Cannabis

Figure 1. Marijuana is the most commonly used illegal drug in the world.

Cannabis, also known as marijuana, is a psychoactive drug from the cannabis plant used primarily for medical or recreational purposes. The main psychoactive component of cannabis is tetrahydrocannabinol (THC), which is one of the 483 known compounds in the plant, including at least 65 other cannabinoids, including cannabidiol (CBD). Cannabis can be used by smoking, vaporizing, or consuming within food or as an extract.

Cannabis has various mental and physical effects, which include euphoria, altered states of mind and sense of time, difficulty concentrating, impaired short-term memory and body movement, relaxation, and an increase in appetite. The onset of effects is felt within minutes if smoked, and about 30 to 60 minutes when cooked and eaten. The effects last for two to six hours, depending on the amount used. At high doses, mental effects can include anxiety, delusions (including ideas of reference), hallucinations, panic, paranoia, and psychosis. There is a strong relation between cannabis use and the risk of psychosis, though the direction of causality is debated.

Physical effects include increased heart rate, difficulty breathing, nausea, and behavioral problems in children whose mothers used cannabis during pregnancy; short-term side effects may also include dry mouth and red eyes. Long-term adverse effects may include addiction, decreased mental ability in those who started regular use as adolescents, chronic coughing, and susceptibility to respiratory infections.

Cannabis is mostly used recreationally or as a medicinal drug, although it may also be used for spiritual purposes. In 2013, between 128 and 232 million people used cannabis (2.7% to 4.9% of the global population between the ages of 15 and 65). It is the most commonly used illegal drug in the world, though it is also legal in some jurisdictions, with the highest use among adults (as of 2018) in Zambia, the United States, Canada, and Nigeria. While cannabis was previously an illicit substance, a majority of states across the United States have legalized the medical use of cannabis with a doctor’s recommendation, and more and more states are also legalizing the recreational use of marijuana.

Figure 2. Addiction experts in psychiatry, chemistry, pharmacology, forensic science, and epidemiology and the police and legal services engaged in delphic analysis regarding 20 popular recreational drugs. Cannabis was ranked 11th in dependence, 17th in physical harm, and 10th in social harm.

To screen for cannabis-related problems, several methods are used. Scales specific to cannabis include the Cannabis Abuse Screening Test (CAST), Cannabis Use Identification Test (CUDIT), and Cannabis Use Problems Identification Test (CUPIT). Scales for general drug use disorders are also used, including the Severity Dependence Scale (SDS), Drug Use Disorder Identification Test (DUDIT), and Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). However, there is no gold standard and both older and newer scales are still in use.

Diagnosis of Cannabis-Related Disorders

The diagnostic criteria of the varying effects of cannabis are listed below, as defined by the DSM-5.    

Cannabis Intoxication

1. recent use of cannabis
2. clinically significant problematic behavioral or psychological changes (e.g., impaired motor coordination, euphoria, anxiety, a sensation of slowed time, impaired judgment, social withdrawal) that developed during, or shortly after, cannabis use
3. at least two of the following signs, developing within two hours of cannabis use: conjunctival injection, increased appetite, dry mouth, or tachycardia
4. symptoms not due to a general medical condition and not better accounted for by another mental disorder
5. specify if perceptual disturbances are present: hallucinations with intact reality testing or auditory, visual, or tactile illusions occur in the absence of delirium

Cannabis Withdrawal

1. cessation of cannabis use that has been heavy and prolonged (i.e., usually daily or almost daily use over a period of at least a few months); three or more of the following signs and symptoms develop within approximately one week after cessation of heavy, prolonged use:

   1. irritability, anger, or aggression
   2. nervousness or anxiety
   3. sleep difficulty (i.e., insomnia or disturbing dreams)
   4. decreased appetite or weight loss
   5. restlessness
   6. depressed mood
2. at least one of the following physical symptoms causing significant discomfort: abdominal pain, shakiness/tremors, sweating, fever, chills, or a headache
3. the signs or symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning
4. the signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance

It should be noted that evidence suggests that withdrawal only occurs in a subset of patients. Symptoms usually begin within the first 24 hours, peak by day three, and can last for up to two weeks. Increased use and more recent use can predict the severity of withdrawal.

Cannabis Intoxication Delirium

This diagnosis relies on the definition of delirium and is appropriate when the following two symptoms predominate in someone who has taken cannabis:

1. Disturbance in attention (i.e., reduced ability to direct focus, sustain, and shift attention) and awareness (reduced orientation to the environment)
2. An additional disturbance in cognition (i.e., memory deficit, disorientation, language, visuospatial ability, or perception).

