“How Can It Be?” by Lauren Daigle

I am guilty
Ashamed of what I’ve done, what I’ve become
These hands are dirty
I dare not lift them up to the Holy One

You plead my cause, you right my wrongs
You break my chains, you overcome
You gave your life, to give me mine
You say that I am free
How can it be?

I’ve been hiding
Afraid I’ve let you down
Inside I doubt that you could love me
But in your eyes, there’s only grace now

You plead my cause, you right my wrongs
You break my chains, you overcome
You gave your life, to give me mine
You say that I am free
How can it be?

Though I fall, you can make me new
From this death, I will rise with you
Oh, the grace reaching out for me, yeah
How can it be, how can it be?

You plead my cause, you right my wrongs
You break my chains, you overcome
You gave your life, to give me mine
You say that I am free, yeah

How can it be, how can it be?

Appalachian Trail

It was the spring of 1948, and a young man from Pennsylvania had to work out of his mind the many sights, sounds, and losses he experienced during World War II. He took a hike. For four months. On August 5, 1948, Earl Victor Shaffer became the first person known to hike uninterrupted the entire length of the Appalachian Trail, from Mt. Oglethorpe in Georgia through thirteen other states to Katahdin in the central-Maine wilderness. He covered more than 2,000 miles of footpath created in the 1920s and ’30s by volunteers and maintained by volunteers ever since. Earl Shaffer, a woodsman, naturalist and poet, went on to become one of those volunteers with the Appalachian Trail Conservancy, and worked with the Conservancy to secure federal protection for the Trail, which is now part of the national park system.

The Appalachian Trail, in 1948, had reached a critical point in its history. Maintenance had lapsed in many areas during World War II, with many active workers serving in the armed services. Storm damage, logging operations, and natural growth had erased or cluttered much of the trail. Marking was often faded or gone. The famous footpath seemed on its way to oblivion. Even the people who had done most to bring the Trail to tentative completion a few years before the war were doubtful about its future. With this in mind, a meeting of the Appalachian Trail Conference was set for June of that year at Fontana Village in North Carolina, to rally the member groups and individuals for an attempt at restoration. While in session, the Conference received by mail a message informing them that Earl Shaffer had started from Mt. Oglethorpe in Georgia April 4th, and was now passing through eastern New York State, and was expecting to reach Katahdin in Maine about August 5th. That was a total of four months to cover the 2,050-mile journey.

I have always wanted to hike the entire length of the Appalachian Trail. I’m sure this is true because of extensive camping growing up. When we started camping as a family in the late 1960s, we used a tent. At some point, we graduated to a pop-up camper. We then progressed to a single-axle camping trailer, and ultimately a double-axle unit. I remember a camping trip one year when I was the last one to wake up and come out of the camper. My mother asked me what I wanted for breakfast. Still half asleep, I said, “Beggs and ‘acon.” Mom said, “What?” I said, “I mean ‘acon and beggs.”

As for wanting to hike the entire trail, there’s much I would need to do in order to remotely guarantee I’d survive. First, I presently weigh 247 pounds. Not the most I’ve ever weighed (261 pounds), but far from trim enough to hike for four continuous months. Second, I truly cannot afford the gear I’d need. Hopefully, that, as well as my weight and BMI, will improve before I face the third factor. My age. I understand that much of the Trail is quite treacherous and often rather steep. Indeed, the “easiest” part of the Trail is in Pennsylvania.

I watched the movie “A Walk In the Woods,” based on the book of the same name written (as experienced) by Bill Bryson during his attempt to hike the entire length of the Appalachian Trail. Check out the trailer for the movie at https://www.youtube.com/watch?v=cOF2LIAp9bw. Neither Bryson nor his hiking companion were spring chickens when they undertook their adventure, which was somewhat comforting to me given my yearning to tackle the Trail in my late 50s. I will admit that the idea of a huge backpack hanging off me for four months is particularly troublesome. In any event, if I am ever in decent enough shape to hike the Trail, I’m certain I will not be going in the dead of winter, nor in the heat of the summer. Hiking the Appalachian Trail from Georgia to Maine is on my bucket list.

