The endocannabinoid system in normal and pathological brain ageing

Bilkei-Gorzó, András

doi:10.1098/rstb.2011.0388

Cited by 114 publications

(94 citation statements)

References 268 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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.…”

Section: Discussionmentioning

confidence: 87%

Long-term effects of marijuana use on the brain

Filbey

Aslan

Calhoun

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

204

196

View full text Add to dashboard Cite

Questions surrounding the effects of chronic marijuana use on brain structure continue to increase. To date, however, findings remain inconclusive. In this comprehensive study that aimed to characterize brain alterations associated with chronic marijuana use, we measured gray matter (GM) volume via structural MRI across the whole brain by using voxel-based morphology, synchrony among abnormal GM regions during resting state via functional connectivity MRI, and white matter integrity (i.e., structural connectivity) between the abnormal GM regions via diffusion tensor imaging in 48 marijuana users and 62 age-and sex-matched nonusing controls. The results showed that compared with controls, marijuana users had significantly less bilateral orbitofrontal gyri volume, higher functional connectivity in the orbitofrontal cortex (OFC) network, and higher structural connectivity in tracts that innervate the OFC (forceps minor) as measured by fractional anisotropy (FA). Increased OFC functional connectivity in marijuana users was associated with earlier age of onset. Lastly, a quadratic trend was observed suggesting that the FA of the forceps minor tract initially increased following regular marijuana use but decreased with protracted regular use. This pattern may indicate differential effects of initial and chronic marijuana use that may reflect complex neuroadaptive processes in response to marijuana use. Despite the observed age of onset effects, longitudinal studies are needed to determine causality of these effects.MRI | orbitofrontal cortex | functional connectivity | resting state fMRI | diffusion tensor imaging

show abstract

Section: Discussionmentioning

confidence: 87%

Long-term effects of marijuana use on the brain

Filbey

Aslan

Calhoun

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

204

196

View full text Add to dashboard Cite

show abstract

“…Given that the expression of the ECS can be modified by aging (Bilkei-Gorzo, 2012), can be different between genders (Battista et al, 2012) and it is related to sustained food intake (Di Marzo et al, 2001), analyses were controlled for age, gender, and BMI. Model 1 included the expression of every ECS marker.…”

Section: Discussionmentioning

confidence: 99%

Peripheral Endocannabinoid System Dysregulation in First-Episode Psychosis

Bioque

García‐Bueno

MacDowell

et al. 2013

Neuropsychopharmacol

View full text Add to dashboard Cite

Several hypotheses involving alterations of the immune system have been proposed among etiological explanations for psychotic disorders. The endocannabinoid system (ECS) has a homeostatic role as an endogenous neuroprotective and anti-inflammatory system. Alterations of this system have been associated with psychosis. Cannabis use is a robust risk factor for these disorders that could alter the ECS signalling. In this study, 95 patients with a first episode of psychosis (FEP) and 90 healthy controls were recruited. Protein expression of cannabinoid receptor 2 (CB2), the protein levels of the main endocannabinoid synthesizing enzymes N-acyl phosphatidylethanolamine phospholipase (NAPE) and diacylglycerol lipase (DAGL), and of degradation enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) were determined by western blot analysis in peripheral blood mononuclear cells (PBMCs). Patients with a FEP showed a decreased expression of CB2 and of both endocannabinoids synthesizing enzymes (NAPE and DAGL) in comparison to healthy controls. After controlling for age, gender, body mass index, and cannabis use, NAPE and DAGL expression remained significantly decreased, whereas FAAH and MAGL expression were increased. On the other hand, FEP subjects with history of severe cannabis use showed a larger ECS dysregulation compared with healthy controls. These results indicate an ECS dysregulation in PBMC of FEP patients. The alteration of the ECS presented at the initial phases of psychosis could be contributing to the pathophysiology of the disease and constitutes a possible biomarker of psychotic disorders and an interesting pharmacological target to take into account for therapeutic purposes.

show abstract

“…Evidence suggests that the endocannabinoid system is critically involved in regulating neural development through activation of neurotrophic factors (Díaz-Alonso et al 2012;Bilkei-Gorzo 2012) and promoting oligodendrocyte maturation (Molina-Holgado et al 2002). Given this regulatory role in white matter growth, it follows that perturbation of this system by chronic exposure to exogenous cannabinoids may alter the development of white matter tracts (Hirvonen et al 2012).…”

Section: Introductionmentioning

confidence: 98%

An MRI study of white matter tract integrity in regular cannabis users: effects of cannabis use and age

et al. 2016

View full text Add to dashboard Cite

Rationale Conflicting evidence exists on the effects of cannabis use on brain white matter integrity. The extant literature has exclusively focused on younger cannabis users, with no studies sampling older cannabis users. Objectives We recruited a sample with a broad age range to examine the integrity of major white matter tracts in association with cannabis use parameters and neurodevelopmental stage. Methods Regular cannabis users (n = 56) and non-users (n = 20) with a mean age of 32 (range 18-55 years) underwent structural and diffusion MRI scans. White matter was examined using voxel-based statistics and via probabilistic tract reconstruction. The integrity of tracts was assessed using average fractional anisotropy, axial diffusivity and radial diffusivity. Diffusion measures were compared between users and non-users and as group-by-age interactions. Correlations between diffusion measures and age of onset, duration, frequency and dose of current cannabis use were examined. Results Cannabis users overall had lower fractional anisotropy than healthy non-users in the forceps minor tract only (p = .015, partial eta = 0.07), with no voxel-wise differences observed. Younger users showed predominantly reduced axial diffusivity, whereas older users had higher radial diffusivity in widespread tracts. Higher axial diffusivity was associated with duration of cannabis use in the cingulum angular bundle (beta = 5.00 x 10−5, p = .003). Isolated higher AD in older cannabis users was also observed. Conclusions The findings suggest that exogenous cannabinoids alter normal brain maturation, with differing effects at various neurodevelopmental stages of life. These age-related differences are posited to account for the disparate results described in the literature.

show abstract

The endocannabinoid system in normal and pathological brain ageing

Cited by 114 publications

References 268 publications

Long-term effects of marijuana use on the brain

Long-term effects of marijuana use on the brain

Peripheral Endocannabinoid System Dysregulation in First-Episode Psychosis

An MRI study of white matter tract integrity in regular cannabis users: effects of cannabis use and age

Contact Info

Product

Resources

About