Studies on [3H]CP-55940 binding in the human central nervous system: regional specific changes in density of cannabinoid-1 receptors associated with schizophrenia and cannabis use

Dean, Brian; Sundram, Suresh; Bradbury, Robyn; Scarr, Elizabeth; Copolov, David L.

doi:10.1016/s0306-4522(00)00552-2

Cited by 375 publications

(239 citation statements)

References 17 publications

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“…The findings of this study add to a growing body of literature from pharmacological (Jones, 1971;Leweke et al, 2000Leweke et al, , 1999bMcGuire et al, 1995), epidemiological (Andreasson et al, 1987(Andreasson et al, , 1988(Andreasson et al, , 1989Arseneault et al, 2002;McGuire et al, 1995;Zammit et al, 2002), genetic (Ujike et al, 2002), neurochemical (Leweke et al, 1999a), and postmortem (Dean et al, 2001) approaches, suggesting that the consumption of cannabinoids (exogenous) and/or brain cannabinoid dysfunction (endogenous) may contribute to the pathophysiology of psychosis and/or schizophrenia (Emrich et al, 1997;Schneider et al, 1998). Clearly, further work is needed to test these hypotheses.…”

Section: Discussionmentioning

confidence: 51%

The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis

D’Souza

Perry

MacDougall

et al. 2004

Neuropsychopharmacol

903

678

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Recent advances in the understanding of brain cannabinoid receptor function have renewed interest in the association between cannabinoid compounds and psychosis. In a 3-day, double-blind, randomized, and counterbalanced study, the behavioral, cognitive, and endocrine effects of 0, 2.5, and 5 mg intravenous delta-9-tetrahydrocannabinol (D-9-THC) were characterized in 22 healthy individuals, who had been exposed to cannabis but had never been diagnosed with a cannabis abuse disorder. Prospective safety data at 1, 3, and 6 months poststudy was also collected. D-9-THC (1) produced schizophrenia-like positive and negative symptoms; (2) altered perception; (3) increased anxiety; (4) produced euphoria; (5) disrupted immediate and delayed word recall, sparing recognition recall; (6) impaired performance on tests of distractibility, verbal fluency, and working memory (7) did not impair orientation; (8) increased plasma cortisol. These data indicate that D-9-THC produces a broad range of transient symptoms, behaviors, and cognitive deficits in healthy individuals that resemble some aspects of endogenous psychoses. These data warrant further study of whether brain cannabinoid receptor function contributes to the pathophysiology of psychotic disorders.

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Section: Discussionmentioning

confidence: 51%

The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis

D’Souza

Perry

MacDougall

et al. 2004

Neuropsychopharmacol

903

678

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“…However, the reductions found in CB 1 receptor expression in several brain regions, and the no change in CB 1 receptor expression in the prefrontal cortex and the cingulate cortex are in contrast to previous human studies. Using [ 3 H]CP-55940 binding, a lack of change in the caudate putamen and an increase in CB 1 receptor expression was reported in the prefrontal cortex of schizophrenic patients when compared with control subjects (Dean et al, 2001). Another study reported an increase in CB 1 receptors in the cingulate cortex of humans with schizophrenia (Zavitsanou et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…However, other studies have not shown cannabinoid-induced disruption of sensorimotor gating (Stanley-Cary et al, 2002;Bortolato et al, 2005). Also, increases in CB 1 receptor density in frontal cortex subregions have been identified in post-mortem schizophrenic brains (Dean et al, 2001;Zavitsanou et al, 2004), and elevated levels of AEA were detected in cerebrospinal fluid (Leweke et al, 1999;Giuffrida et al, 2004;Leweke et al, 2007) and blood (De Marchi et al, 2003) of anti-psychotic naïve schizophrenics.…”

Section: Introductionmentioning

confidence: 99%

Effect of social isolation on CB1 and D2 receptor and fatty acid amide hydrolase expression in rats

et al. 2008

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Rearing rats in isolation has been shown to produce behavioral and neurochemical alterations similar to those observed in psychoses such as schizophrenia. Also, a dysregulation in both the endocannabinoid and dopaminergic systems has been implicated in schizophrenia. The aim of this study was to determine if there are differences in CB 1 receptor and fatty acid amide hydrolase (FAAH) protein expression, as well as D 2 dopamine receptor expression in different brain regions in rats reared in different environmental conditions. Twenty-one day old male Sprague-Dawley rats were either reared in individual cages (isolated rats) or in group cages of 6 per cage (group housed rats) for 8 weeks. Quantitative fluorescence immunohistochemistry was performed on brain slices using antibodies specific to the CB 1 or D 2 receptor, or the enzyme FAAH. Raising rats in isolation led to a significant decrease in CB 1 receptor expression in the caudate putamen and the amygdala, a significant increase in FAAH expression in the caudate putamen and the nucleus accumbens core and shell, and no significant change in D 2 receptor expression in any region studied. These results indicate that the endocannabinoid system is altered in an animal model of aspects of psychosis. This implies that rearing rats under different housing conditions may provide new insight into the role of the endocannabinoid system in the development of psychoses.

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“…The hypothesis that a dysfunction in endocannabinoid signaling may be associated with schizophrenia is further supported by studies showing that endocannabinoid levels in cerebrospinal fluid (CSF) (Leweke et al, 1999b) and plasma (Yao et al, 2002;De Marchi et al, 2003) as well as CB 1 receptor expression (Dean et al, 2001) are abnormal in schizophrenic patients. The interpretation of these results is obscured, however, by the small number of subjects involved, the interference of concurrent drug therapy, and the lack of systematic comparison with other mental disorders in which endocannabinoid signaling also might be dysregulated.…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Anandamide Levels are Elevated in Acute Schizophrenia and are Inversely Correlated with Psychotic Symptoms

Giuffrida

Leweke

Gerth

et al. 2004

Neuropsychopharmacol

431

340

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The endocannabinoids are a family of bioactive lipids that activate CB 1 cannabinoid receptors in the brain and exert intense emotional and cognitive effects. Here, we have examined the role of endocannabinoid signaling in psychotic states by measuring levels of the endocannabinoid anandamide in cerebrospinal fluid (CSF) of acute paranoid-type schizophrenic patients. We found that CSF anandamide levels are eight-fold higher in antipsychotic-naïve first-episode paranoid schizophrenics (n ¼ 47) than healthy controls (n ¼ 84), dementia patients (n ¼ 13) or affective disorder patients (n ¼ 22). Such an alteration is absent in schizophrenics treated with 'typical' antipsychotics (n ¼ 37), which antagonize dopamine D 2 -like receptors, but not in those treated with 'atypical' antipsychotics (n ¼ 34), which preferentially antagonize 5HT 2A receptors. Furthermore, we found that, in nonmedicated acute schizophrenics, CSF anandamide is negatively correlated with psychotic symptoms (r S ¼ À0.452, P ¼ 0.001). The results suggest that anandamide elevation in acute paranoid schizophrenia may reflect a compensatory adaptation to the disease state.

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Studies on [3H]CP-55940 binding in the human central nervous system: regional specific changes in density of cannabinoid-1 receptors associated with schizophrenia and cannabis use

Cited by 375 publications

References 17 publications

The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis

The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis

Effect of social isolation on CB1 and D2 receptor and fatty acid amide hydrolase expression in rats

Cerebrospinal Anandamide Levels are Elevated in Acute Schizophrenia and are Inversely Correlated with Psychotic Symptoms

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