Recreational Eu-Affectives: rationally designed, neuro-affective enhancers of the future – beyond MDMA and GHB
Introduction
The current global situation regarding the abuse of psychotropic substances, whether legal or illicit, is troubling. The abuse of drugs not only poses great hazards to the physical and neuro-affective health of their users, but also implies a vast scope of negative social implications as well as great economic burden. Since the passage of the Controlled Substances Act of 1970, a powerful apparatus has grown in the United States dedicated to end the abuse of psychotropic substances. Foremost, the Drug Enforcement Administration (DEA), which was created in order to fight "an all-out global war on the drug menace" (1), constitutes the ultimate symbol of an institutionalized-governmental endeavor to prevent the abuse of illicit psychoactive substances. However, the present global trends in drug abuse, especially in the United States, reveal that neither the DEA nor any other anti-drug campaign has been able to even closely approach this goal of drug control. In fact, large-scale epidemiological studies suggest the contrary: it seems that especially the use of “club drugs” is still on the rise (2, 3).But even if the war on drugs eventually accomplishes its mission, there will still be ethanol as a legal, socio-politically accepted psychotropic option that severely threatens the physical and mental health of its users. The abuse of alcohol has reached, especially in the western world, alarming public dimensions with countless negative implications.
I claim that it is rationally as well as ethically imperative to replace physically and neuro-affectively hazardous compounds with rationally designed chemical agents that users will prefer over already existing drugs of abuse and that will not only leave their physical and mental health undamaged but possibly enrich neuro-affective functioning in the long-term.
2. Drug abuse - the troubling reality
The war on drugs has been incisively pursued, especially by the DEA in the United States. Statistical facts such as the amounts of various popular drugs of abuse seized by the DEA, for instance the drug-seizures for the year 2007 of 96713 kilograms of cocaine, 625 kilograms of heroin, 356472 kilograms of marijuana, 1086 kilograms of methamphetamine, and 5636305 hallucinogenic dosage units or the number of drug-related arrests in 2007 of 27780 (4), might be viewed as impressive evidence for the continual success of the war on drugs. However, these figures might instead be seen as striking support for the skeptical view that the anti-drug agenda is ineffective and perhaps even fundamentally misguided.The following statistics remarkably reveal the outstanding prevalence of psychotropic substance abuse in the United States in the last decades. The Office of National Drug Control Policy found that, between 1988 and 1995, Americans spent 57.3 billion dollars on drugs, broken down as follows: 38 billion on cocaine, 9.6 billion on heroin, 7 billion on marijuana (4). The statistics of the abuse of the popular psychostimulant methamphetamine is another example of the thriving consumption of illicit drugs; it particularly highlights the popularity of drug abuse among youth. According to the 2005 National Survey on Drug Use and Health (NSDUH), an estimated 10.4 million people aged 12 or older (4.3 percent of the population) have tried methamphetamine at some time in their lives. Approximately 1.3 million reported past-year methamphetamine use, and 512000 reported current (past-month) use. Moreover, the 2005 Monitoring the Future (MTF) survey of student drug use and attitudes reported 4.5 percent of high school seniors had used methamphetamine within their lifetimes, while 8th-graders and 10th-graders reported lifetime use at 3.1 and 4.1 percent, respectively (4).
Further strong evidence for the continued, flourishing abuse of drugs despite major governmental-institutionalized, yearlong efforts is a recently released study of the National Institute on Drug Abuse which states that “most illicit drugs hold steady” (5). Similar discouraging predictions are being put forth by a recent National Drug Intelligence publication: it states that despite declines in cocaine availability and abuse, demand for the drug will likely remain high in the near term. Also treatment admissions for addiction to the popular psychoactive substance MDMA, also known as “Ecstasy”, may increase in the near term (5).
