Is it Murder ?

15. May 2012 by stationmanager.

In Los Angeles, former-doctor Hsiu-Ying “Lisa” Tseng was arraigned on three counts of second-degree murder in the deaths of three of her patients who overdosed on drugs she’d prescribed.

According to District Attorney Steve Cooley, Tseng’s case is a first for Los Angeles County - but around the country, as drug deaths have surpassed car accidents as the number one cause of unnatural death for Americans, more prosecutors are taking this step.
“We think it sends the right message to medical practitioners who use their license as a doctor to act as a drug dealer,” Cooley told Crimesider.

The Associated Press reports that according to a DEA affidavit, Tseng wrote more than 27,000 prescriptions over a three-year period starting in January 2007 - an average of 25 a day.

In Ohio, a state ravaged by prescription drug abuse, Assistant U.S. Attorney Timothy Oakley says that going after doctors who run so-called “pill mills,” where patients can obtain large quantities of painkillers and other drugs with little or no medical examination, has become a priority for his office.

And so far, they’ve had success: Last year, an Ohio jury convicted former-doctor Paul Volkman on four counts of illegal drug distribution that resulted in death. According to the sentencing memorandum prepared by the U.S. Attorney’s office, “For almost three years, Volkman gave hundreds of pills to anyone who paid the cash necessary to get in the door and swore that they were not a member of law enforcement… during the course of this conspiracy, Volkman was the top physician purchaser of oxycodone in the country.”
In February, Volkman received four life sentences for his crimes.
Currently, two South Florida doctors are under indictment for first-degree murder for the deaths of patients to whom they dispensed prescription drugs. According to the criminal complaint, Dr. Sergio Rodriguez killed three people “through the unlawful prescription of a controlled substance, Oxycodone, by means of a prescription issued in bad faith and not in the course of his professional practice.”

And last August, Dr. Gerald Klein was charged with first degree murder in the death of Joseph Bartolucci, who, according to the state attorney’s office obtained prescriptions for more than 200 pills from Klein’s clinic in Feb. 2009, including 150 hydromorphone and 30 Xanax tablets; he died the next day of combined drug toxicity. Klein’s co-defendants, the clinic owner and manager, have both pleaded guilty to second-degree murder. Klein is due back in court in July.

Florida State’s Attorney Michael McAuliffe told Crimesider in an email that these guilty pleas represent the first time an American “pill mill” owner has been successfully prosecuted for murder. His office calls the effort to crack down on these clinics “Operation: Prescription for Death.”

For years, prosecutors have had success charging doctors with negligence and involuntary manslaughter when their care of a person is deemed irresponsible. In January, a Los Angeles jury convicted Michael Jackson’s doctor, Conrad Murray, of involuntary manslaughter for injecting the pop star with a sleep-inducing drug normally used only in hospital settings. Murray was sentenced to four years in jail.

But it’s a long way from involuntary manslaughter - which implies no malice, or conscious disregard for life - to first- or second-degree murder. In the Tseng case, Cooley says he will argue the legal theory of “applied malice” - which says that someone who knows their actions are so reckless that there is a high potential for death, can be held criminally responsible for that death.

Colorado-based attorney Lisa Wayne says that such charges seem to her a legal overreach.

“In my opinion it overlooks the fact of the individual taking responsibility for actually taking the drugs,” says Wayne, who is the president of the National Association of Criminal Defense Lawyers. “I think there are far better ways to go after doctors who violate the standard of care than to criminally prosecute them.”

Wayne points to civil litigation, which has long been an avenue of recourse for people who believe they have been treated negligently by a physician. And outside of court, there are options as well, like taking away a doctor’s license to practice medicine.

Diane Hoffman, a professor of law at the University of Maryland who has written about physicians charged in patient deaths, says she worries that charges like those in the Tseng case will have a “chilling effect” on doctors’ willingness to treat patients with chronic pain.

