One study showed that the use of cannabidiol reduced aggressive reactions after episodes of social isolation. The work was carried out on mice by researchers from theUniversity of São Paulo from the Ribeirão Preto School of Medicine. The results were published in the journal Progress in Neuro-Psychopharmacology and Biological Psychiatry. Scientists who have studied the behavior of mice have come to this conclusion.
Our study shows that cannabidiol has an effect on reducing aggressiveness and that the substance plays the role of an aggression inhibitor because it facilitates the activation of two receptors: the 5-HT1A receptor, responsible for the effects of the neurotransmitter of serotonin and Receptor CB1, responsible for the effects of endocannabinoids, ”said Francisco Silveira Guimarães, professor at FMRP-USP and head of the study.
The research was conducted according to a so-called "resident-intruder" protocol, which consists of isolating mice several days and after a while, placing another subject in their space to assess their reaction.
"Over the past 20 years, cannabidiol has been studied in many settings, but few studies have examined its effects on aggressive behavior," Guimarães said.
The researchers divided the rodents into five groups each consisting of six to eight male individuals. The mice in the first four groups received different doses of cannabidiol. The latter group did not receive CBD and was used as a control group. As expected, the mice in the group that did not receive cannabidiol reacted almost immediately to the presence of the intruder by noticing it. The reaction took an average of two minutes after the invader was placed in their space.
Rodents in the first group received less cannabidiol and reacted four minutes after the introduction of the "invader".
Those in the second group, where the amount of substance administered was slightly greater, reacted within 11 minutes. In the third and fourth groups, with higher doses, there was no significant inhibition of animal aggressiveness.
“This result on the reduced effect of cannabidiol at higher doses was already expected. In other experiments, such as testing the antidepressant potential of cannabidiol, higher doses resulted in moderate effects, the researcher said.
The new study, also including scientists from USP's Applied Neuroscience Research Support Center, was conducted as part of the thematic project "New perspectives on the use of drugs modifying atypical neurotransmitters in the treatment of neuropsychiatric disorders", supported by the São Paulo Research Foundation. Research is also supported by the National Council for Scientific and Technological Development (CNPq).
Professor Guimarães says isolation-induced aggression is a classic behavioral pattern used in the experiments. “The aggression induced by isolation can be alleviated by the administration of anxiolytic drugs, antidepressants or antipsychotics. Some preclinical and clinical results indicating that cannabidiol has such properties, we decided to test its effect on induced aggressiveness, ”he said.
The data is essential to subsidize research for the development of new drugs.
In the body's central nervous system is a group of receptors called the endocannabinoid system, which researchers believe controls appetite, mood, pain sensation, memory, and other important functions.
The endocannabinoid system is made up of several different receptors, including the CB1 receptor. When the CB1 receptor comes in contact with THC, it induces the psychoactive effects associated with "getting high"; however, when the CB1 receptor comes in contact with CBD, not only does it not cause psychoactive effects, but it prevents THC from interacting with the CB1 receptor.
This allows CBD to inhibit some of the negative effects caused by THC such as anxiety and memory loss including aggression.
Summary
Long-term living in only one dwelling increases aggressive behavior in mice, a condition called isolation-induced aggression or territorial aggression, which can be alleviated by anxiolytics, antidepressants and antipsychotic drugs. Preclinical and clinical results indicate that cannabidiol (CBD), a non-psychotomimetic compound, has anxiolytic, antidepressant and antipsychotic properties. Few studies, however, have investigated the effects of CBD on aggressive behavior. Here, we examined whether CBD could mitigate the aggressive behavior induced by social isolation in the resident intruder test. Male Swiss mice (7-8 weeks) were housed in a single housing for 10 days (resident mice) to induce aggressive behaviors, while mice of the same sex and age (intruder mice) were housed in groups . During the test, the intruder was placed in the resident's cage and aggressive behaviors initiated by the resident, including latency on first attack, number of attacks, and total duration of aggressive encounters, were recorded. The involvement of 5-HT1A and CB1 (CB1R) receptors in the effects of CBD has also been studied. All the doses of CBD tested induced anti-aggressive effects, indicated by a decrease in the number of seizures. CBD, in intermediate doses, also increased the latency to attack the intruder and decreased the duration of aggressive encounters. No dose of CBD disrupted locomotor behavior. The anti-aggressive effects of CBD were attenuated by 5-HT1A receptor antagonist WAY100635 and CB1 antagonist AM251, suggesting that CBD decreases aggressive behaviors induced by social isolation through a mechanism associated with activation of 5-HT1A and CB1 receptors. In addition, CBD decreased the expression of the c-Fos protein, a marker of neuronal activity, in lateral periaqueductal gray (lPAG) in socially isolated mice exposed to the resident intruder test, indicating a potential involvement of this region of the brain in the effects of the drug. Taken together, the results suggest that CBD can be therapeutically useful for treating the aggressive behaviors that are usually associated with psychiatric disorders.
