I. Introduction
According to the National Survey on Drug Use and Health, 21.5 million American adults, aged 12 and older, battled a substance abuse disorder in 2014 (1). In the surgeon general’s 2016 report, it was further reported that with around “78 people dying from overdose every day, only 10% of people with addictions ever receive any sort of help towards recovery” (2). Furthermore, instances of drug abuse and addiction impose a significant communal burden on American society, costing close to $200 billion in healthcare, criminal justice, legal and lost workplace production/participation costs in 2007 alone (1). Given alarming individual and shared repercussions that accompany rising drug consumption, it is unsurprising that the neurobiology of the brain has become a subject of remarkable scrutiny and investigation. After all, acquiring a thorough grasp of the adaptations that drug exposure elicits in individual neurons of the brain proves of vital import to the ultimate objective of developing appropriate and effective means to curb addiction.
In light of such observations, this paper surveys existing research on addiction and the neurobiology of the brain. This incorporates a discussion of the upregulation of the cAMP pathway, and its effects on GABA production and release. Following a detailed overview of the molecular and cellular basis of addiction, the paper proceeds to interrogate the efficacy, as well as the notable defects, of two main methods of redress conventionally adopted to tackle addiction: methadone maintenance, and education/advertising initiatives such as D.A.R.E. and Just Say No. Following a balanced examination of the salient strengths, and prominent shortcomings, that relate to each of these approaches, this paper ultimately advocates in favor of methadone maintenance as the comparatively more authoritative approach to combatting addiction; this conclusion is substantiated by ways of drawing compelling connections between medication-assisted therapies, and the neurobiology of the brain.
II. Addiction and the Neurobiology of the Brain
At its core, addiction is a biological process which concerns itself with the effects that repeated exposure to a biological agent (drug) has on a biological substrate (brain) over time (3). Complex behaviors – including dependence, tolerance, sensitization and craving – are thus symptomatic of an addicted state in which significant alterations have been made to the routine functioning of neural circuits.
Although drugs of abuse are in many ways chemically divergent, they share important commonalities (4). Among a number of observable congruences between such diverse substances is the following – drugs of abuse activate the mesolimbic dopamine system or the ‘rewards pathway’ of the brain, which induces increased firing of dopamine neurons in the ventral tegmental area (VTA) of the midbrain; the VTA is widely implicated in the natural reward circuitry of the brain (4). Drugs of abuse also facilitate an increase in the quantity of dopamine released into the nucleus accumbens (NAc) and other regions of the limbic forebrain; this limbic forebrain regulates processing memory and emotional information (4). [See Figure 1]
Moreover, chronic consumption of drugs of abuse result in significant modifications of reinforcement mechanisms and motivational states, as the euphoric effects accompanying overstimulation strongly reinforces the behavior of drug use (4). The downregulation of dopamine receptors, which takes place as the brain adjusts to dopamine surges, only then serves to augment the prospect of abuse and addiction, as the individual is driven to consume increased quantities of drugs in order to bring dopamine functions back to ‘normal’ or baseline (4). This is related to the concept of dependence, which specifically refers to an altered physiological state that emerges in light of continued drug exposure; with dependence, the cessation of drug use triggers symptoms of withdrawal (4).
