Cannabidiol or ketamine for preventing the impact of adolescent early drug initiation on voluntary ethanol consumption in adulthood.
Carles Colom-Rocha, Cristian Bis-Humbert, M Julia García-Fuster
Frontiers in Pharmacology 2024 DOI: 10.3389/fphar.2024.1448170 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Male and female Sprague-Dawley rats |
| Interventions | cannabidiol ketamine |
| Duration | Adolescent treatment from postnatal days 29 to 38; ethanol access for 6 weeks in adulthood |
| Topics | Addiction CBD Esketamine Ketamine |
| Keywords | Addiction risk factors Adolescence Rodent models Sex differences Therapeutical options Addiction-prevention Adolescent-alcohol-exposure Substance-abuse-treatment Animal-research Sex-based-therapeutics |
| Citations | 3 |
| Key points | Adolescent ethanol exposure, alone or with cocaine, increases voluntary ethanol consumption in adulthood, and cannabidiol or ketamine (in females) can reduce this consumption. |
Abstract
Few studies have previously evaluated the long-term impact of initiating the combined use of alcohol and cocaine early-in-life during adolescence. Our preclinical study characterized changes in affective-like behavior and/or voluntary ethanol consumption emerging later on in adulthood induced by a prior adolescent drug exposure, as well as tested therapeutical interventions (i.e., cannabidiol or ketamine) to prevent the observed effects. We performed three independent studies with male and female Sprague-Dawley rats, treated in adolescence (postnatal days, PND 29-38) with non-contingent paradigms of ethanol, cocaine, their combination or vehicle. Later on, adult rats were (1) scored for their affective-like state (forced-swim, elevated-plus maze, novelty-suppressed feeding, sucrose preference), (2) allowed to freely drink ethanol for 6 weeks (two-bottle choice), or (3) treated with cannabidiol or ketamine before given access to ethanol in adulthood. No signs of increased negative affect were observed in adulthood following the adolescent treatments. However, adolescent ethanol exposure was a risk-factor for later developing an increased voluntary ethanol consumption in adulthood, both for male and female rats. This risk was similar when ethanol was combined with adolescent cocaine exposure, since cocaine alone showed no effects on later ethanol intake. Finally, rats exposed to adolescent ethanol and pretreated in adulthood with cannabidiol (and/or ketamine, but just for females) reduced their ethanol voluntary consumption. Our data provided two therapeutical options capable of preventing the impact of an early drug initiation during adolescence by decreasing voluntary ethanol consumption in adult rats.
Comparable studies
Other preclinical and animal studies on ketamine for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| R-(-)-ketamine modifies behavioral effects of morphine predicting efficacy as a novel therapy for opioid use disorder. Morphine-dependent rats and mice | 2020 | Preclinical study | |
| The effects of (2R,6R)-hydroxynorketamine on oxycodone withdrawal and reinstatement. Male and female oxycodone-dependent mice | 2023 | Preclinical study | |
| Characterizing the therapeutical use of ketamine for adolescent rats of both sexes: Antidepressant-like efficacy and safety profile. Adolescent rats of both sexes, including naïve and early-life stressed (maternal... | 2025 | Preclinical study | |
| Exploring ketamine's reinforcement, cue-induced reinstatement, and nucleus accumbens cFos activation in male and female long evans rats. Long Evans rats | 2024 | Preclinical experimental study | |
| Brain acid sphingomyelinase controls addiction-related behaviours in a sex-specific way. Male and female mice with forebrain ASM overexpression | 2025 | Experimental study |