Cannabis-Related Disorders

In January 2014, Colorado became the first state in the United States to legalize marijuana for recreational purposes, marking the beginning of what will likely become the end of marijuana prohibition. Marijuana was legal in the United States until 1937, when Congress passed the Marijuana Tax Act, effectively making the drug illegal. The American Medical Association (AMA) opposed the legislation at the time of its passage. Additionally, from 1850 to 1942, marijuana was listed in the US Pharmacopoeia, the official list of recognized medical drugs. Cannabis was marketed as extract or tincture by several pharmaceutical companies and used for ailments such as anxiety and lack of appetite.

Despite the medical establishment's views on the benefits of marijuana, the passage of the Comprehensive Drug Abuse Prevention and Control Act of 1970 classified marijuana as a Schedule I drug, defined as a category of drugs not considered legitimate for medical use. Other Schedule I drugs include heroin, phencyclidine (PCP), and lysergic acid diethylamide (LSD).[1]

A significant paradox and disconnect continues to exist between the federal government's outdated policies versus changing state laws, the general public's perception and acceptance of marijuana, and even former President Barack Obama. In discussing his own marijuana use with New Yorker editor David Remnick, President Obama commented, "As has been well documented, I smoked pot as a kid, and I view it as a bad habit and a vice, not very different from the cigarettes that I smoked as a young person up through a big chunk of my adult life. I don’t think it is more dangerous than alcohol." He elaborated that marijuana was actually less dangerous than alcohol "in terms of its impact on the individual consumer."[2]

Currently, 38 states and the District of Columbia have legalized marijuana for medicinal purposes, with many others actively considering the issue. Additionally, a survey by NBC News/The Wall Street Journal shows that the majority of Americans support legalizing marijuana.[3] Federal policy changes have attempted to redress the inconsistencies between federal and state law. In 2009, the Justice Department issued a federal medical marijuana policy memo to the Drug Enforcement Administration (DEA), Federal Bureau of Investigation (FBI), and US Attorneys instructing prosecutors not to target medicinal marijuana patients and their providers for federal prosecution in states where medicinal marijuana has been legalized. In the summer of 2010, the Department of Veteran Affairs issued a department directive to "formally allow patients treated at its hospitals and clinics to use medical marijuana in states where it is legal, a policy clarification that veterans have sought for years."[4]

In the Netherlands, where the distribution of marijuana has been legalized, the effect of decriminalization has had little effect on the consumption rate of cannabis.[5] In 2004, Reinarman et al looked at the consumption of marijuana rates between San Francisco and Amsterdam to see what effect decriminalization had on these different populations.[6] The results showed that the consumption habits between the two populations were negligible. Little evidence has shown that the decriminalization of cannabis has changed the consumption habits of the populations involved.[7]

While there is a rich history of anecdotal accounts of the benefits of marijuana and a long tradition of marijuana being used for a variety of ailments, the scientific literature in support of medicinal uses of marijuana is less substantial. Considered one of the first scientifically valid papers in support of marijuana’s medicinal benefit, in 2007, Dr. Donald Abrams and colleagues published the results of a randomized placebo-controlled trial examining the effect of smoked cannabis on the neuropathic pain of HIV-associated sensory neuropathy and an experimental pain model. The authors concluded that smoked cannabis effectively relieved chronic neuropathic pain in HIV-associated sensory neuropathy and was well tolerated by patients. The pain relief was comparable to chronic neuropathic pain treated with oral drugs.[8]

According to Harvard Medical School's April, 2010 edition of the Harvard Mental Health Letter[9] : Consensus exists that marijuana may be helpful in treating certain carefully defined medical conditions. In its comprehensive 1999 review, for example, the Institute of Medicine (IOM) concluded that marijuana may be modestly effective for pain relief (particularly nerve pain), appetite stimulation for people with AIDS wasting syndrome, and control of chemotherapy-related nausea and vomiting.

These widely held beliefs in the medical community supporting the medicinal benefit of marijuana are starting to gain support in the form of rigorous empirical evidence demonstrating its clinical benefit and limited potential for harm. In 2012, the AMA published a landmark study that followed more than 5,000 patients longitudinally over 20 years. The results of the study were somewhat surprising. Although many had assumed that regular exposure to marijuana smoke would result in pulmonary function damage, similar to the deleterious effects seen with regular tobacco smoke exposure, the study convincingly demonstrated that regular exposure to marijuana smoke did not adversely affect lung function. Even more surprising, regular marijuana smokers demonstrated increased total lung function capacity.

