When noradrenaline kicks too much ass…

…it’s a nice idea to crank it down a bit.

I have it in my head that serotonin and noradrenaline aren’t my best friends (Effexor, an SNRI, was an absolutely horrid experience). I’ve often thought this. And I’ve often thought that the holy grail of happiness, monoamine neurotransmitter balance, being understood, too-high noradrenaline might be an ignored problem for many depressives.

Noradrenaline (norepinephrine) is a nasty little chemical when it misbehaves. It serves various functions, but as a stress hormone it can get out of hand when our mental state gets out of hand. When it’s good, it provokes a temporary fight-or-flight response, provides anti-inflammatory help around neurons, helps with decision-making; when it’s not good it can cause anxiety, and thus some damage (hypertension, adrenaline (its downstream product) and cortisol overflow, neuronal toxicity and on and on…). So in my opinion any means of kicking down NA might not be a bad idea if there aren’t too many negative side-effects. 

I wonder if one can reduce NA by reducing nutritional precursors (egg, meat, nuts, dairy, soy); I know I do better when I eat less protein; others may also. Tyrosine and phenylalanine (tyrosine’s precursor) are needed to produce NA (and therefore, adrenaline), so reducing intake of these sources is an interesting question…

…on the other hand, I know that I can never have too much dopamine (that’s why I love opiates: all the dopamine goodness without the NA release), so I’m curious about finding a way to lessen NA production because DA is the precursor for NA; and the less protein I eat, the less DA I produce and the less beneficial DA effects I get… I really would like to be able to chow down on more protein.

~So… how to reduce an overproduction of noradrenaline without reducing dopamine…

…this is my folly.

Dopamine beta hydroxylase converts dopamine to noradrenaline, which then converts to adrenaline. In my searches I stumbled upon and found ways to inhibit this step in conversion. For example, Etamicastat is a novel (?) drug used for the treatment of heart failure and hypertension, but I wonder how well it would work off-label for help with NA overload, once it’s approved for sale. There are other DβH inhibiting drugs around (disulfiram, dopastin, bupicomide, tropolone), but who knows which can legally be used off-label?… though I really think it might be worth a try…

…I might even try, myself.

Interestingly, fusaric acid is a natural DβH inhibitor. It is isolated from Fusarium fungi, and one species, Fusarium venenatum, is used for some kind of whacked-out neolithic foodstuff marketed as Quorn. Though used in research, fusaric acid is considered a toxic by-product… curious, though.

Separation distress and the importance of valued people

I stumbled onto two interesting authors, Jaak Panksepp and Douglas Watt…

“‘Big Pharma,’ as big business, seeks antidepressants that may become billion-dollar blockbuster drugs. Accordingly, it may neglect drugs that are off-patent (e.g., buprenorphine) as well as those that only serve a small subset of the population. Many authors (ever since Valenstein, 1998) have argued that the pharmaceutical industry may be exercising an increasingly distorting influence on prescription and treatment landscapes for the whole of medicine in the United States. This may be particularly true in relationship to depression, where many depressed patients are never referred to psychotherapy and instead are only put on first-line antidepressant drug regimens under the simplistic aegis that depression is “just a chemical imbalance.” These trends take place despite evidence that pharmacology is often only partially effective in depression (see recent STAR*D reports: Rush, 2007; Rush, Trivedi, & Fava, 2003) and despite evidence that patients suffering from trauma-related depressions do quite poorly treated alone with psychopharmacology without psychotherapy”

 Far be it from me, an academically untrained but round-eyed acolyte of the big world, to feel at all qualified to take on the authors’ implication that depression may be the result of anything but “a chemical imbalance” though an initial “trauma” may have initiated the process, and the chemical imbalance following the trauma can’t be fixed wholly pharmacologically. But I’ll state modestly that some day soon, almost every state of depression, whatever the cause, will be cured chemically sans psychotherapy…

…psychotherapy definitely has a purpose… probably always will; intelligent people understand that they have subjective limitations regarding self-awareness, and some have an interest in resolving recurring, stunting issues, or simply gaining insight for the sake of growth with the help of trained facilitators. But some day drugs will blow away our depression, regardless, with remaining only a curious interest in why we do the things we do and think what we think, for the sake of treating ourselves and others better.

~But my little declaration is not the reason for this post. Jaak Panksepp and Douglas Watt really have their stuff goin’ on, and are speaking my language. My personal theory of depression (…depression not caused by an innate anomaly) involves three roots: an unsuitable industrial diet, inappropriate exercise (not enough and chronic cardio), and stressors, including modern stressors (pollution, lifestyle etc). In this piece, the authors deal with separation stressors leading to a “protective” state of depression (do I smell the pernicious stench of dynorphin again?).

Whether or not this thesis is correct, the thing that jumps out and reminds me is the importance of keeping one’s self as engaged and socially involved as possible. Clearly (if only for the production and cultivation of calming oxytocin, which is known to sustain opioid reward in the brain), the importance of maintaining and nurturing relationships with people we value and who give us value in return can’t be overstated in a world that increasingly creates and promotes options for insularity and “aloneness”.

Equally, one must have a healthy hierarchy of values…

…if not, being depressed and alone might actually be a better situation than being depressed with people who don’t elevate us… don’t challenge us to go higher, but erode our quality of life, sense of self-esteem and our quest for happiness. In this case, until one has redeveloped a healthy sense of worth through proper diet, appropriate exercise, a low-stress lifestyle, and insight perhaps helped by psychotherapy, I think sometimes we can wait until we are in a better state to nurture rewarding relationships with quality people…

…just relax, and be good to yourself first.