Тег: Inhibitor

How to Search and Check Drugs for Increasing Inhibitor of Violence?

Кто-то может задаваться вопросом, как находить препараты, эффективные для усиления ингибитора насилия, наподобие продвигаемых на наших ресурсах? Да и как уже известные препараты можно было бы легко перепроверить? Если коротко – всё делается простым перебором «кандидатов», обнаруженных в различных исследованиях и статьях, каждый из которых проверяется на животных. И организовать опыты может практически любой, у кого есть достаточно свободного места в доме/квартире/даче. Простейший вариант парадигмы резидента-нарушителя (стандартного опыта на агрессию) является лёгким в проведении, а если всё делать самостоятельно, финансовые расходы будут минимальными.

Для начала необходимо приобрести в зоомагазине или взять у кого-то чётное количество мелких грызунов (крыс или хомяков, обязательно всех самцов). Все особи разделяются на две группы: «резидентов» и «гостей» («нарушителей»). «Резиденты» всегда рассаживаются по отдельным клеткам, «гости» – хомяки тоже по отдельным клеткам, а вот крыс стоит держать по несколько особей. Клетки размещаются подальше друг от друга, желательно в разных комнатах.

«Резиденты» должны побыть в изоляции минимум неделю, а лучше две. После проверяем «резидентов», помещая в клетку с ними «гостя» на 5 минут, записываем всё на видео и пересматриваем. Если нападения занимают не менее 10% длительности опыта или настолько интенсивны, что опыт пришлось прервать, значит «резидент» пригоден. Иногда необходимо провести несколько таких опытов с разницей не менее 3 дня (при этом хомяков разделяем по конкретным парам, а в случае крыс проводим ротацию «гостей»), но если какие-то «резиденты» так и не становятся агрессивными, они исключаются из опытов и отпускаются.

В совсем упрощённом варианте можно начать с дозировок препаратов как человеческая, делённая на 200 для крыс и на 1000 для хомяков. Впрочем, лучше будет для конкретного препарата поискать в сети любые опыты (даже не связанные с агрессией) и отталкиваться от дозировки, предлагаемой там. Препарат можно, например, размешать в воде и, держа особь одной рукой, ввести в пасть шприцом без иглы другой рукой. Также можно попробовать подмешать препарат в пищу, но тогда придётся проконтролировать, чтобы вся дозировка была принята.

В случае крыс пригодным «резидентам» за час до опыта даём принять препарат. Что касается хомяков – даём препарат и «резиденту», и «гостю», поскольку в их случае «гость» тоже может быть агрессивным. Также при необходимости можно проводить ежедневный приём препарата в течение какого-то периода, сделав последний приём тоже за час до опыта. После проведения опыта просматриваем запись. Если уровень нападений сильно снизился или они вообще прекратились, значит препарат работает! При отсутствии результата можно пробовать повышать дозировки, при этом контролируя, чтобы не снижалась активность особей в целом (так мы подтвердим, что эффект именно антиагрессивный, а не седативный).

After each experience with medications, it is advisable to isolate subjects for at least one week and conduct a control experiment to determine the baseline aggression, as some medications can have a very long-lasting effect. It is recommended to store medications separately from the room with “residents” in airtight containers, since the evaporation of some medications can reduce the aggressiveness of animals.

If testing an inhaled medication (e.g., essential oils), transfer the cage with the “resident” to an isolated room without ventilation, spray or vaporize a larger amount of the drug there to allow them to strongly smell its strong scent (e.g., using an aroma lamp for essential oils), let the “resident” inhale the vapors for an hour and conduct the experiment. Make sure that the vapors do not get into the room where other “residents” are kept.

Therefore, it is desirable to test any medications so that before using them on aggressive representatives of our species, you suddenly don’t find out that you were sold some kind of fake, and you can personally verify that enhancing a violence inhibitor is a real thing!

Voluntarist, Bitarch

What is the point of inhibitor weapons and what makes them better than classic lethal ones?

Unfortunately, our skeptics still may not understand the fundamental point of the idea about developing combat means to enhance the violence inhibitor. They suggest “don’t waste time,” develop a classical army and invest in traditional lethal weapons. But let’s break it down – why they are wrong.

1) Increasing mobilization potential by several orders of magnitude – unlike what is typically observed with soldiers armed with lethal weapons, drones with this means in the sky will not be shot at, even by those possessing a strong variant of violence inhibitor from birth! And this is even more relevant to opposition forces than armies of states, because among anti-authoritarian people there will be fewer psychopaths willing to kill easily than in the security structures protecting the status quo.

