By Mark S. Gold, MD


The current opioid crisis has produced shocking headlines, conflicting data, and far too much tumult and hyperbole by those who don’t understand the genetic and epigenetic influences that drive drug initiation, addiction and the mortality rate associated with opioids. As a result, there is plenty of finger pointing, but too few answers.

Opioid addiction in epidemic proportions is nothing new. Opium, as it’s known in its most natural state, has negatively impacted individuals and entire cultures for thousands of years. The first known cultivation of opium poppies occurred in Mesopotamia, approximately 3400 BC by Sumerians who called the plant hul gil, the “joy plant”.

That milky fluid from the poppy plant contains a number of compounds including morphine, codeine and the baine. Opium can be dissolved in alcohol creating a tincture called laudanum, which was popular in Europe and America in the late 19th century. At the same time, opium dens were scattered throughout the western frontier as a result of Chinese immigrants who came here to work on the railroads. Heroin, morphine and other opium derivatives remained unregulated and legal until 1920 when the US Congress recognized the danger and enacted the “Dangerous Drug Act” which served to keep opium based narcotics out of the mainstream, which was highly successful until the mid 1960’s.

The Evolving Trend of America’s Drug Problem
In the late 1960s and 70’s, the use of marijuana, LSD and other mind-altering drugs dominated the headlines. Returning soldiers from Viet Nam, who had barely reached their 20’s, were introduced to cheap Asian heroin on the battlefield and many returned addicted. At the same time, Harvard psychiatrist, Dr. Timothy Leary told a generation of students to “drop out and turn on” referring to LSD, and many did just that. The devastation resulting from drug use, and the images of stoned teens at anti-war protests were indelibly etched on our national consciousness and drug use became a reality in the American mainstream that would never go away.

In the 1980s, the recreational use of cocaine by the young and affluent, snorted through rolled up 100 dollar bills was quickly usurped by the crack epidemic that decimated our inner cities and gave birth to a national anti-drug movement. The “Just Say No” mobilized millions of scared and angry parents whom pressured local authorities and successfully stigmatized drug use which resulted in the largest decline in adolescent drug use ever.

By the 1990s, amateur chemists produced dangerous analogues known as “designer drugs” such as ecstasy (MDMA). Before being outlawed by the FDA, legions of private psychotherapists were using MDMA in their clinical practice to assist their patients in quieting their neuroticism and ridding themselves of the guilt and shame that had tainted their “true selves”. By the mid 90’s a cheap, “smokeable” form methamphetamine became the newest scourge in our land. Initially dubbed as “the poor man’s cocaine” rural America was hit particularly hard by the onslaught of meth and thousands died.

As the 21st century emerged, attitudes about drug use were changing and some thought it better to destigmatize drug use and just treat the overdoses, emergencies and serious addictions. The unprecedented use of heroin among celebrities and supermodels ensued, followed by young adults and middle and upper middleclass teenagers—was dubbed “Heroin Chic,” further blurring the line between the use of so-called “hard drugs” and so called “soft, recreational drugs,”. This radical change in the public’s perception and tolerance of drug use set the stage for the recent manifestation of the evolution of addiction in the US. That is, the non-medical abuse of prescription drugs, primarily opioids and benzodiazepines followed by heroin.

The lax prescribing practices and policies regarding opioids, resulted in thousands of drugs abusers and addicts whom simply added prescription opioids to their “menu” of intoxicants. For high school and college age kids, the use of prescription opioids as a party drug became increasingly popular. But when used while binge drinking, accidental death from respiratory failure occurred more frequently.

Changing Policies and Laws
In the last 5 years, prescribing policies and laws have been tightened, which effectively shut down the major pill mills, making illicitly attained prescription opioids harder to attain and much more expensive. Consequently, many prescription opioid abusers found that heroin was both cheaper and easier to find. At the same time, the Mexican Cartel, which was losing millions from the legalization of cannabis in the US, began filling the demand for opioids by making fentanyl and adding it to cheap Mexican heroin. At the same time the manufacturing of look-a-like prescription pain pills that contained fentanyl hit the streets. This is what killed the music icon Prince. Namely, because fentanyl is 50-100 times stronger than morphine. Potentially addictive prescription medications used for the treatment of pain include:
• Hydrocodone (Vicodin, Lortab, Norco, and their generics, Zohydro ER, a new long acting hydrocodone).
• Oxycodone (Percocet, Percodan, Roxicet, Roxycodone, Oxycontin and their generics)
• Oxymorphone (Opana, Opana ER, and their generics.)
• Hydromorphone (Dilaudid, Exalgo ER, and their generics)
• Demerol
• Tramadol (Ultram, Ultram ER, Ultracet, and their generics)
• Morphine (Avinza, Kadian, MS Contin, and their generics)
• Fentanyl ( Actiq, Duragesic, Fentora, and their generics)

