Introduction - 7 July 2005 Leap
Universal Living Memory
E=MCsquared
Evolution equals memory times circulation that is recurrent/repeating
Happiness is what we feel when our biochemicles - of emotion, the neuropeptides and their receptors, are open and flowing freely. It is a scientific fact that we feel what others feel. - emotional resonance. The oneness of all life is based on this simple reality.
Our molecules of emotion are all vibrating together.
--- Candace PertPlanetary Rhythms
Today iZ the day, it started.
London Bombing: Grokking beauty and the Beast
* now we go to workNschool...again.*
LEAPING LINKS:
* Quantum Mind: www.quantummind.net
* Grokking Love: Grokking Love
* ShamYnic Medicinal Foods: Eating Spitural Intelligence
I Love Chicken
I Love Pomegranate Juice
Notes of focus:
And so to every sailor, soldier, airman, and marine who is involved in this mission, let me say you're doing God's work.
~ President George Bush December 1992
In his scintillating article on the Somalian incursion, Harper's editor Lewis Lapham, one of the few left-liberals who remains staunchly anti-foreign intervention, quotes the above words from our recent president. (Lewis H. Lapham, "God's Gunboats," Harpers Magazine, February) Lapham notes that Bush issued his "prelate's benediction" to the troops even though lacking "both the miter and the shepherd's staff." He also notes – in a timely reminder to those conservatives who have not yet re-examined their devotion to the preceding president – that on that very same December day Ronnie Reagan, speaking at Oxford University, urged the United Nations to develop "an army of conscience" to confront the "evil (that) still stalks the planet" even after the death of the Soviet Union. Since it is difficult to imagine evil stamped out from the world very quickly, this presumably implies a permanent standing world army to vanquish and keep down evil and sin in whatever quarter of the globe they might raise their ugly heads. In short, a permanent global Crusade.
Remedy of disfunctional hypo-well "the big Wallow"
haha..bust my gut laughing...and singing "listen listen chilgren".....lalalalalal...why all the suffering today..why does it begin just this way..karma? DNA photonic expressions? raptilian tendencies?...lalalalala
Ponder on this children...OK..go PONDER the WOLLAR.....
** *** PONDER 554 **** ***** ****** *******
Eating Spiritual Intelligence
http://www.biopsychiatry.com/
http://mdma.net/
http://www.hedweb.com/hedethic/hedon1.htm
"I feel absolutely clean inside, and there is nothing but pure euphoria. I have never felt so great or believed this to be possible. The cleanliness, clarity, and marvelous feeling of solid inner strength continued throughout the rest of the day and evening. I am overcome by the profundity of the experience..."
It's all very well being told our descendants will experience every moment of their lives as a magical epiphany.
For emotional primitives and our loved ones at present, most of life's moments bring nothing of the sort.
In centuries to come, our baseline of emotional well-being may indeed surpass anything today's legacy wetware can even contemplate.
Right now, however, a future Post-Darwinian Era of paradise-engineering can seem an awfully long way off.
Mainstream society today has a desperately underdeveloped conception of mental health.
There's clearly a strong causal link between the raw biological capacity to experience happiness and the extent to which one's life is felt to be worthwhile. High-minded philosophy treatises should complicate but not confuse the primacy of the pleasure-pain axis.
So one very practical method of life-enrichment consists in chemically engineering happier brains for all in the here-and-now. Yet how can this best be done?
Any strategy which doesn't subvert our inbuilt hedonic treadmill of inhibitory feedback mechanisms in the CNS will fail. Political and socio-economic reforms offer at best a lame stopgap. To the scientific naturalist, all routes to happiness must ultimately be biological: "culture" must be neurochemically encoded to exert its effects. Some of these routes to happiness involve the traditional environmental detours.
They are too technical, diverse and futile to tackle here. If the quality of our lives is to be significantly enhanced in the long term, then the genetically predisposed set-point of our emotional thermostats needs to be recalibrated. The malaise-ridden norm typically adaptive in humanity's ancestral environment must be scrapped.
So while we wait for germ-line gene-therapy to become standard, it's worth considering instead how ordinary early twenty-first century Homo sapiens can sustainably maximise emotional well-being with only present-day pharmacology to rely on.
No less importantly, how is it possible to combine staying continuously high with retaining one's sense of social and ethical responsibility to other people and life-forms?
Extracting reliable information on this topic is extraordinarily difficult for laity and professionals alike. The layman is more likely to be given heavily slanted propaganda. Unvarnished fact might confuse his supposedly uneducated and functionally diminutive brain. Career-scientists, on the other hand, are bedevilled by a different problem.
Access to funds, laboratories, raw materials, journal publication, professional preferment, and licenses to conduct experimental trials is all dependent on researchers delivering results their paymasters want to hear. The disincentives to intellectual integrity could scarcely be greater; and they are cloaked in such reputable disguise.
By way of illustration, it's worth contemplating one far-fetched scenario. How might an everlasting-happiness drug - a drug which (implausibly!) left someone who tried it once living happily-ever-after - find itself described in the literature?
"Substance x induces severe, irreversible structural damage to neurotransmitter subsystem y. Its sequelae include mood-congruent cognitive delusions, treatment-resistant euphoria, and toxic affective psychosis."
Eeek! Needless to say, no responsible adult would mess around with a potent neurotoxin under this description.
Several excellent researchers play the game by the rules. They keep their heterodox opinions to themselves. Others find such cognitive dissonance too unpleasant. So they gradually internalise the puritanical role and tendency to warped scientific prose expected of them. [Whereas horribly-tortured experimental animals, for instance, blandly get "used" and "sacrificed", certain drugs always get "abused" by "drug-abusers"] On the other hand, some of the most original and productive minds in the field of psychopharmacology - pre-eminently Alexander Shulgin - have already been silenced. Many more careers have been intellectually strangled at birth or consigned to professional oblivion.
The danger of poisoning the wells of information, for whatever motives, is straightforward. When young people discover they have been lied to or deceived, over cannabis for instance, they will pardonably assume that they have been lied to or deceived over the dangers of other illegals too. And this, to put it mildly, would be exceedingly rash.
Most recently, the Internet daily delivers up an uncontrollable flood-tide of fresh ideas to counter official misinformation. Unfortunately, a lot of it isn't much more objective in content or style than the professional journals it complements. Devising one's own system of filtering and quality-control to drown out the noise is a challenging task for anybody.
Eating Spiritual Intelligence
SOME DEAD ENDS
One spectacularly incompetent route to a lifetime of happiness involves taking unsustainable psychostimulants such as cocaine or the amphetamines. In the short term, their activation of the sympathetic nervous system tends to elevate mood, motivation and energy. Users tend to talk a lot. Self-confidence is enhanced: these are "power drugs". Physical strength and mental acuity are variably increased. Whereas cocaine blocks the neuronal re-uptake of the catecholamine neurotransmitters noradrenaline and dopamine, amphetamine triggers to a much greater extent their synaptic release. It feels coarser, lasts longer and costs less.
In either case, libertarian indignation that the State presumes to subject its citizens to totalitarian-style mind-control should not obscure the fact that for most purposes these are not useful drugs. This is because the central nervous system supports a web of mutually inhibitory feedback-mechanisms. In response to a short-term increase of mood-mediating monoamines in the synapses, the genes and neuronal receptors re-regulate. So at best no real long-term benefit is derived from the use of such compounds. Neither cocaine nor amphetamine yield the sustained activation of intracellular signal-transduction cascades needed to cheat the hedonic treadmill and keep us happy.
Some people continue to take psychostimulants casually for years without serious harm. Yet the potential risks of adverse physical, psychological and social ill-effects are high. Hence their use is best discouraged.
The "depressant" opioids are somewhat more benign. They are effective painkillers. They can also be extremely pleasurable. In classical antiquity, Aristotle - admittedly not always the soundest authority on medical matters - classified pain as an emotion. Opium was a traditional remedy for melancholic depression; its efficacy is arguably superior to Prozac, though controlled clinical trials are lacking. In "animal models", opioids reverse the depressed behavior, learned helplessness and neuroendocrine responses associated with clinical depression. By contrast, opioid antagonists such as naloxone exacerbate them. To confuse matters further, sufferers of depression typically share an increased sensitivity to pain; and modern so-called "antidepressants" can themselves act as "physical" painkillers. Conversely, mu-opioid receptor agonists offer both unsurpassed pain-relief and extraordinary emotional well-being. There is clearly an intimate link between "physical" and "emotional" pain. In defiance of dualist metaphysics, the opioids tend to be best at banishing both.
Contemporary medical orthodoxy classifies drug-induced bliss as an "adverse side-effect" of analgesics - even in the terminally ill. Yet we could all do with having our native endorphin systems enriched. Next century and beyond, the customised site-selective successors to today's opioid drugs will play a critical role in promoting emotional superhealth.
