New Insights in the Involvement of the Endocannabinoid System and Natural Cannabinoids in Nicotine Dependence

Saravia, Rocío; Ten-Blanco, Marc; Pereda-Pérez, Inmaculada; Berrendero, Fernando

doi:10.3390/ijms222413316

Cited by 7 publications

(6 citation statements)

References 181 publications

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“…26 Upregulation of CB1R in these regions is associated with the development of nicotine and cocaine addiction. 27,28 In the present study, we confirmed that oxycodone could evaluate the expression of CB1R in the hippocampus (Figure 3A), suggesting that the dysregulation of the ECS is also linked to oxycodone abuse. During the development of synapse, CB1R can mediate the activation of Cdk5 and cause neurobehavioral abnormalities in mice postnatally exposed to alcohol.…”

Section: Discussionsupporting

confidence: 81%

“…Regions of highest expression include the basal ganglia, cerebellum, olfactory bulb and hippocampus 26 . Upregulation of CB1R in these regions is associated with the development of nicotine and cocaine addiction 27,28 . In the present study, we confirmed that oxycodone could evaluate the expression of CB1R in the hippocampus (Figure 3A), suggesting that the dysregulation of the ECS is also linked to oxycodone abuse.…”

Section: Discussionsupporting

confidence: 79%

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Blockade of endocannabinoid system by oxytocin attenuates memory deficits in oxycodone‐treated rats

et al. 2022

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Oxycodone is a highly prescribed opioid and its abuse has been rampant. Accumulating evidence shows that the cannabinoid CB1 receptor (CB1R) plays a key role in mediating rewarding effects to opioids. However, the downstream signalling of CB1R induced by oxycodone remains unclear. The neuropeptide oxytocin is well known as a potential remedy for drug addiction. Thus, our study aims to explore the mechanism of oxycodone-induced learning and memory deficits underlying the endocannabinoid system (ECS) and the effect of oxytocin. Rats were intraperitoneally injected with oxycodone once a day for eight consecutive day. Novel object recognition, resident-intruder and Morris Water Maze tests were employed to assess the cognitive, social and spatial memory of the rats after oxycodone withdrawal. The (co-)expression of CB1R, cyclin-dependent kinase 5 (Cdk5), regulatory protein p25, tau and phosphorylated tau was measured 1 day after the last behavioural test. The histopathological staining and synaptic density in the hippocampus were observed as well. We found that oxycodone upregulated the expression of p-GSK3β, co-expression of p-Cdk5 and p25 through CB1R. This finding was accompanied by elevation of pSer396, pSer404 in the tau, and reduction of the number of neurons, dendritic spines and synaptic density in the hippocampus. Furthermore, i.c.v. treatment with oxytocin ameliorates memory deficits in oxycodone-treated rats through inhibition of the ECS. We propose further studies on the clinical use of this neuropeptide, which may potentially cure drug addiction.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 79%

Blockade of endocannabinoid system by oxytocin attenuates memory deficits in oxycodone‐treated rats

et al. 2022

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“…Although it was not surprising that rimonabant reduced the subjective effects of cannabis, evidence that this medication also reduces the reinforcing effects of nicotine was one of many clues that targeting the eCB may have potential to treat a range of SUDs. To start preclinically, CB1R antagonists reduce nicotine reinforcement [see (Saravia, Ten-Blanco, Pereda-Pérez, & Berrendero, 2021 ; Spanagel, 2020 )], presumably by blocking eCBs from disinhibiting dopaminergic neurons in the ventral tegmental area [see (Asth, Santos, & Moreira, 2022 ; Butler & Le Foll, 2020 )]. These findings appear consistent with human imaging data [summarized by (Hirvonen et al, 2018 )] – with cannabis, THC acts on CB1Rs directly and thereby downregulates CB1Rs in neocortical brain regions but not in the basal ganglia, midbrain, or cerebellum.…”

Section: Substance Use Disordersmentioning

confidence: 99%

The endocannabinoid system as a putative target for the development of novel drugs for the treatment of psychiatric illnesses

Hill,

Haney,

Hillard

et al. 2023

Psychol. Med.

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Cannabis is well established to impact affective states, emotion and perceptual processing, primarily through its interactions with the endocannabinoid system. While cannabis use is quite prevalent in many individuals afflicted with psychiatric illnesses, there is considerable controversy as to whether cannabis may worsen these conditions or provide some form of therapeutic benefit. The development of pharmacological agents which interact with components of the endocannabinoid system in more localized and discrete ways then via phytocannabinoids found in cannabis, has allowed the investigation if direct targeting of the endocannabinoid system itself may represent a novel approach to treat psychiatric illness without the potential untoward side effects associated with cannabis. Herein we review the current body of literature regarding the various pharmacological tools that have been developed to target the endocannabinoid system, their impact in preclinical models of psychiatric illness and the recent data emerging of their utilization in clinical trials for psychiatric illnesses, with a specific focus on substance use disorders, trauma-related disorders, and autism. We highlight several candidate drugs which target endocannabinoid function, particularly inhibitors of endocannabinoid metabolism or modulators of cannabinoid receptor signaling, which have emerged as potential candidates for the treatment of psychiatric conditions, particularly substance use disorder, anxiety and trauma-related disorders and autism spectrum disorders. Although there needs to be ongoing clinical work to establish the potential utility of endocannabinoid-based drugs for the treatment of psychiatric illnesses, the current data available is quite promising and shows indications of several potential candidate diseases which may benefit from this approach.

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“…Regarding AEA and 2-AG, studies have provided conflicting results about their reinforcing properties for nicotine and nicotine withdrawal. However, AEA and 2-AG could have opposite roles in relapse to nicotine-seeking behavior [421].…”

Section: Animal Studiesmentioning

confidence: 99%

Molecular Alterations of the Endocannabinoid System in Psychiatric Disorders

Navarro

Gasparyan

Navarrete

et al. 2022

IJMS

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The therapeutic benefits of the current medications for patients with psychiatric disorders contrast with a great variety of adverse effects. The endocannabinoid system (ECS) components have gained high interest as potential new targets for treating psychiatry diseases because of their neuromodulator role, which is essential to understanding the regulation of many brain functions. This article reviewed the molecular alterations in ECS occurring in different psychiatric conditions. The methods used to identify alterations in the ECS were also described. We used a translational approach. The animal models reproducing some behavioral and/or neurochemical aspects of psychiatric disorders and the molecular alterations in clinical studies in post-mortem brain tissue or peripheral tissues were analyzed. This article reviewed the most relevant ECS changes in prevalent psychiatric diseases such as mood disorders, schizophrenia, autism, attentional deficit, eating disorders (ED), and addiction. The review concludes that clinical research studies are urgently needed for two different purposes: (1) To identify alterations of the ECS components potentially useful as new biomarkers relating to a specific disease or condition, and (2) to design new therapeutic targets based on the specific alterations found to improve the pharmacological treatment in psychiatry.

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New Insights in the Involvement of the Endocannabinoid System and Natural Cannabinoids in Nicotine Dependence

Cited by 7 publications

References 181 publications

Blockade of endocannabinoid system by oxytocin attenuates memory deficits in oxycodone‐treated rats

Blockade of endocannabinoid system by oxytocin attenuates memory deficits in oxycodone‐treated rats

The endocannabinoid system as a putative target for the development of novel drugs for the treatment of psychiatric illnesses

Molecular Alterations of the Endocannabinoid System in Psychiatric Disorders

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