#56974: Cannabis and Cannabis Use Disorders

Analyses of several adoption, family, and twin studies that examined the relationship between cannabis use and heritable factors determined that the use of cannabis (and other licit and illicit substances) is due in part to genetic vulnerability and an overlap of environmental influences [28,29]. There appear to be substantial genetic influences on measures of cannabis involvement that correlate with progression to greater levels of addiction, and an individual's vulnerability to cannabis abuse/dependence is shaped by a common susceptibility to multiple substance abuse and also by risk factors unique to cannabis. Researchers in one twin study clarified the basics of this theory in their conclusion, stating that genetic factors predispose individuals to substance use/abuse whereas environmental experiences determine which class of psychoactive substances a predisposed individual will prefer over another [30]. In a meta-analysis evaluating the relative magnitude of the influence of genetic and environmental factors on problematic cannabis use, researchers estimated that the proportion of the total variance attributable to genetics was 51% in men/boys and 59% in women/girls [29].

The euphoriant potential of cannabis is probably the single most important characteristic in sustaining its widespread and often chronic recreational use. This effect varies greatly with dose, route of administration, expectation, environment, and personality of the user. However, dysphoric reactions to cannabis are not uncommon. In some cases, use may result in severe anxiety and panic, unpleasant somatic sensations, and paranoia. Anxiety-panic reactions are the most common adverse psychological effects of cannabis use. Flashbacks, whereby the original drug experience (usually dysphoria) is re-experienced weeks or months later, are possible and may represent a psychological reaction similar to that of post-traumatic stress disorder [45].

Following an initial period of excitement after acute ingestion of cannabis, a generalized CNS depressant effect is observed. This may lead to drowsiness and sleep toward the end of a period of intoxication [45].

The changes in perception that result from cannabis and THC affect all sensory modalities. Color and sound perception may be heightened, and musical appreciation may be increased. Temporal and spatial perception is distorted, impairing judgment of distance and time. Even after small doses, persons under the influence of cannabis consistently overestimate the passage of time. Persistent visual changes, some lasting for months, have been documented [45].

As noted, the initial period of excitement and increased motor activity after cannabis ingestion is followed by a state of physical inertia, with ataxia, dysarthria, and general incoordination possibly lasting for several hours. Motor performance, including measurements of body sway, tracking ability, pursuit motor performance, hand-eye coordination, reaction time, and physical strength, is demonstrably impaired [45].

The effects of cannabis on cognitive processes are characterized initially by subjective feelings of accelerated speed of thought, flight of ideas that may seem unusually profound, and a crowding of perceptions. Higher doses can result in out-of-control thoughts, fragmented thinking, and mental confusion. Cannabis is associated with short-term memory deficits; it is believed that these deficits may be caused by an attention deficit combined with an inability to filter out irrelevant information and the intrusion of extraneous thoughts. Memory lapses may contribute to the distortion in the perception of time and poor psychomotor performance in complex tasks [45].

Even low doses of THC (5–15 mg) can significantly impair an individual's ability to perform complex or demanding tasks, including those involved in fine hand-eye coordination, complex tracking, divided attention tasks, visual information processing, digit code tests, and alternate addition-subtraction tasks [45]. Psychomotor performance further deteriorates at higher doses, and impairment can persist several hours following a single dose [45].

Cannabis typically decreases aggression and increases sociability. However, some individuals, particularly those under stress and predisposed to violence, become aggressive after taking cannabis. Research has shown that cannabis users with a history of aggression have a 60% greater likelihood of perpetrating partner violence than nonusers [89]. Violent behavior may be more common among those with acute paranoid or manic psychosis induced by cannabis and polydrug use [45].

Cannabis use can lead to a range of short-lived psychiatric symptoms, including depersonalization, derealization, a feeling of loss of control, fear of dying, irrational panic, and paranoid ideas [90]. After taking a large dose of THC, vulnerable or heavy users may temporarily experience a form of drug-induced psychosis [91]. This is classified in the DSM-5-TR as cannabis intoxication with perceptual disturbances or as a substance-induced psychotic disorder and is diagnosed if the hallucinations are not better explained by another medical or mental disorder and if the symptoms appear during or within two hours of substance use or withdrawal [6]. The frequent use and rising potency of cannabis suggest that young people may have their first episode of psychosis earlier than historically usual [91].

