Opioid use disorder (OUD) is a
substance use disorder
Substance use disorder (SUD) is the persistent use of drugs (including alcohol) despite substantial harm and adverse consequences as a result of their use. Substance use disorders are characterized by an array of mental/emotional, physical, and ...
characterized by cravings for
opioid
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
s, continued use despite physical and/or psychological deterioration, increased tolerance with use, and withdrawal symptoms after discontinuing opioids.
Opioid withdrawal symptoms include nausea, muscle aches, diarrhea, trouble sleeping, agitation, and a low mood.
Addiction
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use o ...
and
dependence are important components of OUD.
Risk factors for OUD include a history of opioid misuse, current opioid misuse, young age, socioeconomic status, race, untreated psychiatric disorders, and environments that promote misuse (social, family, professional, etc.).
Complications may include
opioid overdose
An opioid overdose is toxicity due to excessive consumption of opioids, such as morphine, codeine, heroin, fentanyl, tramadol, and methadone. This preventable pathology can be fatal if it leads to respiratory depression, a lethal condition that ca ...
,
suicide
Suicide is the act of intentionally causing one's own death. Mental disorders (including depression, bipolar disorder, schizophrenia, personality disorders, anxiety disorders), physical disorders (such as chronic fatigue syndrome), and s ...
,
HIV/AIDS
Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...
,
hepatitis C
Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...
, and problems meeting social or professional responsibilities.
Diagnosis may be based on criteria by the
American Psychiatric Association
The American Psychiatric Association (APA) is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the largest psychiatric organization in the world. It has more than 37,000 members are involve ...
in the
DSM-5
The ''Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition'' (DSM-5), is the 2013 update to the ''Diagnostic and Statistical Manual of Mental Disorders'', the taxonomic and diagnostic tool published by the American Psychiatric ...
.
If more than two of 11 criteria are present during a year, the diagnosis is said to be present.
Opioids include substances such as
heroin
Heroin, also known as diacetylmorphine and diamorphine among other names, is a potent opioid mainly used as a recreational drug for its euphoric effects. Medical grade diamorphine is used as a pure hydrochloride salt. Various white and brow ...
,
morphine
Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...
,
fentanyl
Fentanyl, also spelled fentanil, is a very potent synthetic opioid used as a pain medication. Together with other drugs, fentanyl is used for anesthesia. It is also used illicitly as a recreational drug, sometimes mixed with heroin, cocain ...
,
codeine,
dihydrocodeine
Dihydrocodeine is a semi-synthetic opioid analgesic prescribed for pain or severe dyspnea, or as an antitussive, either alone or compounded with paracetamol (acetaminophen) (as in co-dydramol) or aspirin. It was developed in Germany in 1908 a ...
,
oxycodone
Oxycodone, sold under various brand names such as Roxicodone and OxyContin (which is the extended release form), is a strong, semi-synthetic opioid used medically for treatment of moderate to severe pain. It is highly addictive and a commonly ...
, and
hydrocodone
Hydrocodone, also known as dihydrocodeinone, is an opioid used to treat pain and as a cough suppressant. It is taken by mouth. Typically it is dispensed as the combination acetaminophen/hydrocodone or ibuprofen/hydrocodone for pain severe eno ...
.
A useful standard for the relative strength of different opioids is morphine milligram equivalents (MME). It is recommended for clinicians to refer to daily MMEs when prescribing opioids to decrease the risk of misuse and adverse effects.
File:Opiates v opioids.png, opiates and opioids
File:Morphine Milligram Equivalents.jpg, MME of common opioids
Long-term opioid use occurs in about 4% of people following their use for trauma or surgery-related pain.
In the United States, most heroin users begin by using prescription opioids that may also be bought illegally.
People with an opioid use disorder are often treated with
opioid replacement therapy
Opioid use disorder (OUD) is a substance use disorder characterized by cravings for opioids, continued use despite physical and/or psychological deterioration, increased tolerance with use, and withdrawal symptoms after discontinuing opioids. Op ...
using
methadone
Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid agonist used for chronic pain and also for opioid dependence. It is used to treat chronic pain, and it is also used to treat addiction to heroin ...
or
buprenorphine
Buprenorphine is an opioid used to treat opioid use disorder, acute pain, and chronic pain. It can be used under the tongue (sublingual), in the cheek (buccal), by injection (intravenous and subcutaneous), as a skin patch (transdermal ...
