Neuroanatomical alterations in people with high and low cannabis dependence, Valentina Lorenzetti et al., 2019

Neuroanatomical alterations in people with high and low cannabis dependence

Valentina Lorenzetti, Yann Chye, Chao Suo, Mark Walterfang, Dan I Lubman, Michael Takagi, Sarah Whittle, Antonio Verdejo-Garcia, Janna Cousijn, Christos Pantelis, Marc Seal, Alex Fornito, Murat Yücel and Nadia Solowij

Australian & New Zealand Journal of Psychiatry, 2019, 1–8



Objectives : We aimed to investigate whether severity of cannabis dependence is associated with the neuroanatomy of key brain regions of the stress and reward brain circuits.

Methods : To examine dependence-specific regional brain alterations, we compared the volumes of regions relevant to reward and stress, between high-dependence cannabis users (CD+, n = 25), low dependence cannabis users (CD−, n = 20) and controls (n = 37).

Results : Compared to CD− and/or controls, the CD+ group had lower cerebellar white matter and hippocampal volumes, and deflation of the right hippocampus head and tail.

Conclusion : These findings provide initial support for neuroadaptations involving stress and reward circuits that are specific to high-dependence cannabis users.

Keywords : Cannabis, dependence, neuroanatomy, magnetic resonance imaging, hippocampus, caudate, pituitary gland, cerebellum



Cannabis dependence (CD) affects over 13 million individuals worldwide and has the second highest global treatment burden for illicit substances (United Nations Office on Drugs and Crime [UNODC], 2016). Over 28% of admissions to treatment services for drug use problems are cannabis- specific (UNODC, 2016). Individuals with CD represent the most vulnerable of cannabis users and experience impaired mental health and well-being relative to recreational cannabis users and non-using controls (Pol et al., 2013). A key feature of dependence is compulsive drug use driven by negative reinforcement (i.e. negative emotions or distress when one cannot access drugs), despite the physical or psychological problems associated with maladaptive use patterns (e.g. neglect of obligations and impaired quality
of life; American Psychiatric Association [APA], 2013).

Drug dependence has been linked to neuroadaptations in neural circuits involved in reward, stress and motivation (Everitt and Robbins, 2016; Koob, 2009; Volkow et al., 2013). Neuroanatomical alterations of structures within these circuits (e.g. hippocampus, amygdala, striatum, and cerebellum) have been found in neuroimaging studies of regular cannabis users (Lorenzetti et al., 2016). However, neuroimaging studies of regular cannabis users have not consistently differentiated cannabis users with and without
dependence/problematic use. Rather, they have compared regular cannabis users poorly characterised for levels of dependence to non-cannabis using controls. It is unclear whether cannabis users with and without CD show dissociable neural alterations as postulated by neuroscientific models of addiction (Everitt and Robbins, 2016; Koob, 2009; Volkow et al., 2013).

To address this knowledge gap, we compared neuroanatomical features between cannabis users with highdependence (CD+), low-dependence (CD−) and controls. Specifically, we examined whether the volumes of brain regions that neuroscientific models of addiction implicate in reward, stress regulation, learning and memory, and emotion regulation differ between these groups. Regions included the amygdala, hippocampus, pituitary, nucleus accumbens (NAc), caudate, putamen, pallidum and the cerebellum (total, grey matter [GM] and white matter [WM]). We hypothesised that CD+ relative to CD− and controls would show reduced medial temporal and cerebellar volumes, and larger volumes of reward and stress regions (i.e. pituitary and striatal regions). We followed up hippocampal volume results with shape analyses to identify alterations specific to hippocampal subregions.