Sex difference in brain CB1 receptor availability in man

Laurikainen, Heikki; Tuominen, Lauri; Tikka, Maria; Merisaari, Harri; Armio, Reetta-Liina; Sormunen, Elina; Borgan, Faith; Veronese, Mattia; Howes, Oliver; Haaparanta‐Solin, Merja; Solin, Olof; Hietala, Jarmo

doi:10.1016/j.neuroimage.2018.10.013

Cited by 76 publications

(60 citation statements)

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“… 71 Because findings for both studies remained unchanged when including prior cannabis use or lifetime cannabis use in our model, cannabis use is unlikely to be a significant confound. Although only men were included owing to sex differences in CB1R, 24 future studies are needed to determine whether female patients show CB1R alterations.…”

Section: Discussionmentioning

confidence: 99%

“…Availability of CB1R was indexed using the distribution volume (V T ) of fluoride 18–labeled FMPEP-d 2 ([3R,5R]-5-[3-methoxy-phenyl]-3-[{R}-1-phenyl-ethylamino]-1-[4-trifluoro-methyl-phenyl]-pyrrolidin-2-one) (study 1) and carbon 11–labeled MePPEP ([3R,5R]-5-[{3-[ 18 F]fluoromethoxy-d2}phenyl]-3-[{R}-1-phenyl-ethylamino]-1-[4-trifluoromethyl-phenyl]-pyrrolidin-2-one) (study 2). Given sex differences in CB1R availability 24 and previous discrepant findings, we only investigated men to remove sex as a source of variability, with the view of investigating women in a subsequent study. 25 …”

Section: Methodsmentioning

confidence: 99%

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In Vivo Availability of Cannabinoid 1 Receptor Levels in Patients With First-Episode Psychosis

et al. 2019

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; for the METSY Group IMPORTANCE Experimental and epidemiological studies implicate the cannabinoid 1 receptor (CB1R) in the pathophysiology of psychosis. However, whether CB1R levels are altered in the early stages of psychosis and whether they are linked to cognitive function or symptom severity remain unknown. OBJECTIVE To investigate CB1R availability in first-episode psychosis (FEP) without the confounds of illness chronicity or the use of illicit substances or antipsychotics. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional, case-control study of 2 independent samples included participants receiving psychiatric early intervention services at 2 independent centers in Turku, Finland (study 1) and London, United Kingdom (study 2). Study 1 consisted of 18 volunteers, including 7 patients with affective or nonaffective psychoses taking antipsychotic medication and 11 matched controls; study 2, 40 volunteers, including 20 antipsychotic-naive or antipsychotic-free patients with schizophrenia or schizoaffective disorder and 20 matched controls.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

In Vivo Availability of Cannabinoid 1 Receptor Levels in Patients With First-Episode Psychosis

et al. 2019

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“…There are similarities in the endocannabinoid system of rodents and humans that suggest the translational relevance of the research. For example, higher densities of CB1 receptors are found in the brains of males than of females in both rodents and humans (Laurikainen et al, 2019). Our results are consistent with sex‐specific effects of exogenous cannabinoids in both rodents and humans, whereby adolescent female rodents and women show greater negative effects than do male rodents and men (Craft et al, 2013).…”

Section: Resultsmentioning

confidence: 99%

Adolescent CB1 receptor antagonism influences subsequent social interactions and neural activity in female rats

Simone

Baumbach

McPherson

et al. 2020

Intl J of Devlp Neuroscience

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We previously demonstrated that repeated exposure to the CB1 receptor antagonist/inverse agonist AM251 in adolescence (PND 30–44) increased social interactions in female rats when tested 48 h after the final exposure to the antagonist. Here, we investigated whether the increased sociality would be present after a longer drug washout period (5 days) in both male and female rats (experiment 1), and sought to identify candidate brain regions that may explain the observed differences in social behaviours between AM251 and vehicle‐treated female rats (experiment 2). While drug‐free, adolescent AM251 treatment increased social interactions in females and not in males. AM251 female rats had increased neural activity (as measured by the expression of early growth response protein‐1; EGR‐1) in the nucleus accumbens shell and cingulate gyrus of the medial prefrontal cortex, with no observed differences in EGR‐1 expression in the dorsal hippocampus, nucleus accumbens core, or prelimbic and infralimbic subdivisions of the medial prefrontal cortex relative to vehicle rats. Together, these results demonstrate a sex‐specific role of adolescent endocannabinoid signalling in the normative development of social behaviours and provide further support for adolescence as a vulnerable period for the effects of altered endocannabinoid signalling.

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“…A limitation of the study was that CB1R availability was only investigated in male volunteers. Given sex differences in CB1R availability [26] and sex differences in the behavioural and functional effects of cannabinoids on neuronal excitability and synaptic plasticity [51], we specifically investigated the association between CB1R and WM in males to reduce the effect of sex as a source of variability. However, future studies are needed to determine if our findings generalize to female patients.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

The neural and molecular basis of working memory function in psychosis: a multimodal PET-fMRI study

et al. 2019

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Working memory (WM) deficits predict clinical and functional outcomes in schizophrenia but are poorly understood and unaddressed by existing treatments. WM encoding and WM retrieval have not been investigated in schizophrenia without the confounds of illness chronicity or the use of antipsychotics and illicit substances. Moreover, it is unclear if WM deficits may be linked to cannabinoid 1 receptor dysfunction in schizophrenia. Sixty-six volunteers (35 controls, 31 drug-free patients with diagnoses of schizophrenia or schizoaffective disorder) completed the Sternberg Item-Recognition paradigm during an fMRI scan. Neural activation during WM encoding and WM retrieval was indexed using the blood-oxygen-level-dependent hemodynamic response. A subset of volunteers (20 controls, 20 drug-free patients) underwent a dynamic PET scan to measure [ 11 C] MePPEP distribution volume (ml/cm 3 ) to index CB1R availability. In a whole-brain analysis, there was a significant main effect of group on task-related BOLD responses in the superior parietal lobule during WM encoding, and the bilateral hippocampus during WM retrieval. Region of interest analyses in volunteers who had PET/fMRI indicated that there was a significant main effect of group on task-related BOLD responses in the right hippocampus, left DLPFC, left ACC during encoding; and in the bilateral hippocampus, striatum, ACC and right DLPFC during retrieval. Striatal CB1R availability was positively associated with mean striatal activation during WM retrieval in male patients (R = 0.5, p = 0.02) but not male controls (R = −0.20, p = 0.53), and this was significantly different between groups, Z = −2.20, p = 0.02. Striatal CB1R may contribute to the pathophysiology of WM deficits in male patients and have implications for drug development in schizophrenia.

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Sex difference in brain CB1 receptor availability in man

Cited by 76 publications

References 95 publications

In Vivo Availability of Cannabinoid 1 Receptor Levels in Patients With First-Episode Psychosis

In Vivo Availability of Cannabinoid 1 Receptor Levels in Patients With First-Episode Psychosis

Adolescent CB1 receptor antagonism influences subsequent social interactions and neural activity in female rats

The neural and molecular basis of working memory function in psychosis: a multimodal PET-fMRI study

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