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Drugs and the Brain

The human brain is the most complex organ in the body. This three-pound mass of gray and white matter sits at the center of all human activity—you need it to drive a car, to enjoy a meal, to breathe, to create an artistic masterpiece, and to enjoy everyday activities. In brief, the brain regulates your body’s basic functions; enables you to interpret and respond to everything you experience; and shapes your thoughts, emotions, and behavior.

The brain is made up of many parts that all work together as a team. Different parts of the brain are responsible for coordinating and performing specific functions. Drugs can alter important brain areas that are necessary for life-sustaining functions and can drive the compulsive drug abuse that marks addiction. Brain areas affected by drug abuse include:

  • The brain stemwhich controls basic functions critical to life, such as heart rate, breathing, and sleeping.
  • The cerebral cortex, which is divided into areas that control specific functions. Different areas process information from our senses, enabling us to see, feel, hear, and taste. The front part of the cortex, the frontal cortex or forebrain, is the thinking center of the brain; it powers our ability to think, plan, solve problems, and make decisions.
  • The limbic system, which contains the brain’s reward circuit. It links together a number of brain structures that control and regulate our ability to feel pleasure. Feeling pleasure motivates us to repeat behaviors that are critical to our existence. The limbic system is activated by healthy, life-sustaining activities such as eating and socializing—but it is also activated by drugs of abuse. In addition, the limbic system is responsible for our perception of other emotions, both positive and negative, which explains the mood-altering properties of many drugs.

How do the parts of the brain communicate?

The brain is a communications center consisting of billions of neurons, or nerve cells. Networks of neurons pass messages back and forth among different structures within the brain, the spinal cord, and nerves in the rest of the body (the peripheral nervous system). These nerve networks coordinate and regulate everything we feel, think, and do.

  • Neuron to Neuron
    Each nerve cell in the brain sends and receives messages in the form of electrical and chemical signals. Once a cell receives and processes a message, it sends it on to other neurons.
  • Neurotransmitters – The Brain’s Chemical Messengers
    The messages are typically carried between neurons by chemicals called neurotransmitters.
  • Receptors – The Brain’s Chemical Receivers
    The neurotransmitter attaches to a specialized site on the receiving neuron called a receptor. A neurotransmitter and its receptor operate like a “key and lock,” an exquisitely specific mechanism that ensures that each receptor will forward the appropriate message only after interacting with the right kind of neurotransmitter.
  • Transporters – The Brain’s Chemical Recyclers
    Located on the neuron that releases the neurotransmitter, transporters recycle these neurotransmitters (that is, bring them back into the neuron that released them), thereby shutting off the signal between neurons.

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To send a message, a brain cell (neuron) releases a chemical (neurotransmitter) into the space (synapse) between it and the next cell. The neurotransmitter crosses the synapse and attaches to proteins (receptors) on the receiving brain cell. This causes changes in the receiving cell—the message is delivered.

How do drugs work in the brain?

Drugs are chemicals that affect the brain by tapping into its communication system and interfering with the way neurons normally send, receive, and process information. Some drugs, such as marijuana and heroin, can activate neurons because their chemical structure mimics that of a natural neurotransmitter. This similarity in structure “fools” receptors and allows the drugs to attach onto and activate the neurons. Although these drugs mimic the brain’s own chemicals, they don’t activate neurons in the same way as a natural neurotransmitter, and they lead to abnormal messages being transmitted through the network.

Other drugs, such as amphetamine or cocaine, can cause the neurons to release abnormally large amounts of natural neurotransmitters or prevent the normal recycling of these brain chemicals. This disruption produces a greatly amplified message, ultimately disrupting communication channels.

How do drugs work in the brain to produce pleasure?

Most drugs of abuse directly or indirectly target the brain’s reward system by flooding the circuit with dopamine. Dopamine is a neurotransmitter present in regions of the brain that regulate movement, emotion, motivation, and feelings of pleasure. When activated at normal levels, this system rewards our natural behaviors. Overstimulating the system with drugs, however, produces euphoric effects, which strongly reinforce the behavior of drug use—teaching the user to repeat it.

Most drugs of abuse target the brain’s reward system by flooding it with dopamine.

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How does stimulation of the brain’s pleasure circuit teach us to keep taking drugs?

