Pharmacological Intervention in Drug and Alcohol Addiction

By Colleen FarrellyHOPR 196

April 22, 2006

Pharmacological Intervention in Drug and Alcohol Addiction

Treatment for drug addiction is a very complicated process, no matter which approach is taken. In order to treat addiction, one must first understand the underlying causes of addiction and the mechanisms by which it continues and progresses. No one field offers a complete explanation and a sure treatment method for addiction. In the field of neuroscience (in treatment, more accurately neuropsychopharmacology), the underlying mechanisms of drug addiction lie within neurochemical imbalances and within the plasticity (ability to adapt) of neuronal synapses within certain brain pathways; treatment, then, consists of correcting these imbalances and attempting to alter the synaptic connections formed from the repeated use of psychoactive substances by administering counteractive drugs.

First of all, it is important to understand the balance of neurotransmitters and the plasticity of synapses. Many of the structures implicated in addiction are part of the limbic system, the structures responsible for regulating essential animal functions, such as eating, sleeping, reproduction, and emotions. Among these areas are the ventral tegmental area (VTA), the nucleus accubens (NA), and the frontal cortex. Many of these neurons release dopamine (and, additionally, glutamate) as their primary neurotransmitter, which reinforces behaviors essential to survival in a similar way to Pavlov’s classical conditioning of his dogs. When psychoactive substances pass from the bloodstream (through a tight glial network called the blood-brain barrier) to these dopaminergic pathways and act on these systems (either directly or indirectly), they create a similar biochemical reinforcement as eating would, and the brain begins to associate the behavior of taking the drug with other necessary biological functions. (This is why highly psychologically addicting drugs are as addicting as they are.) In addition, the drug-associated stimuli and subsequent reward response create new structure and organization

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among affected neurons: postsynaptic sites (which receive the neurotransmitters) adapt to the excess dopamine by creating more receptor sites and new connections are formed and reinforced as the same stimuli are presented.1

For example, in the mesolimbic dopaminergic system (including the VTA and NA), neurons become primed (changed in structure and in connection) with the repeated drug-taking stimuli (setting, ritual, drug ingestion itself) so that the neurochemistry of the system becomes classically conditioned to associate the drug-taking stimuli with pleasure. This conditioning continues to become stronger as long as the drug is taken. When the person ceases use, the adaptation is still present, and the brain will think it is missing something necessary for survival. In this way, withdrawal will produce the opposite effects as intoxication of the particular drug will (called the “law of opposites”). For example, cocaine intoxication produces euphoria; withdrawal from cocaine produces dysphoria.

Eventually, the neurochemical balance and postsynaptic receptor sites (both of which cause the physical dependence seen in addiction) will return to normal and the conditioning will become dormant. However, the neuronal pathway connections between the stimuli and pleasure will still exist (psychological dependence), so that when the person is presented with a drug-taking stimulus (perhaps a pipe for the crack addict or a favorite bar for the alcoholic), the connections created between neurons will still carry the message that the drug is coming (much the same way that seeing a carved turkey when one has not eaten in a day will produce hunger and salivation), and the person will experience a “drug-hunger,” or a craving, for the drug. This is termed the “reinstatement paradigm,” and it is the biggest challenge in treating addiction, as the synaptogenesis (forming of new connections) during the formation of an addiction is not easily reversed once it is established.2

1 Self, pg. 3982 Self, pg. 445-448

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Pharmacology offers several treatment options for addiction by correcting either the binding of psychoactive substances or by correcting existing chemical imbalances. Agonists are substances which act upon neurotransmitter receptors in the same way that endogenous substances (which are naturally produced by the body) would. For example, enkephalins (a type of endogenous opioid) bind to a receptor kappa-1; opiates such as morphine have a similar chemical structure to enkephalins and will fit into the receptor site like the right key will fit into a given lock. Antagonists, on the other hand, block receptor sites or bind to the substance so that the substance (endogenous or other) will not be able to bind; antagonists produce no signal in the receptor cell, much the way the wrong key will produce no effect on opening the lock. In addition, some substances can be partial agonists. These substances will bind well enough to receptor sites that they will produce some effect in the receptor cell, but they do not elicit the same magnitude of response as an agonist would. In this way, they can function as an agonist or an antagonist, as they block the true agonists from binding. These properties become especially important in treating overdoses and in treating a patient’s withdrawal symptoms.3

