Cannabis Use Is Quantitatively Associated with Nucleus Accumbens and Amygdala Abnormalities in Young Adult Recreational Users

“All participants also completed the State Trait Anxiety Inventory Form (STAI; Spielberger et al., 1983) to assess anxiety, the Hamilton Depression Rating Scale (HAM-D; Hamilton, 1960) to assess depression, and the Ten-Item Personality Inventory (TIPI; Gosling et al., 2003) to assess personality characteristics.”

“All participants completed the Alcohol Use Disorder Identification Test (AUDIT; Saunders et al., 1993) to check for problem drinking; any potential participant scoring above an 8 was excluded from inclusion in the final cohort of matched participants.”

“In voxel-based morphometry analyses, gray matter density is compared across the entire brain at every voxel, allowing the detection of differences in small or large regions, which can be topographically specified with high accuracy (Ashburner and Friston, 2000) even though all brains have been normalized.”

“All participants also completed the State Trait Anxiety Inventory Form (STAI; Spielberger et al., 1983) to assess anxiety, the Hamilton Depression Rating Scale (HAM-D; Hamilton, 1960) to assess depression, and the Ten-Item Personality Inventory (TIPI; Gosling et al., 2003) to assess personality characteristics.”

“Converging findings in the addiction literature implicate these regions as being important to the impact that marijuana may have on the brain (for review, see Koob and Volkow, 2010).”

“First, the nucleus accumbens and amygdala have been implicated in non-drug reward processing (Blood and Zatorre, 2001; Breiter et al., 2001), as well as with the euphoria associated with the rewarding effects of drugs (Breiter et al., 1997; Gálvez-Buccollini et al., 2008; Gilman et al., 2008).”

“Our observations indicate that such changes may occur before dependence, which is intriguing in the context that the amygdala appears to play an important role in drug craving (Breiter et al., 1997; Childress et al., 1999; Bonson et al., 2002).”

“First, the nucleus accumbens and amygdala have been implicated in non-drug reward processing (Blood and Zatorre, 2001; Breiter et al., 2001), as well as with the euphoria associated with the rewarding effects of drugs (Breiter et al., 1997; Gálvez-Buccollini et al., 2008; Gilman et al., 2008).”

“First, the nucleus accumbens and amygdala have been implicated in non-drug reward processing (Blood and Zatorre, 2001; Breiter et al., 2001), as well as with the euphoria associated with the rewarding effects of drugs (Breiter et al., 1997; Gálvez-Buccollini et al., 2008; Gilman et al., 2008).”

“Dendritic arborization changes may relate to an increase in dopamine, because acute administration of drugs of abuse (e.g., THC; Chen et al., 1990) produces increases in extracellular levels of dopamine (DA) in the nucleus accumbens (Pontieri et al., 1995).”

“9% increase in the number of dendritic branches and increased density of dendritic spines in the shell of the nucleus accumbens in amphetamine- and cocaine-treated rats (Robinson and Kolb, 1999) and this increase appears to persist long after acute administration.”

“Furthermore, global measures of volume lack information on detailed topography within a given brain structure (Filipek et al., 1989; Filipek et al., 1994; Makris et al., 1999; Fischl et al., 2002).”

“Whole-brain T1-weighted 1 mm isotropic structural scans were collected using a 3D multiecho MPRAGE sequence (176 sagittal slices, FOV 256 mm, TR 2530 ms, TI 1200 ms, 2 GRAPPA acceleration, TE 1.64/3.5/5.36/7.22 ms, BW 651 Hz/px, Tacq 6:03 min; van der Kouwe et al., 2008).”

“Our observations indicate that such changes may occur before dependence, which is intriguing in the context that the amygdala appears to play an important role in drug craving (Breiter et al., 1997; Childress et al., 1999; Bonson et al., 2002).”

“These exposure-dependent deformations may precede more pronounced volumetric changes, because others have reported a reduction in amygdala volumes in long-term, heavy users (Yücel et al., 2008; Schacht et al., 2012).”

“Marijuana users completed a timeline follow-back (Sobell et al., 1986) asking them to indicate, for the past 90 d, the days that they smoked marijuana.”

“Dendritic arborization changes may relate to an increase in dopamine, because acute administration of drugs of abuse (e.g., THC; Chen et al., 1990) produces increases in extracellular levels of dopamine (DA) in the nucleus accumbens (Pontieri et al., 1995).”

“THC binds to endogenous cannabinoid (CB1) receptors located in brain regions including the nucleus accumbens and amygdala (Burns et al., 2007).”

“The density increase was localized to a large area, which clearly represents the extended amygdala as defined by Heimer and Alheid (1991), a neuroanatomical entity implicated in addiction (Koob, 2003).”

“Second, animal studies have demonstrated that exogenous and endogenous cannabinoids can significantly alter synaptic transmission in the nucleus accumbens (Lupica et al., 2004) and in the amygdala (Azad et al., 2004).”

“Such an observation is also consistent with data showing a negative correlation between level of cannabis dependence and amygdala gray matter density (Cousijn et al., 2012).”