More specifically, an up-regulation of the cAMP pathway responsible for cell communication takes place with chronic drug consumption; this phenomenon was initially observed in cultured neuroblastoma x glioma cells but was later also detected in neurons in response to repeated opiate administration (3). Chronic opiate exposure leads to a compensatory up-regulation of the cAMP pathway, which then arouses physiological tolerance (3). Tolerance refers to reduced drug responsiveness given repeated exposure to a constant drug dosage (4). This up-regulation has multiple effects, which manifests through increased concentrations of adenylyl cyclase, cAMP-dependent protein kinase A (PKA) and other components of this signaling pathway (3). This up-regulation is what eventually leads to increased GABA release during withdrawal; GABA is a calming neurotransmitter in the central nervous system whose neurons inhibit firing by dopaminergic neurons (3). Given that an up-regulated cAMP pathway results in increased GABA release during withdrawal and a reduction in the firing of dopaminergic and serotonergic neurons, it is clear that chronic administration of drugs of abuse results in palpable neurobiological changes. In this particular case, it elicits a reduction in dopaminergic neurotransmission from the VTA to the NAc, facilitating an aversive withdrawal state, which naturally then incentives continued drug abuse (3). [See Figure 2]
III. Methadone Maintenance
Given the demonstrated neurobiological effects of addiction and withdrawal, it is crucial to thoroughly interrogate the efficacy of substance abuse treatments that have been marketed as efficacious antidotes to drug abuse. Methadone treatment is one such method and involves the administration of methadone over a protracted period of time as treatment for opioid addiction to substances such as heroin (5). Such therapeutic dosing is contingent upon, and tailored to, individual patient needs, and generally requires that patients visit dispending clinics daily (6). When administered at constant daily milligram doses, methadone maintenance stabilizes patients and relieves withdrawal systems that customarily accompany complete abstinence from drug consumption (6). Methadone does so by binding to the mu receptors on nerve cells, which are the opioid receptor sites of action for heroin and other major opiates.
Methadone maintenance is often considered to be the first line of treatment, as it has proven superior to other non-agonist treatments such as detoxication, wait-list controls, abstinent-focused rehabilitation and placebo controls (7). Agonists are substances that instigate physiological responses when bound to a receptor. Consequently, its virtues are largely self-evident, and its continued practice appears unsurprising as clinical observations have evinced that methadone-maintenance allows for relatively steady-state sustained plasma levels, with peak plasma levels usually less than twice the trough levels, which suggests a timed-release mechanism that makes it well-suited for daily interval dosing (8). Unlike short-acting opiates (including heroin), the binding of methadone in body tissues, and its gradual, subsequent release into circulation, are what allows for the prolonged pharmacological actions of methadone in patients receiving regular dosages (8).
Another argument that supports the use of methadone maintenance is that early cross-tolerance or ‘narcotic blockade’ studies have illustrated that an individual on methadone seeking to get ‘high’ on heroin is unlikely to experience any desired or adverse effects; this derives from the strength of the stabilization and tolerance effects of methadone (8).
Despite such salient advantages, methadone maintenance does not exist without prominent imperfections. One such disadvantage is that the anti-tuberculosis drug, rifampin, accelerates methadone metabolism in the liver and its rapid removal from the body; this proves problematic given that opiate addicts are significantly more vulnerable to tuberculosis, and thus often require rifampin in order to treat their bacterial infections (8). The rapid metabolism of methadone consequently results in withdrawal symptoms in patients otherwise consuming a healthy dose of methadone (8).
In addition, high attrition rates observed within the first month, partly tied to the heavy reliance on methadone clinics to dispense daily dosages, function as a notable impediment; this speaks to the taxing nature of methadone maintenance treatments, which require significant investments in time (9). As an opioid itself, methadone is also susceptible to abuse and overdose (8). This derives from its full agonist action, which means there is no ceiling to the respiratory depression or sedation that it can induce; methadone overdose can subsequently be fatal if dosages are not properly managed (10). With respect to these particular shortcomings, buprenorphine, which is amenable to flexible dosing, is often posited as a workable alternative (though, it proves less effective than methadone at fixed medium or high doses) (10).
Consequently, a thorough overview of methadone maintenance reveals several poignant assets, as well as material failings, that leaves space for us to consider other proposed methods of redress for addiction and drug abuse.
IV. Educational Programs
One such alternative method is educational and advertising campaigns, such as Just Say No and D.A.R.E, the former of which was championed by Nancy Reagan in the 80s and early 90s, and the latter of which originated in 1983 from a local drug prevention program jointly sponsored by a school district in Los Angeles and the city police department. Both Just Say No and D.A.R.E are drug prevention programs designed to stave off addiction by obstructing the acquisition and consumption of drugs of abuse in the first place (11). Consequently, in response to the very real public health emergency that is the contemporary drug crisis, Just Say No and D.A.R.E offer an alternative model to medication-based therapies in that they focus primarily on encouraging potential abusers to avoid drug use through awareness campaigns and pedagogic tutorials; these programs also acknowledge the import of improving psychosocial behavior (i.e., peer-pressure resistance) as a means to thwart drug use (11).