2) Greater public support and less outrage about brutality from sympathizers, which is especially important for a weaker side.

3) The possibility of using inhibitor means in civilian life against domestic abusers, unlike the complete uselessness of classical weapons like tanks and artillery during peacetime (billions are spent on their production, maintenance, and crew training annually from taxes, and this does not benefit society at all, and it is particularly burdensome for more free societies compared to authoritarian ones).

4) Safety of manufacture for the manufacturers themselves – inhibitor drugs cannot accidentally explode during manufacturing, transport or storage; even accidental exposure to workers will do them no harm.

5) Even cluster munitions (CMWs) can be humane. Replicable (“contagious”) vector vaccines have already been tested on animals and their effectiveness was recognized, meaning there are no technological barriers for developing “contagious” gene therapy to enhance the violence inhibitor. Of course, this is a very risky solution, but believe me, anyone would rather catch a “new cold” than be defeated by classical CMW types like nuclear or VX gas.

6) Extremely low cost and simplicity of production of the dose of the inhibitor drug. Of course, developing the first dose may cost billions and require complex equipment, but the cost of reproducing each subsequent one will be on the level of the current cost of doses of popular vector vaccines. The need for equipment and materials to reproduce is not comparable to the equipment needed to produce classical weapons (the equipment easily fits in an apartment, while factories producing artillery shells or tanks occupy square kilometers and are easily vulnerable to air strikes).

7) Extremely small weight of the “combat part” and little energy is required for successful defeat (it’s enough to pierce the skin anywhere on the body). In theory, it’s possible to create a drone the size of a bee, which is already a real technology – not science fiction!

8) Humane mines with no demining problems – after the war, classic mines can remain dangerous for civilian populations for many decades, while inhibitors in traps are quickly neutralized by environmental factors.

As a final note – why not tranquilizers to temporarily sedate the enemy? Indeed, science fiction often features plots where instead of lethal weapons, darts with tranquilizers are used. However, in real life and especially in combat conditions, this is difficult to implement because even a small dose of any tranquilizer won’t have an effect, while too large a dose will be fatal, and the dose needs to be calculated for each person individually, primarily taking into account their body weight. On the other hand, for most inhibitory drugs, the therapeutic window (a “dynamic range” when the dosage already gives an effect but is not yet lethal) will be extremely wide, and one dosage can be boldly applied to any person.

VoluntaristBitarch

A hardware problem cannot be solved with software

When a capacitor on your motherboard bulges, you resolder it rather than trying to solve the problem by changing some variable in the Windows registry. When a shock absorber in your car dies, you certainly won’t go in and reprogram the electronic control unit in the hope that the problem can be solved without “dirty work.” But for some reason, when it comes to malfunctions in human “hardware,” many mistakenly believe that these problems can be solved purely “programmatically” (through philosophy, religion, social institutions), without therapeutic intervention in the defective systems of the body.

This misconception is especially noticeable in discussions about the violence inhibitor. But in fact, it is exactly the same kind of hardware system as processor elements like the ALU and registers. If a processor has physical defects or has degraded, no firmware update will help — this sad lesson was well learned by owners of the latest generations of Intel “stones.” Likewise, in the case of a degenerate rapist, no amount of persuasion will help — the problem is purely “hardware,” it is in his “noggin.” It’s time to accept the truth and abandon the illusions: hardware (physical) problems require a corresponding hardware solution (action in the real world)!

Voluntarist, Bitarch

“Anti-Lorentz” is impossible in practice

We once examined the question of why using a certain drug that suppresses the function of a person’s violence inhibitor (or as we also called it, “Anti-Lorenz” agents) has little practical utility and effectiveness, but is capable of leading to serious problems. However, this was presented from the perspective of social processes, whereas now we will delve deeper into the biological essence of this issue.

As we know, the violence inhibitor is managed by the brain’s serotonergic system, specifically the 5-HT1A and 5-HT1B receptors, as well as the MAO-A, TPH2, and SERT proteins associated with their function, encoded by the corresponding genes (for simplicity, we will call all of these “variables”). And we can assume that only a specific, quite narrow combination of these variables creates a high risk of developing violence inhibitor dysfunction in a particular individual. After all, only a tiny fraction of the population (no more than 1–2%) has increased psychopathic predispositions in any population.

