Category Archives: Cocaine

Experimental Injection Reduces Cocaine Craving

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MedicalResearch.com Interview with:

Ana-Clara Bobadilla, Ph.D. Postdoctoral scholar in the laboratory of Peter Kalivas, Ph.D MUSC  Photo by Sarah Pack Medical University of South Carolina

Dr. Ana-Clara Bobadilla (Sarah Pack, photographer)

Ana-Clara Bobadilla, Ph.D.
Postdoctoral scholar
in the laboratory of Peter Kalivas, Ph.D
MUSC 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: The Brain-derived neurotrophic factor (BDNF) is a growth factor that has well-described effects in the survival, growth and differentiation of neurons during development of the central nervous system, but it also maintains a role during adulthood in learning, memory and various disorders such as addiction. Several clinical studies show increased BDNF levels in the serum of cocaine- or alcohol-dependent patients compared to controls (D’Sa et al., 2011; D’Sa et al., 2012). In preclinical research, a wealth of studies shows that chronic exposure to drugs of abuse impacts BDNF expression in different parts of the brain, including the main regions comprised in the reward circuitry, the cortex and the nucleus accumbens (for a comprehensive review, see Li & Wolf, 2015). Conversely, altering BDNF expression or transmission has profound effects on the response of the brain to drugs (see McGinty et al., 2010). Importantly, BDNF effects are often region-specific, meaning that an increase in BDNF expression in one region can decrease the effects of drug exposure in the brain while the same increase in another region can have opposite effects (Li et al., 2013). Because BDNF transmission can modify the expression of a wide range of genes leading to long-term modifications, numerous studies administer BDNF early in the drug exposure protocol and focus on the long-term changes induced by the growth factor.

In this study, we microinjected BDNF directly in the nucleus accumbens minutes before measuring cocaine craving in a well-known rodent model of relapse. We found that BDNF induces a robust decrease in craving that lasts for at least 3 days post-treatment. The inhibitory effect of BDNF is not seen when animals are tested for sucrose, a very strong reward for rats, suggesting that this effect is specific to cocaine.

Moreover, cocaine craving is only decreased when BDNF is microinjected before the craving test, but has no effect when injected a day before the craving test or in the home cage, indicating a time-specificity in addition to the region-specificity previously described.  Continue reading →

Bariatric Surgical Approach To Increase Bile Acids May Reduce Cocaine Reward

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MedicalResearch.com Interview with:

Aurelio Galli, Ph.D. Professor of Molecular Physiology & Biophysics and Psychiatry & Behavioral Science Associate Director for Research Strategy Vanderbilt Brain Institute

Dr. Galli

Aurelio Galli, Ph.D.
Professor of Molecular Physiology & Biophysics and Psychiatry & Behavioral Science
Associate Director for Research Strategy
Vanderbilt Brain Institute

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The study builds on evidence that bile acids influence the brain’s reward system. Bile acids are normally released from the gall bladder into the upper part of the small intestine, where they emulsify fats for absorption, before being recycled further down the small intestine. In bile diversion surgery, an experimental treatment for weight loss, bile is released at the end of the small intestine, increasing the amount of bile acids that enter the general circulation.

Mice treated with this surgery have less appetite for high-fat foods, which suggests that bile acids affect brain reward pathways.

We demonstrated that mice receiving the surgery also showed less preference for the cocaine-associated chamber, indicating that cocaine was probably less rewarding. Continue reading →

Gene Deficit May Give Immunity to Effects of Cocaine

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MedicalResearch.com Interview with:
“Cocaine concealed in washing powder” by The National Crime Agency is licensed under CC BY 2.0

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Drug addiction is a chronically relapsing neuropsychiatric disease that affects 15.5 million people in Europe at a cost of 65.7 billion euros per year. All addictive drugs have in common to cause an artificial increase in the release of a neurotransmitter called dopamine, a very basic effect that can be found in all studied animal species from the fly to the man. The release of dopamine takes place in a region of the brain called the ventral striatum, or Nucleus Accumbens (NAc), which is directly involved in reward and reinforcement processes. An excess of dopamine release by the dopaminergic neurons projecting to the NAc from the Ventral Tegmental Area (VTA) triggers long-term changes in the brain, which can lead to addiction.

