airway, breathing, and circulation. Patients with lethargy and coma should receive supplemental oxygen, assessment and support of airway and breathing, and vascular access. Patients with apnea or at risk for aspiration should undergo rapid sequence endotracheal intubation and receive assisted ventilation (table 2). (See "Emergency endotracheal intubation in children", section on 'Indications' and "Rapid sequence intubation (RSI) outside the operating room in children: Approach", section on 'Indications'.)
●Measure rapid blood glucose to exclude hypoglycemia (table 3).
●Administer naloxone to patients presenting with features of opioid intoxication. Naloxone will not reverse coma due to cannabis toxicity (table 4).
The duration of coma is typically one to two days [59,60,75,76]. Full recovery is expected with supportive care.
Seizures — Seizures have rarely been described after cannabis intoxication in children and may be associated with co-ingestants (eg, cocaine) [58,60,62,76]. Initial treatment of toxin-associated seizures consists of benzodiazepines (eg, lorazepam or midazolam). If seizures persist despite multiple doses of benzodiazepines, then treatment for status epilepticus caused by toxins, as described in the table and algorithm, is warranted (table 5 and algorithm 1). (See "Management of convulsive status epilepticus in children".)
Agitation — Dysphoria with agitation is not a common presentation in pediatric cannabis exposure. However, if symptoms of marked anxiety or agitation develop, benzodiazepines (eg, lorazepam) are frequently effective and have a low adverse effect profile.
Adolescents and adults
Mild intoxication — Mild intoxication with dysphoria is a common presentation in either naïve or chronic cannabis users after ingestion or inhalation of a high-potency product such as an edible or concentrate. Most patients can be managed with a dimly lit room, reassurance, and decreased stimulation. Short-acting benzodiazepines (eg, lorazepam) can be helpful in controlling symptoms of anxiety and have a low side effect profile.
Severe intoxication — Severe physiologic effects are rare after cannabis use, and their presence should prompt the clinician to consider co-ingestion of other recreational drugs (including cocaine, amphetamines, and phencyclidine) or coexisting mental illness. (See 'Adolescents and adults' above.)
Marked agitation or combativeness not responsive to reassurance and benzodiazepines may necessitate the use of other medications, depending upon the cause, and is rarely encountered with intoxication from cannabis alone. The approach to sedation of the acutely agitated or violent adult is discussed in detail separately. (See "Assessment and emergency management of the acutely agitated or violent adult", section on 'Chemical sedation'.)
Chest pain — Chest pain in association with cannabis use should be managed according to etiology as follows:
●Acute coronary syndrome – Substernal squeezing chest pain suggestive of myocardial ischemia or infarction may occur rarely in association with cannabis use [65,66,68,69,81,82]. Patients complaining of chest pain suggestive of coronary insufficiency should be evaluated for acute coronary syndrome and treated accordingly (table 6). (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department", section on 'Clinical presentation' and "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department", section on 'Management'.)
●Pneumothorax or pneumomediastinum – Inhalation and breath-holding during cannabis use may cause a pneumothorax or pneumomediastinum with sharp, pleuritic chest pain and subcutaneous crepitus. Management of a pneumothorax depends upon its size and includes oxygen administration and, if necessary, evacuation with needle decompression or chest tube insertion. (See "Treatment of secondary spontaneous pneumothorax in adults", section on 'Initial management of first event'.)
No specific treatment is necessary for uncomplicated pneumomediastinum. (See "Spontaneous pneumomediastinum in children and adolescents", section on 'Management'.)
●Asthma exacerbation – Cannabis use may cause chest tightness with bronchospasm and wheezing. Standard therapy for status asthmaticus should be provided (table 7). (See "Acute exacerbations of asthma in adults: Emergency department and inpatient management".)
Gastrointestinal decontamination — Activated charcoal has little efficacy in patients with symptomatic cannabis intoxication because they generally present well after the time of ingestion (three hours or longer). In young children, clinical toxicity after ingestion may also include rapid onset of altered mental status or vomiting, which may raise the risk of aspiration if activated charcoal is administered. In addition, the clinical effects of cannabis ingestion are often self-limited without gastrointestinal decontamination, and good outcomes occur with supportive care alone.
There is no role for gastrointestinal decontamination after toxicity caused by inhaled cannabis.
Cannabis hyperemesis syndrome — Cannabis hyperemesis syndrome (CHS) is typically seen with chronic cannabis use in older adolescents and adults. It can also occur after acute or acute-on-chronic use [108,109].
●Clinical manifestations – Patients may complain of cyclic abdominal pain, vomiting, or nausea that is typically relieved by hot showers or baths. Acute treatment consists of symptomatic care including intravenous (IV) fluid hydration, antiemetics, and benzodiazepines [110,111]. Cessation of cannabis use is also recommended.
●Management – For cannabis users who present for the first time with mild abdominal pain and vomiting likely due to CHS, our approach is as follows:
•Administer antiemetics (eg ondansetron [preferred] or metoclopramide). Give benzodiazepines (eg, lorazepam) if vomiting persists.