The authors report, “Marijuana may have beneficial effects on pain control, appetite, mood, and management of other chronic symptoms. Our findings suggest that occasional use of marijuana for these or other purposes may not be associated with adverse consequences on pulmonary function.”[10]

The AMA is urging the federal government to change the classification of marijuana from a Schedule I drug to enable further clinical research on marijuana. Additionally, Harvard Mental Health Letter's authors point out that while marijuana works to relieve pain, suppress nausea, reduce anxiety, improve mood, and act as a sedative, the evidence that marijuana may be an effective treatment for psychiatric indications is inconclusive.[11]

In a systematic review published as a “Report of the Guideline Development Subcommittee of the American Academy of Neurology”, the authors performed a systematic review of medical marijuana from 1948 to November 2013 to identify the role of medical marijuana in the treatment of multiple sclerosis (MS), epilepsy and, movement disorders. The authors concluded that medical marijuana was found to be effective for treating MS-related pain or painful spasms.[11]

While marijuana may have medicinal benefits, its use in excess by some individuals can lead to marked impairment in social and occupational functioning. Published in 2013, the fifth edition of TheDiagnostic and Statistical Manual of Mental Disorders (DSM-5) included significant changes to substance-related and addictive disorders. DSM-5 combined the previously separate categories of substance abuse and dependence into a single disorder of substance use, specific to the substance (eg, Alcohol Use Disorder, Cannabis Use Disorder). The Text Revision of the DSM-5 was published in 2022. It recognizes the following 5 cannabis-associated disorders:[12]

• Cannabis Use Disorder

• Cannabis Intoxication

• Cannabis Withdrawal

• Cannabis-Induced Mental Disorders

• Unspecified Cannabis-Related Disorder

An example of Cannabis sativa is shown in the image below.

Case study

Mr. X, a 19-year-old single white male presents complaining of apathy, lack of motivation, and an increasing sense of social isolation. He tried marijuana for the first time at age 15, when he was a junior in high school, and quickly started smoking on a daily basis. He would spend nights and then days with friends, getting "stoned," experiencing the "giggles" and relishing the inevitable "munchies." He quickly noticed that smoking marijuana seemed to quell feelings of anxiety he experienced in social settings. Having graduated from high school a year earlier, he describes unfulfilled plans to attend college, which were foiled by his inability to submit the requisite applications. He describes half-hearted attempts to secure employment and now resides in the basement of his parent's house, supported by them. He describes a typical day in the following fashion:

Upon waking, usually in the late morning, he invariably takes a bong hit or smokes a joint, to "get going." Then he spends a significant amount of time preparing breakfast—he feels the marijuana heightens his culinary senses and he takes great joy in cooking and preparing a large meal.

Following breakfast, he retires back to his room in the basement and spends the next several hours playing video games online. When he senses that he is slowing down and feeling sleepy, he will smoke more marijuana because it gives him more energy and improves his mood.

He will typically break from his immersion in the online gaming world for a late lunch, repeating his earlier efforts associated with breakfast. Occasionally, he will go to the local park to play basketball with the kids that are still in high school. Previously a successful athlete in high school, he feels like he has lost a step and his reflexes on the court are not as quick as they used to be.

He has taken to selling a baseball card collection he painstakingly acquired when he was younger to raise money to pay for his marijuana, and, as that collection has dwindled, he has started to grow marijuana in his basement. He describes his first efforts as generating a meager plant that bears a resemblance to the sad Christmas tree from Charlie Brown.

He does not understand why he no longer has a girlfriend or why it has become difficult to meet new girls. He seems perplexed by his last girlfriend's complaints that he had become boring and it seemed like he was "letting life pass him by." He reports that his parents seem to be growing increasingly frustrated with him and reports arguing with them over his marijuana use—they identify it as a problem, he disagrees. He no longer goes out at night and instead spends most of his time smoking and playing video games alone in his room in the basement.

He denies any difficulty sleeping, although he does not remember dreaming anymore and cannot remember the last dream he had. He reports some cognitive difficulties associated with decreased ability to concentrate and some short-term memory problems. He reports feeling occasionally irritable when too much time passes in between smoking and feels that marijuana makes him less irritable. He is interested in being more social, more engaged, and feeling like he is achieving his goals but seems unable to explain why he cannot accomplish what he sets out to do.