Cocaine is a prototypical addictive drug, since it is heavely abused in Western societies and extensively studied in animal models as well as humans.

We discovered that mice lacking the Maged1 gene showed a marked decrease in cocaine-elicited release of dopamine in the NAc and were entirely unresponsive to cocaine at behavioral level. In fact, they did not show any behavioral reaction normally observed after cocaine treatment, such as cocaine-elicited hyperlocomotion, sensitization (an increased effect of the drug following repeated administrations) or addictive behaviors, such as increased preference for places where the animal expects to obtain a cocaine reward or cocaine self-administration.

In a subsequent set of experiments, the researchers tried to identify what brain regions are responsible for Maged1 influence on cocaine effects and found that Maged1 expression is specifically required in the prefrontal cortex, and not in the neurons producing dopamine in the VTA, for the development of cocaine sensitization and dopamine release.  Continue reading →

Mitochondrial Link To Cocaine Addiction Explored

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“cocaine photo” by Imagens Evangélicas is licensed under CC BY 2.0MedicalResearch.com Interview with:
Mary Kay Lobo, PhD
Associate Professor
University of Maryland School of Medicine
Department of Anatomy and Neurobiology
Baltimore, MD 21201 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Altered energy balance has been studied in drug abuse but the fundamental source of energy, mitochondria, has not been well examined.  In this study we found that a molecular regulator of mitochondrial fission (division) is increased in the nucleus accumbens, a major brain reward region, of rodents exposed to repeated cocaine and postmortem samples of cocaine dependent individuals.  We further found that mitochondrial fission is increased in a nucleus accumbens neuron subtype in rodents that self-administer cocaine. Pharmacological blockade of mitochondrial fission can prevent physiological responses to cocaine in this neuron subtype while reducing cocaine-mediated behaviors.  Finally, genetic reduction of mitochondrial fission in this neuron subtype in the nucleus accumbens can reduce drug (cocaine) seeking in rodents previously exposed to cocaine. In contrast, increasing mitochondrial fission, in this neuron subtype, enhances cocaine seeking behavior.

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Cocaine Overdoses Rising Especially Among African Americans

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MedicalResearch.com Interview with:
“Cocaine” by Nightlife Of Revelry is licensed under CC BY 2.0Dr. Dave Thomas PhD
Health Scientist Administrator
National Institute on Drug Abuse 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: At the National Institute on Drug Abuse, we support research on all forms of drug use, and are aware that cocaine misuse is on the rise.  We are aware that various forms of drug use can have greater prevalence by race, sex, age and other population characteristics.

The main finding of this paper is that cocaine overdose rates are on the rise and that that the group hit hardest is the non-Hispanic black population.

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Overdose Deaths Increase Across Urban Status, Sex and Race Lines

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MedicalResearch.com Interview with:
“Pills” by Kurtis Garbutt is licensed under CC BY 2.0Christopher M. Jones, PharmD
Office of the Assistant Secretary for Planning and Evaluation
Office of the Secretary
U.S. Department of Health and Human Services 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Drug overdoses are the leading cause of injury death in the United States, resulting in approximately 52,000 deaths in 2015. Although prescription drugs, in particular opioid pain relievers, were primarily responsible for the rapid expansion of this large and growing public health crisis, illicit drugs (heroin, illicit fentanyl, cocaine, and methamphetamines) now are contributing substantially to the problem. Understanding differences in illicit drug use, illicit drug use disorders, and overall drug overdose deaths in metropolitan and nonmetropolitan areas is important for informing public health programs, interventions, and policies.

