Illegally Manufactured Fentanyl Linked to Rise in Overdoses

The increasing distribution of illicitly manufactured fentanyl (IMF) across the United States, and the sharp rise in overdose deaths linked to this drug, are causing more concern about a growing threat to public health and safety.

According to a report published online August 25 in Morbidity and Mortality Weekly Report (MMWR), the number of drug products obtained by law enforcement that tested positive for fentanyl (fentanyl submissions) increased by 426% from 2013 through 2014. Deaths related to synthetic opioids (excluding methadone) increased by 79% during that period.

“An urgent, collaborative public health and law enforcement response is needed to address the increasing problem of IMF and fentanyl deaths,” said the report’s authors, led by R. Matthew Gladden, PhD, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention (CDC).

Pharmaceutical fentanyl, a synthetic opioid 50 to 100 times more potent than morphine, is approved for the management of surgical/postoperative pain, severe chronic pain, and breakthrough cancer pain. IMF, which is unlawfully produced fentanyl obtained through illicit drug markets, is commonly mixed with or sold as white powder heroin.

Starting in 2013, the production and distribution of IMF increased to unprecedented levels. In 2015, the Drug Enforcement Administration (DEA) and the CDC issued nationwide alerts identifying increases in fentanyl-related overdose deaths in multiple states.

The current report documents changes in synthetic opioid–related overdose deaths among 27 states where death certificates consistently report drugs involved in overdoses. These changes were highly correlated with fentanyl submissions, but not with fentanyl prescribing, which remained relatively stable.
The report identified eight states where increases in fentanyl submissions and synthetic opioid deaths were primarily concentrated. In these “high-burden” states, the synthetic opioid crude death rate increased 174%, and the rate of reported fentanyl submissions increased by 1000%.

These high-burden states were located in the Northeast (Massachusetts, Maine, and New Hampshire), the Midwest (Ohio), and the South (Florida, Kentucky, Maryland, and North Carolina). Increases in synthetic opioid deaths in high-burden states disproportionately involved non-Hispanic white men aged 25 to 44 years.

The strong correlation between increases in fentanyl submissions, primarily driven by IMF, increases in synthetic opioid deaths, mostly related to fentanyl, and uncorrelated stable fentanyl prescriptions rates supports the hypothesis that IMF is driving the increases in fentanyl deaths, according to the report’s authors.

“The high potency of fentanyl and the possibility of rapid death after fentanyl administration, coupled with the extremely sharp 1-year increase in fentanyl deaths in high-burden states, highlights the need to understand the factors driving this increase,” the authors write.

The authors note a number of limitations to their findings. One is that because synthetic opioid deaths include those involving drugs other than fentanyl, the absolute number of synthetic opioid deaths should be considered “a proxy” for the number of fentanyl deaths.

Also, whereas drug submissions vary over time and from region to region, the findings are restricted to 27 states, and testing for fentanyl deaths might vary across jurisdictions.

Ohio and Florida

Data on fentanyl-related overdose deaths in Ohio and Florida further suggest that the problem of IMF is rapidly expanding, according to a second report also published in the current issue of MMWR. The study highlights a sharp increase in fentanyl deaths between 2013 and 2015 in these two states that parallels an increase in fentanyl submissions.

The study was carried out by the University of Florida and the Ohio Department of Public Health, in collaboration with the CDC, and was written by Alexis B. Peterson, PhD, Epidemic Intelligence Service and the National Center for Injury Prevention and Control, CDC, and colleagues.

Investigators found that from 2013 to 2014, fentanyl submissions increased 494% in Florida and 1043% in Ohio. This, they note, was “concurrent” with a 115% increase in fentanyl deaths in Florida and a 526% increase in Ohio. They also saw a “sharp increase” in fentanyl submissions and fentanyl deaths in Florida from December 2014 to February 2015.
In contrast, fentanyl prescription rates (per 1000 population) for the full year (2013-2014) increased only 5% in Florida and declined 7% in Ohio.

Death Demographics

Dr Peterson and colleagues note that the demographics of fentanyl-related deaths now “mirror” those of people dying from heroin overdose. For example, in Florida, fentanyl deaths increased almost 2.5 times faster among men (163%) than women (68%), with the most rapidly increasing rate among those aged 14 to 34 years. In contrast, US death rates involving prescription opioids are highest in an older group, those aged 45 to 54 years.

