My dosing theory for “scary” drugs (and a poke at the trashy values of the collective and how they affect me)

These drugs have two things in common; one is their incredible efficacy when used by rational, lucid people who want to live a full healthy life:

cocaine, amphetamine, methamphetamine, methylphenidate (narcolepsy, ADD, off-label depression)

morphine, heroin, codeine, oxy’s, opium, tramadol, buprenorphine (chronic pain, off-label depression, anxiety)

marijuana (sedation/stimulation, anxiety, pain relief, depression)

benzodiazepines, barbiturates (sedation, anxiety)

psilocybin (pain, depression)

The second thing they have in common is the difficulty getting a prescription for them because they are either illegal, or stupid people exist in the world; so instead of letting them voluntarily take themselves out of the gene pool like nature intended, the State, many moons ago, had taken upon its self the uninvited task of taking care of these dullards at the expense of my liberty and my right to procure the drug of my choice, in the name of some false “altruism” or “greater good” because maladroits get themselves into trouble with drugs (as if they wouldn’t without drugs); and somehow society would become a dangerous or less safe place otherwise, or some such nonsense.

It’s telling that, because we’re caught in this frame of nanny-statism and legalities, one of the main things drug researchers peel their eyes for, like hawks, are drugs that make us feel really good, too good, too soon. Fear of litigation is a reason we have “safe”, mediocre, usually inefficacious modern psychiatric drugs that have little value and crappy side-effects, yet are continually stuffed down the throats of trusting, half-witted souls, a few of whom actually get some benefit (bless you)… I wonder if visionary, progressive pdocs who have to dole out this junk feel any kind of guilt or frustration. I know that I would feel weary if I could not script, off-label, drugs like methamphetamine (desoxyn), laudanum (yes, it still exists in the pharm repertoire) or marijuana.

~But, I think there’s something else afoot here as well:

…”‘k, so you guys at MumsdrugCo have developed this drug that gets rid of depression. Right on; I could sure use it. Umm, can I try it? No? It makes volunteers in clinical studies too happy… so it’ll make me feel really good, and… we, don’t… want this… do we? ‘K, I guess you guys know what you’re doing… I suppose. Umm, I have to tell you though: all the antidepressants I’ve tried over the years have done nothing for me except make me feel worse. I felt better when I didn’t take them at all. I’ll tell you what did work very well, though; opium and dextroamphetamine; dextroamphetamine worked on an as-needed basis, maybe twice a week. Then I discovered that opium targeted as much of an extent what was wrong with me. Opium cycled on for a while, then cycled off for a month, then back on really does help me a lot.

“You say I shouldn’t do that? Why? I could get into trouble with it? Know something? I think you’re projecting; I think you could get into trouble with it because you would doubt yourselves in my situation. Know what else? I think, because you and the legislators who govern you don’t trust yourselves, you won’t let drugs through that could benefit so many smart people, and now we all have to suffer because of stupid people and your own self-doubt. And as usual, given the reigns of state authority, like any cop, doctor or politician, notwithstanding your fear of litigation, you feel free and qualified to impose your values upon me; and the things you value are more often than not, of little value.”

Jesus and John Galt wept.

~Certain patients who can’t take care of themselves or are not capable of thinking rationally or projecting plans for the future should follow the advice of their doctors only, and ignore the following…

…but for those of us who crave a happy productive life, “scary” drugs are, in my opinion, among the best for what ails rational people. Some get positive results from taking very small, scientific daily “lifting” doses, titrating up when necessary, then after a few months, tapering down and off for a period of time (maybe a month; maybe two); then starting again. I don’t think it’s in our interest to take any psych drug, pharm or not, continuously without cycling off (well, more serious cases like schizophrenia or bipolar might be a different story). The brain is plastic and in a state of constant homeostasis, and I think more harm than good results from a constant bombardment of exogenous chemicals… who do you want to be when you’re seventy?

