Origins of Addictive Behavior: a nature heritage or a neuropsychiatric nurtured reality?

Luis Alberto Coelho Rebelo Maia. Professor Auxiliar do Departamento de Psicologia e Educação da UBI. Doutorado em Neuropsicologia Clínica pela UBI e Universidad de Salamanca – Departamento de Psicobiología, Psicología Básica y Metodología de las ciências del comportamiento / Instituto de Neurociências de Castilla y León.

Abstract

In this paper we present a revision on the origins of Addictive Behavior and related neural basis. Although there are abundant specific bibliography and professions focusing on addictions treatment, the reasons why people started with addictive behaviors and consequently maintain are still not well understood. This article explores the construction, meaning, and impact of addiction in historical and psychological perspective. The challenge to the usual concept of addictions causes has significant implications for medical practice and for treatment programs. Furthermore, with this article we present the phenomena of Multifactorial Polygenic Heritage as a possible theory for the explanation of addictive behavior, being consequently important for its prevention and treatment. The roles of social, cultural, and population differences, as they may relate to addictive behaviors, are explored.

Keywords: Addiction; Vulnerability; History of Drugs, Neuropsychiatry of Drugs

Orígenes del comportamiento adictivo: ¿un patrimonio de la naturaleza o una realidad neuropsiquiátrica adquirida?

Resumen

En este documento presentamos una revisión sobre los orígenes del comportamiento adictivo y sus bases neurales. Aunque hay abundante bibliografía específica y profesiones centrándose en el tratamiento de adicciones, todavía no se entienden bien las razones por lo que las personas comenzaron con comportamientos adictivos y los mantienen. Este artículo explora la construcción, significado e impacto de la adicción en una perspectiva histórica y psicológica. El desafío para el concepto habitual de causas de adicciones tiene importantes repercusiones para la práctica médica y para los programas de tratamiento. Por otra parte, con este artículo presentamos los fenómenos del patrimonio poligénico multifactorial como una teoría posible para la explicación del comportamiento adictivo, con consecuencias importantes para su prevención y tratamiento. Las funciones sociales, culturales y las diferencias de población, en lo que se puede referir a comportamientos adictivos son explorados.

Palabras-clave: Adicción; Vulnerabilidad; Historia de las Drogas; Neuropsiquiatría de las Drogas.


Origens do comportamento aditivo: Herança natural ou Uma realidade neuropsiquiátrica adquirida?

Resumo

Neste artigo apresentamos uma revisão sobre as origens do comportamento aditivo e as suas bases neurais. Embora haja abundante bibliografia específica, bem como profissões no campo, enfocando o tratamento de dependências e os motivos que levam as pessoas a iniciarem os seus comportamentos de adição e, consequentemente, mantê-los, estes ainda não são bem compreendidos. Este artigo explora a construção, significado e impacto da dependência numa perspectiva histórica e psicológica. O desafio ao conceito usual de causas de dependências tem implicações significativas para a prática médica e para programas de tratamento. Além disso, neste artigo apresentamos os fenómenos da Herança Poligénica Multifatorial como uma possível teoria para a explicação do comportamento de dependência, sendo consequentemente importante para a sua prevenção e tratamento. São ainda explorados os papéis sociais, culturais e as diferenças de população, bem como eles podem incidir sobre os comportamentos de dependência.

Palavras – chave: Adição, Vulnerabilidade; História das drogas; Neuropsiquiatria das Drogas

INTRODUCTION

The term “addiction” was initially used by medical and moral authorities as a medical condition to characterize what was till that time denominated of “habitual drunkenness”, used in the late 18th century(1-2). The term addiction did not exist before that date and rapidly evolved for the field of actual illegal drugs, which at that time only drugs were used in majority on the field of medicine, like the opiate morphine, in the case of Veterans of America Civil War (1861-1865). The terminology “Addiction” has been currently used as a general term to cover up a subject with a number of other expressions that has been used: particularly “alcoholism”; and well before, “inebriety,” in the extended records of talking with reference to alcohol; and “dependence,” in contemporary nosologies (3).

The most widespread psychoactive drug used by mankind, since ancient and biblical times is alcohol, and a simple glance in the Old Testament demonstrate the importance in psychological effects, and even in terms of genetic influence, as well as moral, environmental and so forth(4-5). Alcohol and opiate substances were the first psychoactive substances used with this purpose already around 5,000 year b.C (6). The deleterious consequences of alcohol abuse or misuse were well recognized in the prehistoric age, and it took mankind a long time to make any real progress in providing help to those individuals who are affected(4). The production of alcohol is the oldest of all intentional psychoactive drugs production. In the same way, the historical searches indicate that fermentation of some fruit or honey is the first remote origin of the first psychoactive agent. Archaeological discoveries reveal that pieces to production and consumption already existed 8.000 b.C and that, at least, in 5.000 b.C. they were used to store honey; it is deduced that honey were fermented and diluted in water (mead or hydromel) and has been the first wine for human consumption(7).