We found that the prevalence of self-reported past-month use of illicit drugs increased significantly across urban status (large metropolitan, small metropolitan, and nonmetropolitan) between 2003-2005 and 2012-2014. Prevalence was higher for males than females, however, in the large metropolitan group, the percentage increase in prevalence from 2003–2005 to 2012–2014 was greater for females (23.4%) than for males (21.6%). There were notable differences by age. During 2012–2014, respondents aged 18–25 years had the highest prevalence of past-month use of illicit drugs for all urban levels. For respondents in this age group, the prevalence increased slightly from 2003–2005 to 2012–2014 in large metropolitan areas while the prevalence remained stable among small metropolitan area respondents and nonmetropolitan area respondents. Past-month use of illicit drugs declined over the study period for the youngest respondents (aged 12–17 years), with the largest decline among small metropolitan area youth.

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Recreational Cocaine Use Activates Addiction Related Brain Mechanisms Sooner Than Previously Realized

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MedicalResearch.com Interview with:

Marco Leyton, Ph.D. Professor, Department of Psychiatry McGill University

Dr. Marco Leyton

Marco Leyton, Ph.D.
Professor, Department of Psychiatry
McGill University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Drug-related cues are potent triggers for eliciting conscious and unconscious desire for the drug. In people with severe substance use disorders, these cues also activate dopamine release in the dorsal striatum, a brain region thought to be involved in hard-to-break habits and compulsions.

In the present study we found evidence that drug cues also activate this same dopamine response in non-dependent ‘recreational’ cocaine users.

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Cancer Drug May Mitigate Compulsive Cocaine Memories

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MedicalResearch.com Interview with:
Dr Stefania Fasano
Cardiff University

MedicalResearch.com: What is the background for this study?

Response: Exposure to drugs of abuse such as cocaine produces intense and long-lasting memories that are critical in the transition from recreational drug-taking to uncontrolled drug use. In the brain, addictive drugs usurp cellular circuits and signalling molecules involved in normal memory processes; hence, these drug-related memories resist extinction and contribute to high rates of relapse. Despite almost five decades of experimental research, there are currently no approved medications for cocaine dependence.

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Why People With Cocaine Addiction Don’t Change?

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MedicalResearch.com Interview with:
Dr Karen Ersche PhD
University of Cambridge
Department of Psychiatry
Brain Mapping Unit
Herchel Smith Building
Cambridge UK

MedicalResearch.com: What is the background for this study?

Dr. Ersche: Cocaine addiction is a major public health problem that is associated with significant harm – not just for the individual, but also for their families and for society as a whole. Without medically proven pharmacological treatments, therapeutic interventions mainly rely on psychosocial approaches, but behaviour in people with cocaine addiction remains extremely difficult to change.

The impetus for this study was to find out why people with cocaine addiction are so resistant to change. One possibility would be that they have a strong tendency to develop habits, which means that they show patterns of behaviour that are not under direct voluntary control.

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Increased Drug Overdoses and Deaths Not Limited To High Intensity Drug Trafficking Areas

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MedicalResearch.com Interview with:

Jeanine Buchanich, Ph.D. Deputy director of the Graduate School of Public Health’s Center for Occupational Biostatistics and Epidemiology Research assistant professor in Pitt Public Health’s Department of Biostatistics University of Pittsburgh

Dr. Jeanine Buchanich

Jeanine Buchanich, Ph.D.
Deputy director of the Graduate School of Public Health’s Center for Occupational Biostatistics and Epidemiology
Research assistant professor in Pitt Public Health’s Department of Biostatistics
University of Pittsburgh

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Buchanich:  Using the Mortality and Population Data System, a unique repository and retrieval system for detailed death data from the National Center for Health Statistics, housed at the University of Pittsburgh Graduate School of Public Health, my team examined overdose deaths in the U.S. from 1979 to 2014. We started with 1979 because changes in reporting cause of death make it impossible to make comparisons with previous years. 2014 is the most recent year for which data are available.

