Effect of prior foot shock stress and Δ9-tetrahydrocannabinol, cannabidiolic acid, and cannabidiol on anxiety-like responding in the light-dark emergence test in rats.
Erin M Rock, Cheryl L Limebeer, Gavin N Petrie, Lauren A Williams, Raphael Mechoulam, Linda A. Parker
Psychopharmacology July 2017 DOI: 10.1007/s00213-017-4626-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | WAY100635 |
| Dose | THC 1 and 10 mg/kg; CBDA 0.1-100 μg/kg; CBD 5 mg/kg; CBDA 1 μg/kg; WAY100635 not stated |
| Duration | Acute or chronic (21 days) |
| Measures | light-dark (LD) emergence test |
| Topics | Anxiety CBD Cannabis |
| Keywords | Anxiolytic Cannabidiolic acid Foot shock Light-dark emergence test Rat Stress Δ9-tetrahydrocannabiol |
| Key findings | THC (1 and 10 mg/kg) produced anxiety-like responding acutely and chronically, while CBDA alone had no effect. Foot shock stress increased anxiety-like behavior in vehicle- and THC-treated rats, but CBDA (0.1-100 μg/kg) or CBD (5 mg/kg) prevented this stress-induced response. WAY100635 reversed CBDA's anxiolytic effect, and combining CBDA or CBD with THC did not alter THC's anxiogenic effect. The authors suggest CBDA and CBD may require a stressor to produce anxiolytic effects. |
Abstract
Cannabis is commonly used by humans to relieve stress. Here, we evaluate the potential of intraperitoneally (i.p.) administered Δ9-tetrahydrocannabiol (THC) and cannabidiolic acid (CBDA, the precursor of cannabidiol [CBD]) to produce dose-dependent effects on anxiety-like responding in the light-dark (LD) emergence test of anxiety-like responding in rats, when administered acutely or chronically (21 days). As well, we evaluate the potential of THC, CBDA, and CBD to reduce anxiogenic responding produced by foot shock (FS) stress 24 h prior to the LD test. In the absence of the explicit FS stressor, THC (1 and 10 mg/kg) produced anxiogenic-like responding when administered acutely or chronically, but CBDA produced neither anxiogenic- nor anxiolytic-like responding. Administration of FS stress 24 h prior to the LD test enhanced anxiogenic-like responding (reduced time spent and increased latency to enter the light compartment) in rats pretreated with either vehicle (VEH) or THC (1 mg/kg); however, administration of CBDA (0.1-100 μg/kg) or CBD (5 mg/kg) prevented the FS-induced anxiogenic-like responding (an anxiolytic-like effect). The 5-hydroxytryptamine 1A (5-HT1A) receptor antagonist, WAY100635, reversed CBDA's anxiolytic effect (1 μg/kg). Combining an anxiolytic dose of CBDA (1 μg/kg) or CBD (5 mg/kg) with an anxiogenic dose of THC (1 mg/kg) did not modify THC's anxiogenic effect. These results suggest the anxiolytic effects of CBDA and CBD may require the presence of a specific stressor.
Comparable studies
Other preclinical and animal studies on cannabis for anxiety, most cited first.
Citations in the library
Cited by 9
- Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties Journal of Translational Medicine October 2, 2020
- Cannabis containing equivalent concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) induces less state anxiety than THC-dominant cannabis Psychopharmacology October 13, 2022
- Involvement of Adenosine A2A Receptors in Anxiety-Like Behaviors in Tetrahydrocannabinol-Treated Mice. Brain and Behavior February 1, 2026
- Evaluating Potential Anxiolytic Effects of Minor Cannabinoids and Terpenes After Acute and Chronic Oral Administration in Rats. Cannabis and Cannabinoid Research September 2023
- Endocannabinoid System and Exogenous Cannabinoids in Depression and Anxiety: A Review Brain Science February 1, 2023
and 4 more in the library
Cites 12
- Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Current Pharmaceutical Design September 12, 2012
- Interactions between cannabidiol and Δ9-THC following acute and repeated dosing: Rebound hyperactivity, sensorimotor gating and epigenetic and neuroadaptive changes in the mesolimbic pathway. European Neuropsychopharmacology February 2017
- Neural correlates of interactions between cannabidiol and Δ(9) -tetrahydrocannabinol in mice: implications for medical cannabis. British Journal of Pharmacology January 2016
- Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: a randomised, double-blind, placebo-controlled study in cannabis users. European Neuropsychopharmacology March 2015
- Cannabidiol potentiates Δ⁹-tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats. Psychopharmacology November 2011
and 7 more in the library