Better Living through Chemistry?

Jill Littrell, PhD
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Reading the article “Risky rise of good-grade pill” in the New York Times on Saturday once again raised the philosophical issue of how to respond to the burgeoning panoply of ways to alter the human condition. I teach a course in Substance Abuse, which I think needs to be retitled Substance Use/Abuse. In the first lecture, I inform the students that we will be looking at each class of chemical, both illegal and legal, in turn. At the end of the class, we can vote on which substances should be on which list. Having studied pharmacology for the last 30 years, I marvel at the process through which, as a society, we collectively decide that one drug is a problem and another is a life enhancing treatment.

The “good-grade pill” referred to amphetamines. While the medical community at one point propagated the perspective that those with ADHD responded differently to amphetamine than those without ADHD, early on this was disproven. Judith Rapport put the entire class on amphetamine and everyone paid better attention on the drugs. Amphetamines increase the availability of dopamine. Dopamine contributes to memory formation and vigilance. Subjectively, an increase in dopamine decreases the cost of exertion. If you want to memorize and sustain effort, amphetamines will enhance your capacity. So should we put amphetamines in the drinking water? The downside is the potential heart attack. If you want to be creative, you need to be loose, not vigilant. For kids, amphetamines block play behavior. The young of most mammalian species engage in play, which seems to be necessary for developing social skills. Moreover, amphetamines increase inclusion bodies, also found in Parkinson’s patients, in a motor section of the brain (the striatum). So are amphetamines a good idea?

Last year, I attended an ethics symposium on the issue of whether the world was ready for a smart pill. The presenters discussed chemicals that will tweak with the glutamate system. It’s well known in neuroscience that the first step of new memory formation involves an initial glutamate signal. As the audience pondered the question of whether to improve upon the human condition, I remembered another seminar at which Joe Tsien discussed his creation of the Doggie Hawser mouse. Tsien tweaked with the gene for a receptor for glutamate and created a mouse with super learning capacity. In the article published on Doggie Hawser, Tsien grappled with the obvious question of “why aren’t all the mice brighter?” Tsien reflected that glutamate is the brain’s major excitatory transmitter. Too much glutamate signaling and a seizure is provoked. During the course of evolution, nature struck the right balance. Death is too much to pay for being super smart.

In terms of my own bottom line perspective, I think each drug should be evaluated in terms of a cost/benefits analysis with the caveat that chemicals that have been around forever are probably a safer bet than some chemical cooked up last week by a pharmaceutical company. In the class session on opiates, I always find in ironic that the world promotes methadone maintenance while abhorring heroin. Both drugs stimulate opiate receptors. Both drugs produce equivalent effects on mood and behavior. Both drugs are addictive and when discontinued, withdrawal symptoms emerge. To avoid withdrawal, methadone has the advantage of requiring only daily administration in contrast to three times per day for heroin. Neither drug has negative impact on any organ system. However, methadone, unlike heroin, can induce cardiac arrhythmias for which pacemakers may be needed. So which drug is better?

In my substance abuse class, I do cover the process of addiction and the terrible consequences. Neuroscience has contributed a wealth of information on this topic. Neuroscientist, Roy Wise, early on noted that all drugs that induce compulsive intake share the property of increasing dopamine. Drugs that are associated with withdrawal (including lithium and antipsychotics), if they don’t increase dopamine, are not associated with compulsive intake. The current view of addiction is that dopamine agonist drugs can capture the brain’s motivational system. The basic motivational system designed to get the organism engaged in goal directed activity, eating, and procreating, gets hijacked by the drug. The motivational system becomes devoted to acquiring a chemical. Ironically, for some people, alcohol can capture the motivational system. For other people, drinking in moderation (two drinks a day), has very beneficial effects.

I am grateful that the pharmaceutical industry exists. At the beginning of the HIV epidemic, it was devastating to watch as friends died. For those infected with HIV, drugs have enabled living, although the drugs have very negative side effects. So I don’t want to destroy the pharmaceutical industry, (although I think it should be a public utility rather than a profit driven enterprise). If a cure can be found by changing life style, this will always be better than ingesting a foreign substance. All pharmaceuticals have side effects. To my knowledge, positive thinking, relating well, eating healthy, and exercising have no down-sides.

Castino, R., Lazzeri, G., Lenzi, P., Bellio, N., Follo, C., Ferrucci, M., Fornai, F., & Isidoro, C. (2008). Suppression of autophagy precipitates neuronal cell death following low doses of methamphetamine. Journal of Neurochemistry, 106(3), 1426-1439.

