Category: Opium

Acupuncture has been used in East-Asian medicine for thousands of years to treat pain, possibly by activating the body's natural painkillers. But how it works at the cellular level is largely unknown.

Using brain imaging, a University of Michigan study provides novel evidence that traditional Chinese acupuncture affects the brain's long-term ability to regulate pain.

The results appear online ahead of print in the September Journal of NeuroImage.

In the study, researchers at the U-M Chronic Pain and Fatigue Research Center showed acupuncture increased the binding availability of mu-opoid receptors (MOR) in regions of the brain that process and dampen pain signals – specifically the cingulate, insula, caudate, thalamus and amygdala.

Opioid painkillers, such as morphine, codeine and other medications, are thought to work by binding to these opioid receptors in the brain and spinal cord.

"The increased binding availability of these receptors was associated with reductions in pain," says Richard E. Harris, Ph.D., researcher at the U-M Chronic Pain and Fatigue Research Center and a research assistant professor of anesthesiology at the U-M Medical School.

One implication of this research is that patients with chronic pain treated with acupuncture might be more responsive to opioid medications since the receptors seem to have more binding availability, Harris says.

These findings could spur a new direction in the field of acupuncture research following recent controversy over large studies showing that sham acupuncture is as effective as real acupuncture in reducing chronic pain.

"Interestingly both acupuncture and sham acupuncture groups had similar reductions in clinical pain," Harris says. "But the mechanisms leading to pain relief are distinctly different."

The study participants included 20 women who had been diagnosed with fibromyalgia, a chronic pain condition, for at least a year, and experienced pain at least 50 percent of the time. During the study they agreed not to take any new medications for their fibromyalgia pain.

Patients had position emission tomography, or PET, scans of the brain during the first treatment and then repeated a month later after the eighth treatment.

Additional authors were Jon-Kar Zubieta, M.D., Ph.D., David J. Scott, Vitaly Napadow, Richard H. Gracely, Ph.D, Daniel J. Clauw, M.D.

Funding was provided by the Department of Army, and the National Institutes of Health.

Journal Reference:

1. Richard E. Harris, Jon-Kar Zubieta, David J. Scott, Vitaly Napadow, Richard H. Gracely, Daniel J. Clauw. Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on μ-opioid receptors (MORs). Journal of NeuroImage, 2009; 47 (3): 1077-1085 DOI: 10.1016/j.neuroimage.2009.05.083

 Taking opioid drugs without a prescription appears relatively common among high school seniors, according to a new report. The most common reasons survey respondents gave for taking the medications included relaxation, feeling good or getting high, experimentation and pain relief.

"Prescription opioids are the foundation for the treatment of acute and chronic pain and these medications are highly efficacious when used properly," the authors write as background information in the article. "However, the non-medical use [without a clinician's orders] of prescription opioids has increased significantly among adolescents and young adults over the past decade in the United States."

Sean Esteban McCabe, Ph.D., of the University of Michigan, Ann Arbor, and colleagues assessed survey responses from five consecutive groups of seniors at public and private high schools throughout the United States between 2002 and 2006. The 12,441 students filled out questionnaires reporting whether they had used opioids such as morphine, opium or codeine for medical or non-medical reasons over the past year or ever in their lifetimes. Those who reported non-medical use selected their most important reasons for doing so from a list of 17 potential motives. The students also were asked about methods used for taking the drugs (for example, smoking or in pill form) and any other substance use habits.

More than one in every ten participants—a total of 12.3 percent—reported using prescription opioids for non-medical reasons in their lifetimes, including 8 percent who reported having done so in the past year. The leading motives were to relax or relieve tension (56.4 percent), to feel good or get high (53.5 percent), to experiment (52.4 percent), to relieve physical pain (44.8 percent) or to have a good time with friends (29.5 percent).

Students who said they used the drugs only for pain relief were less likely to also report heavy drinking or other drug use than were those who took them for other reasons or who reported multiple motivations that included pain relief. "Future clinical and research efforts should attempt to differentiate between motives for non-medical use of prescription opioids because the present study identified subtypes that were significantly associated with medical use of prescription opioids and substance use behaviors," the authors write.