Impact on at least one of these variables “upward” is quite capable of significantly strengthening the inhibitor function (eliminating the ability to initiate violence). Thus, in experiments on animals and humans, the mere activation of 5-HT1A or 5-HT1B receptors, or the enhancement of serotonergic function through impact on SERT activity, selectively eliminated violent behavior. At the same time, impact on any of the variables “downward” does not guarantee the weakening of the inhibitor (restoration of the ability to initiate violence), as was, for example, shown with the blocking of 5-HT1A and 5-HT1B receptors in animals.

On the other hand, there are strong grounds to believe that attempts to actively exert such an influence can cause serious mental disorders—increased anxiety, depression, suicidal thoughts, and other pathologies related to the serotonergic system. Initially, such problems are often not particularly pronounced in psychopathic personalities simply because the narrow combination of “variables” required for this is evolutionarily maintained (with a bouquet of disorders, they simply would not have had reproductive success). In fact, according to research, violence inhibitor dysfunction itself is a “point” rather than an extensive disruption in brain function.

Why is all this important in practice? In the tasks of strengthening and weakening the violence inhibitor, there is a huge disparity in complexity. To put it simply—even in a successful attempt to weaken the violence inhibitor by suppressing any “variable,” it will not be possible to guarantee that this effect will not be reversible if someone applies agents to strengthen a certain “variable” to the person who did this. However, one can certainly guarantee serious side effects. In one of the experiments on rats using the neurotoxin 5,7-DHT, which affects the serotonergic system, although it was possible to increase their aggressiveness, this effect was reversed by introducing small doses of serotonin into the brain. A similar neurotoxic effect is exerted, for example, by methamphetamine, which at high intensity of intake is capable of increasing a person’s psychopathy. But most likely this effect is also reversible in the same way, and the result of weakening the inhibitor with “meth” in such a case will be a lack of result and the causation of serious harm to health.

And what if the aggressor does not know the specific time when they will have the practical opportunity to use violence? They would need to constantly take multiple drugs to weaken all “variables.” But constantly maintaining such a balance of “variables” so that simultaneously: 1) it is enough to weaken the violence inhibitor, 2) it is not yet enough to cause neurophysiological disorders, 3) it is enough to overcome the effect of agents for strengthening the inhibitor—is hardly possible in real life at all.

Ultimately, an attempt to weaken the violence inhibitor will only lead to serious neurophysiological and mental disorders, but will provide no guarantee against its reinforcement under appropriate influence. Practically effective and safe “Anti-Lorenz” agents turn out to be simply science fiction.

Voluntarist, Bitarch

What exactly in our brain makes us non-violent

Voluntarist, Bitarch

Extremely interesting and important results were demonstrated by experiments on the use of anti-aggressive agents in mice and rats. It turned out that some of them are capable of reducing the manifestation of attacking aggression on their part, while not affecting defensive aggression and other non-aggressive forms of behavior and social communication. To be more specific, we are talking about agonists that activate serotonin 5-HT1A/1B receptors.

These results align with the theory that many species possess innate inhibitors of aggressive behavior, which prevent causing harm and killing members of their own species. In the case of humans, a model of the violence inhibition mechanism (VIM) was even developed, which also explains the development of empathy. Based on this theory, violence in intraspecific relationships should be viewed as a pathological rather than a natural form of behavior. Especially since even in many territorial, social, and armed species, the level of lethal violence still does not exceed 1%, and according to various evidence, only no more than 2% of people do not experience strong resistance to committing murder.

We also see that defensive aggression, unlike attacking aggression, is indeed a natural form of behavior, and the work of the violence inhibitor does not stop it in the presence of an immediate threat to life in the environment. This was well demonstrated by the administration of the 5-HT1A agonist alnespirone to rats. It had an extremely selective effect; the strong reduction in aggressiveness did not prevent the rats from resorting to defensive behavior when encountering an aggressive peer.

Various genetic evidence demonstrates that certain variants of the 5-HT1A/1B receptor genes, as well as three other genes associated with the 5-HT system—TPH2, MAO A (also known as the “warrior gene”), and SERT—lead to increased aggressiveness in animals and humans. For example, in one study, impulsive and aggressive alcoholics were found to have differences in the 5-HT1B gene compared to healthy people and non-aggressive alcoholics. This study covered two different groups of people: Finns and a Native American tribe. Mutations in the MAO A gene have long been known as a cause of abnormal manifestations of aggression in men.

According to the violence inhibition mechanism model, the direct result of its dysfunction is calloused-unemotional (CU) traits in children and psychopathy in adults. Changes in the function of 5-HT1B receptors in certain parts of the brain were found in people with aggressive traits and psychopathic traits. A difference in the 5-HT1B gene genotype was present in children with calloused-unemotional traits.