Sostek, A. J., Buchsbaum, M. S., & Rapoport, J. L. (1980). Effects of amphetamine on vigilance performance in normal and hyperactive children. Journal of Abnormal Child Psychology, 8(4), 491-500.

Soetens, E., E’Hooge, R., & Hueting, J.E. (1993). Amphetamine enhances human-memory consolidation. Neuroscience Letter, 161 (1), 9-12.

Related MiA Blogs:
The NY Times: When Stimulants are Bad
Stimulants for Good Grades: A Legitimate Use or an Abuse?

12 COMMENTS

  1. One sentence triggered my attention: “I marvel at the process through which, as a society, we collectively decide that one drug is a problem and another is a life enhancing treatment.”.

    Chemistry and chemistry research is working at a certain scale of time. Culture and collective assumptions about chemistry are evolving at a different scale of time, and in a way that might match in complexity the dynamics of the brain network.

    In the same way human higher-level reasoning trumps the power of an individual neuron (but evolves much more slowly, and is much less reactive), I do believe that eventually collective intelligence trumps and transcend the finding of any individual or group of individual.

    In any case, thanks for helping move collective intelligence ahead!

  2. Interesting how dopamine is the neurohormone du jour now that serotonin has had its 15 minutes of fame.

    Or is it that, the mental illness market being saturated, drug companies are now pursuing the lucrative addiction market, softening up public opinion by claiming a pivotal role for dopamine in addiction?

    See this March 2012 US congressional briefing by the Friends of the National Institute on Drug Abuse (NIDA) “co-sponsored by 24 organizations and organized by the APA’s [American Psychological Association’s] Science Government Relations Office” http://www.thefriendsofnida.org/030112_event.asp

    “….The National Institute on Drug Abuse (NIDA) follows a multipronged strategy in researching medications development, focusing on 1) medications already approved for other disorders with potential application to addiction treatment, 2) new compounds that can interact with recently discovered targets in brain circuits affected by addiction, 3) the use of biological agents (e.g. vaccines and engineered enzymes) that retard entry of addictive drugs into the brain, and 4) the combined effects of medications with existing and novel behavioral therapies….”

    This corresponds with recent changes in the DSM-5 enlarging diagnoses of addiction.

    Alkermes, Inc., the pharma behind Risperdal Consta (coincidentally a dopamine antagonist), was a prominent sponsor. Alkermes products http://www.alkermes.com/Products/Key-US-Products and pipeline here http://www.alkermes.com/Research-and-Development/Pipeline

    I would take all the news about the role of dopamine in addiction with a grain of salt, or maybe a shot of Risperdal Consta. My intuition is it’s going to turn out to be “chemical imbalance” redux.

      • True. I might have a reflex reaction to any mention of the “big 3” neurotransmitters. Who knows, one of these theories may yet pan out.

        Attributing addiction to dopamine may not imply a drug solution to you, but it means Risperdal Consta to Alkermes! Makes sense to shoot those darned unreliable addicts up with drugs.

  3. Chemicals both illegal and legal usually are voluntarily taken. You wrote “In my substance abuse class, I do cover the process of addiction and the terrible consequences.”
    Would you also cover the involuntary taken chemicals and the terrible consequences?
    Dr. Nancy C. Andreasen nytimes.com/2008/09/16/health/research/16conv.html
    “losing brain tissue … as much as 1 percent per year.”
    Where the psychiatrist is addicted to forcing chemicals on their patient.

  4. Perhaps its all about chemistry, when we see a bigger picture?
    Underlying cognition, is the essential need of organismic homeostasis?

    “LIFE AS HOMEOSTASIS

    Living organisms are self-replicating and self-sustaining dynamic chemical systems. They obtain energy from, and information about, their environment – including its chemical, physical, geological, and biological components. A feature that distinguishes living from non-living matter was identified by Claude Bernard.

    This is homeostasis – the maintenance of a constant internal environment despite changes in the external environment. A second feature of all known life, first proposed explicitly by Schleiden and Schwann, is that living things are composed of spatial compartments, called cells.

    Cellular homeostasis requires a system of integrated feedback and feedforward, producing adaptive responses to, and anticipation of, ultimately uncontrollable changes in the properties of the outside world.

    As life evolves, it extends its reach by maintaining its constant internal environment in new external environments, previously inhospitable. _John F. Allen, Ph.D. “Journal of Cosmology, 2010.”

    As self-awareness evolves, it extends its reach by maintaining its constant internal environment in new passing moments?

    Origins, Abiogenesis and the Search for Life in the Universe. http://www.amazon.com/dp/0982955219