…I would rather live a month or two with depression, knowing that I’m going to feel better again in a while when I resume dosing up, than take a chance that my personal chemistry hasn’t had a time of rest and a chance to get back to “normal”, as bad as “normal” might be (and who knows? maybe I’ll feel better drug-free for a while, or…?). I don’t want my neurons (at least) to be permanently twisted some day…

…so I think cycling on and off is the way to go if one doses every day. I’m in a cycling off period right now because, frankly, I think doctors are up their asses with daily scientific fixed dosing. I don’t buy into the theory that the body must take this smooth bombardment, on and on, even when the patient knows in their gut it’s time to taper off, at least for a while.

~So in one week I’ll be opiate-free, and will not take it for at least one month. I’ll keep you posted on how I feel during this time. It has not been hard to taper; I should say rather, it hasn’t been hard because I’ve had some great help from benzo’s for anxiety, trazodone to knock me for the night, and baclofen (an amazing wonder drug) for everything else; wow, this combo works well.

~Another dosing schedule is possible; if one prefers to not dose every day, dosing every three days, or twice a week can work too. It’s not “scientific”, in that the body doesn’t have a constant level of chemical within, but who can tell me that a doctor knows best what works for me if I achieve acceptable results taking a substance on an as-needed basis?… and besides, how do we know that it is not healthier to keep the body on alert and “guessing” what’s going to happen next, instead of on a predictable course of action that the body sees through, laughs at and compensates for?…

…so, when I start dosing again in about five weeks, I’m going to try this theory and let you know how it goes…

…I think we’re going to be pleasantly surprised.

~Now, if only these market products were available, unscripted, from legal vendors, would we finally be free to experiment openly and share our results with each other instead of having to skulk about on the net, like criminals. Imagine the added bonus of lower prices thanks to competition and no Organised Crime dictating cornered markets.

…oh well. I can dream for that day.

~Let me know what works for you. Feel free to talk about any drug used off-label for the last six months at least, and what your system is. I’m curious.

Refractory depression & kappa system over-activation?

Sometimes I wonder if Nature likes us much. She seems to hate to see nice people who deserve it in an unconditionally happy state. Sometimes I think that she thinks that we are still in the paleolithic, and really happy people are impractical idiots who don’t have the wit to perceive danger, so quickly weed themselves out of the gene pool before reproducing to their full potential… so she does something about it. She “helps” them…

…is happiness an anomaly? I know this question is beat to death and naive, and I’m being facetious. Considering modern hunter-gatherers, primitive localist cultures supposedly most in line with our “ideal emotional state”, one might believe that perfect emotional homeostasis is more prevalent per capita with them because they live in an environment with stressors more compatible with our evolution compared to industrial cultures, and maybe it is; but even with these Peoples, emotional states go crooked, and when they do, they don’t twist toward unbridled joy.

Our bodies have a disheartening way of efficiently maintaining a skewed emotional equilibrium that, for too many of us, leans away from euphoria. Euphoric people are rare, though we’ve all known that guy/girl who seems to be in a constant and enviable state of bliss, always living in a sunrise. Not much seems to trigger a bad mood in these people. I have to wonder if, woe not being within a normal state of equilibrium, this state of apparent irrational cheerfulness isn’t a defect as well, albeit a lucky and fortunate one (though the line between happy and manic might be thin; and how much of a cost in longevity might this state of chronic “up” incur? On the other hand, does depression produce as much or more longevity-sapping in a body?).

I’m looking at the role of kappa (κ) opioid receptors and dynorphin endogenous opioid peptides and the implications for depression from a faulty κ system. Have some refractory depressives been given the curse of an overactive κ system? If so… shit. But, if so, despite the overwhelming complexity and interaction of our amazing/intimidating biology, maybe this is a good enough place as any for a depressive to start looking for some long overdue answers.

There is a world to know and I’m not getting too much into κ agonism/dopamine; dynorphin links with/CREB/NMDA receptors; the fact that dynorphin is produced in different areas in the nervous system with various functions; other neurotransmitters; hormones like prolactin or enzyme connections yadayada and will mostly be ignored here. It all turns into an overwhelming mess and would just numb the mind of anyone who isn’t a geek. Hell, I’m feeling numb just writing this paragraph…

…I just want to know the kappa system’s role in depression and how to stop it.

