Understanding opioids and opiate use disorder requires knowledge of the history of opium. The opium poppy was first cultivated in Mesopotamia in 3400 B.C. In the 17th century, Mughals extended the tradition of taking opium to the Indian militaries. In 1793, The British East India Company took control of the trade of opium in the subcontinent. During the US Civil War, it was used broadly as an analgesic, causing many veterans to become addicted to morphine. The German chemical company Bayer produced a morphine derivative called heroin to reduce addiction.1
In the United States, morphine was used to treat pain, anxiety, and tuberculosis in the mid-19th century. Heroin was promoted as a cough suppressant, a more effective analgesic, and a morphine addiction detox; thus it was considered a “magic drug.” Although heroin production reduced addiction, opioid abuse became more rampant during this period, and by 1924, heroin became illegal.
A ruling by the United States Supreme Court allowed only doctors to prescribe opioids to alleviate addiction. By 1920, doctors were unable to prescribe opioids for addicted patients. To reduce abuse, the Drug Abuse Control Amendment was passed in 1965.2 By the year 1970, the FDA had arranged these substances as planned through the Controlled Substances Act. These drugs are arranged into five Schedules. Schedule I drugs are dangerous with no medicinal uses. Schedules II-V step down based on the potential for abuse; Schedule V drugs have no reasonable chance to cause addiction. In 1973, President Richard Nixon announced the drug war and established a drug control agency.
Although the United States has passed laws prohibiting the abuse of opioids, the FDA has approved opioids for medical use. The FDA approved oxycodone as Percodan® in 1950 and Vicodin® in 1978. In 1990, the use of opioids extended from cancer pain management to non-cancer pain management. To better control pain, pharmaceutical companies have developed extended-release drugs such as fentanyl, morphine, oxycodone and hydromorphone.3 Although these drugs are used for pain management, they are still highly abused today. Opioids began as a “magic drug,” but due to abuse, it led to the opioid epidemic that is seen today. The consumption of opioids for controlling pain is constantly being assessed to limit abuse.
Anyone taking opioids may develop physical dependence, even if they are taken exactly as prescribed. However, it may also be part of a medical condition known as opioid use disorder (OUD). OUD occurs when finding and taking opioids becomes a problem and you cannot stop using the drug. OUD is a chronic recurrent disease and is characterized by a pattern of problems and concerns stemming from acquiring and taking opioids. Despite personal, medical and psychosocial consequences, it still exceeds the expected results.4
Individuals with OUD are generally resistant to opioids and have withdrawal symptoms when they are stopped. The mortality rate of OUD patients is 6 to 20 times the overall population.5 Among survivors, even after 10 years of follow-up, the prevalence of stable withdrawal of opioids was still less than 30%, and many people who used opioids continued to use alcohol and other drugs. The psychological and social burden of OUD includes unemployment, economic issues, homelessness, and legal issues. In fact, OUD was found to have the greatest disease burden from any illegal drug.
Morbidity as well as mortality related to opioid usage has increased considerably. In 2013, the number of prescription opioid deaths was 16,000, which is a 2.5-fold increase since 2001. The number of heroin deaths was 8,000, an increase of five times over the same period.6 In the United States, 100 individuals die every day due to overdosage, about half of which come from prescription opioids and about one-fifth from heroin. Overdose has exceeded car accidents as the chief cause of accidental death in the country.
Opioids comprise nearly one-third of prescription drug overdoses. Moreover, their mortality rate exceeds all other forms of drug poisoning deaths in the United States. From 2004 to 2008, it is estimated that over half of drug-related medicinal emergencies were because of opioids. Throughout the same period, the number of visits to emergency departments due to non-medical opioid use has doubled.
In 2016, the overdose of opioids killed more than 42,000 people, and the entire number of opioid overdose fatalities since 1999 has exceeded 350,000. Since 2013, deaths due to illicitly manufactured fentanyl has enlarged significantly.8
Naturally occurring opioids (plant alkaloids from the opium poppy) as well as synthetic (artificial) and semi-synthetic opioids are considered narcotic drugs, including statutory prescriptions and illegal varieties. Opioids not only reduce the perception of the central nervous system’s pain signals but also produce effects that make them a target of abuse and high addiction. The reasons for opioids effectiveness may correspondingly make them hazardous. At minor doses, opioids can give a feeling of drowsiness, but greater doses may slow down breathing as well as heart rate, leading to death. The feeling when taking opioids will lead to a desire to continue to experience the emotional state that may cause addiction.10
Opioids, represented by morphine, produce pharmacological effects including:
Hedonic (“reward”) effects
This occurs by working on receptors situated on the cell membrane of neurons.11 The primary role of opioids in the nervous system is to inhibit the release of neurotransmitters.
Opioids play a role in the central and peripheral nervous systems, namely:
In the central nervous system, opioids have special effects in several areas, which include the spinal cord.