Researchers also uncovered evidence that the percentage of fentanyl deaths in which the victim tested positive for other illicit substances, such as cocaine and heroin, increased significantly over the study period.

In Ohio, factors associated with fentanyl deaths included a current diagnosis of a mental health disorder and a recent release from an institution, such as jail, a rehabilitation facility, or a hospital.

“Persons recently released from an institution are at particularly high risk for opioid overdose because of lowered opioid tolerance resulting from abstinence during residential treatment or incarceration,” they write. “Interventions such as provision of naloxone and continuation of medication-assisted treatment after release have been shown to be effective for this group.”

Increased naloxone access is “critical” given fentanyl’s potency and the possibility of its causing rapid death, they add.

Their findings, the authors say, suggest that the surge in fentanyl deaths in Florida and Ohio is closely related to increases in the local IMF supply as opposed to diverted pharmaceutical fentanyl.

“Distinguishing whether an overdose involves IMF or [pharmaceutical fentanyl] is critical for targeted interventions because overdose risk profiles differ.”

Warning System

The relationship between fentanyl deaths and fentanyl submissions suggests that law enforcement testing data on drug cases could act as an “early warning system” to identify changes in the illicit drug supply, the authors write.

Multidisciplinary strategies from public health agencies, harm reduction communities, emergency medical services, law enforcement, and treatment services for substance use disorders might have the greatest impact on public health, given the close relationship between fentanyl mortality and confiscation of IMF, they continue.

The report pertaining to Florida and Ohio also had limitations, many of them similar to those of the first report. Among those cited was the underestimation of the numbers and rates of fentanyl deaths, as not all overdose deaths were tested for fentanyl.

How Does a Heroin Overdose Kill You ?

Heroin is one of the most addictive drugs in the world, and thousands will die every year from a heroin overdose. Used for centuries for anything from a cough to pain relief, the potential for addiction and death was not fully realized until 1900. Heroin was made illegal in 1920, leaving millions of addicts desperate for opiate drugs.

Categorically, heroin is a central nervous system depressant, synthesized from the psychoactive chemicals in the opium poppy. Both opium and heroin can result in life-threatening central nervous system depression.

The Effects of Heroin: Addiction and Withdrawals
Snorted, smoked or injected, heroin reaches the brain through the bloodstream quickly. Once there, it binds to the opioid receptors, resulting in the relief of anxiety and pain. In effect, it gives the user a calm, euphoric sensation of escape from reality that can last for several hours.

Addiction occurs upon repeated use of the drug. The user’s brain has been, in essence, “hijacked” by heroin. It becomes dependent on the drug to feel good. In addition, it needs more and more of the drug to achieve the same results (tolerance).

When the user “comes down”, or stops using the drug, withdrawal symptoms occur. They are typically the opposite of what it feels like be high. Withdrawals are also a big incentive for people to keep using. Commonly, this is known as being “dope sick”.

Withdrawal symptoms include:

Depression and Anxiety
Irritability
Body aches and increased pain sensitivity
Runny nose, tears
Diarrhea, stomach pain and spasms
Nausea and vomiting
Fever
Seizures
Insomnia

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While not fatal, symptoms are extremely unpleasant can can result in severe depression and suicidal feelings.

Signs of a Heroin Overdose

Overdoses may occur for several reasons. One, heroin is illicit and unregulated, so it is not often possible to know the actually purity (potency) of the drug. It is fairly unpredictable.
Also, the heroin may be laced (combined) with another drug. Fentanyl is common. Fentanyl is also a synthetic opioid, but many times more powerful than heroin. It can easily be fatal on its own accord. When mixed with heroin, the effects can multiply drastically.
Finally, multiple drug intoxication also increases the risk of overdose. For example, drinking alcohol or taking other depressants can also amplify the effects of all substances in question.
Consequently, heroin kills because it slows down the central nervous system, including respiration, to a fatal degree.