"Notably, we found that more than seven in every 10 non-medical users of prescription opioids motivated by pain relief reported a lifetime history of medical use of prescription opioids," they continue. Other studies indicate that many adolescents obtain opioids from their own previous prescriptions. "These results suggest that appropriate pain management and careful therapeutic monitoring could contribute to reductions in the non-medical use of prescription opioids among adolescents."

Screening efforts should be used to differentiate between adolescents who need help with pain management and those who need a more comprehensive assessment for substance use disorders, they conclude.

The development of the manuscript and the data collection were supported by research grants from the National Institute on Drug Abuse, National Institutes of Health.

Journal Reference:

1. Sean Esteban McCabe, PhD; Carol J. Boyd, PhD; James A. Cranford, PhD; Christian J. Teter, PharmD. Motives for Nonmedical Use of Prescription Opioids Among High School Seniors in the United States Self-treatment and Beyond. Arch Pediatr Adolesc Med., 2009;163(8):739-744

Overconsumption of fatty, sugary foods leads to changes in brain receptors, according to new animal research at Johns Hopkins University School of Medicine.  The new research results are being presented at the 2009 annual meeting of the Society for the Study of Ingestive Behavior (SSIB). The results have implications for understanding bulimia and other binge eating disorders.

Dr. Bello and colleagues report that either continuous eating or binge eating a high fat, high sugar diet alters opioid receptor levels in an area of the brain that controls food intake. Opioids are a family of chemicals with actions similar to those of morphine; however, opioids exist naturally in the brain and have been linked to feelings of pleasure and euphoria. “These results are interesting because we saw changes in opioid receptor gene expression in a brain area that controls how much we eat during a meal”, said Bello.

The new findings suggest that overconsumption of highly palatable foods maintains bingeing by enhancing opioids in the brain, and that increased opioids could be a factor involved in binge eating disorders. These findings may help to understand the biological basis of eating disorders.

This research was supported by NIH DK19302 and DK078484.

The lead author was Nicholas Bello, Dept. of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.

  Co-authors were F. CASSEUS, M.T. CHUANG, B.A. MITCHELL, Z.W. PATINKIN, P. SINGH, T.H. MORAN. Johns Hopkins University, School of Medicine, Dept. Psychiatry and Behavioral Sci., Baltimore, MD, USA

Chemical dependency and recovery in patients and physicians are closely examined in a series of articles and editorials in the July 2009 issue of Mayo Clinic Proceedings. The subject is especially timely. As the immense challenges, including potential tragedies, of prescription chemical addiction and abuse are being discussed, these articles offer crucial overview, direction and optimism.

Addiction to and abuse of prescription opioid drugs are prevalent, and they exact an immense toll on patients, physicians and society, according to Steven Passik, Ph.D., Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center, New York, in "Issues in Long-Term Opioid Therapy: Unmet Needs, Risks, and Solutions."

Opioid drugs have been used by humans for thousands of years and are the longest continuously used class of medications, explains William Lanier, M.D., editor-in-chief of Mayo Clinic Proceedings. Dr. Lanier and Evan Kharasch, M.D., Ph.D., Department of Anesthesiology, Washington University in St. Louis, authored the editorial "Contemporary Clinical Opioid Use: Opportunities and Challenges." It summarizes the recent increased interest in this drug category.

Opioid medications are chemicals that work by binding to specific receptors, particularly in the nervous system and gastrointestinal tract; decrease perception of pain and reaction to pain; and increase pain tolerance. Side effects include sedation, respiratory depression and constipation. When opioid consumption is ongoing, physical dependence can and will develop. This, in turn, can lead to problematic withdrawal upon abrupt discontinuation of medication. Dependence, coupled with the feeling of euphoria these drugs can produce, leads to abuse.

According to Dr. Lanier, the recent growing interest in opioids stems from five sources: advances in the design of these drugs; expansion and innovation in methods of drug delivery; increased public awareness of pain management options and the appropriateness of aggressively treating pain as the "fifth vital sign" and pain relief as a fundamental human right; growing recognition of the serious consequences of opioid misuse, misadventure and addiction; and medicolegal aspects of practitioners' prescribing practices and legal consequences for under- or overprescribing.

In addition to individuals who have chronic pain, both cancer and non-cancer related, anesthesiologists have the greatest risk of opioid dependence and abuse among health care providers. Also in the high-risk group for health care providers are nurse anesthetists and sedation nurses. Challenges specific to these groups are discussed by Michael Oreskovich, M.D., Washington Physicians Health Program in Seattle, and Ryan Caldeiro, M.D., Department of Psychiatry and Behavioral Sciences at the University of Washington, Seattle, in "Anesthesiologists Recovering From Chemical Dependency: Can They Safely Return to the Operating Room?"