.
Such treatment reduces the risk of death.
Additionally, they may benefit from
cognitive behavioral therapy
Cognitive behavioral therapy (CBT) is a psycho-social intervention that aims to reduce symptoms of various mental health conditions, primarily depression and anxiety disorders. CBT focuses on challenging and changing cognitive distortions (suc ...
, other forms of support from mental health professionals such as individual or group therapy,
twelve-step program
Twelve-step programs are international mutual aid programs supporting recovery from substance addictions, behavioral addictions and compulsions. Developed in the 1930s, the first twelve-step program, Alcoholics Anonymous (AA), aided its members ...
s, and other peer support programs. The medication
naltrexone
Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been found t ...
may also be useful to prevent relapse.
Naloxone
Naloxone, sold under the brand names Narcan (4 mg) and Kloxxado (8 mg) among others, is a medication used to reverse or reduce the effects of opioids. It is commonly used to counter decreased breathing in opioid overdose. Effects begin withi ...
is useful for treating an
opioid overdose
An opioid overdose is toxicity due to excessive consumption of opioids, such as morphine, codeine, heroin, fentanyl, tramadol, and methadone. This preventable pathology can be fatal if it leads to respiratory depression, a lethal condition that ca ...
and giving those at risk naloxone to take home is beneficial. In 2020, the CDC estimated that nearly 3 million people in the U.S. were living with OUD and more than 65,000 people died by opioid overdose, of whom more than 15,000 were heroin overdoses. Recent estimates of the number of people living with OUD and annual opioid overdoses worldwide are 16 million and 120,000, respectively.
Diagnosis
The
DSM-5
The ''Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition'' (DSM-5), is the 2013 update to the ''Diagnostic and Statistical Manual of Mental Disorders'', the taxonomic and diagnostic tool published by the American Psychiatric ...
guidelines for the diagnosis of opioid use disorder require that the individual has a significant impairment or distress related to opioid uses.
To make the diagnosis two or more of 11 criteria must be present in a given year:
#More opioids are taken than intended
#The individual is unable to decrease the number of opioids used
#Large amounts of time are spent trying to obtain opioids, use opioids, or recover from taking them
#The individual has cravings for opioids
#Difficulty fulfilling professional duties at work or school
#Continued use of opioids leading to social and interpersonal consequences
#Decreased social or recreational activities
#Using opioids despite being in physically dangerous settings
#Continued use despite opioids worsening physical or psychological health (i.e. depression, constipation)
#
Tolerance
#
Withdrawal
Withdrawal means "an act of taking out" and may refer to:
* Anchoresis (withdrawal from the world for religious or ethical reasons)
* ''Coitus interruptus'' (the withdrawal method)
* Drug withdrawal
* Social withdrawal
* Taking of money from a ban ...
The severity can be classified as mild, moderate, or severe based on the number of criteria present.
Addiction
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use o ...
and
dependence are components of a
substance use disorder
Substance use disorder (SUD) is the persistent use of drugs (including alcohol) despite substantial harm and adverse consequences as a result of their use. Substance use disorders are characterized by an array of mental/emotional, physical, and ...
; addiction is the more severe form.
Signs and symptoms
Opioid intoxication
Signs and symptoms of
opioid intoxication include:
[
* Decreased perception of pain
* Euphoria
* Confusion
* Desire to sleep
* Nausea
* ]Constipation
Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...
* (pupil constriction)
* Bradycardia (slow heart rate)
*Hypotension
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
(low blood pressure)
* Hypokinesis (slowed movement)
*Head nodding
*Slurred speech
*Hypothermia
Hypothermia is defined as a body core temperature below in humans. Symptoms depend on the temperature. In mild hypothermia, there is shivering and mental confusion. In moderate hypothermia, shivering stops and confusion increases. In severe ...