Excerpts from the book “Walking With Spring” by Earl V. Shaffer.

For more information about the Trail click on the link http://www.appalachiantrail.org/home/community/news.

Knowing the Voice of Jesus

“The one who enters by the gate is the shepherd of the sheep. The gate-keeper opens the gate for him, and the sheep hear his voice. He calls his own sheep by name and leads them out. When he has brought out all his own, he goes ahead of them, and the sheep follow him because they know his voice. They will not follow a stranger, but they will run from him because they do not know the voice of the stranger. I am the good shepherd. I know my own and my own know me, just as the Father knows me and I know the Father. And I lay down my life for the sheep. I have other sheep that do not belong to this fold. I must bring them also, and they will listen to my voice. So there will be one flock, one shepherd.” (John 10:2-5, 14-16)

John’s gospel cites the phrase “I am” together with seven sets of names to record metaphors for Christ. Jesus says, “I am the bread of life.(6:35, 48), “I am the light of the world” (8:12; 9:5), “I am the gate” (10:7,9), “I am the good shepherd” (10:11, 14), “I am the resurrection and the life” (11:25), “I am the way, the truth, and the life” (14:6), and “I am the vine” (15:1,5). All these pictures are expanded in ways that teach us more thoroughly about the grace that rescues, restores, establishes, nourishes, indwells, enlightens, guides, protects, saves, and raises us. Each of these statements provides ample ground for meditation. Jesus’ description of Himself as the shepherd also brings comfort and assurance to those of us struggling to discern His voice in our contemplative prayer. All those who are His sheep know His voice. He knows us and we know Him. If we trust Him to shepherd our lives, we will not follow a stranger.

Opiate Epidemic

The following are excerpts from the cover story in National Review dated February 29, 2016, titled From Oxy to Overdose: How Prescription-Drug Abuse Unleashed a Heroin Epidemic, by Kevin D. Williamson.

Ground Zero in the opiate epidemic isn’t in some exotic Taliban-managed poppy field or some cartel boss’s fortified compound. It’s right there at Walgreen’s, in the middle of every city and town in the country.

The author begins with an interview of a heroin addict he conducted in Birmingham, Alabama. The addict described several street names for heroin. “Sand, because it’s brown. Or diesel. Or killa or 911…the 911 they call it because they want you to know it’s potent, that you’ll have to go to the emergency room.”

That’s a weird and perverse and nasty kind of advertising, but then dope-buying psychology isn’t very much like Volvo-buying psychology. Crashing is just another part of the ride. One spiteful dealer boasts about spiking his product with excessive amounts of fentanyl, an all-business pharmaceutical analgesic used for burn victims and cancer patients, that particular dealer’s plan being to intentionally send overdosed users to the hospital or the morgue…for marketing purposes. Once the word got out about the hideous strength of his product, addicts were scrambling to try it.

The young man being interviewed is barely old enough to buy a beer. He describes the past several years of his life “dope-sick and stealing,” going from job to job. Eight jobs in six months. Robbing his employers blind, alienating his family, descending. He was an addict on a mission. “You’re always chasing that first shot of dope, that first high. And the first one for me almost killed me. I was 17 or 18 years old, and I met a guy who had just got out of prison, doing a 13-year sentence for heroin possession and distribution…I was snorting heroin when I met up with him, and set him up with my connection. He offered to shoot me up, and I wanted to do it. And I remember him looking me in the eyes and telling me, ‘If you do this, you’ll never stop, and you’ll never go back.’ And I said, ‘Let’s do it.'”

This particular opiate odyssey starts off in a Walgreen’s. What seems to be killing what used to be the white working class isn’t diabetes or heart disease or the consumption of fatty foods and Big Gulps from 7-Eleven, but alcohol-induced liver failure, along with overdoses of opioid prescription painkillers and heroin. The use of heroin has increased dramatically in recent years as medical and law-enforcement authorities crack down on the wanton overprescription of oxy and related painkillers. Which is to say: While we were ignoring criminally negligent painkiller prescriptions, we helped create a gigantic population of opioid addicts, and then, when we started paying attention, first thing we did was take away the legal and quasi-legal stuff produced to exacting clinical standards by Purdue Pharma (maker of OxyContin), and other drug manufacturers. So, lots of opiate addicts, but fewer prescription opiates available.

