As is known, the brain’s serotonergic (5-HT) system plays a key role in the regulation of aggression and is responsible for the function of the violence inhibition mechanism in humans. Therefore, it has become the target of many studies aimed at developing the most effective anti-aggressive agents. Of course, there are many substances that have shown efficacy in animal experiments. But now we will list some of those that have already been tested in humans.
In experiments on mice and dogs, the administration of tryptophan, which is a precursor to serotonin, had an anti-aggressive effect without disrupting other behaviors. But what about application to humans? In some experiments, it reduced aggressiveness and hostility, as well as increased trust and generosity. Other bioactive supplements that affect serotonergic function can also be useful (for example, inositol reduces hostility in humans, and S-adenosylmethionine reduced aggressiveness in experiments on patients with schizophrenia).
In many animal experiments, it has been shown that certain 5-HT1A and 5-HT1B receptor agonists (drugs that activate them) are capable of suppressing offensive aggression without affecting defensive behavior and other forms of activity. In humans, the laboratory agent eltoprazine was tested for a similar effect with the aim of “inhibiting destructive behavior without other significant behavioral, psychiatric, or somatic side effects.” In a number of trials on aggressive patients with dementia, intellectual disability, psychotic disorders, and personality disorders, it did not lead to an overall improvement in their condition, but significantly reduced aggressiveness with minimal to no side effects. Also, in one experiment, the agent zolmitriptan, which has a similar effect, significantly reduced aggression associated with alcohol consumption.
Selective serotonin reuptake inhibitors (SSRIs), although they may have side effects, have been most extensively tested in humans regarding violence. In patients with personality disorders, fluoxetine reduces the risk of aggressive behavior by 4 times. In one experiment, it also significantly reduced violence committed by alcoholics toward their loved ones. In another experiment, paroxetine successfully eliminated aggression associated with primary psychopathy (implying heartlessness and lack of empathy), and this was not the result of a sedative effect. It appears that primary psychopathy is linked to dysfunction of the serotonin system. Sertraline was once tested on violent recidivists, and it proved effective in correcting their behavior. Also, in several experiments, citalopram improved participants’ ability to recognize facial expressions of fear (and recognizing distress signals from others is important in the work of a violence inhibitor), increased their generosity, and made them more prone to choosing to avoid harming people in certain types of moral dilemmas.
It is also worth mentioning psychedelics, which are agonists of 5-HT1A and 5-HT2A receptors that are capable of stimulating empathy and prosocial behavior in humans. In one experiment, psilocybin even led to a sustained reduction in predisposition toward authoritarian political views, and it is believed that it could be very useful in treating psychopathy and antisocial behavior. Additionally, any experience of its use, as showed by a study of criminal behavior among 480 thousand American adults, significantly reduces the risk of committing violent assaults.
Finally, let us note some other examples. For instance, omega-3 intake leads to a moderate reduction in both reactive (impulsive) and proactive (instrumental) aggression, which may be linked to improvements in the function of the violence inhibitor. Substances affecting 5-HT1A receptors are also found in essential oils, the inhalation of which proved effective in reducing aggressiveness in people with cognitive impairments. Furthermore, the possibility of using probiotics (bifidobacteria and lactobacilli), which participate in the metabolism of tryptophan and serotonin in the body, for the therapy of violent behavior is already being studied.
