Drug Usage the Use Drugs

Drug Usage

The use drugs to affect conscious states dates back almost to the origins of humanity. In fact, the pollen of eight medicinal plants was found in a 60,000-year-old tomb in Iraq, and in the Assurbanipal library, researchers found lists of medicinal plants inscribed on tablets (Changeux 1998). Shamans and other mystical and spiritual teachers have long used substances such as opiates, to induce trance-like states in order to communicate with spirits and deities in the 'other' worlds (Changeux 1998). Moreover, both the Old and New Testaments repeatedly refer to the use of wine, from Noah's and Lot's alcoholic stupors to the wedding at Cana and the Last Supper (Changeux 1998). It seems that drugs, whether alcohol or hallucinogenic drugs such as peyote and opiates, have a long history among human beings. Greek philosopher, Epicurus, proposed that human beings are pulled forward toward and by nature to seek pleasure, thus it would seem that the human brain must have pleasure centers that keep humans in constant search of fulfillment (Changeux 1998). However, the explanation for drug usage, particularly drug addiction, is not quite that simplistic. Social environment has long been blamed for drug usage and addiction, yet that did not explain why one family member became addicted, while others did not. Recent studies indicate that drug usage and addiction may be primarily blamed on genetics, thus an individual's genetic make-up may determine whether he or she is vulnerable to drug and/or alcohol addiction.

The word "pharmacon" initially referred to the magic of plants to heal and to the evil spirit or demon that caused the disease within the body (Changeux 1998). Eventually, the mysteries of plants were replaced by rational medicine, and diagnoses were made and remedies proposed based on the active principles of plants that were later defined as chemical substances, and thus pharmacological agents, resulting in a powerful and socially beneficial means of regulating the use of drugs (Changeux 1998).

During the sixteenth century, the recreational use of pharmacologically active derivatives of plants, such as tobacco and coffee, became popular in Western society, yet throughout the nineteenth century, the usage of "artificial paradises," such as hashish and opium, was generally limited to select groups, namely a few societal elites, along with poets and artists (Changeux 1998). Interestingly, many physicians became recreational users of mind-altering drugs when the syringe and hypodermic needle was invented. When author Emile Zola wrote that the compulsive use of alcohol was directly linked to poverty and social distress, his book, L'Abattoir, was a dramatic literary evocation of the drug abuse that plagues Western society today, resulting in global drug trafficking and causing major health problems for individuals and society at large (Changeux 1998).

As drug abuse became more wide-spread, repressive laws were enacted without regard to its social origins. Nineteenth-century laws were directed at preventing criminal use of poisons (as opposed to pharmaceutical use), therefore the usage of substances with euphoric effects was not repressed (Changeux 1998). Although opiates became illegal during World War I, it was sometime during the 1950's before the distinction between the patient and the user was officially established. In 1970, France introduced therapy as an alternative to imprisonment for individuals who were addicted to drugs however it was met with limited success (Changeux 1998). Despite strongly repressive laws throughout the world, and the astronomical amount of monies spent on anti-drug wars, drug abuse remains an alarming health hazard around the globe (Changeux 1998). Illicit drugs are blamed for 35% of new cases of AIDS in the United States alone. Between 1985 and 1994, heroin related deaths in U.S. metropolitan areas rose from 1,300 to 3,500 (Changeux 1998). Thus, even with the threat of imprisonment and the very real inevitability of acquiring major health problems, many individuals appear to simply ignore the warning signs and continue to use drugs. Is the cause environmental or biological?

The National Institute on Drug Abuse defines drug addiction as a "chronic, relapsing disease, characterized by compulsive drug seeking and use, and by neurochemical and molecular changes in the brain," and like other chronic diseases, drug addiction can have serious effects on the body's organs, resulting in an increase vulnerability to other diseases, such as HIV and viral hepatitis (Science 2006). Often, addiction is the result of abuse, which is the use of illegal drugs or the inappropriate use of legal drugs to produce pleasure, alleviate stress, and/or alter or avoid reality, yet the "risk factors for addiction and protective factors against it can be environmental as well as genetic" (Science 2006).