Unfortunately, present-day opioids are flawed. Taken at fixed dosage, they lose some of their euphoriant and analgesic effect as tolerance sets in; opioid drugs are physiologically addictive. Overdoses can cause respiratory depression; physical pain, by contrast, is a potent respiratory stimulant. When taken recreationally, opioids inspire a dreamily contented disengagement from the problems of the world. Their use diminishes the drive to constructive activity as consumers in today's competitive global marketplace. More insidiously, excess consumption of narcotics inhibits the release of endogenous opioids normally induced by social interaction with friends and family. By diminishing the craving for human companionship, the addict substitutes one form of opioid addiction for another. Thus junkies are usually "selfish".
The physical risks of opioid use shouldn't be exaggerated. Most of the problems that users suffer ultimately derive less from their choice of drug itself than from the illegal status of narcotics in prohibitionist society. Yet even if they were legal and given away in cereal packets, opioids wouldn't make a good choice of mood-booster - or at least not in their present, crudely non-specific guise. Kappa-agonists, for instance, impair dopamine function. They have dysphoric and psychotomimetic effects: one might as well drink ethyl alcohol spiced with meths. The paradise-engineers of posterity will surely weed out such adulterants from their elixirs altogether.
Eating Spiritual Intelligence
MARIJUANA
By contrast to today's opioids, marijuana isn't usually addictive in the traditional sense of the term.
It can still be habit-forming. Marijuana has euphoriant, psychedelic and sedative properties. Experiments with stoned rats suggest the drug reduces the amount of corticotrophin-releasing factor (CRF) in the amygdala. Excess secretion of CRF is associated with abnormalities in the HPLA axis and depression. The rebound surge of CRF on ceasing cannabis-use is associated with increased vulnerability to stress and a withdrawal-reaction, arguably one good reason not to stop in the first instance. A dysfunctional response to stress, linked to a chronically overactive HPLA axis, causes anxiety disorders and depression; CRH-type 1 receptor antagonists like antalarmin are being investigated as potential anxiolytics and antidepressants. The deeper roots of our malaise lie buried in the evolutionary past.
The primary psychoactive ingredient in marijuana is THC, tetrahydrocannabinol. Smoking or eating marijuana and its complex cocktail of compounds may rarely trigger episodes of depersonalisation, derealisation and psychosis. Sometimes it can induce paranoia, particularly in advocates of The War Against Drugs.
More commonly, marijuana just leaves the user pleasantly and harmlessly stoned. It's fun. Sleepiness, pain relief and euphoria are typical responses. Indeed the first brain-derived substance found to bind to our cannabis receptors was christened "anandamide", a derivative of the Sanskrit word for internal contentment.
Getting high may thus serve as an innocent recreational pastime in an uncaring world.
Yet marijuana is not a wonderdrug. Cognitive function in the user is often impaired, albeit moderately and reversibly. Marijuana interferes with memory-formation by disrupting long-term potentiation in the hippocampus. One of the functions of endogenous cannabinoids in the brain is to promote selective short-term amnesia. Forgetting is not, as one might have supposed, a purely passive process.
Either way, choosing deliberately to ingest an amnestic agent for long periods is scarcely an ideal life-strategy. It's especially flawed given the centrality of memory to human self-identity. Some artists and professional bohemians, it is true, apparently do find smoking grass an adjunct to creative thought. For persons of a more philistine temperament, on the other hand, it's hard to see such a drug as a major tool for life-affirmation or the development of the human species.
This does not, one ought scarcely need to add, suggest marijuana users should be persecuted and criminalised.
Eating Spiritual Intelligence
The disparate drugs we label "psychedelics" -
lysergamides like LSD-25, tryptamines like DMT and psilocybin, and phenethylamines such as mescaline - are sometimes exhilarating. At best, they are life-transforming and soul-enriching. They can certainly be mind-wrenching. Taking major psychedelics can generate experiences too outlandish for our conceptual framework to accommodate. We haven't even names for the strange new modes of perception, selfhood and introspection their biochemical pathways disclose.
Unfortunately, one can’t look after the kids, fill in one’s tax forms or carry out one’s social responsibilities while tripping on LSD. Psychedelics are typically too bizarre, exotic and ineffable in their effects to integrate into the rest of one’s life. By trapping most of us in "ordinary" waking consciousness, selfish DNA stumbled on a cunning trick to help its vehicles leave more copies of itself. Worse, the psychedelics aren't primarily euphoriants. They don’t directly stimulate the pleasure-centres and guarantee the user a good trip.
Both the serotonin- and catecholamine-like families trigger psychedelia mainly via their role as partial agonists of the 5-HT2a receptors in the central nervous system; 5-HT2 heteroreceptors exert a tonic inhibitory effect on the striatal dopaminergic neurons. Such agents aren’t a dependable choice of clinical or recreational mood-brightener, whether in the short- or long-term.
Depressives, neurotics and other troubled souls in search of enlightenment are most likely to undergo nightmarish freak-outs. Psychotic derealisation isn't illuminating - or fun. The drug-naive mind can’t make an informed choice of whether to explore radically altered states. For aspiring psychonauts can’t know, in advance, the true nature of what they may be choosing - or missing.
Ultimately, when our well-being is genetically hardwired and invincible, psychedelia can be safely explored. The study of consciousness can become an experimental discipline. The synthesis of tomorrow’s designer-psychedelics may unleash a revolution without precedent. Until then, psychedelic drugs are too unpredictable - and our dark, darwinian minds are too poisoned - responsibly to promote their use.
Apparently by contrast, the empathogen "hug-drug" Ecstasy (methylenedioxymethamphetamine; MDMA)
offers a wonderfully warm, sensuous, loving, and empathetic peak experience to the first-time user - "a brief fleeting moment of sanity" [Dr Claudio Naranjo].
MDMA enhances the release of serotonin and dopamine at the synaptic terminals; it also inhibits their reuptake. In consequence, distrust, suspicion and jealousy evaporate. They are replaced by a serene sense of universal love.
The sensorium remains clear. Emotion is intensified. Much recreational drug-use tends to be self-centred. It is often branded as selfish.
Yet here is a "penicillin of the soul" which promises to subvert our DNA-driven tendency to self-aggrandisement.
Disappointingly, whether due to enzyme-induction or other causes not fully understood, most users never fully recapture the magic of their first few trips. Moreover ecstasy is neurotoxic to serotonergic axons. It may even be harmful at sub-therapeutic doses. As the uncertain process of neural recovery sets in, heavy users in particular may experience the subtle long-drawn-out reversal of all the good effects they initially enjoyed from the drug. Taking a post-trip selective serotonin re-uptake inhibitor (SSRI) such as fluoxetine (Prozac) 2-6 hours afterward is prophylactic against the measurable post-E serotonin dip otherwise experienced some 48 hours later. Yet taking SSRIs on a regular basis largely nullifies the already attenuated benefits of prolonged ecstasy use.
In any case, the duration of the peak experience is a mere 90 minutes. So taking ecstasy scarcely amounts to a full-scale strategy for life either. It does, on the other hand, deliver an exquisite foretaste of the beautiful forms of consciousness that ultimately await us.
Another tantalising and deliciously sensuous hint of the sublime is offered - infrequently and unpredictably - by gamma-hydroxybutyrate (GHB). GHB usually takes the form of a clear, odourless, slightly salty-tasting liquid. It's also an endogenous precursor and metabolite of the inhibitory neurotransmitter GABA. GHB is non-toxic; but it mustn't be mixed with alcohol or other depressants. It's metabolised quickly to carbon dioxide and water.
GHB's steep dose-response curve means naive users run the severe risk of falling asleep. When used lightly in recreational rather than stuporific or anaesthetic doses, GHB is a touchy-feely compound which typically induces deep muscular relaxation, a sense of serenity, and feelings of emotional warmth. Often it enhances emotional openness and the desire to socialise. Tactile sensitivity and the appreciation of music are enriched. Most remarkably, the moderate user may awake refreshed after a deep restful sleep: GHB appears temporarily to inhibit dopamine-release while increasing storage, leading to the brightened mood and sharpened mental focus of a subsequent "dopamine-rebound".
GHB acts both as a disinhibitor and an aphrodisiac. The intensity of orgasm is heightened. Hence GHB is potentially useful in relieving the psychopathologies of prudery and sexual repression. Unfortunately, its therapeutic value has been eclipsed by its demonization in the mass-media. Stories of chaste virgins turning into sex-crazed nymphomaniacs make great copy and poor medicine.
Moreover GHB is sometimes confused with the amnestic "date-rape" benzodiazepine, flunitrazepam - better-known as the potent and fast-acting sedative-hypnotic "forget pill", Rohypnol. Bought on the street, GHB may be confused with all sorts of other substances too.
