SÃO PAULO, Brazil — There’s plenty of debate about the possible benefits and dangers of marijuana. One of the drug’s ingredients however, has less of a controversial reputation. Scientists at the University of São Paulo’s Ribeirão Preto Medical School finds cannabidiol (CBD), which studies say can improve health, can also lower aggression in animals.
“Our study shows that cannabidiol can inhibit aggressiveness and that it does so by facilitating the activation of two receptors: the 5-HT1A receptor, responsible for the effects of the neurotransmitter serotonin, and the CB1 receptor, responsible for the effects of endocannabinoids,” explains study leader Francisco Silveira Guimarães in a media release.
CBD does not cause the same psychotropic effects as marijuana’s more famous ingredient, tetrahydrocannabinol (THC). Previous studies show that cannabidiol actually inhibits some of the effects of THC. “Cannabidiol has been studied in various contexts for the past 20 years, but very little research has been done into its effects on aggressive behavior,” says Guimarães.
Testing CBD on aggressive mice
Isolation-induced aggression is a behavioral model commonly used in experiments. Researchers use the resident-intruder test, which they say induces aggressiveness in animals kept in isolation for several days. Scientists can curb this type of aggression with anxiolytic, anti-depressant, or antipsychotic drugs. Since CBD possesses some of the same properties as these medications, the study tests it on this kind of aggressiveness.
Study authors split the mice into five groups, administering different doses of cannabidiol to each. One group was given no cannabidiol as a control. This group behaved as expected when intruders entered their areas, attacking about two minutes after confronting the intruder.
The group receiving five milligrams per kilogram of CBD delay attacking for four minutes after the intruder arrives. The total number of attacks on intruders also fell by half. The third group, receiving 15 mg/kg, turns out to be the least aggressive in the study. Researchers find increasing the dosage for the other groups in the experiment has no additional effects. In the 30 mg/kg and 60 mg/kg groups aggressiveness wasn’t curbed, but actually rises slightly.
“This reduction in the effect of cannabidiol at higher doses was expected from the results of other studies. In experiments to investigate its potential as an antidepressant, for example, higher doses led to lower effects after an initial gain. In our experiment, if we had tested 120 mg/kg on a group of mice, we might not have obtained any inhibition of the resident’s aggressiveness at all,” Guimarães reports.
Chemical balancing act
Cannabidiol helps the body activate the 5-HT1A serotonin receptor. In a second round of experiments on mice, Guimarães’ team administered increasing doses of the 5-HT1A receptor inhibitor, known as WAY100635, to see if the anti-aggressive effect of CBD could be canceled out or blocked in any way.
They find WAY100635 appears to inhibit the cannabidiol effects. Mice that were given WAY100635 before the CBD attacked intruders at about the same frequency as the control group.
The researchers also test the theory that cannabidiol inhibits an enzyme which metabolizes the endocannabinoid anandamide, adding an anti-aggressive effect to cannabidiol. Endocannabinoids are neurotransmitters in the central nervous system. Anandamide binds to type 1 cannabinoid receptors (CB1) in the brain. These receptors are also activated by THC.
The researchers tested their theory by conducting a resident-intruder experiment using AM251, a CB1 receptor inhibitor, combined with CBD The results are similar to their WAY100635 experiment. Guimarães adds their studies suggest cannabidiol alters aggressive behavior by some sort of mechanism which activates 5-HT1A receptors and CB1 receptors.
“We don’t yet know how the 5-HT1A and CB1 receptors affect aggressiveness in mice, but the activation mechanisms involved appear to be different in each case.”
The study is published in the journal Progress in Neuro-Psychopharmacology and Biological Psychiatry.