Treatments of Opiate Addiction: Current Techniques and Studies with Implications for Future Treatments
Introduction
Snort it. Smoke it. Shoot it. Heroin is addictive and dangerous any way you get it.
Recent epidemiological studies suggest that the incidence of heroin abuse has continued to increase since the 1980s in several major cities of the United States, with heroin-related emergency room visits in the United States, up from 38,063 in 1988 to 72,221 in 1995 (Herman and Iversen 1997). At the same time of the rise of heroin usage, purity levels of heroin that were at 5 to 7 percent (1960s) can now be 90 to 95 percent pure (Martin-Morris 1997) (although this varies as a function of location and time period). Such potency means users can get addicted sooner, and the risk of an accidental overdose has increased.
Heroin use nearly doubled among high school students between 1991 and 1995, according to a study supported by the National Institute of Drug Abuse (NIDA). During those same four years, according to findings released in July of 1996, there was an upward trend in heroin use among 8th, 10th and 12th graders (Martin-Morris 1997).
When 4,664 12- to 17-year-olds were asked if "heroin was a great risk," only half said that it was, according to the 1994 National Household Survey on Drug Abuse, led by the Department of Health and Human Services (Martin-Morris 1997). The numbers behind heroin and other opiate-related substances in the United States are endless. The problems that arise because of the extremely life-threatening, addictive nature of opiates cross all boundries of generations, cultures and socioeconomic groups. The illegal use of opiates are also linked to problems beyond the health of the dependent individual. Therefore with the proper and effective treatment of opiate addicts will be effective ways in reducing illicit opiate drug use, reducing crime, enhancing social productivity, and reducing the spread of viral diseases such as acquired immunodeficiency syndrome (AIDS) and hepatitis.
It is the purpose of this paper to examine some of the current treatments and latest breakthroughs in our understanding of the neurobiological workings of opiate abuse. Hopefully, the newest facts about how opiates work in the human body will help us in developing the best possible treatments for opiate-related problems in the future.
Evidence that Opiate Dependence is a Medical Illness
One of the first steps in most effectively treating a disorder is to know exactly what kind of disorder one is dealing with. Is the dependence a disorder of willpower and the mind. Or is the dependence something that actually changes the physiology of a person, making it physically more difficult to simply quit or stay abstinent. Depending on what the nature of a disorder is, the best treatment can range from support sessions with other substance abusers to the consumption or intraveinous intake of actual medication. The point is, the better one understands the disorder, the better one can treat it.
In the past, opioid dependence was always viewed as a problem of motivation, willpower, or strength of character. Yet during the past two decades, there has been much data accumulating on the neurobiological aspects of opiate dependence. According to recent studies, "whatever conditions may lead to opiate exposure, opiate dependence is a brain-related disorder with the requisite characterisitcs of a medical illness" (NIH Consensus Conference 1998). Some arguments for classifying opioid dependence as a medical illness include: (1) consistent medical history, signs. and symptoms among those who are opiate abusers despite varying cultural, ethnic, and socioeconomic backgrounds; (2) very strong tendency to relapse or fall back into addiction after long periods of abstinence; (3) opiate cravings that induces one to even self-administer the drug, despite strong social consequences; (4) and pathophysiologic changes in the brain after much constant exposure to opioids (NIH 1998).
Therefore, like any other medical illness, opiate dependence will have varying causative mechanisms. With such characteristics of a medical illness, NIH Consensus Conference in 1998 (suggested after extensive studies with comprehensive literature and key experts in the field of neuroscience) that opiate dependency should not only be recognized as a true medical illness but should consequently be treated like one as well.
Opium and its Derivatives
The narcotic drug widely known as Opium is produced from the drying resin of unripe capsules of the opium poppy, Papaver somniferum. Over the ages in the world and recent decades in the United States, opium has taken many different yet very similiar forms. In its commerical form, opium is a chestnut-colored globular mass, sticky and rather soft, but hardening from within as it ages. It is processed into the alkaloid morphine which has long served as the chief painkiller in the practice of medicine. Opiates are the psychoactive alkaloid components or derivatives of opium. Some semi-synthetic opioid derivatives include heroin, hydromorphone, oxycodone, and etorphine. And there are still other derivatives that a fully synthetic such as miperidine, methadone, propoxyphene and fentanyl.