The clerks the author encountered at the Walgreen’s in Birmingham are super friendly, but the place is set up security-wise like a bank. That’s to be expected. This particular location was knocked over by a young white man with a gun the summer before last, an addict who had been seen earlier lurking around the CVS down the road. This is how you know you’re a pretty good junkie: The robber walked in and pointed his automatic at the clerk and demanded oxy first, then a bottle of cough syrup, and then, almost as an afterthought, the $90 in the till. Walgreen’s gets robbed a lot. In January, armed men stormed the Walgreen’s in Edina, Minnesota, and made off with $8,000 worth of drugs, mainly oxy. In October, a sneaky young white kid made off with more than $100,000 worth of drugs, again, mainly oxy and related opioid painkillers, from a Walgreen’s in St. Petersburg, Florida.

In 2013, Walgreen’s paid the second-largest fine ever imposed under the Controlled Substances Act for being so loosey-goosey in handling oxy at its distribution center in Jupiter, Florida that it enabled untold quantities of the stuff to reach the black market. The typical pharmacy sells 73,000 oxycodone pills a year; six Walgreen’s in Florida were going through more than 1 million pills a year at each location. That’s six million doses of oxy. A few years before that, Purdue Pharma was fined $634.5 million for misleading the public about the addictiveness of oxycodone.

The current spike in overdoses is related to a couple of things. One proximate cause is the increased use of fentanyl to spike heroin. Heroin, like Johnnie Walker, is a blend. The raw stuff is cut with fillers to increase the volume, and then that diluted product is spiked with other drugs to mask the effects of dilution. Enter the fentanyl. Somebody, somewhere, has got his hands on a large supply of the stuff, either hijacked from legitimate pharmaceutical manufacturers or produced in some narco black site in Latin America, for the express purpose of turbocharging heroin. Fentanyl, on its own, isn’t worth very much on the street. It might get you numb, but it really doesn’t get you high, and such pleasures as are to be derived from its recreational use are powerfully offset by its tendency to kill you dead. But if the blend is artfully done, then fentanyl can make stepped-on heroin feel more potent than it is.

In high places, there are stirrings of awareness about heroin’s most recent ferocious comeback, but it has taken a while. Congress recently held hearings, and Senator Kelly Ayotte, the charismatic young New Hampshire Republican, introduced the Heroin and Prescription Opioid Abuse Prevention, Education, and Enforcement Act of 2015. The bill is currently on ice in the Judiciary Committee. One of the key aspects of the bill would convene a task force.

The public perception of heroin is like that of AIDS a generation ago. It is seen as a problem for deviants. AIDS was for perverts who liked to have sex with men at highway rest stops, and heroin is a problem for toothless pillbillies who turn to the needle after running out of oxy, and for whores and convicts and menacing black men in ghettos. Heroin, this line of thinking goes, is a problem for people who deserve it. Nobody seems to care because of who is affected. There are two problems with that. One, it’s unethical. Two, it isn’t true. It isn’t just the born-to-lose crowd and career criminals and deviants and undesirables. It’s working-class white men and college-bound suburban kids too.

There are 8,173 Walgreen’s locations filing 894 million prescriptions a year, and that big record-breaking fine doesn’t look so big up against $77 billion in sales a year. CVS does $140 billion a year, filling one-third of all U.S. pharmaceutical prescriptions. In a country of 319 million, there were 259 million opiate-painkiller prescriptions written last year. There were 47,000 lethal overdoses in the U.S. in 2014, almost 30,000 of which were prescription painkillers and heroin. Some 94 percent of heroin users told researchers that they got into heroin because the pills they started on became too expensive or too difficult to find. Heroin was cheap and plentiful. How do we keep up with all those pills? Where do they go? Somebody knows. It’s time we address this rapidly growing health concern head on.



