CBD and behaviour

Literature review

Anxiety

The endocannabinoid system plays an intimate role in the regulation of stress responses.
Chronic environmental stress downregulates CB1 receptors, which in turn reduce levels of AEA and increase levels of 2-AG, where decreased AEA levels are associated with the progression of stress response and increased anxiety behaviour.

In murine studies, anxiolytic effects of CBD at doses of 5–60 mg/kg were found to be mediated through the activation of CB1 and CB2 receptors as well as serotonin receptors.

Rodent and human studies on the effect of CBD in alleviating anxiety showed mixed results.

Humans - a recent comprehensive review article concluded that there is not enough evidence that CBD is effective in treating anxiety
- Black et al., 2019, ‘Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis’, Lancet Psychiatry, vol. 6, pp. 995-1010. https://doi.org/10.1016/S2215-0366(19)30401-8.
BUT inter-species differences in cannabinoid receptor number and location between humans and dogs so human studies are not translatable.

Literature Review

CBD as an anxiolytic

CBD shows anxiolytic-like effects with mice in the elevated plus maze and in the Vogel conflict test.
In humans it was found to lower anxiety in stressful situations
The mode of action of CBD as an anxiolytic molecule is not well understood. Most probably it involves action as a serotonin receptor 1A (5-HT1A) agonist, enhancement of adenosine signaling through inhibition of uptake or inhibition of the GPR55 receptor.

Dog studies:

Method:

DOGS: 40 adult dogs, of three breeds (Labrador Retrievers, Beagles, and Norfolk Terriers), with a mean age of 4.1 years
Randomly allocated into control and treatment groups, then randomly allocated into two stressor groups
- STRESSOR: dogs were either left alone in a familiar room (n=21) or underwent a short car journey (n=19).
Treatment: CBD dose @ 4mg/kg BW with breakfast, 2 hrs prior to testing.Control received a placebo oil.
Measured physiological and behavioural markers pre, during and post-test.

Findings:

During car travel, CBD treated dogs were scored as significantly less “sad,” and also had a smaller decrease in “relaxed” ratings from baseline to test when compared to the placebo treated dogs.
Dogs that received the CBD treatment also had significantly lower serum cortisol concentrations than dogs that received a placebo
Dogs who received CBD were rated as being significantly less “stressed,” “sad,” “tense,” and “uncomfortable” and more “explorative” during the separation event than dogs who received the placebo.
Consistent with this, dogs who received the CBD also exhibited less whining and sitting behaviour and travelled further when they were left alone.
Collectively these characteristics are suggestive of a more relaxed emotional state in CBD treated dogs.

Aim: to evaluate the influence of CBD on behavioral responses to fear-inducing stimuli in dogs.

Method:

16 dogs
design: replicated 4 × 4 Latin square design experiment with treatments arranged in a 2 × 2 factorial design, blinded
- Groups: (1) control, (2) CBD (1.4mg CBD/kg BW/d), (3) trazodone (100mg for 10–20 kg BW, 200mg for 20.1–40 kg BW), (4) both CBD and trazodone. Dosed for 7 days
Fear induced by fireworks model of noise for 6 mins.
Measurement: cortisol analysis. Behaviors were video recorded, and heart rate (HR) sensors were fitted for collection of HR and HR variability parameters.
Research personnel administering treats and analyzing behavioral data were

Findings:

the fireworks model successfully generated a fear response.
Trazodone lowered plasma cortisol (P < 0.001)
Plasma cortisol was not significantly lowered by CBD or the combination of CBD and Trazadone.
Neither CBD nor trazodone affected the duration of inactivity (P = 0.918 and 0.329, respectively).
Trazodone increased time spent with tail relaxed (P = 0.001).
CBD tended to increase HR (P = 0.093) and decreased the peak of low- and high-frequency bands (LF and HF, P = 0.011 and 0.022, respectively).

Aim: to determine the influence of CBD on the daily activity of adult dogs.

Method:

24 dogs of various mixed breeds, research animals
Design: randomized complete block design
treatments targeted at 0 and 2.5mg (LOW) and at 5.0mg (HIGH) CBD/kg body weight (BW) per day split between two treats administered after twice-daily exercise
Activity monitors were fitted to dogs’ collars for continuous collection of activity data.

Findings:

CBD (LOW and HIGH) did not alter the total daily activity points (P = 0.985) or activity duration (P = 0.882).
CBD tended (P = 0.071) to reduce total daily scratching compared with the control.
In the afternoon, dogs receiving HIGH tended (P = 0.091) to be less active than the control.
CBD did not affect the activity duration during exercise periods (P = 0.143).

aggressive behavior toward human beings decreased significantly over time in the CBD group (P = 0.004), unlike the control group in which there was no significant reduction over time (P = 0.09).
However, the difference between these groups was not significant (P = 0.078).
stereotyped behavior and displacement activity events did not decrease (P = 0.545 and P = 0.923, respectively).
CBD treatment did not change the dogs’ attention (P = 0.09) and interaction with the environment (dozing, P =0.225; sniffing, P= 0.287).