Severe chronic pain includes that produced by cancer and such non-cancer conditions as back injury and surgery. Opioids are a cornerstone of pain management for individuals in these categories, according to Howard Smith, M.D., Department of Anesthesiology, Albany Medical College, N.Y. In "Opioid Metabolism," he writes that approximately 10 percent to 20 percent of physicians will develop a substance abuse problem during their career, a rate similar to or exceeding the general population. For anesthesiologists, according to Drs. Oreskovich and Caldeiro, the increased risk is cited as an occupational hazard because of the highly addictive medications they administer to patients daily.

Health care professionals helping patients with chronic pain must balance aggressive treatment with the need to minimize the risks of misuse and abuse, according to Dr. Passik. In "A Comparison of Long- and Short-Acting Opioids for the Treatment of Chronic Noncancer Pain," Charles Argoff, M.D., and Daniel Silvershein, M.D., both from the Department of Neurology, Albany Medical College, N.Y., write that management of chronic non-cancer pain, for example, requires comprehensive assessment of each patient; the establishment of a structured treatment regimen or program; ongoing reassessment of the pain condition and the response to therapy; and a continual appraisal of the patient's adherence to the treatment. Their colleague, Dr. Smith, stresses the importance of understanding the metabolism of opioids in individual patients.

Keen awareness by family and friends of potential addiction is crucial for physicians and other health care providers, not to mention the general public, who might be at risk, according to "Chemical Dependency and the Physician" by Keith Berge, M.D., Department of Anesthesiology, Mayo Clinic; Marvin Seppala, M.D., Hazelden Foundation, Center City, Minn.; and Agnes Schipper, J.D., Mayo Clinic Legal Department. Especially important is that family, friends and co-workers of health care providers confront any suspected addiction and abuse because of the potential harm that might befall the individual and his or her patients. Health care facilities should have written policies and procedures in place to assist when these highly emotionally charged situations involving health care providers occur, Dr. Berge and his colleagues write. Long-term recovery and sobriety can be achieved with appropriate treatment, aftercare and monitoring, they add.

New opioid formulas designed to minimize abuse are now in late-stage development and could help, Dr. Passik says. These drugs are chemically designed to diminish euphoric effects, thus possibly reducing problematic use. For now, responsibility coupled with expertise, insight, diligence and compassion are among the components that can meet the challenges of opioid use in pain management, the authors agree.

Journal References:

1. Passik et al. Issues in Long-term Opioid Therapy: Unmet Needs, Risks, and Solutions. Mayo Clinic Proceedings, 2009; 84 (7): 593 DOI: 10.4065/84.7.593
2. Oreskovich et al. Anesthesiologists Recovering From Chemical Dependency: Can They Safely Return to the Operating Room?Mayo Clinic Proceedings, 2009; 84 (7): 576 DOI: 10.4065/84.7.576
3. . Opioid Metabolism. Mayo Clinic Proceedings, 2009; 84 (7)
4. Argoff et al. A Comparison of Long- and Short-Acting Opioids for the Treatment of Chronic Noncancer Pain: Tailoring Therapy to Meet Patient Needs. Mayo Clinic Proceedings, 2009; 84 (7): 602 DOI: 10.4065/84.7.602
5. . Chemical Dependency and the Physician. Mayo Clinic Proceedings, 2009; 84 (7)

 Using an opioid drug to induce a hibernatory state in rats reduces the damage caused by an artificial stroke. Researchers have shown that those animals put into the chemical fugue suffered less behavioral dysfunctions after a period of cerebral artery blockage than control rats.

Cesar Borlongan, a neuroscientist at the University of South Florida Center for Aging and Brain Repair, in Tampa, FL, worked with a team of researchers from the National Institutes of Health, USA, to investigate the role of the opioid system in brain injury and protection. He said, "Studies in hibernating and active squirrels have shown that 'natural hibernation' has anti-ischemic effects. We've shown that a drug that induces hibernation can achieve similar results".