Signs and Symptoms

Awake, but unable to talk
Body is very limp
Face is very pale or clammy
Fingernails and lips turn blue or purplish black
For lighter skinned people, the skin tone turns bluish purple, for darker skinned people, it turns grayish or ashen.
Breathing is slow and shallow, erratic, or stopped altogether]
Pulse (heartbeat) is slow, erratic, or undetectable
Choking sounds, or a snore-like gurgling noise (sometimes called the “death rattle”)
Vomiting
Loss of consciousness and unresponsive to outside stimulus

If you notice someone exhibiting these signs, you should immediately call 911. Fortunately, a heroin overdose is not instantaneous, and can be stopped if caught in time.

Treatment
First responders, such as emergency medical personnel, commonly use the anti-overdose drug Narcan (naloxone) to reverse the effects of an overdose and save a life.

Naloxone is an opioid antagonist, meaning that it blocks the life-threatening effects of an opioid overdose. In the case of more powerful opioids, such as fentanyl. more than one dose may be required to reverse an overdose. However, naloxone is usually a very effective antidote, and many pharmacies throughout the country have begun to allow the purchase of naloxone without a prescription.

Areas In The U.S. With The Highest Alcohol Consumption And Drug Use

Areas in the U.S., such as New England, the Midwest, and the Southwest all have their own tendencies toward substance abuse. Just like food, entertainment, and hobbies. these diverse parts of the country consist of certain trends in terms of drug use and alcohol consumption.

The Substance Abuse and Mental Health Services Administration (SAMHSA) releases a yearly survey of Americans over age 12. This survey asks the participant if they have used narcotic painkillers for recreational purposes, or have consumed marijuana, cocaine, or alcohol. States were subsequently ranked based on the population’s use of each of the four substances.

The results were bad news for Colorado and northern New England states.

Colorado was the #1 consumer of the three drugs as well as alcohol. Marijuana has been legalized in Colorado, so it’s of no surprise that the state is among the top consumers.
However, Colorado has the distinction of being top in all categories, including illicit drug use.

Marijuana is also heavily consumed in Washington, Alaska, and Oregon, which have also legalized the drug. Oregon was also a top consumer of recreational opioids.

Vermont, Massachusetts, and New Hampshire are among the top consumers of cocaine, marijuana, and alcohol. Maine and Connecticut also lead in two of those categories. New York residents are heavy cocaine consumers.

Washington D.C., like Colorado, is a bit of an outlier in terms of substance use. It stands out at a high ranking within its area, being closer in consumption of substances to northern New England.

The most religious areas of the U.S. is the Southeast and Bible Belt. Many counties are dry, and folks there have traditionally reported using less substance use in general. However, many of top users of prescription painkillers are in this area, including Arkansas, Alabama, Oklahoma, Louisiana, and Virginia.

States in the Midwest and Plains are not among the highest consumer of any illicit drugs. However, Wisconsin, Minnesota, and North Dakota have a high proportion of alcohol users – likely stemming from a pattern established during the Scandinavian and German mass migration.

In the West, Californians, Arizonians. and New Mexico residents do their fair share of cocaine. This is probably due to the proximity to the Mexican border and heavy trafficking of the drug coming from the south. Arizona is also among the top in recreational use of painkillers.

Factors in substance abuse variations may include differences in state legislation, industry regulations, tradition, regional drug markets, religious and cultural mores, and socioeconomic population traits.

The Difference between Opiates and Opioids

It’s human nature to avoid suffering, and one of the most frequent reasons why people seek medical treatment from a doctor is to help with pain relief. When over-the-counter pain relievers don’t provide the relief that a patient is seeking, the doctor can prescribe a stronger pain medication.

However, when not used according to the doctor’s instructions, or used for a long period of time they can lead to drug addiction.

Difference Between Opiates And Opioids
Opiates: A Natural Pain Remedy
Opiates are alkaloids derived from the opium poppy. Opium is a strong pain relieving medication, and a number of drugs are also made from this source.

Types Of Opiates

Morphine
Codeine
Heroin
Opium
Opioids: Synthetic Pain Medications
Opioids are synthetic or partly-synthetic drugs that are manufactured to work in a similar way to opiates. Their active ingredients are made via chemical synthesis. Opioids may act like opiates when taken for pain because they have similar molecules.