(low body temperature)
Opioid overdose
Signs and symptoms of opioid overdose include, but are not limited to:[Kosten TR, Haile CN. Opioid-Related Disorders. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. ''Harrison's Principles of Internal Medicine, 19e'' ''New York, NY: McGraw-Hill; 2014. http://accessmedicine.mhmedical.com/content.aspx?bookid=1130§ionid=79757372 Accessed 9 March 2017.]
* Pin-point pupils may occur. Patient presenting with dilated pupils may still be experiencing an opioid overdose.
* Decreased heart rate
* Decreased body temperature
* Decreased breathing
* Altered level of consciousness
An altered level of consciousness is any measure of arousal other than normal. Level of consciousness (LOC) is a measurement of a person's arousability and responsiveness to stimuli from the environment.
A mildly depressed level of consciousn ...
. People may be unresponsive or unconscious.
* Pulmonary edema
Pulmonary edema, also known as pulmonary congestion, is excessive edema, liquid accumulation in the parenchyma, tissue and pulmonary alveolus, air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia an ...
(fluid accumulation in the lungs)
* Shock
Shock may refer to:
Common uses Collective noun
*Shock, a historic commercial term for a group of 60, see English numerals#Special names
* Stook, or shock of grain, stacked sheaves
Healthcare
* Shock (circulatory), circulatory medical emergen ...
* Death
Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
Withdrawal
Opioid withdrawal
Opioid withdrawal is a set of symptoms (a syndrome) arising from the sudden withdrawal or reduction of opioids where previous usage has been heavy and prolonged. Signs and symptoms of withdrawal can include drug craving, anxiety, restless legs, ...
can occur with a sudden decrease in, or cessation of, opioids after prolonged use. Onset of withdrawal depends on the half-life of the opioid that was used last. With heroin this typically occurs five hours after use; with methadone, it may take two days. The length of time that major symptoms occur also depends on the opioid used. For heroin withdrawal, symptoms are typically greatest at two to four days and can last up to two weeks. Less significant symptoms may remain for an even longer period, in which case the withdrawal is known as post-acute-withdrawal syndrome
Post-acute withdrawal syndrome (PAWS) is a hypothesized set of persistent impairments that occur after withdrawal from alcohol, opiates, benzodiazepines, antidepressants, and other substances. Infants born to mothers who used substances of depen ...
.
*Agitation[
*Anxiety][
*Muscle pains]
*Increased tearing
Tearing is the act of breaking apart a material by force, without the aid of a cutting tool. A tear in a piece of paper, fabric, or some other similar object may be the result of the intentional effort with one's bare hands, or be accidental. U ...
[
*]Trouble sleeping
Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
[
*Runny nose][
*Sweating][
*Yawning][
*]Goose bumps
Goose bumps, goosebumps or goose-pimples are the bumps on a person's skin at the base of body hairs which may involuntarily develop when a person is tickled, cold or experiencing strong emotions such as fear, euphoria or sexual arousal.
The ...
[
*]Dilated pupils
Mydriasis is the dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, trauma, or the use of certain types of drugs.
Normally, as ...
[
*Diarrhea][
*Fast heart rate][
*High blood pressure][
*Abdominal cramps][
*Shakiness][
*Cravings][
*Sneezing][
Treatment of withdrawal may include methadone and buprenorphine. Medications for nausea or diarrhea may also be used.]
Cause
Opioid use disorder can develop as a result of self-medication
Self-medication is a human behavior in which an individual uses a substance or any exogenous influence to self-administer treatment for physical or psychological conditions: for example headaches or fatigue.
The substances most widely used in sel ...
. Scoring systems have been derived to assess the likelihood of opiate addiction in chronic pain patients. Healthcare practitioners have long been aware that despite the effective use of opioids for managing pain, empirical evidence supporting long-term opioid use is minimal.[Noble M, Tregear SJ, Treadwell JR, Schoelles K. Long-term opioidtherapy for chronic noncancer pain: a systematic review and meta-analysis of efficacy and safety. J Pain Symptom Manag 2008;35:214–28.] Many studies of patients with chronic pain have failed to show any sustained improvement in their pain or ability to function with long-term opioid use.