Drugs, Brains and Behavior

Many people do not understand why or how other people become addicted to drugs. It is often mistakenly assumed that drug abusers lack moral principles or willpower, and that they could stop using drugs simply by choosing to change their behavior. In reality, drug addiction is a complex disease, and quitting takes more than good intentions or a strong will. In fact, because drugs change the brain in ways that foster compulsive drug abuse, quitting is difficult, even for those who are ready to do so. Through scientific advances, we know more about how drugs work in the brain than ever, and we also know that drug addiction can be successfully treated to help people stop abusing drugs and lead productive lives.

What is Drug Addiction?

Addiction is defined as a chronic, relapsing brain disease that is characterized by compulsive drug seeking and use, despite harmful consequences. It is considered a brain disease because drugs change the brain—they change its structure and how it works. These brain changes can be long-lasting, and can lead to the harmful behaviors seen in people who abuse drugs. Addiction is a lot like other diseases, such as heart disease. Both disrupt the normal, healthy functioning of the underlying organ, have serious harmful consequences, and are preventable and treatable, but if left untreated, can last a lifetime.

Why Do People Take Drugs?

In general, people begin taking drugs for a number of reasons.

To feel good. Most abused drugs produce intense feelings of pleasure. This initial sensation of euphoria is followed by other effects, which differ with the type of drug used. For example, with stimulants such as cocaine, the “high” is followed by feelings of power, self-confidence, and increased energy. In contrast, the euphoria caused by opiates, such as oxycodone or heroin, is followed by feelings of relaxation and satisfaction.

To feel better. Some people who suffer from social anxiety, stress-related disorders, and depression begin abusing drugs in an attempt to lessen feelings of distress. Stress can play a major role in beginning drug use, continuing drug abuse, or relapse in patients recovering from addiction.

To do better. Some people feel pressure to chemically enhance or improve their cognitive or athletic performance, which can play a role in initial experimentation and continued abuse of drugs such as prescription stimulants or anabolic/androgenic steroids.

Curiosity and “Because others are doing it.” In this respect, adolescents are particularly vulnerable because of the strong influence of peer pressure. Teens are more likely than adults to engage in risky or daring behaviors to impress their friends and express their independence from parental and social rules.

If Taking Drugs Makes People Feel Good or Better, What’s the Problem?

When they first use a drug, people may perceive what seem to be positive effects; they also may believe that they can control their use. However, drugs can quickly take over a person’s life. Over time, if drug use continues, other pleasurable activities become less pleasurable, and taking the drug becomes necessary for the user just to feel “normal.” They may then compulsively seek and take drugs even though it causes tremendous problems for themselves and their loved ones. Some people may start to feel the need to take higher or more frequent doses, even in the early stages of their drug use. These are the telltale signs of an addiction.

Is Continued Drug Abuse a Voluntary Behavior?

The initial decision to take drugs is typically voluntary. However, with continued use, a person’s ability to exert self-control can become seriously impaired; this impairment in self-control is the hallmark of addiction. Brain imaging studies of people with addiction show physical changes in areas of the brain that are critical to judgment, decision making, learning and memory, and behavior control. Scientists believe that these changes alter the way the brain works, and may help explain the compulsive and destructive behaviors of addiction. No single factor determines whether a person will become addicted to drugs.

Although taking drugs at any age can lead to addiction, research shows that the earlier a person begins to use drugs, the more likely he or she is to develop serious problems. This may reflect the harmful effect that drugs can have on the developing brain; it also may result from a mix of early social and biological vulnerability factors, including unstable family relationships, exposure to physical or sexual abuse, genetic susceptibility, or mental illness. Still, the fact remains that early use is a strong indicator of problems ahead, including addiction.

Smoking a drug or injecting it into a vein increases its addictive potential. Both smoked and injected drugs enter the brain within seconds, producing a powerful rush of pleasure. However, this intense “high” can fade within a few minutes, taking the abuser down to lower, more normal levels. Scientists believe this starkly felt contrast drives some people to repeated drug taking in an attempt to recapture the fleeting pleasurable state.