It should be noted that dozens of genes and a large number of systems influence aggressiveness. However, the violence inhibitor remains a specific mechanism expressed by a limited number of receptors and genes. Firstly, this is simply important for inhibiting aggression most effectively. Secondly, other forms of pharmacological intervention, such as the use of antipsychotics (like haloperidol), beta-blockers, drugs affecting GABA neurotransmitters, and 5-HT2 receptor agonists and antagonists (many psychedelics belong to the former), result only in a non-selective reduction of aggressiveness, suppressing defensive aggression and other forms of behavior, and causing side effects.

Understanding the nature of the violence inhibitor and its limitation to a small number of receptors and genes can not only tell us a lot about violence itself, but also help in creating a solution aimed against it as a pathological form of behavior inherent in a minority of people. And the essence of such a solution is simple: returning to them the inhibiting control over aggression that is natural for the majority, through the use of appropriate pharmacological or even gene-therapeutic drugs.

This material briefly describes the content of the article titled “Neurophysiology and Genetics of the Violence Inhibition Mechanism“, which you may refer to for greater detail.

Violence is an evolutionarily failed strategy

Voluntarist, Bitarch

In justification of intraspecific violence as a completely normal phenomenon in nature, one sometimes hears the argument about the selfishness of the gene. Since all biological evolution is primarily the evolution of genes striving for the most efficient preservation and copying of themselves, and only after that the evolution of individuals and populations, then intraspecific violence is not a problem at all. On the contrary—if a carrier of a gene committed violence, they gained an advantage over their conspecifics and passed this gene on. This means that intraspecific violence is a useful tool in the evolution of genes, and no violence inhibitor, slowing down aggression toward representatives of one’s own species, can exist, as it would contradict the attainment of such an evolutionary advantage by specific genes.

The idea that the evolution of genes takes precedence over the evolution of individuals and populations is a correct theory that there is no sense in disputing. But genes do not exist in a vacuum. Genes are carried by specific individuals who are part of specific populations. How the relationships between these individuals unfold will become the decisive factor in the preservation and transmission of genes. And violence will indeed give an advantage to a specific gene, provided it does not mean that gene’s own elimination. But what if it does?

Let’s take those species whose representatives possess strong innate weaponry and have no significant possibility of escaping violence (for example, due to the limited habitat range of the population or an extremely social lifestyle). It is precisely in such species that the inhibition (restraint) of intraspecific violence is observed. When one wolf exposes its neck or belly to another wolf, the latter becomes unable to bite its conspecific; no raven will peck another raven in the eye with its very sharp beak, even during a fight for food; venomous snakes conduct territorial clashes according to clearly defined rituals, without using their venomous teeth and not even demonstrating them to their opponent; oryx antelopes also ritualize battles, while they can freely use their sharp horns against lions. There are many such examples.

What is the benefit of the gene in such behavior? It is that a violent attack on a conspecific, given the latter’s strong weaponry, can end with the death of the aggressor itself with an impermissibly high probability. This means that the gene will not be preserved or passed on; it will simply perish along with its carrier. Only those genes will be passed on whose carriers, in such a situation, do not get into fights unnecessarily (or more accurately, do not initiate them at all, but only defend themselves if someone else has already initiated one). That is, the most advantageous evolutionary strategy for a gene is “cooperation” (let’s call it that) with the gene responsible for inhibiting violent behavior in the carrier.

This is a universal rule for biological evolution. Increasing weaponry of population representatives combined with frequent social contacts between them increases the negative consequences of intraspecific violence, at a certain point making them completely impermissible. As a result, only those genes survive whose carriers were able to compensate for this effect by suppressing violent behavior, meaning they were predisposed to have a sufficiently strong version of a violence inhibitor. The higher the weaponry of the population representatives, the less advantageous an evolutionary strategy violence becomes, and the more advantageous becomes the inhibition of violence.

This understanding should also be applied to humans—the most heavily armed species on the planet, whose weaponry is now growing at a giant pace along with the development of scientific and technical progress. The average person already possesses an inhibition of violence toward other people, but there remain those who suffer from a dysfunction of this neurobiological mechanism. Such people will sooner or later use weapons of mass destruction, which, with scientific and technical progress, are becoming increasingly accessible to recreate, especially regarding biological threats, where a catastrophic scenario could occur literally tomorrow. This means that violence is an evolutionarily failing strategy for humans!