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Cannabidiol reduces aggression, according to a study by the University of Sao Paulo

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New study finds cannabidiol helps reduce social isolation aggression

One study found that the use of cannabidiol reduced aggressive reactions after episodes of social isolation. The work was done 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 demonstrates that cannabidiol has an effect on reducing aggression and that the substance acts as an inhibitor of aggression because it facilitates the activation of two receptors: the 5-HT1A receptor, responsible for the effects of the neurotransmitter 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," said Guimarães.

The researchers divided the rodents into five groups each composed of six to eight male individuals. Mice from the first four groups received different doses of cannabidiol. The last group did not receive CBD and was used as a control group. As expected, mice in the no-cannabidiol group 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 higher, reacted within 11 minutes. In the third and fourth groups, with higher doses, there was no significant inhibition of animal aggression.

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"This result on the reduced effect of cannabidiol at higher doses was already expected. In other experiments, such as the antidepressant test of cannabidiol, higher doses resulted in moderate effects, said the researcher.

The new study, which also includes scientists from USP's Applied Neuroscience Research Support Center, was conducted under the Thematic Project. "New perspectives on the use of atypical neurotransmitter medications 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 that isolation-induced aggression is a classic behavioral model used in experiments. "The aggression induced by isolation can be alleviated by the administration of anxiolytic, antidepressant or antipsychotic drugs. Some preclinical and clinical results indicating that cannabidiol has such properties, we decided to test its effect on induced aggression, "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, memory, and other important functions.

The endocannabinoid system consists of several different receptors, including the CB1 receptor. When the CB1 receptor comes into contact with THC, it causes the psychoactive effects associated with "becoming high"; however, when the CB1 receptor comes into contact with CBD, it not only does 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

Living in a single long-term housing increases aggressive behavior in mice, a condition called isolation-induced aggression or territorial aggression, which can be mitigated by anxiolyticsantidepressants and antipsychotic medications. Preclinical and clinical results indicate that cannabidiol (CBD), a non-psychotomimetic compound, has anxiolytic, antidepressant and antipsychotic properties. Few studies, however, have studied 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 the aggressive behaviors initiated by the resident, including latency during the first attack, the number of attacks and the total duration of the aggressive encounters, were recorded. The involvement of 5-HT1A and CB1 (CB1R) receptors in the effects of CBD was also studied. All doses of CBD tested induced anti-aggressive effects, indicated by a decrease in the number of attacks. CBD, at intermediate doses, also increased latency to attack the intruder and decreased the duration of aggressive encounters. No dose of CBD disrupted locomotor behavior. The antiaggressive effects of CBD were attenuated by the 5-HT1A WAY100635 receptor antagonist and the CB1 AM251 antagonist, suggesting that CBD decreases the aggressive behavior induced by social isolation by 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 pereductal gray (lPAG) in socially isolated mice exposed to the resident intruder test, indicating a potential implication 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.

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