“Doctors should believe their patients and not be put in a position where they’re trying to scrutinize them,” says Hoffman. “Are you prescribing within the standard of practice? That’s a medical question. And it seems the DEA and prosecutors are looking to physicians to be enforcers of the law rather than (being) doctors.”

James Tierney, a professor at Columbia University and the director of the National State Attorneys General Project, says he understands - to some degree - why law enforcement is using murder charges to try and make a dent in the major, and by many accounts, growing, public health problem of prescription drug abuse.
“The current opioid problem is like a sinking ship with 40 holes in it,” he says. “The effort to use criminal law to is an effort to plug some of those holes.”

Tierney, Hoffman and Wayne all say that while some particularly egregious examples of doctors using their licenses to irresponsibly dole out drugs for money may be worthy of prosecution, the practice will do little to put a dent in the health care crisis that is prescription drug abuse.

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Addiction Vaccines under Development

9. May 2012 by stationmanager.

Up to now, vaccines have been used effectively against a variety of infectious diseases, but what if they could be developed to treat and/or prevent addiction?

Take smoking, for example. Someone who wanted to quit would go through their usual lighting up routine, but when nicotine does not arrive in the brain, they would probably extinguish the cigarette and not light another. Without feeling nicotine’s effects, it is likely they would view smoking as a waste of money.

Or consider a vaccine against methamphetamine: Snorted or injected, the drug would not give the user a high, so what would be the point of going to the trouble of scoring this illegal drug in the first place?

Now both vaccines, for nicotine and for methamphetamine, have gone beyond the dreaming stage. Recently, the National Institute on Drug Abuse (NIDA) awarded “visionary” grants to 2 scientists who believe that in the not-too-distant future, vaccines will be available not just for smallpox and whooping cough but also for substance abuse.

Two scientists proposing to develop vaccines against methamphetamine and nicotine have been selected to receive NIDA’s second Avant-Garde Awards for Innovative Medication Development Research.

The scientists, Thomas Kosten, MD, from Baylor College of Medicine, Houston, Texas, and Peter Burkhard, PhD, from the University of Connecticut, Storrs, will each receive $500,000 per year for 5 years from NIDA to support their research.

Addiction vaccines could be life-changing for the estimated 22 million drug abusers in the United States. NIDA estimates that every year, addiction costs the country $84 billion in direct healthcare costs, lost earnings, crime, and accidents. The cost trend is rising, and researchers hope that addiction vaccines may reverse it, not only by treating addicts but also by immunizing young people before they become addicted.

Just like regular vaccines, substance abuse vaccines work by provoking the immune system to produce antibodies, which then causes the body to suspend and reject the drug before it reaches the brain. That is the goal, but thus far, success in humans has been elusive.

Dr. Thomas Kosten

Dr. Kosten is working on a novel human methamphetamine vaccine, and since at this time there is no US Food and Drug Administration (FDA)–approved medication for methamphetamine addiction, his research could have substantial effect.

Dr. Burkhard’s peptide nanoparticle antinicotine vaccine would be administered intranasally, which would be easier and less painful than an injection. He believes his de novo peptide design, coupled with nicotine, will induce a strong immune response against nicotine without the need for other chemicals to enhance it, leading to fewer adverse effects and a less expensive vaccine.

Addiction Interrupted

Both vaccines are expected to enter initial clinical trials within 5 years. They both work essentially in the same way: They induce a patient’s immune system to generate antibodies that then bind to the target drug, forming compound molecules that are too large to move from the bloodstream to the brain. Once the drug is denied access to the patient’s brain, it cannot produce the reinforcement or “high” that is the major component of the motivation to continue using it. In short, the familiar addiction cycle — drug use, resultant brain stimulation, and then a subsequent desire for continued drug use — is interrupted.

The science behind vaccines for addiction goes back to the 1950s, when researchers developed a vaccine against fatal overdoses of the heart drug digitalis.

Then, in the 1970s, at the University of Chicago, researchers working with monkey models were successful in creating antibodies to heroin in their subjects by attaching molecules of heroin to a protein from cow’s blood. This is the model on which Dr. Kosten has based his research.

