Single cannabidiol administration affects anxiety-, obsessive compulsive-, object memory-, and attention-like behaviors in mice in a sex and concentration dependent manner.
Carley Marie Huffstetler, Brigitte Cochran, Camilla Ann May, Nicholas Maykut, Claudia Rose Silver, Claudia Cedeno, Ezabelle Franck, Alexis Cox, Debra Ann Fadool
Pharmacology, biochemistry, and behavior January 2023 DOI: 10.1016/j.pbb.2022.173498 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Adult wildtype C57BL/6J mice and Kv1.3 knockout mice of both sexes |
| Intervention | Cannabidiol (CBD) |
| Dose | 10 or 20 mg/kg |
| Duration | Single injection; memory tested at 1 h and 24 h |
| Measures | marble-burying test, light-dark box (LDB), short (1 h) and long-term (24 h) object memory test, elevated-plus maze (EPM), object-based attention task |
| Topics | Anxiety Cannabis CBD |
| Keywords | ADHD Memory Potassium channel |
| Key findings | Acute CBD had immediate behavioral effects that depended on dose, sex, and anxiety state: it reduced anxiety-like behavior in wildtype mice but increased it in Kv1.3 knockout mice, reduced long-term object memory in wildtype males at the lower dose, and altered attention-like behavior only in knockout mice, with females losing attention and males improving it. |
Abstract
The behavioral effects of cannabidiol (CBD) are understudied, but are important, given its therapeutic potential and widespread use as a natural supplement. The objective of this study was to test whether a single injection of CBD affected anxiety-like or attention-like behavior, or memory in wildtype mice or mice with reported trait anxiety due to a targeted gene-deletion in a voltage-dependent potassium channel, Kv1.3. Wildtype C57BL/6 J and Kv1.3-/- mice of both sexes were reared to adulthood and then administered an intraperitoneal injection of 10 or 20 mg/kg CBD. Mice were behaviorally-phenotyped using the marble-burying test, the light-dark box (LDB), short (1 h) and long-term (24 h) object memory test, the elevated-plus maze (EPM), and the object-based attention task in order to assess obsessive compulsive-, anxiety-, and attention-like behaviors, and memory. We discovered that acute CBD treatment reduced marble burying in male, but not female mice. CBD was effective in lessening anxiety-like behaviors determined by the LDB test in both male and female wildtype mice, whereby the effective dose required to observe the effect in females was less. In Kv1.3-/- mice, CBD increased anxiety-like behaviors in the LDB in both sexes at the higher concentration of CBD and it similarly increased anxiety-like behavior in females in the EPM at the lower concentration of CBD. Long-term object memory was reduced in male wildtype mice at the lower concentration of CBD. Finally, ADHD- or attention-like behaviors were not altered by CBD in wildtype mice, but in Kv1.3-/- mice, females were observed to have a loss in attention while males demonstrated improved attention. We conclude that administration of a single dose of CBD has immediate effects on mouse behavior that is dose, sex, and anxiety-state dependent - and that these behavioral outcomes are important to examine in parallel human trials.
Comparable studies
Other preclinical and animal studies on cannabis for anxiety, most cited first.