Still in biblical terms, alcohol utilization has been well described in quote several passages from bible and has been related alcohol use with inhalational anesthesia, hypnosis and amnesia, chronobiology, amongst other subjects(8). From the Bible Book of Proverbs (p. 123) they quote the Proverb 20: “Wine makes men foolish and strong drink makes men come to blows”, as well as the Book of Genesis, 19, “And that night they made their father take much wine... and the older daughter went into his bed; and he had no knowledge of when she went in or when she went away and so the two daughters of Lot were with child by their father”.

Parting from these passages, some authors made several extrapolations. They state that probably some grapes were left in some place, like a hole in a rock, about 6,000 years ago (8). Progressively, “they deteriorated and became a viscous mass, under the action of the sun and invisible creatures (yeasts), which quenched the thirst of some primitive hungry man… alcohol’s stimulating-depressing effect had just been discovered”. In its review, the authors suggest that Ethanol was the first substance intentionally used in order to make surgery possible. As example of that, they state that ethanol was the only anesthetic drug (in form of wine) used by barber-surgeons from the Napoleonic army, that invaded Russian in 19th Century. This therapeutic utilization was interrupted because the non-significant therapeutic index and problems in intentionally awaking patients, and culminated with the interruption of these procedures in the early 20th Century.

In terms of curiosity, these inebriating and amnesic effects served as the basis for the first written known description of an incest relation between Lot (Abraham’s nephew) and his two daughters (altogether they have left from Sodome) (8). From these relation got alive the origins of Moabite and Amanite tribes. According to the authors this lascivious effect of alcohol to facilitate rape was replaced by the benzodiazepine flunitrazepam (Rohipnol), legally banned in several countries (although they have been first developed as benzodiazepine drug used as a hypnotic and in anesthesia), because its capacity to cause semiconciousness and memory blackouts (several unwanted sexual encounters were reported by victims of sexual assault under the influence of this drug)(8). As another example of anesthetic effect of alcohol they quote the Book of Marc 15, “And they gave him wine mixed with myrrh; but he did not take it”, were the refuse from Jesus was considered has a refuse of the anesthetic effect of alcohol, preferring to suffer the pain of crucifixion from 9:00 a.m. to 3:00 p.m. in the Golgotha hill.

Pulque is, probably, the oldest fermented drink in pre-Hispanic Mexico(9). The culture of the Maguey (a variation of Pulque) is almost as old as the origins of agriculture in America. There are testimonies that inform on the culture of the maguey in the zone of Tehuacán towards year 6 500 b.C. Its utilization was strictly reserved to ritual purposes and only by tribal leaders or sorcerers, being its utilization by ordinary people severely repressed. In equal way “the earliest confirmed evidence for wine dates back to 5.000 b.C. This evidence is in the form of tartrate deposits on a pot from the Zagros Mountains of Iran. It is questionable whether wine could predate this discovery by more than a thousand years as it, perhaps, required the advances in pottery which took place at this time. Before this discovery, the oldest confirmed evidence for grapes within human settlements was in pips from wild vines dating from c 4500 BCE”(10). Some claim that there is evidence for cultivated grapes dating back to c 8000 BCE, in the so called Noah Hypothesis, although there is no evidence to relate founds of this period to cultivated varieties and also, the evidences found are so few as to make this date doubtful(10). Like the historian Edward Gibbon, affirm that wine search was one of the reasons that had taken the Barbarians to invade the Europe (11). Also, Grapevine is the most cited plant in the Bible and the first miracle of Jesus was to convert water into wine in the weddings of Canaan; also The Mediterranean armies, since the antiquity, had always drunk wine; The Justinian Code prescribed posca, sour wine and water, as part of the ration of the soldiers; The drunkenness of Alexander, the Great, and of its father, Filipe, became famous and proverbial; Passed two millennia, and the Napoleonic armies continued to receive wine; one hundred million liters had been more than bought for the French soldiers; In World War II the military ration of the Frenchmen arrived up to one liter daily; But in the year of 1917, the French army bought 120 million liters (11).

Other remarkable categories of agents that modify states of minds are vegetables, or herbal varieties, like plants. For instance, people from the Waley of Rivers Tigres and Eufrates (3.000 b.C) consumed Amapola (a plant) to produce euphoria and “well-being” (the same plant was reported in India, 1500 b.C, as a “wonderful plant”) (9). Hallucinogenic Solanaceae use, like Belladonna, Datura and the Mandragora, goes back to old testimonies of Middle and Far East; in Europe, they were bound traditionally with witchcraft, being used in ceremonial and therapeutic contexts. Levitation phenomena are attributed to them, as well as telepathy and fantastic physical feats. In Eurasia the muscaria amanita, a psychoactive fungus used by shamans of Siberia in its rituals was very abundant (12).