Another major precedent for these 2 new addiction vaccines is the work of California researcher Kim D. Janda, PhD, from Scripps Research Institute in La Jolla, who made headlines in July when his team announced it had produced a vaccine against heroin’s effects in rats. His laboratory’s rodents stopped helping themselves to the drug after they received a vaccine, and it is thought they did so because the heroin stopped having any effect.

However, that success followed a serious setback in Dr. Janda’s work on another vaccine: A phase 2 clinical trial for a nicotine vaccine based on his work had disappointing results. Patients receiving the vaccine only quit smoking at the same rate as those receiving placebo, so the trial was haltedTo date, none of Dr. Janda’s vaccines has received FDA approval, and despite successes in animal models in his laboratory, they have not yet produced consistent results in humans.

As Dr. Janda recently told the New York Times,: “The big problem plaguing these vaccines right now is difficulty predicting in humans how well it’s going to work.”

That difficulty was revealed in widely anticipated cocaine vaccine studies, in which a bacterial protein plus a molecule that is a cocaine look-alike trained the immune system to produce antibodies that bind to any cocaine in the bloodstream.

“Like Wiping Out Switzerland”

In a 2010 vaccine study at Columbia University, New York City, conducted by Margaret Haney, PhD, with crack cocaine addicts, the level of antibodies in the volunteers varied widely. Only 38% of the cocaine users produced enough antibodies to quell the drug’s effects, and of those, only half stayed off the drug more than half the time. In a 2008 analysis of 34 behavioral studies in cocaine, methamphetamine, and marijuana addictions, improvement was seen in 67% of the addicts. “You can’t expect a medication or vaccine alone to take care of addiction,” said Dr. Haney.”I am entirely humble about that.”

Dr. Nora Volkow

NIDA Director Nora D. Volkow, MD, said Dr. Kosten and Dr. Burkhard were awarded the grants because they have already demonstrated proficiency in the laboratory with vaccines. “They also have clear plans for initiating clinical trials within an accelerated period of time,” said Dr Volkow. And that’s the goal of NIDA’s Avant-Garde Grant Program: “[T]o support investigators of exceptional creativity who propose bold and highly innovative new research approaches that have the potential to produce a major impact on the treatment of drug abuse.”

Seven million people die from smoking addiction every year. That’s like wiping out Switzerland. It’s a tremendous step forward to have a vaccine to prevent smoking, not only for these 7 million who die but also for the other countless millions who are living with their smoking addiction.

Nicotine presents a particular challenge in developing a vaccine against it, as on its own it is completely nonimmunogenic. “So you have to couple it to a carrier to induce an immune response,” he added.

Dr. Peter Burkhard

Dr. Burkhard heads the Burkhard Protein Design Group at the University of Connecticut, which has developed proprietary methods to synthetically produce nanosize protein particles. “Our greatest challenge is generating as strong an immune response as possible to induce the effect we’re looking for,” he said. “The idea has been around for awhile, and other companies have brought it into clinical trials, where they have shown that it works, but it only works if you have really high levels of antibodies. Most of the clinical trials have failed for this reason, because they were only able to induce antibodies in about 30% of the population. And that’s simply not good enough.”

Dr. Burkhard’s 18-nm particles are produced in his group’s laboratory after first being designed on a computer.

“We predict a peptide sequence that is then able to self-assemble into a particle with icosahedral symmetry,” he said. “Then we go into the lab to synthesize this peptide by biotech procedures, expressing it in [Escherichia coli], purifying it, and then refolding it. With those nanoparticles, the next step is coupling the nicotine molecule to the nanoparticle.”

No Guarantees

Under the NIDA grant timeline, Dr. Burkhard plans to spend the first year and a half developing an effective nanoparticle vaccine, “so that we can be sure that we do get enough antibodies.”

