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

Psychopharmacology (Berl). 2017 Jul;234(14):2207-2217. doi: 10.1007/s00213-017-4626-5. Epub 2017 Apr 20.


Rationale: Cannabis is commonly used by humans to relieve stress.

Objectives and methods: 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.

Results: 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.

Conclusion: These results suggest the anxiolytic effects of CBDA and CBD may require the presence of a specific stressor.

Keywords: Anxiety; Anxiolytic; Cannabidiol; Cannabidiolic acid; Foot shock; Light-dark emergence test; Rat; Stress; Δ9-tetrahydrocannabiol.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Anxiety / drug therapy*
  • Anxiety Disorders / drug therapy*
  • Cannabidiol / pharmacology*
  • Cannabinoids
  • Cannabis*
  • Dronabinol / pharmacology*
  • Male
  • Rats
  • Receptor, Serotonin, 5-HT1A / chemistry
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Serotonin / metabolism*
  • Serotonin 5-HT1 Receptor Antagonists / pharmacology*


  • Anti-Anxiety Agents
  • Cannabinoids
  • HTR1A protein, human
  • Serotonin 5-HT1 Receptor Antagonists
  • Receptor, Serotonin, 5-HT1A
  • Cannabidiol
  • Serotonin
  • Dronabinol
  • cannabidiolic acid