Marijuana is a euphoriant that can cause sedation or dysphoria that is used by smoking or ingestion. Acute effects are usually mild, and can include tachycardia, conjunctival injection, and impaired cognitive function; myocardial injury has also been reported. Diagnosis is by history and urine testing. Observation is usually sufficient for acute intoxication. Psychological dependence can develop with chronic use, but very little physical dependence is clinically apparent. Chronic use can cause cannabinoid hyperemesis syndrome and is associated with infertility, psychosis, and cognitive impairment.
Marijuana is a derived from the cannabis sativa plant, and its main psychoactive ingredient is delta-9-tetrahydrocannabinol (THC). Many synthetic cannabinoids have been illicitly developed for recreational use.
The body produces endogenous cannabinoids that activate cannabinoid receptors. They help regulate appetite, pain sensation, and memory.
Street names for marijuana include Bud, Blunt, Dope, Ganja, Grass, Hash, Mary Jane, Pot, Reefer, and Weed.
There are several cannabinoid therapeutic medications that have been approved by the US Food and Drug Administration (FDA). Several are for treatment of nausea and vomiting associated with cancer chemotherapy and contain dronabinol (a synthetic oral form of THC) or nabilone (a synthetic substance similar to THC). In addition, an oral solution of cannabidiol is available to treat certain uncommon forms of childhood seizure disorders. Cannabidiol (commonly termed CBD oil) is one of the primary natural cannabinoids of the marijuana plant. Cannabidiol has minimal psychoactive properties and its recreational use is not associated with a high potential for abuse.
Pathophysiology of Marijuana Use
Delta-9-THC binds at cannabinoid receptors, which are present throughout the brain. The biological mechanisms underlying THC effects are poorly understood.
The body produces endogenous cannabinoids that activate cannabinoid receptors. They help regulate appetite, pain sensation, and memory.
In the United States, the most common route of use of marijuana is smoking in cigarettes made from the flowering tops and leaves of the dried plant, or as hashish, the pressed resin of the plant. After smoking marijuana, onset of effects is within minutes and duration of effects in typically 4 to 6 hours.
The legalization of marijuana for recreational purposes in the United States in certain states has created a manufacturing industry that produces marijuana products that are ingested (called "edibles"), insufflated, vaporized, and applied topically.
The potency of marijuana has increased over the past few decades from 2 to 3% in the 1980s, to about 4% in 1995 to about 12% in 2014. The average THC content in cannabis samples seized by the Drug Enforcement Agency (DEA) increased from 3.96% in 1995 to 16.14% in 2022 (1).
Pathophysiology reference
1. ElSohly MA, Mehmedic Z, Foster S, Gon C, Chandra S, Church JC. Changes in Cannabis Potency Over the Last 2 Decades (1995-2014): Analysis of Current Data in the United States. Biol Psychiatry. 2016;79(7):613-619. doi:10.1016/j.biopsych.2016.01.004
Symptoms and Signs of Marijuana Toxicity
The effects of use of smoking marijuana are euphoria and relaxation. It produces a dreamy state of consciousness in which ideas seem disconnected, unanticipated, and free-flowing. Time, color, and spatial perceptions may be altered. Edibles typically contain more THC per serving than the plant, leading to a higher chance of dysphoria.
Physical effects are mild in most patients. Tachycardia, conjunctival injection, and dry mouth occur regularly. Concentration, sense of time, fine coordination, depth perception, tracking, and reaction time can be impaired for up to 24 hours, which are hazardous in certain situations (eg, driving, operating heavy equipment). Appetite often increases.
Case reports have described myocardial ischemia after THC ingestion (1, 2).
Marijuana may exacerbate or even precipitate psychotic symptoms in schizophrenics, even those being treated with antipsychotics. Some of reported psychological effects seem to be related to the setting in which the drug is taken. Anxiety, panic reactions, and paranoia have occurred, particularly in naive users.