An advantage to such educational and advertising campaigns is that the long-lasting reputation of programs such as Just Say No and D.A.R.E. lend credence and legitimacy to its continued efforts. Moreover, it benefits from wide-ranging approval, as parents themselves have largely articulated affirmative feedback given the widely-held belief that police officers function as effective educators, and that the integration of role-playing exercises withholds tremendous potential for success (11).
Though such instructional initiatives bypass some of the concerns vocalized against pharmacological approaches, such as high attrition rates, it also falls prey to extraordinarily salient critiques. A 2009 analysis of 20 studies of school-based D.A.R.E. programs revealed that students who underwent training were about as likely to try drugs as those who abstained (12). Keith Humphreys, the former drug policy adviser under President Barack Obama, further proclaimed that fear-based advertising has produced no observable and manifest benefits in the past few decades. Consequently, such initiatives appear inundated with skepticism, as studies have repeatedly highlighted its questionable efficacy.
Another compelling critique articulated against Just Say No and D.A.R.E. is that its rhetoric seemingly aligns the broad category of drugs with a menacing and vicious “other”; this “other” appears to arise from collective personal failure in particular communities, rather than from a wide-reaching public health crisis (13). More specifically, the rhetoric adopted by such campaigns alienates drug users and portrays them as toxic and deceptive criminals (13). Consequently, a pervasive shortcoming of such campaigns lies in its reductive, largely racialized characterization of the drug epidemic (13). This criticism appears largely confined to this method of redress alone, as methadone maintenance does not face such censure with regard to its public image.
Finally, the most persuasive appraisal of the defects underlying Just Say No and D.A.R.E originates from the observation that it fails to account for the neurobiology of addiction. While methadone maintenance acknowledges the science of withdrawal, such educational programs focus exclusively on halting drug consumption through intellectual literacy; this overlooks the complex neurobiology of addiction and withdrawal.
V. Conclusion
Given this balanced assessment of the principal strengths and noteworthy drawbacks that permeate both methadone-maintenance and educational/advertising initiatives such as Just Say No and D.A.R.E, I am compelled to claim that the former proves significantly more effective and appropriate than the latter. While the latter is certainly relevant in the grand scheme of augmenting awareness with regards to the pernicious nature of drug consumption and addiction, the use of methadone-maintenance proves to be a significantly more well-tested and validated approach to resolving the issue of addiction. This derives from the fact that the use of methadone pays due respect to the neurobiology of addiction and withdrawal and builds on the proven ways in which drugs of abuse affect the rewards pathway and reconfigures the firing of dopaminergic and serotonergic neurons.
Furthermore, I find it extraordinarily difficult to endorse educational and advertising campaigns that prove harmful in their reductive, racialized approach to characterizing drug abuse; that such campaigns have overwhelmingly portrayed addiction as a personal and moral failing, rather than a broad societal failure, appears as a grave ethical oversight I find myself unwilling to ignore.
As for the critiques: I sympathize with many of them. But, I am confident that a medication-based approach remains the most viable means of approaching addiction, a phenomenon that, at its core, concerns itself with the rewiring of numerous mechanisms in the brain. Though inconvenient with regards to having to visit clinics on a daily-basis, such exertion seems well worth the bother given its considerably more potent results.
Finally, though buprenorphine has been posited by some detractors as a viable alternative against methadone-maintenance, its lackluster performance with regards to retention rates leaves me unconvinced that it would be a superior pharmacological remedy (14). All in all, I believe that methadone-maintenance can certainly be further investigated in order to better retention rates and address some of its other salient critiques. However, given the above analysis, methadone-maintenance remains the most compelling approach to mitigating the incredibly grave phenomenon of drug abuse and addiction.