It seems clear that the effectiveness and ideology of the war against drugs might be criticized. However, a hard-to-dispute fact that the governmental-institutionalized effort to curtail the abuse of drugs strikingly reveals is that all known psychotropic substances that have been and are currently recreationally abused do pose physical and neuro-affective hazards to their users. Various studies have confirmed that chronic MDMA users exhibit significantly higher scores for depression. Besides, MDMA users exhibit difficulties in coding information into long-term memory, display impaired verbal learning, are more easily distracted, and are less efficient at focusing attention on complex tasks (6). It has been shown that chronic methamphetamine users, even abstinent ones, exhibit high levels of psychiatric symptoms, particularly depression and attempted suicide, but also anxiety and psychotic symptoms (7). The chronic abuse of cocaine is also correlated with psychopathological symptoms including depression (8). This is just a very short listing of some of the negative impacts of commonly abused drugs on users’ physical and mental health. The scope of undesirable side-effects that the chronic or even occasional use of presently available illicit psychoactive compounds afflicts upon their users is much wider and troubling than this brief representation can reveal. Thus, whether or not any governmental-institutionalized anti-drug agenda is ideologically ill-advised, it certainly is not misguided in the sense that it tries to curtail the use of seriously flawed substances.
3. The war on “some” drugs - ethanol
Ethanol has globally prevailed as the socio-politically accepted drug of choice, especially in the western world. But despite its socially accepted usage, ethanol does not offer its users a healthy solution to consciousness-enhancement. In fact, it poses a similar physical and neuro-affective threat as some other illicit psychoactive alternatives. One might argue that the legal availability and socially permitted, even encouraged widespread consumption of alcoholic beverages stands in paradoxical contrast to the socio-political attitude towards those psychotropic compounds declared as illicit. However, this inconsistent situation might only appear as absurd at first glance but actually reveal something fundamental and deep-rooted about the human predisposition to (ab)using consciousness-altering substances. I will explore this train of thought more thoroughly in the next section. For now, all I want to emphasize with the following alcohol-related statistics is the fact that ethanol is a legal, widely used psychotropic substance that poses major threats to the physical and mental health of its users.Revealing the troubling popularity of ethyl alcohol consumption among youth, it has been established that overall the prevalence of underage (ages 12-20) past-month alcohol use and binge drinking has been unchanged since 2002 in the US. In 2006, about 10.8 million persons (28.3 percent) in this age group reported drinking in the past month (9). Thus, the (ab)use of alcohol among underage youth has been discomfortingly high with no significant decrease in the last couple of years. Facts and figures regarding alcohol-related health issues published by the World Health Organization (WHO) are not comforting either. Alcohol is estimated to cause about 20-30% of oesophageal cancer, liver cancer, cirrhosis of the liver, homicide, epilepsy, and motor vehicle accidents worldwide. Besides, the WHO estimates that worldwide alcohol causes 1.8 million deaths (3.2% of total) and 58.3 million (4% of total) of Disability-Adjusted Life Years (DALYs). And globally, alcohol consumption has increased in recent decades (10). Thus, it is clear that alcohol, in spite of its socio-political status, does not constitute a flawless psychotropic substance.
Besides, if one evaluates the qualities of a psychoactive compound, a thorough investigation of its phenomenology is as crucial as an examination of its mental and physical health impacts. Even upon a quick examination of alcohol’s phenomenology, it becomes clear that the alcohol-induced texture of consciousness is substantially flawed in many ways. I think that among the plethora of phenomenological shortcomings of alcohol intoxication are heightened aggressivity potential and impaired decision-making skills. From a social and humanitarian perspective, it seems obvious that a psychotropic compound should ideally offer its users reduced feelings of aggression along with an unhampered ability to make reasonable decisions.
Therefore, although alcohol is socio-politically accepted and widely used in many parts of the world due to its culturally long and arguably rich history, it unfortunately displays a wide range of undesirable physical and mental health impacts as well as affective-phenomenological shortcomings.