The counties with the largest increases in overdose death rates were clustered in southern Michigan; eastern Ohio and western Pennsylvania; eastern Pennsylvania, New Jersey and much of southeastern New York; and coastal New England. Counties in the Midwest, California and Texas have seen little to no increase in overdose death rates.

We cross-referenced the mortality data with counties in the High Intensity Drug Trafficking Areas program, which was created by Congress in 1988 to provide 31 high drug-trafficking areas of the U.S. with coordinated law enforcement resources dedicated to reducing trafficking and production. High Intensity Drug Trafficking Areas with high overdose death rates were mostly concentrated in Appalachia and the Southwest U.S., whereas such areas with lower death rates were near the borders in California, Texas and southern Florida.

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Sustained Release Dexamfetamine Reduced Cocaine Use in Crack Addicts

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MedicalResearch.com Interview with:

Mascha Nuijten MSc Researcher/ PhD candidate Brijder Research (PARC) The Hague The Netherlands

Mascha Nuijten

Mascha Nuijten MSc
Researcher/ PhD candidate
Brijder Research (PARC)
The Hague
The Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Crack-cocaine dependence is a complex disorder, for which no proven effective pharmacotherapy is yet available. Prior to our study, sustained-release dexamfetamine was found to be a promising treatment for cocaine dependence in several studies, but no studies so far had shown a convincing benefit in terms of substantial cocaine use reductions. Therefore, we investigated the efficacy of sustained-release (SR) dexamphetamine in a robust dose of 60 mg/day in chronic crack-cocaine dependent patients.

We found that the number of days of cocaine use decreased with almost 40% in the dexamfetamine group, compared with 9% in the matched placebo group. In addition, the number of cocaine self-administrations on days that patients used crack-cocaine decreased with 43% in the dexamfetamine group and with 7% in the placebo group. Thus, SR dexamfetamine both contributed to cocaine abstinence and to cocaine use reductions.

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Cocaine Chief Cause of Cardiovascular Death In Young People

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MedicalResearch.com Interview with:
Luis F. Callado M.D., Ph.D.
Department of Pharmacology
University of the Basque Country
CIBERSAM

Medical Research: What is the background for this study? What are the main findings?

Dr. Callado: Cocaine is the most commonly used illicit stimulant drug in Europe. The use of cocaine has become a major issue for drug policy, with also important health implications, including potentially lethal cardiovascular complications. In this way, several case series have suggested a relationship between cocaine use and cardiovascular diseases in young adults. Furthermore, cocaine use has been also associated with sudden and unexpected death.

Our results demonstrate that the recent use of cocaine is the main risk factor for sudden cardiovascular death in persons between 15 and 49 years old. Thus, persons that consumed cocaine recently presented a 4 times higher risk for sudden cardiovascular death than those who did not use cocaine. The morphological substrate of sudden cardiovascular death associated to cocaine use is a structural pathology not diagnosed in life. Usually, sudden death is the first manifestation of the disease.

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Cocaine: Brain Reward Circuitry Altered, even in Former Users

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MedicalResearch.com Interview with:
Krishna Patel, M.S.
Clinical Data Analyst
Hartford Hospital|Institute of Living
Olin Neuropsychiatry Research Center
Hartford, CT-06106

MedicalResearch.com: What are the main findings of the study?

Answer:  We looked at brain response to a monetary incentive delay (MID) task in current and former cocaine users compared to healthy controls using functional MRI. The task measures aspects of sensitivity to rewards and punishments. Current cocaine users showed abnormal under-activation in reward circuitry compared to healthy controls. In some of those regions former cocaine users (who had an average of 4years of abstinence from cocaine) also showed abnormalities. These former users also showed over-activation in the ventral tegmental area of the midbrain, (an important region containing dopamine cell bodies) compared to both healthy controls and current cocaine users. Current and former cocaine users also scored higher on specific impulsivity measures, compared to healthy controls.
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