He does not seem to appreciate that his heavy and chronic marijuana use is a significant cause of his symptoms. He indicates that overall he enjoys smoking marijuana and believes it makes it easier for him to enjoy his days, which have become more difficult lately as he appreciates the stark difference between the quality of life he is enjoying compared with his peers who are now working or attending college.

The term cannabinoid refers to compounds that can activate either the cannabinoid receptor 1 (CB1) or CB2 receptor, or both. Additionally 50-60 additional substances have been isolated from cannabis that do not activate the CB1 or CB2 receptors. Delta-9-tetrahydrocannabinol (THC) is recognized as the major psychoactive component of cannabis (see the image below). THC potently activates the G-protein–coupled cannabinoid receptor CB1 and modulates the cannabinoid receptor CB2.[13, 14]

Cannabidiol is considered the most abundant nonpsychoactive cannabinoid in cannabis. It is the constituent thought now to reduce many of the undesirable effects of THC; it significantly reduces the anxiety and psychoticlike symptoms that can be associated with THC. It is currently under investigation for use as an anxiolytic and antipsychotic. Double-blinded tests on volunteers have demonstrated its usefulness as an anxiolytic in anxiogenic test situations. Animal and human studies also suggest that it has a pharmacologic profile similar to atypical antipsychotics; as such, cannabis is being considered as an alternative effective treatment for schizophrenia.[15] However, THC has been more extensively studied; therefore, much of our understanding of the physiological changes induced by marijuana is predicated on the binding and metabolism of THC.

Smoking is the most common and efficient means of ingestion, with the dose being titrated by the user through varying the depth and frequency of inhalation; thus, the delivery mechanism poses a challenge for cannabis as a medication. THC can also be extracted by fat-containing foods or dissolved in oil for pharmaceutical purposes.

Synthetic cannabinoids exist that are more potent and somewhat more water soluble. Currently, the following 2 medications containing synthetic THC are US Food and Drug Administration (FDA) approved:

• Dronabinol (Marinol): This drug is indicated for anorexia associated with weight loss in patients with AIDS and nausea and vomiting associated with cancer chemotherapy in patients who have not responded adequately to conventional antiemetic treatments.

• Nabilone (Cesamet): This drug is indicated for nausea and vomiting associated with cancer chemotherapy in patients who have not responded adequately to conventional antiemetic treatments.

After intake, THC undergoes metabolism to an inactive metabolite (8-11-DiOH-THC) and to a highly active metabolite (11-OH-delta-9-THC). The half-life of THC is approximately 4 hours. The long life of the active metabolite is explained by the incorporation of the compound in lipid storage depots and similar storage sites in muscle tissue. Thirty to 60% of THC, in all forms, is excreted in feces; the remaining amount is excreted in urine.

The endocannabinoid system is now understood to be a complex lipid–signaling network in which different proteins play specific roles in controlling or modulating a variety of physiological and pathophysiological processes.[14] Delta-9-THC is believed to exert all of its effects on the brain via the CB1 receptor. High densities of CB1 receptors are found in the cerebral cortex (especially frontal), basal ganglia, cerebellum, anterior cingulate cortex, and hippocampus. They are relatively absent in the brainstem nuclei. Stimulation of these receptors causes monoamine and amino acid neurotransmitters to be released. Endogenous ligands for CB1 receptors include anandamide and 2-arachidonylglycerol—the endocannabinoids.

Frequency

Marijuana remains the most commonly used illicit drug. In 2020, 17.9% of people aged 12 years or older (49.6 million people) used marijuana in the past year.[16]

According to the 2021 Monitoring the Future survey, the percentage of students who reported using marijuana (in all forms, including smoking and vaping) within the past year decreased significantly for 8th, 10th, and 12th grade students.[17]  

• 8th graders: 7.1% reported using marijuana in the past year in 2021, compared to 11.4% in 2020
• 10th graders: 17.3% reported using marijuana in the past year in 2021, compared to 28.0% in 2020
• 12th graders: 30.5% reported using marijuana in the past year in 2021, compared to 35.2% in 2020

Throughout their lifetime, approximately 9% of the American adult population has met criteria for a cannabis use disorder.[18]

An estimated 80.5 million European adults have used marijuana at least once and it is widely accepted that it is the most frequently used illicit substance in Western countries.[19]

Mortality/Morbidity

Cannabis consumption has never directly resulted in mortality, and no fatalities have been documented that identify cannabis consumption as the etiologic agent. However, cannabis consumption has been associated with multifactorial deaths, including marijuana-related accidents and deaths attributed to abuse of alcohol and other illicit substances.[20]