Cannabis-induced psychosis has the potential to require hospital admission. During the initial diagnosis, this psychosis may be misidentified as schizophrenia, as patients may display characteristic schizophrenic symptoms, such as delusions of control, grandiose identity, persecution, thought insertion, auditory hallucinations, altered perception, and blunted affect [86].

Acute doses of cannabis may induce tachycardia with peripheral vasodilatation, which can result in postural hypotension and a slight decrease in body temperature. Cardiac output may be increased by as much as 30%, accompanied by increased cardiac work and oxygen demand. Because of this, cannabis can aggravate pre-existing heart disease. The absorption of relatively large amounts of carbon monoxide from smoking cannabis also contributes to the long-term cardiovascular risk of chronic cannabis use [45]. Reddening of the conjunctivae, a characteristic sign of cannabis use, is the result of widespread vasodilation [41].

Cannabis smoke contains many of the same constituents as tobacco smoke (minus the nicotine), including bronchial irritants, tumor initiators (mutagens), tumor promoters, and carcinogens. The tar from cannabis smoke also contains higher concentrations of the carcinogens benzanthracenes and benzopyrenes than tobacco smoke tar. Smoking a cannabis cigarette results in inhalation of three times the amount of tar of a tobacco cigarette, and respiratory tract retention is greater than smoking a tobacco cigarette. As a result, cannabis use may result in impairment of lung function, leading to airflow obstruction and hyperinflation [41,45].

Although many carcinogens and tumor promoters are common to tobacco and cannabis smoke, differences in the active constituents result in different biologic outcomes. Molecules in tobacco smoke enhance carcinogenic pathways through several mechanisms. In contrast, molecules in cannabis smoke inhibit carcinogenic pathways through down-regulation of immunologically generated free radical production (the innate response to inhaled smoke and particulate); THC blockade of enzymatic conversion of smoke constituents into carcinogens; the absence of cannabinoid receptors in respiratory epithelial cells (which maintains DNA damage checkpoint mechanism integrity with prolonged cannabis smoke exposure); and the anti-angiogenic, tumor-retardant, and anti-inflammatory activity of many cannabinoid smoke constituents [93]. Large studies assessing the potential risk of lung cancer with chronic cannabis use have reached different conclusions, with one finding no increased risk and another reporting a twofold increase in the risk of lung cancer among long-term heavy users [94,95]. Additional research is necessary to parse these findings.

A University of California, San Francisco, study found that vaporizing cannabis eliminates many of the harmful combustion byproducts (e.g., benzene, naphthalene, toluene, other aromatic hydrocarbon toxins) and greatly reduces tar and carbon monoxide from the inhaled charge [43]. Therapeutic plasma THC levels are slightly increased with this administration, and it was determined that vaporizing cannabis is safer than smoking.

Cannabinoids, including THC, bind to androgen receptors, and cannabis is considered antiandrogenic. However, the drug's effects on fertility are unclear. Chronic cannabis ingestion appears to have negative effects on sperm quality (e.g., a reduction in the volume and number of spermatozoa, changes in morphology and motility) [96]. In women, regular cannabis smoking may be associated with suppression of ovulation. Chronic use may cause galactorrhea in women and gynecomastia in men. Endocrine changes resulting from cannabis use may be significant in prepubertal users, in whom cannabis use may suppress sexual maturation as well as social and personal development and learning of coping skills. There is no evidence of teratogenicity during pregnancy, but some studies suggest low neonatal birth weight from chronic maternal cannabis smoking, possibly related to fetal hypoxia and placental complications [41,45]. In a large study, prenatal cannabis use was associated with significantly greater odds of low birth weight and small for gestational age, but not preterm birth [129]. This effect was particularly marked among heavy users (weekly or more frequent).

There is some evidence that offspring of mothers who consumed cannabis during pregnancy may be at increased risk for behavioral and conduct problems, impaired executive functioning, and poor school achievement [97]. In addition, adolescents who regularly use cannabis may have impairments of learning and personal development. However, the possible effects of cannabis consumption on educational performance are difficult to demonstrate [90]. As noted, social development and the acquisition of coping skills may also be stunted. In one study, onset of cannabis use before 17 years of age was associated with a significantly increased risk of cannabis dependence, use of other illicit drugs, suicide attempt, depression, and welfare dependence by 30 years of age [98].

