Cannabis: An Overview of the Empirical Literature


Marijuana (also referred to as cannabis) is a drug that is derived from the flowers, stems, leaves, and seeds of the hemp plant ( Cannabis sativa ). Cannabis is the generic term that refers to the psychoactive substances derived from the plant, including cannabis-like substances (e.g., synthetic cannabinoid compounds). In this chapter, we utilize the term cannabis, but it should be noted marijuana is used as frequently in the literature. The need for public health awareness and evidence-based clinical care for cannabis use and its disorder remains a major health care priority in the United States and beyond. Indeed, cannabis has been the most widely used illicit substance in the United States for the past 30 consecutive years, with approximately 12% of individuals 12 years of age or older having used cannabis in the past year. An estimated 9% of persons who have ever used cannabis will become dependent, with prevalence estimates of 17% among those who start using cannabis in adolescence and upwards of 50% among daily users. These rates in the United States represent a significant public health concern considering that several well-documented negative consequences have been associated with daily or weekly drug use (e.g., disrupted cortical development, increased risk of severe medical and psychiatric disease, increased risk of motor-vehicle accidents, and impaired lifetime achievement).

The overarching aim of the present chapter is to provide an overview of cannabis use and its disorder. The chapter is organized into seven sections. In the first section we describe the prevalence of cannabis use and cannabis use disorder. In the second section we clarify the nature of cannabis use in terms of its pharmacokinetics and acute intoxication features. The third section details the classification of cannabis use disorder using the current diagnostic nomenclature. The fourth section discusses the motivational bases for use of the drug. In the fifth section we provide a synopsis of some problems associated with cannabis use and disorder, including health problems, social problems, and psychological disturbances. The sixth section provides a summary of the scientific work focused on cannabis, the reasons for its use, and users’ relative success in quitting. In the final section, we describe some practically oriented clinical issues for primary care medical practitioners to consider in terms of the recognition and treatment of cannabis use and its disorder.


Cannabis has been the most widely used illicit substance for 30 consecutive years in the United States, with approximately 12% of individuals (12 years of age or older) having endorsed cannabis use in the past year. Of those who have ever used cannabis, nearly 9% of individuals will become dependent. Among those who initiated cannabis use in adolescence, an estimated 17% will become dependent, while 50% of daily cannabis users will become dependent. Probability estimates of transitioning from cannabis use to dependence indicate that cannabis is associated with a high rate of dependence potential. For example, the probability that cannabis users develop dependence is approximately 9%, half of whom develop dependence within 5 years after initial onset of cannabis use, which is faster than the transition of nicotine or alcohol dependence. Furthermore, greater levels of use are related to an increased risk for dependence. Studies suggest that the rate of dependence is 20%–30% among those persons using cannabis on a regular (weekly) basis. Cosubstance use with cannabis is common, and approximately 80% of cannabis users met criteria for an additional substance use disorder (e.g., alcohol, nicotine). It is important to note that the current prevalence estimates are based on the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition, Text Revision (DSM-IV-TR), which was revised in 2013 ( Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition [DSM-5] ). This update resulted in changes to the classification of disordered cannabis use, which may affect the prevalence estimates. However, to date, the bulk of the literature has naturally reported prevalence estimates prior to the update.