Our brains are wired to ensure that we will repeat life-sustaining activities by associating those activities with pleasure or reward. Whenever this reward circuit is activated, the brain notes that something important is happening that needs to be remembered, and teaches us to do it again and again without thinking about it. Because drugs of abuse stimulate the same circuit, we learn to abuse drugs in the same way.

Why are drugs more addictive than natural rewards?

When some drugs of abuse are taken, they can release 2 to 10 times the amount of dopamine that natural rewards such as eating and sex do.15 In some cases, this occurs almost immediately (as when drugs are smoked or injected), and the effects can last much longer than those produced by natural rewards. The resulting effects on the brain’s pleasure circuit dwarf those produced by naturally rewarding behaviors.16,17The effect of such a powerful reward strongly motivates people to take drugs again and again. This is why scientists sometimes say that drug abuse is something we learn to do very, very well.

Long-term drug abuse impairs brain functioning.

What happens to your brain if you keep taking drugs?

For the brain, the difference between normal rewards and drug rewards can be described as the difference between someone whispering into your ear and someone shouting into a microphone. Just as we turn down the volume on a radio that is too loud, the brain adjusts to the overwhelming surges in dopamine (and other neurotransmitters) by producing less dopamine or by reducing the number of receptors that can receive signals. As a result, dopamine’s impact on the reward circuit of the brain of someone who abuses drugs can become abnormally low, and that person’s ability to experience anypleasure is reduced.

This is why a person who abuses drugs eventually feels flat, lifeless, and depressed, and is unable to enjoy things that were previously pleasurable. Now, the person needs to keep taking drugs again and again just to try and bring his or her dopamine function back up to normal—which only makes the problem worse, like a vicious cycle. Also, the person will often need to take larger amounts of the drug to produce the familiar dopamine high—an effect known as tolerance.

Decreased Dopamine Transporters in a Methamphetamine Abuser18

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How does long-term drug taking affect brain circuits?

We know that the same sort of mechanisms involved in the development of tolerance can eventually lead to profound changes in neurons and brain circuits, with the potential to severely compromise the long-term health of the brain. For example, glutamate is another neurotransmitter that influences the reward circuit and the ability to learn. When the optimal concentration of glutamate is altered by drug abuse, the brain attempts to compensate for this change, which can cause impairment in cognitive function. Similarly, long-term drug abuse can trigger adaptations in habit or non-conscious memory systems. Conditioning is one example of this type of learning, in which cues in a person’s daily routine or environment become associated with the drug experience and can trigger uncontrollable cravings whenever the person is exposed to these cues, even if the drug itself is not available. This learned “reflex” is extremely durable and can affect a person who once used drugs even after many years of abstinence.

What other brain changes occur with abuse?

Chronic exposure to drugs of abuse disrupts the way critical brain structures interact to control and inhibit behaviors related to drug use. Just as continued abuse may lead to tolerance or the need for higher drug dosages to produce an effect, it may also lead to addiction, which can drive a user to seek out and take drugs compulsively. Drug addiction erodes a person’s self-control and ability to make sound decisions, while producing intense impulses to take drugs.

The New Face of Heroin

The explosion of drugs like OxyContin has given way to a heroin epidemic ravaging the least likely corners of America – like bucolic Vermont, which has just woken up to a full-blown crisis.
Read more: http://www.rollingstone.com/culture/news/the-new-face-of-heroin-20140403

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Drug overdose deaths surge

Drug overdose deaths continue to surge in the United States, with most fatalities linked to the illicit use of prescription painkillers, new government statistics reveal.

Drug overdose deaths increased 23 percent between 2010 and 2014, with more than 47,000 Americans dying in 2014, the U.S. Centers for Disease Control and Prevention (CDC) data released Tuesday shows.

But updated numbers from the CDC also show that more than 52,000 people died from a drug overdose in 2015, and just over 33,000 of those deaths (63 percent) involved a prescription or illicit opioid.

The CDC noted, in its national update released Dec. 16 in the Morbidity and Mortality Weekly Report, that more than 300,000 Americans have lost their lives to an opioid overdose since 2000.

Heroin continues to be the deadliest narcotic in the United States, killing nearly 11,000 people in 2014 — nearly one of every four overdose deaths that year, according to the report by Margaret Warner, of the CDC’s National Center for Health Statistics, and colleagues. Their findings were published Dec. 20 in the agency’s National Vital Statistics Reports.