According to position papers on the treatment of opioid dependence published by the United Nations Office on Drugs and Crime
The United Nations Office on Drugs and Crime (UNODC; French: ''Office des Nations unies contre la drogue et le crime'') is a United Nations office that was established in 1997 as the Office for Drug Control and Crime Prevention by combining the ...
and the World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
, care providers should not treat opioid use disorder as the result of a weak moral character or will but as a medical condition. Some evidence suggests the possibility that opioid use disorders occur due to genetic or other chemical mechanisms that may be difficult to identify or change, such as dysregulation of brain circuitry involving reward and volition. But the exact mechanisms involved are unclear, leading to debate over the influence of biology and free will.
Mechanism
Addiction
Addiction
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use o ...
is a brain disorder
Central nervous system diseases, also known as central nervous system disorders, are a group of neurological disorders that affect the structure or function of the brain or spinal cord, which collectively form the central nervous system (CNS). Th ...
characterized by compulsive drug use despite adverse consequences. It is a component of substance use disorder and its most severe form.
Overexpression of the gene transcription factor ΔFosB
Protein fosB, also known as FosB and G0/G1 switch regulatory protein 3 (G0S3), is a protein that in humans is encoded by the FBJ murine osteosarcoma viral oncogene homolog B (''FOSB'') gene.
The FOS gene family consists of four members: FOS, F ...
in the nucleus accumbens
The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for " nucleus adjacent to the septum") is a region in the basal forebrain rostral to the preoptic area of the hypot ...
plays a crucial role in the development of an addiction to opioids and other addictive drugs by sensitizing drug reward and amplifying compulsive drug-seeking behavior. Like other addictive drug
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use o ...
s, overuse of opioids leads to increased ΔFosB expression in the nucleus accumbens. Opioids affect dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
neurotransmission
Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron), ...
in the nucleus accumbens via the disinhibition of dopaminergic pathways as a result of inhibiting the GABA-based projections to the ventral tegmental area
The ventral tegmental area (VTA) (tegmentum is Latin for ''covering''), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is the ...
(VTA) from the rostromedial tegmental nucleus The rostromedial tegmental nucleus (RMTg), also known as the tail of the ventral tegmental area (tVTA), is a GABAergic nucleus which functions as a "master brake" for the midbrain dopamine system. It is poorly differentiated from the rest of the v ...
(RMTg), which negatively modulate dopamine neurotransmission. In other words, opioids inhibit the projections from the RMTg to the VTA, which in turn disinhibits the dopaminergic pathways that project from the VTA to the nucleus accumbens and elsewhere in the brain.
The differences in the genetic regions encoding the dopamine receptors for each individual may help to elucidate part of the risk for opioid addiction and general substance abuse. Studies of the D2 Dopamine Receptor, in particular, have shown some promising results. One specific SNP is at the TaqI RFLP (rs1800497). In a study of 530 Han Chinese heroin-addicted individuals from a Methadone Maintenance Treatment Program, those with the specific genetic variation showed higher mean heroin consumption by around double those without the SNP. This study helps to show the contribution of dopamine receptors to substance addiction and more specifically to opioid abuse.
Neuroimaging has shown functional and structural alterations in the brain. A 2017 study showed that chronic intake of opioids such as heroin may cause long-term effects in the orbitofrontal area (OFC), which is essential for regulating reward-related behaviors, emotional responses, and anxiety. Moreover, neuroimaging and neuropsychological studies demonstrate dysregulation of circuits associated with emotion, stress and high impulsivity.
Dependence
Opioid dependence can occur as physical dependence
Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certai ...
, psychological dependence
Psychological dependence is a cognitive disorder that involves emotional–motivational withdrawal symptoms—e.g. anxiety and anhedonia—upon cessation of prolonged drug abuse or certain repetitive behaviors. It develops through frequent exp ...
, or both. Drug dependence is an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake). Dependence is a component of a substance use disorder. Opioid dependence can manifest as physical dependence
Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certai ...
, psychological dependence
Psychological dependence is a cognitive disorder that involves emotional–motivational withdrawal symptoms—e.g. anxiety and anhedonia—upon cessation of prolonged drug abuse or certain repetitive behaviors. It develops through frequent exp ...
, or both.
Increased brain-derived neurotrophic factor
Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the cano ...
