Consequences of Marijuana Use: Cognitive Effects

2015

Marijuana has long been thought to affect cognitive function. Early reviews, however, concluded that the scientific evidence for long-term deficits was inconclusive. This conclusion remains appropriate if one is referring to gross deficits with severe impairment of functioning. More recent findings from well-controlled studies indicate that cannabis use can lead to subtle, selective cognitive impairment, although the functional significance of these deficits remains unclear. Specifically, tasks requiring “higher cognitive function” show significant deficits associated with chronic and frequent use of cannabis. The ability to organize and integrate complex information appears compromised, most likely due to an impact of cannabis on memory and attentional processes. A considerable research literature in this area has accumulated. Here, we provide a summary of the types of deficits associated with marijuana use in more recent studies and comment on the possible mechanisms involved.

Psychomotor Performance

Psychomotor performance measures provide a means of evaluating basic cognitive functions such as response slowing. We begin with a summary of this literature because general deficits in this area can affect performance on most other cognitive tasks. The Digit Symbol Substitution Task (DSST) has been the most commonly used measure of psychomotor performance in cannabis studies. Marijuana- or oral-THC-produced decrements in DSST response speed and accuracy have been observed in some studies, but not in others. Marijuana’s effects on other psychomotor tasks have also proved inconclusive. Performance decreases on circular lights, standing steadiness, and pursuit rotor-tracking tasks have been reported in some studies, while others have found no significant effects on circular light, tracking, card sorting, or reaction time tasks.

With some exceptions, dose appears to partially account for between-study differences. Significant adverse effects are typically observed with higher doses, and dose-response effects have been observed in some studies that used multiple-dosing procedures. In summary, there appears to be moderately strong evidence that marijuana or THC used at higher doses can impair performance on some psychomotor tasks. This literature does not indicate a pervasive response slowing, such as decrements on simple reaction time tasks. Rather, tasks that are affected appear to depend more heavily on attention and motivation. As discussed later, cannabis intoxication may reduce the steady state of motivation. Because performance on most cognitive tests is influenced by the degree of attention and motivation directed toward the specific task, determining how cannabis affects these processes is necessary for better understanding its influence on cognitive processing.

Attention and Memory

Acute Effects

Laboratory research on the acute effects of cannabis use on memory has generally shown subtle effects that appear linked to dose and an associated attention or learning deficit. Research on immediate word recall, digit span, and digit recognition tasks has produced equivocal results. Some studies show evidence of impaired performance on short-term memory tasks following marijuana intoxication, while others have not. Dose-related effects can explain some but not all of these conflicting outcomes, as impairment was evident primarily in studies that examined higher doses.

Cannabis intoxication also affects the subjective perception of time. Time estimates are shorter and time productions are longer in subjects after smoking marijuana compared to placebo or no drug use. Cannabis intoxication does not appear to affect the ability to reproduce a time interval that has been modeled. The mechanismfor this temporal processing impairment is not clear, but deficits in attention warrant consideration.

The effects of marijuana on longer-term memory tasks (retrieval of information following a significant lapse in time) have proven more reliable across studies. Smoked marijuana has produced deficits in the recall of word lists and of prose material presented to subjects in placebo-controlled studies. Interestingly, when retrieval cues are used, the impairment of marijuana on these memory tasks may be obviated. Such findings suggest that effects on attentional or learning processes may be primary mechanisms for memory performance deficits associated with cannabis use. Indeed, marijuana has been shown to disrupt the ability to learn novel tasks. Moreover, marijuana-or THC-related deficits have generally been observed on divided attention tasks in which subjects must monitor multiple stimuli concurrently and make responses based on their observations.

Methodological differences across studies make it difficult to interpret findings on cannabis and memory. Nonetheless, this literature indicates that the acute effects of cannabis on memory are moderate at most, and are likely dose-dependent. The mechanism for these effects remains unclear, but deficits in attention and learning appear involved. How motivational factors impact these findings is also not clear. Interestingly, one early study reported that subjects performed better on memory tasks when they knew that the effects of marijuana on memory were being tested.

Chronic Effects

Studies of chronic effects of cannabis on cognitive processes have tried to examine the effects of chronic use while controlling for acute intoxication effects. A series of studies by Solowij (1999) examined the long-term effects of cannabis use on attentional processes. Regular cannabis users’ performance on an auditory selective-attention task was measured after at least 24 hours of abstinence from cannabis use. Cannabis users’ performances were significantly worse than matched controls, suggesting an inability to filter out complex irrelevant information. These findings were replicated in a second study that also demonstrated an association between years of marijuana use and the severity of attentional focus and information integration deficits. Moreover, a reduction in event-related potentials (P300 amplitude), a purported marker of cognitive processing, coincided with the observed cognitive deficits.

