03/22/22

Hardwiring Young Brains

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The U.S. Department of Health and Human Services published a report in 2009, “Addressing Prescription Drug Abuse in the United States”, that noted a significant milestone was surpassed with prescription drugs. “For the first time in the U.S., drug overdose deaths outnumbered deaths due to motor vehicle crashes.” In 1999, opioids were involved in 30% of drug overdose deaths. By 2010, this had risen to 60%. Prescription opioid-related overdose deaths then outnumbered overdose deaths from all illicit drugs such as heroin and cocaine.

Opioids are getting the most attention as result of their potential to lead to an overdose, but other classes of psychotherapeutic drugs are also misused. The 2020 National Survey on Drug Use and Health (NSDUH), showed that prescription stimulants, tranquilizers or sedatives such as benzodiazepines are also misused. The 2020 NSDUH defined the misuse of prescription drugs as “use in any way not directed by a doctor, including use without a prescription of one’s own; use in greater amounts, more often, or longer than told to take a drug; or use in any other way not directed by a doctor.” Among people 12 and older 5.8% (16.1 million people) misused prescription psychotherapeutic drugs in 2020.

The 16.1 million people in 2020 who misused prescription psychotherapeutic drugs in the past year included 9.3 million people who misused prescription pain relievers, 6.2 million people who misused prescription tranquilizers or sedatives (including 4.8 million past year misusers of benzodiazepines), and 5.1 million people who misused prescription stimulants.

Surprisingly, the most recent information on the top abused prescription drugs was from 2016 by Statistica and 2017 by GEN, Genetic Engineering & Biotechnology News. GEN listed the top 20 abused drugs ranked by sales data, as did Statistica. The rankings according to revenue are almost identical. Not only have Statistica and GEN failed to continue their monitoring of prescription drugs in this way, I could find no other agency or organization that had done so. I wonder if the pharmaceutical companies had anything to do with this failure.

Statistica put their findings in handy chart (see above) but GEN did not. However, there was added information in the GEN article. This included a brief observation that fifteen of the top twenty drugs showed reduced overall sales from the previous year, likely from the lower prices of generics. Gen said that according to GlobalData, sales for ADHD drugs like Adderall and Concerta were projected to more than double by 2024, from $6.1 billion in 2014 to $13.9 billion. See the chart below which is composed of information in the GEN article.Eight of the listed drugs were opioids. All but five were scheduled as Controlled Substances by the DEA, meaning they have an addictive potential. Methylphenidate, an ADHD stimulant found in Ritalin, Concerta and Daytrana, was in three different drugs on the list as well as the generic drug. Zoloft (sertraline), an antidepressant SSRI, made the list in two different drug forms. Celecoxib, an arthritis treatment, was found in three drugs. Ironically, buprenorphine, one of only three drugs approved for the treatment of opioid misuse, was itself on the list of most abused prescription drugs, with only OxyContin listed ahead of it in pain reliever sales.

Reflecting on the implications of this information for drug treatment, a few questions arise. Are individuals (or parents in the case of ADHD medications) cautioned about the potential for developing an addiction when they or their children are first prescribed any of these drugs? Does the presence of medications like sertraline (Zoloft) and celecoxib on these lists point to a conundrum when they demonstrate a misuse potential but were not listed as controlled substances by the DEA? Does the reality of these medications being abused raise concerns for other medications in the same drug class?

According to ClinCalc, Zoloft was the 12th most prescribed drug, with 7.7 million patients and 37.2 prescriptions. Forbes said it was often a first line medication for depression, anxiety and PTSD. None of the above abused drugs had more total prescriptions. Zoloft and other antidepressants like it are beginning to be viewed as addictive, so we may see more SSRIs on future most abused prescription drug lists. Long-term users seem to go through withdrawal when stopped too abruptly. See “Are Antidepressants Worth the Risk?

Misuse of Prescription Drugs by Class

Returning to the 2020 NSDUH, the report also gave information on the misuse of prescription stimulants, tranquilizer or sedative misuse, benzodiazepine misuse and pain reliever misuse.

Prescription stimulant misuse included amphetamine (i.e., Adderall XR) and methylphenidate (i.e., Ritalin, Concerta, Daytrana) products. Among people aged 12 and older, 1.8 percent of the population (or 5.1 million people) misused prescription stimulants in the past year. The percentage was highest among young adults aged 18 to 25 at 4.8% (or 1.6 million people). All other age categories hovered between 1 and 2 percent.