In addition, drug metabolism is important to pharmacology and its efforts to treat addiction. When a drug is ingested, it must eventually be broken down, or metabolized, for elimination, much the same way food must be digested before it can leave the body. Enzymes within the liver accomplish this through a series of steps, until the final product of the reactions and their by-products can be removed from the body. Catalysts, special proteins, speed up the rate of the reaction and the metabolic processes. In this way, catalysts can speed up the slowest step in metabolism (referred to as the rate-limiting step) and change which products stay in the body for the longest period of time. Certain drugs can either act as catalysts themselves to speed up the metabolism of a substance or can bind to catalysts or enzymes to slow the metabolic

3 Perrine, pg. 18-19

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process down. This becomes especially important in the long-term treatment of addiction.4

These aforementioned properties carry several implications for addiction treatment with pharmaceuticals. First, the primary types of neurotransmitters involved in the patient’s addiction (dopamine in cocaine dependence, for instance) will dictate which drug is prescribed. It would make no sense to treat cocaine addiction (which works on the dopaminergic and norepinephrine systems) with a drug that works on the endogenous opioid systems. Second, the functions of drug action and desired effect on the patient must match. If someone has overdosed on heroin, a drug that treats opiate cravings will not necessarily reverse the effects of the overdose. The situation and the drug administered must match. Lastly, catalytic drugs or drugs inhibiting catalysts must match the patient’s situation. If a certain metabolite (product created during substance break-down) produces an unpleasant effect that might cause a person to avoid taking a certain substance, the administered drug must prolong the length of time before that metabolite is broken down, so that it can accumulate in the body, producing its unpleasant effect. In all, care must be taken to match the patient’s circumstances and drug(s) of choice with the right prescription.

From this, drugs used in treating addiction can be categorized according to function and according to the abused substance for which they will work best. The first category includes drugs used in overdoses, the most common of which is used in the reversal of opiate overdoses. These drugs either block receptor sites or prevent the substance from binding by changing the substance’s chemical structure. The second category includes the maintenance drugs, typically used in treating heroin addiction. These drugs prevent withdrawal but do not produce the euphoric effects of heroin, and they try to eliminate the use of needles (and, hence, prevent the spread of HIV and other transmitted diseases among addicts). The third category encompasses drugs used in

4 Perrine, pg. 124

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detoxification. These slowly ease patients off drugs without having to experience full-blown withdrawal symptoms. The fourth category is for anti-craving drugs. These drugs block cue-triggered cravings from the prior synaptogenesis upon onset of the addiction and help prevent relapse. Finally, some drugs are used in the treatment of pain in recovering patients or in patients on maintenance programs. These are important, as certain drugs of addiction primarily take away pain (such as the opiates) and as the introduction of pain to such patients may trigger relapse into the addiction.

First, drugs can be used to reverse overdoses. In opiate overdoses, the patient receiving the drug, called naloxone, will often be hypotensive, disoriented and possibly experiencing respiratory failure. Naloxone is an opiate antagonist that prevents the binding of the ingested opiate. It must be administered either intravenously or intramuscularly, as stomach enzymes will break it down. Naloxone is a very powerful antagonist, as 1 mg will block 25 mg of heroin. Typically, a .5-10 mg dose is administered, and the patient is gradually brought out of the overdose. The dosage is then taped by 60% until all the symptoms have subsided and the patient has finally recovered from the overdose. Naloxone is non-addicting and will produce no signs of withdrawal itself. Overdose drugs also exist for alcohol overdoses; the primary drug is Ro 15-4513, which blocks the neurochemical effects of alcohol intoxication by working on the GABAerigic system (the primary system involved in alcohol’s effects). Ro 15-4513 is a benzodiazepine (anti-anxiety drug) and binds to GABA receptors. These drugs have been especially important in emergency medicine, as naloxone will prevent patient death and undo the acute effects of opiate usage and as Ro 15-4513 will reduce a severely intoxicated person’s belligerent or anxious behavior-quite important in patients receiving treatment for injuries sustained while intoxicated (car accidents, falls, or fights)—so that doctors can more easily assess injuries and treat the patient.5