Solowij and colleagues also reported significant deficits in a study of long-term, heavy cannabis users interested in quitting their marijuana use. Increased perseveration on the Wisconsin Card Sorting Test and decreased memory on a verbal learning task were observed, and the severity of impairment increased with the duration of regular marijuana use. Similarly, Leavitt and colleagues reported that the duration of chronic cannabis use was related to deficits on tasks of verbal learning, complex reaction time, complex reasoning, and short-term memory. Pope and Yurgelun-Todd reported similar deficits in a study of heavy versus light marijuana-using college students with shorter histories of cannabis use. Again, a 24-hour abstinence period was required prior to testing. Heavy marijuana users made significantly more perseverative errors on the Wisconsin Card Sorting Test, had poorer recall on a verbal learning task, and showed other deficits on specific tasks compared to light users. The authors characterized their findings as deficits of the attentional/executive system involving mental flexibility, learning, and sustained attention.

Two controlled studies of adolescent marijuana abusers reported deficits in specific types of memory and learning tasks, further extending the potential impact of cannabis use to a younger sample. In addition, early onset of chronic cannabis use has recently been associated with impaired reaction time in visual scanning tasks but this relationship was not observed in late-onset users. This finding suggests the possibility of a specific vulnerability for development of an attentional impairment during early adolescence, and raises further concern about the impact of regular cannabis use on cognitive development and school performance.

To our knowledge, only one study has examined whether cognitive impairment related to chronic cannabis use recovers following cessation of use. Ex-users (last use ranging from three months to six years), current long- and short-term users, and nonusers performed a selective attention task and event-related potentials were recorded. Findings suggested that ex-cannabis smokers continued to show impairment in their ability to filter out irrelevant information, although some evidence of partial recovery was noted.

Historically, interpretation of findings on the chronic effects of cannabis use has been limited by multiple confounding variables such as possible acute marijuana intoxication effects, variable marijuana use histories, unknown cognitive abilities prior to marijuana exposure, concurrent use of other drugs, demographic influences, and comorbidity with other mental or physical illnesses. Recent studies have made strong efforts to control for many of these variables, however, important confounds remain. For example, some studies have required a brief period of abstinence prior to testing to control for the acute intoxicating effects of cannabis. However, this procedure introduces another potential confound, i.e., whether acute withdrawal effects impact performance testing. Moreover, as in studies of the acute effects of cannabis on cognitive performance tests, adverse effects on motivation may contribute to the deficits observed in studies of chronic cannabis use and performance. That is, chronic users may not expend as much effort toward testing as those in control groups.

Notwithstanding the methodological issues inherent to this research, the literature strongly suggests that chronic marijuana use can impair performance on various types of cognitive tests, specifically those thought to involve complex cognitive processes. These deficits may increase in form and severity in relation to the duration of exposure to cannabis. Future research is needed to better elucidate the processes that cause performance deficits and to determine their functional significance.

Academic Performance

Cannabis use has been linked to low grade-point averages, decreased school satisfaction, negative attitudes toward school, poor overall school performance, and absence from school. Early cannabis use (prior to age 16) is associated with dropping out of school before graduating high school. However, causality between cannabis use and poor academic achievement has not been established. Cannabis use also correlates significantly with delinquency, other drug problems, poor mental health, family dysfunction, and relationships with deviant peers, each of which is a likely contributor to academic problems. Studies that have statistically controlled for these factors have reported mixed results regarding the impact of cannabis use and academic performance.

Although one might expect that the adverse effects of cannabis use on attentional and complex cognitive processing would have some direct influence on optimal academic performance, the extent of this influence, if any, is unknown. Similarly, if cannabis use adversely affects motivation, one would expect a subsequent negative impact on academic performance through a decreased effort directed toward school work. The aforementioned other psychosocial problems associated with frequent cannabis use and concomitant effects on motivation to achieve in school would likely have a greater impact on a youth’s academic performance than the subtle cannabis-related deficits in complex processing observed in laboratory studies. Whether marijuana use is a primary cause of academic problems or the converse, educational and behavioral problems lead to marijuana use, remains at issue.

Driving Performance

The effects of cannabis intoxication on driving have been examined using driving simulators and road tests during which lane position, emergency decisions (braking latency), and risk-taking behavior (speed, passing attempts, headway distance) are assessed. Studies on lane position have produced mixed results. Cannabis intoxication has been shown to adversely affect performance in emergency situations. When no warnings are provided, performance in emergency situations declines and brake latency increases. Cannabis has also been shown to adversely affect one’s ability to attend to extraneous stimuli while driving, which may contribute to poor performance in emergency situations.

