Potentially effective treatment of violent behavior in humans

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Violent behavior, including different forms of abuse and physical attacks, is a huge problem in human relationships. However, relying on simple persuasion or even behavioral psychotherapy can often be ineffective or overly demanding approaches. Therefore, it is crucial to consider a potentially faster and more effective approach that involves treating violent behavior with medications.

It is known that humans have a violence inhibition mechanism, which causes them to experience an aversive reaction to harming other people. The serotonergic system of the brain is responsible for this mechanism and the regulation of aggression in general[1][2]. Therefore, it is reasonable to conclude that the most effective treatment of violent behavior should focus on restoring its healthy functioning. And now, we will look at a number of medications that can help people who are prone to committing violence.

Before considering more serious pharmacological solutions, we should look into the use of common bioactive supplements or natural remedies. For example, tryptophan, a serotonin precursor, may be a good option. The recommended dosage ranges from 500 milligrams to 5 grams per day[3]. In experiments on animals, tryptophan had a selective anti-aggressive effect[4][5]. And in some human trials, it reduced aggressiveness and hostility and increased trust and generosity[6][7][8][9][10]. Other supplements that affect serotonergic function, such as 5-HTP (reduced aggression in animal experiments), inositol (reduced hostility in humans), S-adenosylmethionine (reduced aggression in patients with schizophrenia), etc., may also be potentially useful[11][12][13].

Mixtures of herbal extracts like Kamishoyosan (also known as Jia Wei Xiao Yao San in Chinese) and Yokukansan (or even just its specific ingredient, Uncaria rhynchophylla extract), as shown in animal studies, may have a selective anti-aggressive effect by affecting the serotonergic system[14][15]. A mixture of extracts called Si Ni San with a similar effect is able to reduce aggression resulting from stress[16][17]. In addition, it is worth considering that other natural remedies (saffron, rosemary, matcha) can affect the serotonergic system in a similar way[18][19][20].

Based on numerous animal experiments and limited human trials, it is believed that drugs activating specific receptors (1A and 1B) of the serotonergic system should be very effective and selective (with no side effects and no disruption of any behaviors other than offensive aggression)[21][22]. Such agents include the previously mentioned mixtures of herbal extracts. Among the widely available drugs with this mechanism of action are triptans, commonly used against migraine. Particularly noteworthy is zolmitriptan, which was successful in reducing aggression in mice and attenuating alcohol-heightened aggression in humans (using 5 milligrams of the medication)[23][24]. Researchers have also proposed testing triptans, specifically a 4-week course of naratriptan, on violent offenders[25].

We should not overlook the use of classic antidepressants, selective serotonin reuptake inhibitors (SSRIs), which lead to a general increase of serotonin in the brain. Although taking them is associated with a risk of unwanted side effects, researchers have tested these drugs more than others for their anti-aggressive effect when administered to humans[26]. For example, individuals with personality disorders who take fluoxetine are 4 times less likely to engage in aggressive behavior than those who do not take SSRIs[27]. A daily intake of 20–60 milligrams of fluoxetine can reduce aggressiveness to a certain extent after 4 weeks, and after 10 weeks, there are significant improvements[28]. In laboratory tests, a single dose of 40 milligrams of paroxetine successfully eliminated aggression associated with primary psychopathy (the typical traits of which are callousness and lack of empathy; these traits are strongly associated with violence inhibitor dysfunction). And it was found that this did not result from sedative or anxiolytic effects. Researchers believe that primary psychopathy is related to dysfunction of the serotonergic system of the brain[29]. Taking 30–40 milligrams of fluoxetine daily for 12 weeks significantly reduced the propensity for both physical and nonphysical aggression in people with alcoholism who were violent toward their spouses or significant others[30]. Taking 100 milligrams of sertraline daily for 3 months has also proven to be an effective approach in correcting the behavior of violent repeat offenders[31]. Finally, it should not be overlooked that in several experiments, citalopram improved the ability of participants to recognize facial expressions of fear (and recognizing such distress cues from other people is important in the functioning of the violence inhibitor), increased their generosity, and made them more likely to choose to avoid hurting people in certain types of moral dilemmas (indicating increased harm inhibition)[32][33][34][35].

Among SSRIs, vortioxetine (most commonly sold under the brand names Brintellix and Trintellix) is particularly noteworthy. Although, due to its novelty, it has not yet been widely tested for its anti-aggressive effect (however, there are already studies on single patients), because of its multimodal mechanism of action, including action on serotonin 1A and 1B receptors, this drug is considered to have a great potential in the treatment of pathological expressions of aggression and to be safer and more effective than other SSRIs[36][37][38][39].

Multiple studies have found that “omega-3” supplementation can moderately reduce both reactive (impulsive) and proactive (instrumental) aggression. The effect is up to 30% in different populations and may be related to improvements in the functioning of the violence inhibition mechanism[40][41].

In addition to all of the above, it is not unreasonable to consider such an approach to the treatment of violent behavior as inhalation of essential oil vapors. These often contain linalool, which acts on serotonin 1A receptors and has been shown to have an anti-aggressive effect in animal experiments[42][43][44]. Many essential oils (bitter orange, neroli, petitgrain, rose, lavender, citronella, lemon, geranium, etc.) have substances with similar mechanisms of action (including the already mentioned linalool, as well as d-limonene, citronellol, geraniol, β-pinene, etc.)[45][46][47][48][49][50][51][52]. It is also worth noting that essential oils have been shown to be effective in reducing aggressiveness in people with cognitive impairment[53].

Taking probiotics can be potentially beneficial (these include Bifidobacterium breve and longum, Lactobacillus plantarum, lactis, and rhamnosus). They can increase tryptophan and serotonin levels in the organism, as well as influence the serotonergic system of the brain through the gut-brain axis[54][55][56][57][58][59]. The possibility of using them for the treatment of violent behavior is already being researched[60].

When using any of these medications, it is important to carefully select dosages and take into account possible side effects. If any of them are present, it is necessary to stop taking the medication that caused them immediately!

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