(BDNF) signaling in the ventral tegmental area
The ventral tegmental area (VTA) (tegmentum is Latin for ''covering''), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is the ...
(VTA) has been shown to mediate opioid-induced withdrawal symptoms via downregulation of insulin receptor substrate 2 (IRS2), protein kinase B (AKT), and mechanistic target of rapamycin complex 2 (mTORC2). As a result of downregulated signaling through these proteins, opiates cause VTA neuronal hyperexcitability and shrinkage (specifically, the size of the neuronal soma is reduced). It has been shown that when an opiate-naive person begins using opiates in concentrations that induce euphoria, BDNF signaling increases in the VTA.
Upregulation of the cyclic adenosine monophosphate
Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transd ...
(cAMP) signal transduction
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...
pathway by cAMP response element binding protein
CREB-TF (CREB, cAMP response element-binding protein) is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes. CREB was first de ...
(CREB), a gene transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
, in the nucleus accumbens
The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for " nucleus adjacent to the septum") is a region in the basal forebrain rostral to the preoptic area of the hypot ...
is a common mechanism of psychological dependence
Psychological dependence is a cognitive disorder that involves emotional–motivational withdrawal symptoms—e.g. anxiety and anhedonia—upon cessation of prolonged drug abuse or certain repetitive behaviors. It develops through frequent exp ...
among several classes of drugs of abuse. Upregulation of the same pathway in the locus coeruleus
The locus coeruleus () (LC), also spelled locus caeruleus or locus ceruleus, is a nucleus in the pons of the brainstem involved with physiological responses to stress and panic. It is a part of the reticular activating system.
The locus coerule ...
is also a mechanism responsible for certain aspects of opioid-induced physical dependence
Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certai ...
.
A study compared the harm and dependence liability of 20 drugs, using a scale from zero to three for physical dependence
Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certai ...
, psychological dependence, and pleasure to create a mean score for dependence. Selected results can be seen in the chart below. Diacetylmorphine
Heroin, also known as diacetylmorphine and diamorphine among other names, is a potent opioid mainly used as a recreational drug for its euphoric effects. Medical grade diamorphine is used as a pure hydrochloride salt. Various white and brow ...
and morphine
Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...
both scored highest, at 3.0.
Opioid receptors
A genetic basis for the efficacy of opioids in the treatment of pain has been demonstrated for several specific variations, but the evidence for clinical differences in opioid effects is ambiguous. The pharmacogenomics
Pharmacogenomics is the study of the role of the genome in drug response. Its name ('' pharmaco-'' + ''genomics'') reflects its combining of pharmacology and genomics. Pharmacogenomics analyzes how the genetic makeup of an individual affects the ...
of the opioid receptor
Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin ...
s and their endogenous
Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell.
In contrast, exogenous substances and processes are those that originate from outside of an organism.
For example, es ...
ligands
In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electro ...
have been the subject of intensive activity in association studies. These studies test broadly for a number of phenotypes
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
, including opioid dependence, cocaine dependence
Cocaine dependence is a neurological disorder that is characterized by withdrawal symptoms upon cessation from cocaine use. It also often coincides with cocaine addiction which is a biopsychosocial disorder characterized by persistent use of coc ...
, alcohol dependence
Alcohol dependence is a previous (DSM-IV and ICD-10) psychiatric diagnosis in which an individual is physically or psychologically dependent upon alcohol (also chemically known as ethanol).
In 2013, it was reclassified as alcohol use disorde ...
, methamphetamine dependence/psychosis
Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...
, response to naltrexone treatment, personality traits, and others. Major and minor variants have been reported for every receptor and ligand coding gene in both coding sequences, as well as regulatory regions.
Newer approaches shift away from analysis of specific genes and regions, and are based on an unbiased screen of genes across the entire genome, which have no apparent relationship to the phenotype in question. These GWAS
In genomics, a genome-wide association study (GWA study, or GWAS), also known as whole genome association study (WGA study, or WGAS), is an observational study of a genome-wide set of genetic variants in different individuals to see if any varian ...
studies yield a number of implicated genes, although many of them code for seemingly unrelated proteins in processes such as cell adhesion
Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indir ...
, transcriptional regulation
In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from al ...
