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OPIATE ADDICTION: ETIOLOGY, SYMPTOMS, AND TREATMENT 1 What’s Poppin’: An Introduction to Opiate Addiction, Etiology, Symptoms, and Treatment Christiane N. Ortiz Bradley University The opium poppy is an annual plant that grows large white, pink, red, or purple flowers. Opium from this plant is only available for a few days in the specific time frame between when OPIATE ADDICTION: ETIOLOGY, SYMPTOMS, AND TREATMENT 2 the petals fall from the plant and when the seedpot matures. These seedpots oxidize into a red substance that later becomes the basis of the medicines that we see today (Ksir, Hart, & Ray, 2008). As more people became exposed to opium, its demand increased. In China, laws against opium smoking were put in place and later, indirectly resulted in the Opium Wars - a struggle between the British and Chinese that resulted in trading rights and reimbursement for merchant opium that had been destroyed (Ksir et al., 2008). Today, the poppy plant is being highly cultivated in South America and approximately 60% of the heroin sold in the United States comes from this region (Ksir et al., 2008). In 2007, the Food and Drug Administration (FDA) estimated that more than 33 million Americans age 12 or older had abused opioids in that year - up from 29 million only five years earlier. Examples of opiates include vicodin, oxycotin, fentanyl, codeine, and heroin. Raw opium naturally contains both morphine and codeine. Acetyl groups on the morphine molecule allow heroin to cross the blood-brain barrier, making it two to three times more potent than morphine (Ksir et al., 2008). Interestingly, fentanyl, which is usually used along with other surgical anesthesia, is about one hundred times more potent than morphine. In the 1970s, researchers discovered that there are selective opioid receptors in the brain. Today, we know these receptors to be called Mu, Kappa, and Delta opioid receptors. However, why are we born with these receptors and are there natural neurotransmitters that activate these receptors? A pair of molecules called leu-enkephalin and met-enkephalin were found to produce affects similar to those of morphine (Ksir et al., 2008). Further, scientists found that endorphins also have similar opioid affects. Tolerance of opiates occurs at different rates because repeated use decreases the euphoric effects. Therefore, to achieve the same feeling, one usually has to OPIATE ADDICTION: ETIOLOGY, SYMPTOMS, AND TREATMENT 3 constantly increase the dose of the drug. Withdrawal symptoms are similar to that of the 24-hour flu including nausea, vomiting, diarrhea, aches, and pains (Ksir et al., 2008). Mu receptors, of which morphine is an agonist, is located in the brainstem and medial thalamus. They are responsible for supraspinal analgesia, respiratory depression, euphoria, sedation, decreased gastrointestinal motility, and physical dependence (Trescot, Datta, Lee, & Hansen, 2008). Kappa receptors, of which ketocyclazocine is an agonist, are located in the brain stem, spinal cord, and otherdiencephalic areas. They are responsible for spinal analgesia, sedation, dyspnea, dependence, dysphoria, and respiratory depression (Trescot et al., 2008). Delta receptors, of which delta-alanine-delta-leucine-enkephalin is an agonist, are located in the brain (Trescot et al., 2008). The responsibilities of Delta receptors and what they are used for is still unclear. Once the receptor is activated, it releases a part of the G protein, which diffuses within the membrane until it reaches its target - either an enzyme or an ion channel. The enzyme or ion channel then alters protein phosphorylation through inhibiting cyclic AMP (cAMP) (Trescot et al., 2008). When these receptors are activated by an opioid agonist, it inhibits voltage-dependent calcium channels, decreasing cAMP levels and blocking the release of pain neurotransmitters in the brain (Trescot et al., 2008). Examples of pain neurotransmitters include glutamate, substance P, and calcitonin gene-related peptide from the nociceptive fibers (Trescot et al., 2008). Dependency to a substance is manifested by at least three of the following occurring at any time over a twelve month period: a strong desire or compulsion to take opioids, difficulties in controlling substance-taking behavior in its onset, termination, and levels of use, a physiological withdrawal state, evidence of tolerance, progressive neglect of alternative OPIATE ADDICTION: ETIOLOGY, SYMPTOMS, AND TREATMENT 4 pleasures or interests because of opioid use, persisting with substance use despite evidence of harmful consequences (Praveen, Law, O’Shea, & Melichar, 2001). In an effort to help those struggling with opiate addiction, there are ways to cope and treat the dependence. The goal of interventions is stabilization (maintenance) treatment, treatments for withdrawal (detoxification) from opioids, and relapse prevention (Praveen et al., 2001). One of the most common interventions is that of Methadone Maintenance Treatment (MMT). Methadone is a synthetic mu-opioid receptor agonist that is used as a treatment option for opioid-dependent individuals. Methadone prevents opiate withdrawal symptoms for approximately 24 hours. Methadone continues to occupy the Mu opioid receptors in the thalamus, caudate, anterior cingulate cortex, and middle temporal and frontal cortices at 22 hours post-administration in past heroin users (McKim, 2007). As researchers work to find other