The opium, juice of a type of poppy, is one of the most known versatile drugs; due its active ingredient, morphine, the opium induces lower pain, produces joy, induces dream and reduces afflictions; the plant of the poppy, well-known like narcotic, always was used like food, forage and oil, but there are historical registries which their psychotropic functions already were known in 3.000 b.C. (13). The first written signs of Opium existence as a plant and its use overcome to the Sumerian times 3000 years b.C, although it is not but in the Ebers Papyrus in century XVI b.C where is found for the first time the reference to opium name in a product list of medical effects, with the following indication: “For children who shout too much hard” (14). Also, the Greek culture knows the plant entirely and therefore Hesiod in century VIII previously mentions it in his works, and cite Morpheus (that in century XIX would give name to Morphine), and until in the very same Odyssey appears the “Nepenthes” like the “drug of the forgetfulness” (14). However, the principles of their systematic use are tie logically to Hippocrates, Herodotus and Theophrastus in century III b. C., time in which already begins the controversy (that would never leave to us) on the medicinal double slide and of dangerous substance (14). Additionally, the Romans, heirs of the Greek culture, know, indicate and use the Opium with naturalness, and thus Galen in century I b.C. introduces in his “triaca magna” and many great contemporary men used it with therapeutic aims like emperor Marco Aurelio who used it to calm his migraines. After a period of relative silence on its use, in the age it mediates the Arabs (who never let use it) spread the use of opium by all its occupied territories, being known that Avicenna dies intoxicated by himself in 1037 (14).

In Middle East, where he was very employed by medicine, it was extended towards India and, later, in century IX, until China, while in western Europe the opium acquired therapeutic importance in century XVI, after the trips of the doctor and Swiss alchemist Paracelsus, whom its spread for diverse aims in laudanum form or in tinctures (12). Initially, in China, Opium was used orally as medicine, and in the later century XVII, the consumption of smoked opium became popular in that country (7). The consumption was increased in an alarming form and the internal production was not sufficient, so that in century XIX, 16.2 million Chinese citizens was addicted to smoked opium (6% of the adult population) (2). In China opium was well-known from century VIII although it began to be used to obtain medicine as a result of its introduction by the Arabs in Asia towards centuries IX and X (14). However, it was not but towards the century XVI that next to the introduction of the use of tobacco by the Dutch and Portuguese sailors that gradually opened the doors to its consumption like means of enjoyment and pleasure, which locates in century XVIII with an intense commerce of opium with India (14). The business was served and thus the British Empire begins to monopolize the transaction of opium in Asia being happened to sell 300 Tons in 1821 to more than 3000 Tons in 1848. According to several authors the attempt to restrain the opium commerce generated two successive wars (1839-1842 and 1856-1858), between England and China, culminating with the Chinese defeat and the obtaining of a series of privileges on the part of England, as the complete legalization of the commerce of Indian opium and the loss of the administration of Hong Kong (2,7).

In equal way, in Europe, in the heat of century XIX, Opium spreads slow but inexorably wrapped by an important tolerance and animated by intellectuals and essayists: Quincey, Musset, Coleridge, Dickens, Scott, Poe, Baudelaire, Gautier, Balzac, and thus one releases list of illustrious guarantee it; so that in the XX the spirit follows: Apollinaire, Modigliani, Toulouse-Lautrec, Picasso and thus until the stubborn defense that in 1929 makes Cocteau in its work “Opium” (14). The purification of opium alkaloids, that already the doctors of Napoleon, Derosne and Seguin, plus the invention of the syringe by Pravaz, causes that morphine extends like the analgesic powder like in all the Wars (Crimen, American Succession, etc.), and also by the richer social layers of Europe, where the equipment of injection for morphine becomes sophisticated models of last fashion and the books on the wonders of the injection are multiplied (14). From this to its generalized prohibition in almost the entire occidental world was just a little step.

Other famous hallucinogens have also millenarian foundation. In America, the old indigenous civilizations also had the custom to use hallucinogenic plants in their ceremonies. After century X, b.C. there is stone-fungus between monuments of Izapa culture (actual Guatemala), as well as in Peru (pipes of ceramics of century IV b.C. with a figure of peyote, an hallucinogenic cactus that contains mescaline) (12). Thus Peyote fungus whose active principle is mescaline, goes back to the pre-Columbian American civilizations, and later its use is even very wide-ranging among North American Indians (Mescaleros Apaches, Comanches Kiowas and Cheyenes); Aldous Huxley, being one of the last intellectuals in proving it and spreading it to the own, in his book “In the doors of the perception” describes the effects of the hallucinogen in itself (15-16). Peyote, for the Indians was something religious, mythical, that the same provided invulnerability sensation that served to discover distant and hidden things; its main alkaloid is the mescaline, that produces an own dissociative syndrome like in schizophrenics, originating chromatic visions and hallucinations (17).

