Cannabis Use Disorder

Cannabis use disorder (CUD) is characterized by the pathologic consumption of cannabis, which is the most commonly used illicit substance worldwide. While cannabis has some beneficial medical uses, it also has the potential to cause intoxication characterized by psychosis or cognitive impairment, especially in chronic use. Unlike most other substances, withdrawal symptoms are mild. There is currently no strong evidence for long-term benefits of pharmacologic or psychosocial interventions in the management of cannabis use disorder. Other factors such as underlying mood or personality disorders or comorbidity with other substance use disorders are associated with a poor prognosis.

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Definition and Epidemiology


Cannabis use disorder (CUD) is defined as chronic (> 12 months) maladaptive use of cannabis. 

  • Intoxication: 
    • Heightened sensitivity to stimuli 
    • Derealization and depersonalization with higher dosage
    • Motor skills are impaired for up to 8–12 hours after ingestion.
    • Delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium and cannabis-induced psychotic disorders may also occur.
  • Withdrawal: 
    • Development of a substance-specific syndrome due to the cessation (or reduction) of substance use
    • Very mild for cannabis and other inhalants/hallucinogen-type drugs
  • Tolerance: 
    • The need to increase the dose of the substance to achieve desired effect (diminished effect if using the same amount of the substance)
    • Evidence for physiological dependence is not strong for cannabis.


  • Cannabis is the most widely used illicit substance.
  • Used by an estimated 192 million people worldwide 
  • About 13 million individuals worldwide suffer from moderate-to-severe cannabis use disorder.
  • Prevalence of CUD declines with increase in age. 
  • Men are more than twice as likely to have CUD as women.


Pharmacologic properties

  • Cannabis is consumed from both naturally occuring and agriculture-selected strains (which have increased potency). 
  • Synthetic formulations available (e.g., “spice,” “K2”)  
  • Common ways of consumption: 
    • Smoking (most widespread) 
    • Vaporizers 
    • Baked into cookies or other sweets
    • Tea
  • THC (tetrahydrocannabinol):
    • The main active and most potent psychoactive component in cannabis 
    • 50% of THC enters the bloodstream via the alveoli in the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs rapidly after inhalation. 
    • THC binds to cannabinoid receptors in the brain’s reward system → results in feelings of euphoria 
    • Synthetic cannabinoids Cannabinoids Cannabinoids are a class of compounds interacting with cannabinoid receptors. The 3 types of cannabinoids are phytocannabinoids (naturally derived from flora), endocannabinoids (endogenous), and synthetic cannabinoids (artificially produced). Cannabinoids have active compounds that are more potent than THC.
  • Cannabinoid receptors are inhibitory G proteins →  inhibit adenylate cyclase → decreases cAMP
  • Cannabinoids are lipophilic → can remain in the body in detectable levels for days to weeks

Medical uses of cannabis


  • Treatment of nausea and vomiting, appetite stimulation:
    • Chemotherapy
    • Multiple sclerosis Multiple Sclerosis Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis
    • AIDS
    • Chronic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain patients
  • Decreasing intraocular pressure in glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma
  • Childhood epilepsy Epilepsy Epilepsy is a chronic brain disorder marked by recurrent and unprovoked seizures. These seizures can be classified as focal or generalized and idiopathic or secondary to another condition. Clinical presentation correlates to the classification of the epileptic disorder. Epilepsy and refractory seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures

Pharmaceutical forms:

  • Dronabinol
  • Nabilone
  • Rimonabant

Clinical Presentation and Diagnosis

To make the diagnosis of cannabis intoxication or withdrawal, a detailed history of cannabis use should be obtained. Urine drug screen aids in confirming the diagnosis. Signs and symptoms are listed below.

Cannabis intoxication

  • No deaths have ever been documented from cannabis intoxication alone. 
  • General: euphoria or feeling relaxed, inappropriate laughter
  • CNS: psychomotor retardation, impairment in motor function
  • Ophthalmologic: conjunctival injection or “reddening” of the conjunctives
  • GI: increased appetite, dry mouth
  • Urine drug screen:
    • Detects the major inactive metabolite 11-Nor-9-carboxy THC
    • Single use can cause detectable levels for up to 3 days. 
    • Chronic use can cause detectable levels for up to 30 days.

Cannabis withdrawal

  • General: mood changes, slight increase in irritability
  • CNS: insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia
  • GI: nausea, decreased appetite

Management and Complications

Management of cannabis intoxication and withdrawal

  • Supportive, psychosocial interventions (e.g., contingency management, groups, etc.).
  • Symptomatic treatment 
  • Antipsychotics may be used for severe intoxication.

