Explaining Addiction Research

Dr. Larry Hansen, Professor of Pathology and Neuroscience at the University of California, San Diego, recently wrote a letter critical of some of our research; the letter was posted to the website of an anti-science organization called “Stop Animal Exploitation Now” and appears to be in support of an anti-animal research demonstration to be conducted on the UCLA campus on July 25, 2011. In the letter, Dr. Hansen’s critique avoids scientific discussion of rationale for and nature of our work, resorting instead to hyperbole and repetition of the general criticisms aimed at biomedical research involving animals by pseudo-scientists who ally themselves with the animal rights movement. We aim to fill the factual void created by his letter in the following description of our work.

What are our experiments about? Amongst addictive drugs, methamphetamine leads the pack: accounting for more treatment seekers in the California system than does any other illicit substance. Methamphetamine addiction is associated with elevated morbidity, including higher rates of communicable diseases like HIV/AIDS, and mortality. It robs young people of their lives and families of their loved ones. Despite this, as of 2011, there is no FDA-approved medication for the treatment of methamphetamine addiction. This is due, at least in part, to the limited insight we have about how methamphetamine affects brain chemistry, hijacking the parts of the brain responsible the ability to feel pleasure and to make good decisions. Our work focuses on the latter – on how methamphetamine changes those brain regions needed to resist temptations and to avoid unhealthy behaviors, leading to the cascade of bad decisions apparent in many people suffering from addictions.

Our goal is to identify those brain abnormalities that cause poor decision-making in methamphetamine addiction, to clarify how aberrations in brain chemistry contribute to these problems and to propose medications that can counteract those effects, with the hope that they will exert a clinical benefit in the treatment of the disorder.

What do our experiments involve? We test human subjects (people with a methamphetamine use problem and healthy unaffected persons), non-human primates and rats. Some of our monkeys and rats are exposed to methamphetamine in a manner that is similar to human methamphetamine abuse. The rationale for this is that the drug will alter their brains in a manner similar to the way it affects the human brain. Dr. Hansen’s assertion that this kind of analysis is impossible, due to differences in brain organization between animals and humans, ignores the evolutionary trends that conserved important neural mechanisms across mammals and more than a century of neuroscience research that controverts his conclusion. In contrast to his seriously erroneous assertion, if monkeys or rats are offered access to methamphetamine in a laboratory, they will voluntarily use/abuse it in high amounts, much like many people will. The lack of methamphetamine abuse in wild animals reflects lack of access, not lack of willingness.

The human and non-human primates participate in behavioral testing and brain imaging (like MRI and PET scans) to assess how brain structure and function changes with methamphetamine dependence. Crucially, however, these methods do not allow us to directly monitor the molecules themselves that cause brain dysfunction in addiction. For that, we must undertake studies of brain matter collected from rats or monkeys after euthanasia (death produced by painless administration of an anesthetic).

Once we identify chemical changes in the brain caused by methamphetamine, we seek to correct those changes with medications. Those that are found to be effective in our animals are then suggested to researchers who conduct clinical trials. Our work has contributed, at least in part, to the rationale supporting clinical evaluation of one medication for methamphetamine addiction.

Do monkeys and rats become addicted? As noted above, animals will willingly take drugs of abuse, just as people do. Though methamphetamine changes the chemistry of the brain regions involved in decision-making in animals a manner similar (possibly identical) to that occurring in humans, the consequences of those biological changes are not the same because of the unique way that addiction affects human social relationships. Anyone who has watched “Interventions” knows that much of the real suffering and pain associated with addictions comes when drug use affects the relationships between the individual struggling with their addiction and those who love them. The damage caused to their relationships, the impact on their parents and children and the failure of their plans and aspirations are all major causes of distress in addicted persons. Animals experience none of this and none of the associated emotional pain. By studying them, we can uncover the secrets of how drugs change brain chemistry, although the psychosocial consequences of addiction are uniquely human.

What are our ethical principles? When it comes to animal research, our ethical principles have two dimensions. First, we embrace – not simply accept – the Animal Welfare Act and the regulatory mechanisms that ensure that animal welfare is a key concern in designing and undertaking animal studies. We use the fewest animals possible and the least harmful methods. We do everything possible to avoid causing pain or distress in our studies, and we alleviate it using state-of-the-art methods when we can. Second, it is our ethical obligation to pursue studies that may alleviate the suffering caused by methamphetamine addiction. Human suffering is real; it is all around us. It is ultimately avoidable, if we understand the problem deeply enough. We believe that people suffering from addictions and the people that love them deserve that every reasonable effort be made to address their problem, and we will, consequently, continue our work.

Sincerely,

Professor Edythe D. London, Ph.D.

Professor J. David Jentsch, Ph.D.