The Brain Continues to Develop Into Adulthood and Undergoes Dramatic Changes During Adolescence.

One of the brain areas still maturing during adolescence is the prefrontal cortex—the part of the brain that enables us to assess situations, make sound decisions, and keep our emotions and desires under control. The fact that this critical part of an adolescent’s brain is still a work in progress puts them at increased risk for making poor decisions (such as trying drugs or continuing to take them). Also, introducing drugs during this period of development may cause brain changes that have profound and long-lasting consequences.

How Science Has Revolutionized the Understanding of Drug Addiction

For much of the past century, scientists studying drug abuse labored in the shadows of powerful myths and misconceptions about the nature of addiction. When scientists began to study addictive behavior in the 1930s, people addicted to drugs were thought to be morally flawed and lacking in willpower. Those views shaped society’s responses to drug abuse, treating it as a moral failing rather than a health problem, which led to an emphasis on punishment rather than prevention and treatment. Today, thanks to science, our views and our responses to addiction and other substance use disorders have changed dramatically. Groundbreaking discoveries about the brain have revolutionized our understanding of compulsive drug use, enabling us to respond effectively to the problem.

As a result of scientific research, we know that addiction is a disease that affects both the brain and behavior. We have identified many of the biological and environmental factors, and are beginning to search for the genetic variations that contribute to the development and progression of the disease. Scientists use this knowledge to develop effective prevention and treatment approaches that reduce the toll drug abuse takes on individuals, families, and communities.

Despite these advances, many people today do not understand why people become addicted to drugs or how drugs change the brain to foster compulsive drug use. The National Institute on Drug Abuse (NIDA) aims to fill that knowledge gap by providing scientific information about the disease of drug addiction, including the many harmful consequences of drug abuse, and the basic approaches that have been developed to prevent and treat substance use disorders. At NIDA, they believe increased understanding of the basics of addiction will empower people to make informed choices in their own lives, adopt science-based policies and programs that reduce drug abuse and addiction in their communities, and support scientific research that improves the Nation’s well-being.


National Institute of Drug Abuse
The Science of Drug Abuse and Addiction
July 2014


Smoking “Wet”

Embalming Fluid-Soaked Marijuana

New High of New Guise for PCP?
By July Holland

The  trend of smoking marijuana soaked in embalming fluid is gaining popularity throughout the United States. The syndrome of intoxication looks nearly identical to that seen following phencyclidine (PCP) use, with agitation, disorganized speech and thoughts, and diminished attention. The author believes that this new trend in drug use involving marijuana also presents a resurgence in PCP use.

Several Case Reports

The first case involves a 28 year old African American male who arrived via ambulance to Bellevue ER for a psychiatric emergency. On admission, he was naked, disoriented to self, place and date, and was grossly psychotic. He referred to himself as “Allah,” “Justice,” and “Jesus.” Vital signs were normal. When asked if he had any drug allergies, the patient replied, “Yeah, wet.” The patient was alternately confused, then agitated, speaking of the coming of the Messiah. He appeared to be actively hallucinating, frequently looking over his shoulder or to his right as if he heard something.

After receiving 2 mg. of Ativan, the patient was able to state his name, and said that he had come on a bus from Philadelphia to Manhattan in order to make a rap album. He was grandiose about his connections to rap stars in New York City. He said he had disrobed on the bus in order to show the passengers that he was a “Native American,” and not a “mixed up American.” He was preoccupied with aliens, surveillance cameras, and robots. He also talked about twins and clones, referring to the “invasion of the double-mint twins.” He repeated paranoid ideation, stating that the Freemasons had a plot against him, and that the aliens had replaced his eye with a camera in order for him to transmit what he was seeing back to their spaceship. He said voices were telling him to “duck,” and to “look for the red spots.” He was easily distracted during the interview, and was sexually inappropriate with the interviewer.

