Cannabis use disorder

Cannabis is one of the most commonly used psychoactive substances globally, trailing only caffeine, alcohol and tobacco. 

Worldwide an estimated 209 million people 15 to 64 years of age used cannabis in 2020, representing about 4% of the global population in that age group. 

The use of cannabis poses a global disease burden that is less than other psychoactive substances, such as alcohol, tobacco, opioids, and stimulants.

In the US an estimated 52.4 million people 12 years or older use cannabis in 2021 representing 18.7% of the community dwelling population in that age group, and 16.2 million persons met the diagnostic criteria for cannabis used disorder.

Cannabis use disorder (CUD) occurs in all age group, but is primarily a disease of young adults. 

The median age of CUD is 22 years. 

In the US the percentage of 18 to 25-year-old individuals with current cannabis use disorder in 2021 was 14.4%. 

A younger age at initiation of cannabis use is associated with the faster development of cannabis use disorder and a more severe cannabis use disorder. 

CUD occurs often among patients with other psychiatric conditions, including other substance abuse disorders. 

About 2/3 of patients with cannabis use disorder have at least 1 other current substance use disorder, most commonly alcohol or tobacco. 

Almost half of persons with CUD have a current psychiatric disorder that is not substance use disorder and includes most commonly: major depression, post traumatic stress disorder, or generalized anxiety disorder. 

The presence of coexisting psychiatric disorders is associated with more severe cannabis use disorder and poorer response to treatment.

In 2016, the Global Burden of Disease Project calculated cannabis use was responsible for an estimated 646,000 years of healthy lifestyle lost to disability, a rate of 8.5 years per hundred thousand persons.

Cannabis use strongly associated with increased motor vehicle crashes, suicidality, and cardiovascular and pulmonary disease.

Most of the cannabis associated conditions and death are probably due to coexisting psychiatric disorders and substance use, rather than to cannabis itself. 

Cannabis uses associated with an estimated 10% of drug related ED visits in the US in 2021.

Cannabis’s major effects are generated by the interaction of THC (delta-9-tetrahydrocannabinol) with the endogenous cannabinoid system.

CB1 receptors are predominately expressed in the CNS, while CB2 receptors are primary expressed in the immune system.

CB1 receptors are found on both neurons and glia throughout the brain, especially in regions that are thought to mediate prominent effects of THC, such as the hippocampus, basal ganglia, cerebellum, cerebral cortex.

Adults who use cannabis over a long-term have down regulation of the brain CB1 receptors.

CB1receptors are also found outside the CNS in the myocardium, vascular endothelium, adipose tissue, the liver, and the reproductive organs.

CB2 receptors are found primarily on immune cells, although some are in the CNS.

THC is a partial agonist at both types of cannabinoid receptors. 

CBD has multiple molecular targets and limited interactions with cannabinoid receptors.

THC is rapidly absorbed when inhaled, appearing in plasma within seconds, with peak concentration, occurring 5 to 10 minutes.

In contrast, oral THC results in slow absorption, with peak plasma concentration occurring in 2 to 6 hours.

Cannabis induces a number of acute psychological and physiological effects, that vary in intensity, and duration to the dose, chiefly of THC, the route of administration, and the degree of tolerance of the user.

Acute psychological effects include: euphoria, relaxation, sedation, increased, appetite (munchies), impaired short term memory, concentration, and psychomotor coordination.

Some individuals experience anxiety, panic attacks, paranoia, especially at high doses. 

Psychotic symptoms are less common. 

Acute physical effects include impaired motor coordination, slurred speech, dry mouth, conjunctival, irritation and redness, tachycardia, orthostatic, hypotension, and horizontal nystagmus.

Smoked cannabis can induce cough, wheezing, dyspnea, increased sputum production, and exacerbate asthma. 

Cannabis can be associated with acute transient, cardiac arrhythmia, including atrial fibrillation, supraventricular tachycardia, PVCs, and sustained ventricular tachycardia.

Cannabis use is associated with impaired driving ability within an associated increase of risk of motor vehicle crashes of 30-40%, compared to blood alcohol concentrations of .08%, which increases the risk of crashes by 250 to 300%.

The time of cannabis and intoxication varies with the route of administration. 

Inhaled, smoked or vaporized cannabis intoxication begins within a few minutes and last 3 to 4 hours. 

Oral administration of cannabis and intoxication begins 30 minutes to 3 hours after ingestion and last 8 to 12 hours. 

People not previously used to cannabis or only use it occasionally typically become intoxicated when they inhale THC at the dose of 2 to 3 mg or ingest orally a dose of 5 to 10 mg.

Intoxication by cannabis is generally mild and self limited, and most individuals never come into medical contact.

Treatment for intoxication is usually associated with severe anxiety, panic attacks, psychotic symptomatology, or severe motor incoordination.

Rarely, in patient treatment is warranted for cannabis intoxication if there is a via mood or psychiatric symptomatology, such as suicide.

 In children who ingest large amounts of cannabis, coma, convulsions, or cardio pulmonary instability may occur.

Management of cannabis intoxication generally occurs without medication. 

No specific antidote is available

A quiet  environment, supportive reassurance is generally adequate care. 

With severe agitation or anxiety benzodiazepines can be given. 

Psychosis usually responds to second generation antipsychotic agents.

CUD is associated with four subacute psychiatric syndrome that persist after the initial 24 hours of acute intoxication or are involve symptoms sufficiently severe to warrant independent clinical attention.

These subacute psychiatric syndrome are suggested by symptoms that begin during or shortly after the cannabis use or withdrawal and resolve within one month after cannabis abstinence. 

Treatment for such subacute, psychiatric syndrome is supportive and symptom oriented.

Cannabis can be associated with anxiety disorders, and comprise 20 to 25% of patients presenting to EDs  with cannabis related symptoms.

During cannabis intoxication transient psychotic symptoms are reported in 5 to 50% of adults.

Psychotic manifestations are associated with a higher risk in patients with family or personal history of psychotic symptoms.

The incident of cannabis induced psychosis is about 3 to 6 per hundred thousand cannabis users.

About 1/5 of patients with cannabis induced psychotic disorder, develop a long-term psychotic disorder indistinguishable from schizophrenia.

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