Cannabis use and neurocognitive functioning in a non-clinical sample of users

Highlights

• We examined the effects of cannabis use on neurocognitive functioning

• We considered the role of alcohol use and premorbid IQ

• Recent users performed most poorly on neurocognitive testing

• Cannabis use severity was associated with lower neurocognitive performance

• Past users performed more poorly on measures of executive function than non-users

Abstract

Objective

With the recent debates over marijuana legalization and increases in use, it is critical to examine its role in cognition. While many studies generally support the adverse acute effects of cannabis on neurocognition, the non-acute effects remain less clear. The current study used a cross-sectional design to examine relationships between recent and past cannabis use on neurocognitive functioning in a non-clinical adult sample.

Method

One hundred and fifty-eight participants were recruited through fliers distributed around local college campuses and the community. All participants completed the Brief Drug Use History Form, the Structured Clinical Interview for DSM-IV Disorders, and neurocognitive assessment, and underwent urine toxicology screening. Participants consisted of recent users (n = 68), past users (n = 41), and non-users (n = 49).

Results

Recent users demonstrated significantly (p < .05) worse performance than non-users across cognitive domains of attention/working memory (M = 42.4, SD = 16.1 vs. M = 50.5, SD = 10.2), information processing speed (M = 44.3, SD = 7.3 vs. M = 52.1, SD = 11.0), and executive functioning (M = 43.6, SD = 13.4 vs. M = 48.6, SD = 7.2). There were no statistically significant differences between recent users and past users on neurocognitive performance. Frequency of cannabis use in the last 4 weeks was negatively associated with global neurocognitive performance and all individual cognitive domains. Similarly, amount of daily cannabis use was negatively associated with global neurocognitive performance and individual cognitive domains.

Conclusions

Our results support the widespread adverse effects of cannabis use on neurocognitive functioning. Although some of these adverse effects appear to attenuate with abstinence, past users' neurocognitive functioning was consistently lower than non-users.

Introduction

Prevalence rates for cannabis use have steadily increased in recent years, with approximately 18.1 million individuals reporting marijuana use within the past month on a National Survey on Drug Use and Health (NSDUH) conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA, 2012). Over the past two decades, an extensive growing body of research has demonstrated that cannabis use adversely affects cognitive performance among measures that target attention (Abdullaez et al., 2010, Medina et al., 2007, Solowij et al., 1995, Solowij et al., 2002), working memory (Kanayama, Rogowska, Pope, Gruber, & Yurgelun-Todd, 2004), verbal learning and memory (Hanson et al., 2010, Harvey et al., 2007, Lisdahl and Price, 2012, Mathias et al., 2011, McHale and Hunt, 2008, Medina et al., 2007, Tapert et al., 2002), and executive functions (Battisti et al., 2010, Gonzalez et al., 2012, Grant et al., 2012, Lisdahl and Price, 2012, Pope and Yurgelun-Todd, 1996, Ranganathan and D'Souza, 2006, Schuster et al., 2012, Solowij et al., 2012).

Delta 9-tetrahydrocannabinol (THC), the primary psychoactive agent of the cannabis sativa plant, is thought to be responsible for the cognitive effects of smoked cannabis (Bisogno and Di Marzo, 2010, Grotenhermen, 2003). Briefly, THC acts by binding to CB1 receptors that are largely distributed through the central nervous system and aids in several important functional roles that modulate neural responses (Gerdeman et al., 2002, Heifets and Castillo, 2009, Yasuda et al., 2008).

Comprehensive reviews of the cannabis and cognition literature are available (see Gonzalez, 2007, Grant et al., 2003, Hart et al., 2001, Lisdahl et al., 2013, Schreiner and Dunn, 2012), which generally support the adverse acute effects of cannabis on cognition; however, non-acute effects remain less clear. Grant et al. (2003) reported that average effect sizes across studies of learning and forgetting among cannabis users were rather small in magnitude. In the same review, similar results were found across all domains of neurocognitive performance, suggestive of minimal adverse effects of cannabis use on neurocognitive performance. In a more recent meta-analysis, Schreiner and Dunn (2012) found that after at least 25 days of cannabis abstinence, there were no residual effects on cognitive performance. Gonzalez (2007) highlighted some of the methodological limitations across studies examining the non-acute effects of cannabis that include heterogeneous participant samples that differ in factors such as severity of substance use, length of abstinence, and the presence of comorbid substance abuse and psychiatric disorders. More recent studies highlighted the moderating role of genetic polymorphisms such as the COMT val158met and 5-HTTLPR genes on the relationship between cannabis use and cognitive performance (Verdejo-García et al., 2013).