In fact, research indicates that genetic factors (including environmental effects on these genes) account for 40-60% of an individual's vulnerability to addiction (Science 2006). Recent studies are beginning to uncover which genes are responsible for making a person more vulnerable, which genes protect against addiction, and how an individual's genes and environment interact. Moreover, there is evidence that people with mental disorders have a greater risk of drug abuse and addiction that the general population (Science 2006).

The National Institute on Drug Abuse cautions that addiction is a complex disease, and no single factor can predict who will become addicted to drugs because addiction is influenced by a myriad of factors including genes, environment and age of first usage (Science 2006). The NIDA refers to addiction as a developmental disease, meaning that it generally begins in adolescence, at a time when the brain is undergoing continuous changes. The prefrontal cortex, which governs judgment and decision-making functions, is the last part of the brain to develop, perhaps explaining why teens are prone to risk-taking and are especially vulnerable to drug abuse, thereby increasing the likelihood of becoming an addict in the future (Science 2006). In one experiment, rats pressed a lever in response to a cue that had originally indicated access to cocaine even though it had been a year since the cocaine had stopped being administered, indicating a strong association in the brain between drug experience and the setting of the drug experience (Science 2006). Thus, long-dormant cravings may be triggered by encountering a particular environment.

In 2005, it was reported that researchers had identified several single nucleotide polymorphisms (SNPs), "small but meaningful allelic variants that result in changes to the shape or structure of a specific receptor or enzyme that relate directly to addiction problems" (Goldman 2005). According to Dr. Wade Berrettini, of the University of Pennsylvania, there is a set of SNPs that influence the binding affinity of the mu (beta) endorphin receptors, of which some are proving to have some predictive value for alcohol and nicotine addiction, as well as for response to addiction treatment (Goldman 2005).

As of the 2005 article, researchers had identified some 25 SNP variants in the gene coding for the mu receptor, however none constitutes a 'gene' for addiction, yet some do seem to alter how the mu receptor functions (Goldman 2005).

Although Berrettini and his colleagues have not yet identified any single variant that shows an increased prevalence among addicts, compared to non-addicts, they have found some differences. For example, they found some alleles in 10% of the African-American population that they did not find in people of European ancestry, which underscores an important guiding principle: "When looking at the influence of small genetic variation on the risk of a given disease state, it is important to compare ill vs. well people of the same racial and ethnic background" (Goldman 2005).

While Berrettini did not identify a specific mu receptor SNP that correlated with heroin addiction, Swedish researchers found a variant called A118G that seems to predict risk of heroin dependence (Goldman 2005). Other studies suggest that the mu receptor may play a part in alcohol dependence because ethanol triggers a release of / 3-enforphin, the key ligand for the mu receptor (Goldman 2005).

In a series of studies looking at multiple mu receptor SNPs in alcohol dependent individuals treated with naltrexone, Berrettini found that in patients who had either the A/G or G/G variants of the Asp40 allele, only 10% relapsed after three months of post-treatment follow-up (Goldman 2005). According to Berrettini, patients with the A/A variant had higher relapse rates, and outcomes were no better for naltrexone than placebo, suggesting that response to the drug may be largely determined by genetic variants in a specific receptor (Goldman 2005). Berrettini "estimated that 25% of the alcoholic population is either homozygous or heterozygous for the G. allele, and it predicts better response to naltrexone" (Goldman 2005). This type of research is opening the door for the possibility of designing treatment protocols based on a person's genetic predispositions and likelihood of responsiveness to specific medications, thus individualized therapy based on pharmacogenomics may ultimately become standard care (Goldman 2005).

Many in the biomedical community consider addiction to be a brain disease caused by persistent changes in brain structure and function, a view that has generated quite a bit controversy, especially among those who think in polarized ways (Leshner 2001). Many people believe that biological and behavioral explanations are alternative or competing ways to understand phenomena, however it is too simplistic to set biology in opposition to behavior, for addiction involves inseparable biological and behavioral components (Leshner 2001). Drug addiction is not merely a failure of will or weakness in character, however having this 'brain disease' does not absolve the addict of responsibility for his or her behavior, but it does explain why an addict feels compelled to continue using drugs (Leshner 2001). Environmental cues that surround an individual's initial drug use and development of the addiction, actually become "conditioned" to the drug use and thus are critical to the problem of addiction (Leshner 2001).