Cannabis use appears to decrease risk-taking behavior in driving situations. An association between cannabis intoxication and a reduction in speed has been observed across studies. In addition, subjects appear more hesitant to perform passing maneuvers and maintain a greater distance from other vehicles when under the influence of cannabis.

Adverse effects on driving performance appear most evident when assessed in close temporal proximity to cannabis ingestion and appear to be dose dependent. Performance decrements have not been shown to persist beyond three hours after ingestion. Negative results have typically been observed in studies that use smaller doses of marijuana, less-complicated driving tests, or less-sensitive assessment techniques. Overall, experimental data suggest that cannabis intoxication can decrease control of automobiles as evidenced by variability in lane position and poor performance in emergency situations. However, drivers may partially compensate for these deficits by engaging in low-risk driving behaviors.

Controlled studies have recently examined the effects of the combination of alcohol and cannabis on driving. Such studies are important as the majority of motor vehicle accidents in which the driver is known to have recently used cannabis also find that alcohol was used by the same driver. One study of driving performance in real-world conditions reported clear synergistic effects of low doses of cannabis and alcohol on road tracking, time out of appropriate lane position, and increased variability in headway distance. Performance in a driving simulator study, however, did not report such clear combination effects, as adverse performance effects observed with either substance alone were not exacerbated by the addition of the other. Such conflicting results are difficult to interpret, and indicate the need for additional studies in this area.

Epidemiological studies have been conducted in the United States and Australia in an attempt to define the role of marijuana in major automobile accidents. A recent review of archival studies using police and laboratory reports assessed the relationship among marijuana use, alcohol use, combined use, and motor vehicle accidents in which serious injuries or fatalities occurred. The authors concluded that use of marijuana alone was associated with reduced risk of a fatal accident relative to drug-free and alcohol-intoxicated related cases. Alcohol alone and in combination with marijuana was found to be a significant risk factor, with the combination showing slightly higher risk than alcohol alone. Studies of nonfatal injuries provided mixed results regarding the relative risk of marijuana use.

These epidemiological studies have several important limitations. First, it is difficult to determine whether the obtained cannabinoid metabolite levels relate to acute intoxication at the time of the accident. Second, cases in which traces of cannabis and another illicit substance are found are typically excluded from these studies. Since the combination of marijuana and other substances, including alcohol, is the most common finding in accident reviews, the relative contribution of marijuana to these accidents cannot be determined. Third, these studies rarely consider the base rates of cannabis use in comparable populations (young adults) and the concomitant accident rates in that population. More sophisticated methods of detecting marijuana intoxication, well-controlled studies, and inclusion of less severe accidents are needed to more fully understand the role of cannabis use in motor vehicle accidents.

Motivation

Marijuana use has long been associated with an “amotivational syndrome” characterized by lethargy, inactivity, loss of motivation, and decreased goal-directed behavior in heavy marijuana smokers. Evidence for such amotivational effects comes primarily from case studies and clinical reports. Some chronic cannabis users attribute impaired vocational or academic performance and loss of ambition to their marijuana use. Moreover, procrastination and impaired motivation are commonly reported as consequences of using marijuana and as reasons for stopping use among heavy users and those seeking treatment.

Controlled field studies have failed to provide clear evidence of an amotivational syndrome. However, these studies have many methodological limitations relating to sample selection and operational definitions of motivation. Most recently, an Australian study of chronic users reported findings that typify this literature. Many users appeared to be underemployed based on their education and abilities but were well integrated into family and community activities. Participants tended to attribute these circumstances as a lifestyle choice rather than an adverse effect of cannabis use. Family members provided mixed reports, as some noted amotivational effects in users, while others cited only positive effects.

Laboratory studies suggest that the motivational effects of cannabis intoxication on operant behavior are dependent on environmental context and contingencies. Miles and colleagues showed increased efficiency and no performance decrements when working for monetary reward while under the influence of marijuana. Pihl and Sigal found that they could reverse performance decrements induced by marijuana intoxication by providing monetary rewards. Other studies have failed to show adverse effects of marijuana on work output. However, the tasks and conditions of these studies may have been insensitive to cannabis effects as participants tended to show maximal performance across conditions.