The relation between witches with ointments (drugs) is a constant since an interrelation its supposed and was appraised and the spoor that suffered; one of the first that occurred account of this was doctor Andrés Laguna and more recently it has been shown by M.J. Harner, that has studied thorough the ointments that used, reaching the conclusion that if not all, the majority contain atropine, powerful alkaloid at least; the cane or broom on which many witches said to fly served to apply the plants that contained it to the sensible vaginal membranes and that that alkaloid produced a deep lethargy to those who of them were worth, to the way of our present drugs - “trips” also denominate the artificial paradises in which the drug addicts submerge day today is something in which they agree who approach the subject with rigor and seriousness (17).

The popular nicotine also has some remarkable evidences. The acclimatization of the plant Nicotiana tabacum in Cuba was developed by the aravacas Indians 2,000 years old before Christ (18). Although some authors have affirmed that it was already present in the old organizations of the east, their most known origin is the American, being accepted that the first culture in using tobacco leaves to smoke them was the Mayan, from 2,000 b.C.(19).

Tobacco is a solanachea plant that grows mainly in the Eastern hemisphere, also cultivated in Turkey, Russia and other countries of Europe (20). Columbus and the conquerors that followed saw it the Indians of the Antillean islands, Mexico, Central America and Brazil smoking tobacco rolls. In a wake of Uaxactún, Guatemala, that dates from century X is the figure of a Mayan priest smoking, who demonstrates that the use of tobacco was well established long before the discovery of America, which also was confirmed by Sahagún (20). The Indians of North America also smoked, in the region of Ontario in a zone called Tionontati (Tobacco Nation) (20). In Europe tobacco was first described in Chronicles of Colombian discoveries as well as India’s adventures. Gonzalo Fernández de Oviedo y Valdez (Historia General de las Indias, Sevilla, 1535), states “Among other reprobables customs the Indians have one is specially injurious and that consists of the absorption of a certain class of smoke to which some call “tobacco” to produce a stupor state (...) absorb the smoke by means of a hollow cane, that is what the Indians call “tobacco” and not to the grass”(18). Also, Columbus was surprised by the use of tobacco in religious and social ceremonies, like those of peace and purification of the spirit, because for the Indians the tobacco had magical powers and pleased the Gods.

Tobacco was considered a panacea, since it was used to fight the asthma, the fevers and convulsions, the intestinal and nervous upheavals and bites of animals (18). There are reports that supports that early in 1560 a.C. tobacco was known in Spain and Portugal. The author stresses the origin of the name Nicotine. According to him, the ambassador of France in Portugal, Jean Nicot, was interested in the use of the plant and when he returned to its country he took tobacco leaves with himself to offer to queen Catherine de Médicis. For that reason, tobacco was called “grass of the queen”, “nicotiana” or “grass of the ambassador”. Catherine de Médicis suffered from strong migraine and the ambassador recommended taking the plant inhaling it by the nose. The pains disappeared and the tobacco began to be used like medicine in France and the rest of Europe. When Linnaeus published its Species Plantorum, he chose the scientific name of Nicotiana tabacum in tribute to Nicot (18). In 1584, Walter Raleigh founded on North America the colony of Virginia, copied from natives the custom to smoke in pipe and the culture of the famous tobacco in Virginia, that was introduced in England in Isabel the Ist Era (18).

The possible therapeutic virtues of tobacco, took the conquerors of Hispanic America to transfer the seeds for their culture to the old continent at the beginning of century XVI; the Spaniards also took their culture towards Prusia and Philippines (from where he moved towards China) and the Portuguese scattered it by Africa, Italy, Iran, Java, India and Japan (2). Rapidly tobacco become the main economic resource of the English colonies and for that, the great marine trips of centuries XVI, XVII and XVIII around the world contributed to take tobacco and the habit to smoke until the coasts of Asia, Africa and the Australian Continent (18). In several oriental countries like Japan, Russia, China and Turkey tobacco’s use was strongly fought initially with drastic measures; for instance, Sultan Murad IV ordered the execution of numerous smokers and, in 1638, the Chinese authorities threatened beheading the tobacco dealers; Turks got up themselves to the world-wide market of tobacco and became heavy smokers, like the Chinese(18).

The earliest reference of the medicinal properties of the cannabis dates from 2700 b. C., when in China was used for the treatment of flue, rheumatic malaria, pains and menstrual upheavals. After that, was widespread throughout history in India, Middle East, South Africa and South America (21). Hemp (sativa cannabis, Marihuana) has been cultivated in China for 4,000 years(6). The Ancient Greeks, and particularly Galen make references about cannabis. Also, Galen in his De alimentorum facultatibus (6, 549-550), write about cannabis’ seed, compared to the seed of agnocastus; jointly with the reference in De simplicium medicamentorum temperamentis ac facultatibus and in De victu attenuante (22).

