Some dead drugs

One spectacularly incompetent route to a lifetime of happiness involves taking illegal 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 catecholamines (noradrenaline; dopamine), amphetamine triggers to a much greater extent their synaptic release as well. It is thus more potent.
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.

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 marginally more benign. They can be extremely pleasurable. Next century, their customised and site-selective successors may play a valuable role in promoting emotional superhealth. We could all do with having our native endorphin systems enriched. Unfortunately, the present crop are physiologically addictive They lose quite a bit of their euphoriant effect as tolerance sets in. Typically, they inspire a dreamily contented disengagement from the problems of the world. They diminish any drive to constructive activity. Sadly, too, their use impairs the release of endogenous opioids normally induced by social interaction with friends and family.

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 exogenous opioids in contemporary society. Yet even if they were legal and given away in cereal packets, they wouldn't make a good choice of mood-booster - or at least not in their present, crudely non-specific guise. kappa- agonists, for instance, have dys phoric 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, however be habit-forming. It has euphoriant, psychedelic and sedative properties. Experiments with stoned rats suggest the drug reduces the amount of corticotrophin-releasing factor 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.

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, it 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. It seems that 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 self-development of the species. This does not, one ought scarcely need to add, suggest users should be persecuted and criminalised.

The empathogen "hug-drug", ecstasy (methylenedioxymethamphetamine; MDMA) offers a wonderfully warm, sensuous, loving, and empathetic peak experience to the first-time user. 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 selfish-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-hydroxybutyric acid (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 and fleeting parody of the life-long chemical nirvana on offer to our transhuman successors.

Alcohol - the traditional date-rape drug of choice - and, most insidiously of all, cigarettes are the really sinister mass-killers. 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 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 ex-British Prime Minister accepted a million-dollar bribe from a leading member of the drug-cartels for her services. Her party's ineffable 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.

Drugs for mental health

Could we live happily ever after? Perhaps. One's interest in the genetically pre-programmed states of sublimity sketched in The Hedonistic Imperative is tempered by the knowledge that one is unlikely to be around to enjoy them.
It's all very well being told our descendants will experience every moment of their lives as a breathtakingly 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 base-line of emotional well-being may indeed exceed 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 neurobiological 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 in-built 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 any effect.
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 late twentieth-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 - one's embarrassment at using the frisson-charged term from the vernacular is revealing - 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 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 sub-system y. Its sequelae include mood-congruent cognitive delusions and several chronic and intractable cases of toxic affective psychosis".
Eeek! Needless to say, no sensible adult would wish to mess around with such 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. 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.