Bupropion, Mood, and Healthy Volunteers

I've always found bupropion to be an extremely fascinating drug. Somewhere in between the world of psychostimulants and more widely prescribed antidepressants, it appears to have the making of a true "psycho-energizer"/thymoleptic. It's even indicated for smoking cessation in those without other psychiatric diagnoses. A couple years back, I wrote an article about it here.
In the article, I hint that many of bupropion's beneficial effects might not be felt in more "normal" people unless higher dosages are used that correspond to its dopamine transporter affinity. However, this abstract points to the idea that lower dosages might provide more beneficial effects on mood for normal individuals:

J Clin Psychopharmacol. 2003 Jun;23(3):233-9.

Neurochemical and psychotropic effects of bupropion in healthy male subjects.

Gobbi G, Slater S, Boucher N, Debonnel G, Blier P.

Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec, Canada.

Bupropion is a weak inhibitor of noradrenaline (NE) and dopamine (DA) reuptake and has no direct action on serotonin (5-HT) neuronal elements. In the rat brain, bupropion suppresses NE neuron firing activity via the activation of alpha(2)-adrenoceptors and increases that of 5-HT neurons through an indirect action on NE neurons. Twenty-five healthy young male volunteers, with no previous history of psychiatric disorders, were randomized to one of four 7-day regimens: placebo, bupropion (150 mg) once daily, bupropion (150 mg) twice a day, and methylphenidate SR (20 mg daily). To assess the activity of the NE reuptake process, the blood pressure response to intravenous tyramine was determined. A decrease in the systolic pressure response to tyramine was considered evidence of NE reuptake inhibition. Effects on 5-HT reuptake were assessed by measuring whole blood 5-HT concentration, with a decrease serving as an index of 5-HT reuptake blockade. The Profile of Mood States (POMS) scale was used to assess behavioral and psychological changes. Neither bupropion nor methylphenidate altered the tyramine pressor response, in contrast to previous data that demonstrated decreases were obtained with NE reuptake inhibitors. Neither drug modified 5-HT concentrations. However, POMS scores revealed that bupropion at a dosage of 150 mg/day increased composedness, agreeability, and energy, whereas 300 mg/day improved only attention. In contrast, methylphenidate improved only energy. These data provide no evidence that bupropion acts as an inhibitor of NE or 5-HT reuptake in healthy humans. Presumably it enhances synaptic availability of NE by increasing release. Yet, because its behavioral profile is different from that of methylphenidate, it may not share all the biochemical properties of psychostimulants.

It should be noted that 300mg of bupropion is usually considered the standard dose for treatment of depression, while 150mg is the starting dose. So it is possible that starting individuals on 300mg had side effects that minimized any positive outcome. They might have been better off had they been allowed to titrate the dose up gradually. But Perhaps this study speaks to a broader concept. "Cosmetic pharmacology" in individuals who do not meet the requirements for severe affective disorders might benefit more from the use of sub-therapeutic doses of antidepressants.