The word “epidemic” has been used to describe the current trend of opioid use, morbidity and mortality. First, and technically speaking, an epidemic is the rapid spread of infectious disease to a large number of people, in a given population, within a short period of time–usually a few weeks or less, with the major focus on the agent, e.g., measles, influenza or HIV. The other two factors of an epidemic are the host (the person who gets sick) and the environment in which the agent and host interact.

We know that drug addiction is not contagious but it is however, selective in the sense that in includes the interplay of genetics and external variables and stressors. Thus, environmental and cultural factors, as well as learned behavior and individual life experiences are relevant to the prevalence of substance use disorder (SUD) and mortality. Genetic and epigenetic factors which determine nearly half the risk of becoming addicted, combined with increased availability, decreased shame and stigma, plus increasingly lax attitudes regarding drug use, conspired to expose genetically vulnerable persons as never before. The consequences have been severe.

Since the dawn of the new millennia the number of overdose deaths involving prescription opioids quadrupled. For treatment professionals on the front lines, this trend towards opioid misuse and addiction among the middle and upper middle class, and the lengths that otherwise law-abiding citizens would go to attain their drugs was shocking at first. As prescription opioids became harder to attain, heroin became the alternative. This caught most of us by surprise due to widely held beliefs that most people would never risk the shame, danger and stigma associated with heroin, nor dare to cross the needle barrier. As I pointed out in my last article in The Sober World (July 2017), https://www.thesoberworld.com/july17_issue.pdf dangerous and often deadly adulterants such as back alley fentanyl, noxious chemicals used in drug processing, and bulking agents such as talc, also caused toxicity and death. Clearly there is much more going on here than just some unscrupulous doctors overprescribing, or big pharma peddling poison to pad their portfolios.

Here are the most recent facts regarding opioids and mortality From 2000 to 2015 more than half a million-people have died from drug overdoses. In 2015 alone, 90 people per day died (over 32,000 annually) as a result of an overdose involving opioids. In contrast, in 2010, 16,651, people died as a result of the misuse and overdose on prescription medications. Certainly, the increasing availability of prescription opioids has contributed to the mortality rate.

Figure 2. The use and abuse of prescription medications is now the second most abused drug among teens

But why have prescription opioids become more available?
There are 2 major reasons. First, in 1999, The Veterans Health Administration launched the “Pain as the 5th Vital Sign” initiative, requiring a pain intensity rating (0 to 10) during all clinical encounters. Endorsed by the Institute of Medicine (IOM), this became standard practice in all primary care in the US.

Did it help?
Studying the outcome of this practice among Veterans, Mularski and colleagues reported. “Routinely measuring pain by the 5th vital sign did not increase the quality of pain management. Patients with substantial pain documented by the 5th vital sign often had inadequate pain management.”

Yet because of this change, more medications were prescribed by practitioners who lacked experience in pain management or addiction medicine.

The second reason is so obvious that we missed it. Last year the IOM reported that over 100 million Americans (one third of the population) currently suffer from legitimate chronic or intractable pain. To put this in better perspective, there are more people suffering from chronic pain than are inflicted with heart disease, cancer and diabetes combined. As the baby boom generation lives longer, they experience a plethora of physical wear and tear and injuries which often result in chronic pain. Yet the IOM reports that only 4 percent of Americans have EVER used an opioid that was not legally prescribed to them. Pain research is quite primitive and the research aimed at non-opioid or non-addicting therapeutics has lagged. In addition, few pain medicine or anesthesia pain experts are trained in addiction medicine and fewer yet are Board Certified in both specialties. The exception is my former fellow, colleague and friend Dr. William Jacobs who is Chief of Addiction Medicine at the Medical College of Georgia. His expertise is unsurpassed, and what we need to advance against this dreadful disease.