Some of its very know effects by nowadays where already descript although being unknown the plethora of effects that are available today (in Galen passages some effects where cited like difficult to digest, cause pain in the stomach, migraine, spoils humors and also produced an altered state of mind in some people, particularly when it was smoked and not eaten. In equal way, Greek people knew about its vapors, and obviously, about its special effects, and the fact that roughly nobody described abuse of this stupefacient in a straight line was maybe due to its rarity (cannabis was not believed to be originally from Greek) or its abnormal consumption (22).

Cannabis is part of THC drugs (Tetrahydrocannabinols). Its effects are well described: when the drug is smoked the effects appear quicker than when ingested, being the primary effects euphoria, relaxation and changes in the perception (23). In heavy consumers more prominent delusions can occur, time notion are modified, the short term memory is affected, mental processes become confused, the person can forget the contents of conversations and be not able to communicate accurately; ultimately, other negative effect are paranoia, respiratory problems, dryness in mouth, cardiac acceleration, psychological dependence and, if the consumer have tendency to develop neuroses and psychoses, the use of cannabis can unchain the problem (23).

Morphine (name in honor to Morfeo, God of the dreams), was isolated of the opium at the beginning of century XIX by the German Fiedrich William Sertüner and happened to replace (along with codeine) the opium in the medical treatments, specially after the introduction of hypodermic injection like therapeutic, in 1855 (2,7). In 1874, was created the first semi synthetic opiate, diacetylmorphine, also well-known as heroin. It was commercialized by Bayer as substitute of the opium and morphine in the detox programs; its effects as a potent pain killer and stimulating effect lead to widespread commercialization and only many years later the commercialization for this aim was interrupted (12). The heroin began to become popular like recreational drug in the United States and England first and, later, in almost the entire world, being sought as the symbol of pernicious effects of drugs (24).

Ecstasy was one of the most popular illegal psychotropic drugs back to the past 1980 era (25). One of the most used drugs amongst youngsters that although most of medical references about de origins is methylenedioxymethamphetamine (MDMA, ecstasy) that makes references of its development as an appetite suppressor, by the German pharmaceutical company Merck in 1912, it is nothing but a common error (26). Although MDMA had been developed in 1912 the first known study in humans was published in 1978, by Shulgin et al. about chemistry, kinetics, dosage, and psychotropic effects (27-28). Only in 1984 it was baptized as “Ecstasy” in California, USA (26).

What about cocaine? In America, the Inca empire (Andean) produced three annual harvests from cocaine leaf (erythroxilum cocaine lam) which were used as analgesic and energizing of daily use, specially due to fatigue produced by height; in the Aztec society, was also used the ingestion of the so called teonanacati fungus and the consumption of peyote with religious aims (6). The leaf of Cocaine (Erythroxylon Cocaine, of Linnaeus), overcomes its beginnings in the historical knowledge by year 2000 b.C., being found artifacts and instruments for its mastication in Chilean and Peruvian coasts; the word Cocaine comes from Khoca that means literally “tree” or “plants” (14), and when it emerges in all his splendor in the pre-Columbian times, locating itself like the center of the religious and social system of the Incas, for whom the plant was a divine gift (29). Other authors states that the use of the stimulating cocaine in America is as old as the use of the alcohol, opium and the cannabis in the old continent and Asia, so that cocaine leaves already were chewed in the Andean region from approximately 5,000 b.C.(30). Erythroxilum cocaine grew at the beginning of wild way but it began to be cultivated in the century X a.C., by the Chibcha Indians of Colombia, that later spread it to south, being used in sacred rituals and medicine procedures (31). In Inca culture where mastication of Cocaine leaf was mainly reserved for aristocracy and the sacerdotal body, except for sometimes specific rituals or in some initiate processes, and the own Americus Vespucci in 1499 is noticed of the behavior of some Indians of Venezuela coast, apparently raised and without fatigue in spite of the work (14).

Before the era of great navigations in century XVI cocaine was not well-known in other places of the world. When the Spaniards arrived, they were surprised with the effects of the leaves chewed by the workers. At a first moment, by religious reasons, they tried to prohibit it but later they used it like stimulating in the operation of the silver mines (2). The consumption by American Natives was attacked and condemned in the first celebrated Ecclesiastical Assembly in Lima in the year of 1551, once it was considered to be related to idolatry and witchcraft (32). It is praised and recommended by their active principle - the cocaine - and their pharmacological effects at the end of century XIX, when Sigmund Freud and Halsted and Hall, used it in their experiments of psychopharmacology and local anaesthesia, respectively (32-33).

Amphetamine is a chemical derivative of ephedrine, synthesized for the first time in 1887 by Rumanian chemistry L. Edeleano, which baptized the substance as phenilisopropilamine. The experimental medical use of amphetamines began in 1920. The role of World War II that lead to its administration to the soldiers in a massive form, with the objective to fight the fatigue and to maintain them alert (2). Almost all the armies used them. For instance, the American army distributed more than 180 million tablets to its combatants; amphetamines also have been used like an agent to improve physical and cognitive performance (doping effects) (2).