Cherek and colleagues cited in Budney et al., used a more sensitive operant measure of motivation in a laboratory study of cannabis intoxication. Subjects could choose to spend time working on a high-demand task that earned monetary reinforcement, or switch to a no-demand task that earned a lower level of reinforcement. With this choice available, subjects spent less time working on the high-demand task when under the influence of marijuana than with placebo, suggesting an amotivational effect. This effect appeared dose dependent and was partially reversed by increasing the magnitude of the reinforcement in the high-demand task. This suggests that amotivational effects of cannabis intoxication may occur by impacting the effects of reinforcement on various types of operant behavior (e.g., change sensitivity). The interaction among cannabis’s behavioral effects and environmental variables needs further study to better understand the association between cannabis use and motivation.

There remains little scientific evidence that chronic cannabis use leads to an amotivational syndrome that could not be accounted for by chronic intoxication. Laboratory studies that compare chronic users with nonusers on performance of operant tasks, while controlling for acute intoxication effects, may provide more important information and address the validity of a chronic effect of cannabis on motivation. Of note, the acute motivational effects on operant performance observed in the laboratory indicate that motivation should be considered when interpreting studies that examine the effects of cannabis on any cognitive or behavioral performance task.

Cannabis Dependence

Whether cannabis use can lead to dependence has been controversial in both the lay and scientific communities. Personal experiences may bias many people toward the perception that cannabis is not addictive. More than one-third of the U.S. population has smoked marijuana in their lifetime. Most have not become addicted and have stopped using without difficulty. Moreover, unlike alcohol, cocaine, heroin, or nicotine dependence, most people are not familiar with personal acquaintances who have had problems with marijuana dependence, nor are sensational accounts of problems associated with marijuana common in the popular media.

The scientific community has also been reluctant to acknowledge the dependence potential of cannabis. Unlike most other drugs that humans abuse, animals do not readily self-administer cannabis (THC) in the laboratory. Because drug-dependence research has a productive history of using animal models to explicate drug dependence, this methodological issue raised serious questions about the abuse potential of cannabis. Further quandries arose when early studies of cannabis (THC) withdrawal did not reveal a syndrome that included substantial physical symptoms such as those observed during classic opioid, barbiturate, or alcohol withdrawal. Until recently, the neurobiology of cannabis was poorly understood, casting further uncertainty on this drug’s addictive potential.

In contrast, the past ten years of basic and clinical research has produced strong evidence for concluding that cannabis can and does produce dependence. Here we review data addressing two facets of the dependence phenomenon: functional (behavioral) dependence and biological (physiological) dependence. Although this distinction can be considered artificial, it appears a logical way to organize new information in this area.

Functional (Behavioral) Dependence

Both the DSM-IV (American Psychiatric Association, 1994) and the International Statistical Classification of Diseases and Related Health Problems, tenth revision (ICD-10) (WHO,ZZZ consider cannabis dependence a reliable and valid diagnostic category of mental disorder suggesting that individuals in the general population experience cannabis dependence in much the same way as they experience other substance dependence disorders. By definition, a diagnosis of dependence indicates that an individual is experiencing a cluster of cognitive, behavioral, or physiological symptoms associated with substance use, yet continues to use the substance regularly. Two epidemiological studies conducted in the United States and another in New Zealand indicate that the lifetime prevalence of marijuana dependence approximates 4 to 5 percent of the population, the highest of any illicit drug.

Such high prevalence of cannabis dependence in comparison to other illicit drugs is clearly due to the greater overall prevalence of cannabis use. The estimated conditional dependence rate for cannabis dependence is lower than most other drugs of abuse, but certainly is not insignificant. That is, the risk of developing marijuana dependence among those who have used marijuana is approximately 9 percent compared to 12 percent for stimulants, 15 percent for alcohol, 17 percent for cocaine, 23 percent for heroin, and 32 percent for tobacco. More frequent cannabis use results in greater risk of dependence. For example, rates of dependence are estimated at 20 to 30 percent among those who have used cannabis at least five times, and even higher (35 to 40 percent) estimates are reported among those who report near daily use.

Clinical studies indicate that the majority of individuals who seek treatment for marijuana-related problems clearly meet DSM dependence criteria. These individuals exhibit substantial psychosocial impairment and psychiatric distress, report multiple adverse consequences, report repeated unsuccessful attempts to stop using, and perceive themselves as unable to quit. A recent report comparing marijuana-dependent outpatients with cocaine-dependent outpatients found that the marijuana patients reported substance-use histories and psychosocial impairment comparable to the cocaine group, but showed less-severe dependence symptoms. The marijuana group was also more ambivalent and less confident about stopping their marijuana use than the cocaine group was about their cocaine use. Although marijuana-dependent outpatients typically do not experience the acute crises or severe consequences that many times drive alcohol-, cocaine-, or heroin-dependent individuals into treatment, they clearly show impairment that warrants clinical attention.