In spite of all the concern surrounding opioids and overdoses, the overwhelming majority of people who use prescription pain relievers for legitimate pain, do so as prescribed. We cannot forget, that for those who are crippled by chronic pain, these medications are life-giving. Having withdrawal signs and symptoms when they cut down or discontinue is normal physiological withdrawal—but it is not addiction. Many other non-opioid medications, produce tolerance and withdrawal upon cessation but this does mean they are addicted. Astute pain management professionals with expertise in addiction medicine are desperately needed to fill the gap and treat those with chronic pain.

The Accidental Addict
The accidental addict can be a person of any age who has never abused drugs or alcohol, but as the result of an acute injury or illness are prescribed a pain medication, usually hydrocodone or oxycodone by a well-intentioned, urgent care physician, or by their primary care physician. The evidence shows that the overwhelming majority of people with acute pain usually do not finish their prescription and recover quickly. Yet for reasons not fully understood, some individuals have an intense euphoric response from the opioids, so much so, that they seek the drug long after their injury has healed and the pain subsided. This represents a very small percent of people with opioid use disorder, nevertheless the consequences of drug misuse and abuse, regardless of how one is initiated never turns out well. Only by understanding the biological, familial and social antecedents of addictive disease can we put the current opioid crisis in proper context and focus on improved prevention and better treatment.

Interpreting the Data
As a researcher and addiction medicine doctor, I have seen first-hand how dangerous and addictive these medications are. As a scientist, my work is informed by the peer reviewed, scientific evidence—animated by years of experience and desire to continue as a translational researcher, fill the gaps in knowledge and educate others on addictive disease. Accordingly, I write summaries of the best available evidence each month. (www.addictionresearchyoucanuse.com) .Yet, interpreting the epidemiological data in regards to opioid mortality is difficult for two reasons. First, the landscape from which data is culled is dynamic and shifting constantly. Second, methodology for epidemiological research is often hampered by predetermined categories for drugs or outcomes, within a static timeframe. For example, if the research question is: To determine mortality related to opioid use, the methodology is to simply review post-mortem toxicology reports that are tabulated from a sample of those who died within a predetermined time frame. The problem is that toxicology screens are effective in detecting the presence of opioids but cannot tell a researcher anything about the deceased’s history or drug tolerance, or previous drug or alcohol use, or previous trauma, co-occurring illness and extenuating circumstances. They rarely report all the other drugs and adulterants in the overdose sample, and cannot determine whether the overdose was accidental, a form of “Russian Roulette”, or a passive suicide attempt accompanied by a wish to die.

For example, an individual develops a high tolerance for oxycodone and is taking 120 mg per day. But now she begins having sleep problems, so she goes to her primary care physician (PCP) with the complaint of insomnia and acute anxiety. But, as drugs addicts often do, she fails to mention the opioids. The PCP does not do a drug screen (because insurance won’t pay for it) and prescribes 0.5 mg of Alprazolam (Xanax) at bedtime, and 0.5 during the day as needed for anxiety. After a few days, the patient is still having trouble falling asleep, so on top of the 120 mg of oxycodone and 3 glasses of wine after dinner, she takes 2 mg of Alprazolam before she goes to bed. Unfortunately, she suffers respiratory distress, stops breathing and dies in her sleep. So, the question becomes, what killed her? Was it the Oxycodone? The Alprazolam? The wine? Her insurance company? Her doctor? Well, technical answer is the combination of Opioid, Alcohol and Alprazolam. The truth is … her Substance Use Disorder, killed her.

So, why do some people get addicted so quickly and others do not? Why do some people hate smoking marijuana or cocaine and others do not?

The quick answer is genetics, both genotype, which is our heritable genetic hard wiring, plus phenotype, which involves the environmental stressors that impact genetic expression, such as trauma or abuse, being a child of a drug user or addict, exposure in utero or in early life, and exposure to drugs during brain development. Epigenetics is the adaptation resulting from external forces that influence and potentially modify genetic expression during conception. Recent research suggest that these adaptations may be passed on to one’s children. Therefore, SUD is a poorly understood, genetically influenced, multifaceted brain disease that require multimodal and multidisciplinary expert treatment of adequate intensity and duration.