, cell structure determination, and RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
, DNA, and protein handling/modifying.
118A>G variant
While over 100 variants have been identified for the opioid mu-receptor, the most studied mu-receptor variant is the non-synonymous 118A>G variant, which results in functional changes to the receptor, including lower binding site availability, reduced mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
levels, altered signal transduction, and increased affinity for beta-endorphin
''beta''-Endorphin (β-endorphin) is an endogenous opioid neuropeptide and peptide hormone that is produced in certain neurons within the central nervous system and peripheral nervous system. It is one of three endorphins that are produced in ...
. In theory, all these functional changes would reduce the impact of exogenous
In a variety of contexts, exogeny or exogeneity () is the fact of an action or object originating externally. It contrasts with endogeneity or endogeny, the fact of being influenced within a system.
Economics
In an economic model, an exogeno ...
opioids, requiring a higher dose to achieve the same therapeutic effect. This points to a potential for greater addictive capacity in individuals who require higher dosages to achieve pain control. But evidence linking the 118A>G variant to opioid dependence is mixed, with associations shown in a number of study groups, but negative results in other groups. One explanation for the mixed results is the possibility of other variants that are in linkage disequilibrium
In population genetics, linkage disequilibrium (LD) is the non-random association of alleles at different loci in a given population. Loci are said to be in linkage disequilibrium when the frequency of association of their different alleles is h ...
with the 118A>G variant and thus contribute to different haplotype
A haplotype ( haploid genotype) is a group of alleles in an organism that are inherited together from a single parent.
Many organisms contain genetic material ( DNA) which is inherited from two parents. Normally these organisms have their DNA or ...
patterns more specifically associated with opioid dependence.
Non-opioid receptor genes
The preproenkephalin gene, PENK, encodes for the endogenous opiates that modulate pain perception, and are implicated in reward and addiction. (CA) repeats in the 3' flanking sequence of the PENK gene was associated with greater likelihood of opiate dependence in repeated studies. Variability in the MCR2 gene, encoding melanocortin receptor
Melanocortin receptors are members of the rhodopsin family of 7-transmembrane G protein-coupled receptors.
There are five known members of the melanocortin receptor system each with differing specificities for melanocortins:
* . MC1R is associat ...
type 2 has been associated with both protective effects and increased susceptibility to heroin addiction. The CYP2B6 gene of the cytochrome P450
Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
family also mediates breakdown of opioids and thus may play a role in dependence and overdose.
Prevention
The CDC gives specific recommendations for prescribers regarding initiation of opioids, clinically appropriate use of opioids, and assessing possible risks associated with opioid therapy. Large U.S. retail pharmacy chains are implementing protocols, guidelines, and initiatives to take back unused opioids, providing naloxone kits, and being vigilant for suspicious prescriptions. Insurance programs can help limit opioid use by setting quantity limits on prescriptions or requiring prior authorizations for certain medications.
Opioid-related deaths
Naloxone
Naloxone, sold under the brand names Narcan (4 mg) and Kloxxado (8 mg) among others, is a medication used to reverse or reduce the effects of opioids. It is commonly used to counter decreased breathing in opioid overdose. Effects begin withi ...
is used for the emergency treatment of an overdose. It can be given by many routes (e.g., intramuscular, intravenous, subcutaneous, intranasal, and inhalation) and acts quickly by displacing opioids from opioid receptors and preventing the activation of these receptors. Naloxone kits are recommended for laypersons who may witness an opioid overdose, for people with large prescriptions for opioids, those in substance use treatment programs, and those recently released from incarceration. Since this is a life-saving medication, many areas of the U.S. have implemented standing orders for law enforcement to carry and give naloxone as needed. In addition, naloxone can be used to challenge a person's opioid abstinence status before starting a medication such as naltrexone
Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been found t ...
, which is used in the management of opioid addiction.
Good Samaritan laws typically protect bystanders who administer naloxone. In the U.S., at least 40 states have Good Samaritan laws to encourage bystanders to take action without fear of prosecution. As of 2019, 48 states give pharmacists the authority to distribute naloxone without an individual prescription.
Homicide, suicide, accidents and liver disease are also opioid-related causes of death for those with OUD. Many of these causes of death are unnoticed due to the often limited information on death certificates.