Studies using simulated driving and flying situations have shown that the use of cannabis has a profound effect on estimations of time and distance and causes impairment of attention and short-term memory. These effects are still discernible 24-48 hours after use of the drug. A linear relationship is noted between level of impairment and serum/saliva THC level in tasks necessary for driving, such as perceptual motor control, motor impulsivity, and cognitive function. A double-blind, placebo-controlled, randomized study showed that therapeutic doses of medicinal THC (dronabinol) impairs driving ability in healthy adults to the same extent as alcohol at blood levels of 0.5–1 mg/mL, suggesting that driving is impaired with even small doses of psychoactive cannabinoids.[21]

Cannabis dependence is associated with morbidity, including impaired occupational and social functioning. Cannabis use can be comorbid with the presence of other psychiatric disorders, characterized by a disordered thought process, perceptual disturbances, or symptoms of anxiety. When marijuana is believed to be the etiologic agent, clinicians may diagnose a cannabis-induced disorder.

Psychotic symptoms represent a significant morbidity associated with cannabis use in select patients. While cannabis and the development of psychosis have been linked, this link is not without considerable controversy and there are differing perspectives on whether this relationship is indeed causal, temporal, or coincidental. Given marijuana's clinical benefits, some have argued that patients diagnosed with psychotic disorders gravitate toward self-medicating with marijuana for these effects, while others have advanced the view that marijuana can help precipitate the onset of psychosis in those who are genetically vulnerable. A study examining this controversial topic concluded that marijuana use can play a "catalytic role" in the onset of psychosis as demonstrated by cannabis use being associated with an association of an earlier age at on onset of psychosis treatment. Unfortunately, this study is not without limitations.[22]

Another article examining this topic observed patients over 10 years and reached some similar conclusions. This study appears to provide additional evidence supporting the hypothesis that cannabis use is associated with an earlier age of onset of psychosis. However, the authors' findings complicate the debate further regarding the potential role of cannabis as an etiologic agent versus its use as self-medication by patients with psychotic symptoms. The authors note that there is a bidirectional relationship between psychosis and cannabis use; cannabis exposure predicted psychosis severity and those with more severe psychotic symptoms were more likely to use cannabis in the future.[23]

A study conducted in Germany stated that the use of cannabis in adolescence is a risk factor for the development of incident psychotic symptoms.[24] This study was not without significant limitations; the study ignored the impact of genetic inheritability as a risk factor in the development of psychosis, the impact of confounding risk factors associated with other drug use (eg, PCP, methamphetamine), and the authors’ assumption that transient psychotic experiences were a surrogate for clinically relevant psychosis.

A meta-analysis examining 83 different studies reached similar conclusions, reporting that cannabis use was associated with an earlier age of onset of psychosis. Unfortunately despite a dearth of evidence, the authors argued that this temporal association supported their personal view that marijuana was an etiological risk factor for the development of psychosis.[25] The exact role marijuana plays in the development of psychosis and whether or not it has any causal role remains a matter of debate and controversy.

Marijuana abuse may be a factor in vehicle or machinery accidents because intoxication affects coordination and motor performance. Perform the appropriate tests for use of marijuana after these accidents.

Race-, sex-, and age-related demographics

Given how widespread cannabis use is globally, across cultures, race is not a significant risk factor associated with cannabis use nor does it represent a useful criterion for identifying acute or chronic marijuana users. However, a study in California demonstrated a significant disparity in arrest rates for users of marijuana based on race. According to the report, from 2004–2008, in Sacramento and San Francisco Counties, black residents were arrested for marijuana possession 4 times as often as white residents. In Los Angeles County, the disparity was more than 3 to 1.[26]

A report looking at factors that could predict transition from abuse to dependence provided additional epidemiological data. According to the authors, rates of cannabis use were higher among white males.[27]

Similarly to other addictive drugs, fewer females than males use marijuana.[16]

Use, abuse, and dependence on marijuana tends to cut across demographics, including age.

See the list below:

• American Council for Drug Education, Basic Facts About Drugs: Marijuana

• National Institute on Drug Abuse, Infofacts, Marijuana

• National Institute on Drug Abuse, Marijuana: Facts for Teens

• Office of National Drug Control Policy, Marijuana

• eMedicineHealth, Substance Abuse Center

• eMedicineHealth, Drug Dependence and Abuse and Substance Abuse

• National Institute on Drug Abuse, Parents and Teachers

When soliciting information related to marijuana use, both acutely and chronically, clinicians are advised to keep in mind the diagnostic criteria discussed below.