4. Drug abuse in the light evolution
It is known that psychotropic compounds have been recreationally used by humans throughout history and across almost all cultures (11). The exact origins are often unknown but it is estimated that, for instance, the use of alcohol in the form of wine was used at least from the time of the early Egyptians. Other well-known and thoroughly studied historical examples of the use of consciousness-altering substances include the use of hallucinogenic mushrooms by pre-Columbian Mexicans as well as the use of cocaine and quinine by South American Indians. This is just a short glimpse into the very rich and complex history of the relationship between humans and psychoactive substances that is intended to hint at the fact that drug use and abuse (a clear distinction of the meanings of those two words is often quite difficult and certainly in some cases dependent on one’s viewpoint; I will limit my use to the term abuse in this paper though this might in some cases be somewhat arbitrary) has been pervasive throughout the history of humankind.This raises the crucial question of the proximate and, more fundamentally, of the ultimate reasons for the abuse of psychoactive substances by humans. The popular author and advocate of integrative medicine Andrew Weil put forth that the very desire to periodically alter consciousness whether by drugs or some other means “is an innate, normal drive analogous to hunger or the sexual drive” (12); as Weil puts it, the abuse of drugs “must represent a basic human appetite” (12). This view might be challenged as ideologically stained since concrete scientific-empirical evidence is missing. However, I argue that there is strong empirical neuro-evolutionary evidence that supports the view that the abuse of rewarding drugs is a powerful neuro-affective predisposition.
It has been established that almost all abused drugs act on brain reward systems. Although the brain evolved to respond not to drugs but to natural rewards, such as food and sex, psychoactive substances so-to-say hijack the brain’s natural reward systems. In the light of evolution, it was important that humans exhibited appropriate psycho-neurobiological responses to natural rewards that were important for survival, reproduction, and fitness. Many neurobiological systems crucially involved in reward, which are either activated by natural stimuli or by psychotropic drugs, are conserved across species from Drosophilae to rats to humans and primarily include dopamine, G-proteins, protein kinases, amine transporters, and transcription factors such as cAMP response element-binding protein (CREB) (13). This neurochemical elucidation of brain reward systems offers an ultimate explanation for the ancient, cross-cultural prevalence of drug abuse. The fact that drug rewards seem to activate the same brain systems as intense natural rewards reveals the deep-rooted neuro-affective power rewarding compounds have.
This neuro-evolutionary paradigm for drug abuse poses, I think, a challenge to any governmental-institutionalized effort to curtail the use of rewarding psychoactive substances. As Kent Berridge points out, there is convincing empirical evidence that rewards, either in the form of natural stimuli or exogenously administered compounds, “act at least as importantly as hedonic incentives, causing neural representations that elicit motivation and goal pursuit, rather than as mere habit reinforcers” (13). This implies that the abuse of drugs by youth is not necessarily fuelled by discontent or mere imprudence, as often touted by anti-drug campaigns, but rather an evolutionarily dictated, neuro-affective propensity to active one’s natural reward systems in a powerful, quick and easy manner. In the words of Stewart and Wise, “drug reward and withdrawal appear to motivate drug-taking behavior primarily via incentive modulation principles rather than directly via simple aversive drives” (14). These neuro-evolutionary paradigms should be taken into consideration when formulating socio-political agendas to deal with the problem of drug abuse.
However, an evolutionary-ultimate explanation does and should not provide justification or authorization. The Naturalistic Fallacy does, unfortunately, all too often rule over rational and ethical decision-making in many socio-political areas. Thus, by revealing the evolutionary roots of the worldwide prevalence of drug abuse I do not intend to argue against any socio-political effort to work against such a “natural” psycho-neurobiological propensity of the human mind-brain. I do not want to declare in a deterministic manner the abuse of drugs as an inevitable evolutionary-dictated, genetically-ingrained behavior of human beings. Nevertheless, by highlighting that almost all drugs of abuse powerfully activate natural reward systems, I intend to elucidate the supreme difficulties that any socio-political anti-drug program will have to face. In this respect, evolutionary-shaped human psycho-neurobiology might well explain the troubling drug-related statistics presented earlier and the apparent ineffectiveness of the war against drugs.
One might view the socio-politically accepted status of alcohol precisely in this light of evolution. Although it might seem paradoxical that there is a single drug of abuse that is socio-politically accepted whereas all other known rewarding compounds are declared as illicit, one could argue that alcohol’s legal status strikingly reveals the strong evolutionary-endowed, psycho-neurobiological propensity of humans to abuse drugs. The cultural-traditional widespread abuse of alcohol might be considered evidence for what Weil advertizes as “a basic human appetite”.
