Cerebellar white-matter changes in cannabis users with and without schizophrenia.

School of Psychology, University of Wollongong, Australia.
Psychological Medicine (Impact Factor: 5.59). 04/2011; 41(11):2349-59. DOI: 10.1017/S003329171100050X
Source: PubMed

ABSTRACT The cerebellum is rich in cannabinoid receptors and implicated in the neuropathology of schizophrenia. Long-term cannabis use is associated with functional and structural brain changes similar to those evident in schizophrenia, yet its impact on cerebellar structure has not been determined. We examined cerebellar grey and white matter in cannabis users with and without schizophrenia.
Seventeen patients with schizophrenia and 31 healthy controls were recruited; 48% of the healthy group and 47% of the patients were long-term heavy cannabis users (mean 19.7 and 17.9 years near daily use respectively). Cerebellar measures were extracted from structural 3-T magnetic resonance imaging (MRI) scans using semi-automated methods, and examined using analysis of covariance (ANCOVA) and correlational analyses.
Cerebellar white-matter volume was reduced in cannabis users with and without schizophrenia compared to healthy non-users, by 29.7% and 23.9% respectively, and by 17.7% in patients without cannabis use. Healthy cannabis users did not differ in white-matter volume from either of the schizophrenia groups. There were no group differences in cerebellar grey matter or total volumes. Total cerebellar volume decreased as a function of duration of cannabis use in the healthy users. Psychotic symptoms and illness duration correlated with cerebellar measures differentially between patients with and without cannabis use.
Long-term heavy cannabis use in healthy individuals is associated with smaller cerebellar white-matter volume similar to that observed in schizophrenia. Reduced volumes were even more pronounced in patients with schizophrenia who use cannabis. Cannabis use may alter the course of brain maturational processes associated with schizophrenia.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Addictions to licit and illicit drugs are chronic relapsing brain disorders that affect circuits that regulate reward, motivation, memory, and decision-making. Drug-induced pathological changes in these brain regions are associated with characteristic enduring behaviors that continue despite adverse biopsychosocial consequences. Repeated exposure to these substances leads to egocentric behaviors that focus on obtaining the drug by any means and on taking the drug under adverse psychosocial and medical conditions. Addiction also includes craving for the substances and, in some cases, involvement in risky behaviors that can cause death. These patterns of behaviors are associated with specific cognitive disturbances and neuroimaging evidence for brain dysfunctions in a diverse population of drug addicts. Postmortem studies have also revealed significant biochemical and/or structural abnormalities in some addicted individuals. The present review provides a summary of the evidence that has accumulated over the past few years to implicate brain dysfunctions in the varied manifestations of drug addiction. We thus review data on cerebrovascular alterations, brain structural abnormalities, and postmortem studies of patients who abuse cannabis, cocaine, amphetamines, heroin, and "bath salts". We also discuss potential molecular, biochemical, and cellular bases for the varied clinical presentations of these patients. Elucidation of the biological bases of addiction will help to develop better therapeutic approaches to these patient populations.
    Acta Neuropathologica 11/2013; · 9.73 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Methamphetamine (METH) is a potent psychostimulant with neurotoxic properties. Heavy use increases the activation of neuronal nitric oxide synthase (nNOS), production of peroxynitrites, microglia stimulation, and induces hyperthermia and anorectic effects. Most METH recreational users also consume cannabis. Preclinical studies have shown that natural (Δ9-tetrahydrocannabinol, Δ9-THC) and synthetic cannabinoid CB1 and CB2 receptor agonists exert neuroprotective effects on different models of cerebral damage. Here, we investigated the neuroprotective effect of Δ9-THC on METH-induced neurotoxicity by examining its ability to reduce astrocyte activation and nNOS overexpression in selected brain areas. Rats exposed to a METH neurotoxic regimen (4×10 mg/kg, 2 hours apart) were pre- or post-treated with Δ9-THC (1 or 3 mg/kg) and sacrificed 3 days after the last METH administration. Semi-quantitative immunohistochemistry was performed using antibodies against nNOS and Glial Fibrillary Acidic Protein (GFAP). Results showed that, as compared to corresponding controls (i) METH-induced nNOS overexpression in the caudate-putamen (CPu) was significantly attenuated by pre- and post-treatment with both doses of Δ9-THC (-19% and -28% for 1 mg/kg pre- and post-treated animals; -25% and -21% for 3 mg/kg pre- and post-treated animals); (ii) METH-induced GFAP-immunoreactivity (IR) was significantly reduced in the CPu by post-treatment with 1 mg/kg Δ9-THC1 (-50%) and by pre-treatment with 3 mg/kg Δ9-THC (-53%); (iii) METH-induced GFAP-IR was significantly decreased in the prefrontal cortex (PFC) by pre- and post-treatment with both doses of Δ9-THC (-34% and -47% for 1 mg/kg pre- and post-treated animals; -37% and -29% for 3 mg/kg pre- and post-treated animals). The cannabinoid CB1 receptor antagonist SR141716A attenuated METH-induced nNOS overexpression in the CPu, but failed to counteract the Δ9-THC-mediated reduction of METH-induced GFAP-IR both in the PFC and CPu. Our results indicate that Δ9-THC reduces METH-induced brain damage via inhibition of nNOS expression and astrocyte activation through CB1-dependent and independent mechanisms, respectively.
    PLoS ONE 01/2014; 9(5):e98079. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Epidemiological studies have shown that the association between cannabis and psychosis is robust and consistent across different samples, with compelling evidence for a dose-response relationship. Because longitudinal work indicates that cannabis use precedes psychotic symptoms, it seems reasonable to assume a causal relationship. However, more work is needed to address the possibility of gene-environment correlation (for example, genetic risk for psychosis causing onset of cannabis use). Moreover, knowledge about underlying biological mechanisms linking cannabis use and psychosis is still relatively limited. In order to understand how cannabis use may lead to an increased risk for psychosis, in the present article we (a) review the epidemiological, neurobiological, and genetic evidence linking cannabinoids and psychosis, (b) assess the quality of the evidence, and finally (c) try to integrate the most robust findings into a neurodevelopmental model of cannabis-induced psychosis and identify the gaps in knowledge that are in need of further investigation. Expected final online publication date for the Annual Review of Clinical Psychology Volume 10 is March 20, 2014. Please see for revised estimates.
    Annual Review of Clinical Psychology 01/2014; · 12.42 Impact Factor


Available from
May 22, 2014