Yet even pure GHB is no magic elixir. Not everyone likes it. GHB's psychological effects are unpredictable and poorly understood. Nausea, dizziness, inco-ordination are common; reaction-time is slowed. GHB does not usually promote great depth of thought. Its very status as "an almost ideal sleep inducing-substance" makes it of limited use to those who aspire instead to be more intensely awake. The lack of any discernible body-count to fuel the periodic moral panics its use induces may allow a partial rehabilitation.
Yet GHB evokes - at best - only a faint, fleeting parody of the life-long chemical nirvana on offer to our transhuman successors.
Eating Spiritual Intelligence
Alcohol - the traditional date-rape drug of choice - and, most insidiously of all, cigarettes are the really sinister mass-killers.
Their total human death-toll so far is around 100 million and climbing. With that poker-faced Alice-In-Wonderland logic popular amongst the world's sleazier governments, not merely do the authorities preserve the legal status of cigarette sales here in the UK on grounds of upholding personal liberty.
The slickly expensive marketing and glamorisation of tobacco products to potential victims is sanctioned on similar grounds too.
We ought to be as shocked at tobacco promotion as we'd certainly feel if instead the billboards urged kids to try heroin because it's cool.
Yet familiarity breeds moral apathy.
Youngsters are typically hooked before they are in any position to make an informed choice of their preferred poison - or even to abstain altogether.
Meanwhile a state-supported export drive targets the poor in vulnerable Third World countries. With a cynicism that almost beggars belief, one celebrated British ex-Prime Minister accepted a million-dollar bribe from a leading member of the drug-cartels for her services.
Her party's Home Secretary then delivered himself of blood-curdling calls for a crack-down on evil drug-pushers(!). He went on to increase the draconian penalties already available for personal users of cannabis.
So long as our governments collude with the organised drug cartels to share out the billions of dollars of tax revenues mulcted from nicotine-addicts - thereby keeping direct taxes visibly down and themselves visibly in office - there seems little hope of a more intelligent approach to psychoactive drugs as a whole.
Eating Spiritual Intelligence
DIRTY MOOD BRIGHTENERS
The commonly recognised legal and illegal recreational drugs offer poor prospects for sustained biological mood-enhancement. So what about the heterogeneous group of compounds uninvitingly labelled as anxiolytics and antidepressants? Have they potentially anything significant to add to most people's quality of life? Official medical doctrine says no. Allegedly, only sufferers from clinically-sanctioned psychiatric disorders will benefit from such agents; though in recent years it has at last been formally recognised that depressive disorders are under-diagnosed and under-treated even by the early twenty-first century's abjectly poor standards of acceptable ill-being.
Most of humanity, however, still doesn't fit any of the official diagnostic boxes.
So can "diagnostic creep" triumph over therapeutic minimalism and enhance their quality of life? Yes.
Must the goal of pharmacotherapy be as limited as Freud's aspiration for psychotherapy: "to transform hysterical misery into common unhappiness"? No.
First, the boring but crucial preliminaries.
Optimal nutrition and exercise will increase the efficacy of all the potential life-enhancers touted here. A rich supply of precursor chemicals (e.g. l-tryptophan, the rate-limiting step in the production of serotonin) can also reduce their effective dosages.
By choosing to eat an idealised "stone-age" diet rich in organic nuts, seeds, fruit and vegetables, and drastically reducing one's consumption of saturated fat (red meat, fried foods), sugar (sweets etc) and hydrogenated oils (found in margarine and refined vegetable oils), then one's baseline of well-being - or at least relative ill-being - can be sustainably lifted. There is mounting evidence too that an omega-3 fatty acid-rich diet is protective against depression and other psychiatric disorders.
Visitors to HedWeb probably don't expect to be assailed by sermons on the benefits of exercise any more than food-faddism. Yet regular and moderately vigorous physical exertion releases endogenous opioids, enhances serotonin function, stimulates nerve growth factors, and leads to a livelier, better-oxygenated brain.
Alas, clean living and wholesome thoughts typically aren't enough. We need stronger medicine to flourish. At first glance, however, the standard, State-rationed chemicals aren't a brilliant bunch.
The so-called minor tranquillisers, the benzodiazepines such as diazepam (Valium) and the shorter-acting temazepam (Restoril), are sometimes useful but still dreadfully crude anti-anxiety agents.
They act primarily on the GABA (gamma aminobutyric acid) receptor complex. GABA functions as the main inhibitory neurotransmitter in the central nervous system. The progress of molecular biology and neurogenetics in unravelling the fiendish complexity of GABA's receptor sub-types should eventually allow more targeted compounds to be developed. These more selective and site-specific drugs will lack the sedative and hypnotic properties of today's marketed brands. In the meantime, benzodiazepines in current use tend to induce dependence, dull consciousness and impair the intellect. So there's not much chance of radical life-enrichment here.
Buspirone (Buspar) is somewhat more promising.
It acts to desensitise the inhibitory autoreceptor 5-HT1A subtype of serotonin receptor. It thereby promotes serotonin release. This means buspirone has mood-brightening properties too. Thus it is useful in anxious depressive states. Buspirone lacks the intellect-clouding effects of other clinical and alcoholic anti-anxiety agents. Yet its weak and equivocal effects on sub-types of dopamine function, while useful for the purposes of commercially touting its lack of "abuse-potential", mean it isn't very exciting or popular. Researchers hope that newer 5-HT1A agonists in the pipeline will be more effective.
The so-called antidepressants fall into several categories.
Their delayed-onset mood-brightening effect is correlated with alterations in the concentration of catecholamines and/or serotonin in the central nervous system, long-term receptor re-regulation, activation of specific transcription factors regulating gene expression, and new nerve-cell growth in the hippocampus.
The tricyclics, prototypically imipramine (Tofranil), and their allies are relatives of the neuroleptic drug chlorpromazine.
Chlorpromazine is also known as Largactil, the notorious "chemical cosh". Tricyclics block to varying degrees the reuptake of serotonin and noradrenaline into the nerve cell terminals from where they are released. The consequent changes in pre- and post-synaptic receptor sensitivity lighten the spirits of 60-70% of the depressives who take them. Perhaps unsurprisingly given their parentage, the tricyclics are all dirty drugs, though some are dirtier than others. Their anti-cholinergic effects harm memory, concentration and intellectual performance.
Their anti-histamine action induces drowsiness and sedation. Their adverse effect on cardiac function makes them dangerous in overdose. Most "euthymic" volunteers on whom they have been tested don't like their dulling effects of consciousness.
Unlike chlorpromazine, the tricyclic antidepressants don't noticeably block the dopamine receptors. But with one notable exception, they do precious little to stimulate dopamine function either. Hence they're not much fun even for the severely depressed people who can benefit from taking them.
For three decades they were the mainstay of the treatment of clinically-acknowledged depression. They contributed to the widely-held medical opinion that anything classed as an antidepressant won't help "normal" people; unless of course they were "really" depressed.
Basically, tricyclics are cheap, nasty and best avoided.
Much better, but still in some ways deeply flawed, are the selective serotonin reuptake inhibitors [SSRIs]. Serotonin, "the civilising neurotransmitter", plays a vital role in mood, memory, appetite, sleep, pain perception and sexual desire.
Fluoxetine (Prozac), fluvoxamine (Luvox, Faverin), paroxetine (Paxil, Seroxat), sertraline (Zoloft, Lustral), and citalopram (Cipramil, Celexa) are currently licensed and marketed. More of their tweaked and enhanced relatives are on the way from pharmaceutical companies eager for a lucrative piece of the action. In a triumph of marketing hype and creative use of patent law if not clinical need, citalopram's S-enantiomer was FDA-licensed in 2002 as "Lexapro".
The SSRIs all differ in their half-lives, chemical structure and precise specificities. Their functional effects are broadly similar, though Prozac is the most activating, longest-lasting and least selective; paroxetine has anticholinergic and sedating antihistaminergic effects; fluvoxamine has the shortest half-life; and citalopram is the most serotonin selective.
The mood-brightening, resilience-enhancing and anti-anxiety properties of the SSRIs really can make a (very) modest percentage of the population feel "better than well". As a class, SSRIs (mostly) don't have the physically unpleasant and cognitively debilitating anticholinergic effects of the tricyclics. SSRIs don't demand the dietary restrictions of the MAOIs.
Their dependence potential and withdrawal reaction is milder than the opioids. A much larger section of the community - folk who daily knock back huge quantities of ethyl alcohol in the socially accepted fashion - could surely gain from the durably enhanced serotonin function that SSRIs can yield.
Such a switch would necessitate a big change in marketing strategy.
The beneficent properties of the SSRIs are celebrated in Peter Kramer's contemporary classic Listening to Prozac.
Kramer has written a remarkably honest book. It's a discursive memoir by a therapist who is forced to admit that many of his clients seemed rapidly to fare far better on a pill than on his industrial-strength regimen of caring talk-therapy.
