One of the most important themes that will be revisited over and over again in this book will be the importance of the opioid addicted individual understanding that, irrespective of the stigma and preconceived notions that greater society may have about addiction in general, opioid addiction is no ones fault, and most certainly not that of addicted individuals themselves.
Ascribing blame to an individual who has developed an addiction to drugs is akin to ascribing a nefarious motive to someone who has contracted a deadly virus; because a virus is by its very nature inanimate, attempting to attach a motive to its host is beyond a moot point. In the ﬁnal analysis, we ﬁnd it counterproductive to ascribe words such as “evil” to ultimately inanimate chemicals like drugs, for drugs have no eﬀect until they enter a living organism, and in fact require that organism’s machinery to produce their eﬀects, not at all unlike a virus. Using this analogy, it is important to bear in mind that the vast majority of viruses are not pathogenic to humans, or “bad.” They are, in fact, necessary for the process of evolution (horizontal gene transfer) and serve a crucial niche function in marine microbiology via a process known as the viral shunt, among other positive functions in biology.
Opioid addiction is a complex, multi-factorial disease that is the result of a conglomeration of factors that aggregate together in one person to produce the phenomenon. [6,7,8] These factors include, but are not limited to, ones genetics, environment, life stressors and, according to arguably the most consequentially important large-scale public health study to emerge in decades, a phenomenon known as Adverse Childhood Experiences (ACE’s.) 
Because these factors are so varied in their origin and distribution, we refer to opioid addiction, and addiction in general, as being a biopsychosocial illness. This is because the eﬀects of one factor, like possessing a genetic predisposition, are diﬃcult to tease apart from other contributing factors like having a mentally ill parent, being a victim of childhood neglect, or coming from an impoverished household, among other things.
Nevertheless, all other things being equal, some factors undoubtedly play a more central role than do others. At the top of the list would be possessing a genetic predisposition, for without that genetic predisposition, addiction itself will not take hold. As to the precise nature of what the predisposing factors may all be, they have not yet been established; however, it has become exceedingly clear to researchers over the past two decades that a genetic predisposition is necessary in order for an individual to go on and develop an opioid addiction. 
A note on language and its power to both stigmatize and redeem. The reader will note that in this book, we intentionally avoid using words such as “clean,” “dirty,” “addict,” and “junkie,” unless they are context dependent and appropriate because these words have traditionally been used as weapons against opioid addicted individuals who are, in the ﬁnal analysis, both equally human and equally deserving of dignity and respect. It would behoove the reader to remind himself or herself that language can be a powerful tool for both good and evil.
The fact that the term “addict” is used so freely by members of both the medical profession and the criminal justice system – and frankly, even by addicted individual themselves – attests to how powerful this word has become as a moniker that serves to both identify aﬄicted individuals and as a pejorative with which to condemn them. We can begin to change that today.
Opioid addiction does not happen in a vacuum. There are other risk factors besides the fundamental genetic vulnerability that come into play, and the weight that must be ascribed to these other factors should be considered to be at least as much as genetics, for just as without genetics, there would be no addiction, without the environment interacting with those genetics, there wouldn’t be addiction. Later on, we will discuss the genetics and epigenetics of opioid addiction, but for now, let us discuss some of the other factors that come into play.
From 1995 to 1997, over 17,000 people were recruited into one of the most extensive longitudinal health studies in the U.S. that looked into the eﬀects of adverse childhood experiences (ACE’s) on public health. Because of the epidemiological value of the data, the study was conducted by the Kaiser Permanente HMO and the Centers for Disease Control, and what has come out of their ﬁndings is genuinely stunning and should serve as a societal wake-up call.
It absolutely bears mentioning that this study, which is still ongoing in diﬀerent locales in the U.S., had its origins in an apparent medical mystery: in 1985, a physician by the name of Vincent Felitti found himself at a loss as to why more than half of the patients enrolled at his obesity clinic in San Diego were dropping out of the program every year for ﬁve years straight, even though they were all successfully losing substantial amounts of weight. It was as if just as they were making signiﬁcant progress in achieving their weight loss goals, they dropped out.
Their withdrawal so puzzled Dr. Felitti that he decided to call in a couple of hundred of the former patients for an exit interview. Many interviews were conducted in which he discovered nothing that could explain these bafﬂing results, until one day, while interviewing a female patient, he misspoke. While he had wanted to ask how old a woman had been during her ﬁrst sexual encounter, he accidentally asked how much she weighed during her ﬁrst sexual experience. The answer he received ﬂoored him: The woman he was interviewing broke down and spoke of incest she endured at the hands of her father when she was just four years old and all of forty pounds.
Over the next few days, as he began to ask the question of the other dropouts, he found something astonishing – nearly every study participant reported similar trauma during childhood. Ever the good scientist and to ensure that he was not introducing any unconscious bias into the interviews, he asked other colleagues to conduct the rest of the interviews. To his astonishment, they all reported the same results – serious childhood trauma in the obesity clinic dropout group.
Dr. Felitti was so intrigued by what he found that he became one of the principal investigators in the ACE’s Study, along with a physician by the name of Robert Anda. They and their colleagues have been following 17,000 members of the Kaiser Permanente health insurance organization since 1995, collecting longitudinal data on their relative health and morbidity. One must bear in mind that they ﬁrst gave each of these patients a ten-item questionnaire (Appendix II) as they initially enrolled in the study between 1995 and 1997, then they simply followed the medical data on each subject. [9,10]
“This was the ﬁrst time that researchers had looked at the eﬀects of several types of trauma, rather than the consequences of just one. What the data revealed was just mind-boggling. I wept. I saw how much people had suﬀered, and I wept.” Robert F. Anda, M.D., M.S. 
