Tag Archives: Addiction research

Speaking of Addiction Research

J. David Jentsch is a Professor of Psychology and Psychiatry & Biobehavioral Sciences at the University of California, Los Angeles. He is the recipient of the 2010 Joseph Cochin Young Investigator Award from the College on the Problems of Drug Dependence and the 2011 Jacob P Waletzky Award for Innovative Research in Drug and Alcohol Abuse from the Society for Neuroscience. He is a member of the Speaking of Research Committee and writes his own blog: the Unlikelyactivist.

This post is the full version of a piece originally written for Substance.com under the title “A Scientist Comes Out Swinging at PETA’s Addiction Research Stance”.

Biomedical research seeks to expose biological principles and mechanisms that cause disease in order to advance from a time where medications and treatments were discovered by chance to one where we reason our way to solutions for human and animal health through scientific discovery. Since the founding of the National Institute on Drug Abuse (NIDA) in 1974 (only 40 years ago), immense progress has been made into understanding, at the level of brain cells and molecules, why some drugs are addictive, why some people are particularly prone to addictive behaviors and how to treat drug use disorders. One of the reasons that so much progress has been made so quickly is that animal models for drug abuse are remarkably accurate and informative.

In the clearest example of all, if you place a laboratory rat into a chamber and allow it to trigger delivery of cocaine, methamphetamine, nicotine, alcohol, heroin, etc., into their bloodstream by voluntarily pressing a button, they will do so. Rats will seek out and voluntarily “self-administer” drugs of abuse, just like people do, precisely because of the remarkable similarity in the reward pathways in the human and rat brain, as well as due to the fact that these drugs act upon brain chemicals in nearly identical ways in rodents and humans. Moreover, if you allow rats to consume the drug daily over a long period of time, a subset of them will progressively become “dependent” upon the drug, just the same way a subset of people that abuse drugs do. Dependence is indicated by the fact that the subject loses control over their drug use and continues to use the drug, despite efforts to abstain. Because of these incredible parallels between humans and animals, we now understand the mechanisms by which drugs of abuse produce reward at a deep level, as well as how these agents encourage drug-seeking and –taking behaviors. For example, we now know how parts of the brain like the nucleus accumbens, amygdala and prefrontal cortex participate in the development of drug-taking behaviors, and we know how crucial brain chemicals like dopamine and glutamate are to these phenomena. This information would not have been possible without responsible and humane research involving a variety of animal models – ranging from invertebrates (fruit flies, roundworms) to rodents (rats and mice) to non-human primates (mostly monkeys).

Rat Rodent Addiction Animal Testing Research

It is reasonable to ask why, given these advances and the value of animal models, we have not yet cured addictions. The answer is simple. When NIDA was founded 40 years ago, we actually knew very little about the basic biology of the brain and its relationship to drug abuse. Decades of basic research were required before we knew enough about the brain pathways involved in reward to further understand how drugs acted on these pathways and changed them in response to long-term drug intake. Decades of basic research, still on-going, was and remains required to identify all the genes, molecules and cell processes that drugs act on but which were unknown to us as recently as 10 years ago. Basic research continues in an attempt to fully describe how the hundreds of billions of nerve cells in the brain work together to create behavior and how the tens of thousands of genes in our genome affect the function of our bodies. Coupled with amazing advances in the technology needed to study the brain, this knowledge from basic research will yield unprecedented progress towards treating addictions, as well as other disorders of the brain (from Alzheimer’s Disease to schizophrenia) will be possible.

So, what has research into the biology of addictions done for us so far? In a recent blog post, Katherine Roe from PeTA claims that only one new medication has been approved for the treatment of alcoholism/alcohol use disorders based upon animal research in recent years, that it has only “limited” effect and that animal research has “green-lighted” decades of failed medication trials. Not only are each of these statements factually wrong, the truth that is subverted by her points actually demands more animal research, not less.

Firstly, there are actually three medications approved for the treatment of alcohol use disorders (one is old and two are new). One new drug naltrexone (that blocks opioid systems in brain) was approved in 1994; in 2004, the FDA approved another medication (acamprosate). Both specifically target brain chemical systems discovered to be important to alcohol’s effects though animal research. In addition, the development of both medicines required animal research since they act on molecules in brain that might be unknown at all without basic research studies in rodents and non-human primates.

Secondly, referring to the efficacy of these medicines as limited seems to misunderstand the nature of pharmacology. These medications do not effectively treat everyone that is medicated with them – but then, no drug used for any disease does. That’s not the way pharmacology works. That said, for tens of thousands of people with alcohol use disorders around the world, they achieve and maintain abstinence thanks to one or both of these medications: something that wouldn’t be possible for them without the medicines. For those people, animal research on alcohol addiction has literally saved their lives.

