Cannabinoid receptors 1 and 2 (CB1 and CB2), their distribution, ligands and functional involvement in nervous system structures — A short review

Svíženská, Ivana Hradilová; Dubový, Petr; Šulcová, Alexandra

doi:10.1016/j.pbb.2008.05.010

Cited by 374 publications

(290 citation statements)

References 196 publications

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“…Our finding of lower FA in the forceps minor tract has been demonstrated in the literature for younger users (Ashtari et al 2009;Filbey et al 2014), although Becker et al (2015) did note higher FA in cannabis users than non-users. This effect on the forceps minor is congruent with the known increased density of cannabinoid type 1 receptors (which are activated by the main psychoactive constituent of cannabis, delta-9-tetrahydrocannabinol (THC)) in frontal brain regions (Svíženská et al 2008). Our finding of reduced FA in a wideranging in age sample provides evidence of a negative impact of cannabis on frontal white matter integrity not just in younger users, but across older users as well.…”

Section: Discussionsupporting

confidence: 81%

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

et al. 2016

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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.

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Section: Discussionsupporting

confidence: 81%

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

et al. 2016

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“…Cannabinoid type-1 receptors (CB1Rs) are highly abundant in many brain regions including frontal areas and are thought to mediate most of the brain cannabinoid system functions (Egertova and Elphick 2000;Kano et al 2009;Katona and Freund 2008;Tsou et al 1998). CB1Rs are densely distributed in cerebral cortex with the highest abundance in the cingulate cortex and association cortical regions of the frontal l o b e ( E g g a n a n d L e w i s 2 0 0 7 ; M a i l l e u x a n d Vanderhaeghen 1992; Svizenska et al 2008). For example, Eggan and Lewis demonstrated a higher density of CB1Rs in the cingulate cortex and associative prefrontal regions compared to primary sensory and motor cortices (2007).…”

Section: Introductionmentioning

confidence: 99%

Activation of cannabinoid system in anterior cingulate cortex and orbitofrontal cortex modulates cost-benefit decision making

et al. 2014

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Despite the evidence for altered decision making in cannabis abusers, the role of the cannabinoid system in decision-making circuits has not been studied. Here, we examined the effects of cannabinoid modulation during costbenefit decision making in the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC), key brain areas involved in decision making. We trained different groups of rats in a delay-based and an effort-based form of cost-benefit T-maze decision-making task. During test days, the rats received local injections of either vehicle or ACEA, a cannabinoid type-1 receptor (CB1R) agonist in the ACC or OFC. We measured spontaneous locomotor activity following the same treatments and characterized CB1Rs localization on different neuronal populations within these regions using immunohistochemistry. We showed that CB1R activation in the ACC impaired decision making such that rats were less willing to invest physical effort to gain high reward. Similarly, CB1R activation in the OFC induced impulsive pattern of choice such that rats preferred small immediate rewards to large delayed rewards. Control tasks ensured that the effects were specific for differential cost-benefit tasks. Furthermore, we characterized widespread colocalizations of CB1Rs on GABAergic axonal ends but few colocalizations on glutamatergic, dopaminergic, and serotonergic neuronal ends. These results provide first direct evidence that the cannabinoid system plays a critical role in regulating cost-benefit decision making in the ACC and OFC and implicate cannabinoid modulation of synaptic ends of predominantly interneurons and to a lesser degree other neuronal populations in these two frontal regions.

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“…Banister and colleagues [4] showed that APICA is a full cannabinoid agonist with comparable affinity for both CB1 and CB2 cannabinoid receptors in vitro, and that CB2 receptors may modulate pain in inflammatory [23] and noninflammatory states [24], via local peripheral mechanisms. Over the last decade, accumulating evidence has shown that CB2 receptors are also widely present in both microglia and neurons [25][26][27]. However, when AM630 was administered before APICA, the significant decrease in locomotor activity in the open field, body temperature and motor coordination in the Rotarod, together with the increased tail flick latency, were not modified.…”

Section: Discussionmentioning

confidence: 98%

“…Melting point was determined by DSC analysis and corresponded to the peak maximum. 1 H NMR spectra was recorded operating at 300 MHz and 13 (25). (Fig.…”

Section: Drugsmentioning

confidence: 99%

Behavioural and pharmacological characterization of a novel cannabinomimetic adamantane-derived indole, APICA, and considerations on the possible misuse as a psychotropic spice abuse, in C57bl/6J mice

Cannizzaro

Malta

Argo

et al. 2016

Forensic Science International

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The novel adamantane derivative APICA (N-(adamantan-1-yl)-1-pentyl-1H-indole-3-carboxamide) was recently identified as a cannabinomimetic indole of abuse. Despite its novel structure, APICA recalls cannabinomimetic indoles, such as representative member JWH-018.In present study, the effects of APICA (1-3 mg/kg, i.p.) were tested in C57BL/6J mice, in the Tetrad task which includes the assessment of: body temperature; locomotor activity and behavioural reactivity; nociception; motor coordination; declarative memory. Furthermore, pre-treatment with the CB1 antagonist AM251 (3 mg/kg, i.p.) or the CB2 antagonist AM630 (3 mg/kg, i.p.) was carried out to characterize APICA activity.Our results show that APICA was able to dose-dependently decrease locomotor activity and behavioural reactivity in the open field, whereas only the highest dose was able to induce hypothermia, analgesia, motor incoordination and recognition memory impairment, with respect to vehicle (p < 0.01; p < 0.001).The pretreatment with the CB1 antagonist AM251 elicited an increase in body temperature, total distance travelled in the open field, latency to fall down in the Rotarod, and a decrease in tail flick latency (p < 0.05; p < 0.01). On the other hand, pretreatment with AM630 did not induced significant differences on APICA effects.This study supports preliminary reports on APICA cannabinomimetic properties, extending its detrimental effects on cognitive function. Moreover, these properties can be attributed to the CB1 receptor activity, indicating APICA as a selective CB1 receptor agonist

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Cannabinoid receptors 1 and 2 (CB1 and CB2), their distribution, ligands and functional involvement in nervous system structures — A short review

Cited by 374 publications

References 196 publications

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

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

Activation of cannabinoid system in anterior cingulate cortex and orbitofrontal cortex modulates cost-benefit decision making

Behavioural and pharmacological characterization of a novel cannabinomimetic adamantane-derived indole, APICA, and considerations on the possible misuse as a psychotropic spice abuse, in C57bl/6J mice

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