Of special relevance to clinical practitioners, many treatment and community studies have examined prevalence rates of cannabis use among different samples with a variety of medical and psychological problems. This is important given psychiatric comorbidity is associated with transition from cannabis use to dependence. For example, 23% of individuals seeking treatment for psychosis report cannabis use, with about half of that group misusing the drug. Cannabis use is associated with earlier first episode of psychosis, which is particularly evident in high-potency cannabis use. These findings are consistent with a recent meta-analysis indicating cannabis abuse/dependence is associated with increased likelihood of transition to psychosis in ultra-high-risk individuals. Another community-based study found that approximately 16% of patients with spinal cord injury used cannabis. Among individuals with current and lifetime chronic pain, the prevalence of past-month cannabis use was 22.9% and 34.9%, respectively. In addition, among HIV-infected individuals, past-month cannabis use is estimated to range from 23% to 65%. Cannabis use disorder is also common among military veterans, which may be underestimated due to underdiagnosis. Other work found that cannabis use is common among recently homeless individuals (16% ). Moreover, data indicate that cannabis use accounts for as much as 25% of the primary drug problems of individuals seeking residential drug treatment. Similarly, among adolescents seeking outpatient services for cannabis abuse or dependence, approximately 38% reported depression and 29% reported acute levels of anxiety. These studies suggest that cannabis use: (1) may be overrepresented among certain vulnerable populations and (2) is a primary clinical concern.

Nature of Cannabis Use: Pharmacokinetics and Acute Intoxication Features


Cannabis can be consumed via smoking (e.g., hand-rolled cigarettes, water pipes, nonwater pipes, vaporizers), ingestion (e.g., mixed into foods or used in the process of brewing tea), transdermally, or rectally. Cannabis shares some qualities with tobacco in that it is composed principally of plant material, often is used via smoking routes (e.g., pipes, joints), and contains a myriad of chemical compounds. Unlike tobacco, however, the active agents in cannabis are cannabinoids (unique to the marijuana plant). There are at least 100 different cannabinoids in marijuana, although the pharmacokinetics of most of these compounds is largely unknown. Of these, the most abundant cannabinoid is tetrahydrocannabinol (THC), which is considered responsible for the main psychotropic effects of cannabis. The THC content of plants from a range of sources and strains varies dramatically. With a focus on improved plant breeding and improved growing techniques, the THC content of cannabis has increased dramatically in a short period of time. As one illustrative example, THC content from a typical cannabis cigarette (joint) in the 1960s was 10 mg, whereas estimates suggest that it currently is around 1 g (or 150–200 mg). Cannabidiol (CBD) is another constituent in cannabis that lacks the same psychoactive effects as THC, and instead appears to act as an antagonist of some of the negative psychoactive effects of THC. Data indicate that CBD has a range of therapeutic effects including anticonvulsant, antipsychotic, analgesic, and neuroprotective properties. In addition, there is growing prevalence in the use of synthetic cannabis compounds, which include oral formulations (pill, capsules) of cannabis that are available for prescription (e.g., nabilone, dronabinol), and other nonmedical synthetic cannabinoids products (e.g., K2, spice).

Since the discovery of a cannabinoid receptor within the brain in the late 1980s, researchers have been able to explicate the process by which THC acts on the brain. Currently, there is evidence of three potential cannabinoid receptors, only one of which is located within the brain (the cannabinoid-1 receptor). When THC is inhaled into the body via cannabis smoking, it passes from the lungs into the bloodstream. Once in the blood, THC attaches to cannabinoid receptors, such as the cannabinoid-1 receptor, adding to or reducing the naturally occurring endogenous ligands for these receptors (e.g., anandamide). The cannabinoid-1 receptor, in particular, has been found to mediate both neurochemical and behavioral properties of these cannabinoids, including tolerance. It also is noteworthy that THC and other cannabinoids move rapidly into fat and other bodily tissues but are released relatively slowly from these tissues back into the bloodstream. Eventually, cannabinoids are cleared from the body via urine and fecal matter, although elimination is relatively slow. The detection window in urine depends upon various factors, including drug dose, form of administration, duration/frequency of use, and individual differences in absorption, metabolism, and excretion. Specifically, urinary detection windows (via 11-nor-9-carboxy-THC [THCOOH] metabolite) ranges from several days in infrequent users to months in frequent users.

