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Cannabis: An Overview of the Empirical Literature
Introduction
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.
Prevalence
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
Pharmacokinetics
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.
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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).
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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.
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