Borlongan and his colleagues dosed the rats with [D-ala2,D-leU5]enkephalin (DADLE), a drug from the same pharmaceutical family as morphine and heroin. They found that, after an experimental stroke, the pretreated animals performed better than control rats in a series of behavioral tests.

The researchers write, "DADLE prevented cell death processes and behavioral abnormalities. The observation that this substance, previously shown to induce hibernation, attenuated deficits inherent in cerebral ischemia provides a new pharmacological target for stroke therapy".

Journal Reference:

1. Cesar V Borlongan, Teruo Hayashi, Peter R Oeltgen, Tsung-Ping Su and Yun Wang. Hibernation-like state induced by an opioid peptide protects against experimental stroke. BMC Biology, 

NewsPsychology (May 17, 2009) — Morphine patches are supposed to reduce use of painkillers, and provide more control over their use in chronic pain conditions. But researchers at the Norwegian University of Science and Technology (NTNU) and St. Olavs Hospital in Trondheim have found otherwise.

The sales of new morphine patches have grown explosively in Norway since they were first introduced to the market in 2005. But researchers at NTNU and St. Olavs Hospital have found this development worrying, because their research shows that these types of plasters are often used incorrectly, or based on the wrong assumptions. The consequences can create drug dependency problems.

“The reason for this incorrect usage is that there is not enough information out there, and a lack of expertise in individuals who are writing prescriptions,” says Professor Petter Borchgrevink, head of the Norwegian National Centre for Complex Disorders.

Should reduce the risk

The patch works in the same manner as a nicotine patch, with the clear difference that a nicotine patch is used to reduce the craving for cigarettes, while a morphine patch is used to reduce pain. But both provide small, steady doses of their active ingredients over a longer time period.

This method of medication is best for patients who need low doses of pain-relieving medicine. In a perfect world, it makes sense: the medication could be more controlled, drug consumption could be reduced, and the risk of dependence should therefore be less.

Now it turns out that incorrect use of the patches can make problems worse, so that the effect is the opposite of what was intended.

An addition, not a substitute

The patch came onto the Norwegian market in 2005. It was the first morphine-like drug marketed for chronic pain that is not caused by cancer. But the danger of misuse was great, and Borchgrevink and Professor Stein Kaasa at NTNU decided to follow up on whether the patches were being used correctly.

The pair started a research project in cooperation with the Norwegian Institute of Public Health. Now the conclusions are clear: Instead of being substituted for another habit-forming medication, the morphine patches were often being given in addition to other drugs.

“This increases the health burden and the risk of addiction, “says Borchgrevink.

He adds that this is especially true for a large group of chronic pain patients that did not use morphine-based medications before given the patch.

Substance abuse a major risk

“For some patients, it would be appropriate to give morphine-like drugs for strong chronic pain”, says Kaasa, who is a specialist in pain relief medicine and director of NTNU’s research group on cancer and palliation.

“The big challenge is to avoid backsliding when it comes to medical indications for the use of the drug; in other words, we don’t want the drug to be given to patients who do not need it. Experience from other countries, including Denmark, shows that the large consumption of morphine and similar drugs by people with chronic pain that is not caused by cancer can provide significant problems with addiction.”

For these patients the use of the patch can amount to substance abuse, and many end up with major addiction problems. Patients who use multiple addictive medications at the same time are particularly vulnerable, Kaasa says.

Significance for other countries

The study was conducted in connection with the Prescription Registry, which was created by the Norwegian Institute of Public Health in 2004. The researchers wanted to find out which patients were being given prescriptions for the patches, and how many got them. They also wanted to know what other kinds addictive medications the patients were using in addition to the patch. 

Professor Svetlana Skurtveit at the Institute of Public Health said that half of all patients were given more than one prescription. More than 90 per cent had used morphine-based medicines before. More than 60 per cent continued to use other drugs in addition to the patch, including morphine preparations and other types of addictive medicines. 

“In the course of a year, sales doubled, and they continue to skyrocket”, Skurtveit says.

The study was published internationally and has received considerable attention. “Our findings may have special significance for countries that don’t yet have a morphine patch on the market”, says Skurtveit.

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The above story is reprinted (with editorial adaptations by newsPsychology staff) from materials provided by The Norwegian University of Science and Technology, via AlphaGalileo.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of NewsPsychology or its staff.

— Fish don't make noises or contort their faces to show that it hurts when hooks are pulled from their mouths, but a Purdue University researcher believes they feel that pain all the same.