For the most part, prescription stimulants to treat ADHD are Schedule II controlled substances. To what extent does their use as the child’s brain develops lead to substance abuse disorders in later years? See the figure below.

Tranquilizer or sedative misuse included benzodiazepine tranquilizers such as alprazolam (Xanax), lorazepam (Ativan), clonazepam (Klonopin) or diazepam (Valium), and muscle relaxants. Among people aged 12 and older, 2.2% (or 6.2 million people) misused tranquilizers or sedatives in the past year. Again, young adults had the highest percentage of misusers with 3.7% (or 1.2 million people).

Benzodiazepines are chemically similar regardless of whether they are prescribed as a sedative or a tranquilizer. Xanax, which is prescribed as a tranquilizer, has an average half-life of 11.2 hours (the length of time for half the dosage to be metabolized). Halcion, a benzodiazepine prescribed as a sedative, has a short half-life of between 1.5 and 5.5 hours. Research had shown that benzodiazepines with a short half-life have a greater dependency potential. Young adults once again had the highest percent of misusers 3.3% (or 1.1 million people).

Digging deeper into pain reliever misuse, the 2020 NSDUH asked respondents to identify specific pain relievers they used over the past year, and then categorized them into subtypes, such as hydrocodone or oxycodone products. Hydrocodone products such as Vicodin, Lortab, Norco, Zohydro ER and generic hydrocodone were the most commonly misused. Among people 12 and older, 1.7% (or 4.7 million people) misused them. There were 1.1% (or 3.2 million people) who misused oxycodone products such as OxyContin, Percocet, Percodan, Roxicodone and generic oxycodone.

No surprise, young adults aged 18 to 25 had the highest percentage of misuse with 4.1% (or 1.4 million people), followed by adults 26 and older with 3.4% (or 7.5 million people). A question arises at this point with regard to young adults. Given the evident pattern with young adults having the greatest potential to develop problems of misuse with stimulants, tranquilizers benzodiazepines and pain relievers, are they cautioned of this potential when they are first prescribed the medications?

Another way of looking at pain reliever misuse noted .1% of people 12 and older misused prescription fentanyl products. This will likely underrepresent people who used and misused illicitly manufactured fentanyl (IMF) from illegal laboratories; and will not include those who used IMF mixed with heroin or sold as heroin (but only contained IMF). The following figure compares past year pain reliever misuse among people 12 and older by the selected pain reliever subtype.

The 2020 NSDUH researchers presented the above data, and then stated that while prescription pain relievers were the second most common form of illicit drug use in 2020, “most past year users of prescription pain relievers did not misuse them in the past year.” They singled out buprenorphine, a Schedule III opioid used as an FDA approved medication for opioid misuse. Then they said the 26.5% of people who reported misusing buprenorphine over the past year meant: “Almost three fourths of past year users of buprenorphine products did not misuse them in that period.”

Another way to present this data is to say that of the .2% of people who go to a doctor for a buprenorphine prescription, supposedly to help them manage or stop their opioid misuse disorder, over 25% reported they misused their buprenorphine in the past year. There is a higher percentage of people admitting they misused buprenorphine than any of the other pain reliever subtypes.

Or you can sort the pain reliever subtypes according to their DEA scheduling as controlled substances.  See the chart below. Misuse with Schedule II pain relievers ranges from 8.9% with morphine to 16.6% with hydromorphone. Schedule IV or Schedule V pain relievers, codeine, at 12.2% and tramadol at 9.0% have noticeably lower misuse percentages, while buprenorphine significantly stands above them all with 26.5% misusing it. Remember it was 4th or 5th in the above noted lists of the most abused drugs in 2016 and 2017. What’s going on?

Despite buprenorphine being a Controlled Substance, it is a prescription drug used to treat opioid misuse disorder. This means it activates the same opioid receptors in the brain that the other opioid drugs above do. The effects may not be the same as with OxyContin or heroin, but it’s still an opioid. The people using buprenorphine for medication-assisted treatment (MAT) already have a history of abusing opioids. Apparently more than 25% of them can’t resist the temptation to abuse the very drug they’re supposed to be using to stop their addictive use of opioids.