It will then take a year to manufacture enough vaccine for his 2-year phase 1 clinical trial. “That’s our expertise, developing these nanoparticles that have been shown to be very immunogenic, and we have some ‘tricks of the trade’ to really tweak the immune system to give us a very strong antibody response. There’s no guarantee that it will work, but we have confidence that we can achieve that,” said Dr. Burkhard.

In addition to his grant to develop a methamphetamine vaccine, Dr. Kosten already has a cocaine vaccine under development. Known as TA-CD, for Therapy Addiction–Cocaine Addiction, this vaccine uses an inactivated cholera protein to bind to cocaine in the user’s bloodstream. The approach is to prevent the addictive substance from ever reaching the brain, and thereby prevent the chemical cascade that results in a euphoric “high.”

It is hoped that without that high, the user’s addictive cycle will be broken. In fact, a blinded, placebo-controlled study of 114 participants conducted by Dr. Kosten and his wife, neuroscientist Therese Kosten, PhD, showed that individuals who received the vaccine were twice as likely to reduce their cocaine use by at least 50% compared with those who received placebo. The study is now under review, and the Kostens are seeking FDA approval for a larger, 300-person, multicenter trial.

What is the scientific principle behind the vaccine? Dr. Kosten explained that although most foreign substances in the body trigger an immune-system response, drugs like cocaine fail to do so because their molecules are too small. They slip across the blood–brain barrier precisely because the molecules are so tiny.

When cocaine is bound to a much larger protein…the immune system creates antibodies to both the larger protein and the drug that it carries. Then, the next time the user administers the drug, the body’s immune defenses attach onto the cocaine and break it down with enzymes.

However, when cocaine is bound to a much larger protein, such as the inactivated cholera protein that has been widely tested and found to be without adverse effects, the immune system creates antibodies to both the larger protein and the drug it carries. Then, the next time the user administers the drug, the body’s immune defenses attach onto the cocaine and break it down with enzymes. “It’s like a big sponge for cocaine,” Dr. Kosten told Medscape Medical News. “The drug remains trapped in the blood until it’s metabolized and made inactive by the liver and secreted in the kidneys.”

Users can thwart the vaccine and their fortified immune system responses by taking more cocaine than their immune system can handle, so the user has to want to slow or stop their cocaine use for the vaccine to be effective in curbing their addiction. And that is why TA-CD is currently thought of as a therapeutic drug, not a preventative, said Dr. Kosten.

Made in China

Other researchers have run into a wall in trying to find a substance that will bind to materials such as tetrahydrocannabinol, or THC, in marijuana, so the body can see that substance.

Dr. Janda has tried to make vaccines against alcohol and marijuana use, but so far the effort has failed. He said that in the case of alcohol, its ethanol molecules have proven to be too small to attach a protein to them, and in the case of marijuana, its main ingredient, THC, hides too well for the immune system to react to it.

Using cholera bacterium as a vector was an essential part of Dr. Kosten’s new cocaine vaccine, he said, because it allows the vaccine to avoid potential viral syndromes associated with other vaccines. In addition, most people in Western countries where cocaine abuse is most severe do not have natural immunity to cholera.

In Dr. Kosten’s methamphetamine vaccine, he is using a Neisseria meningitis protein as a vector.

Dr. Volkow believes the field of drug abuse treatment is on the cusp of a large paradigm shift.

A successful vaccine will make it easier for addicted individuals to establish and maintain abstinence. It will reduce the chances that isolated lapses into drug taking escalate into protracted relapses. Ideally, a single dose will remain effective for months or longer.

“Vaccines have a unique role to play in a comprehensive strategy to help people overcome addictions. A successful vaccine will make it easier for addicted individuals to establish and maintain abstinence. It will reduce the chances that isolated lapses into drug taking escalate into protracted relapses. Ideally, a single dose will remain effective for months or longer,” she said.

Although NIDA views vaccines as a potentially powerful tool to aid addicts from their illegal drugs, pharmaceutical companies are not lining up with research grants, say these researchers.

They believe the pharmaceutical companies do not see much money to be made in a shot that is given once every 6 months, and also perhaps because the companies are not anxious to associate their companies with drug addicts.