The number of individuals who enroll in treatment for marijuana-related problems is not small. Treatment-seeking for marijuana abuse or dependence increased twofold between 1992 and 1996, such that the percentage of illicit-drug-abuse-treatment admissions in U.S. state-approved agencies for marijuana (23 percent) approximated that for cocaine (27 percent) and heroin (23 percent) (SAMHSA). The response to treatment and relapse rates observed among marijuana-dependent outpatients appeared similar to those observed with other substances of abuse. In summary, clinical evidence for a cannabis dependence disorder is strong and indicative of a disorder of substantial severity.

Biological (Physiological) Dependence

Physiological dependence has typically been determined by evidence of tolerance or withdrawal. Tolerance to the physiological, cognitive, and social effects of marijuana or cannabinoids has been well documented. Controlled human laboratory studies have clearly shown that tolerance develops to the subjective high, heart rate increases, social interaction deficits, and some of the cognitive and psychomotor performance deficits associated with cannabis or THC ingestion. In contrast, many regular marijuana users report a lack of tolerance to the subjective effects of marijuana use, with some reporting a sensitization effect (less of the drug is needed to produce the desired effect). Sensitization has not been demonstrated in controlled studies, and some have suggested that this phenomenon may be related to learning how to smoke more efficiently or to better identify the effects of cannabis.

Withdrawal has generally been deemed a more robust indicator of dependence than tolerance. Early nonhuman studies of cessation of THC administration provided evidence of a withdrawal response, but the effects were mild and inconsistent. Early studies with humans in residential laboratories also found evidence of withdrawal. Common symptoms included decreased appetite, irritability, restlessness, sleep difficulties, and uncooperativeness. These effects were characterized as mild, transient, and without serious medical complications, and thus considered clinically insignificant when compared to the dramatic medical and physiological symptoms associated with severe opiate or alcohol withdrawal.

The discovery of a cannabinoid receptor and the synthesis of a cannabinoid antagonist renewed scientific interest in cannabis dependence and withdrawal. Antagonist-challenge studies demonstrated a marked, precipitated withdrawal syndrome in rats and dogs. Two placebo-controlled inpatient studies with humans, using moderate doses of oral THC and smoked marijuana, demonstrated withdrawal effects that included anxiety, decreased contentment and food intake, depressed mood, irritability, restlessness, sleep difficulty, and stomach pain. Controlled outpatient studies have now begun to demonstrate the reliability and validity of these withdrawal effects and examine their timecourse.

Clinical studies indicate that the majority of persons seeking treatment for cannabis dependence, including adolescents, report histories of cannabis withdrawal. For example, in our research clinic the majority (57 percent) of marijuana-dependent outpatients reported experiencing >6 symptoms of at least moderate severity during previous abstinence attempts. Severity was associated with more frequent marijuana use.

Cannabis withdrawal is not currently recognized in the DSM-IV, which concludes that the clinical significance of the syndrome has yet to be established. We expect that findings from recent research will result in its inclusion in the next revision of the DSM. Cannabis withdrawal syndrome resembles behaviors observed during nicotine withdrawal. It appears common among treatment seekers and may warrant attention in clinical settings. Additional research is needed to better determine its prevalence, timecourse, and severity.

Other recent neurobiological findings further support the conclusion that cannabis can produce dependence. The documentation of an endogenous cannabinoid system with identified cannabinoid receptors (CB1 and CB2) and an endogenous cannabinoid-like substance (anandamide) established that the actions of cannabinoids in the brain occur in a manner similar to that of other drugs with well-recognized addictive potential such as opiates or benzodiazepines. The aforementioned precipitated-withdrawal studies demonstrated that withdrawal from cannabinoids likely occurs via a similar process as other abused drugs. Studies that have examined neurochemical responses in animals following exposure to and withdrawal from cannabinoids have observed reductions in mesolimbic dopamine transmission and elevations in extracellular-releasing-factor concentrations in the limbic system that closely resemble the responses seen with other major drugs of abuse. The behavioral consequences of these neurobiological changes are consistent with the type of negative affective symptoms reported by patients withdrawing from marijuana and other substances, and may be primary contributing factors to the development and maintenance of drug dependence. In summary, research findings from the 1990s indicate that the biological risk factors for cannabis dependence appear more similar to other well-recognized addictive drugs than was previously believed.

Selections from the book: “Handbook of the Medical Consequences of Alcohol and Drug Abuse” (2004)