The patient was re-evaluated the morning after he he was seen in the ER. His psychotic symptoms were gone. He was no longer delusional, was fully oriented, and was able to give personal medical history. He stated that every time he uses “wet” he has similar symptoms. He said, “I become hilarious. I can rhyme better. It makes me emotional, and I feel uncontrollably funny.” He described “wet” as being readily available in Philadelphia, where a small glasine envelope of tea leaves soaked in embalming fluid is sold for five dollars. He explained that he often mixes the leaves with marijuana. He said he was unaware that the tea leaves may contain PCP.

PCP and embalming fluid seem to be historically and semantically intertwined. The term “embalming fluid” was used to refer to PCP in the seventies, considered by some to be a marketing ploy. Embalming fluid has reportedly been used to cover the smell of PCP in order to evade drug-sniffing dogs. Many Internet postings mentioning “wet” or “dank” include the possibility that the fluid will contain PCP. The U.S. Department of Health and Human Services Marijuana Reality Check Kit, an online source of information about marijuana, warns of pot being spiked with other illicit drugs such as cocaine, crack, PCP and embalming fluid.

Workers at an adolescent drug treatment center in Olathe, Missouri estimated that 25% of  their patients had used “wet” (known locally as “dank”). Barbara Banks, assistant director of the facility, cited the low price and availability of “wet” and reported that “dank houses” were beginning to appear in the region. An intake interviewer and counselor for a drug treatment center in Angleton, Texas reports seeing tree patients whom he feels were permanently afflicted from the habit of smoking “wet.” He described short-term memory loss, lethargy, lack of motivation, and a decrease in spontaneous speech. He likened the syndrome to one he has seen due to long-term inhalant abuse.

A young man in Connecticut cut his wrists and drank floor stripper while intoxicated with “wet.” Driven by his psychosis, he reportedly had an urge to kill himself “before they get me.” Police felt the patient was acutely paranoid at the time of his arrest. Psychiatrists documented the patient as being agitated and delirious, and said he was having auditory, visual and tactile hallucinations at the time of his initial evaluation. Three days later, during his hospital stay, he was still exhibiting bizarre posturing, but was not quite catatonic. On the fourth day, he was noted to be euphoric, expansive and grandiose. He was giggling frequently, and showed poor judgment and was overly friendly. He offered cash to many staff members.

A 23 year old “wet” smoker in New York City described the high he achieved as feeling incapacitated, and referred to being “stuck.” He was afraid he was going to hurt himself and that others were out to hurt him. He heard a distant male voice calling his name. He knew where he was, but had no idea as to the time of day or the day of the week. He noted often forgetting what he was saying while speaking. He also said he would “lose time” while high. He admitted to being gay, and said he often had unprotected sex with other males while high. He said he would typically feel “out of control,” “horny,” and “elated.”

In summary, it is unclear whether the practice of smoking marijuana or tea leaves soaked in embalming fluid connotes a new type of intoxication, or whether what is currently being observed is PCP intoxication that simply has a new name or gimmick to aid in its allure and sales. More analysis of liquid samples purported to be embalming fluid would be helpful in answering this question. It is possible that there are long-term adverse effects from the practice of smoking “wet.” More reports need to be gathered. Obviously, this is a serious matter of public health. Clearly, intoxication with this drug severely clouds a person’s judgment. This is especially true regarding its effects on “safe sex” practices.




Why Do Addicts Take a Drug That No Longer Gives Pleasure?

People who have used cocaine for a long time report a paradoxical-seeming experience: The pleasure they get from taking the drug decreases even as the drug intensifies its hold over their behavior.

A recent NIDA-supported study sheds light on why this might be. Researchers shows that, in mice, a cocaine-induced imbalance in the activity of two key populations of neurons in the reward system persists for a longer period after repeated exposure to the drug. For long-term users, the researchers suggest, this change could both weaken the cocaine “high” and strengthen the compulsion to seek the drug.