“Pharma does not see a profit in these vaccines, and only sees great risk in this population due to their lifestyle and [potential for] overdoses,” said Dr. Kosten.

Dr. Kosten is taking his methamphetamine vaccine manufacturing and clinical trial to China, as his greatest challenge has been in finding a domestic manufacturer. “We’ve had no success doing this in the United States, but we have had success in China. We will manufacture the vaccine in China and do clinical trials there after getting Chinese FDA approval about 3 years from now. A placebo-controlled study will compare vaccinated [groups] to placebo groups during a 6-month outpatient clinical trial. We’ll have the vaccine in humans in 4 years and have a commercial product in 10 years,” he said.

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My Daddy Drinks Too Much

23. April 2012 by stationmanager.

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LSD ‘helps alcoholics to give up drinking’

16. April 2012 by stationmanager.

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Researchers at the Norwegian University of Science and Technology analysed earlier studies on the drug between 1966 and 1970.Patients were all taking part in alcohol treatment programmes, but some were given a single dose of LSD of between 210 and 800 micrograms.

Dangers of LSD

•        During a trip the person may put themselves in danger without realising it such as thinking they can fly and trying to jump off a high building.

•        In some people, especially if LSD is taken in high doses, the drug can cause intense anxiety and panic attacks.

•        Some people experience flashbacks, reliving a bad trip weeks or even months after it happened.

•        In those already vulnerable, LSD may be the trigger for psychotic illness. Paranoia and other symptoms typical of schizophrenia may occur.

For the group of patients taking LSD, 59% showed reduced levels of alcohol misuse compared with 38% in the other group.

This effect was maintained six months after taking the hallucinogen, but it disappeared after a year. Those taking LSD also reported higher levels of abstinence.

The report’s authors, Teri Krebs and Pal-Orjan Johansen, said: “A single dose of LSD has a significant beneficial effect on alcohol misuse.”

They suggested that more regular doses might lead to a sustained benefit.

“Given the evidence for a beneficial effect of LSD on alcoholism, it is puzzling why this treatment approach has been largely overlooked,” they added.

Prof David Nutt, who was sacked as the UK government’s drugs adviser, has previously called for the laws around illegal drugs to be relaxed to enable more research.

He said: “Curing alcohol dependency requires huge changes in the way you see yourself. That’s what LSD does.

“Overall there is a big effect, show me another treatment with results as good; we’ve missed a trick here.

 

 

  