κ receptor/dynorphin overactivity is implicated in depression. Apparently Nature in her often disappointing wisdom has forced us to prevent, in her opinion, an irrational and self-destructive state of elation (yay. thanks a lot). I don’t think we can cure an imbalance at this time, so I’d be happy enough to just control it… somehow. And since I believe that happiness is our birthright, I think it behooves me to search for a way out of this kappa mess and fight back any way I can… screw this

Dynorphin is a varying group of opioid peptides that act as neurotransmitters. Dynorphin has the strongest affinity, and is the primary peptide, for the κ receptor. It is also a very potent endogenous opioid pain-killer. Its other functions deal with learning and memory, emotional control and stress response. The problem is, unlike its relatives endorphin and enkephalin, it doesn’t make one feel good; Quite the opposite, actually. A protein called CREB activates a gene that makes dynorphin. CREB triggers this “down” by increasing dynorphin… …and stress/pain triggers the whole cascade; no stress=no dynorphin release/kappa receptor overactivity=no “down”.

Opioid peptides endorphin and enkephalin release dopamine by disinhibiting dopamine pathways and help to make us feel good. Dynorphin doesn’t like us to feel good, so inhibits dopamine release (as do kappa receptors). In fact, dynorphin inhibits dopamine more and more with repeated illicit drug use, so would rather we overdose on drugs than let us feel good.

…stupidjerkdynorphin.    ;(

So it seems that there is a mood balancing act between dynorphin and endorphin/enkephalin.

To be fair, maybe part of the role of the kappa system is involved in learning to avoid certain situations, as if to condition one what to not do, via unpleasant stimulus; [eg: rodent bites… “ouch”… kappa activation… “I feel depressed. I’m never doing that again.”] …Well, who knows? ‘Tis but a theory. And maybe κ activation makes one numb, pain-free and “down” as a survival mechanism; possibly as a way to force lucidity and introspection and help one deal with a problem in a bad situation. Speculation, I know.

So, it seems that a goal for some depressives may be to find a relatively safe method for blocking dynorphin (or whatever else may increase dynorphin activity; perhaps CREB, for example), and thus put to a stop its well-meaning but apparently misguided effects. Learned helplessness is another negative side effect of kappa overstimulation, no doubt partly because dopamine, our driving, motivating neurotransmitter, is inhibited; disinhibition would go a long way to fighting depression. Also, blocking dynorphin allows glutamate, an excitatory neurotransmitter involved in learning and memory, to be released and restore functional plasticity in the hippocampus, reversing the phenomenon of learned helplessness…

…as well, non-pharmaceutical ways to reduce stress cannot be stressed enough: relaxing enjoyable activities that produce a somewhat meditative state and help to take one out of one’s self for a while really do work. I’ve found that relaxation through the senses (charcoal burning resin like frankincense and myrrh for smell, low lighting and a warm atmosphere for sight, meditative music for hearing, caressing and sex for touch, slowly eating good whole food for taste) work well for the short-term, like at home after work. Absolutely worth it…

…but, for god’s sake, don’t start taking downers like benzo’s to try to control stress/kappa to achieve the desired effect. Jeez, the last thing we need is a dependency on these things, which are the worst, in terms of physical addiction complications… really, I would rather be hooked on opies than benzo’s any day.

~Thus, buprenorphine shines its beacon of hope once again. It is not only a partial agonist at the Mu (μ) receptor (which produces a much valued non-euphoric state for therapy), but is also a κ antagonist, which effectively blocks dynorphin from κ receptors and creates a non-depressive state. Bupe may not only be just the thing for some with endorphin deficiency syndrome, but may also help people with a skewed dynorphin/κ system or even, perhaps, general depression and dysthymia.


Btw, if you think I’ve missed something, please feel free to comment for everyone’s benefit.