The Bad News
Although the abuse of illicit prescription drugs is less prevalent than alcohol or marijuana use disorders among adults, the long-term trends cited in the recent Substance abuse and Mental Health Service Administration (SAMHSA) report indicate that in spite of the Herculean efforts to educate the public regarding the dangers of opioids and other illicit drugs, the impact in reducing the prevalence of Americans whom use, abuse, become addicted to, and die from using pain killers and sedative hypnotic drugs is negligible.

Clearly, we are spending far too much time and resources talking about a single class of drugs, and pointing fingers at bad doctors and “Big Pharma” as the cause. In reality cocaine production has increased due to demand, and accordingly smuggling drugs into the US has increased, prices are down, and deaths from overdose are common. Current drug prevention efforts are woefully underfunded but needed more than ever. Why? Because 8,000 young people will pick up and use an intoxicant for the very first time today, and another 8000 tomorrow, and another 8000 the day after tomorrow, and another 8000…You get the point? Do the math—it’s shocking and unsustainable.

What to do
Recently the National Academies of Sciences, Engineering and Medicine convened to address the problem of illicit use of prescription opioids. They reported that. “Years of coordinated efforts will be required to contain and reverse the harmful societal effects of the country’s ongoing prescription and illicit opioid epidemic” I agree. The committee’s specific recommendations include:
• Changing the culture of prescribing, partially through enhancing education for physicians and the general public.
• Investing in treatment for the millions of individuals with opioid use disorder and removing impediments to those treatments. Also, improving health-care provider education for opioid-use disorder.
• Preventing overdose deaths, including access to naloxone (also known by its brand name Narcan) and safer injection equipment.
• Weighing societal impacts, not just an individual’s, regarding opioids, such as incorporating public health considerations into the FDA’s current framework for making regulatory decisions regarding opioids.
• Investing in basic research, particularly to better understand the nature of pain and the neurobiology of the intersection between pain and opioid-use disorders. In addition, increasing the investment in developing nonaddictive alternatives to opioids for pain management.

Medically Assisted Treatment
A number of medications are now available to treat opioid use disorders. These medications can be used for both acute withdrawal and for long term recovery. Recent evidence shows that these medications have helped opioid-addicted persons become free from the mental anguish, preoccupation and craving for opioids.

There are 3 types of medication currently available for this purpose. Drugs like Naloxone (Narcan) have been used to prevent death from overdose for several decades. A first cousin of naltrexone, Vivitrol, is now available in a long acting formula to prevent opioid relapse.

Medications for MAT include:
1. Full agonists: Methadone (Dolophine or Methadose), which activate opioid receptors.
2. Partial agonist, buprenorphine (Subutex, Suboxone, Zubsolve), which also activate opioid receptors but produce a muted euphoric response, and mediate craving.
3. Antagonists which are versions of naltrexone, which I helped develop in the 1980’s (Revia, Depade, Vivitrol). These medications block the opioid receptors and negate the rewarding and toxic effects of opioids.

Medically Assisted Therapy alone is generally not enough. Continuous care, as would be provided for any chronic lifethreatening disease is essential. Effective treatment combines social support, psychological, and psychiatric treatment as needed, 12 Step Recovery (or similar programs), and continuous monitoring via drug testing–plus, aggressive treatment of co-occurring psychiatric or medical illness, such as depression or Hepatitis C. This model is the treatment approach most MDs choose for themselves, recommend for their colleagues, and known to be effective over the long haul. If outcome is measured in treatment retention and overdose prevention, MATs—especially methadone— are quite effective.

Until new therapeutics, vaccines and treatment modalities are tested and made available, those looking for treatment should only consider centers with the most experienced and credentialed clinicians, that offer multimodal, evidenced based treatment, and provide individualized care. These centers offer the best hope of those suffering from opioid addiction.

Mark S. Gold, MD, Chairman of the RiverMend Health Scientific
Advisory Boards, is an award-winning expert on the effects of
opiates, cocaine, food and addiction on the brain. His work over
the past 40 years has led to new treatments for addiction and
obesity which are still in widespread use today. He has authored
over 1000 medical articles, chapters, abstracts, journals, and
twelve professional books on a wide variety of psychiatric research
subjects, including psychiatric comorbidity, detox and addiction
treatment practice guidelines. www.rivermendhealth.com