Although there is little evidence to support a correlation between depression and infrequent cannabis use, a modest association between early-onset or heavy, habitual cannabis use and later depression has been reported [105]. Because there is little evidence of an increased risk of later cannabis use among patients diagnosed with depression, the self-medication hypothesis is not supported. However, research has shown that depression and chronic use of cannabis are associated, and evidence indicates that heavy cannabis use may increase depressive symptoms in some users. It is important to note that this correlation may be the result of common social, family, and contextual factors that increase the risk of both heavy cannabis use and depression. Overall, heavy cannabis use appears to play a minor role in explaining population rates of depression [106].

Healthcare professionals have observed a possible association between habitual cannabis use and psychosis for many years. However, there is considerable disagreement regarding the degree of causation attributable to cannabis use in the development of psychosis among users without an obvious vulnerability to this effect (e.g., genetic factors).

There is biologic evidence of a possible causal relationship between cannabis use and psychosis, particularly in relation to non-affective schizophrenia-spectrum disorders [107,108]. When administered intravenously, delta-9-THC has been found to induce dose-dependent positive and negative psychotic symptoms in individuals with schizophrenia; an interaction between cannabis use and a polymorphism of the catechol-o-methyltransferase gene that codes for dopamine has also been reported [107].

In theory, cannabis use may precipitate a psychosis in several ways [90]:

Based on the literature, it is likely that cannabis use induces psychotic disorders in vulnerable individuals, defined as those with a history of unusual experiences that may be in part genetically mediated [107]. The relationship between cannabis use and vulnerability may explain the small (two to three times) increase in risk for psychosis among cannabis users. This interaction has also been used to elucidate the lack of large increases in the incidence rates of psychoses to correspond with the increase in cannabis use rates among young adults and the earlier age of onset of schizophrenia-form disorders in cannabis users [107].

There appears to be at least some evidence linking cannabis use to the development of psychotic disorders, but some argue that the studies have been flawed. Criticisms of studies linking cannabis and psychosis include failure to separate organic and functional psychotic reactions to cannabis; insufficient discrimination between psychoses; and lack of weighing the evidence for and against the category of cannabis psychosis [90]. Although there is evidence to support the belief that cannabis use may contribute to psychosis in certain circumstances, the possible causal mechanisms are complex [90].

A review of evidence from multiple trials demonstrated a likely causal relationship between cannabis use (particularly frequent, chronic use) and psychotic illness, particularly schizophrenia-spectrum disorders [108]. Furthermore, onset of psychotic symptoms in persons with schizophrenia is earlier (by 2.7 years) in those who use cannabis than in nonusers [108]. The first psychotic episode in cannabis users is more likely to present with positive symptoms (e.g., hallucinations, delusions) than negative symptoms (e.g., apathy, social withdrawal) than first episodes in individuals who do not use cannabis.

One study recruited 97 volunteers with psychosis (i.e., schizophrenia, schizoaffective, or bipolar psychosis) and 64 controls. Participants were categorized using history of cannabis use into nonusers, adolescent-onset users, and late-onset users. The researchers were testing the hypothesis that individuals with psychosis and a history of adolescent cannabis use would have better global neuropsychological performance compared with those with psychosis and no cannabis use history. Neuropsychological performance was measured using the Brief Assessment of Cognition in Schizophrenia (BACS) battery. Scores were significantly higher in individuals with psychosis and adolescent cannabis use compared with those with psychosis and no prior cannabis use. Adolescent cannabis use was associated with better cognitive function in schizophrenia but not bipolar psychosis [109].