Symptoms and signs references
1. Aissaoui H, Boulouiz S, El-Azrak M, Bouchlarhem A, Elouafi N, Bazid Z. Cannabis-induced myocardial infarction in a 27-year-old man: Case report. Ann Med Surg (Lond). 2022;80:104054. Published 2022 Jun 25. doi:10.1016/j.amsu.2022.104054
2. Gunawardena MD, Rajapakse S, Herath J, Amarasena N. Myocardial infarction following cannabis induced coronary vasospasm. BMJ Case Rep. 2014;2014:bcr2014207020. Published 2014 Nov 12. doi:10.1136/bcr-2014-207020
Diagnosis of Marijuana Toxicity
History and physical examination
Urine drug test
For psychosis, psychiatric evaluation
The diagnosis of marijuana intoxication is usually made by history, when a patient reports use of what they believe to be marijuana and demonstrates typical symptoms. The overall clinical picture of tachycardia and conjunctival injection are consistent with marijuana use, but not specific enough to exclude other substance use.
Routine urine drug screening tests test for delta-9-THC, but these tests may give false-positive or false-negative results and only indicate use within the last month.
In adults, because toxicity is usually mild and self-limited, a diagnosis of marijuana toxicity should be considered in a patient with severe or persistent altered mental status after smoking or ingestion of a substance only if other etiologies have been excluded. The exception to this is in patients who report first-time use of marijuana or using a much larger amount than usual.
In people who use marijuana at least once a week, a urine toxicological screen will be positive and provide no additional information about the acute complaint. In this patient population, the diagnosis of marijuana toxicity can only be confirmed with a quantitative test, serum or urine. However, it can be difficult to interpret the result of a quantitative tests without a prior value for comparison.
In children, particularly in places where marijuana use is legal, clinicians caring for young children should consider marijuana or, more broadly, THC ingestion, in children with altered mental status with no other apparent explanation. In children younger than 5 years, doses greater than 5 mg/kg of THC have been associated with respiratory depression requiring supplemental oxygen.
In children, a urine toxicological screen that detects THC is sufficient to confirm the diagnosis in a patient with concordant symptoms. For legal reasons, a confirmatory quantitative test can be performed.
Treatment of Marijuana Toxicity
Observation
For oral ingestion within 2 hours, sometimes activated charcoal
For chest pain, ECG and sometimes serial troponin testing
For cannabinoid hyperemesis syndrome, IV fluids, antiemetics, haloperidol, and topical capsaicin
For persistent psychosis, psychiatric care
Preventing absorption
Activated charcoal may be considered within 2 hours after ingestion of marijuana, but the benefit of use charcoal should be weighed against the risk of emesis.
Otherwise, gastrointestinal decontamination has no role in management of marijuana intoxication.
Enhancing excretion
There is no role for urinary alkalinization in marijuana toxicity.
Mitigating toxicity
Most patients with marijuana intoxication require only observation and supportive measures.
For patients with chest pain after consuming an edible form of THC, an ECG should be obtained. Serial troponin levels may also be obtained if patient have risk factors for coronary artery disease.
Patients with cannabinoid hyperemesis syndrome may require IV fluids, antiemetics, haloperidol, and topical capsaicin (applied to the abdomen). Anecdotal reports suggest haloperidol or topical capsaicin may be effective, but this has not been evaluated in clinical studies.
Chronic Use of Marijuana
Complications
Cannabinoid hyperemesis syndrome (CHS) may develop in frequent users of marijuana. This is a syndrome of cyclic episodes of nausea and vomiting. The frequency, dose, and duration of marijuana use that are associated with developing CHS are not known.
Hot bathing ameliorates these symptoms and, if this is reported by a patient, it is a clinical clue to the diagnosis.
The main treatment is to discontinue use of marijuana. Symptoms usually resolve spontaneously within 48 hours after use in discontinued, although persistent symptoms despite cessation have been reported.
High-dose smokers can develop pulmonary symptoms (episodes of acute bronchitis, wheezing, coughing, and increased phlegm), and pulmonary function may be altered, manifested as large airway changes of unknown significance. However, obstructive airway disease does not develop, even in daily smokers.
There is no evidence of increased risk of head and neck or airway cancers, as there is with tobacco.
Frequent, heavy marijuana use can cause infertility. Marijuana smoking may reduce sperm count (1). Women who smoke marijuana have decreased fertility (2).
Habitual marijuana use is associated with significant cognitive impairment and anatomic changes in the hippocampus, particularly if marijuana use begins in adolescence. A sense of diminished ambition and energy is often described by users.
