Cannabidiol tempers alcohol intake and neuroendocrine and behavioural correlates in alcohol binge drinking adolescent rats. Focus on calcitonin gene‐related peptide's brain levels
Giuseppe Tringali, Gianluca Lavanco, Valentina Castelli, Giuseppe Pizzolanti, Martin Kuchař, Diego Currò, Carla Cannizzaro, Anna Brancato
Phytotherapy Research July 31, 2023 DOI: 10.1002/ptr.7972 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Adolescent male rats |
| Intervention | Cannabidiol |
| Dose | 40 mg/kg |
| Topics | Cannabis CBD |
| Keywords | Binge drinking Calcitonin gene-related peptide Endocrinology Prefrontal cortex Ventral tegmental area Amygdala Corticosterone Nucleus accumbens Neuropeptide Poison control Hormone Dopamine |
| Citations | 17 |
| Key points | Adolescent alcohol binge drinking alters CGRP expression in affect-related brain regions and induces behavioral and neuroendocrine abnormalities that can be partially reversed by cannabidiol treatment. |
Abstract
Alcohol binge drinking is common among adolescents and may challenge the signalling systems that process affective stimuli, including calcitonin gene-related peptide (CGRP) signalling. Here, we employed a rat model of adolescent binge drinking to evaluate reward-, social- and aversion-related behaviour, glucocorticoid output and CGRP levels in affect-related brain regions. As a potential rescue, the effect of the phytocannabinoid cannabidiol was explored. Adolescent male rats underwent the intermittent 20% alcohol two-bottle choice paradigm; at the binge day (BD) and the 24 h withdrawal day (WD), we assessed CGRP expression in medial prefrontal cortex (mPFC), nucleus accumbens (NAc), amygdala, hypothalamus and brainstem; in addition, we evaluated sucrose preference, social motivation and drive, nociceptive response, and serum corticosterone levels. Cannabidiol (40 mg/kg, i.p.) was administered before each drinking session, and its effect was measured on the above-mentioned readouts. At BD and WD, rats displayed decreased CGRP expression in mPFC, NAc and amygdala; increased CGRP levels in the brainstem; increased response to rewarding- and nociceptive stimuli and decreased social drive; reduced serum corticosterone levels. Cannabidiol reduced alcohol consumption and preference; normalised the abnormal corticolimbic CGRP expression, and the reward and aversion-related hyper-responsivity, as well as glucocorticoid levels in alcohol binge-like drinking rats. Overall, CGRP can represent both a mediator and a target of alcohol binge-like drinking and provides a further piece in the intricate puzzle of alcohol-induced behavioural and neuroendocrine sequelae. CBD shows promising effects in limiting adolescent alcohol binge drinking and rebalancing the bio-behavioural abnormalities.
Comparable studies
Other preclinical and animal studies on CBD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain Spontaneously hypertensive rats (SHRs) and Wistar rats | 2014 | Animal experimental study | |
| Δ-9-Tetrahydrocannabinol and Cannabidiol produce dissociable effects on prefrontal cortical executive function and regulation of affective behaviors Rats | 2018 | Experimental study | |
| Optogenetic brain‐stimulation reward: A new procedure to re‐evaluate the rewarding versus aversive effects of cannabinoids in dopamine transporter‐Cre mice Transgenic dopamine transporter (DAT)-Cre mice | 2021 | Experimental study | |
| Effects of inhaled cannabis high in Δ9-THC or CBD on the aging brain: A translational MRI and behavioral study 19-20 month old mice | 2023 | Randomized controlled trial | |
| Multi-level therapeutic actions of cannabidiol in ketamine-induced schizophrenia psychopathology in male rats. Male rats | 2024 | Experimental study |
Citations in the library
Cited by 4
- Cannabidiol or ketamine for preventing the impact of adolescent early drug initiation on voluntary ethanol consumption in adulthood. Frontiers in Pharmacology 2024
- Perinatal LC-ω-3-PUFA supplementation offsets prenatal THC-induced cognitive deficit via sex-specific modulation of hippocampal neuroplasticity. European Journal of Pharmacology June 1, 2026
- Prenatal THC exposure and binge-like alcohol drinking in early adolescence: From sex-specific drinking vulnerability to abnormal endocannabinoid-dopamine nexus in the nucleus accumbens. Journal of Psychopharmacology February 27, 2026
- Gestational THC exposure perturbates hippocampal mitochondrial respiration in the memory-impaired adolescent progeny: Is there a role for mitochondrial CB1 receptor? Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie June 2025