A Distorted Ratio

Drs. Congwu Du and Yingtian Pan and colleagues at Stony Brook University in New York and at NIDA injected two groups of mice with a single dose of cocaine (8 milligrams per kilogram of body weight). One group of mice had already been exposed to the drug daily for 2 weeks, and the other, a control group, was receiving the drug for the first time. Using a novel dual-imaging and measurement technique*, the researchers tracked the drug’s impact on activity levels of two populations of medium spiny neurons (MSNs) in the striatum of the two groups of mice.

One of two MSN populations observed by the researchers interacts with dopamine via receptors called D1R. When activated by dopamine, striatal D1R MSNs give rise to pleasurable feelings, motivate an animal or a person to repeat the experience that yielded these feelings, and promote the conversion of such motivation into action by stimulation neurons in the brain’s motor cortex. The other MSN population interacts with dopamine via a different receptor, called D2R. When activated, D2R MSNs counter the effects of the D1R MSNs. They attenuate euphoria and drug seeking and inhibit the motor cortex.

In the experiment, Drs. Du and Pan found that immediately after the cocaine injection, D1R MSN activation increased and D2R MSN activated decreased, both in the mice that had been exposed daily to the drug and in those being exposed for the first time. As a result, in both groups, the ratio of D1R MSN to D2R MSN activation shifted sharply in favor of the D1R MSNs and their reward- and motivation-promoting effects.

At 5 to 7 minutes post-injection, however, the D1R to D2R activity ratios diverged between the two groups of mice. In the control mice, D1R activation rapidly fell back to its baseline level, causing the D1R to D2R ratio to also return to near baseline. In the mice that had been exposed daily to cocaine, in contrast, the cocaine-induced D1R activation increased steadily over the entire 30 minutes that the animals were observed. As a result, D1R to D2R rose higher and remained elevated longer in the daily-exposed mice holds in people as well, it could help explain why long-term users of cocaine report less euphoria from taking the drug.

The researchers propose that the drawn-out time course of cocaine-induced D1R to D2R MSN activation following repeated exposure will also enhance an animal’s or a person’s drive to seek the drug. Dr. Pan explains, “Dopamine both activates and inhibits brain circuits, and normally this dual action produces healthy behavioral outcomes. Cocaine upsets this balance. It enhances the D1R MSN signaling that normally puts a brake on those behaviors. In our experiment, we showed that this imbalance is short lived in mice when they are exposed to the drug for the first time, but long lasting in mice that have already been repeatedly exposed.”

More Research is Needed

“The research field had not put much effort into separating how these two dopamine receptor systems are involved in rewiring the brain exposed to chronic cocaine use, or their effects on compulsive intake of the drug,” says Dr. Nora D. Volkow, NIDA Director and a collaborator on the study. “This work highlights the importance of the relative participation of D1R versus D2R signaling.”

Drs. Du and Pan have more work to do to show that their observations account for long-term cocaine users’ reduced enjoyment and increased compulsion to use the drug. As a first step, they plan to examine whether increasing the D1R to D2R MSN activity ratio indeed increases animals’ drug-seeking behavior. This will be very challenging, says Dr. Du, because it will require adapting their imaging technique to monitor MSNs in awake and moving animals. To date, they have used it only with anesthetized and restrained animals.

Another outstanding question is whether long-term cocaine use actually changes the time course of D1R MSN activation in people as it does in mice. Dr. Pan notes that although research has not yet addressed this question, imaging studies conducted in Dr. Volkow’s laboratory have shown that cocaine dampens D2R signaling in people as well as mice. If further investigations confirm the researchers’ hypotheses, says Dr. Volkow, “treatments that strengthen D2R signaling could help people stop using cocaine.”


Park, K.; Volkow, N.D.; Pain, Y.; Du, C. Chronic cocaine use dampens dopamine signaling during cocaine intoxication and unbalances D1 over D2 receptor signaling. The Journal of Neuroscience, 33(40):15827-15836, 2013.

*To achieve their observations, Drs. Du and Pan developed a dual-imaging technique based on a novel microprobe that was used for visualizing individual neurons deep within the brain. The technique enabled them to distinguish the populations of D1R and D2R MSNs, and to track moment-to-moment changes in each one’s calcium levels. Calcium levels directly reflect a neuron’s level of activation.