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The Dark Side of Addiction

4. April 2012 by stationmanager.

Drug addiction is a chronic relapsing disorder. Neurobiological changes are the basis for compulsive drug-taking, accompanied by loss of control over drug intake and the emergence of a negative emotional state when access to the drug is blocked.[1,2] Clinically, a distinction is made between the escalated drug use of addiction and the occasional but limited taking of drugs with the potential for abuse and dependence.[2]
As addiction develops, neuroplastic brain reward systems are transformed.[3] This is the “dark side” of drug addiction: the decline in normal reward-related neural mechanisms and persistent recruitment of the brain’s antireward systems that accompany drug use.[3] Progressive worsening of the brain reward system perpetuates compulsive use of the drug.[4]
George F. Koob, PhD, of the Scripps Research Institute in La Jolla, California, studies the behavior of rodents in an effort to understand the neuropharmacologic and neuroadaptive mechanisms that enable the crossover from occasional, controlled drug user to the behaviors of an addict.[5] Knowledge of these neurochemical systems may elucidate vulnerability to addiction and suggest pharmacotherapies for drug addiction.[3]
Cycle of Addiction
Drug addiction has elements of both an impulse control disorder and a compulsive disorder that are mediated by separate but overlapping neural circuits. The individual with an impulse control disorder experiences an increasing sense of tension or arousal before committing the impulsive act such as drug-taking; pleasure, gratification or relief during the act; and in some cases, regret, self-reproach or guilt following the act.[4] The individual with a compulsive disorder feels anxiety and stress before the compulsive, repetitive act, and relief from stress by performing the act. In the progression from an impulsive disorder to a compulsive disorder, the motivation for the behavior shifts from positive reinforcement to negative reinforcement, when removal of the aversive state increases the probability of the behavior.[3] Drug addiction follows this pattern in a collapsed cycle of addiction involving 3 stages:
• Binge/intoxication;
• Withdrawal/negative affect; and
• Preoccupation/anticipation (craving).
Addiction involves a long-term persistent plasticity of the neural circuits that control 2 different reward systems: declining function of brain reward systems driven by natural rewards and stimulation of antireward systems that bring on aversive states.[3]
Brain Reward System
Studies of the acute reinforcing effects of drugs of abuse in the binge/intoxication stage have identified the neurobiological substrates involved in the reward response. Drugs with the potential for abuse and dependence, such as the opioid analgesics, initially produce positive reinforcing effects from actions at the ventral tegmental area in the midbrain and the nucleus accumbens and amygdala of the basal forebrain.[2] Activation of the mesocorticolimbic dopamine pathway is the primary route of positive reinforcement in addiction for psychostimulant drugs, but the opioid peptides (endorphins), serotonin, and gamma-aminobutyric acid (GABA) have key roles for nonpsychostimulant drugs. These so-called “reward neurotransmitters” induce hedonic effects of euphoria and a feeling of well-being.
Brain Antireward System
Withdrawal from a drug of abuse induces symptoms of negative affect such as dysphoria, depression, irritability, and anxiety. Dysregulation of brain reward systems involves some of the same neurochemical pathways implicated in the drug’s acute reinforcing effects, but in this case, they represent an opponent process.[4,6] During acute abstinence, increases in brain reward thresholds (a higher set point for drug reward) are a consequence of altered reward neurotransmitters. This in turn may contribute to the negative motivational state of withdrawal and vulnerability to relapse.[2] Neurochemical changes during opioid withdrawal include decreases in dopaminergic and serotonergic transmission and increased sensitivity of opioid receptor transduction mechanisms. Escalating doses of opioids, like those seen in the human pattern of morphine or heroin use, are associated with profound alterations in the function of mu-opioid receptors.[1] A decrease in baseline reward mechanisms leads to an increase in drug intake to compensate for the shift in reward baseline.[7]
For the addict, the situation deteriorates.[8] Stress response systems of the body contribute to the negative emotional state associated with abstinence and can exacerbate drug taking throughout the addiction cycle. In response to taking the drug, the neuroendocrine system kicks in to attempt to restore the brain to normal function.[2] Chronic drug use adversely affects the hypothalamic-pituitary-adrenal axis, disrupting regulation of hypothalamic corticotropin releasing factor (CRF). Particularly important is activation of CRF in the extrahypothalamic brain stress system of the extended amygdala. The extended amygdala is a structure comprised of the bed nucleus of the stria terminalis, the central nucleus of the amygdala, and a transition zone in the medial subregion of the nucleus accumbens and a major projection to the lateral hypothalamus.[8] CRF controls hormonal, sympathetic, and behavioral responses to stress. During acute withdrawal of the drug, production of adrenocorticotropic hormone, corticosterone, amygdala CRF, norepinephrine, dynorphin, and inhibition of neuropeptide Y induce brain arousal, stress-like responses, and a dysphoric, aversive state. The activation and recruitment of brain and hormonal stress responses contribute to a deviation in brain reward set point.[7] These are the sources of negative reinforcement that lead to compulsive drug-seeking behavior and addiction.