Traditional Forms of Treatment
At the time being, two types of treatment programs are usually used for most opioid addicts. One type are therapuetic communities which require the drug abuser to take personal responsibility for his or her problem. Usually, the main concept behind this form of treatment is that the opioid abuser is "emotionally immature" (Petersen 1999) and must be given a second chance to grow up. This form of treatment typically will involve harsh encounters with other members of the community. Reward systems for good behavior involves the support of others, with the status and privelege rewards.
The second type of therapy is treatment by the use of opioid substitutes. One such substitute is a substance the National Institute of Health's Consensus Conference of 1998 recommended in a recent study called methadone hydrochloride (Ernst and London 1997). The main idea behind substitutes is to help the user gradually reduce and eventually stop heroin use while taking away the need to finding the drug on the street. Another more recent substitute is the drug naltrexone. It is nonaddictive but does not provide an equivalent "high;" it also cannot be used by persons with liver problems, which are common amonst addicts.
Newest Form of Treatment - Rapid Opiate Detoxification
From Tel Aviv to New York City, it is considered the hottest treatment available. With claims such as "They (a pair of Toronto doctors, Peter Garber and Mark Greenberg) saved my life," (Fennell 1997). The latest and most radical procedure is known as "rapid opiate detoxification." At clinics in some 10 cities around the world it has been used thousands of times. It all started in Canada on Oct. 30, when a pair of Toronto doctors, Peter Garber and Mark Greenberg, began to offer it at a methadone clinic.
Rapid opiate detoxification is based on the work of psychiatrists Karl Loimer of Vienna, Austria, and Colin Brewer of London (Strang et al. 1997). In the late 1980s, they discovered that two drugs, naloxone and naltrexone, had a remarkable effect on the opiate receptors located in the locus coeruleus area of the brain stem. Bonding with the receptors, the drugs displace any traces of the highly addictive opiates that are found in heroin, methadone and some other drugs. Basically, naloxone and naltrexone eliminate the body's craving by cleaning the system (Barrtner and Gooberman 1997).
Patients undergo general anesthesia to ease the trauma of rapid withdrawal. Their bodies are then flooded with naltrexone and naloxone, which cut the withdrawal time from the norm of almost 40 hours to five or six. Side-effects, including vomiting and severe chills, can last up to a week. But so far, Garber and Greenberg report, all of their patients say they have lost their craving for heroin and methadone.
According to U.S. studies, 76 per cent of addicts taking the rapid detox cure have stayed off opiates for at least six months, compared with only about 15 per cent who go through normal detoxification centers (Fennel 1997). But some critics remain unconvinced. In an issue of the British Medical Journal, Strang, Bearn, and Gossop wrote, "enthusiasm must be tempered with caution and scientific scrutiny" (Strang et al. 1997). Critics say that it is still too early to be celebrating. There is still not enough long term data available from controlled studies and until there is adequate scientific evidence of the effectiveness and safety of ROD, this teqnique should be used only in clinical trials.
Brain Imaging Studies and their Future Implications of Therapy
An understanding of the neurobiological substrates of brain dysfunction associated with excessive use of opiates is critical for the future development of effective treatments for opiate-related disorders. At the Brain Imaging Center of the National Institute on Drug Abuse in Baltimore, Maryland, Ernst and London have been conducting studies on brain images produced under the effects of certain commonly abused substances such as heroin, cocaine, and marijuana.
Noninvasive brain imaging provides data that would allow new research to be able to make more in vivo assesments of brain function under different conditions that characterize various stages of an addictive cycle. One of the main teqniques used included positron emission tomographies (PET). PETs are the imaging techniques that requires a cyclotron as an on site source of short-lived positron-emitting isotopes (e.g. 11C, 18F, 15O,13N). PETs can measure such brain functions as cerebral metabolism, blood flow and volume, oxygen use, and the formation of neurotransimitters.