Joseph Garner, an assistant professor of animal sciences, helped develop a test that found goldfish do feel pain, and their reactions to it are much like that of humans. 

"There has been an effort by some to argue that a fish's response to a noxious stimuli is merely a reflexive action, but that it didn't really feel pain," Garner said. "We wanted to see if fish responded to potentially painful stimuli in a reflexive way or a more clever way."

Garner and Janicke Nordgreen, a doctoral student in the Norwegian School of Veterinary Science, attached small foil heaters to the goldfish and slowly increased the temperature. The heaters were designed with sensors and safeguards that shut off the heaters to prevent any physical damage to a fish's tissue.

Half of the fish were injected with morphine, and the others received saline. The researchers believed that those with the morphine would be able to withstand higher temperatures before reacting if they actually felt the pain. However, both groups of fish showed a response at about the same temperature.

Because both groups of fish wriggled at about the same temperature, the researchers thought the responses might be more like a reflex than a cognitive reaction to experiencing pain. The reflexive response is similar to a person involuntarily moving a hand off a hot stove with which they had come into contact. The reaction happens before a person actually experiences pain or understands that they have been hurt.

Upon later observation in their home tanks, however, the researchers noticed that the fish from each group were exhibiting different behaviors.

"The fish given the morphine acted like they always had: swimming and being fish," Garner said. "The fish that had gotten saline – even though they responded the same in the test – later acted different, though. They acted with defensive behaviors, indicating wariness, or fear and anxiety."

Nordgreen said those behavioral differences showed that fish can feel both reflexive and cognitive pain.

"The experiment shows that fish do not only respond to painful stimuli with reflexes, but change their behavior also after the event," Nordgreen said. "Together with what we know from experiments carried out by other groups, this indicates that the fish consciously perceive the test situation as painful and switch to behaviors indicative of having been through an aversive experience."

Garner believes that the morphine blocked the experience of pain, but not behavioral responses to the heat stimulus itself – either because the responses were reflexive or because the morphine blocked the experience of pain, but not the experience of an unusual stimulus.

"If you think back to when you have had a headache and taken a painkiller, the pain may go away, but you can still feel the presence or discomfort of the headache," Garner said.

Those with saline both experienced pain in the test, as well as responding to it, and were able to cognitively process that pain, thus causing the later fear and anxiety.

"The goldfish that did not get morphine experienced this painful, stressful event. Then two hours later, they turned that pain into fear like we do," Garner said. "To me, it sounds an awful lot like how we experience pain."

The findings could raise questions about slaughter methods and how fish are handled in research. Garner said standards of care could be revisited to ensure fish are being treated humanely.

Journal Reference:

1. Nordgreen et al. Thermonociception in fish: Effects of two different doses of morphine on thermal threshold and post-test behaviour in goldfish (Carassius auratus). Applied Animal Behaviour Science, 2009; DOI: 10.1016/j.applanim.2009.03.015

Researchers at the Hebrew University of Jerusalem have found a way to maintain the pain-killing qualities of morphine over an extended period of time, thus providing a solution for the problem of having to administer increasing dosages of the drug in order to retain its effectiveness.

One of the limitations in long-term use of morphine for pain relief is the rapid development of tolerance. The effectiveness of morphine declines quickly, and one must increase the dosage in order to preserve effective pain relief. However, the increased dosage also increases negative side effects.

The Hebrew University researchers, Prof. Yehuda Shavit and his graduate student Gilly Wolf of the Psychology Department, found that administration of morphine causes a substance called interleukin-1 to be released.

Under normal circumstances, interleukin-1 plays an important role in survival. In case of tissue damage, nerve injury, or inflammatory reaction, inteleukin-1 is released and sets off a process which increases the sensitivity to pain in the injured area. This pain serves as a warning signal, telling the body that there is a problem that should be attended to. In case of chronic pain, morphine is still the drug of choice for pain relief.

However, since prolonged administration of morphine raises the level of interleukin-1, thereby enhancing pain sensitivity, the effectiveness of morphine as a pain killer is steadily reduced, requiring greater dosages with accompanying negative side effects.

The Hebrew University researchers were able to show in animal experiments that administering morphine together with another drug that blocks the activity of interleukin-1 provides more effective pain relief over the long term without having to increase the dosage.