Cannabis-Induced Psychotic Disorder

1. presence of delusions or hallucinations.
2. evidence from the history, physical examination, or laboratory findings of either one of the following:
   1. The symptoms in the first criterion developed during or soon after cannabis intoxication or withdrawal.
   2. The disturbance is not accounted for by a psychotic disorder that is not substance-induced.
   3. Evidence that the symptoms are accounted for by a psychotic disorder that is not substance induced might include the following:
      1. The symptoms precede the onset of substance use (or medication use).
      2. The symptoms persist for a substantial period (e.g., about a month) after the cessation of acute withdrawal or severe intoxication or are substantially more than what would be expected, given the type or amount of the substance used or the duration of use.
      3. Other evidence suggests the existence of an independent non-substance-induced psychotic disorder (e.g., a history of recurrent non-substance-related episodes).
      4. The disturbance does not occur exclusively during delirium.
      5. The disturbance causes clinically significant distress or impairment in social, occupational, or other areas of functioning.

Cannabis-Induced Anxiety Disorder

1. panic attacks or anxiety predominate in the clinical picture

2. evidence from the history, physical examination, or laboratory findings of the following:

   1. The symptoms in the first criterion developed during or soon after substance intoxication or withdrawal.
   2. The disturbance is not better accounted for by an anxiety disorder that is not substance-induced. Evidence that the symptoms are better accounted for by an anxiety disorder that is not substance induced might include the following:
      1. The symptoms precede the onset of substance use.
      2. The symptoms persist for a substantial period (e.g., about a month) after cessation of acute withdrawal or severe intoxication or are substantially more than expected given the type or amount of the substance used or the duration of use.
      3. Other evidence suggests the existence of an independent non-substance-induced anxiety disorder (e.g., a history of recurrent non-substance-related episodes).
   3. The disturbance does not occur exclusively during delirium.
   4. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Cannabis-Induced Sleep Disorder

1. a prominent and severe disturbance in sleep
2. evidence from the history, physical examination, or laboratory findings of both of the following:
   1. The symptoms in the first criterion developed during or soon after cannabis intoxication or after withdrawal from or exposure to it.
   2. The disturbance is not better explained by a sleep disorder that is not substance/medication-induced. Such evidence of an independent sleep disorder could include that:
   3. The symptoms precede the onset of cannabis use.
   4. The symptoms persist for a substantial period (i.e., about a month) after the cessation of acute withdrawal or severe intoxication.
   5. There is other evidence suggesting the existence of an independent non-substance/medication-induced sleep disorder (i.e., a history of recurrent non-substance/medication-related episodes).
   6. The disturbance does not occur exclusively during delirium.
   7. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

The Chronic Effects: Cannabis Use Disorder

Cannabis abuse and dependence were combined in the DSM-5 into a single entity capturing the behavioral disorder that can occur with chronic cannabis use and named cannabis use disorder, it is defined as:

1. a problematic pattern of cannabis use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period:
   1. Cannabis is often taken in larger amounts or over a longer period than was intended.
   2. There is a persistent desire or unsuccessful efforts to cut down or control cannabis use.
   3. A great deal of time is spent in activities necessary to obtain cannabis, use cannabis, or recover from its effects.
   4. Craving, or a strong desire or urge to use cannabis.
   5. Recurrent cannabis use results in failure to fulfill role obligations at work, school, or home.
   6. Continued cannabis use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of cannabis.
   7. Important social, occupational, or recreational activities are given up or reduced because of cannabis use.
   8. Recurrent cannabis use in situations in which it is physically hazardous.
   9. Cannabis use continues despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by cannabis.
2. tolerance, as defined by either: (1) a need for markedly increased cannabis to achieve intoxication or desired effect or (2) a markedly diminished effect with continued use of the same amount of the substance
3. withdrawal, as manifested by either (1) the characteristic withdrawal syndrome for cannabis or (2) cannabis is taken to relieve or avoid withdrawal symptoms

It has the following specifiers:

• in early remission—After full criteria for cannabis use disorder were previously met, none of the criteria for cannabis use disorder has been met for at least three months but less than 12 months (with an exception provided for craving).
• in sustained remission—After full criteria for cannabis use disorder were previously met, none of the criteria for cannabis use disorder has been met at any time during 12 months or longer (with an exception provided for craving).
• Severity is graded as either mild, moderate, or severe depending on if two to three, four to five, or six or more of the above criteria are present.

Epidemiology

Nearly 4% of the global population was using cannabis in 2015. Amongst teenagers, 8% in the United States and 16% in Europe report use. 9% of all users experience addiction of which nearly a fifth began to use in adolescence. There is limited evidence for cannabis use among the elderly. However, its consumption may be considered to be increasing as legal permission for its medical use may justify its use among former non-users.