Researchers have linked new high-potency cannabis strains with increased emergency admissions for psychosis, implicating not only higher levels of THC but also the absence of CBD, which ordinarily tempers the psychotomimetic effects of THC [110,111]. A British study noted that the typical cannabis product available in the United Kingdom before 2000 was hashish resin, containing essentially equal parts THC and CBD (each up to 4% by weight), and that the typical high-potency herbal cannabis that now dominates the market contains 12% to 18% THC and less than 1.5% CBD. (This is also typical of cannabis available in the United States, particularly strains grown in California [112].) Researchers suspect that the rise in admissions for psychosis is related to this shift. The study concluded that individuals with a longer duration of use and with a preference for high-potency cannabis are at a much greater risk for enduring psychosis than individuals who occasionally smoke hashish [110]. This is supported by research showing that cannabis psychosis is THC dose dependent and that CBD can reverse indicators of THC-induced psychosis in test subjects [111,113].

There has also been criticism of the belief that chronic heavy cannabis use leads to an amotivational syndrome, described as personality deterioration with loss of energy and drive to work [90]. Some have argued that the supporting evidence for this theory largely originates from uncontrolled studies of long-term cannabis users in various cultures and may be a reflection of ongoing intoxication in frequent users of the drug [90]. More research in this area is required.

One study used a two-round design to rule out concomitant risk factors responsible for the connection from marijuana intake to lower general self-efficacy. A total of 505 college students completed measures of marijuana use, demographics, personality, other substance use, and general self-efficacy in two assessments one month apart. Marijuana use forecast lower initiative and persistence, even after ruling out baseline covariates (e.g., demographics, personality traits, alcohol or tobacco use, self-efficacy) and taking into account the precedence of the processes (e.g., initiative, effort, persistence, alcohol, cigarette and marijuana use). Results showed that only marijuana intake significantly and longitudinally prompted lower initiative and persistence, providing partial support for the marijuana amotivational syndrome, underscoring marijuana as a risk factor for decreased general self-efficacy and offering insights into future research [114].

Cannabis use has also been linked to the development of panic disorder [115]. A study involving 1,000 people 18 to 25 years of age found that 22% reported panic attacks or anxiety symptoms during cannabis intoxication, with women twice as likely as men to report these symptoms [90]. Conversely, in a study of nearly 7,000 adults, the presence of social phobia and panic disorder predicted progression from casual use to cannabis use disorder [116].

An individual's experience of cannabis intoxication may be variable; the same person given the same dose at different times may report different subjective effects. Although many users report a calming, tranquilizing effect, cannabis use may provoke feelings of anxiety or panic in some cases. For patients for whom cannabis use induces panic, a history of previous panic attacks (while sober) may not be present. A study of 66 panic disorder patients found that 24 experienced their first panic attack within 48 hours of cannabis use [117]. It has been suggested that cannabis may provoke anxiety reactions via gamma-aminobutyric acid (GABA) antagonism, which may provoke CNS excitatory neurotransmission and brain hyperexcitability.

Ingestion of high doses of delta-9-THC produces intense anxiety in nearly all users predisposed to anxiety, and the high THC:CBD ratio of cannabis available today may lead to a rise in anxiety/panic disorders among cannabis users in general [112]. In fact, studies indicate that CBD alone has promise in the treatment of social anxiety [118].

Antisocial behavior commonly occurs among cannabis users, and this is particularly evident among adolescent users. Adolescents who use cannabis regularly are at risk of experiencing delinquency, school failure, physical and psychological problems, and selling illegal drugs [19].

Cannabinoid hyperemesis syndrome (CHS) is characterized by severe cyclic nausea and vomiting in chronic (usually heavy) cannabis users [119]. It is a relatively rare adverse effect, but increasing case reports have been noted with the liberalization of cannabis in several states [120]. Individuals with CHS experience temporary relief of symptoms with hot baths or showers, and compulsive bathing is often an identifying feature (differentiating the condition from other causes of cyclic vomiting) [121]. Typically, patients begin with recurrent nausea and progress to intense, persistent vomiting with continued use of cannabis.

The underlying pathogenesis of CHS is unclear, although several theories have been presented. One theory is that the enteric emetic effects of cannabis (e.g., decreased gastrointestinal motility) may promote emesis by over-riding the antiemetic effects mediated by the CNS [121]. Symptoms resolve with cessation of cannabis use; relapse to use often results in a recurrence of the syndrome.