Cannabis intoxication

Cannabis intoxication is defined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR),[12] as the following:

• Recent use of cannabis

• Clinically significant problematic behavioral or psychological changes (eg, impaired motor coordination, euphoria, anxiety, sensation of slowed time, impaired judgment, social withdrawal) that developed during, or shortly after, cannabis use

• Two or more of the following signs, developing within 2 hours of cannabis use:

  • Conjunctival injection

  • Increased appetite

  • Dry mouth

  • Tachycardia

• Symptoms not due to a general medical condition and not better accounted for by another mental disorder

Clinicians are instructed to specify if this is occurring with perceptual disturbances—hallucinations with intact reality testing or auditory, visual, or tactile illusions occur in the absence of delirium.

Cannabis use disorder

Cannabis use disorder is defined by DSM-5-TR as the following:

• A problematic pattern of cannabis use leading to clinically significant impairment or distress, as manifested by at least 2 of the following, occurring within a 12-month period:

  • Cannabis is often taken in larger amounts or over a longer period than was intended.

  • There is a persistent desire or unsuccessful efforts to cut down or control cannabis use.

  • A great deal of time is spent in activities necessary to obtain cannabis, use cannabis, or recover from its effects.

  • Craving, or a strong desire or urge to use cannabis.

  • Recurrent cannabis use resulting in a failure to fulfill major role obligations at work, school, or home.

  • Continued cannabis use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of cannabis.

  • Important social, occupational, or recreational activities are given up or reduced because of cannabis use.

  • Recurrent cannabis use in situations in which it is physically hazardous.

  • Cannabis use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by cannabis.

  • Tolerance, as defined by either a (1) need for markedly increased cannabis to achieve intoxication or desired effect or (2) markedly diminished effect with continued use of the same amount of the substance.

  • Withdrawal, as manifested by either (1) the characteristic withdrawal syndrome for cannabis or (2) cannabis is taken to relieve or avoid withdrawal symptoms

Clinicians are instructed to specify the following:

• 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 3 months but for 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 a period of 12 months or longer (with an exception provided for craving).

Cannabis withdrawal

Cannabis withdrawal is defined by DSM-5-TR as the following:

• Cessation of cannabis use that has been heavy and prolonged (ie, 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 1 week after cessation of heavy, prolonged use:

  • Irritability, anger or aggression

  • Nervousness or anxiety

  • Sleep difficulty (ie, insomnia, disturbing dreams)

  • Decreased appetite or weight loss

  • Restlessness

  • Depressed mood

  • At least one of the following physical symptoms causing significant discomfort: abdominal pain, shakiness/tremors, sweating, fever, chills, or headache

• The signs or symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

• 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.

Compared with other illicit substances with clearly defined withdrawal states and associated symptoms, the definition of a cannabis withdrawal syndrome (CWS) had remained controversial. Previously, as no evidence was available of increasing tolerance associated with cannabis use, making the diagnosis of cannabis dependence with physiological dependence has remained controversial, if not impossible.

Although prior studies have attempted to illustrate the existence of CWS, these studies have had significant limitations. Additionally, until recently, there has been a dearth of any prospective studies assessing the occurrence of CWS. However, a prospective study focused on assessing the course of CWS symptoms among patients dependent on cannabis who were seeking detoxification. This study seems to support evidence of a clinically relevant CWS that the authors qualify as "only expected in a subgroup of cannabis-dependent patients."[28] Its definition and inclusion in DSM-5, is consistent with the symptoms described by these researchers. While DSM-5 defined the timeframe as occurring within 1 week after cessation of prolonged, heavy use, the authors of this prospective study on CWS specified symptoms are believed to occur following a 24-hour period of abstinence, peaking at day 3 following abstinence andlasting 1–2 weeks.[28, 29]

The authors recommended subgrouping cannabis-dependent patients undergoing detoxification into those with no or only very mild CWS and those with moderate-to-strong CWS. Risk factors that seemed to predict which subgroup patients could be classified by included recent cannabis intake and last amount of cannabis consumed prior to hospitalization, with patients reporting recent and more cannabis consumption before hospitalization as more likely to report symptoms of CWS.[28] A withdrawal scale predicated on a study of 49 cannabis-dependent subjects may have reliability in assessing the severity of cannabis withdrawal symptoms.[30]

