In considering the results of this meta-analysis, we have to acknowledge a number of possible limitations. First of all, studies varied broadly in terms of total amount of cannabis use. However, the high inconsistency in reporting the total amount between different studies did not allow quantifying the heterogeneity of this putative moderator. Furthermore, smoked cannabis contains different compounds with opposing effects, which include not only THC but also CBD. Interestingly, a recent whole brain structural imaging study found inverse correlations of bilaterally hippocampal grey matter concentration with the ratio of THC/CBD. In particular, the authors found positive correlations with CBD, pointing to a putative neuroprotective effect of this molecule in the hippocampal region. This result can help to explain the above divergent results in cannabis users with inconsistent findings. Furthermore, the observed inconsistencies may also be the consequence of variations of street cannabis strengths.[54, 56] In our investigation, most of the reviewed papers do not adequately consider this fact and more attention should be paid in conducting further studies. Additionally, apart from THC and CBD, there are other compounds, such as delta-8-THC, tetrahydrocannabivarin and cannabinol, which all have different effects, and their roles have not yet been broadly investigated in the available literature. Furthermore, there may be genetic variations in sensitivity to such effects even amongst non-psychotic users. Comparing results between studies presented in this meta-analysis is also hindered by differences in inclusion criteria and design of the studies. Not all studies used DSM-IV criteria for cannabis dependence or abuse and studies varied in how they set criteria to define their cannabis using and non-using group. Also, a considerable overlap between cannabis and other illicit drug use may have played a confounding role. In particular, some of the included samples presented a significant history of alcohol abuse[30, 36, 29] or nicotine dependence.[30, 29] Moreover, although we carefully excluded the presence of comorbid psychotic diagnoses, some samples were presenting other psychiatric problems, either diagnosed or self-reported. However, the majority of the reviewed samples did not have any comorbid psychopathologies. Of the three samples presenting comorbidities, two samples presented psychopathology in a significant minority of the sample: in Lopez-Larson et al., one participant had past depression and one a history of heavy alcohol use; in Cousijn et al., no participants were reported with a diagnosis of attention deficit hyperactivity disorder. The study by Ashtari et al. examined samples with a high proportion of participants with a number of comorbid current and past disorders, including post-traumatic stress disorder (n = 2), attention deficit hyperactivity disorder (n = 2), and oppositional defiant/conduct disorder (n = 4). Finally, it is relevant to acknowledge that, even though a correlation between cannabis use and hippocampal volume reduction has been found, correlation is not causation and our meta-analysis of cross-sectional studies does not allow us to infer a causal role for any of the variables. Though few studies have taken a longitudinal approach whilst investigating the relation between cannabis use and structural abnormalities, a recent study suggests that some structural abnormalities could predate the onset of cannabis use.