LSD was accidentally discovered by Swiss chemistry Albert Hoffman in 1938 when it tried to find an analogous substance to stimulate circulatory system, being commercialized by Sandoz factory under the name of Delycid, with the alleged objective of facilitate psychotherapy and to fight some upheaval like chronic alcoholism, sexual anomalies, etc.; when it was verified that the drug produced unforeseeable effects, it was finally forbidden (6).

At this point, let us remind the title of this paper: Origins of Addictive Behavior: nature or nurture? And let us think a little about it.

Some authors present a recent review about the denominated “paradox of drug reward in human evolution” and the evaluation of the paradox between evolutionary biology’s punishment model and neurobiology’s reward model (34).

The current existing models of drug reward have effectively bypassed the paradox by ignoring the evolved function of plant drugs and the probable co-evolution of plant defensive compounds and herbivore nervous systems. The principal conclusions was that there are some major assumptions underlying the current evolutionary reward models that should take into that:

a) “drugs are an evolutionary novelty;
b) humans (and mammals) are inherently vulnerable;
c) and hedonic reward best characterizes the psychological and physiological responses to drug exposure” (34).

They consider the contradictory evidence that shows that most of abuse drugs are derived from toxic elements, developed to be toxic and avoid and repeal enemies (e.g Butolin Toxine) (34). Also, the authors suggest that, as an hypothesis that the nature of human substance abuse could have evolved in order to exploit antiparasitic property of plant toxins, amongst other possibilities. Independently of the best hypothesis found, they suggest more and deeper neurochemichal research to explain the apparent tendency for humankind drug abuse (34).

Considering the distribution of drugs in natural environments in ancestral ages, if we consider that resources were limited and so probably the overactivity of salient (wanting) behavior. So, there is no reason to postulate the development of dopaminergic reward cortico-mesolimbic system in terms of a “built-in regulatory system of salience” (35). By that reason, the author postulate that factors like genetic and environmental ones could have no consequences in ancient environments, because of their limitations. This could be a factor that could have leaved us more vulnerable to addictive behavior, mostly, according to the author, the development of ancient psychotropic plant chemicals (35).

We present a table I with some landmarks of evolutionary addictive behavior and drug discover.

Table 1. Landmarks on addictive behavior (35)

a) Archaeological records indicate the presence of psychotropic plants and drug use in ancient civilizations as far back as early hominid species about 200 million years ago.
b) Roughly 13,000 years ago, the inhabitants of Timor commonly used betel nut (Areca catechu), as did those in Thailand around 10,700 years ago.
c) At the beginning of European colonialism, and perhaps for 40,000 years before that, Australian aborigines used nicotine from two different indigenous sources: pituri plant (Duboisia hopwoodii) and Nicotiana gossel. North and South Americans also used nicotine from their indigenous plants N. tabacum and N. rustica.
d) Ethiopians and northern Africans were documented as having used an ephedrine-analog, khat (Catha edulis), before European colonization.
e) Cocaine (Erythroxylum coca) was taken by Ecuadorians about 5,000 years ago and by the indigenous people of the western Andes almost 7,000 years ago. The substances were popularly administered through the buccal cavity within the cheek. Nicotine, cocaine, and ephedrine sources were first mixed with an alkali substance, most often wood or lime ash, creating a free base to facilitate diffusion of the drug into the blood stream. Alkali paraphernalia have been found throughout these regions and documented within the archaeological record. Although the buccal method is believed to be most standard method of drug administration, inhabitants of the Americas may have also administered substances nasally, rectally, and by smoking. Many indigenous civilizations displayed a view of psychotropic plants as food sources, not as external chemicals altering internal homeostasis.
f) The perceived effects by these groups were tolerance to thermal fluctuations, increased energy, and decreased fatigue, all advantageous to fitness by allowing longer foraging session as well as greater ability to sustain in times of limited resources.

g) The plants were used as nutritional sources providing vitamins, minerals, and proteins rather than recreational psychotropic substances inducing inebriation. Due to limited resources within ancient environments, mammalian species most probably sought out CNS neurotransmitter (NT) substitutes in the form of psychotropic allelochemicals, because nutrient NT-precursors were not largely available in the forms of food. Therefore, drugs became food sources to prevent decreased fitness from starvation and death. It is believed that early hominid species evolved in conjunction with the psychotropic flora due to constant exposure with one another. This may be what eventually allowed the above civilizations to use the flora as nutritional substances, therefore increasing both their fitness and viability.

In the same line, psychotropic drugs could have evolved to present allelochemical reactivity in order to deal with threats from herbivores and pathogenic invasions, as if they were an imitation of mammalian neurotransmitter system, that act like competitive binders, obstructing normal functioning of central nervous system (34-35). This ideas reinforce that where the evolution of mammalian brains and psychotropic drugs where co-dependent, that is to say that existed an ecological interaction and influenced one another in terms of evolution (34). One set of examples to reinforce this hypothesis, but maybe the most striking one is that in the mammalian CNS we found opioid receptors, but the truth is that the body do not provide any natural opioid substance by himself (so that could be pretty more logical that some environmental effect forced the mammalian organism to develop receptors to exogenous opioids) (35).