5 Perrine, pg. 87, and Feldman, pg. 657

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The second category is that of the maintenance drugs. These drugs are mainly used in the treatment of opiate addiction. Methadone, which was invented as a possible treatment for heroin withdrawal in the 1930s, has long been used as a maintenance drug. Methadone maintenance programs came into existence in 1963 and were created by Dr. Vincent Dole and Dr. Marie Nyswander in New York City. The main concept is to substitute a non-euphoric opiate addiction (methadone) for a euphoric one (heroin), an orally-administered one for an injection-administered one. Methadone is a slow-acting opiate, meaning that it has a substantial time between dosage administration and the onset of withdrawal symptoms (which tend to be milder than the ones caused by heroin), allowing the patient to center his or her life around something other than his or her opiate addiction. In addition, maintaining a constant blood opiate level (rather than the highly variable one with heroin use), a patient’s immunological and neuroendocrinal responses are substantially better, leading to better overall health. By providing this service to opiate-dependent patients, these patients should not have to find money to get the drugs to stave withdrawal, and they should not have to interact with drug dealers. Ideally, this would allow them to function better in society, reduce crime rates among addicts, and allow for better health, as no needles (or needle-sharing!) are necessary.

However, a study done by the Institute for Social Research at the University of Michigan has found that the methadone maintenance program has not reduced any of these problems substantially and that it has also failed to lessen illicit drug use among its participants, as well as failed to lessen the spread of HIV infection among users.6 In addition, the United States of America has put many regulations on the length of methadone treatment for heroin addicts.7 Six-year success rates for

6 Feldman, pg. 5477 These include a demonstrable minimum of one year of opiate addiction with current evidence of opiate use and abuse.

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willing participants are around 40% when used in addition to counseling or group therapy.8

LAAM is another maintenance drug that has been used in place of methadone. Like methadone, LAAM is a synthetic, long-acting opiate agonist (with duration of up to 96 hours, three times that of methadone) that is cheaply produced. It, too, relieves the patient’s cravings, redirects activity from drug-obtaining behaviors, lowers the chances of HIV infection, promotes better immunological functioning, and leads to less mortality (from either overdoses or from violent encounters with heroin dealers). In fact, LAAM at first seemed to work even better than methadone, but it has since been linked to cardiotoxic reactions (especially with prolonged usage), leading to its eventual removal of use from maintenance programs.9

Maintenance programs, on the whole, have created much social and political controversy, as their aim is to replace one addiction with another, rather than attempt to get the patient off of drugs altogether. This seems to undermine America’s War on Drugs and its anti-drug campaigns. Some view it as a soft-on-drugs stance, while others view it as more successful at preventing the adverse social and medical consequences of heroin addiction than the maintenance programs really are. Perhaps the programs serve as a compromise between the two stances on the problem of heroin addiction.

Another category of drugs used in the treatment of addiction are the drugs used in detoxification. These are important, as they lesson the symptoms of withdrawal, which can either be unpleasant enough to trigger the patient to reuse the substance or, in the case of withdrawal from depressants like alcohol, can be life-threatening in severe cases. Drugs used in detoxification typically are agonists of the substance previously used by the patient and gradually wean the patient off drugs altogether. Two of the substances with which detoxification drugs are used are to ease withdrawal are opiates and alcohol.8 Feldman, pg. 5479 Meyer, pg. 270

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First, any opiate can be substituted when the patient is addicted to an opiate and is experiencing withdrawal symptoms. Typically, opiate withdrawal symptoms include diarrhea, cramps, fatigue, anxiety, fever, tremor, hypothermia, nausea, vomiting, cold sweats, and piloerection (hence the term “cold turkey” used for the cessation of opiate use without pharmacological intervention) and vary in severity and duration depending on usual dosage, intervals between dosages, duration of opiate use, and the patient’s psychological well-being. Severe cases may last for several weeks. Usually, detoxification drugs (such as methadone) are substituted in dosages similar to the patient’s typical dosage and decreased by about 10% per day until the patient is drug-free. This process can be sped up or slowed down depending on how the patient reacts to the gradual withdrawal. Another drug, an alpha-2-adrenergic receptor agonist called clonidine, has been used to ease withdrawal symptoms, but this drug tends to produce profound sleepiness and has become a street drug outside of detoxification centers. Although these drugs lessen the severity of withdrawal symptoms, they also prolong the duration of withdrawal, which can occasionally pose problems for patients in short-term treatment programs.10

Alcohol withdrawal, however, must be monitored closely, as severe withdrawal symptoms (called delirium tremens, or DTs), such as seizures, hallucinations, and occasionally death can result, in addition to the usual withdrawal symptoms of nausea, vomiting, sweats, tremors, tachycardia, anxiety, and headaches. Most of the symptoms occur as a consequence of alcohol’s interactions with GABA and glutamate receptors within the brain, so drugs working on these systems (which will show a cross-tolerance in response to alcohol tolerance) are usually administered. Benzodiazepines, such as diazepam (Valium), are prescribed for the relief of anxiety and for the prevention of seizures. Haloperidol, a typical anti-psychotic used in the treatment of positive schizophrenic symptoms, is given to reduce the occurrence of hallucinations. Like opiate withdrawal, the symptoms of