Shavit, who is the Leon and Clara Sznajderman Professor of Psychology at the Hebrew University and whose specialty is psychoneuroimmunology, expressed hope that this research will make it possible for clinicians to make use of morphine, together with substances that block interluekin-1, in order to bring about better pain relief with lower dosages and with minimized side effects. The research will be presented at a conference on pain research on May 3 on the Mount Scopus campus of the university. The conference is open to journalists and to people in the field.

 Scientists know that alcohol affects the brain, but the specifics remain unclear. One possibility is that alcohol may increase or decrease the release and the synthesis of endogenous opioid peptides – endorphins, enkephalins and dynorphins – in distinct brain regions important for drug addiction.

For the first time, a rodent study has confirmed that low to moderate levels of alcohol alter beta-endorphin release in the midbrain/Ventral Tegmental Area (VTA) region, producing the pleasant effects that likely reinforce alcohol consumption.

"Some of the functions of opioid peptides are similar to those of the opiate morphine," explained Christina Gianoulakis, a professor in the departments of psychiatry and physiology at McGill University, and the study's corresponding author. "Like morphine, endogenous opioid peptides can induce analgesia and a mild euphoric effect, reduce anxiety, and may lead to a general feeling of well being. Therefore, increased release of endogenous opioid peptides in response to drinking could be partially responsible for the mild euphoric and anxiolytic effects associated with low to moderate amounts of alcoholic beverages." Gianoulakis is also with the Douglas Mental Health University Institute.

"The brain's natural opioids have been implicated in many physiological functions such as pain and pleasure," added Dzung Anh Le, a senior scientist at the Centre for Addiction and Mental Health, University of Toronto. "Alcohol has long been thought to release these peptides, but previously the only way to confirm this was to rely on test tube experiments using extracted tissue samples, and findings from these studies were indirect and offered extremely limited interpretation."

Le said that researchers suspected that dopamine was a key brain chemical in one of the most heavily implicated pathways likely involved in drug and alcohol addiction, the VTA.

"One mechanism by which alcohol produces its euphoric or rewarding effects is through the stimulation of natural opioid peptides in the VTA, which consequently activates dopamine in this critical pathway," Le said. "Until now, no one has been able to answer whether alcohol is actually capable of triggering opioid release in the VTA."

Researchers injected male Sprague-Dawley rats with either saline or alcohol (0.8, 1.2, 1.6, 2.0, and 2.4 grams alcohol/kg of body weight). Using an in vivo microdialysis technique, study authors tracked the response of endorphins, enkephalins, and dynorphins at the level of the midbrain, including the VTA.

"We found that low to moderate but not high doses of alcohol increase the release of beta-endorphin in the VTA, one of the brain regions shown to be important for mediating the rewarding effect of alcohol," said Gianoulakis. "This supports a role of beta-endorphin in mediating some of the rewarding effects of alcohol. However, the same doses of alcohol that increase beta-endorphin release in the VTA have no significant effect on the release of enkephalins and dynorphins, the other two families of endogenous opioid peptides we examined."

Gianoulakis said that readers should remember that it is the low to moderate doses of alcohol that are associated with mild euphoria, decreased anxiety and a general feeling of well being. "On the other hand, high doses of alcohol are known to induce sedative and hypnotic effects, and often increase rather than decrease anxiety."

"This research has confirmed a role of endogenous opioids in mediating alcohol addiction, and has delineated a pathway within which they may be involved," said Le. "It also goes further to specifically isolate an opioid peptide that may be most critically involved in a specific region of the brain. Endorphins are the natural peptides that most closely mimic the pharmacological properties of morphine, and of the three opioid families, they likely produce the greatest 'high.'"

Furthermore, Le added, methods used in this study are groundbreaking. "Dr. Gianoulakis and her team can track changes over time in living and freely moving animals," he said. "This has a profound implication on research in this area, as the effects of alcohol can be measured from an intact 'living' brain, in animals that are relatively uninhibited and unstressed within their environment."

Both Gianoulakis and Le said these findings will help future treatment options.

"VTA beta-endorphin appears to play a significant role in alcohol reinforcement, and may partially explain the effectiveness of naltrexone – an opioid receptor antagonist currently used as treatment of alcoholism – in reducing alcohol consumption by some individuals," said Gianoulakis.