Kramer's discussion of "cosmetic psychopharmacology" and "designer personalities", however, enraged traditionalists. For chemical Calvinist orthodoxy finds the notion that people should have a right to choose pharmacologically who and what they want to be profoundly offensive.
Two common problems limit the usefulness of SSRIs, at least when taken on their own. The problems stem from the indirect inhibitory effect of Prozac-style drugs on dopamine function, a consequence of deliberate selective targeting of the serotonin system.
First, SSRIs can compromise libido and sexual performance. This isn't always a disadvantage in over-excitable young males. It can still be a very distressing phenomenon for people too embarrassed to talk about it.
Technical performance difficulties can sometimes be counteracted by taking the blood vessel dilators apomorphine or phentolamine; the alpha2-adrenergic antagonist yohimbine; the phosphodiesterase inhibitor sildenafil (better known as the sexual rocket-fuel Viagra); or a dopamine agonist, licit or otherwise, before bedtime action.
Yet this is scarcely an ideal solution.
Second, though some subjects may feel mildly euphoric, in other users the SSRIs serve more as mood-stabilisers and -flatteners in their lives. By increasing the user's emotional self-sufficiency, too, SSRIs may subtly change the "balance of power" in personal relationships - for good or ill. In some cases, SSRIs may even act as thymoanaesthetisers which diminish the intensity of felt emotion; by contrast, a mood-brightening serotonin reuptake-enhancer like tianeptine may intensify emotion instead. Affective flattening may be welcome to someone in the pit of unmitigated clinical depression.
It is scarcely a life-enriching property for "normal" people who lack any convenient diagnostic category which acknowledges their malaise.
Eating Spiritual Intelligence
THE DOPAMINE CONNECTION
What's missing, crucially, is vigorous and prolonged stimulation of meso(cortico-)limbic dopamine function.
This is really much more fun than it sounds. The currently available experimental evidence has persuaded many - but not all - researchers that the mesolimbic dopamine system serves as the final common pathway for pleasure in the brain.
Enhanced responsiveness of post-synaptic dopamine D2/D3 receptors is crucial to long-term emotional well-being. Insofar as they work, all "serotonergic" and "noradrenergic" mood-brighteners eventually act on the mesolimbic dopamine pathway, albeit in differing degrees and with varying delay.
New anti-Parkinsonian agents, notably pramipexole (Mirapex), ropinirole (Requip), and cabergoline (Dostinex) owe their potential role as fast-acting pro-sexual antidepressants to their dopaminergic action. Likewise, the possible mood-brightening effect of low doses of the dopamine receptor antagonist amisulpride (Solian), more commonly considered an antipsychotic agent, is explicable because amisulpride preferentially blocks the presynaptic dopamine D2/D3 autoreceptors; dopaminergic transmission is thereby enhanced.
The full story is inevitably complex.
Dopamine agonists and reuptake inhibitors are often inadequate long-term mood-brighteners by themselves. The mesolimbic dopamine system mediates reward-signalling, incentive salience and a sense of urgency and significance, not the essence of pure bliss. Dopamine isn't itself the magic pleasure-chemical, though its functional role in conjunction with glutamate and mu opioid agonists in regulating medium spiny neurons of the rostral shell of the nucleus accumbens is crucial. Researchers into affective disorders readily get over-attached to one particular neurotransmitter system, its receptor sub-types and their signal-transduction cascades. Traditionally, serotonin and noradrenaline have attracted the fiercest rival partisans.
"Dopaminergic" (and opioid) agents, by contrast, are suspect. They are politically incorrect since they are potentially "abusable". Moreover it can be argued that the research and development of safe and sustainable E-like empathogens and socialbilizers is as morally urgent as the license of safe and sustainable euphoriants. At any rate, enhanced mesolimbic dopamine release, exclusively or otherwise, enriches the intensity of experience; increases pleasure and libido, and potentially boosts cognitive performance.
Even better, whereas some dopaminergics are potentially toxic, some dopamine-enhancing agents may have neuroprotective properties as well.
So what are the other contemporary options for chemical life-enhancement?
METHYLPHENIDATE; MINAPRINE; NOMIFENSINE
A SSRI can be combined ("augmented" sounds more soothing to the official medical ear) with a dopaminergic such as methylphenidate. As Ritalin, methylphenidate is prolifically dispensed to American schoolchildren for different purposes altogether. In spite of its structural relationship to amphetamine, methylphenidate resembles in many ways a benign version of cocaine, yet with a much longer half-life. It blocks the reuptake, but doesn't significantly release, the catecholamines noradrenaline and dopamine. If it is taken in sustained-release form or combined with an SSRI, all of which have anti-obsessive-compulsive properties too, then the likelihood of dose-escalation is minimised.
Chewing coca leaves with a dash of powdered lime is a nutritious and energising way to sustain healthy mood. Unfortunately, it is not very good for one's teeth.
A more cautious but still interesting option might be minaprine (Cantor). Minaprine blocks the reuptake of both dopamine and serotonin. It is also in some degree cholinomimetic. Thus it may exhibit both mood-brightening and nootropic properties. Much more research is needed.
Merital (nomifensine) showed great promise as a pleasantly stimulating dopaminergic that also potently inhibits the reuptake of noradrenaline and - to a much lesser extent - serotonin. It was marketed by its manufacturers Hoechst with the slogan "vive la difference!" Merital was withdrawn from licensed use after the discovery of its rare side-effect of precipitating a serious blood-disorder. For retarded melancholics, however, it was typically a very effective and well-tolerated mood-brightener with minimal side-effects. The risk/reward ratio of its carefully-monitored use may have been misjudged.
BUPROPION; AMINEPTINE
Bupropion (Wellbutrin) is possibly less effective than nomifensine. Yet it's useful because it lacks the adverse effects on sexual function characteristic of the SSRIs. In some subjects - particularly women - libido, arousal, and the intensity and duration of orgasm may actually increase. Bupropion mildly blocks the reuptake, but diminishes the release, of dopamine. This may account for reports of its diminished propensity to induce mania in the genetically susceptible. Its active metabolites block the reuptake of noradrenaline.
Marketed as Zyban, bupropion is good for giving up smoking. Scandalously, bupropion isn't licensed and marketed as an antidepressant in Europe - though doctors may prescribe Zyban to non-smoking depressives "off-label".
Amineptine (Survector) is a clean-ish, (relatively) selective dopamine reuptake blocker. Higher doses promote dopamine release too. Amineptine is pro-sexual and liable occasionally to cause spontaneous orgasms. It is a mild but pleasant psychostimulant and a fast-acting mood-brightener. Unlike other tricyclics, it doesn't impair libido or cognitive function. Unlike typical stimulants and other activating agents, it may actually improve sleep architecture. Scandalously, amineptine isn't licensed and marketed in Britain and America. For it is feared it might have "abuse-potential". FDA pressure recently led to its withdrawal in Europe too.
This drove it onto the pharmaceutical grey market, discomfiting doctors and patients alike.
REBOXETINE; ADRAFINIL; MODAFINIL
Reboxetine (Edronax) is a well-tolerated, highly selective "noradrenergic" agent. Crudely, whereas serotonin plays a vital role in mood, noradrenaline is essential to maintaining drive, vigilance and the capacity for reward. There's a fair bit of evidence that chronically depressive people have dysfunctional and atypical noradrenergic systems - particularly their alpha2- and beta-adrenoceptors.
Reboxetine itself typically doesn't have the disruptive effects on cognitive function or psychomotor performance common to older clinical mood-brighteners - though alas antimuscarinic effects are still not completely absent. The new NorAdrenaline Reuptake Inhibitors (NARIs) - and dopaminergics like amineptine (Survector) - may be especially good for drive-deficient "anergic" states where the capacity for sustained motivation is lacking; and for melancholic depressives with a poor ability to cope with stress.
Reboxetine may be safely combined with an SSRI. More surprisingly, preliminary studies suggest reboxetine can actually reverse tranylcypromine-induced hypertensive crises. The "cheese effect" is triggered by ingesting tyramine-rich foods. Thus NARIs plus MAOIs may prove a potent form of combination-therapy.
Depressive hypersomniacs who fare poorly on SSRIs, or can't get hold of amineptine or EC-licensed reboxetine, might consider trying a so-called eugeroic ("good arousal") agent instead.
Alpha1-adrenergic agonists like adrafinil (Olmifon) and modafinil (Provigil) are centrally-acting psychostimulants that can brighten mood and sharpen mental focus. They stimulate the noradrenergic post-synaptic receptors, increase glutamatergic transmission, and activate the wakefulness-promoting orexinergic neurons, thereby boosting alertness, memory and energy.