Acute Intoxication Features

THC can produce a range of acute psychosensory experiences including perceptual distortions (e.g., hallucinogenic properties), relaxation, anxiety, acute paranoia, inhibition, and so on. Periods of intoxication depend on use patterns and potency but tend to last for at least a few hours. The acute effects of THC also impair executive functioning, including working memory, attentional and information processing, and impulsivity, as well as psychomotor performance on complex, demanding tasks. There is a dose-dependent relation between THC and psychomotor and cognitive impairment, with higher doses being associated with more impairment for more demanding tasks. Although cognitive impairment for hours after exposure to THC is a well-replicated phenomenon in laboratory studies, there has been consistent debate about the permanent cognitive effects of THC. Data are mixed as to whether there are long-term effects of THC on impulsivity; however, attention and working memory appear to be largely unaffected. Although decision-making and risk-taking behavior are not consistently affected by acute intoxication, one study found that heavy cannabis users who abstained from cannabis use had impaired decision-making capacities and great risk-taking tendencies. The observed deficits appear to be more clearly documented among chronic, heavy cannabis users, relative to occasional or light users.

Classification of Cannabis Use Disorder

According to the DSM-5, cannabis use disorder is used to classify problematic cannabis use (see Table 24.1 for the diagnostic criteria for cannabis use disorder). Cannabis use disorder is a pattern of problematic cannabis use despite significant problems from use that produce cognitive, behavioral, and physiological symptoms due to continued cannabis use. These symptoms broadly reflect impaired control (symptoms 1–4), social impairment (symptoms 5–7), risky use (symptoms 8–9), and pharmacological criteria (symptoms 10–11). Unique to the current diagnostic formulation is the unidimensional diagnostic classification, which reflects a range of the disorders, from mild to severe in form. Specifically, three severity specifiers are used based on the number of symptoms present: mild (presence of 2–3 symptoms), moderate (presence of 4–5 symptoms), and severe (presence of 6 or more symptoms). This is in contrast to the prior diagnostic classification of cannabis use disorders in the DSM-IV-TR, which included two disorders that were designed to reflect harmful consequences of frequent use (marijuana abuse) relative to more severe compulsive use (marijuana dependence).

Table 24.1

Criteria for Cannabis Use Disorder.

  • A.

    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 resulting in a failure to fulfill major 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 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.

    • 10.

      Tolerance, as defined by either of the following:

    • (a) A need for markedly increased amounts of cannabis to achieve intoxication or desired effect

    • (b) Markedly diminished effect with continued use of the same amount of cannabis

    • 11.

      Withdrawal, as manifested by either of the following:

    • (a) The characteristic withdrawal syndrome for the cannabis ( see A and B of the criteria set for cannabis withdrawal, Table 24.2 )

    • (b) Cannabis (or closely related substance) is taken to relieve or avoid withdrawal symptoms

From APA. Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition (DSM-5). Washington, DC: American Psychological Association; 2013.

This change to the diagnostic classification was based in part on the limited empirical data that supported the validity of distinguishing marijuana abuse and dependence, and lack of scientific consensus for a marijuana dependence syndrome. Data indicate that the five most commonly endorsed symptoms are: hazardous use (24.8%), persistent desire/attempts to stop or cut down (15.9%), craving (13.9%), continued use despite interpersonal problems (10.7%), and neglect of work/school/home responsibilities (10.4%).

One additional change in the diagnostic classification of cannabis use disorder is the recognition of cannabis withdrawal syndrome (see Table 24.2 for list of common cannabis withdrawal symptoms ), which can contribute to difficulties in quitting cannabis. Based on the DSM-5-defined cannabis withdrawal symptoms, one study found that 11.9% of cannabis users met criteria for cannabis withdrawal, male relatives of female users were significantly more likely to report withdrawal symptoms (16.4% vs. 9.0%), and withdrawal symptoms are moderately heritable. Finally, the DSM-5 includes the addition of cannabis craving, or strong desire or urge to use cannabis.

Table 24.2

Cannabis Withdrawal (Criteria A and B).

  • A.

