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Cannabidiol attenuates methamphetamine-induced cardiac inflammatory response through the PKA/CREB pathway in rats

Please use this link to access publication Abstract Background Methamphetamine (MA) abuse is a major global public health problem. However, it is not yet known whether cannabidiol (CBD) has protective effects on MA-induced cardiotoxicity. The present study investigated whether CBD has protective effects on MA-induced cardiac damage in rats via the protein kinase A/cyclic adenosine monophosphate (cAMP)-response element-binding protein (PKA/CREB) pathway. Methods A total of 30 rats were randomly divided into 5 groups. The rats were administered MA (10 mg/kg) by intraperitoneal (IP) injection once a day for 4 weeks, and with CBD (40 or 80 mg/kg, IP) treatment 1 h before the MA...
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Cannabidiol Effect on Cue-Induced Craving for Individuals with Opioid Use Disorder Treated with Buprenorphine: A Small Proof-of-Concept Open-Label Study

Abstract Background: Opioid use disorder (OUD) remains a major public health concern. Despite the use of medications for OUD such as buprenorphine, the current gold-standard treatment, relapse in the context of increased craving remains common. Cannabidiol (CBD) has been shown to reduce cue-induced craving in individuals with OUD, but among those who were not receiving any buprenorphine treatment. This small proof-of-concept open-label study sought to evaluate the effect of CBD on cue-induced craving among individuals with OUD who were being actively treated with buprenorphine. Methods: Participants (n = 5) received CBD (Epidiolex) 600 mg once daily for 3 consecutive days in an openlabel manner....
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Cannabidiol but not cannabidiolic acid reduces behavioural sensitisation to methamphetamine in rats, at pharmacologically effective doses

Abstract Rationale Cannabidiol (CBD) and cannabidiolic acid (CBDA) are non-psychoactive components of the cannabis plant. CBD has been well characterised to have anxiolytic and anticonvulsant activity, whereas the behavioural efects of CBDA are less clear. Preclinical and clinical data suggests that CBD has antipsychotic properties and reduces methamphetamine selfadministration in rats. An animal model that is commonly used to mimic the neurochemical changes underlying psychosis and drug dependence is methamphetamine (METH) sensitisation, where repeated administration of the psychostimulant progressively increases the locomotor efects of METH. Objective The aim of this study was to determine whether CBD or CBDA attenuate METH-induced sensitisation of locomotor hyperactivity...
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Cannabidiol treatment prevents drug reinstatement and the molecular alterations evoked by amphetamine on receptors and enzymes from dopaminergic and endocannabinoid systems in rats

Abstract In psychostimulant drug addiction, relapse is the most concerning outcome to be managed, considering there is no approved treatment for this neuropsychiatric condition. Here, we investigated the effects of the CBD treatment on the relapse behavior triggered by stress, after being submitted to the amphetamine (AMPH)-induced conditioned place preference (CPP) in rats. To elucidate the mechanisms of action underlying the CBD treatment, we evaluated the neuroadaptations on dopaminergic and endocannabinoid targets in the ventral striatum (VS) and ventral tegmental area (VTA) of the brain. Animals received d,l-AMPH (4 mg/kg, i.p.) or vehicle in the CPP paradigm for 8 days. Following the first CPP test, animals were treated with CBD (10 mg/kg, i.p.) or its vehicle for 5 days and subsequently submitted...
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Reducing Effect of Cannabidiol on Alcohol Self-Administration in Sardinian Alcohol-Preferring Rats

Introduction: Cannabidiol (CBD) is a major cannabinoid extracted from Cannabis sativa with no abuse potential. Data from recent rodent studies suggest that amelioration of alcohol-motivated behaviors may be one of the numerous pharmacological effects of CBD. This study was designed to contribute to this research, assessing the effect of CBD on operant oral alcohol self-administration in selectively bred Sardinian alcohol-preferring (sP) rats, a validated animal model of excessive alcohol consumption. In addition, this study investigated the effect of CBD on operant self-administration of a highly palatable chocolate solution in Wistar rats. Materials and Methods: Male sP rats were trained to lever respond for alcohol (15% v/v) under the...
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Cannabidiol inhibits methamphetamine-induced dopamine release via modulation of the DRD1-MeCP2-BDNF-TrkB signaling pathway

