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OPIATE ADDICTION: ETIOLOGY, SYMPTOMS, AND TREATMENT
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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
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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
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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
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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,
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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
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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
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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). FDA acts to reduce harm from opioid drugs. Retrieved from http://
www.fda.gov.
Kling, M. C., Carlson, R. E., Borg, L., Zametkin, A., Matochik, J. A., Schluger, J., Herscovitch,
P., Rice, K. C., Ho, A., Eckelman, W. C., & Kreek, M. J. (2000). Opioid receptor imaging
with Positron Emission Tomography and [F]Cyclofoxy in long-term, methadone-treated
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former heroin addicts. The Journal of Pharmacology and Experimental Therapeutics, 295,
1070-1076.
Ksir, C., Hart, C. L., & Ray, O. (2008). Drugs, society, and human behavior (12th ed.). New
York, NY: McGraw-Hill.
Leri, F., Tremblay, A., Sorge, R. E., & Stewart, J. (2004). Methadone maintenance reduces
heroin- and cocaine-induced relapse without affecting stress-induced relapse in rodent
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McKim, W. A. (2007). Drugs and behavior: An introduction to behavioral pharmacology (6th
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Praveen, K. T., Law, F., O’Shea, J., & Melichar, J. (2001, September 20). Opioid dependence.
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Reimer, J., Verthein, U., Karow, A., Schafer, I., Naber, D., & Haasen, C. (2011). Physical and
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