5. Post-Shulgin: Rationally Designed “Eu-Affectives”
An ethically justified, rational prescription I will now proceed to the essential part of this paper in which I will offer a prescription for the heavy global burden of drug abuse. I argue that taking all aspects of the present worldwide situation of drug abuse into account, the most rational, ethically imperative solution would be to direct scientific research into the rational design of rewarding chemical compounds. Ideally, such a scientifically-guided, governmental-institutionalized agenda should result in the development of rationally designed, socio-politically accepted, commercially available, recreationally used psychotropic compounds that exhibit a highly desirable affective profile and a complete lack of physical as well as neuro-affective short- or long-term drawbacks. Since such a psychoactive compound or (most likely) compound-mixture would be fundamentally different from any known drug of abuse, I propose here a new nomenclature for such a novel class of consciousness-altering substances that is free of the stigma associated with the word “drug”. I think that “Eu-Affective” is an apt term that captures the essence of these rationally designed, recreationally used neuro-affective enhancers.
5.1 The ethical argument:
With regards to the use of psychotropic compounds, ideological as well as ethical considerations are as crucial as scientific-empirical evidence. Therefore, I want to first propose my rational-drug-design solution with special regards to ethical issues going along with it. As already pointed out, it would be ethically blind-sighted if the use of psychotropic substances was permitted on the basis of an evolutionary-ultimate explanation. Naturalistic-Fallacy-like arguments should never taint the socio-political decision-making landscape. Thus, even if there obviously exists a strong evolutionary-dictated, neuro-affective predisposition to the abuse of rewarding compounds, this does not ethically justify a massive, worldwide scientific quest for the ideal Eu-Affectivum. Such a Euaffactive project seems to warrant thorough ethical investigations.However, there already exists a socio-politically accepted, commercialized and massively used psychotropic substance, namely alcohol. This strikingly simplifies all ethical considerations regarding this Euaffective-revolution I propose here. It is a given fact that globally a large segment of society abuses alcohol within a socio-politically accepted, commercialized framework. Thus, I do not propose here to introduce a new psychotropic compound into a drug-free society, but rather to replace a seriously flawed psychotropic cultural endowment as well as the plethora of illicitly abused alternatives with a rationally designed, neuro-affective-enhancing compound(-mixture). Given this rationale, I argue that such a euaffective-project is not ethically questionable in any way but rather constitutes, prima facie, a morally imperative strategy.
5.2 The Wealth of Benefits:
I want to outline now the abundant wealth of benefits that a rationally designed Euaffectivum would not only offer each individual user but society at large. Although all presently known drugs of abuse are flawed overall, some of them can offer instructive, perhaps even hope-inspiring insights that could potentially guide a Euaffective-revolution. I deem the popular drug of abuse 3,4-methylenedioxymethamphetamine (MDMA), which is colloquially known as “Ecstasy”, as a seriously flawed yet highly informative psychotropic substance. Various anecdotal accounts of the MDMA experience reveal that its phenomenal-affective effects are remarkable. The pharmacologist and chemist Alexander Shulgin describes the MDMA-induced state of consciousness with the following inspiring words: “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, and through the next day. I am overcome by the profundity of the experience” (14). Other user-reports are similarly enthusiastic and approving. The Chilean anthropologist Claudio Naranjo finds the following words for the MDMA-experience: “The perception of things and people is not altered or even enhanced, usually, but negative reactions that permeate our everyday lives beyond our conscious knowledge are held in abeyance and replaced by unconditional acceptance. This is much like Nietzsche's amor fati, love of fate, love of one's particular circumstances. The immediate reality seems to be welcomed in such MMDA-induced states without pain or attachment; joy does not seem to depend on the given situation, but on existence itself, and in such a state of mind everything is equally loveable" (15).Although these accounts might be disregarded as drug-induced delusions, the phenomenal-affective reality of MDMA revealed by these anecdotal accounts cannot be denied. In comparison to the socio-political drug of choice alcohol, MDMA seems to offer a profoundly positive state of consciousness. Although many people enjoy the experience of alcohol-intoxication, it seems likely that nobody would view any alcohol-experience in such an enthusiastic, highly approving light as Shulgin and Naranjo do with their MDMA-experiences. The alcohol-experience can certainly not be described as profound or wonderful; in the best case, it is pleasant. Thus, given these striking differences between the alcohol- and MDMA-experience, it does not seem surprising that many adolescents, seeking out novel, rewarding thrills, are intrigued by this psychoactive ring-substituted amphetamine-derivative that can induce such highly rewarding states of consciousness and that thus Ecstasy use is sharply on the rise among youth (2). More importantly, it seems that the MDMA-consciousness is actually preferable to that of alcohol from a sociopolitical point of view.