Other cannabis-induced disorders

Cannabis intoxication delirium

Cannabis intoxication delirium, a cannabis-induced disorder, relies on the definition of delirium and this diagnosis is appropriate when the following 2 symptoms predominate:

• Disturbance in attention (ie, reduced ability to direct focus, sustain, and shift attention) and awareness (reduced orientation to the environment)

• An additional disturbance in cognition (ie, memory deficit, disorientation, language, visuospatial ability, or perception)

Cannabis-induced psychotic disorder

Cannabis-induced psychotic disorder is defined by DSM-5-TR as follows:

• Presence of one or both of the following symptoms:

  • Delusions

  • Hallucinations

• Evidence from the history, physical examination, or laboratory findings of either one of the following:

  • The symptoms in the first criterion developed during or soon after substance intoxication or withdrawal.

  • The involved substance is capable of producing these symptoms.

• The disturbance is not better accounted for by a psychotic disorder that is not substance induced. Evidence that the symptoms are better accounted for by a psychotic disorder that is not substance induced might include the following:

  • The symptoms precede the onset of the substance use (or medication use).

  • The symptoms persist for a substantial period (eg, about a month) after the cessation of acute withdrawal or severe intoxication or are substantially in excess of what would be expected given the type or amount of the substance used or the duration of use.

  • Other evidence suggests the existence of an independent non–substance–induced psychotic disorder (eg, a history of recurrent non–substance–related episodes).

• The disturbance does not occur exclusively during the course of a delirium.

• The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Cannabis-induced anxiety disorder

Cannabis-induced anxiety disorder, categorized as a cannabis-induced disorder, is defined by the DSM-5-TR as follows:

• Panic attacks or anxiety predominate in the clinical picture.

• Evidence from the history, physical examination, or laboratory findings of either of the following:

  • The symptoms in the first criterion developed during or soon after substance intoxication or withdrawal.

  • The involved substance is capable of producing the symptoms in the first criterion.

• 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:

  • The symptoms precede the onset of the substance use (or medication use).

  • The symptoms persist for a substantial period (eg, about a month) after cessation of acute withdrawal or severe intoxication or are substantially in excess of what would be expected given the type or amount of the substance used or the duration of use.

  • Other evidence suggests the existence of an independent non–substance–induced anxiety disorder (eg, a history of recurrent non–substance–related episodes).

• The disturbance does not occur exclusively during the course of a delirium.

• The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Cannabis-induced sleep disorder

DSM-5-TR defines this as follows:

• A prominent and severe disturbance in sleep.

• There is evidence from the history, physical examination, or laboratory findings of both of the following:

  • The symptoms in the first criterion developed during or soon after cannabis intoxication or after withdrawal from or exposure to it.

  • Cannabis is capable of producing the symptoms in the first criterion. 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 symptoms precede the onset of the cannabis use; symptoms persist for a substantial period (ie about a month) after the cessation of acute withdrawal or severe intoxication; or there is other evidence suggesting the existence of an independent nonsubstance/medication-induced sleep disorder (ie, a history of recurrent nonsubstance/medication-related episodes).

• The disturbance does not occur exclusively during the course of delirium.

• The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Unspecified cannabis-related disorder

This category applies to presentations in which symptoms characteristic of a cannabis-related disorder that cause clinically significant distress or impairment in social, occupational, or other important areas of functioning predominate but do not meet the full criteria for any specific cannabis-related disorder or any of the disorders in the substance-related and addictive disorders diagnostic class.

A thorough mental status examination is an integral component of every patient assessment. Key mental status findings associated with cannabis use, cannabis-induced, and cannabis-related disorders include the following:

• Mood: Acute use may be associated with feelings of euphoria, uncontrollable laughter, increased appetite, and difficulty concentrating. In chronic use or withdrawal, patients may report a depressed mood characterized by apathy, lack of motivation, irritability, loss of interest in typical activities, difficulty concentrating, and possibly isolation.

• Affect: Acutely, affect may span the spectrum from euphoric to anxious. In chronic use, affect may be constricted or flat.

• Thought process and content: As in any mental status examination, assessing the patient for the presence of suicidality or homicidality and taking appropriate action is critical. Patients may demonstrate flight of ideas, loose associations, and, in some cases, delusions and hallucinations.

• Cognition: In both acute and chronic use, difficulty concentrating and memory impairment are common.