Several studies have described a link between chronic, heavy marijuana use and psychiatric disorders, including schizophrenia, depression, anxiety, and abuse of other substances (3-6). A causal relationship has not been shown.
Use in pregnancy and lactation
The effect of prenatal marijuana use on neonates is not clear. Decreased fetal weight has been reported, but when all factors (eg, maternal alcohol and tobacco use) are accounted for, the effect on fetal weight appears to lessen (7). However, because safety has not clearly been proven, marijuana should be avoided by pregnant women and those who are trying to become pregnant.
THC is secreted in breast milk. Although harm to breastfed infants has not been shown, breastfeeding mothers, like pregnant women, should avoid using marijuana.
Tolerance and dependence
Psychological dependence can develop with chronic use, but very little physical dependence is clinically apparent. Management of the underlying pattern of substance use typically consists of behavioral therapy in an outpatient drug treatment program.
Withdrawal
Cessation after frequent, heavy use can cause a mild withdrawal syndrome. Symptoms include insomnia, irritability, depression, nausea, and anorexia.
The timing of onset of withdrawal symptoms is variable but often begins about 12 hours after the last use. Symptoms peak at 2 to 3 days and last up to 7 days.
Marijuana is a euphoriant that can cause sedation or dysphoria. psychological dependence can develop with chronic use, but very little physical dependence is clinically apparent. Acute effects are usually mild, and can include tachycardia, conjunctival injection, and impaired cognitive function; myocardial injury has also been reported. Diagnosis is by history and urine testing. Observation is usually sufficient for acute intoxication. Chronic use can cause cannabinoid hyperemesis syndrome and is associated with infertility, psychosis, and cognitive impairment.
Chronic use references
1. Ilnitshky S, Van Uum S: Marijuana fertility. CMAJ/ JMAC 191(23):E638, 2019.
2. Mumford SL, Flannagan KS, Radoc JG: Cannabis use while trying to conceive: A prospective cohort study evaluating associations with fecundability, live birth and pregnancy loss. Human Reproduction 36(5):1405–1415, 2021. https://doi.org/10.1093/humrep/deaa355
3. Moore TH, Zammit S, Lingford-Hughes A, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet. 2007;370(9584):319-328. doi:10.1016/S0140-6736(07)61162-3
4. Marconi A, Di Forti M, Lewis CM, Murray RM, Vassos E. Meta-analysis of the Association Between the Level of Cannabis Use and Risk of Psychosis. Schizophr Bull. 2016;42(5):1262-1269. doi:10.1093/schbul/sbw003
5. Gobbi G, Atkin T, Zytynski T, et al. Association of Cannabis Use in Adolescence and Risk of Depression, Anxiety, and Suicidality in Young Adulthood: A Systematic Review and Meta-analysis [published correction appears in JAMA Psychiatry. 2019 Apr 1;76(4):447. doi: 10.1001/jamapsychiatry.2019.0464.]. JAMA Psychiatry. 2019;76(4):426-434. doi:10.1001/jamapsychiatry.2018.4500
6. Lev-Ran S, Roerecke M, Le Foll B, George TP, McKenzie K, Rehm J. The association between cannabis use and depression: a systematic review and meta-analysis of longitudinal studies. Psychol Med. 2014;44(4):797-810. doi:10.1017/S0033291713001438
7. Gunn JK, Rosales CB, Center KE, et al. Prenatal exposure to cannabis and maternal and child health outcomes: a systematic review and meta-analysis. BMJ Open. 2016;6(4):e009986. Published 2016 Apr 5. doi:10.1136/bmjopen-2015-009986
Key Points
Marijuana a euphoriant that can cause sedation or dysphoria. It is derived from the cannabis sativa plant, and its main psychoactive ingredient is delta-9-tetrahydrocannabinol (THC). .
Acute effects are usually mild, and can include tachycardia, conjunctival injection, and impaired cognitive function; myocardial injury has also been reported.
Diagnose with history and urine testing.
Manage with observation. For patients with chest pain, evaluate with ECG, serial serum troponin levels, and continuous cardiac monitoring.
Psychological dependence can develop with chronic use, but very little physical dependence is clinically apparent. Cannabinoid hyperemesis syndrome is seen in chronic users and is treated with hydration, antiemetics, haloperidol, and capsaicin.
Drug Information for the Topic