But the threat posed by the more powerful synthetic opioids, such as fentanyl, is rising exponentially as these drugs become more widely used, the investigators found.

In 2015, death rates for all synthetic opioids other than methadone increased 72 percent, while heroin death rates increased about 21 percent, the CDC reported. And the increases cut across all demographic groups, regions, and in numerous states.

Meanwhile, the death rate specifically from fentanyl more than doubled in a single year, rising from 1,905 deaths in 2013 to 4,200 deaths in 2014, according to the report by Warner’s team.

“The report really highlights what we are seeing in the emergency department,” said Dr. Robert Glatter, an emergency physician with Lenox Hill Hospital in New York City.

“We’re seeing a surge in the number of patients who are very difficult to resuscitate, who require high levels of naloxone [a medication that reverses effects of overdose]. With these patients, we often suspect synthetic opiates,” Glatter explained.

According to Emily Feinstein, director of health law and policy for the National Center on Addiction and Substance Abuse, fentanyl is a synthetic opioid manufactured largely in China that is 50 times more potent than heroin.

Glatter said that people addicted to painkillers — such as oxycodone (Oxycontin) and morphine — have increasingly turned to street drugs like heroin as enforcement restricts the availability of prescription opioids.

But, Feinstein added, heroin has opened the door for synthetic opioids like fentanyl.

“Synthetics are cheaper than heroin to make, and we’re seeing them flood the United States,” she said. “Drug dealers are cutting heroin with these synthetic drugs because it’s cheaper, and it actually makes the drug more potent. If you don’t know the heroin you’re using is being cut, the normal dose you usually take becomes deadly.”

Warner and colleagues created their new report based on a new method that uses the text from death certificates to identify specific drugs involved in overdose deaths.

The 10 most deadly drugs in 2014 were: heroin (23 percent of overdose deaths); cocaine (12.4 percent); oxycodone, (11.5 percent); alprazolam/Xanax (9 percent); fentanyl (8.9 percent); morphine (8.5 percent); methamphetamine (7.9 percent); methadone (7.4 percent); hydrocodone/Vicodin (7 percent); and diazepam/Valium (3.7 percent).

The dramatic rise in fentanyl’s death toll between 2013 and 2014 might be due to the CDC’s new method of analyzing overdose deaths, combined with increased awareness of the danger posed by the synthetic, said Dr. Harshal Kirane. He is director of addiction services at Staten Island University Hospital in New York City.

“While I think that does capture an aspect of what’s happening in the real world, part of me is curious whether that’s part of a more systematic effort to identify fentanyl during autopsies,” Kirane said.

Feinstein pointed out that greater emphasis needs to be placed on treating addicts, particularly those who survive an overdose, through use of a drug like naloxone (Narcan).

Drugs that help a person survive an opioid overdose “put you into immediate withdrawal,” Feinstein said. “You feel sick, you feel miserable, you feel awful and you have really strong cravings. And hospitals are just releasing these people, rather than putting them into effective treatment that will prevent a relapse,” she explained.

The new report by Warner’s team also underscores the role physicians play in this ongoing epidemic, Glatter said.

“We need to turn away from the knee-jerk response of using opiates to treat pain,” he said. “We have to embrace a change, because we are the ones responsible for writing these prescriptions. We have to search for other solutions.”

The new findings also highlight a threat that’s been somewhat overshadowed by opioids — the number of deaths caused by benzodiazepine drugs, such as Xanax and Valium, Kirane said.

“In my eyes, that still remains somewhat a silent epidemic in our country,” Kirane said. “A tremendous amount of emphasis is being given the role of opioids, but benzo prescribing still remains largely unbridled in our country.”

In examining the regional impact of overdose deaths from 2014 to 2015 in 28 U.S. states, the authors of the MMWR study found that the three states with the largest percentage increases in rates of deaths due to synthetic opioids other than methadone were New York, Connecticut and Illinois. The three states with the largest percentage increases in rates of heroin deaths were South Carolina, North Carolina and Tennessee, while Connecticut, Massachusetts, Ohio and West Virginia had the largest total rate increases in heroin deaths.

More information For more on prescription drug abuse, visit the U.S. Department of Health and Human Services.