    Cessation of cannabis use that has been heavy or prolonged (i.e., usually daily or almost daily use over a period of at least a few months).

  • B.

    Three (or more) of the following signs and symptoms develop within approximately 1 week after Criterion A:

    • 1.

      Irritability, anger, or aggression

    • 2.

      Nervousness or anxiety

    • 3.

      Sleep difficulty (e.g., insomnia, disturbing dreams)

    • 4.

      Decreased appetite or weight loss

    • 5.


    • 6.

      Depressed mood

    • 7.

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

Data from Budney AJ, Hughes JR, Moore BA, Vandrey R. Review of the validity and significance of cannabis withdrawal syndrome. Am J Psychiatry . 2004;161 (11):1967-1977; Levin KH, Copersino MI, Heishman SJ, Liu F, Kelly DL, Boggs DL, et al. Cannabis withdrawal symptoms in non-treatment-seeking adults cannabis smokers. Drug Alcohol Depend . 2010;111(1):120-127.

Although limited research to date has examined the comparability of the previous and current diagnostic criteria, one study found considerable diagnostic agreement between DSM-IV and DSM-5 (92.9% agreement), although slightly higher prevalence estimates were observed in the DSM-5 definition relative to the DSM-IV (41.0% relative to 39.4%). However, this pattern of results has not been observed consistently. For example, lower diagnostic correspondence has been observed for cannabis use disorder (kappa range .43–.79 depending on the number of symptoms endorsed), and is less concordant relative to other substance use disorders (alcohol, cocaine, and opioid). Other data indicate that DSM-5 cannabis use disorder is less prevalent than DSM-IV abuse/dependence, which has been observed only in European American cannabis users, but not African American users. Diagnostic shifts have been deemed minimally related to the removal of the legal problems criterion or addition of the craving criterion. Regarding severity thresholds, 67%-97.5% of marijuana dependent individuals per the DSM-IV-TR definition would meet criteria for a severe cannabis use disorder, indicating relatively strong diagnostic concordance. However, greater discrepancies are observed among those with a marijuana abuse diagnosis: 56% received a diagnosis of mild cannabis use disorder, 21% received a moderate cannabis use disorder diagnosis, and 23% received no diagnosis. Indeed, interrater diagnostic reliability was lower for mild cannabis use disorder, relative to moderate or severe cannabis use disorder, although all DSM-5 cannabis use disorders showed greater reliability relative to DSM-IV abuse/dependence disorders. More data are needed to estimate the prevalence of the DSM-5 cannabis use disorder, at varying severity levels.

To date, researchers have employed standardized interviews to index cannabis diagnoses in a manner identical to those for other types of substances (e.g., alcohol, tobacco). At the same time, in contrast to the diagnostic classification system, pattern of cannabis use (quantity/frequency of use) is not considered. Despite this, it has been more common historically to denote cannabis use variability by asking respondents to indicate their level of use (e.g., frequency) over a specified period of time. From this perspective, having participants specify the frequency, and perhaps quantity, of cannabis use also can be a common assessment method. Collectively, then, deciding on whether nosological classification and/or a use-oriented assessment protocol (i.e., volume and frequency) is indicated may depend on the specific clinical need or research question being posed and the theoretical basis for it.

Motivational Bases of Cannabis Use

Researchers and clinicians also have increasingly found merit in applying motivational models to understand and clinically intervene with cannabis use and its disorder. This work has built from the motivational study of alcohol and tobacco use. At the most basic level, such an approach recognizes that there are a number of distinct motives for using cannabis that can vary both between and within individuals. That is, two individuals may use cannabis for different reasons, and one individual may use for multiple types of reasons. Motivational models predict that distinct motives may theoretically be related to particular types of problems. For example, specific motives may play unique roles in various aspects of use (e.g., addictive use, withdrawal symptoms, craving) or problems related to use (e.g., psychological disturbances, risk-taking behavior). Thus enhancing efforts to explicate cannabis use motives empirically will presumably facilitate the nature of cannabis use and its disorders as well as linkages between cannabis use and its clinically important correlates, as it has for alcohol and tobacco use.