Most of the times, the way to describe the beginnings of ancient drug utilization is based on the artifacts that remains from older eras and is target of the study of the so called archeobotany or archaeoethnobotany(36).

For example, considering hallucinogenic drugs, hallucinogenic plants are most of the times considered as the principal source of psychoactive drugs (37). The authors state that these drugs must be used to reach deep altered states of consciousness. It’s also stated that several investigators believe that this was particularly accurate during the Tiwanaku empire expansion, surrounding the era of 500-1000 A.D., along the Atacama Desert of Chile. In equal way, emphasize the roll that artifacts played in those conclusions, such as decorated snuffing tablets and tubes, as well as grave goods during this period (“until now the type of drugs consumed in this paraphernalia has been unclear”) (37).

About the archeological discovers in Shumla Cave number 5, Rio Grande, Texas, USA, and states that the identification of mescaline, in that sample, strengthens the evidence that native North Americans considered and used the psychotropic properties of peyote for at least 5700 years ago(38). Prior studies have shown that the utilization of psychotropic drugs in that region of North Mexican and South American border could be dated from 8500 BC (39).

There are several studies that stress a possible genetic factor in facilitation of drug use initiation like in nicotine (40), alcohol (41) and a plethora of drugs. For instance, in a study of two groups with more than one thousand female twins, monozygotic and dizygotic, were evaluated possible association of genetic influence on drug use(42). They found some evidences that genetic influences have a say to vulnerability to drug use, and each category of drugs, apart from hallucinogens, presents distinctive genetic influences. The genetic influence of vulnerability was superior for heroin than for other drugs (42). In other separated studies including samples of twins of both sexes, suggest a superior genetic weight in men for vulnerability to drug abuse/dependency reaching 60-80% of the genetic weight in the development of drug use and abuse (43-44).

Some authors presented a literature review on family and in two well known phases of drug addiction treatment and processes: engagement and treatment (45). According to the cited sources, the article highlights the necessity for addict patients to be treated along with their families (some authors suggest Familiar Therapy) so that adequate results could be expected. The importance of socio-cultural issues can influence institutional treatment and call attention for the necessity that treatment of addict’s patients and their families, as well as effective preventive action programs (45). These point gains considerable relevance since it is well known the dependence developed by intra-uterine via in pregnant mothers that continues the use and abuse of drug during pregnancy, with proved deleterious effects for her siblings (46). Some examples are the fetal alcohol syndrome (47), neonatal withdrawal syndrome(48), neonatal abstinence (49), effects of pre-natal exposure by cocaine, amphetamines and heroin (50-51), etc.

For example, in a recent study with 1836 subjects tried to “examine substance use and dependence among cocaine dependent subjects and their siblings compared to individuals recruited from the same neighbourhood and their siblings in order to better understand family and neighbourhood contributions to the development of dependence” (p. 14)(52). Cocaine dependent subjects came from treatment centres and community-based subjects were sample-matched to cocaine dependent cases, with one full sibling for each case and community-based subject. The results show a higher risk rate of cocaine and other substances use in siblings of cocaine users. Nevertheless, the authors conclude that Cocaine dependence is characterized by poly-substance use and dependence. Stressing that the prevalence of substance dependence in the community subjects was higher than reported for the general population, they state that cocaine dependent cases probably live in higher-risk communities, characterized by an elevated prevalence of substance dependence (52).

Although all data presented, many researchers and also a great part of social general opinion, support ideas from the Institute for Health and Social Policy, from USA, that suggest that the most important factors for the initiation and continuation of drug utilization are societal factors, that could include the tolerance for drug utilization - perceptions of negative social and health consequences of the use of these drugs - as well as the availability and the ways the drugs are set in the market (53). In our opinion, this type of hypothesis appears not to consider the possible inner predisposition for drug consumption, based on the well known vulnerability model. Generally speaking, the idea is that in drug abuse (whether in initiation or in chronic abuse) at least three major factors should be taken into consideration: the psycho emotional subject, the environment and the “genetic subject”. This could be considered as a Multifactorial Polygenic Heritage. Several studies strongly suggests this for alcohol dependence starting in animal (54), human first-degree relatives of alcoholics (55), adopted Childs from alcoholic and non-alcoholic biologic parents(56), monozygotic and dizygotic twins (57), siblings of alcoholics compared with nonalcoholics in terms of risk factor (58). The same hypothesis has been putted for other drugs although at a lower rate of published data. For the importance and clearness of ideas we transcribe here a part where this point is strongly approached (59):

If genetic factors are involved in drug abuse, what does this mean? First, we must realize that genes do not directly cause behavior.