10 Perrine, pg. 90

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alcohol withdrawal vary according to the usual dosage, duration of use, and periods between use—as well as if the patient has ever sustained a head injury, such as a concussion or a traumatic brain injury. Also like opiate withdrawal, drugs used in alcohol detoxification are gradually tapered until the patient is substance-free.11

In the treatment of addiction, detoxification is certainly a step in the process, but it is not the last step. After a patient has undergone withdrawal, he or she ideally must not return to substance use or will likely return as a detoxification or overdose patient once more. Two types of rehabilitation drugs are used to try to keep the patient from relapsing: aversion therapy drugs and anti-craving drugs. When used in conjunction with long-term counseling and group meetings (such as Alcoholics Anonymous, Narcotics Anonymous, or Cocaine Anonymous), these drugs can be very effective in preventing relapse in substance-dependent patients.

The first type of relapse-prevention drugs includes those used in aversion therapy. Aversion therapy lies on the classical conditioning principles that the patient uses the substance of choice because he or she perceives its effects as pleasant. If the substance no longer produces the sought-after pleasant effects, the patient will eventually become reconditioned to associate the substance with unpleasant effects and cease use of the substance. Aversion therapy incorporates drugs that will create such unpleasantness with the patient’s self-administration of alcohol.

Disulfiram is one such drug used in treating alcohol dependence. It inhibits an enzyme called aldehyde dehydrogenase, which is part of the metabolism of alcohol (see diagram below).

11 Feldman, pg. 658

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This allows levels of blood acetaldehyde to rise, producing tremor, nausea, severe vomiting, and diarrhea with the ingestion of as little as 7 ml of alcohol. The drug was accidentally discovered in the 1940s by Jens Hald, who was studying disulfiram in the treatment of intestinal parasites. After accidentally ingesting a small amount of the compound, he went to the local tavern with friends, drank brandy, and became violently ill, discovering the first aversion-therapy drug for alcohol dependence treatment.12 As disulfiram produces such violent illness, it is contraindicated in patients within the stages of early recovery, as relapse is common within this stage, and it is most effective in patients who also participate in counseling and a recovery program such as Alcoholics Anonymous.

Several anti-craving drugs exist for the treatment of alcohol or opiate dependence. These drugs either block the association pathways in the VTA or NA created during the addiction process (implicated in the workings of stimuli-induced drug craving) or block the pleasure when the patient relapses into use. Many of the effective drugs in this category work on both systems. Naltrexone, nalmefone, acomprosate, and, to some extent, ibogaine, are such drugs.

Naltrexone is an anti-craving drug used in the treatment of both alcohol and heroin dependence. It is an opiate antagonist (working on the mu and delta receptors of the endogenous opioid system), which can also be used in overdose treatment and as a rapid detoxification drug, that produces no noxious side effects in the case of patient relapse. It can be taken orally as little as 3 times per week, and it blocks the effects of opiate use, as well as blocking craving in both opiate- and alcohol-dependent patients. In alcohol-dependent patients, naltrexone is very effective in reducing relapse rates and reducing consumption rates in those who do relapse. A 1992 University of Pennsylvania study found that 73% of patients taking naltrexone remained sober during the experimental 12-week period, compared to the 45% of patients receiving

12 Feldman, pg. 658-659

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a placebo.13 A similar study was conducted by McClellan with regard to the effects of naltrexone in the treatment of heroin-dependent patients systematically exposed to drug-use cues, but the study needed to be abandoned because the levels of cravings experienced by the patients became hazardous. However, a study of naltrexone’s efficacy in treatment of opiate-dependent physicians produced a 74% one-year success rate.14 In all, naltrexone works very well in highly-motivated patients while producing minimal side effects, even with the ingestion of the substance of choice.