As cannabis withdrawal symptoms may be a factor contributing to continuing cannabis use, medications alleviating these symptoms could be useful. Unfortunately, there is little research completed that evaluates the effectiveness of potential treatment medications on cannabis withdrawal in humans. According to completed studies, no medication, including selective serotonin reuptake inhibitors, mixed-action antidepressants, atypical antidepressants, anxiolytics, and norepinephrine reuptake inhibitors, has been shown to definitively decrease cannabis use by humans [3,137,138,139].

There is some evidence that bupropion may be effective in lessening the symptoms of cannabis withdrawal [140]. Bupropion facilitates abstinence from cigarette smoking, in part through its ability to decrease negative mood symptoms, and because similar mood symptoms have also been associated with cannabis withdrawal, it was suggested that this medication may have a place in the treatment of cannabis withdrawal. The authors of one study found that bupropion resulted in less craving for the drug, but other studies have reported worsened mood and continued sleep difficulties, possibly caused by bupropion-associated enhanced norepinephrine activity [3,140,141]. A 2019 systematic review found that bupropion was likely of little value in the treatment of cannabis dependence [137].

Other researchers have evaluated the role of nefazodone because of its demonstrated effectiveness in clinical populations with conditions also associated with cannabis withdrawal, including depression, agitation, and anxiety. In a 2009 study, nefazodone decreased irritability and the severity of cannabis dependence, but it is unclear if these effects would ultimately result in improved long-term abstinence [141].

A third study evaluated the effectiveness of divalproex, which was chosen for testing based on evidence of successful treatment of some symptoms associated with cannabis withdrawal, such as irritability and mood lability [3,142]. Divalproex was not found to positively affect cannabis withdrawal symptoms; in fact, many withdrawal symptoms (e.g., anxiety and irritability) increased compared to placebo. Divalproex also resulted in psychomotor performance disruptions. Most small studies to date find little relevant effect of divalproex for cannabis withdrawal symptoms [143].

Treatment of cannabis withdrawal with gabapentin has shown some promise in a pilot clinical trial [139]. Although the dropout rate was very high (72%), 1,200 mg per day significantly reduced withdrawal symptoms compared to placebo and resulted in decreased cannabis use among those participants that remained [144].

Another agent evaluated for its effect on attenuating cannabis withdrawal is dronabinol (oral delta-9-THC) [142]. Use of dronabinol in the treatment of withdrawal symptoms is based on the concept of substituting a longer-acting, pharmacologically equivalent drug for the abused substance to stabilize the patient, with the intent to gradually withdraw the substituted drug. Oral delta-9-THC is successful in markedly reducing withdrawal symptoms, including self-reports of drug craving, anxiety, misery, anorexia, and sleep disturbance [145]. Although use of dronabinol is associated with improved withdrawal symptoms and treatment retention, it has not been shown to reduce cannabis self-administration [145]. Another 11-week trial examining the effects of dronabinol on cannabis use disorder showed no statistical difference between the placebo group and those receiving dronabinol combined with motivational enhancement and relapse-prevention therapy [146]. However, there was a reduction in both groups, likely due to the addition of behavior therapy.

An issue of potential concern related to treating cannabis-dependent patients with dronabinol is the abuse potential. Abuse liability is influenced by the neurochemical effects as determined by the route of administration, drug concentrations, and the maximum drug concentrations. Thus, administration of dronabinol would be expected to produce much less reinforcement than smoked cannabis. Another advantage is that, unlike smoked cannabis, dronabinol is not associated with adverse pulmonary effects. Considering all of these factors, the benefits of dronabinol in the treatment of cannabis withdrawal appear to outweigh potential risks [3].

One study compared the treatment efficacy of oral dronabinol and the synthetic THC analogue nabilone [147]. The results showed that nabilone has a longer time to peak effect, is more sustained, has fewer negative cognitive effects, and results in greater mood enhancement characteristics compared to dronabinol. Also, the effects are more dose-related, perhaps making it the better option for cannabinoid-replacement withdrawal treatment. Although dronabinol also decreases symptoms of cannabis withdrawal, the drug is ineffective in preventing relapse [147]. Researchers hope nabilone can prove effective for both purposes in clinical trials.