Craving and Relapse
The preoccupation/anticipation stage of the addiction cycle is mediated via afferent projections to the extended amygdala and nucleus accumbens. There are different stimuli for craving a drug of abuse, leading to relapse. It can be drug-induced, cue-induced, or stress-induced.[3]
Chronic relapse is a significant problem in drug addiction, with about half of all addicts relapsing into drug taking.[8] Addicts can return to compulsive drug taking long after acute withdrawal exhibiting behavior that corresponds to the preoccupation/anticipation stage of addiction.[4] Drug-related cues and stressors are a powerful inducement to return to drug use.[8] Areas of the brain associated with drug and cue-induced reinstatement are the prefrontal cortex (orbitofrontal, medical prefrontal, prelimbic/cingulate), and the basolateral amygdala. The neurotransmitters involved in relapse are dopamine, opioid peptides, glutamate, and GABA. Relapse can also be precipitated by stress and the release of CRF, glucocorticoids and norepinephrine. Many different stressors can provoke drug craving and drug-seeking behavior.[8]
Animal Studies
It has been possible to study the effects of both short- and long-term exposure to drugs of abuse in a rodent extended-access model. This animal model has been used to study the transition from drug use to addiction, including such behaviors as escalating drug intake driven by dependence, self-administering drug despite adverse consequences, and a narrowing of the behavioral repertoire for drug seeking.[5,7] Extended access to drugs of abuse produces dramatic increases in drug intake and dependence over time that mirror human behavior. Extended access also produces anxiety-like responses mediated by an increase in extracellular CRF secreted by the central nucleus of the amygdala during withdrawal, effects that are reversed by CRF receptor antagonists. Giving a CRF receptor antagonist blocks excessive drug taking, providing promise for a possible treatment for addiction.[6]
Evidence from animal research also supports the similarities between stress and drugs of abuse in their effects on neurochemistry, electrophysiology, and morphology of neurons in the reward pathway. Exposing a rodent to an acute stressor increases the release of CRF and corticosterone in the hypothalamic pituitary adrenal axis, which in turn activates CRF in the amygdala. Molecular studies support the concept that stress and addictive drugs act through common molecular mechanisms within similar brain circuits to perpetuate the addiction cycle.[8] The long-lasting nature of addiction suggests that changes in gene expression might be required for the development and persistence of this disease.[8]
Summary
Rewards are pleasurable, but addictions hurt. The neurobiological underpinnings of reward and addiction involve different but overlapping neuroanatomic circuits.
Addiction is not a single incident, but rather occurs by a series of events initiated by the acute rewarding effects of drugs followed by a transition into chronic drug use.[8] Drug addiction is associated with a long-term persistent decrease in the function of normal motivational systems driven by 2 sources: (1) decreased function of brain reward systems (mediating natural rewards) and (2) increased antireward systems recruited in an opponent process to excessive activation of the brain reward system.
The deficit state for normal reward that is produced by excessive drug taking, rather than a hyperactive or sensitized reward state for drugs per se, is the motivation to seek drugs. Excessive drug taking results in not only the short-term amelioration of the reward deficit but also in suppression of the antireward system.[5]
Acute withdrawal of all major drugs of abuse increases brain reward thresholds, anxiety-like responses, and CRF in the amygdala that are of motivational significance. The amygdala has powerful emotional machinery, and brain stress responses recruit its dark side. Worsening of the underlying neurochemical dysregulations (decreased dopamine and opioid peptide function, increased CRF activity) lead to a chronic deviation of reward set point that is fueled not only by dysregulation of reward circuits but also by recruitment of brain and hormonal stress responses.[5] Brain arousal stress systems in the extended amygdala may be important not only for the negative emotional states that drive dependence on drugs of abuse but also may overlap with the negative emotional components of chronic pain syndromes.
________________________________________
References
1. Koob G, Kreek MJ. Stress, dysregulation of drug reward pathways, and the transition to drug dependence. Am J Psychiatry. 2007;164:1149-1159. Abstract
2. Koob GF. The neurobiology of addiction: a neuroadaptational view relevant for diagnosis. Addiction. 2006;101(Suppl 1):23-30. Abstract
3. Koob GF, Le Moal M. Plasticity of reward neurocircuitry and the ‘dark side’ of drug addiction. Nat Neurosci. 2005;8:1442-1444. Abstract
4. Koob GF, Le Moal M. Addiction and the brain antireward system. Annu Rev Psychol. 2008;59:29-53. Abstract
5. Koob G. The dark side of addiction: relevance to pain medicine. Paper presented at: the 24th Annual Meeting of the American Academy of Pain Medicine; February 12-16, 2008; Orlando, Florida.
6. Koob GF, Le Moal M. Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology. 2001;24:97-129. Abstract
7. Cleck JN, Blendy JA. Making a bad thing worse: adverse effects of stress on drug addiction. J Clin Invest. 2008;118:454-461. Abstract
8. Adinoff B. Neurobiologic processes in drug reward and addiction. Harv Rev Psychiatry. 2004;12:305-320. Abstract