At sensible dosages, they are remarkably free of side-effects. However, the approval process in the USA is so slow, costly and bureaucratic, and the marketing hurdles typically so formidable, that foreign companies are often deterred from seeking FDA acceptance.
[modafinil was licensed by the FDA as Provigil for the treatment of narcolepsy in Dec 1998] So elderly people continue to suffer the prescription of mildly dementing anticholinergics like the dumb-drug tricylcic imipramine. Adrafinil, by contrast, is at least as successful as hepatotoxic Anglo-Saxon products at treating the cognitive and memory impairments of incipient senility.
Fortunately, a "French" drug like adrafinil can now be ordered over the Net; but it ought to be available at the local corner-store. It has the commercial disadvantage of being cheap.
MIRTAZAPINE; NEFAZODONE; VENLAFAXINE; ROLIPRAM
NARIs are normally activating. Anxious and depressive insomniacs, on the other hand, may benefit more from "dual-action" mirtazapine or nefazodone.
Mirtazapine (Remeron) is a structural analogue of the off-patent mianserin (Bolvidon). It is a comparatively new drug - a so-called NaSSA. By blocking the inhibitory presynaptic alpha2 adrenergic autoreceptors and stimulating only the 5-HT1A receptors, mirtazapine enhances noradrenaline and serotonin release while also blocking two specific (5-HT2 and 5-HT3) serotonin receptors implicated in dark moods and anxiety.
By contrast, stimulation of the 5-HT2A receptors accounts for the initial anxiety, insomnia and sexual dysfunction sometimes reported with the SSRIs; stimulation of the 5-HT3 receptors causes nausea.
Unfortunately, mirtazapine is a potent blocker of the histamine H1 receptors too. So it tends to have a somewhat sedative effect. This profile may be good for agitated depressives and insomniacs. Again, it is scarcely a recipe for life-affirmation.
Nefazodone (Serzone) is another newish, "dual action", mainly serotonergic agent. It inhibits the reuptake of serotonin while displaying post-synaptic 5-HT2A-receptor antagonism. This may be useful for anxious depressives; but again, it may cause feelings of weakness, drowsiness and lack of energy. Nefazodone is less likely to cause priapism than its older cousin trazodone (Desyrel). It is less likely to cause sexual dysfunction than the SSRIs.
Venlafaxine (Effexor) is a phenethylamine. Thus it's a benign if distant chemical cousin of MDMA. Its manufacturers launched it as "Prozac with a punch". Venlafaxine inhibits the neuronal reuptake of serotonin, noradrenaline and dopamine in descending order of potency. If dopaminergically augmented, it offers another opening for creative psychopharmacology. Such augmenation-therapy remains (almost) clinically unexplored. Taken on its own at low dosage, venlafaxine acts primarily as a serotonin re-uptake inhibitor. At the high-level dosages most suitable for melancholic and hypersomnic temperaments, its noradrenergic (and weakly dopaminergic) action becomes more pronounced. Like the SSRIs, it is useful for a broad spectrum of disorders beyond clinical depression.
It is possible that duloxetine (Cymbalta), due to be FDA-licensed in 2003, and milnacipran (Ixel), available in Europe, may be more effective than venlafaxine for a segment of the population that can benefit from dual serotonin-noradrenaline reuptake inhibition. But it takes time to separate genuine therapeutic advance from drug company hype, typically not until the patent expires.
Phosphodiesterase-inhibitors, both selective (e.g. rolipram) and unselective, are another under-used option. The next few decades will take us much closer to the real intra-cellular action. For it is here that our minds will ultimately be healed, genetically or otherwise.
HYPERICUM
Hypericum is important for a different reason altogether. Many constitutionally unhappy people refuse to have anything to do with orthodox western medicine. They won't take "unnatural" pharmaceutical products at all. In consequence, they spend much of their lives trapped in a squalid psychochemical ghetto of chronic low spirits. The only sort of remedy that they'll conceivably contemplate taking must carry a "natural" label and soothingly "herbal" description.
Unfortunately, most folk remedies are only marginally effective. The few that work - Cannabis sativa, coca and Papaver somniferum - are typically if perversely illegal.
Plants tend to manufacture psychotropics because they poison or debilitate creatures tempted to eat them - not to heal our psychic woes.
Thus the Wisdom Of Nature is a quaint piece of make-believe. Even so, hypericum, the active ingredient in St John's Wort, appears to be an effective mood-brightener and anxiolytic - by today's standards at least.
Its side-effect profile and efficacy in mild-to-moderate depression compares favourably with its synthetic counterparts. Hypericum's blend of serotonin-reuptake inhibiting and (mild) MAO-inhibiting properties (not a combination otherwise to be explored with potent synthetics: the risk of the potentially fatal serotonin syndrome is too great) contributes to - without wholly explaining - its generally benign effects.
Once again, much more research is needed, preferably not bankrolled by the makers of lucrative competing products. Faith in the integrity of biological psychiatry would be greater if the strongest predictive factor in the outcome of any published clinical trial wasn't the identity of the funding body.
INOSITOL
One further remedy, albeit at "unnatural" doses, is worth noting. Inositol levels tend to be low in depressives and high in euphoric people.
Taking myo-inositol as a food supplement in doses of 12g and more per day represents perhaps the first successful use of the precursor strategy for a second messenger rather than a neurotransmitter in the search for long-term mood-brightening agents.
Inositol and its derivatives serve as messenger molecules within the nervous system. The molecule itself is a naturally occurring isomer of glucose. It is a key intermediate of the phosphatidyl-inositol cycle. This is a second-messenger system used by several noradrenergic, serotonergic and cholinergic receptors. Adult westerners typically consume about one gram of inositol per day in their food.
The richest dietary sources are fruits, nuts, beans and grains. The mood-darkening ("stabilising") effect of lithium in manically euphoric people may be explicable in terms of its inositol-depleting effect.
Potentially, if taken in high doses, inositol seems to be a good way of lightening the spirits and diminishing anxiety in "euthymic" and depressed people alike.
Dosages of even 50g and more reportedly produce no toxic side-effects. This regimen shouldn't be attempted unsupervised by people with a history of bipolar disorder. As usual, much more research is in order.
One "problem" is that naturally-occurring compounds - such as inositol and SAMe - can't be patented. So the scope for high profit-margins is diminished. Progress is unlikely to be brisk.
THE MAO INHIBITORS
A further option involves using both some of the oldest and the newest drugs on the block, the monoamine oxidase inhibitors (MAOIs). The older irreversible MAOIs certainly shouldn't be combined with SSRIs, and inadvisably with stimulants and many other drugs. Yet both old and new, they do have some very interesting properties.
Monoamine oxidase has two main forms, type A and type B. They are coded by separate genes. MAO may be inhibited with agents that act reversibly or irreversibly; and selectively or unselectively; these categories are not absolute.
MAO type-A preferentially deaminates serotonin and noradrenaline, and also non-selectively dopamine;
type B primarily metabolises dopamine, phenylethylamine (the "chocolate amphetamine") and various trace amines.
The substantial mood-elevating properties of the MAOIs were discovered quite by chance in a US veterans hospital early in the 1950s.
Many patients given the anti-tuberculotic drug iproniazid were not merely cured of their tuberculosis. They became exceptionally happy as well. The animated enthusiasm for life of a previously crotchety bunch of old soldiers disconcerted their doctors.
For it transpired that their new-found euphoria wasn't just an understandable reaction to being cured of physical disease.
MAOIs typically have mood-brightening properties as well. At the time, there was no accepted and clinically-effective treatment for depression. Fortunately, via the usual circuitous routes, the appropriate lessons were eventually drawn. Many millions of people were successfully treated with MAOIs in consequence.
Sadly, the role of MAO in deaminating tyramine (from the Greek word tyros, meaning cheese) wasn't at first understood.
Certain MAOI-treated patients suffered hypertensive crises after eating varying amounts of tyramine-rich aged cheese; and several died.
It is now recognised that the use of any MAOI which is both irreversible and unselective must be accompanied by dietary restrictions.
But the adverse publicity of the initial inexplicable fatalities, combined with the introduction of a succession of dirty but sometimes tolerably effective tricyclic compounds, sent the use and reputation of MAOIs into a precipitous decline from which they still haven't fully recovered.
The older non-selective and (more-or-less) irreversible inhibitors tranylcypromine (Parnate), phenelzine (Nardil) and isocarboxazid (Marplan) are nonetheless valuable drugs.
Outside the USA, they tend to have been eclipsed by the selective and reversible moclobemide. Similar therapeutic agents are in the pipeline. Of greater interest still are central-nervous-system-selective compounds, notably one known (not indeed especially widely) as MDL-72394. MAOIs which lack the peripheral effects of currently explored drugs herald an exciting new therapeutic window of opportunity.