Physical signs and symptoms associated with cannabis use are particularly relevant to the diagnosis of cannabis intoxication. Clinicians are advised to identify at least 2 or more of the following physical symptoms, occurring within 2 hours of cannabis use, as defined by DSM-5-TR criteria:

• Conjunctival injection

• Increased appetite

• Dry mouth

• Tachycardia

Additionally, patients may demonstrate physical symptoms associated with cannabis withdrawal syndrome.

Other adverse physical and psychological manifestations associated with marijuana abuse are as follows:

• Sweating

• Headaches

• Restlessness

• Forgetfulness

• Visual distortions

• Lack of concentration

• Paranoia

• Mood changes

• Perceptual changes

• Feeling impersonal

• Panic disorder

• Amotivational syndrome

• Delusions

• Psychosis

Risk factors among adolescents that may increase the likelihood for marijuana abuse include the presence of comorbid substance use and environmental stressors, including difficulty in school.

Urine testing

Cannabinoids can be detected in the urine for as many as 21 days after use in persons chronically using marijuana, because these lipid-soluble metabolites are slowly released from fat cells into the blood; however, 1-5 days is the normal urine-positive period.

The primary method for urinalysis detection is enzyme immunoassay or radioimmunoassay. This method is inexpensive, quick, and accurate. This is also useful for confirmation of abstinence.

Urine samples are difficult to obtain from people who are addicted, and providing a urine sample is easily evaded. Urine toxicology testing should be performed under supervised conditions to ensure reliability of results.

Gas chromatography in combination with mass spectrometry and/or thin-layer chromatography is used to confirm positive results, especially in legal proceedings.

With all types of tests mentioned, including thin-layer chromatography, false-negative results tend to be more common than false-positive results.

Blood testing

Blood samples may be used to measure quantitative levels of cannabinoids.[31] Serial monitoring of tetrahydrocannabinol (THC)–COOH to creatinine ratios can distinguish between recent use and residual excretion. To assess the extent of cannabis use, determination of free and bound THC-COOH can be useful.

Blood analysis is the preferred method of detection for interpretation of acute effects. The cannabis influence factor is a tool used to interpret concentrations of THC and its metabolites in forensic cases. Absolute driving inability has been proposed in the case of cannabis influence factor of 10 or higher. The higher the cannabis influence factor, the more recent the cannabis abuse.

Blood samples must be taken within a prescribed 8-day period, and THC-COOH concentration greater than 75 ng/mL is associated with regular consumption of cannabis. THC-COOH concentration less than 5 ng/mL is associated with occasional consumption.

Hair analysis

Hair analysis is not a sensitive enough tool to detect cannabinoids.[31] THC, and the main metabolite THC-COOH, do not incorporate to a great extent into hair. TCH-COOH is not highly bound to melanin. Hence, concentrations in hair are much lower when compared with other drugs of abuse. Because TCH is present in cannabis smoke, it can also be incorporated into hair simply by second-hand exposure.

Saliva testing

Saliva testing is a newer technology for detection. The presence of delta-9-THC in oral fluid is a better indication of recent use than the presence of 11-nor-delta-9-THC-9-COOH detected in urine. Therefore, the probability that a user is experiencing effects is higher. This may prove especially useful in the monitoring of driving while under the influence.

Although no confirmatory imaging study exists for marijuana use, pilot investigations involving neuroimaging of marijuana smokers performing various mental tasks have revealed many differences in comparative levels of activity in many regions of the brain with respect to controls.

Functional MRI and diffusion tensor imaging techniques demonstrate significant differences in the magnitude and pattern of signal intensity change within the anterior cingulate and the dorsolateral prefrontal cortex while performing standardized tasks in chronic marijuana smokers compared with healthy controls.

Neuroimaging studies, such as CT scanning, MRI, and positron emission tomography scanning, are extensively used to study the neurobiological effects of cannabis abuse but are not clinically useful in the definitive determination of recent abuse.

Acute intoxication of cannabis usually resolves unremarkably within 4–6 hours and is best managed by the following measures:

• Frequent reassurance and maintenance of a nonthreatening environment

• Minimal stimuli

• Use of a specifically assigned nurse to calm the patient

• Judicious use of benzodiazepines when significant anxiety is present

People who use marijuana and are suffering from biological, psychological, or social impairment from marijuana use should be evaluated and, if necessary, treated by a psychiatrist.