While studying integrated regional brain activity, two independent PET studies demonstrated that acute administration of opiates often revealed a reduction in cerebral metabolism but no discrete pattern of changes in brain activity has emerged (London, et al. 1990; Walsh et. al. 1994). A third study on the acute effects of opioids on regional brain function, fentanyl was administered to healthy voluteers without histories of drug abuse (Firestone et. al. 1996). Although values of rCBF (regional cerebral blood flow) increased in cingulate and prefrontal cortices and caudate nuclei, it is still difficult to make clear correlations because absolute rates of rCBF were not determined, and effects of fentanyl on rCBF may relfect direct actions of the drug on the cerebral vasculature rather than on neural activity (Ernst and London 1997).
One of the studies was examining abnormalities in the brains of chronic substance abusers. The particular "stage of substance use" examined was opiate withdrawal. This study demonstrated D2 receptor availability that decreased by 18 0n patients dependent on opiates compared with controls (Ernst and London 1997). When opiate antagonist was administered to produce an intense withdrawal experience, no change in D2 receptor availabilty was found. These results suggested that chronic opiate administration resulted to a down-regulation of D2-like receptors, but that acute opiate withdrawal was not associated with a significant enough change in intrasynaptic dopamine to alter D2-like receptor availablility.
The following is a summary of the type of image results found in various studies of the effect of opiates and other substances on the brain. With each brain image finding there is a matching therapeutic implication or aspect to consider in the future when developing a treatment:
Stage of Substance Use Brain Imaging Findings Therapeutic Approach
Responses to morhine, cocaine, and other drugs of abuse
Reduction in cerebral glucose metabolism Antagonism of euphoria by inhibiting the decrease in cortical metabolism
Opiate withdrawal Lower normalized rCBR, particularly in anterior cingulate and temporal coritces Cognitive-behavioral therapy to activate the cingulate and temporal cortices.
No changes in dopamine D2 receptor occupancy
Therapies other than those aimed at modifying D dopamine receptors
Craving
Activation of memory circuits by drug-related stimuli
Cognitive or pharmacological therapies aimed at the amygdala, which links episodic memories to emotion.
Source: (Ernst and London 1997)
The Opioid System, the Functional Anatomy of Reward Circuits and their Future Implications of Therapy
There have been many studies being conducted on the anatomy of reward circuits and the expression of certain critical molecules in the context of some key structures which mediate drug reward and drug addiction. One such example is the recent research that has been done by Curran and Watson using a dual in situ hybridization procedure that has focused on the anatomy of nucleus accumbens and the coexpression of opioid peptides and opioid receptor with certain dopaimine receptor subtypes (Curran and Watson 1995). There has been a great deal of recent interest in the anatomy of the accumben (Nacc) because it is considered to be part of the ventral striatum along with parts of the olfactory tubercle and the ventral and medial portions of the caudate putamen (CPu) (Akil et. al. 1997).
The results from the colocalization experiments of Curran and Watson indicated that there are differences between caudate putamen and the accumben in the expression of opiod molecules and dopamine receptors. These differences and some other different anatomical connections of these two nuclei may be involved in the ability of dopamine and opiate drugs to produce rewarding effects in the accumben but not in the caudate putamen (Akil el al. 1997). The receptors D1, u (mu), and k(kappa) are coexpressed in the region of cell clusters within the accumben. It is thought that these structures are in a region where "motivational properties of dopaminergic and opiate drugs are processed" (Akil et al. 1997). This is significant and have important implications to future therapies because the location of the motivational properties is now known. With this knoweldge, future treatments may involve the targetting of these specific regions to help improve the effectiveness of treating patients with opiate disorders.
Conclusion
From the newest rapid opiate detoxification techniques to the latest images of the brain glucose metabolism under the effect of opiates one message is very clear: opiate addiction dangerous and all efforts are needed in finding the best forms of treatment. As much of the research indicates, the first step to developing effective treatments for the dependency of opiates is to first recognizes that opiate dependency is a medical disorder. So the next step in developing effective treatments is conducting more research to have a better understanding of how opiate addiction really works at a molecular level. By knowing the molecular mechanisms, researchers can develop better medications and techniques that would target certain key cellular regions such as the cell clusters within the accumben. But the final step of all, will be the cost. In order for many of these various research studies to be conducted, costs to fund them must be met. To realize that these costs are necessary they must be compared to the alternative costs. The costs of breaking the law, the costs of purchasing drugs, the costs of society, the costs of a life.
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