"While current alcoholism treatment blocks opioids in a nonspecific fashion, this research suggests that a more targeted approach would be more beneficial," said Le. "Researchers now have to specifically target endorphins in the VTA to see if it really does affect alcohol abuse and craving."

"Readers should understand that drinking only low amounts of alcohol will increase endorphin release and produce pleasant effects," said Gianoulakis. "Thus, if after consumption of about two drinks of alcohol an individual does not experience the pleasant effects of alcohol, he or she should stop drinking. Consumption of high amounts of alcohol will not only fail to increase the release of endorphins, but may stimulate other systems in the brain that may lead to the development of anxiety and depression."

The study was funded by the Natural Sciences and Engineering Research Council of Canada.

Journal Reference:

1. Samuel Jarjour et al. Effect of Acute Ethanol Administration on the Release of Opioid Peptides from the Midbrain Including the Ventral Tegmental Area. Alcoholism: Clinical & Experimental Research, June 2009

 Naltrexone, an opioid antagonist approved in 1994 by the U.S. Food and Drug Administration for alcohol-dependence (AD) treatment, can reduce relapse rates among AD patients. Research on naltrexone's effectiveness on nicotine dependence is less clear, although researchers believe it may be helpful for specific smoker subgroups.

A new study has found that naltrexone can help non-AD smokers who drink heavily on a social basis.

"This was a smoking cessation trial," explained Andrea C. King, a psychologist and associate professor in the department of psychiatry at the University of Chicago, and first author of the study. "We examined smokers who did not have any other current addiction – besides tobacco – or mental or medical disorders, which may have confounded the results. The range of alcohol drinking was from abstainer to heavy social drinker."

King and her colleagues examined 78 study participants (43 men, 35 women) drawn from a larger study looking at the effectiveness of naltrexone on smoking cessation. Of the 78, 34 were randomly assigned to receive naltrexone; 44 received a placebo. Dosage at 25 mg daily began three days prior to the quit date, and then continued at 50 mg daily for eight weeks. Drinking and liver enzyme levels were monitored, and all participants received nicotine patches (to ease withdrawal symptoms) and behavioral counseling for up to four weeks following the quit date.

"Naltrexone, at 50 mg oral daily, when added to counseling and patch, significantly decreased heavy drinking rates in smokers enrolled in smoking cessation," said King. "Persons with the heaviest drinking patterns appeared to benefit the most from naltrexone, in terms of alcohol and smoking outcomes; it also increased their quit rates more so than in lighter drinkers."

King noted that that these results are likely based on the strong inter-connections between drinking and smoking for many individuals.

"Both nicotine and alcohol may stimulate brain reward pathways connected to endogenous opioids – meaning the 'endorphins' which are feel-good brain chemicals – as well as dopamine," she said. "An opioid blocker like naltrexone therefore may benefit persons who use both substances concurrently." She and her research team are trying to replicate these findings with a larger group of participants.

"If we do support these findings with a larger sample, then use of naltrexone could be expanded to drinkers-smokers who are trying to quit smoking," she said. "While quitting smoking is difficult for many, it may be especially hard for smokers who also drink alcohol, because the two are often used together, and drinking can dose-dependently trigger smoking urges and behavior. A medication like naltrexone, in addition to a standard quality smoking cessation program, may help this hard-to-treat subgroup of smokers who face additive health consequences from the co-use of these substances. This is significant also because naltrexone is well tolerated and safe."

Until then, she advised individuals who are trying to quit smoking to create a clear plan of action. "Stick with your plan, and learn from your mistakes, and try again if not successful. For some, it takes several attempts before being successful. FDA-approved medications and either group or individual counselling improve one's chances substantially. Tobacco is the number one modifiable health problem of our time. Persons with alcohol problems who also smoke are at more risk of dying prematurely from tobacco-related causes than they are of alcohol-related causes."

Co-authors of the ACER paper were: Dingcai Cao of the Department of Surgery, Catherine Vanier of the Pritzker School of Medicine, and Tracie Wilcox of the Department of Medicine, all at the University of Chicago. The study was funded by the University of Chicago Cancer Research Center, the General Clinical Research Center, and the National Institute on Alcohol Abuse and Alcoholism.

Journal Reference:

1. . Naltrexone Decreases Heavy Drinking Rates in Smoking Cessation Treatment: An Exploratory Study. Alcoholism: Clinical & Experimental Research, June 2009