Another anti-craving drug which has yielded promising results in alcohol-dependent patients is acomprosate, a partial agonist for glutamate receptors (specifically, NMDA channels). It has doubled the rate of abstinence among alcohol-dependent patients, lessoning drinking days by an average of nearly 50%. Like naltrexone, the best outcomes were obtained in patients who also received counseling or attended some sort of group therapy.15

Two less-studied anti-craving drugs are nalmefone and ibogaine. Nalmefone is an opiate antagonist, also used as an overdose-reversal drug, which has proven beneficial in preventing cravings among alcohol-dependent patients. Ibogaine is an antagonist drug which works primary on glutamate and dopamine receptors (though it may play a role in modifying kappa-opioid receptors). It comes from a type of African shrub and is thought to have psychedelic effects, though it does not work on the same receptors (5-HT) as other hallucinogens, such as LSD. In studies conducted in the Netherlands, Israel, and St. Vincent, it has shown promising results in blocking cravings in cocaine-dependent patients, as well as heroin-dependent and alcohol-dependent patients. However, ibogaine and its derivatives are considered Schedule I drugs in the United States, and medical experimentation is prohibited.16

13 Feldman, pg. 65914 Feldman, pg. 54715 Feldman, pg. 65916 Abrams, pg. 24-25

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In addition to the drugs directly affecting drug addiction treatment, drugs prescribed for pain relief in drug-dependent and recovering patients are important as well. “Few engender as much anger and hostility among physicians and other health-care providers as alcoholics and heroin addicts. The diagnosis of either condition immediately serves to make the person’s complaints and past medical history suspect.”17 This is because opiate-dependent patients seeking pain relief present several problems to physicians.

First is the problem of obtaining an accurate account of medical problems and drug usage from the patient. Patients may try to conceal the true amount of narcotics they take for both fear of physician disbelief and for fear that the physician may be unwilling to prescribe the high dosages of narcotics that they may need for adequate pain relief due to an acquired tolerance. Without this information, it becomes hard for the physician to figure out what dosage to prescribe. Several factors necessitate the high dosages required to treat pain in recovering patients. First, the opiate-dependent patient has acquired a cross-tolerance to all other narcotics. It is not that the patient desires to become high of the pain medications, but, rather, that a low dose will not relive the pain. Additionally, it is not because the patient has experienced a decrease in pain tolerance that he or she needs for pain relief, but because the opiate tolerance and subsequent synaptic changes have produced a lowering of pain thresholds, so that even seemingly innocuous stimuli can trigger pain receptors to signal the sensation of pain.

In addition to the problems of tolerance and obtaining an accurate drug history, the physician may be faced with the question of what to prescribe and how much to prescribe. Non-narcotics are recommended before narcotics, and tranquilizers are contraindicated in substance-dependent patients. However, if non-narcotics (such as NSAIDS, including aspirin and ibuprofen) do not provide adequate pain relief, low doses of narcotics can be given until the dosage has been raised high enough to

17 Stimmel, pg. 387

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relieve the pain but still low enough to not produce sedation or euphoria. If the patient is going through detoxification, a short-acting parenteral narcotic can be substituted for the detoxification drug, and the patient can gradually be weaned from the prescribed narcotic. All in all, pain management is very important in the treatment of addiction, as chronic or acute pain can trigger relapse into drug use.18

Neuropsychopharmacology has provided many contributions to the field of addiction studies, both with regard to the development of addiction and to the treatment of addiction. It has offered solutions to cases of overdose, has made detoxification and maintenance possible, and has offered solutions to the cravings that often hinder recovery, as well as offered a solution to pain in substance-dependent patients. However, it has not offered absolute solutions to the problems and has a far way to go before the field can offer more effective treatments.

First, drugs that reverse opiate overdoses, such as naloxone, have both positive aspects and negative aspects. Naloxone can prevent death in patients who have overdosed, who would once have died from respiratory failure. However, the person (or the person’s friends) has to seek medical help for the drug to be administered and hence reverse the overdose symptoms. If he or she is alone, the person may not be able to do this or be willing to do such, as non-medical use of opiates is illegal. In addition, naloxone also may not cause withdrawal itself, but by blocking the binding of opiates, it can induce opiate withdrawal in dependent patients.

Similarly, maintenance drugs, such as methadone, possess both positive aspects and negative ones. One the positive side, methadone can allow opiate-dependent patients to regain normal societal function—finishing school, holding a job, caring for a family—that would be nearly impossible otherwise. In addition, methadone maintenance programs can reduce the chance of HIV infection, as it eliminates the need for needles and cookers, and can also reduce mortality rates from other infection

18 Stimmel, pg. 381-391

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(from lowered immunological response) and from violent confrontations with dealers or from overdose.