5.2.1. The quest for Social Tonic-Therapeutics (STTs)
MDMA offers a euaffective-model that has to be considered in a large social context. I argue that rational drug design should be primarily directed towards the development of so-called social tonic-therapeutics that exhibit an entactogenic, sympathogenic and sociabilizing neuro-affective profile. The French psychiatrist Claude Rifat classified MDMA as well as gamma-hydroxybutyrate (GHB), an endogenous substance of mammalian metabolism that is becoming increasingly popular in the “club scene” (2), as members of a new category of psychopharmacological agents, namely the so-called “sociabilizers”; members of this psychotropic kind induce profound pro-social feelings (16). Studies with rats confirm the pro-social effects of MDMA. And recently it has been shown that MDMA and GHB do, in fact, cause release of the pituitary neuropeptide oxytocin (17). It remains to be determined precisely how oxytocin fits into the neuro-affective architecture of emotions, which is presently based mainly on monoaminergic principles (18). In any case, empirical evidence strongly suggests that oxytocin plays a crucial role in inducing pro-social behavior. The potential of certain psychoactive drugs to induce the desire to socialize should not be disregarded as mawkish outpourings of “drugged-up” clubbers. I believe that oxytocinergic euaffectives could offer an invaluable opportunity for a peaceful social system to emerge. Especially in comparison with alcohol, the affective phenomenology of drugs such as MDMA and GHB should be viewed in a welcoming and approving light. It would be myopic and, more importantly, ethically untenable to let cultural preoccupations prevail over modern rational-ethical opportunities.The sociabilizing-dimension of such Euaffectives as touted here should be further enriched with an affective entactogenic and sympathogenic profile. The term “entactogen” was first coined by the medicinal chemist David E. Nichols who considered derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine to constitute a novel class of therapeutic compounds (19). Since there is some controversy regarding the precise distinction between the meanings of “entactogen” and “empathogen”, I will shortly delineate an adhoc nomenclature framework. First, I propose that the entactogenic dimension of a rationally designed Euaffective refers to a wide scope of nuanced affective qualities primarily centered on euphoria. Second, I suggest that the sympathogenic dimension refers to a wide scope of affective qualities centered on feelings of sympathy.
Thus, I argue that the primary goal should be to develop a psychoactive compound (-mixture) that induces the strong desire to socialize, that makes its user deeply feel with and care for other people, and that makes its user feel extraordinarily well. I believe that such a rationally designed social tonic-therapeutic could not only transform the quality of recreational social gatherings in the short-term, but might enable long-lasting positive changes regarding social life in general.
It is clear that while MDMA’s affective phenomenology is, I think, highly desirable in that it displays all three of the above-mentioned affective components to varying degrees (20), MDMA is overall hazardous and poses great risk to its users’ physical and mental health. However, the fact that psychopharmacological intervention has the power to restructure the neuro-affective architecture of consciousness in such a desirable way as MDMA does reveals the potential of a Euaffective-revolution to develop rationally designed psychotropic compounds that will be superior, foremost affectively, but also neurobiologically and physiologically to presently available drugs of abuse.