Recognizing the practical importance of theoretically delineating and empirically measuring cannabis use motives, Simons and colleagues developed the Marijuana Motives Measure. Studies have evaluated the factor structure of the Marijuana Motives Measure among young adults in the United States ( n = 161), young adults and adolescents in France ( n = 114), young adult cannabis users in the United States ( n = 227), and young adult frequent cannabis users in the Netherlands ( n = 600). Using a combination of exploratory and onfirmatory factor analytic approaches, the Marijuana Motives Measure demonstrated a multidimensional measurement model across extant work—specifically, a five-factor solution denoting Enhancement, Conformity, Expansion, Coping, and Social motives for cannabis use, each with satisfactory levels of internal consistency, and preliminary evidence for routine motives (i.e., using cannabis out of boredom, out of habit.) The Comprehensive Marijuana Motives Questionnaire is another self-report assessment developed by Lee and colleagues that taps 12 different motivational aspects of use: Enjoyment, Conformity, Coping, Experimentation, Boredom, Alcohol, Celebration, Altered Perceptions, Social Anxiety, Relative Low Risk, Sleep, and Availability. This measure was developed and validated among young adult college students (n = 346) and suggests that this population may have several unique reasons for using cannabis. It is also worth noting that existing assessments of cannabis motives assume cross-situational consistency; however, motives may change within a person depending on situational characteristics.

Existing motivation-oriented work on cannabis is important in terms of informing the understanding of how and why cannabis use may be related to certain patterns of substance use, problems related to use, and psychological problems. For example, using the Marijuana Motive Measures, greater levels of Coping, Enhancement, Social, and Expansion motives for cannabis use have each been found to be concurrently significantly associated with frequency of past 30-days of cannabis use. These associations between motives for use and frequency of use do not appear to be attributable to other alternative factors such as amount of time being a cannabis user or other types of concurrent substance use. Moreover, coping motives appear to be uniquely related to likelihood of having cannabis dependence, at least cross-sectionally. Using the Comprehensive Marijuana Motives Questionnaire, coping and sleep/rest motives are uniquely related to cannabis-related problems. However, the exact directional relation between cannabis motives and patterns of cannabis use remains underexplored. It is noteworthy that other work suggests that specific motives may be relevant to the understanding of psychological vulnerability. For example, coping motives for cannabis use, but not other motives, have been significantly predictive of negative affect, anxious arousal, and anhedonic depressive symptoms, especially among more frequent users relative to less frequent/occasional users. These types of findings may have important theoretical implications for a better understanding of previous research linking cannabis use to affect-based psychological vulnerability.

Negative Correlates of Cannabis Use and Its Disorders

Historically, cannabis has been viewed by some as a less severe, or “soft,” drug, and policy shifts toward medicalization and legalization of cannabis have been observed in recent years. Although significant variability presently exists in legality of cannabis across states in the United States, there is increasing public support for the legalization of cannabis. Specifically, recent public opinion data from 2015 indicate that 53% of adults in the United States are in favor of legalizing cannabis, which is in contrast to 2006 data when 32% were in favor of legalization. In contrast, scientific study has provided a corpus of empirical evidence that cannabis use and its disorders are associated with a number of clinically significant problems. Indeed, there are several empirically documented negative consequences of frequent or problematic cannabis use (typically defined as weekly or daily use). These negative effects are evident in physical, social, interpersonal, and, more recently, psychological realms. In this section of the chapter, we describe some examples of work pertaining to possible negative correlates of cannabis use.