SELEGILINE (l-deprenyl)
A recent New York study showed that smokers had on average 40% less of the enzyme, monoamine oxidase type-B, in their brains than non-smokers. Levels returned to normal on their giving up smoking. Not merely is the extra dopamine in the synapses rewarding. The level of MAO-b inhibition smokers enjoy apparently contributes to their reduced incidence of Parkinson's and Alzheimer's disease. Unfortunately they are liable to die horribly and prematurely of other diseases first.
One option which the dopamine-craving nicotine addict might wish to explore is switching to the (relatively) selective MAO-b inhibitor selegiline, better known as l-deprenyl.
Normally the brain's irreplaceable complement of 30-40 thousand odd dopaminergic cells tends to die off at around 13% per decade in adult life. Their death diminishes the quality and intensity of experience. It also saps what in more ontologically innocent times might have been called one's life-force.
Eighty percent loss of dopamine neurons results in Parkinson's disease, often prefigured by depression. Deprenyl has an anti-oxidant , immune-system-boosting and dopamine-cell-sparing effect. Its use boosts levels of tyrosine hydroxylase, growth hormone, superoxide dismutase and the production of key interleukins.
Deprenyl offers protection against DNA damage and oxidative stress by hydroxyl and peroxyl radical trapping; and against excitotoxic damage from glutamate.
Whatever the full explanation, deprenyl-driven MAOI-users, unlike cigarette smokers, are likely to be around to enjoy its distinctive benefits for a long time to come, possibly longer than their drug-naïve contemporaries.
For in low doses, deprenyl enhances life-expectancy, of rats at least, by 20% and more. It enhances drive, libido and motivation; sharpens cognitive performance both subjectively and on a range of objective tests; serves as a useful adjunct in the palliative treatment of Alzheimer's and Parkinson's disease; and makes you feel good too.
It is used successfully to treat canine cognitive dysfunction syndrome (CDS) in dogs. At dosages of below 10-15 mg daily, deprenyl retains its selectivity for the type-B MAO iso-enzyme. At MAO-B-selective dosages, deprenyl doesn't provoke the "cheese-effect"; tyramine is also broken down by MAO type-A. Deprenyl isn't addictive, which probably reflects its different delivery-mechanism and delayed reward compared to inhaled tobacco smoke.
Whether the Government would welcome the billions of pounds of lost revenue and a swollen population of energetic non-taxpayers that a switch in people's MAOI habits might entail is unclear.
MOCLOBEMIDE
Humans now have the capacity to choose their own individual level of activity or inhibition of the two primary monoamine oxidases.
This does not quite enable the fine-tuning of personality variables with the functional equivalent of a graphic equaliser.
It still represents a promising start. In MAO-inhibition, as in life, more is not always better. Excessive dosages of l-deprenyl intake, for instance, may actually shorten, not increase, life expectancy - at least in Parkinsonians if it's combined with l-dopa. And levels of above 80% inhibition of MAO-A may lead to a sharp and possibly unwanted fall in dopamine synthesis.
Repairing Nature's niggardliness will be a priority for the decades ahead.
Moclobemide (Manerix, Aurorix), the "gentle MAOI", is both a selective and reversible inhibitor of MAO-A. It marks the first RIMA to win clinical acceptance. It lacks anti-cholinergic side-effects. No dietary restrictions are needed. It is valuable as more than a mood-enhancer. For moclobemide is often useful in overcoming social phobia, panic disorder, obsessive-compulsive symptoms, irritability and aggression owing to the way it enhances serotonin function. (The casual use of gobbledygook such as "enhanced x function" will rightly alert the reader that many complications are being skirted or omitted. Those hungry for the greater technical detail of a non-popular account can rest assured the literature will leave them feeling abundantly well-nourished).
TRANYLCYPROMINE
Gentleness doesn't suit everyone. Moclobemide isn't much good at lifting deep melancholy. Tranylcypromine (Parnate), on the other hand, is one of the older and non-selective MAOIs - and is often none the worse for it.
Structurally related to amphetamine, it's generally the most stimulating, dopaminergic and relatively fast-acting of the MAOIs. Some doctors are uncomfortable with its properties. This isn't just because of the dietary restrictions it demands. In adequate doses, it tends to induce a mild euphoria even in "normal" subjects.
In fact, its nicest effects, as for all of the compounds cited here, will vary in nature and extent from person to person. To some extent, optimal dosage and long-term drug-regimen of choice can be discovered only by cautious empirical investigation.
Tranylcypromine is of course vastly preferable to the amphetamines and cocaine. Yet frequently and perversely, the more hazardous the drug, then the easier it is to get hold of in our society.
The carcinogenic cocktail that carries off more people than all other toxins combined can be purchased quite legally and effortlessly at any tobacconist or newsagent. Obtaining the less lethal - but scarcely desirable - street opioids and psychostimulants requires a little more exertion. Yet they can still be readily purchased in pubs and clubs in all the big towns and cities.
Most of the more beneficent drugs discussed here, on the other hand, are available on a prescription-only basis. They're not illegal to possess.
But they are hard to obtain short of visiting countries where they're available over-the-counter or paying high mail-order prices for an uncertain service.
If the central principle at stake were the preservation of a drug-free society, then some sort of totalitarian (or, more euphemistically, paternalistic) argument could be cobbled together for violating personal freedom so oppressively.
Yet that's rarely the issue. For in most cases, the issue effectively amounts, not to drugs or no drugs, but to allowing people the choice to opt for better ones. Perhaps 80% of the population in Western countries currently drink alcohol or smoke cigarettes.
Often they do both. Whether viewed in terms of mortality, morbidity or overall quality of life, we'd be far better off if we switched to enhancing dopaminergic, serotonergic and cholinergic function by the relatively safe and often crudely effective agents touched on here; and to the much more exciting products currently in the pipeline.
As a basic minimum, people shouldn't be legally robbed of the right to do so.
This freedom of choice isn't conventional wisdom. It will be suggested that the level of medical expertise required to make informed choices exceeds that of the average layperson; and a quasi-priestly caste wielding the power of the prescription-pad would doubtless wish to keep it that way.
But the intrinsic difficulty and complexity of psychopharmacology or nutritional medicine, say, doesn't demand greater mental effort than, for instance, all those thousands of grimly unnatural hours spent by school students learning mathematics.
Moreover it's far more interesting to study something palpably relevant to one's emotional well-being than something that demonstrably isn't.
The notion of an education system geared to schooling people in, and for, happiness would nonetheless strike adherents of the reigning educational orthodoxy as abhorrent were it not so largely incomprehensible.
WORKING FOR A DRUG-FREE FUTURE
Suppose, for a moment, that the reproductive success of our DNA had been best served by coding for ecstatically happy vehicles rather than malaise-haunted emotional slum-dwellers.
If this had been the case, then none of the pharmacological interventions discussed in The Good Drug Guide would be necessary.
Life-long well-being would seem only "natural". We would all enjoy gloriously fulfilled lives. Each day would be animated by gradients of bliss.
Unpleasant states of mind would be viewed as a tragic aberration.
They'd be diagnosed as a freakish but clinically treatable type of psychopathology.
Of course, it didn't work out that way. Instead, the inclusive fitness of our genes has been promoted by the "natural" manufacture of some of the most vicious psychological adaptations imaginable.
The rot goes deeper.
Selfish DNA can count on innumerable dupes to act as its distal representatives even today. The need for "character-building" emotional pain gets justified with all manner of sophistries, both religious and profane.
Suffering is good for you, one may be told. It's all part of life's rich tapestry.
It exists because it was good for our genes. Apologists for mental pain are serving as the innocent mouthpieces of the nasty bits of code which spawned them.
If pressed, DNA's unwitting spokesmen would presumably disavow the connection. Yet if one were purposely building an intelligent robotic survival-machine, then endowing it with the illusion of free-will would prove a highly fitness-enhancing adaptation.
It's a trick which our genes merely stumbled upon; and then blindly exploited.
Fortunately, within the next few centuries humanity will be able to outwit its ancient genetic masters. Our present status as throwaway genetic vehicles will finally be subverted.
When heavenly well-being becomes the genetically predestined norm of mental health, then the very notion of tampering with our new-won "natural" condition and feeling "drugged" will come to seem immoral.
It will also seem perverse. Why should anyone want to contaminate the divine ecstasy of their spirituo-biological soul-stuff with chemical pollutants? No thanks.
Today's twisted victims of the primordial genetic code, on the other hand, view the notion of sullying their natural state of being through drugs with a much more deep-seated ambivalence.
They adopt it as a near-universal practice.
Given the inadequacy of the third-rate stopgaps on offer, and the lack of serious drug-education, it's scarcely surprising we're so poor at using them.
Thus concerned parents are surely right to worry about the trashy street drugs taken by their kids.
Yet with the right new genes and designer-drugs, there's no reason why mature Post-Darwinian life shouldn't just get better and better.