Types Of Opioids

Methadone
Percocet, Percodan, OxyContin (oxycodone)
Vicodin, Lorcet, Lortab (hydrocodone)
Demerol (pethidine)
Dilaudid (hydromorphone)
Duragesic (fentanyl)
How Opiates And Opioids Work
Both of these types of drugs alter the way that pain is perceived, as opposed to making the pain go away. They attach onto molecules that protrude from certain nerve cells in the brain called opioid receptors. Once they are attached, the nerve cells send messages to the brain that are not accurate measures of the severity of the pain that the body is experiencing. Thus the person who has taken the drug experiences less pain.

Drugs in these classes also affect how the brain feels pleasure. A person who takes them who is not in pain will experience a feeling of elation, followed by deep relaxation and/or sleepiness.

Addiction To Opiates And Opioids
When people use these medications only to treat pain as directed and for a short time, they are less likely to become addicted. Prescription drug addiction occurs when patients develop a tolerance for the level of medication they have been described and no longer get the same level of relief.

They may not have the same expectations for relief as their physicians and may equate the term “painkillers” with the medication being able to take away all of their pain, while their doctor may be thinking in terms of pain management, which means bringing the pain to a level where they can function at a reasonable manner. When expectations do not match, patients may take more of the pain medication than prescribed to get a higher level of relief and in turn develop a drug addiction issue.

Alcohol causes at least Seven kinds of Cancer

There is “strong evidence” that alcohol causes seven cancers, and other evidence indicates that it “probably” causes more, according to a new literature review published online July 21 in Addiction.

Epidemiologic evidence supports a causal association of alcohol consumption and cancers of the oropharynx, larynx, esophagus, liver, colon, rectum, and female breast, says Jennie Connor, MB, ChB, MPH, from the Department of Preventive and Social Medicine, University of Otago, in Dunegin, New Zealand.

In short, alcohol causes cancer.

This is not news, says Dr Connor. The International Agency for Research on Cancer (IARC) and other agencies have long identified alcohol consumption as being causally associated with these seven cancers.

So why did Dr Connor, who is an epidemiologist and physician, write a new review? Because she wants to “clarify the strength of the evidence” in an “accessible way.”

There is “confusion” about the statement, “Alcohol causes cancer,” explains Dr Connor.

Public and scientific discussion about alcohol and cancer has muted the truth about causality, she suggests.

“In the public and the media, statements made by the world’s experts are often given the same weight as messages from alcohol companies and their scientists. Overall messages become unclear. For these reasons, the journal [Addiction] has tagged this piece [her review] as ‘For Debate,’ ” she told Medscape Medical News.

The use of causal language in scientific and public discussions is “patchy,” she writes.

For example, articles and newspaper stories often use expressions such as “alcohol-related cancer” and “alcohol-attributable cancer”; they refer to a “link” between alcohol and cancer and to the effect of alcohol on “the risk of cancer.”

These wordings “incorporate an implicit causal association, but are easily interpreted as something less than cancer being caused by drinking,” observes Dr Connor.

“Stop drinking alcohol” is a catch phrase that could be ― but is not ― akin to “stop smoking,” she also suggests.
Currently, alcohol’s causal role is perceived to be more complex than tobacco’s, and the solution suggested by the smoking analogy — that we should all reduce and eventually give up drinking alcohol — is widely unacceptable,” writes Dr Connor.

The newly published review “reinforces the need for the public to be made aware of the causal link between alcohol and cancer,” said Colin Shevills, from the Alcohol Health Alliance UK, in a press statement.

“Research shows that only around 1 in 10 people [in the UK] are currently aware of the alcohol-cancer link,” he said.

“People have the right to know about the impact of alcohol on their health, including its link with cancer, so that they can make informed choices about how much they drink,” added Shevills.

The lack of clarity about alcohol causing cancer, Dr Connor believes, is related to alcohol industry propaganda as well as the fact that the “epidemiological basis for causal inference is an iterative process that is never completed fully.”

What the Epidemiology Says

Dr Connor writes that the strength of the association of alcohol as a cause of cancer varies by bodily site. The evidence is “particularly strong” for cancer of the mouth, pharynx, and esophagus (relative risk, ~4-7 for ≥50 g/day of alcohol compared with no drinking) but is less so for colorectal cancer and liver and breast cancer (relative risk, ~1.5 for ≥50 g/day).