Health-Related Problems

One of the foremost negative effects of cannabis use is long-term cognitive impairment. A wealth of research indicates that long-term and heavy cannabis use may cause neuropsychological impairment, which may last even after abstinence. For example, one large study of 1037 individuals followed from birth until age 38 examined the longitudinal association between intelligent quotient (IQ) and cannabis use. Data indicated that (a) individuals who persistently met criteria for regular cannabis use and/or cannabis dependence had significant declines in global IQ a loss of approximately 6 IQ points). These effects were significant after adjusting for other drug dependence, tobacco use, alcohol dependence, schizophrenia, and number of years of education. It is notable that early onset of cannabis use was linked to greater IQ decline (initiation of cannabis use in adolescence vs. adulthood). Persistent cannabis dependence was also associated with decreased likelihood of pursuing education after high school and greater attention/memory problems identified by a collateral informant. Moreover, the effects of cannabis cessation did not fully restore neuropsychological functioning among individuals who initiated cannabis use in adolescence.

There have been a series of important large-scale prospective studies documenting the negative effects of cannabis over time on pulmonary functioning (e.g., Sherrill et al. and Tashkin et al. ). Although the results across investigations are not fully consistent, they converge on the observation that greater duration of cannabis use is related to increased bronchitis symptoms (e.g., coughing, wheezing). Some data also indicate that the combination of smoking tobacco and cannabis relative to tobacco alone is associated with greater odds of respiratory symptoms and increased odds of having chronic obstructive pulmonary disease if more than 50 cannabis cigarettes were used in lifetime. Some data indicate that among certain subpopulations of users (e.g., those using cannabis more frequently), the negative medical effects of this drug are, perhaps, even more clinically noteworthy. For example, frequent cannabis use is associated with an increased risk of severe respiratory illnesses, especially chronic bronchitis ; however, pulmonary effects are not similarly observed among lighter/occasional lifetime users. In addition, there are studies of the relation between cannabis use and cancer. Epidemiological data indicate that heavy cannabis use (smoking at least 50 cannabis cigarettes in lifetime) is associated with a twofold increased risk of developing lung cancer ; however, controlled studies of these cancer-related negative effects of cannabis use are underrepresented in the literature. Overall, more research is needed to understand the effects of inhaled cannabis on the effects of pulmonary health.

It is also noteworthy that some research suggests that cannabis use may be related to poor cardiovascular health, especially following acute cannabis use and among those with coronary artery disease, although the mechanism underlying this risk is not well understood. Cannabis use is also associated with impaired immune system functioning, but these investigations, again, have not been consistently replicated. Upon close inspection of these studies, it becomes clear that some of the inconsistencies of these investigations may be related to problems in the measurement of cannabis use, individual differences in use, or confounded by other health risk behaviors (e.g., tobacco smoking). A similar set of issues is evident for linkages between cannabis use and impaired reproductive effects. Here, nonhuman research suggests that heavier cannabis use is related to impaired reproductive capacity, but controlled evidence among humans is currently lacking.

It should be noted that although most research has focused on elucidating putative negative health consequences or correlates of cannabis use, there has been scientific and clinical interest in possible health benefits of the drug. Namely, cannabis use has been suggested to improve certain disease symptoms (e.g., by decreasing eye pressure, involuntary movement, and perceived pain) and stimulate appetite. Although this body of work is complicated, the strongest evidence of possible health benefits for cannabis use appears to be focused on increasing appetite, decreasing nausea and vomiting, preventing systemic weight loss, and possibly improving pain tolerance.

Social Problems

In addition to the potential risk of a number of negative physical consequences, adverse social consequences related to certain types of cannabis use have been reported (e.g., frequent users, such as those who use on a daily or weekly basis). Lynskey and Hall, for example, reviewed evidence suggesting that cannabis use was a contributing factor to impaired educational attainment, and others have found that cannabis use leads to reduced workplace productivity, as well as impaired judgment within hours after cannabis use (e.g., among airline pilots). It is possible that (1) cannabis use causes poor educational attainment, (2) cannabis use is a consequence of poor educational attainment, (3) both are true, or (4) shared risk factors increase the likelihood of both cannabis use and poor educational performance (e.g., cognitive impairment, attention-deficit/hyperactivity disorder). Although the direct patterning of effects is unknown, a consistent pattern emerges: the greater the amount of use (measured in frequency of use or severity of use), the greater the impairment. The specific mechanism(s) underlying these use-related effects are as yet theoretically and empirically unspecified.