With respect to MDMA, some instructive empirical findings accentuate that the large gap which presently exists between a desirable affective-phenomenal profile and the somatic-neurobiological pitfalls of drugs of abuse can theoretically be closed. The negative impacts that drugs of abuse currently exhibit are generally natural yet unwanted responses of the intricate biochemical processes of the neuro-affective machinery. Theoretically, these physiological responses can be attenuated or even prevented through precise, exogenous pharmacological intervention. For instance, it has been shown that the MAO-b selective inhibitor deprenyl can attenuate MDMA neurotoxicity (21), that the NMDA antagonist memantine can prevent MDMA-induced cognitive impairments (22) and that minoxidil as well as phosphodiesterase-5 inhibitors, such as the popular erectile dysfunction medicine sildenafil, can prevent MDMA-induced serotonergic degeneration (23, 24). And there is no reason to believe that any of these psychopharmacological agents would significantly interfere with, for instance, the pro-social effects of MDMA. It is quite unlikely that most MDMA-users make use of any of these psychopharmacological measures; at the moment perhaps for their own good since it is still unknown if such interventions are safe. However, what these pharmacological damage-control tools highlight is that in the future there could exist a sophisticated psycho-pharmacopeia that offers potent affective enhancement without somatic-neurobiological shortcomings. Although there still remain many psychopharmacological unknowns, it has been convincingly established that MDMA’s primary affective characteristics of euphoria and empathy are due to its releasing and reuptake-inhibiting effects on the biogenic amines dopamine and serotonin (27). Anecdotal reports, especially by Alexander Shulgin in his famous book PiKHAL regarding various monoamine-releasers such MDMA, MBDB, MDA, etc. show that the ratio of the degrees to which the biogenic amines, dopamine, serotonin and norepinephrine, are being released is crucial to the resulting affective profile of each compound (14). Thus, I think it would be worthwhile to more rigorously investigate the precise neuro-affective characteristics of various monoamine releasers and their possible combinations. So far, such studies have been focused on the behavioral profile elicited by psychotropic compounds in animals. However, animal studies fail to elucidate the nuanced affective phenomenology of psychoactive drugs. Thus, I argue that “neuro-phenomenology” should become a prominent scientific discipline that investigates the precise phenomenal-affective profile of psychotropic compounds in humans, which could not only enable the development of potent yet benign Euaffectives but also that of more effective psychiatric medications.
It seems reasonable to speculate that it is or will be possible to rationally design a potent, non-neurotoxic, long-lasting monoamine-releaser cocktail that exhibits a highly desirable entactogenic, sympathogenic and sociablizing profile. Also, a large-scale, commercialized Euaffective-revolution could even result in a wide variety of entactogenic, sympathogenic sociabilizers with nuanced affective signature profiles. Currently, there is an effort to develop novel monoamine-releasers to develop therapeutic “agonist-approach” agents for stimulant addiction. Interestingly, while MDMA has been shown to cause depletions of serotonin, potentially leading to depressive mood in its users, the novel dual-action dopamine-serotonin releasers PAL-286 does not cause such 5-HT deficits (24). I argue that such relatively benign psychotropic agents should be investigated as novel, possibly non-neurotoxic, recreational Euaffectives. Also, while so far a mono-agent approach to drug development has predominated in both pharmaceutical as well as “underground” (e.g. Shulgin) psychopharmacological research, it seems rational to employ a poly-agent strategy to optimize the neuro-affective profile of a Euaffective.
It is still unclear in how far the various serotonin receptor-subtypes are causally involved in affective qualities such as empathy. However, it seems that, for instance, the serotonin receptor-subtype 1A is involved in the pro-social feelings induced by MDMA (25). Thus, the administration of a selective 5-HT 1A agonist, such as 8-OH DPAT, might induce an affective profile of pro-social, empathetic feelings. Speculatively, combining 8-OH DAPT with a non-selective dopamine-agonist might already offer a novel poly-agent Euaffective with mildly entactogenic, sympathogenic and sociabilizing qualities without leading to long-term serotonin depletions or neurotoxicity. Also, novel potent, selective nonpeptidic oxytocinergic agonists are already under development (18). Interestingly, the novel dual-agent therapeutic Oxytrex, which consists of a mixture of the potent semi-synthetic opiate oxycodone and of the mu-opioid receptor antagonist naltrexone in ultra-low-dose concentration, promises to offer opioidergic well-being in a relatively sustainable, tolerance- and dependence-devoid manner (26). Thus speculatively but optimistically, it seems possible that future poly-agent Euaffectives might contain non-addictive, tolerance-resistant, benign agonist/antagonist opiate-mixtures which potentially can deeply enrich its subjectively rewarding profile.