“The density increase was localized to a large area, which clearly represents the extended amygdala as defined by Heimer and Alheid (1991), a neuroanatomical entity implicated in addiction (Koob, 2003).”

“First, the nucleus accumbens and amygdala have been implicated in non-drug reward processing (Blood and Zatorre, 2001; Breiter et al., 2001), as well as with the euphoria associated with the rewarding effects of drugs (Breiter et al., 1997; Gálvez-Buccollini et al., 2008; Gilman et al., 2008).”

“Second, animal studies have demonstrated that exogenous and endogenous cannabinoids can significantly alter synaptic transmission in the nucleus accumbens (Lupica et al., 2004) and in the amygdala (Azad et al., 2004).”

“Furthermore, global measures of volume lack information on detailed topography within a given brain structure (Filipek et al., 1989; Filipek et al., 1994; Makris et al., 1999; Fischl et al., 2002).”

“A study examining the structural effects of cannabis on the prefrontal cortex reported greater gray matter density in the precentral gyrus of marijuana users (Matochik et al., 2005).”

“Furthermore, diffusion tensor imaging studies have shown that cannabis use may affect the integrity of white matter fiber tracts in prefrontal regions (Gruber and Yurgelun-Todd, 2005).”

“It is also the most widely used illicit drug on college campuses (Mohler-Kuo et al., 2003).”

“All acquisitions were automatically positioned using AutoAlign (van der Kouwe et al., 2005).”

“These results extend prior studies showing that drugs of abuse that are known to elevate DA release are associated with structural abnormalities in the brain and related disruptions in behavior (Makris et al., 2004; Makris et al., 2008).”

“These methods have been used previously (Breiter et al., 1997; Makris et al., 2008; Blood et al., 2010; Blood et al., 2012).”

“Furthermore, global measures of volume lack information on detailed topography within a given brain structure (Filipek et al., 1989; Filipek et al., 1994; Makris et al., 1999; Fischl et al., 2002).”

“, Bechara, 2001), and functional MRI and magnetic resonance spectroscopy studies have shown that cannabis use may affect the function of this region (Quickfall and Crockford, 2006; Hermann et al., 2007).”

“…prefrontal cortex dysfunction is involved with decision-making abnormalities in addiction (e.g., Bechara, 2001), and functional MRI and magnetic resonance spectroscopy studies have shown that cannabis use may affect the function of this region (Quickfall and Crockford, 2006; Hermann et al., 2007).”

“Animal studies show structural changes in brain regions underlying these functions after exposure to 9tetrahydrocannabinol (THC), the main psychoactive component of cannabis (Lawston et al., 2000; Downer et al., 2001).”

“Although some studies have shown volume reductions in the hippocampus, amygdala, and cerebellum, others have not shown such effects (see Lorenzetti et al., 2010 for review).”

“These exposure-dependent deformations may precede more pronounced volumetric changes, because others have reported a reduction in amygdala volumes in long-term, heavy users (Yücel et al., 2008; Schacht et al., 2012).”

“These methods have been used previously (Breiter et al., 1997; Makris et al., 2008; Blood et al., 2010; Blood et al., 2012).”

“Therefore, we ensured that no participant exhibited overt signs of intoxication based on a four-item marijuana intoxication scale developed in our laboratory that was designed to assess four signs of acute intoxication (Karschner et al., 2011): increased resting heart rate ( 100 beats/minute), congestion of the conjun…”

“Animal studies show structural changes in brain regions underlying these functions after exposure to 9- tetrahydrocannabinol (THC), the main psychoactive component of cannabis (Lawston et al., 2000; Downer et al., 2001).”

“Third, animal studies have shown that structural abnormalities can occur in the nucleus accumbens of THC-treated animals (Kolb et al., 2006).”

“For example, subcortical structural alterations have been reported in thalami of patients with schizophrenia (Harms et al., 2007; Kang et al., 2008; Coscia et al., 2009; Harms et al., 2010), obsessive-compulsive disorders (Kang et al.”

“These methods have been used previously (Breiter et al., 1997; Makris et al., 2008; Blood et al., 2010; Blood et al., 2012).”

“The coordinates (in millimeters) of these ROIs were based on the max vox of the difference cluster constrained by the anatomical segmentations of the nucleus accumbens and amygdala (Gasic et al., 2009) observed in the left hemisphere structures and the mirror location of these maxima in the right hemisphere.”

“, 2008), Parkinson’s disease (McKeown et al., 2008), and Tourette’s syndrome (Wang et al.”

“Moreover, its use is increasing among adolescents and young adults (Henry et al., 2003), partially due to society’s changing beliefs about cannabis use and its legal status.”

“These results have been replicated using nicotine (Gonzalez et al., 2005) and cannabis (Kolb et al., 2006).”

“Because THCCOOH, the main secondary metabolite of THC, can be detected in urine several weeks after last use (Fraser et al., 2002), a urine test alone could not determine with certainty whether participants were acutely intoxicated.”