As another example, cannabis use has been linked to fatal traffic accidents and general driving impairment. Cannabis is the most common illicit drug detected among drivers who were tested for drugs. , The prevalence of positive cannabis results among drivers who died in a motor vehicle crash have increased from 4.2% in 1999 to 12.2% in 2010 ; this increase was not observed for positive alcohol results. Driving-simulation and on-road studies indicate that reaction time, road tracking, speed, divided attention, and visual processing speed are impaired by THC, although these results have not been consistently documented, perhaps due to variability in methodological approaches. In addition, data convincingly indicate that performance is increasingly impaired as blood concentrations of THC increase, and that the risk associated with cannabis is incrementally increased when considered used with alcohol.

Other work suggests that frequent or more severe cannabis use may lead to using more severe forms of other drugs (e.g., widely publicized, but sometimes controversial, gateway theories of the developmental nature of substance use patterns). One overarching limitation to the vast majority of work linking certain types of cannabis use to social and interpersonal functioning, and even future use of other substances, is that there is a dearth of (controlled) prospective evaluations. Thus conclusions drawn from extant work should be viewed conservatively.

Psychological Problems

There have been a variety of psychological problems associated with cannabis use and its disorder. Perhaps the most well-known psychological problem(s) associated with cannabis use has been psychotic-spectrum disorders. There are numerous lines of empirical evidence that have provided robust evidence of an association between cannabis use and psychotic-spectrum disorders. Indeed, case reports of cannabis use have documented that such drug use can precede the onset of certain psychotic-spectrum disorders such as schizophrenia at higher rates than expected by chance of psychosis among regular cannabis users. Although the directional nature of the cannabis-psychotic-spectrum problem association has been the subject of consistent intellectual debate (e.g., Hambrecht et al. ), one position has been that the use of cannabis may actually increase the risk of psychotic-spectrum disorders. Consistent with this cannabis-to-psychotic symptoms/disorders perspective, the acute effects of cannabis use have been found to contribute to the elicitation of psychotic episodes and exacerbations of such symptoms among previously afflicted persons (e.g., the recurrence of psychotic symptoms ). Other research has found that intravenous THC administered to antipsychotic-treated patients with schizophrenia and nonpsychiatric controls exacerbated positive schizophrenic symptoms in the patient sample and induced positive symptoms in controls. Neuroimaging studies have also found similarities between neural networks impaired by cannabis use and those known to be implicated in the etiology of schizophrenia (see Loeber et al. for a review). Finally, in a meta-analytic review of the existing empirical literature, Semple and colleagues concluded that the early use of cannabis increased the risk of schizophrenia or a schizophrenia-like psychotic illness by approximately threefold. Although a model indicating that cannabis may lead to psychotic-spectrum disorders provides only one possible way in which these factors may be related, it documents the importance of understanding cannabis in the context of severe mental illness. It is worth noting that the scientific literature also indicates that cannabidiol (CBD) may attenuate the effects of THC on psychosis symptoms ; in turn CBD may have beneficial antipsychotic effects. This area of study requires further attention.