Researchers (i.e., Pope et al., 2001, Pope et al., 2002) have tested attention among current heavy cannabis users, former heavy cannabis users, and control subjects on days 0, 1, 7, and 28 of abstinence. On all four occasions, no significant between-group differences were found in attention performance despite impairments in other cognitive domains (i.e., learning and memory), which persisted up to 7 days of abstinence. After 28 days of abstinence, learning and memory impairments were no longer found. In a study that used a shorter abstinence period (i.e., 24 h), cannabis users showed both longer reaction times and delayed processing speed compared with controls (Solowij et al., 1995, Solowij et al., 2002). Using fMRI, Chang, Yakupov, Cloak, and Ernst (2006) found that marijuana users and controls demonstrated similar task performance on visual attention. However, both active and abstinent marijuana users showed activation differences across prefrontal, medial parietal, and occipital brain regions during the task, suggesting neural adaptation in chronic marijuana users.

A recent longitudinal study (Meier et al., 2012) that examined the effects of cannabis use on IQ and neuropsychological functioning suggested that the long-term effects of cannabis use may be more profound, as demonstrated by a drop from childhood average to adult low-average full-scale IQ among cannabis users.

Frequency and amount of cannabis use have also been associated with neurocognitive performance in some studies. Studies have found that THC levels in urine are associated with the severity of cognitive impairment (Fried et al., 2002, Pope et al., 2001). Using event-related potentials as a measure of brain functioning, Theunissen et al. (2012) found that THC significantly reduced P100 levels among heavy cannabis users. Similarly, Lane, Cherek, Tcheremissine, Lieving, and Pietras (2005) found that subjects exposed to a high dose of THC (3.6%) demonstrated significantly greater risk-taking than subjects receiving lower doses of THC.

Together, these studies suggest that the magnitude of adverse effects of cannabis on cognition varies depending upon the frequency of use, and length of abstinence. However, findings have been mixed, calling attention to the need to further systematically examine how level and frequency of cannabis may affect neurocognition among diverse and representative samples.

Considering that 51.8% of the population reports being current alcohol drinkers and 31.3% of heavy alcohol users also report using illicit drug (SAMHSA, 2012), it is difficult to ascertain whether the observed neuropsychological deficits among cannabis users are the direct results of cannabis use. Recent evidence suggests that heavy drinking during adolescence and young adulthood is associated with poorer neurocognitive functioning during the young adult years (Brown et al., 2000, Giancola et al., 2001, Hanson et al., 2011, Sher et al., 1997, Tapert and Brown, 1999). Therefore, consideration of comorbid alcohol may be an important area of examination in studies of the effects of cannabis on neurocognition.

The purpose of the current study was to examine the effects of cannabis use in a non-clinical sample of adults. We recruited individuals who reported recent cannabis use (in the last 4 weeks), remote cannabis use (longer than 4 weeks), and no use. We chose 4 weeks as our abstinence cut-point based upon the work of Pope et al., 2001, Pope et al., 2002. Our study hypotheses were as follows: (H1) recent users (i.e., those who reported using cannabis in the last 4 weeks) will demonstrate poorer neurocognitive performance than non-users and past users; (H2) past users will demonstrate poorer performance than non-users, although to a lesser degree than recent users; (H3) among recent and past cannabis users, abstinence (of cannabis) will be associated with higher neurocognitive performance; and (H4) among recent users, frequency of cannabis use in the last 4 weeks and number of times used per day will be negatively associated with neurocognitive performance. Alcohol use variables (frequency and amount used) were included in statistical models as covariates to control for the effects of alcohol when examining the effects of cannabis on neurocognitive performance.