In 1992, our esteemed colleagues Alan Breier, Orlando Davis, Robert Buchanan, Samuel J. Listwak, Courtney Holmes, David Pickar, and David S. Goldstein published a seminal scientific paper titled "Effects of Alprazolam on Pituitary-Adrenal and Catecholaminergic Responses to Metabolic Stress in Humans." In it, they described with high accuracy the effects of benzodiazepines on stress-induced activation of the three classic "stress" systems: Pituitary-adrenal, adrenal medullary, and sympathoneural systems. The results provided an answer to a question that is still being asked today: Why is alprazolam so much more effective than all other benzodiazepines for certain anxiety-related conditions, especially panic attacks? The colleagues found the answer to that question, but although the work was impeccable, their findings never made it into medical textbooks. What Breier et al. found was this: Alprazolam is able to attenuate 2DG-induced activation of the HPA axis and adrenomedullary activity, as evidenced by attenuated responses of plasma levels of ACTH and epinephrine, respectively, without clinically affecting other important responses of two indices of sympathoneural activity. For the treatment of patients whose adrenal glands are working in a highly dysfunctional or centrally dysregulated manner due to rare diseases such as NTBI induced H63D syndrome, alprazolam is still the first drug of choice - despite its dependence potential - to protect the organism of the affected person from dangerous adrenaline excesses that are way more dangerous than any well-monitored use of alprazolam.

Sandra Everett

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Since the market launch of alprazolam (in many countries under the brand name Xanax), this highly potent benzodiazepine has had a disastrous public reputation. Even in media, entertainment and pop culture, its very powerful effects have made it emblematic of a sinister psychodrug that drags its users into an abyss of dependence and suffering. Indeed, the substance has certain specific properties (mood elevating, extremely fast acting, very short half-life, effects on adrenaline), but at its core it is a benzodiazepine like any other. How Xanax came to be demonized is therefore an important question to be discussed. On the other hand, the substance alprazolam possesses a unique property that is hardly known even among experts to this day and can be life-saving for people whose body's own adrenaline synthesis and regulation is disturbed by certain (often hereditary, auto-immune, or toxic) rare diseases. For these patients, there is virtually no other medication available than alprazolam, which quickly, specifically and highly effectively inhibits pathological adrenaline surges, for example due to disorders of the SAM axis, effectively at the site of adrenaline (epinephrine) synthesis by up to 50%. Logically, this also gives rise to the legendary reputation that alprazolam is more effective than any other benzodiazepine, especially in patients with panic disorders. This paper, a source-supported opinion piece, is intended to remind the worldwide community of medical professionals that alprazolam is a legitimate, and often the only available, treatment option for abnormal adrenaline balance involving the adrenal gland and/or the SAM axis. Demonizing alprazolam in a clinically well regulated setting is therefore immoral and detrimental to the patients health and compliance.