Therefore, when those cues are present at a later time, "they elicit anticipation of a drug experience and thus generate tremendous drug craving" (Leshner 2001). This type of cue-induces craving is one of the most frequent causes of drug use relapses, independently of whether drugs are available and even after years of abstinence (Leshner 2001).

In March 2006, it was reported that researchers from Liverpool, England discovered a gene that directly affects the risk of an individual vulnerability of addiction to the Class A drug (James 2006). Researchers tested 700 cocaine users and 850 non-users in Brazil, where use of crack and cocaine is widespread, and found that individuals (some 30%) who had a particular variant of a gene called the Dopamine Transporter were more likely to become dependent on cocaine (James 2006). A small number of participants who had two copies of the DAT gene, one from each parent, were 50% more likely to become addicted (James 2006). Previous research has demonstrated that cocaine weakens the DAT's ability to help control the amount of dopamine in the body, "giving the effect of a drug's high" (James 2006).

According to Professor John Quinn of the University of Liverpool, this research proves that much of an individual's "desire to use, and re-use cocaine depends on their genetic make-up" (James 2006). The findings from this study could help develop drugs to treat cocaine addiction and better understand the effect of other addictive substances, such as tobacco and alcohol (James 2006). "Genes are passed on from our parents, so if your mother and father both had this gene and were cocaine users, then you could be at a high risk of becoming dependent," said Quinn (James 2006).

The study, which was published in the journal of the American Academy of Sciences, has been hailed as one of the most important-ever in understanding addiction.

The study was conducted in collaboration with the Medical Research Council (MRC) Social, Genetic and Developmental Research Center at the Institute of Psychiatry, King's College, London (James 2006).

According to the lead investigator, Dr. Gerome Breen, "This study is the first large-scale search for a genetic variant influencing the risk of developing cocaine addiction or dependence...The target we investigated, DAT, is the single most important in the development of cocaine dependence" (James 2006). This research helps in the understanding of the development of cocaine addiction and could influence the design and use of drugs to treat cocaine addiction in the future (James 2006). Although repeated exposure to cocaine will lead to compulsive use in everyone, for some people the addiction to the drug will manifest more quickly because of a genetic difference (James 2006). Professor Homero Vallada, from the University of Sao Paulo Medical School, noted

It would be our hope that this is the first of many finding showing how genes, as well as environment, contribute to our risk for addiction...and may help predict pharmaceutical drug response to patients and how they might respond to different forms of psychological therapies"

Genetic and common environmental influences contribute to twin associations for substance use, yet twin concordance rates may vary by environmental setting, thus suggesting the presence of genetic-environmental interactions (Eaves 2005). Researchers explored socio-regional moderation of alcohol use in Finland and showed how extra-familial environmental influences can exert potent moderating effects on the expression of genetic and environmental influences on adolescent drinking patterns (Eaves 2005). Results suggest that genetic factors contributed to alcohol use to a greater extent in urban settings compared with rural settings, while common environmental factors assumed greater importance in rural settings (Eaves 2005). "Community level factors, including the proportion of young adults in the regional area, the frequency of migration in and out of a region and the relative amount of money spent on alcohol in an area, were found to moderate influences on alcohol use among drinking adolescents, rather than urban vs. rural residency" (Eaves 2005).

Although the importance of genetic influences on adult alcohol use has been well supported, adolescent samples have only recently been included in the research and highlight the importance of both environmental and genetic influences on teen substance use and abuse (Eaves 2005). According to Lindon Eaves, the next step in behavioral genetic research "is to examine the interplay between genetic and environmental factors (e.g., the modification of genetic risk factors by environmental risk and protective factors)" (Eaves 2005). Eaves writes in the July 01, 2005 issue of the Journal of Studies on Alcohol:

An adoption study by Riggins-Caspers et al. (2003), found zero-order correlations between biological risk as measured by biological parent psychopathology) and indicators of adolescent problem behaviors for the total sample were small to moderate and explained around 6% of the variance, leading to the conclusion that genetic influences on problem behavior were minimal.