Recapitulation and future outlook:
If the present negative attitude towards the rational design of rewarding psychotropic compounds persists, there will soon be a gross, unfortunate mismatch between the ever-increasing psychopharmacological armamentarium of modern science and the dreary neuro-affective profile of available drugs of abuse, either legal or illicit. Given that the present path of alcohol-centrism will be followed for much longer, it seems likely that illicit designer drugs of the future might likely offer a vastly more sophisticated, benign psycho-neurobiological profile than alcohol. However, on the other hand it seems unlikely that the illicit, “underground” designer drug movement could produce anything similar to what a massive, socio-politically accepted, institutionalized-governmental, commercialized agenda of rationally designing Euaffectives could achieve. A rapid scientific advance of the possibilities of biotechnology-assisted psychopharmacology would render the present global preoccupation with alcohol not only an outdated, cultural neuroticism but also an ethically untenable shortcoming of socio-political decision making.If the vast scope of negative impacts caused by the wide-spread recreational use of presently available drugs is taken into account, ranging from unwanted physical as well as neuro-affective side-effects to alarming socio-economic drawbacks, the rapid advance of scientific knowledge, especially in the area of modern biotechnology, should be rationally as well as ethically viewed as a remarkably promising solution to the global burden of drug abuse. I claim that it is a rationally and ethically imperative strategy to develop recreational Euaffectives in a massive, rigorously academic, governmental-institutionalized manner, employing such promising modern scientific methods and techniques that are increasingly used in the pharmaceutical sector such as combinatorial chemistry, systems biology, RNA inference, etc. Speculatively yet optimistically, I argue that the rapidly advancing fields of pharmacoproteomics and pharmacogenomics will soon further broaden the scope of the neuro-affective promise of Euaffectives.
As is the case in traditional psychopharmacological research, great technical, economic as well as ethical challenges will face such a project as formulated here. Expensive, uncertain, elaborate long-term in-vitro, in-vivo, pre-clinical as well as clinical studies will have to be carried out. However, since the development of recreational Euaffectives will not be driven by the same sense of urgency, as is the case with psychiatric medications, the benefit-risk ratio can be vastly shifted towards the benefits aspect of drug design. Besides, I predict that once there is enough socio-political support for such a Euaffective-revolution, there will be a rapidly growing economic force effectively advancing progress in this field. This would not only lead to safer as well as more enjoyable Euaffectives, but also to a rapid expansion of scientific knowledge in such fields as neuroscience, neurobiology as well as psychopharmacology. This, in consequence, would enable psychiatric illnesses to be cured not only faster but also more effectively. Besides, although this essay only shortly elaborates on the remarkable benefits that rationally designed Euaffectives could have on the social fabric of human life, this seems to be a remarkably positive prospect that deserves much more emphasis and analysis than can be given here. It is of course highly speculative, but powerful entactogens, sympathogens and sociabilizers of the future might be able to reduce the occurrence of crimes, wars as well as interspecies conflict in general, which is presently often spurred instead of attenuated by drugs of abuse.
Thus, although the wine-connoisseur might be appalled by the prospect of an alcohol-free society, future generations who will be recreationally and legally using rationally designed, highly enjoyable and safe Euaffectives, likely will be grateful to be spared the pitfalls of cultural myopia.