•Provide fluid repletion (eg, 1 L of normal saline or buffered crystalloid solution such as lactated Ringer over one hour).
•Perform evaluation to exclude other etiologies for the symptoms or potential complications of excessive vomiting:
-Complete blood count with differential
-Serum electrolytes
-Blood urea nitrogen and serum creatinine
-Serum lipase
-Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
-Radiographic imaging if concern for esophageal or bowel perforation, cholecystitis, or bowel obstruction; choice of imaging depends upon specific concern and may include plain radiographs (eg, posteroanterior and lateral chest, supine and upright abdomen) or abdominal ultrasound
•For patients who do not respond to supportive measures (conventional antiemetics and fluid repletion) and for whom alternative causes of nausea, vomiting, and abdominal pain have been excluded, we suggest a trial of topical capsaicin.
•For patients who are refractory to all prior interventions and persist with moderate to severe abdominal pain and vomiting, we suggest droperidol (observational studies have used 0.625 or 1.25 mg) or haloperidol (0.05 to 0.1 mg/kg, maximum single dose 2.5 mg).
We advise all patients with CHS to forego further cannabis use and offer mental health or substance use treatment referral (see "Cannabis use disorder in adults"). The patient must understand that it may take several weeks of cannabis abstinence for symptoms to resolve and that symptoms may worsen or return if cannabis is resumed. However, it is difficult for many patients to abruptly abstain from cannabis use. For these patients, the clinician can advise use of products with decreased potency and reduced frequency of use with an ultimate goal of abstinence.
For patients with protracted symptoms who present repeatedly to the emergency department with frequent vomiting and retching, it is reasonable to individualize treatment, which may involve earlier or primary use of droperidol or haloperidol to control symptoms. An evaluation to exclude other etiologies of symptoms or complications of repeated vomiting are still appropriate in these patients, especially those whose symptoms are poorly controlled.
Evidence for the use of capsaicin and dopamine antagonists for CHS include:
•Capsaicin – Limited observational evidence (case reports and case series) suggests that topical capsaicin cream (supplied in concentrations of 0.025 to 0.1%) applied once in a thin film over the abdomen may improve acute severe abdominal pain and emesis in patients not responsive to ondansetron or benzodiazepines [108,112-116]. It is hypothesized that capsaicin may provide relief by its potent agonism on the transient receptor potential vanilloid 1 (TRPV1) receptor. In a small retrospective cohort of 43 patients treated for CHS in the emergency department, use of capsaicin cream decreased total medications administered and reduced opioid requirements; two-thirds of patients required no further treatment prior to discharge [117]. In a separate retrospective cohort study of 201 patients with CHS, capsaicin cream was associated with greater efficacy for symptom relief than other treatments but was not associated with lower rates of admission or return emergency department visits within 24 hours [118]. Thus, capsaicin may be useful in the acute treatment of CHS. However, our experience suggests that patients may not tolerate the discomfort of capsaicin use at home.
•Dopamine antagonists – Case reports have documented the successful use of dopamine antagonists such as haloperidol and droperidol to abort severe episodes of hyperemesis. [108,119-121]. In a randomized, blinded trial of 33 adults with cannabis use and active emesis, haloperidol was superior to ondansetron in improvement of self-rated abdominal pain and nausea and decreased time to discharge from the emergency department [122]. (See "Cyclic vomiting syndrome", section on 'Chronic cannabis use'.)
DISPOSITION — Disposition is determined by several factors including patient age, social circumstances, duration of toxicity, and type of symptoms as follows:
●Children – The duration of symptoms after acute cannabis exposure in children can vary from 4 to 48 hours depending upon the dose ingested [8,9]. Patients with persistent vomiting, altered mental status, seizures, or excessive, purposeless motor activity (hyperkinesis) warrant hospital admission.
Patients who remain asymptomatic or become asymptomatic following exploratory ingestion of legally acquired cannabis products may be discharged after a brief observation period (eg, four to six hours after ingestion).
Regardless of whether cannabis is legal in a given jurisdiction, any concerns about the nature of a cannabis exposure in a child warrant involvement of a child abuse or social work team to determine additional social evaluation and potential need for reporting to child protection services. (See "Child abuse: Social and medicolegal issues", section on 'Reporting suspected abuse'.)
●Adolescents and adults – Most symptoms after acute cannabis use in adults and adolescents resolve within a few hours and will not require hospital admission.
Hospital admission may rarely be needed for prolonged delirium or agitation requiring repeated doses of benzodiazepines or antipsychotics. These patients should also be screened for substance use disorders and mood disorders, and, if needed, undergo psychiatric consultation and appropriate referrals to substance-use treatment programs. (See "Cannabis use disorder in adults".)
The disposition for patients with complications of cannabis use depends upon the degree of illness and response to therapy. Patients with proven myocardial infarction or pneumothorax requiring chest tube thoracostomy warrant hospital admission to an appropriate level of care.
ADDITIONAL RESOURCES
Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)
The Partnership at Drugfree.org maintains a drug guide for 40 commonly abused drugs including common slang terms.
Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cannabis use disorder and withdrawal" and "Society guideline links: General measures for acute poisoning treatment" and "Society guideline links: Poisoning prevention" and "Society guideline links: Treatment of acute poisoning caused by recreational drug or alcohol use".)
SUMMARY AND RECOMMENDATIONS
●Epidemiology – Serious cannabis intoxication is rare in adolescents and adults. Exploratory ingestions of cannabis products have caused life-threatening toxicity in young children. (See 'Epidemiology' above and 'Children' above.)
●Clinical manifestations
•Children – Ingestion of cannabis by young children may cause (see 'Children' above):
-Life-threatening coma with apnea or depressed respirations
-Seizures
-Effects of intoxication as described below for older patients (limited exposures)
Children may warrant testing for other potential causes of altered mental status depending upon whether the exposure is known and based upon specific physical findings. (See 'Other ancillary studies' above and 'Children' above.)
•Adolescents and adults – Cannabis intoxication in adolescents and adults causes (see 'Adolescents and adults' above):
-Tachycardia
-Blood pressure changes (hypertension, or in older adults, orthostatic hypotension)
-Conjunctival injection
-Dry mouth
-Increased appetite
-Nystagmus
-Signs of intoxication such as ataxia, slurred speech, euphoria, perceptual changes, and psychomotor impairment
Chest pain may arise from pneumothorax, exacerbation of pulmonary disease such as asthma, or (uncommonly) myocardial ischemia. (See 'Adolescents and adults' above.)
Investigation for other intoxicants may be indicated if symptoms are prolonged, or if other marked physiologic abnormalities exist such as hyperthermia, acidosis, significant rhabdomyolysis, or end-organ toxicity. Otherwise, no specific testing is necessary. (See 'Adolescents and adults' above.)
●Diagnosis – Regardless of age, acute cannabis intoxication is a clinical diagnosis. Urine drug screens can be helpful in confirming the diagnosis in young children because any positive result identifies acute exposure in the setting of major toxicity. Urine drug screens are less helpful in adolescents and adults and are not routinely needed for diagnosis or management. (See 'Diagnosis' above and 'Drug testing for cannabinoids' above.)
●Management
•Supportive care – Expected toxicity and treatment differs by age:
-Children – Young children may require management of coma and respiratory depression, which frequently requires endotracheal intubation along with exclusion of hypoglycemia and other causes of altered mental status.
For children with marked anxiety or agitation, we suggest treatment with a benzodiazepine (eg, lorazepam) (Grade 2C). (See 'Agitation' above.)
Lorazepam is also warranted for patients who develop seizures; convulsive status epileptics requires further treatment as summarized in the algorithm (algorithm 1) and discussed in detail separately. (See "Management of convulsive status epilepticus in children".)
Any concerns about the nature of a cannabis exposure in a child requires involvement of a child abuse or social work team to determine additional social evaluation and potential need for reporting to child protection services. (See 'Disposition' above.)
-Adolescents and adults – Mild intoxication with dysphoria can be managed with a dimly lit room, reassurance, and decreased stimulation. For patients with ongoing anxiety despite these measures, we suggest benzodiazepines (eg, oral lorazepam) (Grade 2C). (See 'Mild intoxication' above.)
Marked agitation or combativeness should prompt consideration of a possible co-ingestion (eg, cocaine, amphetamines, phencyclidine [PCP]) or coexisting mental illness. Management of the acutely agitated or violent adult is discussed in detail separately. (See "Assessment and emergency management of the acutely agitated or violent adult", section on 'Chemical sedation'.)
Chest pain in association with cannabis use requires identification and treatment of the underlying etiology (eg, acute coronary syndrome, pneumothorax, or asthma exacerbation). (See 'Chest pain' above.)
•Gastrointestinal decontamination – For patients who ingest cannabis or cannabis-containing products or food, we suggest not administering activated charcoal because of the potential for rapid onset of altered mental status with apnea or seizures in young children and lack of efficacy in otherwise symptomatic patients (Grade 2C). (See 'Gastrointestinal decontamination' above.)
•Cannabis hyperemesis syndrome (CHS) – CHS is a clinical syndrome of cyclic abdominal pain, vomiting, or nausea in older adolescents and adults with chronic cannabis use. Relief of symptoms with hot showers or baths is a common feature.
Management includes (see 'Cannabis hyperemesis syndrome' above):
-Antiemetic therapy – We suggest ondansetron as the first-line agent (Grade 2C); metoclopramide is a reasonable alternative. If vomiting persists, we suggest a benzodiazepine (eg, lorazepam) (Grade 2C).
-Fluid repletion.
-Laboratory evaluation to exclude other etiologies or to identify complications of excessive vomiting.
-For patients unresponsive to supportive measures (conventional antiemetics and fluid repletion) and for whom alternative causes of nausea, vomiting, and abdominal pain have been excluded, we suggest a trial of topical capsaicin (Grade 2C).
-For patients with persistent moderate to severe abdominal pain and vomiting despite the above interventions, we suggest droperidol or haloperidol (Grade 2C).
-All patients should receive counseling regarding the need to decrease cannabis use (both potency of products and frequency of use) and referral to support abstinence.
