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.

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.

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.

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.

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.

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?

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.