This may not go here, but I sure cant file it right after that Opus in Push's section, so I thought I would paste the first few paragraphs from the Good Drug Guide. Heres a little taste of what helped me when I was down, and gave me strength to quit. If you make it to the end I will give you a gold star, plus you will have a lot of [censored] to spout at your next dinner party.
Peace,
Gileas, who really believes this guy is on to the Truth (capital T)



Good Drug Guide Introduction to Modern Life and the Solutions to its Problems:

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 "antidepressants" can themselves act as "physical" painkillers. Conversely, mu-opioid receptor agonists offer both unsurpassed pain-relief and extraordinary emotional well-being; and delta-opioid agonists and enkephalinase inhibitors can function as antidepressants. 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; by contrast, physical pain is a potent respiratory stimulant. When taken recreationally, opioids inspire a dreamily contented disengagement from the problems of the world. Their use diminishes our 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 opioid drugs were legal and given away in cereal packets, such drugs 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.

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 E 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 na�ve 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 scientific 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.

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, benzodiazepines such as diazepam (Valium), chlordiazepoxide (Librium), alprazolam (Xanax), lorazepam (Ativan), clonazepam (Klonopin) and the shorter-acting sedative-hypnotic temazepam (Restoril), are 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. Ideally, these more selective and site-specific drugs will lack the sedative, amnestic and hypnotic properties of today's brands. Activation of GABA(A) receptors containing the alpha 1 subunit is responsible for benzodiazepine-induced sedation and memory deficits. It is hoped that newly-synthesised agonists selective for the alpha 2 GABA(A) receptor subtype may finally deliver a non-sedating antianxiety drug. Merck's investigational L838,417 is one such candidate. Human trials are eagerly awaited. The first non-benzodiazepine, non-sedating/amnesiac drug of its class to reach the market may prove to be DOV Pharmaceutical's ocinaplon. Ocinaplon is a GABA alpha-2 modulator. It exerts its anti-anxiety effect at doses (allegedly) substantially lower than doses that induce measurable sedation, amnesia, muscle relaxation and incoordination. Ocinaplon is in phase III clinical trials for anxiety (autumn 2004). In the meantime, currently licensed benzodiazepines tend to induce dependence, impair memory and psychomotor peformance, dull consciousness and cloud the intellect. So there's not much chance of radical life-enrichment here, for now at least.

Buspirone (Buspar) might seem more promising. It acts to desensitise the inhibitory autoreceptor 5-HT1A subtype of serotonin receptor. It thereby promotes serotonin release. This means that 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. Unlike the benzodiazepines, it's not fast-acting. Researchers hope that newer 5-HT1A agonists in the pipeline will be more effective. Alas any therapeutic gain is likely to be modest. In June 2004, the FDA determined that Organon's gepirone (Ariza) was "not approvable".

The ill-assorted drugs we today call 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, least selective and most likely to provoke dose-related akathisia; paroxetine has anticholinergic and sedating antihistaminergic effects; fluvoxamine most commonly induces nausea and 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 usually 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 (sometimes) 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 older 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; a phosphodiesterase type-5 inhibitor like sildenafil (better known as the sexual rocket-fuel Viagra), long-acting tadalafil (Cialis) or newly licensed vardenafil (Levitra); or a dopamine agonist, licit or otherwise, before bedtime action. Investigational drugs that heighten female sexual arousal (e.g. melanocortin agonists like PT-141) are another option. Yet this is scarcely an ideal solution. One of the major signs of depression is loss of interest in sex and reduced libido. So it's questionable whether the FDA and the pharmaceutical industry should continue to promote serotonergic "antidepressants" that are anti-sexual; and collude to suppress antidepressants that are pro-sexual.

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.

I warned you about my long posts. I am surprised no one has anything to say - not "what new age crap" or "who is sthe smartass that wrote it?" or, as I felt "my god, this is me, its scarey and its over NOW"
Gileas, alone in the dark

Okay Gileas, I confess I read the whole thing. It was actually very informative. Thanks for sharing.

Light

I read most of it, but the words were too big.

I was afraid it was going to be both too boring and academic to serve the function I wanted - which was to help explain some of the elementary components which helped me decide to quit recreational narcotics use on top of narcotics use perscribed for legitimate pain from massive trauma. The post above, if read with care, explains my most insightful influences that provived legitimate and academic evidence of the damages I was causing myself, and the harm to my ability to participate in life.

I suppose I can try to rewrite it, but I dont think its that interesting for people to read about what components gave me the strength and reason, to kick, and the ability to overcome the fear of life without drugs, and to look forward to what I had been denying myself for so long.

Gileas, long winded and of questionable value at times, if my posts arent readable, they can be worse than silence