In the peripheral nervous system, the role of opioids affect the intestinal wall. However, it is responsible for constipation.
In peripheral tissues such as joints, opioids work in reducing tenderness and swelling.
Recent developments in the field of molecular biology for opioid receptors have established the fact that there are three categories of opioid receptors, namely m, d and k.12 These receptors are part of a big family of receptors with seven transmembrane amino acids. Pharmacological readings have presented that opioid peptide (which are naturally occurring) such as beta-endorphin preferentially interrelates with the m receptor. Enkephalin interacts with the d receptor, and similarly, dimorphism interacts with the k receptor. Morphine has a complex attraction towards them receptor than other opioid receptors. Furthermore, the discovery of opioid receptors with molecular structure offers a more precise process for opioid-related studies.
Heroin is considered as an illegal, extremely addictive drug which is processed from morphine, a natural ingredient from pods of specific kinds of poppy. It is usually traded as a white and brown powder with sugar, starch, milk powder or quinine. Uncontaminated heroin is bitter, white, dust-like powder mostly from South America (sometimes Southeast Asia) that took over the US market east of the Mississippi River. High-purity heroin can also be smoked, which seems attractive to novel users as it eradicates the stigma related to injecting drug use. “Black tar” heroin is as thick as roof tar or as hard as coal, mainly produced in Mexico. Dark color linked with black tar heroin is produced by crude oil processing procedures that leave impurities. Contaminated heroin is commonly dissolved, diluted as well as injected into the veins, the muscles, or beneath the skin. Common adverse effects comprise respiratory depression (reduced breathing), dehydration, lethargy, impaired psychological function, constipation, as well as addiction.13
Opium is the first substance of opioids. Opium is extracted from Papaver somniferous, a poppy flower. Opium is a viscous brown resin obtained by collecting and drying latex ejected from poppy pods. Once extracted, opium contains two major groups of alkaloids; psychoactive ingredients belong to alkaloids without central nervous system impacts.14 Morphine is a common and dominant alkaloid in opium, responsible for most of the harmful effects. Opium is gradually being replaced by various synthetic opioids and general anesthetics. Some isolated opium derivatives are morphine, codeine and quinine. Opium is abused in most countries, but the illegal production of the drug and its derivatives are still registered.15
Opiates are frequently used for the treatment of patients with chronic, non-malignant pain. There are many controversies regarding the definition, incidence and predisposing factors for opioid abuse in chronic pain management. Recently, the amount of non-medical prescription opiate consumers (those taking prescription opiates to achieve ecstatic effects) has increased significantly.
Data from the National Drug Use and Health Survey presented that the number of new non-medical users increased by three digits between 2002 and 2014, and clinical management data recommend that the utilization of non-medical prescription opioids are more prevalent in rural areas.16
Codeine is considered a natural opioid and is usually used as a painkiller. This effect lasts only for a limited number of hours, so it is frequently prescribed with acetaminophen or aspirin.17 Codeine is accessible in tablets, capsules or liquids, and many trademark names are being sold in addition. Codeine has several street names such as Captain Cody, the Cody, Lean, Elementary School boy, as well as Purple Drinking.
Fentanyl is more effective than morphine and is most commonly used to manage patients with severe or postoperative pain. Moreover, it is also used by people who are substantially tolerant to opioids. It can be used as a lozenge, injection, or skin patch. It is also common that fentanyl is being used in the manufacturing of fake medicines and recognized as an illegal drug such as heroin and cocaine.18 This increases the risk factors associated with opioid because users often don’t know about fentanyl.
Dilaudid is the brand name for hydromorphone. It is mainly used in hospital settings and is administered intravenously after surgery. Dilaudid is used for short-term relief of pain and can also be used as oral liquids, tablets and suppositories.19 In illegal use, Dilaudid may be referred to as D or Dillies, Footballs, Juice, and Smack.
Hydrocodone (trade names including Vicodin and Norco, etc.) is used in managing patients with moderate and extreme pain caused by chronic diseases, injuries or surgery. It can be used as an oral syrup and an oral tablet.20 When sold on the black market, it may be called Watson-387.
Methadone is most often associated with those who seek to safely quit heroin addiction. However, it is also used as an opioid painkiller and may be misused. It has tablets and liquid forms, and street names include Amidone and Fizzies.21 When used in the black market as illegal drug, it is called “chocolate chip cookie.”
Morphine is a natural opiate that is marketed under the Duramorph and MS Contin brands. It is prescribed for treatment of severe persistent pain, particularly in cancer patients. This painkiller can be used as an injection, capsule, tablet and a suppository. On the street it might be referred to as M, but it is also known as Miss Emma, Monkeys, and White Things.