Thirdly, the fact of the matter is that the desperate need for medications for drug and alcohol abuse has led both NIDA and the National Institute on Alcoholism and Alcohol Abuse (NIAAA) to undertake many clinical trials for medications before there was adequate evidence for efficacy in animal models. Many of the failed clinical trials involved these kinds of medicines. Therefore, if one is concerned about the failure of clinical trials (and we certainly should be), we should be calling for more investment in research, including in research involving animal models. Saying that animal research had “green-lighted” every single medication is simply and unequivocally wrong.

It is for all these reasons that the drug abuse research community is incredibly supportive of animal-based research. The pre-eminent professional society in this area – the College on the Problems of Drug Dependence – which includes epidemiologists, neuroscientists, clinical psychologists and psychiatrists and policy experts has published a statement clarifying their position on animal research:

There is an urgent need to know more about psychoactive drugs, particularly those features that lead some individuals to escalate initial use into regular use or dependence.  Research with laboratory animals will play a key role in these and related efforts… The College on Problems of Drug Dependence recognizes the value and importance of drug abuse research involving laboratory animals and supports the humane use of animals in research that has the potential to benefit human health and society. Such research plays a vital role in acquisition of the new knowledge needed to understand and reduce drug abuse and its associated problems.

Because drug and alcohol abuse are diseases with far-ranging health effects, contributing to death from overdose, cancer, stroke and metabolic disease, all of the National Institutes of Health (NIH) have a clear interest in seeing research end addictions. Animal activists’ claims that former NIH director Elias Zerhouni has spoken against the value of animal research are misleading given that he has recently made his opinion clear:

I understand that some have interpreted these comments to mean that I think that animals are no longer necessary in medical research. This is certainly not what I meant. In fact, animal models and other surrogates of human disease are necessary — but not sufficient — for the successful development of new treatments. In short, animal models remain essential to the basic research that seeks to understand the complexities of disease mechanism.

Overall, opposition to animal research on addictions seems to require a deep misunderstanding of basic science research, of the state of current scientific understanding of addictions and their treatment and of basic principles of biology, like pharmacology. It also defies the overwhelming consensus of the scientific and drug abuse treatment community that emphasizes the critical need for more research, including animal-based research, in that effort.

J. David Jentsch

To learn more about the role of animal research in advancing human and veterinary medicine, and the threat posed to this progress by the animal rights lobby, follow us on Facebook or Twitter.

Do animals suffer from human diseases?

A common argument heard against the use of animals in research is that animals do not naturally suffer from the same conditions as humans do.  Thus, the argument goes, it makes no sense to study human disease in animals.

However, my UCLA colleagues Barbara Natterson-Horowitz MD and Kathryn Bowers, authors of Zoobiquity, explain that the opposite is the case. The book along with videos explain how is that animals and humans indeed get many of the same diseases, and how knowledge from animal and human health is being used to improve the well being of both.

For example, often times it is stated that addiction is merely human problem.  But explained in the video below, animals also seek such substances in the wild, often with tragic consequences.

It is thus not surprising that scientists have made tremendous advances to study how substances alter the brain reward circuits that underlie such behavior.  You can learn more about addiction by visiting SfN’s brain facts web-site here.  For more examples of naturally occurring conditions, such as STD, eating disorders and breast cancer, are shared across species watch these other videos.

We should also remember that a disease does not need to occur naturally at a high frequency in animals for studies of animal models of it to be highly informative. An excellent example of this is the study of genetically modified mice, where in just the past week we have posted links on our Facebook and Twitter pages to articles discussing important scientific insights and promising therapeutic approaches by researchers studying the genetic disorder Rett syndrome, breast cancer,  the human prion protein diseases fatal familial insomnia and Creutzfeldt-Jakob disease, and HIV transmission. These examples, and the study of naturally occurring animal diseases mentioned earlier, serve to highlight the need for scientists to use a wide variety of species and disease models as they strive to understand biological systems and develop tomorrow’s medicines.

Speaking of Research

Oregon Scientists seek to understand the roots of Alcoholism

Just a year ago Professor David Jentsch wrote here about the importance of animal research in developing better ways to treat addiction; now Jim Newman of the Oregon National Primate Research Centre (ONPRC) has written in OregonLive about how research in monkeys is helping us to understand alcoholism and other forms of alcohol abuse, which are among leading causes of death, injury and illness in the United States.

In an interview yesterday with ABC20/20 ONPRC scientist Kathy Grant discusses the importance of research on Rhesus macaques in improving our understanding of why consumption of alcohol differs between  individuals, information which she hopes will help to prevent and treat alcohol abuse.

Speaking of Research wish Professor Grant and her colleagues well in their efforts to reduce the damage done to our society by alcohol abuse.