A small study (11 participants) of daily cannabis users found that nabilone decreased reversed withdrawal-related irritability, sleep disturbances, and anorexia, though psychomotor skills were impaired [18]. Nabilone (8 mg per day) also decreased the rate of relapse, indicating the need for further research [18]. Another small study of 11 non-treatment-seeking participants examined the effects of zolpidem (a sedative hypnotic) versus a zolpidem/nabilone combination on three factors, each tested in a different phase of the study. Withdrawal-related symptoms were decreased in both groups, and the combination drug (zolpidem/nabilone) showed decreases in self-administration of cannabis but small increases in certain abuse-related subjective capsule ratings [21]. More research is needed to determine the effectiveness of nabilone alone or in combination with other drugs.

In another study, 25 adult outpatients were randomized to either six weeks of placebo or divalproex, then switched to the alternate treatment for an additional six weeks. No significant between-groups differences were found in regards to treatment retention, with 38% of divalproex subjects and 33% of control subjects completing the entire study. Persons started on divalproex did not display better outcomes in terms of improvement in cannabis use or psychological symptoms than those started on placebo. All 25 patients had low blood levels of the study medications, suggesting poor compliance. However, retention during the first eight study weeks was high (>75%), suggesting the medication was discontinued because it was poorly tolerated in this population [21]. Other medications studied for alcohol relapse prevention, including buspirone, baclofen, and mirtazapine, have proven ineffective for cannabis relapse prevention [25,37,137].

N-acetylcysteine (NAC), an over-the-counter supplement, has been studied in adolescents with cannabis use disorder [139]. NAC is thought to reinstate normal glutamate activity that is disrupted by chronic cannabis use. The participants who received NAC (1,200 mg twice daily) and contingency management were more than twice as likely to have a negative drug screen compared to those receiving only contingency management [38]. However, a 12-week trial of NAC in more than 300 adults with cannabis use disorder did not show the same results. When compared to placebo, the NAC group had no statistically significant reduction in the results of urine cannabinoid tests [42]. Further research into the efficacy of NAC with regard to adolescents versus adults is warranted.

Although clozapine is known to be effective in the treatment of patients with schizophrenia and substance use disorders, its side effect profile limits its clinical utility. A small pilot study comparing clozapine and the second-generation antipsychotic ziprasidone, both agents were found to decrease cannabis use [44]. Ziprasidone was associated with fewer side effects and better compliance with treatment than clozapine. The American Psychiatric Association recommends that patients diagnosed with schizophrenia and cannabis use disorder should be offered pharmacotherapies effective for the treatment of cannabis withdrawal and relapse prevention in addition to psychotherapy [46].

Cannabis users seeking therapy to quit may participate in standard counseling that is typically offered in community-based substance abuse clinics. Individual drug counseling emphasizes abstinence from cannabis and other drugs through use of self-help groups and a 12-step approach [31].

Contingency management (CM) approaches to adult substance abuse are effective behavioral interventions to increase drug abstinence and other treatment goals when integrated with other effective psychosocial treatments [47]. Essentially, CM interventions use reinforcement or punishment contingencies to increase or decrease the frequency of predetermined therapeutic and behavioral objectives [19]. Contingency management programs have been found effective to decrease rates of relapse among patients in treatment for cannabis use disorders [47].

Relapse prevention assists patients with decreasing their vulnerability to relapse by addressing topics such as lifestyle balance and managing high-risk situations [135].

Social support is based on the necessity of group support for change. Topics discussed in the group setting include getting and giving support, dealing with denial and mood swings, and interacting with peers who continue to use cannabis [135].

In brief motivational interviewing, a therapist provides feedback from a comprehensive assessment using motivational interviewing techniques. The therapist also instructs subjects on cognitive-behavioral therapy (CBT) techniques that could be used to abstain from cannabis use [48,135].

One study compared a cognitive-behavioral relapse-prevention treatment; a brief, two-session motivational intervention; and a delayed-treatment control group [48]. The active treatment interventions resulted in greater reductions in cannabis use than delayed treatment. Four months post-intake, participants in the two active groups reported reduced cannabis use compared to the delayed treatment group, reductions in frequency of use per day, lower number of dependence symptoms, and fewer problems related to cannabis use. At 16-month assessment, cannabis use increased in both active treatment groups but was lower than pretreatment levels. Urine drug screens were not obtained, and all drug use data was based on self-report and collateral verification.