However, several problems exist with these programs. First, by giving the opiate-dependent patient an opiate drug, if he or she takes heroin in addition to the methadone, and overdose can quickly result, and the possibility of contracting HIV by sharing needles or cookers increases greatly, as does the possibility of violent encounters with dealers. Second, methadone maintenance programs do not solve the problem of addiction; they consist of merely substituting one addiction for another. The dependent patient is still drug-dependent, albeit a better functioning drug-dependent patient. If the goal is to achieve sobriety, providing drugs for the dependent patient will not allow progress towards this goal. In addition, compliance issues arise in maintenance programs, as the patient must show up to receive the drug and must refrain from using other drugs to avoid overdosing. In all, these programs do not serve their purpose as effectively as once hoped and should probably be re-evaluated or restructured to lessen the problems of compliance.

In addition to the previous two pharmacological interventions, detoxification drugs offer advantages and have disadvantages. One advantage to detoxification is that slow, controlled withdrawal is safer and more comfortable than rapid, uncontrolled withdrawal. Patients have lower morality rates when withdrawing form depressants like alcohol and also are more likely to stay clean if withdrawal is not as painful as they may have previously experienced when trying to get off the drug without medical intervention. This means that long-term sobriety is more likely to be achieved and the patient will stay in treatment long enough to learn strategies for living life without the use of drugs. However, detoxification itself is not a long-term solution to addiction. Without other interventions (such as counseling or an after-care group), the patient is unlikely to stay clean. Pharmacological intervention in detoxification is a beneficial first step, but it is not a solution in and of itself.

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Anti-craving drugs and aversive drugs can provide another step in treatment after detoxification is complete and can play a role in achieving long-term sobriety. These drugs have many positive features, as well as some negative ones. First, anti-craving drugs and aversion-therapy drugs are useful in relapse-prevention. One-year success rates have been as high as 70% in recent studies, over two times as high as success rates without such intervention. In highly motivated individuals, these drugs can help drug-dependent patients to stay drug-free for over a decade.19

However, the drugs only prevent cravings or produce unpleasant affects with relapse when the patient takes them. Only two week after cessation of disulfiram treatment, relapse will produce none of the adverse affects. Two problems can contribute to patient non-compliance. Some patients express the view that these drugs are crutches and that they do not need them to stay sober. Other patients may decide to use again in frustration with sobriety, in essence deciding that either “one won’t hurt” or that they “quit” recovery, “do not care anymore,” and should be able to drink if they so desire (both essentially a denial of denial of their problem).20 In these cases, the anti-craving drugs will not help prevent relapse because the dependent patient has decided to stop taking them.

Therefore, such drugs are not really a solution for the problem of addiction. The best results are obtained by patients involved in counseling or who attend group meetings also. Patients must also be highly motivated to comply with the doctor’s orders (which group meetings and support can instill). Much of the addicted population (especially opiate-dependent patients) are not this motivated and do not have a very strong support system, so drugs such as naltrexone are only a real solution for an estimated 10% of the addicted population.21 Due to such a small number of individuals who would benefit from such, their manufacture is not very profitable to the companies with the money and resources to

19 Perrine, pg. 12720 DeWors, pg. 22-2321 Feldman, pg. 547

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manufacture them. In all, anti-craving drugs—when used by a motivated patient with a strong support base—can be a very effective tool in preventing relapse, but they are not a solution to addiction and are not appropriate for the entire addicted population.

Lastly, pain medications have benefits in the treatment of addiction, as well as serious potential for harm. If used properly under the watchful eye of a physician, they can relieve the pain that may impede or sabotage recovery. However, if a narcotic is used for pain relief and is not carefully administered, it may do more harm than good, either producing relapse in opiate-dependent patients or creating another addiction in other recovering patients.

In all, neuropsychopharmacology offers insight into the biological causes of addiction by examining pathway-alteration and receptor adaptation, as well as providing solutions to addiction. One such solution is the development of overdose-reversal drugs, which can save lives and make treatment of injuries easier. In addition, pharmacology has offered a possible solution for the social and medical problems caused by heroin addiction by substituting that addiction for a more innocuous opiate addiction. Another solution that pharmacology offers is a way to safely withdrawal a drug-dependent patient from drugs, which reduces mortality rates and increases the likelihood that a patient will stay with his or her rehabilitation program. Additionally, pharmacology has produced promising drugs to fight cravings in recovering patients, helping them to achieve long-term sobriety. Lastly, pharmacology has offered a solution to the pain-relapse connection by providing pain relief to drug-dependent individuals. However, just as pharmacology has offered potential solutions to drug addiction, it does not hold all the answers, as pharmacological treatments yield the best results when used with other treatments (such as 12-step programs) and as compliance issues can hinder recovery progress. In all, pharmacology is a promising field in the understanding and the treatment of addictions.

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