OxyContin is the trade name for oxycodone. It can be used as an all-weather treatment for patients suffering from moderate to severe pain. Moreover, it is also prescribed when pain is expected to last longer and comes in tablet form. There are five forms of oxycodone: immediate release tablets, continued release tablets, immediate release capsules, sustained release pills, as well as solutions.22 All forms are oral. On the street, OxyContin may be called O.C, Oxy or Hillbilly Heroin.
Short-term effects of opioids, as well as morphine derivatives, comprise:
Due to the high concentration of several opioids and brain interactions, the drug is still highly addictive and sometimes causes measurable addiction symptoms within three days. Opiates also relax the iris, producing a needled or precisely positioned pupil. This is one of the main symptoms of opioid abuse and is difficult to hide.23
Long-term effects comprise:
Abdominal distention and bloating
Liver impairment (particularly the abuse of drugs that mix opioids with acetaminophen)
Brain damage because of hypoxia caused by respiratory depression
If use is reduced or stopped, the body will adjust according to the drug and will develop withdrawal symptoms such as:
Muscle as well as bone ache
Vomiting as well as colds with goosebumps (“cold turkey”)
The more a person uses opioids, the more likely they are to rely on them. Frequent use may lead to tolerance over time. Long-term consumption may cause physical and mental dependence.25
Although it is very beneficial for the treatment of pain, opioids may cause physical dependence as well as addiction. As stated by the National Institute on Drug Abuse, there are around 2.1 million individuals in the United States and 264 to 360 million people worldwide who abuse opioids. If the amount of opioid consumption is reduced, people experience physical withdrawal symptoms, specifically if drugs are taken at higher doses over a few weeks.
Several systems in our body are changed when opioids are taken in excess for a longer period of time. The exit effect occurs because your body takes a while to adjust to the opioids that are no longer in the system. Opioids bind to the opioid receptors located in the brain, spinal cord and gastrointestinal tract and will work as long as opioids are attached to receptors.26 The brain essentially makes opioids control a range of effects, such as:
Lower Respiratory Rates
Help Prevent Depression as Well as Anxiety
However, the body is not capable to produce large amounts of opioids, which is sufficient to manage the pain of broken legs. Also, the body certainly does not produce large amounts of opioids. Opioids and illegal drugs are similar to these naturally present opioids, affecting the body in a variety of ways, namely:
Opioids impact the brainstem by slowing down or reducing coughing, which controls breathing and heartbeat.
Opioids can act on the specific zones of brain called the limbic system, controlling sentiments and yielding feelings of satisfaction or relaxation.
Opioids relieve pain by acting on the spinal cord, which sends information from the mind to other parts of the body.27
Opioid agonists such as non-steroidal anti-inflammatory drugs (aspirin) can successfully control acute opioid withdrawal. Insomnia and anxiety must be actively treated with drugs such as hydroxyzine, diphenhydramine, trazodone, clonidine or benzodiazepine (sedatives).
Care must be taken while using sedatives such as benzodiazepines, which several patients frequently abuse, even though new opioid agonists (e.g. buprenorphine) are commonly used as they physiologically target opioid receptors and therefore more effectively alleviate symptoms of acute withdrawal. Buprenorphine can be tapered or converted to dose over several days for deterioration prevention of drug-assisted retrieval. Buprenorphine could also be taken alone, however more preferably it is given in mixture with naloxone.
Naloxone has minimal absorption when given orally, however if transferred and administered intravenously, it is biologically effective. Buprenorphine replaces additional opioids, so the initial dose must not be given until adolescents have moderate withdrawal symptoms.28
The gold standard is medicine-assisted therapy (MAT), in which drug therapy is combined with some form of counseling or behavioral therapy. Drugs which are used for the management of opioid abuse along with addiction include:
Counselling on opioid abuse as well as addiction could help in the transformation of attitudes as well as behaviors associated with drug consumption. In addition, establishing a healthy lifespan and adhering to different types of treatment such as medication is helpful. In general, behavioral therapy (when provided separately) has limited efficacy in solving the complex symptoms and physical aspects of OUD.31 Therefore, behavioral therapy has been in the context of structured methods (e.g. accommodation programs) in completing detoxification and stabilization to prevent recurrence or most effectively in the context of medication-assisted treatment (MAT) with approved drugs such as the combination use of methadone, buprenorphine or naltrexone. When provided in the context of MAT, the role of behavioral therapy is to improve adherence to drugs, address aspects of diseases not covered by drug therapy, and address specific weaknesses in drug therapy.
In addition, the accommodation program combines housing and behavioral services. Patients live with their peers so they can support one another and remain healthy. The Hospitalization Program combines health care in addition to addiction treatment facilities to provide services to persons with medical complications. Hospitals may possibly provide concentrated outpatient management. All kinds of treatments are organized and typically comprise diverse types of psychotherapy as well as behavioral therapy.32