Addiction Research as an Example of Translational Biomedical Research

In science, “translation” embodies the concept that data gathered in one situation is meaningful for data gathered in another. Applied biomedical research seeks to translate laboratory research into effective treatments or cures. It spans many levels of study. In oncology (the field of cancer biology), some individuals study how cancerous cells grown in a dish operate and grow and how best you can destroy them. Others study tumor growth in animal models; they do this because the behavior of cells in a dish does not always fully predict how cancer will grow in a living body. Because we want to understand how cancer occurs and progresses in humans, yet other scientists use epidemiological or imaging techniques to directly study cancer patients. Information gained at one level informs and fosters the understanding of information gathered at other levels. No single experiment or scientist answers everything – it’s the collective work of the larger group of researchers working at all levels that pushes things forwards. This is how translation is made possible.

A hotly debated question in translational research is whether data gathered in animals 1) always, 2) often, 3) rarely or 4) never is meaningful for our understanding of human biology. Though most scientists and clinical practitioners feel strongly that it is often predictive, explicit examples are required to convince the broader public.  Clear evidence of translational value is found in research on the biology of drug addictions – something that I study in my laboratory. A large number of both rats and humans find drugs of abuse (cocaine, heroin methamphetamine, nicotine, etc.), when ingested, to be incredibly rewarding and will engage in significant drug-seeking behaviors to obtain it. In that sense, the study of these drugs’ effects on rats translates well (though not perfectly) to its effects on humans. Importantly, it translates “well enough” to make the rat a useful model organism in which to explore how drugs of abuse take control of some individuals by altering their brain chemistry. We have made excellent progress in this area over the last 15 years.

Of all areas of biomedical research, the study of the brain poses the biggest challenge for translational research because it is this organ that differs most across species. There is no doubt that a mouse’s brain is dramatically different from that of a monkey which is still different from that of a human. But do those superficial differences matter? Not as much as you might think! Let’s go back to the earlier example of drug abuse. Addictive drugs are chemicals that, when ingested, make their way into the brain where they alter the activity of brain cells, consequently changing the function of circuits in the brain that mediate reward. This is why they make people experience euphoria, relaxation and a sense of well-being after they take them. Remarkably, despite obvious differences in the brain, rats also very much enjoy the effects of these drugs. When offered an opportunity, they will take them voluntarily (e.g., press a button to trigger an injection of the drug). Even more impressively, even fish find addictive drugs rewarding. So, actually, despite the superficial differences, there is a huge amount going on in the brain that is similar across model organisms. This is because the anatomical differences between rat and human brains are actually much smaller than what is shared between them: common sets of circuits with similar functions.

This point is crucial. If fish and rats can be used to predict some of the responses of humans to addictive drugs, they can be used in translational research to explore the therapeutic effects of drugs used to treat brain disorders, such as addictions, as well.

It is important, however, to distinguish between what an animal model can reveal and what it cannot. In the case of chemical addictions, animal models can help you to understand the physiological and basic behavioral processes that drugs act on to alter the body. Again, studying the effects of an addictive drug in rats can help us to understand how it alters the reward circuit and how that relates to drug seeking. Here, translation is excellent. At the same time, it does not fully recapitulate the psychosocial consequences of drug taking in people. Because the drug is available for free, rats do not have to steal to get money to buy it. Because they are not expected to show up to work on time and be productive, drug use does not cause them to get fired from their jobs. Because they do not get married, they are not at risk of divorce when their drug-taking behavior gets out of control. Because they do not share needles, they are not at risk of hepatitis C or HIV infection. So, from a biological perspective, study of addiction can be modeled well in rats, but the psychosocial consequences are not. Rat researchers have revealed the neural mechanisms by which addictive drugs act in exquisite detail, and all modern, FDA-approved treatments for drug dependence arose from basic, mechanistic studies in animals (examples include Revia for the treatment of alcohol dependence and Chantix for smoking cessation). Clinical researchers then are able to tell us whether and how these treatments affect psychosocial functions in drug users. In that sense, like our colleagues who study cancer, we integrate study from many levels together to fully understand the biology and psychosocial consequences of drug abuse and its treatment.

It is because research at many levels integrates so well that providers of clinical intervention often closely study and attend to studies conducted in animals. An international society called the College on the Problems of Drug Dependence brings together scientists, physicians and social workers who are particularly interested in solving problems relating to addiction. Here, each attendee carefully studies the results of the other researchers – with studies in humans designed based upon clinical observations, and clinical tests being spurred by rat studies.  There is little doubt in the group – whether one consults patient-oriented researchers or people that examine cells growing in a dish – that studies of living animals are a critical part to the overall translational effort to stem the impact of addictions on affected individuals. Though animal research will not solve all of the mysteries of addiction, or of any complex human disease process, it is a foundational part of most areas of biomedical research and patients, patient advocacy groups and treatment providers overwhelmingly support it.

Regards

David Jentsch