In another study, 136 cannabis-dependent adults, 18 to 25 years of age, referred by the criminal justice system, were randomized to one of four treatment conditions. CM consistently produced positive effects in terms of treatment retention and cannabis use, both of which were specifically targeted. There were few significant main effects for motivational enhancement therapy/cognitive-behavioral therapy (MET/CBT) over drug counseling. However, additional analysis suggested that a combination of CM and MET/CBT resulted in better outcomes than MET/CBT without CM and drug counseling plus CM. All three treatments were found to be significantly more effective than drug counseling without CM. Participants assigned to MET/CBT continued to reduce the frequency of their cannabis use through a six-month follow-up. The study population was noteworthy in that the participants were primarily young African American men with an average of five arrests by 21 years of age, 43% of whom met diagnostic criteria for antisocial personality disorder. Most had not completed high school and were unemployed [31].

In another study, efficacy of two brief interventions for cannabis-dependent adults across three study conditions was compared: two sessions of MET; nine sessions of multicomponent therapy (MET, CBT, and case management); and a delayed treatment control. The study followed 450 adult cannabis smokers with a diagnosis of cannabis dependence at baseline who were evaluated at 4, 9, and 15 months following treatment assignment. The nine-session intervention produced superior outcomes compared with the two-session treatment in terms of reductions in cannabis use and its consequences up to 12 months following treatment termination. The two-session treatment was more effective in use reduction than the control. Overall, the findings suggest that both substance abuse treatment programs and behavioral healthcare providers should consider making cannabis-specific treatment more available and accessible. The authors also conclude that cannabis-focused treatments may be necessary for this population to achieve abstinence or to significantly reduce cannabis use. Complete abstinence is not the only clinically meaningful outcome of treatment, and when given the opportunity, many cannabis abusers respond to treatment primarily by cutting back rather than quitting entirely [134].

A study of 90 cannabis-dependent adults seeking treatment randomly assigned participants to receive CBT, abstinence-based voucher incentives, or a combination of CBT and vouchers for 14 weeks. The authors found that, during treatment, abstinence-based vouchers were effective for facilitating prolonged periods of cannabis abstinence. CBT did not contribute to during-treatment abstinence, but it did enhance the post-treatment maintenance of the initial positive effect of vouchers. These results indicate that abstinence-based vouchers are a valuable treatment option, the use of which leads to greater rates of cannabis abstinence during treatment in comparison with a commonly used CBT for cannabis dependence [51].

The American Psychiatric Association notes that treatment of cannabis use disorder with CBT and MET may be improved with the concurrent use of CM strategies [46]. Combined treatment results in improved initial and long-term abstinence.

Approximately 3.9 million high school students (15.8%) used cannabis at least once in 2019 [9]. Among the 1.1 million adolescents who did not receive substance use treatment in the past year, 98.5% did not feel that they needed treatment, 0.9% felt that they needed treatment but did not make an effort to obtain it, 0.6% felt that they needed treatment and made an effort to obtain it, and only 1.5% felt that their use was problematic and sought help/treatment [8]. These findings suggest the need for interventions to increase motivation for change and encourage treatment entry for this population.

One study of the efficacy of psychosocial treatments in this patient population included 97 adolescents who had used cannabis at least nine times in the previous month. Participants were randomized to either an immediate two-session motivational enhancement intervention or a three-month delayed treatment control. The majority (two-thirds) of the sample described themselves as in the pre-contemplation or contemplation stages of change regarding cannabis use. Cannabis use and negative consequences were assessed at baseline and at three-month follow-up, and the assessment battery was carefully constructed to not appear biased toward demanding change. Both groups significantly reduced cannabis use at the three-month follow-up, with an overall reduction in cannabis use by 16% (6 fewer days) over a 60-day period. Although reductions were modest and no differences between treatments were observed, the study succeeded in recruiting non-treatment-seeking adolescent cannabis smokers who were predominantly in the early stages of readiness for change, overcoming barriers in reaching adolescents who were frequent cannabis users [52].

