The Important 0.1 Percent

(Nineteenth in a series of topical blogs based on chapter by chapter excerpts from Opiate Nation. Translation into most languages is available to the right.)

DNA sequences for any human is approximately 99.9 percent identical to every other human. That means that only 0.1 percent of our genetic makeup is unique to us. Genes are functional units of DNA that make up the human genome. But don’t be fooled into thinking that 0.1 percent variation is insignificant. It is nearly 3 billion base pairs of DNA which boils down to 3 million differences that determine our physical features like hair and eye color and health risks or protection from diseases such as heart disease, diabetes – and addiction. Genes influence the numbers and types of receptors in peoples’ brains, how quickly their bodies metabolize drugs, and how well they respond to different medications.

The National Institute of Drug Abuse (NIDA) reports that family studies that include identical twins, fraternal twins, adoptees, and siblings suggest that as much as half of a person’s risk of becoming addicted to nicotine, alcohol, or other drugs depends on his or her genetic makeup. Scientists estimate that genes – including the effects environmental factors have on a person’s gene expression, called epigenetics – account for between 40 and 60 percent of a person’s risk of addiction.

Epigenetics – epi meaning “above” – is the study of functional, and sometimes inherited, changes in the regulation of gene activity and expression that are not dependent on gene sequence. This means exposures or choices people make can actually “mark” (remodel) the structure of DNA at the cell level. So epigenetic regulatory systems enable the development of different cell types (e.g., skin, liver, or nerve cells) in response to the environment. These epigenetic marks can affect health and even the expression of the traits passed to children. For example, when a person uses cocaine, it can “mark” the DNA, increasing the production of proteins common in addiction which is believed to correspond with drug-seeking behaviors.

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The Best Laid Plans

Mac Miller – 26 year old rapper – died of an apparent overdose last week. One more beautiful young person lost in the prime of life. Friends and fans have unanimously said he was one of the sweetest guys they’d ever known with a great sense of humor. Miller spoke openly about his struggles with addiction over the years: “It just eats at your mind, doing drugs every single day, every second. It’s rough on your body.”

August 31st is International Overdose Awareness Day. I think we are all very aware of the enormous and continuing-to-rise number of drug––mostly opioid––overdose deaths. It is clear from conversations with many of the famous and not-famous users, like our son, that they have every intention of controlling their addiction and no intention of overdosing. But something goes wrong…

Dr. Jana Burson, an addiction treatment physician in North Carolina, has a great blog (https://janaburson.wordpress.com/) with insights gathered from her patients, many of whom are long-term opiate abusers. “I’m not gonna overdose. I know my limits.” Dr. Burson writes in August 2017: “I really hate hearing these words. Usually patients say this in response to my concerns about their pattern of drug use while I’m prescribing methadone or buprenorphine. But many patients feel they are the experts. They can’t imagine making a deadly mistake with their drug use. But I’ve heard this phrase from people who are now dead from overdoses.”

She recently cited a study in Australia 2013, where overdose deaths have risen steadily since 2007. In that country, unlike the U.S., heroin use is declining while prescription opioid misuse is rising. This study looked at non-fatal overdoses in very experienced people who inject drugs––an average of 21 years of IV drug use––half of whom were in a MAT (Medication Assisted Treatment) drug program.

Most of these overdoses happened in private homes––many the subjects said they were impaired by alcohol or benzodiazepines. Over a third of the subjects had used fentanyl, a very powerful illicit opioid, leading up to the overdose. The authors of the study concluded that these experienced drug users were aware of common risks for overdose, yet drug intoxication from sedatives such as alcohol or benzodiazepines may have clouded the user’s thinking when injecting opioids. They also found that unexpected availability of drugs contributed to overdoses.

This was our son’s story: It was his first night after 6 months in sober living––but it was not his first night using again. He had been on Percocet for oral surgery (a huge mistake) a month before he overdosed and then had returned to IV heroin use the week before his overdose. He had been drinking with friends the first night in his new apartment––his decision making abilities were impaired. We are not sure exactly how much heroin he injected, and since it was Black Tar heroin from Mexico, the strength is absolutely unpredictable. What we do know from the autopsy is that he had many times more heroin in his body than a fatal dose. His was an overdose that he would not survive. Was this his last conscious thought: “I’m not gonna overdose. I know my limits.”?