Elsevier

Drug and Alcohol Dependence

Volume 155, 1 October 2015, Pages 275-283
Drug and Alcohol Dependence

Cortical thinness and volume differences associated with marijuana abuse in emerging adults

https://doi.org/10.1016/j.drugalcdep.2015.06.016Get rights and content

Highlights

Abstract

Background

The prevalence of marijuana (MJ) use among youth and its legalization for medical or recreational use has intensified public health endeavors of understanding MJ effects on brain structure and function. Studies indicate that MJ use is related to impaired cognitive performance, and altered functional brain activation and chemistry in adolescents and adults, but MJ effects on brain morphology in emerging adults are less understood.

Methods

Fifteen MJ users (age 21.8 ± 3.6, 2 females) and 15 non-user (NU) participants (age 22.3 ± 3.5, 2 females) were included, demographically matched on age, education and alcohol use. High-resolution structural MR images were acquired at 3 Tesla. Cortical thickness (CT) and volumetric analyses were performed using Freesurfer. A priori regions of interest (ROI) included orbitofrontal and cingulate cortices, amygdala, hippocampus and thalamus.

Results

Whole brain CT analysis did not result in significant group differences in a priori ROIs but revealed MJ users had significantly less CT (i.e., thinness) in right fusiform gyrus (rFG) compared to NU (p < 0.05). Thalamic volume was significantly smaller in MJ users compared to NU (right, p = 0.05; left, p = 0.01) and associated with greater non-planning (p < 0.01) and overall impulsivity (p = 0.04). There were no other group differences.

Conclusions

RFG cortical thinness and smaller thalamic volume in emerging adults is associated with MJ abuse. Furthermore, smaller thalamic volume associated with greater impulsivity contributes to growing evidence that the thalamus is neurobiologically perturbed by MJ use. Collectively, altered thalamic and rFG structural integrity may interfere with their known roles in regulating visuoperceptual and object information processing.

Introduction

In 2013, 180.6 million or 3.9% of the world population aged 15–64 used marijuana (United Nations Office on Drug and Crime, 2013). In the US, the rate of past month marijuana use among adolescents aged 12–17 years increased from 6.7% to 7.9% between 2007 and 2011 (SAMHSA, 2013). It is expected that the prevalence of marijuana use will continue to escalate at a rapid rate in the US across all age groups, given the recent legalization of medical and recreational use, and a decrease in public perception of harm associated with MJ use (Palamar et al., 2014, Schuermeyer et al., 2014). Accordingly, 54.6% of adolescents aged 12–17 perceived smoking marijuana once or twice a week as a “great risk” in 2007, which has decreased to 44.8% in 2011 (SAMHSA, 2013). Therefore, a better understanding of the long-term effects of marijuana on the brain, particularly the developing brain, as young adolescent users transition into emerging adulthood (ages 18–24), is an increasingly important public health endeavor. To this end, previous studies show that when marijuana use was initiated before age 17, the negative impact of chronic marijuana use on cognitive function and brain morphology can last several years and may even be permanent (Gruber et al., 2011, Jacobus et al., 2009, Jacobus et al., 2014, Meier et al., 2012, Schweinsburg et al., 2008b, Wilson et al., 2000). As such, investigating the effects of marijuana exposure initiated during adolescence and continuing during emerging adulthood on vulnerable prefrontal and subcortical regions will offer unique insight into structural consequences of short-term persistent marijuana use in emerging adults.

The major psychoactive component in marijuana (MJ) is delta-9-tetrahydrocannabinol (THC). The main cannabinoid receptor in the brain is the CB1 receptor, which is a G-coupled protein that is widely distributed throughout the central nervous system (CNS), with greatest densities in the associational areas of frontal and limbic lobes, cerebellar cortex, thalamus, pallidum, amygdala, hippocampus and substantia nigra pars reticulata (Glass et al., 1997). Marijuana use can broadly affect cognitive processes, and prior research demonstrates MJ-related alterations in executive functioning, attention, memory, learning, decision-making, and processing speed (Becker et al., 2014, Lisdahl et al., 2014, Meier et al., 2012, Swift et al., 2008). Moreover, MJ use has been associated with mental health issues, including co-morbid mood symptoms, especially depression and anxiety (Weinstein et al., 2013), lower age of onset of psychosis, mania, increased risk of suicide attempts and a more severe course of illness (Kvitland et al., 2014). The effects of MJ on mood and other psychiatric symptoms has been linked to the ability of the endocannabinoid system to modulate the activity of other neurotransmitter systems, energy metabolism and immune functions (Leweke and Koethe, 2008).