Kamon et al. reported the results of a 14-week feasibility study of family-based CM with 19 adolescents 15 to 18 years of age [19]. The intervention consisted of a clinic-administered, abstinence-based incentive program; parent-directed CM targeting substance use and conduct problems; a clinic-administered incentive program targeting parental participation; and individual CBT for the adolescent patients. Twice-weekly urine and breath testing was conducted to monitor substance use. The adolescents attended an average of 10.3 of 14 weekly sessions; parents attended an average of 10.6 sessions. By the end of treatment, substance use, externalizing behaviors, and negative parenting behaviors had decreased. Based on results of the urine testing, abstinence increased from 37% at intake to 74% by the end of the study period; 53% of adolescents were abstinent 30 days post-treatment. The efficacy of a family-based CM model to treat adolescent substance use and conduct problems was demonstrated [19].

Cannabis is the most commonly used illicit drug among persons with mental illness and is associated with increased rates of recurrent psychiatric symptomatology and relapse [53]. Among adults 19 years of age or older in 2019, those with a past-year serious or any mental illness were more likely than those without mental illness to be users of marijuana (39.8% and 32.5% vs. 14.2%) [9]. Unfortunately, the amount and quality of research regarding the psychosocial treatment of these patients is limited. In one study, researchers conducted a randomized, single-blind controlled comparison of routine care with a program of routine care integrated with motivational interviewing, cognitive behavior therapy, and family or caregiver intervention in patients with comorbid schizophrenia and substance use disorder (including cannabis misuse) [53]. They found that the integrated treatment approach resulted in significantly greater improvement in patients' general functioning than routine care alone at the end of treatment and at one year follow-up [53]. Longer and more intensive treatment may be necessary for dually diagnosed patients, particularly those with chronic mental illness [54]. Randomized controlled trials of interventions within "real world" mental health systems among adults with severe mental disorders suggest that cannabis use is amenable to treatment in these settings among people with psychotic disorders. Additionally, trials of guided interventions among cannabis users indicate that while brief interventions are associated with reductions in cannabis use, longer interventions may be more effective. These trials suggest that treatment with antipsychotic medication is not associated with a worsening of cannabis cravings or use and may be beneficial [60]. More research with this population is necessary in order to draw definitive conclusions.

Relative to the more established AA, there are few studies published on NA. However, the studies that have been conducted reveal important information about how NA functions to help the new member abstain from drug use.

Improvement in psychological functioning as a result of NA involvement has been observed [80]. Studies have shown that individuals who have been off drugs and involved with NA for longer periods tend to have lower trait anxiety and higher self-esteem scores. Those who are abstinent for more than three years exhibit levels of anxiety and self-esteem similar to the general population [80].

Being active as an NA sponsor over a one-year period has been found to be strongly associated with substantial improvements in sustained abstinence rates, which suggests that providing direction and support to other newer addicts is a way to enhance the likelihood of one's own abstinence [82].

One study sought to explore the factors related to treatment retention in NA members [92]. The authors interviewed 12 NA members who had been recovered for more than two years. After gathering (and analyzing) data through purposeful sampling and recording and transcribing participants' interviews, two main areas related to treatment retention were revealed: personal-psychological factors (e.g., self-knowledge, change of attitude, self-confidence) and social factors (e.g., interaction with others, reforming social/familial relationships, receiving support). The authors concluded that providing the necessary special care and support following the user's elimination of physical attachment would lead to elimination of psychological dependence as well [92].

Marijuana Anonymous (MA), a self-help program specific to persons with a desire to stop using cannabis, was formed in California in 1989 by cannabis addicts who felt their addiction to cannabis was not taken seriously in other 12-step meetings. MA is modeled after AA and NA, and members use the same 12-step model. MA meetings can be found in 36 states in the United States and in many countries [99].

In a study of 1,288 male patients, participation in a 12-step program predicted maintenance of cannabis abstinence and the re-initiation of abstinence after a relapse [122]. Participation in 12-step groups during and after treatment has been associated with positive outcomes among substance users, including cannabis-dependent patients [123]. Clinicians should encourage 12-step group participation as an aspect of treatment. A study conducted by Laudet identified two major obstacles to 12-step program participation: motivation and readiness for change and the perceived need for help [123]. Other obstacles to participation include perceived convenience and scheduling issues. This underscores the importance of promoting motivation for change and the need to assess patient beliefs regarding experiences with 12-step programs on a case-by-case basis in order to find a good fit between patient needs and 12-step resources [123].