“ACEs have created a chronic public health disaster.” Robert Anda, M.D., M.S. 
What researchers found has been truly earth-shattering in its consequences. For each ACE an individual accumulated, there was a corresponding increase in morbidity and mortality from all causes, with the degree of morbidity and mortality being easily predicted decades ahead of time just by the relative accumulation of Adverse Childhood Experiences. There is truly no specialty of medicine that is exempted from these ﬁndings, and that includes opioid addiction treatment. [7,9]
An ACE score of four makes one ten times as likely to inject drugs, seven times as likely to develop alcoholism, twelve times more likely to attempt suicide, and 32 times more likely to be labeled with a behavioral or cognitive problem than a child with no ACEs. The numbers from the study are truly stunning, especially considering that even when the children were removed from the toxic environment, the lasting damage had been done. 
What requires mentioning at this point is that a high ACE score neither predestines an individual into becoming an opioid addict nor causes one to develop a mental illness; as such, not all people with traumatic childhoods come out for the worse. There is such a thing known as resilience. What can probably best be said about resilience among trauma survivors is that it, too, is most likely the luck of the genetic draw, to use a phrase. 
In the late 1970s at Simon Fraser University in British Columbia, a psychologist by the name of Bruce Alexander did some hard thinking followed by experimentation regarding opioid addiction and its causes. His experiment was called Rat Park (rats were his subjects), and the crucial result that he came up with was that animals do not automatically become addicted to opioids just because opioids are present in the environment. He found that something else was necessary to create addiction-like behavior in the rats – a lack of social connection and a poor, unenriched environment.
Since his paper appeared in 1978, Rat Park lost its funding from Simon Fraser University, and the results have been slightly modiﬁed from the original paper. It turns out that genetics also play a signiﬁcant role in which individual rats become addicted to opioids. Just as there are strains of rats resistant to opioid addiction, so too are there strains of rats that are more susceptible to develop addiction. 
This has signiﬁcant implications for the genesis of human opioid addiction. As has been mentioned before, the development of opioid addiction does not happen in a vacuum. There have to be vulnerable individuals with certain environmental constraints. This goes a long way toward explaining why the vast majority of people can take or leave opioids, with only a small minority who go on to develop severe addiction.
In light of the Rat Park experiment, one begins to understand why, in some respects, opioid addiction is also disease of loneliness. Lack of social connection is a primary cause of addiction, and then later becomes one of the results of opioid addiction as social ostracism in response to the addiction creeps in. For someone who is not already traumatized, a lack of social connection can be inconsequential, at best. For someone who is already coming to the scene with serious trauma, a lack of social connection can be the nail in the proverbial coﬃn.
The aforementioned causes of opioid addiction are an enormous part of the whole picture, but they do not explain everything.
One of the issues that has puzzled researchers over the decades is why individuals no longer physically addicted to opioids relapse, even after having been abstinent and in recovery for long periods of time. One hint lies in the particular tenacity of opioid addiction. There is strong evidence that opioid use by vulnerable individuals induces long-term, epigenetic changes in some regions of the brain that are crucial for motivation and goal-directed behavior. We will look at some of these changes in later chapters.
The sheer tenacity of severe opioid addiction is the reason why any traditional negative consequences of use have no eﬀect on the addicted individual’s likelihood for relapse, whether they have been abstinent for one day, one year, or one decade. Even though it has been known for at least 100 years that opioid addiction has the highest rates of recidivism, our criminal justice system and healthcare system as a whole have been largely ignorant of this. The abysmal recovery rates for abstinent opioid addicted individuals have served as a living and dying testimony to this reality.
The tremendous number of myths, the brutality of the stigma, the lack of up-to-date useful information, and the lack of more widespread availability of clinics to serve this patient population have all served as additional incentives for the examination of this issue. Some readers may wonder why the emphasis is essentially entirely focused on methadone, with little to no reference to buprenorphine (Suboxone). The answer is quite straightforward: Suboxone, and its other proprietary and generic versions, is still very, very expensive when compared with methadone, and the long-term data on Suboxone maintenance is not nearly as robust as is the data on MMT. 
Adding to the complications, fewer and fewer insurers are covering Suboxone/buprenorphine treatment, making it less and less accessible to the very people who would beneﬁt from it.  For this reason, the choice for focusing on methadone was made, as methadone is the ﬁrst opioid agonist treatment ever to become widespread, over many decades, and in many countries throughout the world.
Another important reason why Suboxone/buprenorphine is not addressed in this book is for the simple reason that Suboxone is not eﬀective for everyone with an opioid addiction, particularly if one happens to have a “heavy,” long-standing addiction, as Suboxone may even put one into a state of withdrawal. Stated another way, methadone will work for anyone with an opioid addiction whereas Suboxone will only work in a particular sub-group of patients, usually those younger and less experienced with opioids.
Looking at the success of well-administered MMT, it is the cheapest and most eﬀective treatment modality available for opioid addiction disorder. [8,29] The costs of other, non-evidence-based treatment modalities can also be measured in real dollars and cents, but these pale in comparison to the human and societal cost of such “treatments.” With abstinence-based treatments, overdoses, both fatal and non-fatal, are just a “normal” part of the picture. We consider this to be an unacceptable outcome in any case, as every human being has the right to live another day. Let us not, in our haste, throw the baby out with the bath-water.