Estimating these same correlations separately, however, for the low and moderate environmental risk groups, as measured by adverse factors present in adoptive parents e.g., psychopathology, divorce and legal problems), showed that biological risk explained almost 20% of the variance in adolescent problem behaviors for the moderate environmental risk group, compared with less than 1% for the low environmental risk group. This suggests that genetic influences on adolescent problem behavior played a larger role in the moderate environmental risk group, whereas genetic influences were negligible in the low-risk environment (Eaves 2005).

The same Israeli researchers who, in 1996, discovered a gene linked to impulsiveness and adventurousness, discovered a year later that the same gene slightly increases an individual's risk of becoming addicted to "hard" drugs (Siegel 1997). The researchers tested the blood of 141 men undergoing drug rehabilitation and compared their genetic make-up with those of 110 men with no history of drug abuse, and found that 29% of the addicts had one form of the gene, compared to only 12% in the non-addict group - thus the addicts were more than twice as likely than non-addicts to have the gene (Siegel 1997).

In 2001, Dr. Susan M. Gordon, director of research at the Caron Foundation, noted that heroin addiction is a bio-psycho-social disease, saying "On the biological front, a large body of clinical research points to a genetic vulnerability that some individuals have to drug abuse in general. This means a child can partially inherit a susceptibility to using heroin from a parent" (Heroin 2001). On the psychological level, research indicates that many heroin addicts also suffer from psychiatric disorders, including depression, anti-social personality disorder, and post-traumatic stress disorder (Heroin 2001). Gordon explains that once in the brain, heroin, much as other drugs of abuse, causes the release of dopamine, neurochemical that mediates pleasure and is critical to the normal functioning of the central nervous system. It is believed that heroin's addictive properties are related to a chronic and unnatural increase in dopamine levels (Heroin 2001). Gordon admits that heroin's characteristics and its interactions with the brain are complex, noting "Much still needs to be learned...But we do know addiction produces a variety of neurochemical and molecular changes in the brain that can have long-term negative effects" (Heroin 2001).

In April 2006, Yale School of Medicine researchers reported that they had identified a genetic linkage for dependence on drugs such as heroin, morphine and oxycontin (Large 2006). In a collaborative effort involving investigators at Yale, the University of Connecticut Health Center, McLean Hospital in Boston, the Medical University of South Carolina, and Boston University, and the National Institute on Drug Abuse, the study, based on date obtained from one of the largest family sets of its kind, was lead by Joel Gelernter, professor in the Department of Psychiatry, and included a sample of 393 small families, most with at least two individuals with opioid dependence (Large 2006). Researchers then searched genetic signposts throughout the entire genome in an effort to find markers (within the same family) that would demonstrate that individuals who share the illness also share marker alleles, or gene variants (Large 2006). This information allowed the researchers to identify the location of genes that influence opioid dependence. According to Gelernter, not only did the researchers find evidence of gene linkage for opioid dependence, they "also found strong evidence of linkage in the family groups for the symptom cluster traits characterized by dependence on substances other than opioids, specifically alcohol, cocaine and tobacco" (Large 2006). These findings provide the first basis to identify genes for opioid dependence from a "genome-wide" investigation and now allow researchers to seek specific genes that modify risk for opioid dependence (Large 2006).

Although environment plays a significant role, substance dependence risk is also genetically influenced, and understanding the genetic factors that influence opioid dependence risk would represent a major step toward understanding the basic biology of the disorder (Large 2006). Gelernter notes, "Once specific genes that increase or decrease risk are known, we will be in a better position to figure out exactly what environmental factors might be and, perhaps, how they can be modified to protect people who are genetically at risk" (Large 2006).

In 2003, a study involving approximately 20,000 participants found that particular genes can influence personality traits that are linked to unhealthy behavior. In an effort to link human behavior and inheritance, researchers at Oxford University researched data from 46 separate studies, focusing on genes that control chemicals used to transmit signals between brain cells (Von Radowitz 2003). Findings revealed that one version of the human serotonin transporter gene, 5 HTT-LPR, was associated with anxious personalities, indicating that "individuals with this gene variant were the sort who find social interaction stressful and may take refuge in substance abuse" (Von Radowitz 2003). Researchers discovered a weaker link between the dopamine D4 receptor and extrovert personality traits, suggesting that such individuals are more likely to smoke tobacco or use drugs due to risk behavior, in other words, they are more inclined to gamble with their health (Von Radowitz 2003).