what this article thinks they found. I think that they found that chronic MJ use was associated with less grey matter (e.g. neurons) in the OFC, and more neural connections in the OFC. That increase in neural connections in this region may be to compensate for the reduced grey matter.
From-
http://www.pnas.org/content/111/47/16913.full
Unlike the animal literature, whether exposure to marijuana leads to long-term changes in human brain structure has been equivocal. To address this limitation, we evaluated brain structural changes associated with chronic marijuana use in a large group of well-characterized marijuana users relative to age- and sex-matched nonusing controls. Our findings provide evidence that heavy, chronic marijuana users have lower OFC gray matter volumes compared with nonusing controls. This finding remained even in the smaller sample of exclusively marijuana users (n = 27, i.e., no comorbid substance use), demonstrating that this effect (i) is robust and (ii) is greater than potential effects of comorbid substance use. Similar decreases in OFC volume have been reported in marijuana using adults (29) and adolescents (12) compared with nonusing controls. Interestingly, a prospective study also found that smaller OFC volumes at 12 y of age predicted initiation of marijuana use at 16 y of age (30). These effects on the OFC are not surprising given that the OFC is a primary region in the reward network, is enriched with CB1 receptors, and is highly implicated in addictive behaviors (23, 24, 31, 32) such as those related to disruptions in motivation (33) and decision making (34, 35). Whereas others have reported alterations in various CB1-enriched regions such as the amygdala, hippocampus, ventromedial prefrontal, OFC, insula, and striatum, our findings are specific to the OFC. Several animal and human studies have demonstrated greater THC-induced down-regulation of CB1 receptors in cortical areas relative to subcortical areas, which support our findings. Given that CB1 receptors are found on excitatory terminals of cortical projection neurons, this alteration in endocannabinoid signaling could affect the plasticity of OFC circuits (36). Unfortunately, the cross-sectional nature of the present study cannot directly address whether these reductions are the cause or the consequence of marijuana use. However, neurotoxic effects of cannabis have been widely reported in the animal literature. Based on the animal literature, potential mechanisms that may lead to OFC reductions due to cannabis neurotoxicity may, therefore, include neuronal loss, changes in cell size, or a reduction in CB1 density. It is possible, however, that these OFC abnormalities may reflect preexisting pathophysiology related to vulnerability to marijuana abuse and dependence.
To determine the potential downstream effects of OFC volume reduction, we evaluated OFC functional (fcMRI) and structural connectivity (DTI). Functional connectivity analysis revealed greater connectivity within the OFC network in marijuana users compared with controls, which is concordant with existing resting-state studies (37) and task-based studies (38, 39). This increased functional connectivity in users may suggest a compensatory mechanism whereby greater network recruitment is engaged to compensate for OFC liability (40). Tomasi et al. (41) illustrated how greater functional connectivity requires higher glucose consumption (?70% of brain’s energy consumption), and, consequently, hubs of higher functional connectivity must be efficient. In their report, the OFC was described as having high glucose efficiency as measured by the ratio between the strength of functional integration (based on rsfMRI and the number of connections of the network nodes) and cerebral metabolic rate of glucose. Taken together, because the OFC is a network hub, observed increase in OFC functional connectivity concomitant with reductions in OFC gray matter may suggest neuroadaptive plasticity.
The findings of greater functional connectivity in OFC network in marijuana users were echoed by increased structural connectivity (i.e., FA) of the forceps minor in marijuana users relative to controls. Greater FA has been suggested to reflect better myelination and/or intact axons (42). Based on RD and AD measurements, it appears that the FA difference between the groups in the forceps minor was driven by lower RD, suggesting greater myelination in the marijuana users. Although not as widely reported, greater white matter microstructure in marijuana users has also been reported by DeLisi et al. (43) in adolescent moderate marijuana users; however, the difference from controls did not reach significance. Greater FA has also been reported in alcohol users (44, 45), which was posited to reflect a premorbid vulnerability for accelerated PFC myelin maturation in those at risk for alcohol use disorders. Among possible explanations for these findings of greater FA in marijuana users include differential effects of cannabis depending on the specific fiber tract. Specifically, because the forceps minor connects the OFC, which is enriched with CB1, it is possible that there are unique neural adaptations to the forceps minor that are unlike other white matter tracts in the brain (e.g., corpus callosum). Others have also reported antiinflammatory properties of cannabis constituents such as cannabidiol (CBD). DTI is sensitive to increased tissue water resulting in decreased FA as a result of inflammation; therefore, it is possible that any antiinflammatory effects of cannabis would lead to greater FA. Lastly, it is also possible that the effects of cannabis (i.e., CBD) may be beneficial to white matter in terms of regulation of mitochondrial activity, antioxidant processes, and modulation of clearance processes that protect neurons on the molecular level (46). Future studies are needed to examine these specific effects on white matter.
Altogether, if these effects are indeed due to neurotoxic effects of cannabis, the inverse relationship between OFC structure and connectivity suggests that OFC gray matter (vs. white matter) is more vulnerable to the effects of THC. Endogenous cannabinoids play an important role in synaptic pruning (47), therefore, introduction of exogenous cannabinoids such as THC might disrupt this system by competing for the receptors and, thereby, inhibiting synaptic pruning particularly in receptor-enriched areas such as the OFC (48). In other words, any premorbid developmental trajectory may be modified by exposure to cannabis, resulting in accelerated OFC myelin maturation. However, although the majority of the animal literature and emergent human studies illustrate the down-regulation of CB1 receptors as a result of THC, we acknowledge that longitudinal studies are needed to address causality of these neural abnormalities (49?–51).
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