Future NSDUH surveys will need to monitor this conundrum with buprenorphine, but the above review of the 2020 NSDUH revealed a concerning age-related problem with prescription drugs. There was a pattern of young adults having the highest frequency of prescription drug misuse with all categories—stimulants, pain relievers, benzodiazepines and tranquilizers. SAMHSA (Substance Abuse and Mental Health Services Administration) stated that the fastest growing drug-related problem with teenagers was prescription drugs. This has the potential to result in life-long challenges with addiction.

Our brains continue to develop until we reach our early- to mid-twenties. During adolescence, the pre-frontal cortex further develops to enable us to set priorities, formulate strategies, allocate attention, and control impulses. The outer mantle of the brain also experiences a burst of development, helping us to become more sophisticated at processing abstract information and understanding rules, laws, and codes of social conduct. Drug use impacts perception—a skill adolescent brains are actively trying to cultivate—and can fracture developing neural pathways. Additionally, as our brains are becoming hardwired during adolescence, the pathways being reinforced are the ones that stick. If those pathways include addiction, the impact may lead to life-long challenges.

03/15/22

Trends in Substance Use and Abuse

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The National Survey on Drug Use and Health (NSDUH) provides information on tobacco, alcohol, and drug use, mental health and other health-related concerns in the US. NSDUH began in 1971 and is conducted yearly in all 50 states and the District of Columbia. The National Survey on Drug Use and Health (NSDUH) for 2020, published in October of 2021, interviewed almost 70,000 people. It is directed by the Substance Abuse and Mental Health Services Administration (SAMHSA), an agency in the U.S. Department of Health and Human Services. NSDUH has been conducted by RTI International, a nonprofit research organization in North Carolina.

Criteria from the DSM-5 were used in order to categorize the substance use disorders (SUD) of the respondents. SUDs are classified by impairment caused by the recurrent use of alcohol or other drugs, including health problems, disability, and the failure to meet major responsibilities at work, school, or home. Respondents were said to have an SUD if they had two or more of the eleven criteria noted on page 27 of the 2020 NSDUH survey. The following figure provided an overview of the number of people aged 12 and older who initially used the noted substances in the past 12 months.

A surprising finding was that there are more people trying hallucinogens for the first time in the past year than cigarettes. This is likely a result of popular and research interest into using hallucinogens such as ketamine and MDMA, to treat mental health issues. See “Psychedelics Are Not a Magic Bullet”, “Give MDMA a Chance?”, “In Search of a Disorder for Ketamine” and other articles on this website.

But it should come as no surprise that the top two substances used for the first time in the past year were alcohol and marijuana. Alcohol is legal in all states and although marijuana is illegal under federal law, recreational marijuana is legal in 18 states and 37 states have legalized medical marijuana. Only in four states, South Carolina, Kansas, Idaho and Wyoming is marijuana still fully illegal. See “Map of Marijuana Legality by State.”

The above figure shows that in the past 12 months, 4.1 million people began using alcohol and 1.3 million people tried a cigarette for the first time. There also were 2.8 million new marijuana users, 1.4 million new hallucinogen users, 1.2 million people who first misused prescription pain relievers, 950,000 new misusers of prescription tranquilizers, and 734,000 new misusers of prescription stimulants. There were also 489,000 new cocaine users and 153,000 new methamphetamine users.

Despite the opioid epidemic, estimates of initial heroin use in the past year were the lowest category of new users at 103,000. Nearly 90 percent of individuals using heroin for the first time did so after the age of 25. Among adults aged 26 or older, 91,000 people initiated heroin use in 2020.

Substance use disorders are with alcohol or drugs; or a mixture of both. There were 40.3 million people 12 or older estimated as meeting the criteria for a SUD in the past year. This included 28.3 million who had an alcohol use disorder (AUD) and 18.4 million who had an illicit drug use disorder (IDUD). Among those individuals with an AUD, 21.9 million had AUD but not an illicit drug use disorder. Among the 18.4 million people with a past year IDUD, 11.9 million has an IDUD but not AUD. This meant there were 6.5 million who met the criteria for both AUD and IDUD. See the figure below.