Please use this link to access this publication. Abstract Rationale Adaptive alteration of dopamine (DA) system in mesocorticolimbic circuits is an extremely intricate and dynamic process, which contributes to maintaining methamphetamine (METH)-related disorders. There are no approved pharmacotherapies for METH-related disorders. Cannabidiol (CBD), a major non-psychoactive constituent of cannabis, has received attention for its therapeutic potential in treating METH-related disorders. However, the major research obstacles of CBD are the yet to be clarified mechanisms behind its therapeutic potential. Recent evidence showed that DA system may be active target of CBD. CBD could be a promising dopaminergic medication for METH-related disorders. Objectives We investigated the...
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Differential Effects of Cannabidiol and a Novel Cannabidiol Analog on Oxycodone Place Preference and Analgesia in Mice: an Opioid Abuse Deterrent with Analgesic Properties

Please use this link to access this publication. Abstract Background and Purpose: This study sought to determine whether cannabidiol (CBD) or a CBD derivative, CBD monovalinate monohemisuccinate (CBD-val-HS), could attenuate the development of oxycodone reward while retaining its analgesic effects. Experimental Approach: To determine the effect on oxycodone reward, animals were enrolled in the conditioned place preference paradigm and received either saline or oxycodone (3.0 mg/kg) in combination with either CBD or CBD-val-HS utilizing three sets of drug-/no drug-conditioning trials. To determine if the doses of CBD or CBD-val-HS that blocked opioid reward would affect nociceptive processes, animals were enrolled in the hot plate and abdominal writhing...
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Cannabidiol in the context of substance use disorder treatment: A systematic review

Please use this link to access this publication. Abstract Introduction Cannabidiol (CBD) is a phytocannabinoid found in the Cannabis plant. CBD has received significant medical attention in relation to its anticonvulsant, anxiolytic, and antipsychotic characteristics. An increasing number of studies focusing on the anti-addictive properties of CBD have recently been published. In this systematic review, we aim to offer a comprehensive overview of animal and human studies regarding the impact of CBD on substance use disorders (SUDs). Methods A systematic search was performed on the PubMed database in February 2021. We included all articles assessing the effects of CBD on substance use disorders. Results The current systematic review suggests...
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New Insights and Potential Therapeutic Targeting of CB2 Cannabinoid Receptors in CNS Disorders

Abstract The endocannabinoid system (ECS) is ubiquitous in most human tissues, and involved in the regulation of mental health. Consequently, its dysregulation is associated with neuropsychiatric and neurodegenerative disorders. Together, the ECS and the expanded endocannabinoidome (eCBome) are composed of genes coding for CB1 and CB2 cannabinoid receptors (CB1R, CB2R), endocannabinoids (eCBs), and the metabolic enzyme machinery for their synthesis and catabolism. The activation of CB1R is associated with adverse effects on the central nervous system (CNS), which has limited the therapeutic use of drugs that bind this receptor. The discovery of the functional neuronal CB2R raised new possibilities for the potential and safe...
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Cannabis use disorder and adverse cardiovascular outcomes: A population-based retrospective cohort analysis of adults from Alberta, Canada

Abstract Aim To measure the association between cannabis use disorder (CUD) and adverse cardiovascular disease (CVD) outcomes. Design and Setting We conducted a matched, population-based retrospective cohort study involving five linked administrative health databases from Alberta, Canada. Participants We identified participants with CUD diagnosis codes and matched them to participants without CUD codes by gender, year of birth and time of presentation to the health system. We included 29 764 pairs (n = 59 528 individuals in total). Measurements CVD events were defined by at least one incident diagnostic code within the study period (1 January 2012–31 December 2019). Covariates included comorbidity, socio-economic status, prescription medication use and health...
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