No gene or set of genes, for example, will directly cause a person to become a drug abuser or to engage in drug-taking behavior.

Instead, genes are segments on chromosomes that code for the production of specific proteins (or serve to regulate the activities of other genes) that are important in the control of behavior. If a gene is absent, a protein that controls the development or function of a physiological system may not be produced. In certain cases, the impact may be obvious, as in the case of phenylketonuria, when failure of a gene to code for the enzyme responsible for metabolism of phenylalanine results in development of a severe form of mental retardation. In other cases, however, the impact of genes on behavior may be less obvious but just as real, as when genetic factors produce a tendency or predisposition to respond in a certain manner. Such is believed to be the influence of genes on a number of behavioral traits and disorders, including alcoholism and drug dependence. Thus, genes are not the sole determinant of alcoholism or drug dependence, but their presence (or absence) may increase the likelihood that a person will become alcoholic or drug dependent. Second, as the above statement indicates, genes do not act alone in determining whether a person will become alcoholic or drug dependent. Our experience in behavioral genetics suggests that both genetic and environmental factors will ultimately be implicated in the etiology of drug abuse. As with alcoholism, simple cause-and effect models will not be sufficient for explaining vulnerability. Rather, various combinations of biological and environmental factors are likely to be identified that function to attenuate or exacerbate an individual's likelihood for becoming drug dependent. Just because an individual has a genetic tendency for developing drug dependence does not mean he or she will necessarily develop the disorder. Whether the disorder develops will ultimately depend on environmental influences.

Certain types of environmental influences are believed to be necessary for a genetically vulnerable person to develop drug dependence. For example, one environmental influence that is essential to the development of the disorder is that an individual must initially engage in drug-taking behavior. Thus, while a person may be genetically loaded for drug dependence, if drugs are never used, that person will never run the risk of becoming drug dependent. The presence of other environmental factors in the development of drug dependence (e.g., drug availability, the manner in which a person uses drugs) is also suspected. These may include environmental influences that operate within the immediate milieu (e.g., family and peer influences) or more broadly (e.g., cultural factors). Third, genes may influence a person's tendency to develop drug dependence in many ways. Most people believe that genetic influences operate by producing an aberrant or idiosyncratic biological response to drugs. For example, genes may make some people more (or less) sensitive to a drug's effect, or they may produce a qualitatively different drug effect in some people than in others. While this may indeed be the case, it is important to recognize that there are mechanisms other than pharmacological mechanisms that may account for genetic effects. One nonpharmacological mechanism is that genes may determine personality characteristics that increase the probability of drug abuse. For example, a person may inherit a sociopathic personality that increases the likelihood of contact and experimentation with drugs.

Cultural factors may in part be genetically determined, which may increase the likelihood of drug use that will eventually lead to increased rates of drug dependence (59).

Of course we do not lose of sight the social impact of drug abuse, like the one, for example, related with crime. For instance, substance abuse is habitually found in violent offenders (60). He mentions data from DSM-IV (1994), “more than one-half of all murderers and their victims are believed to have been intoxicated with alcohol at the time of the murder.” (60)

In terms of etiology, most attention in the drug abuse field has been focused on psychosocial factors that contributes to drug experimentation by adolescents (59).

A variety of community factors and individual vulnerabilities pressure drug abuse patterns and trends within a geographic area and throughout a particular phase and, contrasting with infectious diseases, drug abuse, and what kind of drugs are used by whom, is more prejudiced by social factors rather than biological ones. The author states, on the other hand, once subjects start on drug abuse, their brains and bodies suffers some alterations and biological and physiological factors happen to be added as important factors (53).

Despite everything that was stressed in this paper, the actual implications of drugs in terms of personal and social levels are shocking. The prison reality (punishment vs. forced treatment during incarceration?) (61-62), the social control strategies (63), direct effects in ruining careers (64), and in homelessness (65), disruptive behaviours (66), other health consequences, as altered sates of cortical activation and neuronal malfunction (67-69), neuropsychological deficits (70-72), and so on.

Furthermore, the complete disaster of scare strategies in drug use prevention is very important (73). Also, the role of media messages about addictive behaviour and deleterious substances or habits should strongly be revised (74). The future, as well as the real present, will probably force us to accept and implement more educative strategies than scaring or punishing strategies to avoid individual drug use initiation.

The answer to our work question: Addiction – nature or nurture? is, naturally, not available by now. However one thing seems to make sense to us. At the beginning of mankind drug use, most of then appear to be started as a recreational use, as part of rituals or cultural pantominas. Furthermore, generations after generations, drugs utilization, or if we prefer, addictive behaviour, became probably coded in our inheritance. Understanding the phenomena of Multifactorial Polygenic Heritage (the interactions of the psycho emotional subject, the environment and the “genetic subject”) could probably be very helpful in preventing and treating addictive behavior.

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