Age is again seen as a factor with the presence of SUDs in the past year. When the figures for substance use disorder were looked at by age, the percentage of people with a past year SUD was highest among young adults aged 18 to 25 (24.4% or 8.2 million people). This was followed by adults 26 or older (14.0% or 30.5 million people).

Among people aged 12 or older, 10.2% (28.3 million people) has a past year AUD. The percentage of people who had past year AUD was highest among young adults aged 18 to 25 (15.6% or 5.2 million people). Again, this was followed by adults 26 or older (10.3% or 22.4 million people).

Among people aged 12 or older, 6.6% (18.4 million people) had an IDUD in the past year. The percentage of young adults aged 18 to 25 (14.6% or 4.9 million people) was higher than the percentages of adults aged 26 or older (5.6% or 12.3 million people) and adolescents aged 12 to 17 (4.9% or 1.2 million people). See the following figure.

However, the vast majority of the population did not have a SUD of any kind in the past year. The 40.3 million people with a past year SUD represent 14.5% of the population aged 12 or older. The remaining 236.6 million people, 85.5% of the population aged 12 or older, had no past year SUD. But when substances are distinguished as marijuana, methamphetamine, cocaine, stimulants, pain relievers and heroin, the number of people with the respective substance use disorder was as follows. Notice that a significant majority of people with an illicit drug use disorder had a marijuana use disorder.

Among people aged 12 or older, 5.1% (or 14.2 million people) has a marijuana use disorder in the past year. With people aged 12 or older, .8% (or 2.3 million people) had a prescription pain reliever use disorder; and 6% (or 1.5 million people) had a methamphetamine use disorder. Among people aged 12 or older .5% (or 1.3 million people) had a cocaine use disorder; .6% (or 1.5 million people) had a methamphetamine use disorder; .3% (or 758,000 people) had a prescription stimulant use disorder; and .2% (or 691,000 people) had a heroin use disorder.

When the use of marijuana, pain relievers and methamphetamines were looked at by age, the percentage of young adults aged 18 to 25 with marijuana use disorder (13.5% or 4.5 million people) was significantly higher than the percentages for adolescents aged 12 to 17 (4.1% or 1.0 million people) or adults 26 or older (4.0% or 8.7 million people). Prescription pain reliever use disorder and methamphetamine use disorder for all three age groups were only nominally different from each other. See the following figure.

There seems to be a clear pattern, particularly among young adults, that beginning marijuana use leads to an increased chance of developing a marijuana use disorder. Data on the perceived risk of harm with the above substances may be one factor explaining where this trend may be headed. Respondents of the 2020 NSDUH survey were asked how much they thought people risk harming themselves physically and in other ways when they used various substances in certain amounts or frequencies.

Among people 12 and older, 70.7% of people thought there was a great risk of harm from smoking one or more packs of cigarettes daily, and 68.7% saw great risk from having four or five alcoholic drinks nearly every day. The percentages of people who thought there was a great risk from cocaine or heroin use once or twice a week were 84.7% and 93.2%, respectively. “In contrast, about one fourth of people (27.4%) perceived great risk from smoking marijuana once or twice a week.” See the following figure.

Young adults aged 18 to 25 in 2020 were less likely than adolescents aged 12 to 17 or adults aged 26 or older to perceive great risk of harm from smoking marijuana weekly. Research has identified associations among adults between decreases in perceptions of great risk of harm from smoking marijuana weekly and increases in marijuana use. Nevertheless, people can experience adverse effects from marijuana use, such as marijuana use disorder or injury resulting from operating a motor vehicle while impaired by marijuana. Therefore, it is necessary to educate young adults about adverse effects of marijuana use.

The growth of the marijuana legalization movement will likely lead to increased marijuana use and disorder over all age groups. The 2.8 million first time users of marijuana in 2020, along with the 14.2 million marijuana users who meet the criteria for marijuana use disorder, and the significantly lower perception of there being a risk of harm from smoking marijuana once or twice a week suggest as much. But that isn’t the only concern the NSDUH 2020 hints at. In the near future, I’ll look at other issues present in the data, so return and search for “NSDUH 2020.”

The NSDUH provides information that can be used to support prevention and treatment programs, monitor substance use trends, estimate the need for treatment and inform public health policy. Let’s hope its information on marijuana and other substances is helping to inform public health policy and is used to develop future prevention and treatment programs.