In the United States, as of 2013, cannabis is the most commonly identified illicit substance used by people admitted to treatment facilities. In the United States, the average adult who seeks treatment has consumed cannabis for over 10 years almost daily and has attempted to quit six or more times.

During pregnancy, 4% of mothers admit to using drugs, most commonly with cannabis. A retrospective cohort study of more than 12 million pregnant women revealed nearly a tripling of cannabis abuse or dependence from 1999 through 2003, and a significant association for perinatal complications. Thirty-five percent of mothers who have used marijuana have done so during pregnancy, and 18% used it while breastfeeding.

As consumption increases among adults, so does the unintended consequence of exposure to children. Between 2005 and 2009, 985 unintentional exposures to children (median age of 1.7 years) were reported. States legalizing marijuana have had a 20-fold increase in calls to poison centers and admissions to critical care units for its exposure.^[1]

Overall, the trend for using cannabis is increasing over time for most, if not all, demographics.

Etiology

Cannabis use varies based on demographics. Research shows college students and young adults most commonly use cannabis to socially conform (42%), to experiment (29%), and for enjoyment (24%). Twelve percent primarily use cannabis to manage stress or relax, and studies show that is it commonly used as a type of self-medication for depression, anxiety, social anxiety, and post-traumatic stress disorder. During pregnancy, mothers who reported using marijuana say they did so primarily to manage depression, anxiety, and stress (63%); pain (60%); nausea or vomiting (48%), and for recreational purposes (39%).

Biologically speaking, impaired inhibition can predispose individuals to substance use disorders. However, healthcare professionals are unsure if this is true for marijuana.

Risk Factors

Certain factors are considered to heighten the risk of developing cannabis dependence, and longitudinal studies over a number of years have enabled researchers to track aspects of social and psychological development concurrently with cannabis use. Increasing evidence is being shown for the elevation of associated problems by the frequency and age at which cannabis is used, with young and frequent users being at the most risk.

The main factors in Australia, for example, related to a heightened risk for developing problems with cannabis use include frequent use at a young age; personal maladjustment; emotional distress; poor parenting; school drop-out; affiliation with drug-using peers; moving away from home at an early age; daily cigarette smoking; and ready access to cannabis. The researchers concluded there is emerging evidence that positive experiences to early cannabis use are a significant predictor of late dependence and that genetic predisposition plays a role in the development of problematic use.

The endocannabinoid system is directly involved in adolescent brain development. Adolescent cannabis users are therefore particularly vulnerable to the potential adverse effects of cannabis use. Adolescent cannabis use is associated with increased cannabis misuse as an adult, issues with memory and concentration, long-term cognitive complications, and poor psychiatric outcomes including social anxiety, suicidality, and addiction.

Treatment

Treatment options for cannabis dependence are far fewer than for opiate or alcohol dependence. Most treatment falls into the categories of psychological or psychotherapeutic, intervention, pharmacological intervention, or treatment through peer support and environmental approaches. No medications have been found effective for cannabis dependence, but psychotherapeutic models hold promise.

The aim of treatment should be to improve the individual’s overall function, which is multiphasic and multifactorial. Supportive treatment may be provided during detoxification; enabling access to psychiatric services allows addressing underlying disorders; psychological counseling can modify behavior, develop healthier coping skills in the face of stressors, and enlighten them as to their temperament.

As cannabis strains become more potent and accessible, the risk will increase for the frequency and severity of serious adverse reactions. For individuals with marked intoxication or withdrawal, or cannabis use disorder, the goal should be a cessation of the drug altogether. A gradual decrease as opposed to abrupt cessation is likely to decrease the discomfort of the withdrawal, and prevent relapse. Cannabis intoxication most often does not require medical management and will self-resolve. Supportive management such as a calm, non-stimulating environment helps patients. Symptomatic treatment can be considered for specific symptoms such as alpha-2-adrenergic agonists or beta-blockers for tachycardia, benzodiazepines for panic attacks, off-label use of first-generation antihistamines for anxiety and restlessness, and neuroleptics for psychosis. It is important to monitor psychological symptoms, which may be features of the withdrawal or part of the patient’s primary psychiatric illness that may not have been previously identified.

Pharmacologic detoxification is still under investigation. A systematic review indicates most studies are preliminary and cannot statistically support clinical rationale as they are small sizes, inconsistent, and have a risk of attrition bias.

There is no medication that is FDA approved to treat cannabis use disorder. Tetrahydrocannabinol does show some potential in treatment, but more information is needed to demonstrate the validity and inform about dosages, duration, formulation, and adjunct therapies. Gabapentin and N-acetylcysteine are also used but have unclear benefits. Another component of cannabis, cannabidiol, holds promise by modulating the serotonergic, glutamatergic, and endocannabinoid systems.