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Drug Education Needed for Doctors

28. March 2012 by stationmanager.

In 2011 a group of physicians descended on Capitol Hill to ask congress to help them fight prescription drug abuse. How? Finally require all health care professionals get real training in prescribing addictive drugs, recognizing signs of addiction, and identifying problematic patterns of use.Most physicians receive little or no training regarding substance abuse and the use of controlled substances that have the potential for addiction. While there are many doctors who prescribe these powerful drugs responsibly, and these drugs are often critically important when used as intended (usually very short-term use or on an as-needed basis), better education will help them recognize drug-seeking behavior and train them to evaluate and refer these patients to treatment the same way they do when they see high blood sugar or blood pressure.

Some years ago a recovering addict with over five years clean and sober related to me a story about their doctor. They had been having some anxiety lately, and had been working on it through meditation, exercise, and nutrition, but still wanted the doctor to check if there might be something else contributing to what felt like sudden bursts of adrenalin: heart racing, sick feeling in the stomach, and shortness of breath. The doctor opined that it must be an anxiety attack.

“I’ll write you a prescription for Xanax,” the doctor told the patient. “Just take one when you feel an attack coming on.”

The recovering addict reminded the doctor that he is in recovery and cannot “just take one” when he feels like it. He would be taking “just one” all the time within a matter of days or weeks.

The doctor’s response was, “One pill isn’t going to send you back to the Garden of Eden.”

Fortunately this recovering addict understood what his doctor did not. ‘Just one’ is not possible for those with addiction. Anyone who has ever been addicted to a drug is 10 times more likely to become addicted again than the general population. My friend declined the prescription and changed doctors.

When we hear about celebrities like Michael Jackson and now Whitney Houston — people with a known history of substance abuse and stints in rehab — getting prescriptions for highly addictive drugs such as Xanax and Valium, we wonder why anyone would even consider prescribing these medications.

However, as long as physicians do not truly understand addiction (that it is a brain disease) and we do not give them tools to intervene when patients are in trouble (treatment is getting harder to cover with insurance), this pattern will continue. We cannot keep beating the drums of blame without creating mechanisms for change.

We often wonder about the family members and friends who wring their hands in despair when a loved one dies and drugs appear to be the cause. Did they really not know this was the potential end to the behavior?

The truth is denial can play a huge part in allowing dangerous behavior to continue. If the celebrity switches from illegal drugs such as cocaine or heroin to something prescribed, such as OxyContin or Valium, the family actually breathes a sigh of relief. They figure it’s prescribed so it must be safe. Nothing could be further from the truth.

Addiction is addiction. Where the drug is obtained (on the street or from the local pharmacy) and the reasons given as to why it’s “needed” (anxiety, insomnia) are really irrelevant once use has escalated to abuse.

I have actually heard of physicians who naively “help” alcoholic patients stay sober by prescribing them Valium to deal with their anxiety now that they aren’t drinking. It’s hard to believe a doctor doesn’t understand that they are just switching the drug of choice, but in fact many do not.

Mandatory education of our nation’s doctors, who by law serve as the gatekeepers of addictive prescription drugs, is long overdue. However, this should not mean we blame doctors for an addict’s behavior. Even if all doctors stopped prescribing addictive drugs, we would still have addiction. It’s a powerful disease, and the biggest obstacle that addicts who want to get better face is lack of access to treatment.

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