advantages of methadone, there is also an attempt to find other forms of treatment and compare their efficacy. Some scientists prefer buprenorphine over methadone as the withdrawal symptoms last longer in methadone patients than they do in buprenorphine patients (Van Den Brink, & Haasen, 2006). However, scientists tend to go back and forth as to which method of treatment is better. The efficacy in Methadone Maintenance Treatment has not only been observed in clinical settings with opioid-dependent individuals, but also in treatment of pregnant women. Since opioid-dependent women do not regularly use contraceptives, pregnancy is common. The immune and endocrine systems of these women stabilize after maintenance therapy and this increases the possibility of becoming pregnant (Soyka et al., 2011). Sadly, many babies are born dependent on opioids and show withdrawal symptoms usually right after birth. Fortunately, OPIATE ADDICTION: ETIOLOGY, SYMPTOMS, AND TREATMENT 5 Methadone Maintenance Treatment has demonstrated a huge improvement in infant outcomes (Soyka et al., 2011). Research suggests that it is better for a mother to be on buprenorphine as it has some advantages over methadone during pregnancy. Not only is the retention rate higher in these women, but there is also a small difference in the presence of withdrawal symptoms in infants born to women taking buprenorphine versus methadone (Soyka et al., 2011). Finally, it is crucial to note that detoxification should be avoided during pregnancy as the results could affect the fetus. Although there are several options for the treatment of opiate addiction, methadone is the most studied and most widely used substance in maintenance treatment (Van Den Brink, & Haasen, 2006). Methadone is given in liquid or tablet form and generally, 40-60 mg of methadone will prevent the experience of the opioid withdrawal syndrome (Soyka et al., 2011). According to Cochrane reviews on detoxification of heroin-dependent patients, the most effective strategy of detoxification is by replacing the illegal short-acting opioid with the longacting opioid agonist methadone (Van Den Brink, & Haasen, 2006). Although there are several caveats of Methadone Maintenance Treatment that one should consider, dosing is a key issue as adequate doses are necessary to increase effectiveness. Retention in MMT depends on these daily dosages as another Cochrane review found that 60 to 100 mg of methadone are more effective than lower dosages in the retention of patients and in reducing the use of heroin and other drugs, such as cocaine, during time in treatment (Van Den Brink, & Haasen, 2006). In a study that investigated the affects of methadone on the use and cravings of opiates and cocaine in rats, researchers found that high doses of methadone had the possibility of minimizing cocaine and heroin seeking behavior (Leri, Tremblay, Sorge, & Stewart, 2004). PET imaging has suggested that receptor availability is reduced by 19 to 32% in these affected regions (Kling et OPIATE ADDICTION: ETIOLOGY, SYMPTOMS, AND TREATMENT 6 al., 2000). Treatment can also lead to physical and mental health improvements as demonstrated by the Global Assessment of Functioning Scale and Modular System for Quality of Life Scale in patients participating in assisted treatment (Reimer et al., 2011). The efficacy of methadone treatment has also been observed in prison-based populations. Studies in Europe, Australia, Puerto Rico, and Canada have shown that Methadone Maintenance Treatment in prison not only reduces drug use, drug injection, and needle sharing, but it produces improvements in institutional behavior and has positive effect on release outcomes (Van Den Brink, & Haasen, 2006). Further, needle exchange programs, in combination with MMT, greatly reduced the risk of exposure of blood-borne pathogens and infections and reduced risky behavior (Van Den Brink, & Haasen, 2006). Just as any other drug, taking methadone has its risks. Among the effects of methadone include sweating, sexual dysfunction, and subtle-to-mild cognitive impairment (Soyka et al., 2011). Since there are many individuals who look to the black market to buy or sell methadone, strict laws and rules are in place to reduce the amount of criminal activity surrounding this synthetic opioid (Soyka et al., 2011). Sadly, studies show that there is a 1% mortality rate due to overdoses among individuals who mix methadone with other drugs that also produce respiratory depression and other interacting effects (Soyka et al., 2011). Further, slow metabolizers of methadone have a higher mortality rate. Forward improvements are being accomplished as we attempt to begin to treat drug abuse issues as medical and public health concerns rather than as criminal justice issues. Methadone is a cost-effective way to treat opiate addiction as it is the best in increasing retention rates and social functioning of recovering addicts. Implications for further studies should study the Delta opioid receptors as we do not have much information on its purpose. Methadone maintenance OPIATE ADDICTION: ETIOLOGY, SYMPTOMS, AND TREATMENT 7 treatment is not only providing addicts the help that they need, but it is also minimizing risky behaviors that affect society as a whole. References (2011, November 8). 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Van Den Brink, W., & Haasen, C. (2006). Evidenced-based treatment of opioid-dependent patients. The Canadian Journal of Psychiatry, 51, 635-646.