“For cancers of the mouth, pharynx, larynx and oesophagus there is a well-recognized interaction of alcohol with smoking, resulting a multiplicative effect on risk,” adds Dr Connor.

Other cancers are also likely caused by alcohol. Dr Connor writes that there is “accumulating research” supporting a causal contribution of alcohol to cancer of the pancreas, prostate, and skin (melanoma).

The exact mechanisms as to how alcohol, either alone or in combination with smoking, cause cancer “are not fully understood,” although there is some supporting “biological evidence,” she says.

One British expert had an opinion about alcohol’s carcinogenicity.

In a statement about the new review, Prof Dorothy Bennett, director of the Molecular and Clinical Sciences Research Institute at St. George’s, University of London, said: “Alcohol enters cells very easily, and is then converted into acetaldehyde, which can damage DNA and is a known carcinogen.”

In the new review, Dr Connor describes various hallmarks of causality that have been found in epidemiologic studies of alcohol and these seven cancers, such as a dose-response relationship and the fact that the risk for some of these cancers (esophageal, head and neck, and liver) attenuates when drinking ceases.
Current estimates suggest that alcohol-attributable cancers at the seven cancer sites make up 5.8% of all cancer deaths worldwide, she states.

The alcohol industry has a lot at stake, she says, which in turn leads to “misinformation” that “undermines research findings and contradicts evidence-based public health messages.”

A recent example comes from New Zealand, where a symposium on alcohol and cancer was covered by national media. An opinion piece by an industry-funded scientist in the capital’s daily newspaper disputed the evidence reported from the conference. That essay was entitled: “To Say Moderate Alcohol Use Causes Cancer Is Wrong.”

The essay included the statement: “While chronic abusive alcohol consumption is associated with a plethora of health problems including cancer, attributing cancer to social moderate drinking is simply incorrect and is not supported by the body of scientific literature.”

But there is no safe level of drinking with respect to cancer, says Dr Connor, citing research about low to moderate levels of alcohol.

This was also the conclusion of the 2014 World Cancer Report, issued by the World Health Organization’s IARC.

The promotion of health benefits from drinking at moderate levels is “seen increasingly as disingenuous or irrelevant in comparison to the increase in risk of a range of cancers,” writes Dr Connor.

Public health campaigns “with clear messages” are needed to spread the word about alcohol’s carcinogenicity.

“I think that the UK is leading the way. Alcohol consumption as a public health issue has had high exposure in the UK over quite a number of years,” said Dr Connor, who provided links to two awareness campaigns, the Balance campaign, and the Balance Northeast campaign.

Earlier this year, the United Kingdom issued new guidelines on alcohol drinking, recommending that men drink no more than women and warning that any amount of alcohol increases the risk of developing a range of cancers.

Organizations in New Zealand are also taking action. The New Zealand Medical Association, the Cancer Society of New Zealand, and the National Heart Foundation have all adopted evidence-based position statements that “debunk” cardiovascular benefits as a motivation to drink and that highlight cancer risks, Dr Connor said.

Call your Republican Representative or Senator and raise Holy Hell!

President Obama signed a bill aimed at addressing opioid addiction Friday, though he called out Republicans for the measure’s shortcomings.

Lawmakers in both parties reached a compromise over the bipartisan Comprehensive Addiction and Recovery Act, though Senate Democrats held out hope until the final hour that they could win more funding for treatment.
“This legislation includes some modest steps to address the opioid epidemic,” Obama said in a statement. “Given the scope of this crisis, some action is better than none. However, I am deeply disappointed that Republicans failed to provide any real resources for those seeking addiction treatment to get the care that they need.”

He also noted that GOP lawmakers had blocked an additional $920 million in funding for addiction treatment.

The bill passed the Senate 92-2 last week, with Sens. Ben Sasse (R-Neb.) and Mike Lee (R-Utah) the only dissenters.

Despite overwhelming support, many Democrats are calling for stronger measures to address the crisis.

“My administration has been doing everything we can to increase access to treatment, and I’m going to continue fighting to secure the funding families desperately need,” Obama said in his statement Friday. “In recent days, the law enforcement community, advocates, physicians, and elected officials from both sides of the aisle have also joined in this call.”

“Now, it’s up to Republicans to finish the job and provide adequate funding to deal with this public health crisis,” he added. “That’s what the American people deserve.”