References:
1. U.S. Drug Enforcement Administration, http://www.usdoj.gov/dea/history.htm
2. & 3: “Pharmacological aspects of the combined use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and gamma-hydroxybutyric acid (GHB): a review of the literature”, Joachim D. et el, Drug and Alcohol Review, Volume 24, Issue 4 July 2005 , pages 359 – 368
4. http://www.usdoj.gov/dea/statistics.html 5. http://www.nida.nih.gov/Infofacts/costs.html 6. “Chronic MDMA (ecstasy) use, cognition and mood.” McCardle K, Luebbers S, Carter JD, Croft RJ, Stough C. Psychopharmacology (Berl). 2004 May;173(3-4):434-9. Epub 2004 Apr 16.
7. “Methamphetamine abuse and impairment of social functioning: a review of the underlying neurophysiological causes and behavioral implications.” Homer BD, Solomon TM, Moeller RW, Mascia A, DeRaleau L, Halkitis PN. Psychol Bull. 2008 Mar;134(2):301-10. Review.
8. “Cocaine use and psychopathology: associations among young adults.” Newcomb MD, Bentler PM, Fahy B. Int J Addict. 1987 Dec;22(12):1167-88.
9. http://www.nida.nih.gov/DrugPages/Alcohol.html
10. http://www.who.int/topics/alcohol_drinking/en/
11. http://www.drug-rehabs.org/drughistory.php
12. “Psycho-active Drugs in Human History”, Andrew Weil
13. “Addiction.” Robinson TE, Berridge KC. Annu Rev Psychol. 2003;54:25-53. Epub 2002 Jun 10. Review
14. “PiKHAL”, Alexander Shulgin
15. “The healing journey”, Claudio Naranjo
16. Claude Rifat
17. “Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration.” Dumont GJ, Sweep FC, van der Steen R, Hermsen R, Donders AR, Touw DJ, van Gerven JM, Buitelaar JK, Verkes RJ. Soc Neurosci. 2009;4(4):359-66.
18. “Primary process affects and brain oxytocin.”Panksepp J. Biol Psychiatry. 2009 May 1;65(9):725-7.
19. “Differences between the mechanism of action of MDMA, MBDB, and the classic hallucinogens. Identification of a new therapeutic class: entactogens.” David E. Nichols
20. "The psychotherapeutic potential of MDMA (3,4-methylenedioxymethamphetamine): an evidence-based review”. Parrott AC. Psychopharmacology (Berl). 2007 Apr;191(2):181-93. Epub 2007 Feb 13. Review.
21. “Monoamine oxidase-B mediates ecstasy-induced neurotoxic effects to adolescent rat brain mitochondria.” Alves E, Summavielle T, Alves CJ, Gomes-da-Silva J, Barata JC, Fernandes E, Bastos Mde L, Tavares MA, Carvalho F. J Neurosci. 2007 Sep 19;27(38):10203-10.
22. “Memantine prevents the cognitive impairment induced by 3,4-methylenedioxymethamphetamine in rats.” Camarasa J, Marimón JM, Rodrigo T, Escubedo E, Pubill D. Laboratory of Pharmacology and Pharmacognosy, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
23. “Minoxidil prevents 3,4-methylenedioxymethamphetamine-induced serotonin depletions: role of mitochondrial ATP-sensitive potassium channels, Akt and ERK”. Goñi-Allo B, Puerta E, Ramos M, Lasheras B, Jordán J, Aguirre N. Department of Pharmacology, School of Medicine, University of Navarra, Spain.
24. “Development o of a rationally designed, low abuse potential, biogenic amine releaser that suppresses cocaine self-administration”. Rothman RB, Blough BE, Woolverton WL, Anderson KG, Negus SS, Mello NK, Roth BL, Baumann MH.Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
25. “Investigation of serotonin-1A receptor function in the human psychopharmacology of MDMA”. Hasler F, Studerus E, Lindner K, Ludewig S, Vollenweider F. J Psychopharmacology 2008 Jul 17
26. “Oxytrex minimizes physical dependence while providing effective analgesia: a randomized controlled trial in low back pain.” Webster LR, Butera PG, Moran LV, Wu N, Burns LH, Friedmann N. J Pain. 2006 Dec;7(12):937-46.
The Euaffectist
The Euaffectist
* * * The Euphenomenological Age
Brave New World by Aldous Huxley
Brave New World Revisited (1958) by Aldous Huxley