To continue: Please follow the many links on the above source page
Good Drug Guide: www.biopsychiatry.com
UTOPIAN PHARMACOLOGY
Mental Health in the Third Millennium
Return to The Energy Body
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First, the boring but crucial preliminaries.
Optimal nutrition and exercise will increase the efficacy of all the potential life-enhancers touted here. A rich supply of precursor chemicals (e.g. l-tryptophan, the rate-limiting step in the production of serotonin) can also reduce their effective dosages.
By choosing to eat an idealised "stone-age" diet rich in organic nuts, seeds, fruit and vegetables, and drastically reducing one's consumption of saturated fat (red meat, fried foods), sugar (sweets etc) and hydrogenated oils (found in margarine and refined vegetable oils), then one's baseline of well-being - or at least relative ill-being - can be sustainably lifted. There is mounting evidence too that an omega-3 fatty acid-rich diet is protective against depression and other psychiatric disorders.
Visitors to HedWeb probably don't expect to be assailed by sermons on the benefits of exercise any more than food-faddism. Yet regular and moderately vigorous physical exertion releases endogenous opioids, enhances serotonin function, stimulates nerve growth factors, and leads to a livelier, better-oxygenated brain.
Alas, clean living and wholesome thoughts typically aren't enough. We need stronger medicine to flourish. At first glance, however, the standard, State-rationed chemicals aren't a brilliant bunch.
The so-called minor tranquillisers, the benzodiazepines such as diazepam (Valium) and the shorter-acting temazepam (Restoril), are sometimes useful but still dreadfully crude anti-anxiety agents.
They act primarily on the GABA (gamma aminobutyric acid) receptor complex. GABA functions as the main inhibitory neurotransmitter in the central nervous system. The progress of molecular biology and neurogenetics in unravelling the fiendish complexity of GABA's receptor sub-types should eventually allow more targeted compounds to be developed. These more selective and site-specific drugs will lack the sedative and hypnotic properties of today's marketed brands. In the meantime, benzodiazepines in current use tend to induce dependence, dull consciousness and impair the intellect. So there's not much chance of radical life-enrichment here.
Buspirone (Buspar) is somewhat more promising.
It acts to desensitise the inhibitory autoreceptor 5-HT1A subtype of serotonin receptor. It thereby promotes serotonin release. This means buspirone has mood-brightening properties too. Thus it is useful in anxious depressive states. Buspirone lacks the intellect-clouding effects of other clinical and alcoholic anti-anxiety agents. Yet its weak and equivocal effects on sub-types of dopamine function, while useful for the purposes of commercially touting its lack of "abuse-potential", mean it isn't very exciting or popular. Researchers hope that newer 5-HT1A agonists in the pipeline will be more effective.
The so-called antidepressants fall into several categories.
Their delayed-onset mood-brightening effect is correlated with alterations in the concentration of catecholamines and/or serotonin in the central nervous system, long-term receptor re-regulation, activation of specific transcription factors regulating gene expression, and new nerve-cell growth in the hippocampus.
The tricyclics, prototypically imipramine (Tofranil), and their allies are relatives of the neuroleptic drug chlorpromazine.
Chlorpromazine is also known as Largactil, the notorious "chemical cosh". Tricyclics block to varying degrees the reuptake of serotonin and noradrenaline into the nerve cell terminals from where they are released. The consequent changes in pre- and post-synaptic receptor sensitivity lighten the spirits of 60-70% of the depressives who take them. Perhaps unsurprisingly given their parentage, the tricyclics are all dirty drugs, though some are dirtier than others. Their anti-cholinergic effects harm memory, concentration and intellectual performance.
Their anti-histamine action induces drowsiness and sedation. Their adverse effect on cardiac function makes them dangerous in overdose. Most "euthymic" volunteers on whom they have been tested don't like their dulling effects of consciousness.
Unlike chlorpromazine, the tricyclic antidepressants don't noticeably block the dopamine receptors. But with one notable exception, they do precious little to stimulate dopamine function either. Hence they're not much fun even for the severely depressed people who can benefit from taking them.
For three decades they were the mainstay of the treatment of clinically-acknowledged depression. They contributed to the widely-held medical opinion that anything classed as an antidepressant won't help "normal" people; unless of course they were "really" depressed.
Basically, tricyclics are cheap, nasty and best avoided.
Much better, but still in some ways deeply flawed, are the selective serotonin reuptake inhibitors [SSRIs]. Serotonin, "the civilising neurotransmitter", plays a vital role in mood, memory, appetite, sleep, pain perception and sexual desire.
Fluoxetine (Prozac), fluvoxamine (Luvox, Faverin), paroxetine (Paxil, Seroxat), sertraline (Zoloft, Lustral), and citalopram (Cipramil, Celexa) are currently licensed and marketed. More of their tweaked and enhanced relatives are on the way from pharmaceutical companies eager for a lucrative piece of the action. In a triumph of marketing hype and creative use of patent law if not clinical need, citalopram's S-enantiomer was FDA-licensed in 2002 as "Lexapro".
The SSRIs all differ in their half-lives, chemical structure and precise specificities. Their functional effects are broadly similar, though Prozac is the most activating, longest-lasting and least selective; paroxetine has anticholinergic and sedating antihistaminergic effects; fluvoxamine has the shortest half-life; and citalopram is the most serotonin selective.
The mood-brightening, resilience-enhancing and anti-anxiety properties of the SSRIs really can make a (very) modest percentage of the population feel "better than well". As a class, SSRIs (mostly) don't have the physically unpleasant and cognitively debilitating anticholinergic effects of the tricyclics. SSRIs don't demand the dietary restrictions of the MAOIs.
Their dependence potential and withdrawal reaction is milder than the opioids. A much larger section of the community - folk who daily knock back huge quantities of ethyl alcohol in the socially accepted fashion - could surely gain from the durably enhanced serotonin function that SSRIs can yield.
Such a switch would necessitate a big change in marketing strategy.
The beneficent properties of the SSRIs are celebrated in Peter Kramer's contemporary classic Listening to Prozac.
Kramer has written a remarkably honest book. It's a discursive memoir by a therapist who is forced to admit that many of his clients seemed rapidly to fare far better on a pill than on his industrial-strength regimen of caring talk-therapy.
Kramer's discussion of "cosmetic psychopharmacology" and "designer personalities", however, enraged traditionalists. For chemical Calvinist orthodoxy finds the notion that people should have a right to choose pharmacologically who and what they want to be profoundly offensive.
Two common problems limit the usefulness of SSRIs, at least when taken on their own. The problems stem from the indirect inhibitory effect of Prozac-style drugs on dopamine function, a consequence of deliberate selective targeting of the serotonin system.
First, SSRIs can compromise libido and sexual performance. This isn't always a disadvantage in over-excitable young males. It can still be a very distressing phenomenon for people too embarrassed to talk about it.
Technical performance difficulties can sometimes be counteracted by taking the blood vessel dilators apomorphine or phentolamine; the alpha2-adrenergic antagonist yohimbine; the phosphodiesterase inhibitor sildenafil (better known as the sexual rocket-fuel Viagra); or a dopamine agonist, licit or otherwise, before bedtime action.
Yet this is scarcely an ideal solution.
Second, though some subjects may feel mildly euphoric, in other users the SSRIs serve more as mood-stabilisers and -flatteners in their lives. By increasing the user's emotional self-sufficiency, too, SSRIs may subtly change the "balance of power" in personal relationships - for good or ill. In some cases, SSRIs may even act as thymoanaesthetisers which diminish the intensity of felt emotion; by contrast, a mood-brightening serotonin reuptake-enhancer like tianeptine may intensify emotion instead. Affective flattening may be welcome to someone in the pit of unmitigated clinical depression.
It is scarcely a life-enriching property for "normal" people who lack any convenient diagnostic category which acknowledges their malaise.
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END PONDER 554 *
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There I was – a bratty, independent kid, with a twisted sense of humor who enjoyed doing illegal things: Entrance into anyplace at all displaying the "No Dogs or Jews Allowed" signs was fun, even though it was clearly understood that – if discovered – neither dog nor Jew would ever be seen again, regardless of age. The best game of all, though, was diving into the Berlin Olympic Pool, and, hiding behind my Teutonic looks, smiling innocently at the guards. But those men were just ordinary cops. When it came to the Gestapo, it was best to quickly and quietly disappear. Oh yes. The Gestapo meant business.
When Benjamin Franklin said, "Those who would give up essential liberty to purchase a little temporary safety, deserve neither liberty nor safety," he was right on!
In 1930’s Germany, "safety" meant "power." The popular sentiment was: "Power will keep us safe. After all, we are the good people, the ones who want to clear the planet earth of all who hinder progress, of all who stand in the way of our good intentions – and the more power our Empire has, the safer we will be, the safer we will make the world." The national slogan, shouted joyfully in the streets, was, after all, "Heute Deutschland, Morgen Die Welt" (translation: Today Germany, tomorrow the World.)
