Of Tranquilizers and Food Additives

salt crystalsWhen is a tranquilizer not a tranquilizer? When it is a salt substitute.

Lithium chloride, which for decades was the treatment choice for stabilizing mood in cases of manic-depressive psychosis (later bipolar disorder), was originally marketed as a salt substitute for heart and kidney patients under the trade name Westsal. Then, in early 1949, patients using the product started dying unexpectedly from the chemical’s hitherto-unknown toxicity. Among the less drastic, but still undesirable, side effects were “drowsiness, weakness, loss of appetite, nausea, tremors, blurred vision, unconsciousness.” The FDA rapidly declared that people should “stop using this dangerous poison at once” but moved not to ban lithium chloride but to reclassify it from a “special dietary food” to a “drug.” (You can find the whole story at this archival Time magazine article.)

Of course, main effects and side effects are all a matter of perspective. Immediately after the discontinuation of its use as a salt-substitute, research by Australian psychiatrist John Cade showed that lithium effectively tranquilizes rats. He soon proposed that it be used as a treatment for mania in humans. Actually, lithium had been used for mania in Europe in the later 19th century, but the practice seems to have been forgotten by the mid-20th century.

The FDA approved for lithium for the treatment of mania in 1970, and it rapidly became quite popular. Lithium use declined as its many side-effects, some severe, were re-discovered in the following decades. Among its unwanted effects include “weight gain, acne with scarring, thinning of hair, and pronounced tremor, usually in the hands but extending to lips and tongue when the person is stressed, or after prolonged use” (see the Wikipedia entry for lithium pharmacology).

By the bye, lithium was once included in the soft drink 7-Up, because it was mistakenly thought to cure hangovers, always a popular selling feature. (Daily Kos item, 7 March 2008).

[Incorrect passage on origins of Thorazine removed. See comments below.]

Tips o’ the hat to Tim Shearon of the College of Idaho and Denis Goff of Randolph College for pointing out good resources on this item.

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About Christopher Green

Professor of Psychology at York University (Toronto). Former editor of the Journal of the History of the Behavioral Sciences. Creator of the "Classics in the History of Psychology" website and of the "This Week in the History of Psychology" podcast series.

4 thoughts on “Of Tranquilizers and Food Additives

  1. Thorazine=hydrazine? Sure, why not? I will believe anything in print on this particular day.

  2. In the process of tracking down the Iproniazid-Rocket Fuel connection, in response to criticisms (above), I found a chapter from a European Observatory on Health Systems and Policies Series reference that does indeed support at least part of this claim:

    “In the early 1950s, an antitubercular drug called iproniazid was developed from left-over V-2 rocket fuel which had been bought cheaply by Hoffman-LaRoche. But when it was used to treat tuberculosis it produced euphoria: newspapers reported TB patients dancing in the corridors. Psychiatrists were soon experimenting with its potential for the treatment of patients with mental disease. Iproniazid was initially considered in the same category as other stimulants. But in 1952 a series of papers were published arguing that it worked by inhibiting the action of an enzyme called monoamine oxidase, thus slowing down the depletion of these monoamines in the brain. And the substances then identified as neurotransmitters in the brain were indeed monoamines – adrenaline, norepinephrine, dopamine (the so-called catecholamines) and serotonin (an indoleamine). Researchers began to suggest that depression and elation themselves were correlated with the levels of these neurotransmitters, these monoamines, in the brain. Initially, there seemed to be one very serious anomaly – the tricyclic antidepressants such as imipramine did not inhibit monoamine oxidase. However, this turned out to be a clue to a mechanism that would be of major significance – that of reuptake. The tricyclics were shown to block the mechanism by which neurones reabsorb and hence conserve the neurotransmitters they secrete, leaving more of the active neurotransmitter present in the synapse for longer. This mode of action has become crucial to the development of the new family of selective serotonin reuptake inhibitors – SSRIs.” (Knapp, McDaid, Mossialos, & Thornicroft, 2007, p. 148)

    Here’s a second source:

    “With the exception of tranylcypromine (a phenylcycloalkylamine), the first MAOIs (e.g. iproniazid, isoniazid, phenelzine, isocarboxazid) were derivatives of hydrazine (originally used as a rocket fuel)” (Stanford, 2001, p. 433)

    More to follow…

  3. Phil appears to be correct here. I misread a source I was using for background information.
    This is what Nikolas Rose has to say about the matter in his chapter in Mental Health Policy and Practice Across Europe (M. Knapp, D. McDaid, E. Mossialos, & G. Thornicroft (Eds), Open University Press, 2007):

    It is well known that the first widely used psychiatric drug was chlorpromazine (Largactil, Thorazine), developed from antihistamines in the years after the Second World War…. The first [antidepressant], imipramine (Tofranil) was also developed from anti-histamines during the early 1950s…. Tofranil was launched in 1958, to some extent inspired by the success of Thorazine and Largactil, and became established as the first ‘tricyclic’ anti-depressant in the 1960s – so-called because of its three-ringed chemical structure. The antidepressant story is also a narrative culminating in the claim to drug specificity – the claim that the drug acts at the neuronal site of the disorder. In the early 1950s, an antitubercular drug called iproniazid was developed from left-over V-2 rocket fuel which had been bought cheaply by Hoffman-La Roche. But when it was used to treat tuberculosis it produced euphoria: newspapers reported TB patients dancing in the corridors. Psychiatrists were soon experimenting with its potential for the treatment of patients with mental disease. (pp. 146, 148)

    I have removed the incorrect passage on Thorazine from the original post.

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