Management of cannabis use disorder

  • Psychotherapy Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. Psychotherapy: cognitive behavioral therapy (CBT) or motivational enhancement 
  • Medications:
    • No strong evidence for any medications 
    • If psychotherapy alone is not effective, adding N-acetylcysteine (if adolescent/young adult) or gabapentin (adults) may be helpful.

Complications of cannabis use disorder

  • Cannabis-induced psychotic disorder: 
    • Psychotic disorder in the setting of cannabis use 
    • More commonly presents with transient paranoid delusions 
    • Chronic cannabis use has been linked with the development of schizophrenia Schizophrenia Schizophrenia is a chronic mental health disorder characterized by the presence of psychotic symptoms such as delusions or hallucinations. The signs and symptoms of schizophrenia are traditionally separated into 2 groups: positive (delusions, hallucinations, and disorganized speech or behavior) and negative (flat affect, avolition, anhedonia, poor attention, and alogia). Schizophrenia later in life.
  • Amotivational syndrome:  
    • Associated with long-term severe cannabis use
    • Can be confounded with underlying mood disorder 
    • Adolescent use of cannabis is linked with use of other substances (gateway drug).

Differential Diagnosis

  • Schizophrenia: a chronic mental health disorder that is characterized by both positive (delusions, hallucinations, disorganized speech or behavior) and negative symptoms (flat affect, avolition, anhedonia, poor attention, and alogia). The disorder is associated with a decline in functioning lasting over 6 months. The use of cannabis may result in psychosis and symptoms similar to schizophrenia Schizophrenia Schizophrenia is a chronic mental health disorder characterized by the presence of psychotic symptoms such as delusions or hallucinations. The signs and symptoms of schizophrenia are traditionally separated into 2 groups: positive (delusions, hallucinations, and disorganized speech or behavior) and negative (flat affect, avolition, anhedonia, poor attention, and alogia). Schizophrenia in the acute phase. Management of schizophrenia Schizophrenia Schizophrenia is a chronic mental health disorder characterized by the presence of psychotic symptoms such as delusions or hallucinations. The signs and symptoms of schizophrenia are traditionally separated into 2 groups: positive (delusions, hallucinations, and disorganized speech or behavior) and negative (flat affect, avolition, anhedonia, poor attention, and alogia). Schizophrenia is with antipsychotics. 
  • Cocaine use disorder Cocaine use disorder Cocaine use disorder is a substance use disorder defined by pathologic consumption of the recreational drug cocaine. Cocaine is an indirect sympathomimetic that blocks the reuptake of dopamine, serotonin, and norepinephrine from the synaptic cleft. This process causes stimulant effects on the body and mind such as euphoria and increased energy. Cocaine Use Disorder: cocaine is an indirect sympathomimetic Sympathomimetic Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators (α, β, or dopamine receptors) of the sympathetic autonomic nervous system. Sympathomimetic drugs are classified based on the type of receptors the drugs act on (some agents act on several receptors but 1 is predominate). Sympathomimetic Drugs that blocks the reuptake of dopamine, epinephrine, and norepinephrine from the synaptic cleft. This process causes a stimulating effect (euphoria, increased energy, irritability, psychosis, decreased appetite, weight loss, and hypersomnia) similar to but more pronounced than cannabis. Withdrawal symptoms include severe depression and fatigue. Management is very similar to cannabis in that there is no direct medication that can be used for cocaine use disorder. 
  • Inhalant intoxication: the abuse of inhalant substances such as glue, paint, or lighter fluid. In order to reach euphoric effects, patients administer inhalers through the mouth (commonly known as “huffing”) or sniff substances through the nose Nose The nose is the human body's primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Anatomy of the Nose. The effect lasts only for several minutes. Signs of acute intoxication range from transient euphoria up to a loss of consciousness. Inhalants result in central nervous inhibition and cardiac arrhythmia. Treatment is supportive, and sedative drugs should be avoided as they tend to worsen intoxication.


  1. Ganti, Latha. (2005). First aid for the psychiatry clerkship: a student-to-student guide. New York :McGraw-Hill, Medical Pub. Div. Chapter 7, Substance related and addictive disorders, pages 80, 92.
  2. Gorelick, D. (2021). Cannabis use and disorder: Epidemiology, comorbidity, health consequences, and medico-legal status. UpToDate. Retrieved February 16, 2021, from
  3. Wang, George. (2021). Cannabis (marijuana): Acute intoxication. UpToDate. Retrieved February 16, 2021, from
  4. Sadock, B. J., Sadock, V. A., & Ruiz, P. (2014). Kaplan and sadock’s synopsis of psychiatry: Behavioral sciences/clinical psychiatry (11th ed.). Chapter 20, Substance use and addictive disorders, pages 644-647. Philadelphia, PA: Lippincott Williams and Wilkins.
  5. Thompson, A. (2021). Clinical management of drug use disorders. DeckerMed Medicine. doi:10.2310/im.13042

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