In another area of research, scientific activity has been focused on addressing the relationship between cannabis and depressive symptoms or problems. The interest in this line of inquiry appears to have been historically fueled by the clinical observation that regular (i.e., on a daily or weekly basis) cannabis users often reported a lack of motivation for completing day-to-day activities (e.g., going to school). The depression-cannabis literature has sometimes identified statistically significant relations between cannabis use and depressive symptoms and disorders. However, the most recent work in this domain has indicated that the strength of such cannabis-depressive associations may be relatively weak, and markedly attenuated, or even nonexistent, after adjusting for common variables such as gender. As one illustrative example, Brook and colleagues completed a study that involved a two-time (1- to 2-year interval) prospective study of Colombian adolescents ( n = 2226; 48.2% female) who were 12- to 17-years-old. Findings indicated that cannabis use in early adolescence did not significantly predict later depressive symptoms (time 2) after controlling for distress and interpersonal functioning in earlier adolescence (time 1). However, among a large sample of Australian adolescents ages 14–15 ( n = 1601) who were followed for 7 years, the prevalence of depression and anxiety increased as the frequency of cannabis use increased. This effect was observed particularly in females, relative to males. This work, when considered in the context of the psychotic-spectrum research, highlights that cannabis should not be considered to have the same types of linkages with all forms of mental illness.

Another area of research has begun to address the relations between cannabis use and anxiety symptoms and disorders. This work was initially stimulated by the observation that cannabis use may acutely promote heightened levels of anxiety symptoms and elicit panic attacks under certain conditions or in certain individuals. For example, when a person is intoxicated from using cannabis, they may experience acute paranoia, escalating anxiety symptoms, and perhaps a panic attack. This type of experience makes intuitive sense in that cannabis can elicit a wide range of acute sensory-oriented experiences and distortions that may be perceived as out of the person’s control and could be interpreted as threatening by some persons who are fearful of such internal stimuli and experiences. Some evidence appears consistent with this perspective. For example, Hathaway found that among weekly users of cannabis ( n = 104), approximately 40% reported having had at least one panic attack related to such use. These prevalence rates are noteworthy in light of lifetime rates of panic attacks among the general population of approximately 5%–8%. Another study found that, after covarying cigarettes per day, alcohol use, and negative affectivity, the interaction between cannabis use and anxiety sensitivity (fear of anxiety and related internal sensations) is related to increased levels of anxiety symptoms among cannabis users who also use tobacco. Thus, certain individual differences such as anxiety sensitivity may be important to consider in understanding the linkages between cannabis use and anxiety states and disorders.

Another study involving a representative sample ( n = 4745) found that a lifetime history of marijuana dependence, but not use or abuse, was related to an increased risk of panic attacks after covarying the effects of polysubstance use, alcohol abuse, and demographic variables. In a more recent investigation, Zvolensky and colleagues prospectively evaluated marijuana use, abuse, and dependence in relation to the onset of panic attacks and panic disorder. Participants at the start of the study were adolescents ( n = 1709) with a mean age of 16.6 years (SD = 1.2; time 1) and were reassessed 1 year later (time 2) and then again as young adults (time 3; mean age = 24.2 years, SD = 0.6). Results indicated that adolescent-onset marijuana use and dependence were significantly prospectively associated with increased odds for the development of panic attacks and panic disorder. However, marijuana use or dependence was not incrementally associated with the development of panic after controlling for daily cigarette smoking. There is also growing research in the area of cannabis and posttraumatic stress disorder (PTSD). For example, nationally representative data indicate that PTSD is associated with increased likelihood of using cannabis in the past year, which was significant after adjusting for cooccurring anxiety and depressive disorders. In addition, among a sample of military veterans exposed to combat who were enrolled in a residential treatment program for PTSD, those who had a cannabis use disorder relative to those without had less change in PTSD symptom severity posttreatment. Collectively, these recent findings underscore the importance of considering the role of cannabis use with regard to understanding anxiety vulnerability.

It is worth noting that the anxiety-cannabis link may be driven by the effects of THC relative to CBD. Indeed, a review of preclinical and clinical studies indicated that CBD is associated with anxiolytic effects relevant to various psychological disorders (PTSD, generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder). This effect was consistently observed in 29 of 33 pretrials and 7 of 10 clinical trials.

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Jan 19, 2020 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Cannabis: An Overview of the Empirical Literature

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