The Germans, then, willingly gave up essential liberty to purchase that safety of power, and the Nazis did an excellent job of facilitating that. They invented the Gestapo, which was an acronym for Geheime Staats Polizei. (translation: Secret State Police.) And the Gestapo was formidable, indeed.
Black, form-fitting uniform jackets, complete with epaulets; black breeches tucked into jack-boots polished to such perfection that they gleamed in all weather; black hats with visors so glossy, they shone in the dark. Oh, yes, these men were quite rightfully feared.
In 1930’s Germany, it was completely proper, fitting and expected for persons to turn in to the authorities anyone even remotely suspected of in some way subverting the government. Neither a suspicion nor an informant was too small: Children over the age of eight, all of whom were members of the Hitler Jugend if they were boys and Bund Deutscher Mädchen if they were girls, were expected to turn in family members – including parents – if they were overheard speaking disrespectfully or seditiously of Hitler or any members of his administration. These kids were trained and propagandized to simply put the "safety" of their great country over the "liberty" of their families. Thus, if even one’s own kids were gleeful informants, can you imagine what the neighbors were?
When someone was turned in, the Gestapo showed up to do the honors. No warrant was needed. Time of day or night was irrelevant. Folks simply got hauled off, and, once taken away, never returned. Gestapo interrogation methods were simple: Torture them till they talk. Most of the time – even if these prisoners had absolutely nothing of value to report – they eventually broke under the torture and simply blurted out whatever they thought the inquisitors wanted to hear. Once they had spoken, off they went to their deaths at the local extermination camp, and if they chose not to speak, well, then the torture continued till they died in the interrogation chamber.
Now, here we are in 2005, in the United States of America, busily trading essential liberties for the safety of power…We, too, understand that "safety" means "power." In today’s America, the administration has taught us carefully and clearly that: "Power will keep us safe. After all, we are the good people, the ones who want to clear the planet earth of all who hinder progress, of all who stand in the way of our good intentions – and the more power our Empire has, the safer we will be, the safer we will make the world."
We do not have a Gestapo, of course. Intimidating black uniforms with jack boots and shiny hat visors to match are as out-dated as 33 1/3 RPM music albums. And, after all, the Gestapo wasn’t very secret. Our current fascist government is so much smoother, sophisticated, slicker than the Nazis ever were. We just have organizations called FBI Federal Bureau of Investigation) and CIA (Central Intelligence Agency.)
And, as reported by the Associated Press (June, 2005), we also have an expanded, broader version of the Patriot Act, which gives the government more liberties with our liberties than ever before. The purpose of this expansion "Has, as its significant purpose, the collection of intelligence...."
On June 29, 2005, CNN TV, along with the LA Times-Washington Post News Service, announced that, In June, 2002, President Bush directed the creation of a new National Security Service within the FBI. This little gem specializes in intelligence and other "national security matters" under the grim direction of John Negroponte, who – given his background of association with South American terrorists – is pretty savvy when it comes to such matters.
The new service combines counterterrorism, intelligence and espionage units, and has been mandated to operate in secrecy as needed. "It will give control of all human intelligence operations to the CIA."
This new department is enthusiastically endorsed by FBI Director Robert Mueller, Attorney General Alberto Gonzalez, CIA Director Porter Goss, and Homeland Security Director Michael Chertoff. What a great new way to prevent terrorism. Now, we not only have secret agents who can conduct all business in secret, but can also use torture
"Torture?" You ask, "Now where did you get that from?"
Our current administration clearly understands the value of torture. After all, when the populace found out about the torture in Abu Ghraib and at Guantánamo – amongst other places – there was no public outcry. Those inquisitors were – and continue to – simply keep us all safe from terrorists. Good job. Not only that, but, now, torture is an officially sanctioned governmental procedure.
The very purpose of the international Geneva Conventions, formulated in 1949 by the Office of the United Nations High Commissioner for Human rights, was created to prevent – ever again – the kind of insane torture and ruthless extermination perpetrated by Nazi Germany. When interrogated, "No physical or mental torture, nor any form of coercion, may be inflicted on prisoners of war to secure from them information of any kind whatsoever." The Geneva Conventions, as a matter of fact, were updated in 1977 to provide greater protections for victims of armed conflict. To wit: "The presence within the civilian population of individuals who do not come within the definition of civilians does not deprive the population of its civilian character." (Article 50)
But, just this spring, Alberto Gonzales, our own Attorney General, opened the door to torture when he stated, "The Geneva Conventions are quaint: They are obsolete."
We all know that torture techniques such as "waterboarding," electroshock, the use of attack dogs on naked prisoners were/are commonplace at Guatanomo. In an article by Robert Zeller (06/24/05, "The Triangle") the USA torture system is made even clearer: The USA, now, routinely sends persons for interrogation to nations that openly condone torture. "Flogging, anal rape, fingernail extraction, amputation, submersion in boiling water and mock executions are standard procedure, often under the eye of American agents" Agents – from the FBI and CIA – are sent as escorts with these prisoners, in order to note all information resulting from these techniques. According to Robert Zeller, "In so doing, the officials who direct these agents are in direct violation of the federal War Crimes Act, a 1996 statute that carries the death penalty."
America, on June 28, 2005, officially refused to back a United Nations protocol against torture, because of fears that this could allow international monitors to visit terrorist suspects in Guantánamo Bay.
But, is the secrecy of our "new" FBI/CIA actually new? On June 6, 2002, the Portland Oregonian reported that former University of South Florida professor, Sami Al-Arian, had his phones bugged, microphones planted in his office, and faxes as well as computer conversations recorded. And, all this took place well before the official conversion of the FBI to "Secrecy." Matter of fact, it was done for nine years, and no evidence was ever discovered making him in any way less than a good US Citizen.
On July 1, 2002, FBI agents searched the San Diego home of Rep. Randy "Duke" Cunningham. No reason was given. No reason HAD to be given. No one is exempt from these new secret agents and what they choose to do. Ordinary citizen or legislator – it doesn’t matter. In they come, and away we go
And who gets hauled off in the night? France Sénécal, who hosts a weekly interview program at Radio Station KDVS 90.3 FM at University of California – Davis, reports the horrifying family experience of "Sitara," a long-time member of "Critical Resistance" who has often been interviewed on France's program.
With no advance notice, with no warning whatsoever, Sitara's aunt and uncle were taken away by government agents during the week of June 22, 2005. They have since been locked away in a detention prison in West Virginia. Sitara states, "They came from Afghanistan about ten years ago, and have since been involved in a long asylum attempt."
"Aunt, uncle and 19-year-old cousin were home after cousin’s graduation from High School on June 22. Suddenly, on graduation day, the doorbell rang, and there stood the government officials and police, saying, "We need to take you for questioning about an investigation we are doing at Dulles airport (where my aunt worked, and my uncle also, until his work permit expired and wasn’t renewed.). They told my 19-year-old cousin that his folks would be back that evening, but, instead, they simply disappeared."
In their West Virginian detention camp, the story they are told regarding the reason for their detention keeps changing, and no one knows what’s going to happen to them. Will they be deported? And, is the young cousin also in danger? No one knows.
So, how far are we removed from the Gestapo of Nazi Germany? As Robert Zeller states, "It (fascism) comes through creating legal nonpersons of citizens and noncitizens alike. It comes through violating human rights standards, sanitizing torture and condoning murder."
As Hermann Goering stated at the Nuremberg trials: "Voice or no voice, the people can always be brought to the bidding of the leaders. That is easy. All you have to do is tell them they are being attacked and denounce the pacifists for lack of patriotism, and exposing the country to greater danger."
On June 14, 2005, Senator Dick Durbin, D-Ill compared US interrogators at Guantánamo with Nazis and other historically infamous figures. By June 21, 2005, he had been pressured by the administration to the point that he issued the following: "Some may believe that my remarks crossed the line. To them, I extend my heartfelt apologies." In this regard, Durbin represents the entire nation: All of us see what sits in front of us. All of us are aware of what is going on. All of us understand that our endorsement of the Patriot Act, the new FBI/CIA does away with our essential freedoms. But, none of us want to "cross the line." Are we that close to the mentality of the German citizenry of the Nazi era? Seems that way, doesn’t it…. Heil Hitler.
***********************************
IT BEGINS NOW! July 7, 2005
AuMASTE' Hippos Wallow for JULY 7th 2005
** Thoughts/ link of the moment:
http://www.sonoran-sunsets.com/rhythms.html
If you wish to upset the law that all crows are black,
it is enough if you prove one single crow to be white.
--- William James
I can real eyes you've had a change of mind,
but what you need is a change of heart.
--- HIC!
posted by HU-MYN at Thursday, July 07, 2005
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