Findings from neuroimaging studies of MJ users, often focused on either adolescent users or adult users, document significant associations between marijuana use and alterations in neurobiology, including brain structure, function and neurochemistry (for review, see Batalla et al., 2013, Martin-Santos et al., 2010, Sneider et al., 2013b). Findings of alterations in brain structure reported using magnetic resonance imaging (MRI) are somewhat heterogenous, however, and the significance of the changes identified using this technology remains controversial because of conflicting findings among existing studies. For instance, while some studies report alterations in whole brain and regional volumes, and in cortical thickness and subcortical volumes (Ashtari et al., 2011, Cousijn et al., 2012, Matochik et al., 2005, Yucel et al., 2008), other investigations fail to report significant differences in brain structure between adult MJ users and comparison subjects (Block et al., 2000, Jager et al., 2007, Tzilos et al., 2005). Importantly, there is mounting evidence that MJ use, particularly exposure to THC, may be more deleterious during adolescence, a time when cognitive development and brain maturation are rapidly ongoing (Lisdahl et al., 2013). For instance, adolescent MJ users exhibit altered frontal region and insula cortical thickness, suggestive of aberrant gray matter (GM) development or maturation that could persist beyond adolescence (Lopez-Larson et al., 2011), and also exhibit alterations in prefrontal cortex, amygdala and cerebellum, some of which are sex-specific (McQueeny et al., 2011, Medina et al., 2009, Medina et al., 2010). It also has been reported that smaller orbitofrontal cortex volumes observed at age 12 years predict initiation of MJ use by age 16 years, whereas volumes of other regions such as amygdala, hippocampus, and anterior cingulate cortex were not predictive of later MJ use (Cheetham et al., 2012). Furthermore, in a longitudinal study of adolescent MJ users, greater lifetime exposure to MJ predicted greater cortical thickness in the left and right superior frontal gyri, left pars opercularis, right pars triangularis, right supramarginal, and left inferior parietal cortex after adjusting for baseline cortical thickness, suggesting that heavy MJ use during adolescence alters the trajectory of cortical GM development (Epstein and Kumra, 2015).

Collectively, previous investigations have focused on identifying regions that exhibit structural alterations related to the effects of MJ use measured during adolescence or during adulthood, but there are few investigations specifically examining structural alterations in emerging adults who initiated MJ use in adolescence. Thus, the present study aimed to characterize potential neurobiological consequences of MJ use on cortical thickness and subcortical volumetric differences in emerging adult MJ users compared with age-matched non-user subjects. A priori regions of interest (ROIs) included orbito-frontal, dorsolateral prefrontal, and anterior cingulate cortices (OFC, DLPFC, and ACC respectively), and superior and middle frontal gyri, as well as subcortical amygdala, thalamus and hippocampus regions.

Frontal ROIs were chosen based on previous reports of MJ-related functional alterations in each region during cognitive task performance. Specifically, altered OFC and DLPFC activity is associated with impaired decision-making and poor adaptation to negative consequences (Bolla et al., 2005), and ACC hypoactivity is associated with error awareness and performance monitoring (Hester et al., 2009) and memory retrieval during spatial navigation (Sneider et al., 2013a). Increased activity has been observed in superior and middle frontal gyri in MJ users during inhibitory processing, suggesting inefficient functional responses and potential overcompensation by neighboring tissue to adequately perform the task (Tapert et al., 2007). Given the sub-optimal functional response of these a priori regions in MJ users during cognitive task performance, it is possible that surface-based cortical thickness analyses will reveal corresponding structural changes, with lower cortical thickness related to MJ use in these regions.

Hippocampus, amygdala and thalamus, regions demonstrating high CB1 receptor distribution (Herkenham et al., 1991), also were selected for volumetric analysis based on evidence that MJ users exhibit functional and neurochemical alterations in these regions related to marijuana use (Ashtari et al., 2011, Bolla et al., 2005, Cousijn et al., 2012, Demirakca et al., 2011, Gilman et al., 2014, Glass et al., 1997, Hester et al., 2009, Mashhoon et al., 2013, Matochik et al., 2005, Schacht et al., 2012, Sneider et al., 2013a, Sneider et al., 2013b, Yucel et al., 2008). Clinical measures of mood and impulsivity were examined relative to cortical thickness and brain volume to further probe potential links with neurobiological consequences of marijuana use.

Section snippets

Participants, demographics and procedure

Fifteen marijuana users (MJ; 2 females, age 21.8 ± 3.6) and fifteen non-user controls (NU; 2 females, age 22.3 ± 3.5) were included in this study. Participants were selected from a larger pool of subjects that underwent structural MRI scanning at McLean Hospital as part of two larger functional magnetic resonance (MR) imaging and MR spectroscopy studies (Silveri et al., 2011, Sneider et al., 2013a). All participants were matched on age, education and alcohol use, and underwent a Structured Clinical

Demographics and substance use

There were no significant differences between MJ and NU groups in age, gender distribution, education or amount of alcohol consumed weekly (Table 1). All MJ use variables are also reported in Table 1.

Clinical data

There were no significant differences between MJ and NU groups on total or subscale scores on the POMS or PANAS (Table 1). MJ users did differ significantly from the NU group on multiple BIS measures (Table 1). MJ exhibited higher scores on the BIS motor (F(1,29)=4.21, p = 0.05, ES = .39) and

Discussion

Emerging adult MJ users exhibited cortical thickness and volumetric differences relative to healthy emerging adult NU. Findings revealed less rFG cortical thickness (i.e., rFG cortical thinness), and smaller thalamic volumes in MJ users. Unlike cortical thinning, which is a continuous measure collected with longitudinal data, ‘cortical thinness’ is a descriptive term that has previously been operationally defined (Mashhoon et al., 2014) as indicating less or lower cortical thickness measured

Conflict of interest

No conflict declared.

Contributors

Drs. Sava, Sneider and Silveri conceptualized the study. Drs. Mashhoon and Sava conducted the data processing and analysis. Drs. Mashhoon, Sava and Silveri drafted the manuscript. Drs. Sneider and Nickerson made contributions and edited the manuscript. Dr. Mashhoon consolidated edits from coauthors. All authors approved the final manuscript.

Role of funding sources

This investigation was supported in part by National Institute on Drug Abuse grants K01DA034028 (YM), R03DA022482 (JTS), and R01DA037265 (LDN), and National Institute on Alcohol Abuse and Alcoholism grant K01AA014651 (MMS).

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