The treatment of marijuana abuse follows the general principals of substance abuse, with particular attention to psychological and social aspects. Marijuana may be one of many drugs abused, and total abstinence from all psychoactive substances (with the exception of caffeine) is the treatment goal. Interventions may include psychiatric evaluation, occupational and family assessment, and implementation of a comprehensive treatment plan.

Psychological issues (eg, denial, minimization, rationalization) must be confronted. Often, cessation of drug use and subsequent cognitive improvement result in self-motivation and changes in the occupational and social well-being of the patient. Lifestyle changes, such as avoiding drug-related situations, may be encouraged.

Identify and address low self-esteem, mood disorders, family problems, and other stresses.

One-to-one therapy, group therapy, and even hospitalization may be necessary components of the treatment plan. (Patients with uncomplicated marijuana use in the absence of other psychiatric or medical problems are rarely hospitalized.)

School-based programs and peer-led groups may be useful in primary prevention of marijuana abuse.

Voucher-based reinforcement of marijuana abstinence among individuals with serious mental illness has proven effective.

Much has been made about marijuana as a “gateway drug.” Under this theory, one would expect a sequential initiation of drug use progressing from licit substances such as alcohol and tobacco to cannabis and moving on to other illicit substances. However, a study conducted across diverse countries and cohorts showed significant violations of this sequential gateway hypothesis and instead has demonstrated “that the strength of associations between substance use progression may be driven by background prevalence rather than being wholly explained by causal mechanisms.”[33]

Gateway violations, such as use of illicit substances prior to cannabis use, were highest in countries with the lowest rates of prevalence of cannabis use, with similar findings of gateway violations associated with alcohol and tobacco in countries with low prevalence rates of use for alcohol and tobacco. Further, the risk for later development of drug dependence may be more affected by the extent of prior use of any drug and the age of onset at which that use began. The implications of this information for drug abuse prevention would imply that prevention efforts may be most effective not simply by targeting drugs perceived to exist earlier in the “gateway” chain, but by efforts designed to prevent all drug use.[33]

As with all efforts to prevent drug abuse, straight-forward education on the risks associated with cannabis may be most effective. Given the increasing ease of access to marijuana, its increasing prevalence of use, and changing societal views, which seem to reflect its increasing acceptance, the scare tactics of old, which attempted to illustrate "reefer madness” may be perceived as out of touch, inaccurate, and therefore ineffective.

Follow-up care should be comprehensive and involve specialist services such as those provided by drug treatment units.

Treatment includes behavior therapy (aimed at reducing the chances of reexposure and establishing coping mechanisms to resist further use); family, group, and individual therapy; and periodic testing of urine to monitor abstinence.

Narcotics Anonymous (NA) is a self-help group organized on principles similar to Alcoholics Anonymous and is useful in helping addicts maintain abstinence.

Adolescent drug programs usually focus on promoting communication skills and age-appropriate behaviors.

Inpatient hospitalization for the treatment of cannabis abuse or dependence is not recommended. Additionally, inpatient treatment is not recommended for cannabis withdrawal syndrome (CWS), as CWS is only expected to occur in a subgroup of users, even among heavy, chronic users.[28]

Short-term, low-dose benzodiazepines for treatment of significant anxiety associated with acute intoxication has been used. Clinicians are advised to use caution when administering benzodiazepines for the treatment of cannabis-induced anxiety, as the anxiety will invariable resolve with no medication over a short period. Drug therapies that diminish cravings for marijuana or intoxicating effects from marijuana use are currently not available.

Overall, a dearth of empirical research has focused on the role of pharmacotherapy in the treatment of cannabis dependence. A double-blinded trial examining the role of nefazodone dosed at 300 mg twice daily and bupropion-SR dosed at 150 mg twice daily demonstrated that neither medication was effective at increasing abstinence or reducing withdrawal symptoms among patients seeking treatment for cannabis dependence.[32]

Class Summary

These agents depress all levels of CNS, which, in turn, reduces anxiety symptoms.

Lorazepam (Ativan)

Lorazepam is used for acute marijuana-associated panic or anxiety symptoms. Monitor vital signs carefully after administration. Watch for respiratory depression, ataxia, and somnolence/excess sedation. Amnesia may follow administration. Effects usually last 5-8 hours. Lorazepam is a sedative hypnotic with a short onset of effects and relatively long half-life. Increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, may depress all levels of the CNS, including limbic and reticular formation. When the patient must be sedated for more than 24 hours, this medication is excellent.