Anxiety: Cannabidiol Blocks Long-Lasting Behavioral Consequences of Predator Threat Stress

Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: Possible involvement of 5HT1A receptors

C. Campos, F. R. Ferreira, F. S. Guimarães 

2012

KEY TAKEAWAYS:

• CBD can prevent the long-lasting anxiogenic effect promoted by traumatic events
• When compared to the control group, the reduction in anxiety behavior was greater with CBD than with the common antidepressant used in PTSD treatment
• CBD anti-stress effects could depend on serotonin (5HT1A) receptor activation; serotonin contributes to the feeling of well-being, reason why it’s often labeled happiness hormone
• The study suggest CBD has beneficial potential for the treatment of PTSD

OBJECTIVES & HYPOTHESIS → The goal of the study was to determine whether CBD could attenuate the long-lasting anxiogenic effect of a severe traumatic event and if the anti-anxiety actions of CBD were 5HT1A receptor-dependent. The study also investigated the influence of CBD on 5HT1A mRNA and BDNF protein expression in brain areas associated with PTSD.

METHODS → The PTSD model was achieved by predator exposure, since it promotes long-lasting anxiogenic effects in rodents, an effect related to symptoms found in PTSD patients. The rats were exposed to either a live or dummy cat (control) and, 7 days after, submitted to a behavioral test. The behavioral test was performed using an Elevated Plus Maze Test (EPM), a crossed apparatus with 4 arms, 2 enclosed by walls and 2 open; rodents naturally avoid the open arms and anxiolytic compounds increase the exploration of these arms. The first experiment evaluated repeated CBD injections. 1 hour after the predator stress session, rats received a first dose followed by daily injections of either vehicle, CBD (5 mg/kg/day) or Paroxetine (antidepressant used in the treatment of PTSD patients) (10 mg/kg/day) for 6 days. 1 day after the last injection, all animals were placed into the EPM while the number of entries and time spent in the open and enclosed arms was recorded to detect anxiety-like behaviors. In the second experiment, the subjects received injections of vehicle or WAY100635 (5HT1A inhibitor) 1mg/kg 10 min before vehicle or CBD (5 mg/kg) administration.

RESULTS → Predator exposure induced a significant fear reaction reflected by an increase in freezing time. Treatment with CBD or paroxetine prevented the long-lasting anxiogenic effects of predator exposure with significant effects in the percentage of entries, time spent in the open arms and the number of enclosed arm entries in the EPM. Cat exposure decreased all these variables. These results suggest that, in addition to acute anxiolytic effects, CBD could also modify the stress-induced plastic changes that are responsible for long-lasting anxiogenic effects.

Compared to cat-exposed vehicle-injected rats, CBD and Paroxetine increased the percentage of entries and time spent in the open arms. Moreover, these differences were even more evident with the use of CBD in comparison to Paroxetine use.

The anti-anxiogenic effects of CBD in rats submitted to the single predator stress session were no longer present when the animals were pre-treated with the 5HT1A receptor antagonist WAY100635. This result indicates that CBD’s anxiolytic effect could be 5HT1A receptor-dependent, which is present in numerous animals including dogs and cats.