Mitigation
The "CDC
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
Clinical Practice Guideline for Prescribing Opioids for Pain-United States, 2022" provides recommendations related to opioid misuse, OUD, and opioid overdose
An opioid overdose is toxicity due to excessive consumption of opioids, such as morphine, codeine, heroin, fentanyl, tramadol, and methadone. This preventable pathology can be fatal if it leads to respiratory depression, a lethal condition that ca ...
s. It reports a lack of clinical evidence that "abuse-deterrent" opioids (e.g., OxyContin), as labeled by the U.S. Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
, are effective for OUD risk mitigation. CDC guidance suggests the prescription of immediate-release opioids instead of opioids that have a long duration (long-acting) or opioids that are released over time (extended release). Other recommendations include prescribing the lowest opioid dose that successfully addresses the pain in opioid-naïve patients and collaborating with patients who already take opioid therapy to maximize the effect of non-opioid analgesics.
While receiving opioid therapy, patients should be periodically evaluated for opioid-related complications and clinicians should review state prescription drug monitoring program systems. The latter should be assessed to reduce the risk of overdoses in patients due to their opioid dose or medication combinations. For patients receiving opioid therapy in whom the risks outweigh the benefits, clinicians and patients should develop a treatment plan to decrease their opioid dose incrementally.
For more specific mitigation strategies regarding opioid overdoses, see Opioid overdose
An opioid overdose is toxicity due to excessive consumption of opioids, such as morphine, codeine, heroin, fentanyl, tramadol, and methadone. This preventable pathology can be fatal if it leads to respiratory depression, a lethal condition that ca ...
.
Management
Opioid use disorders typically require long-term treatment and care with the goal of reducing risks for the individual, reducing criminal behavior, and improving the long-term physical and psychological condition of the person.[ Some strategies aim to reduce drug use and lead to abstinence from opioids, while others attempt to stabilize on prescribed methadone or buprenorphine with continued replacement therapy indefinitely.][ No single treatment works for everyone, so several strategies have been developed including therapy and drugs.][
Though treatment reduces mortality rates, the first four weeks after treatment begins and the four weeks after treatment ceases are the riskiest times for drug-related deaths.] These periods of increased vulnerability are significant because many of those in treatment leave programs during these periods.
Medication
Opioid replacement therapy (ORT) involves replacing an opioid
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
, such as heroin
Heroin, also known as diacetylmorphine and diamorphine among other names, is a potent opioid mainly used as a recreational drug for its euphoric effects. Medical grade diamorphine is used as a pure hydrochloride salt. Various white and brow ...
, with a longer-acting but less euphoric opioid.[Richard P. Mattick et al.]
National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD): Report of Results and Recommendation
/ref> Commonly used drugs for ORT are methadone
Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid agonist used for chronic pain and also for opioid dependence. It is used to treat chronic pain, and it is also used to treat addiction to heroin ...
and buprenorphine
Buprenorphine is an opioid used to treat opioid use disorder, acute pain, and chronic pain. It can be used under the tongue (sublingual), in the cheek (buccal), by injection (intravenous and subcutaneous), as a skin patch (transdermal ...
, which are taken under medical supervision. , buprenorphine/naloxone is preferentially recommended, as the addition of the opioid antagonist naloxone
Naloxone, sold under the brand names Narcan (4 mg) and Kloxxado (8 mg) among others, is a medication used to reverse or reduce the effects of opioids. It is commonly used to counter decreased breathing in opioid overdose. Effects begin withi ...
is believed to reduce the risk of abuse via injection or insufflation without causing impairment when used appropriately ( sublingual administration). Naltrexone
Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been found t ...
, a μ-opioid receptor antagonist, also blocks opioids' euphoric effects by occupying the opioid receptor, but it does not activate it, so it does not produce sedation, analgesia, or euphoria, and thus has no potential for abuse or diversion. Buprenorphine, methadone, and naltrexone are approved by the U.S. Food and Drug Administration (FDA) for medication-assisted treatment (MAT). In the U.S., the Substance Abuse and Mental Health Services Administration (SAMHSA) certifies methadone opioid treatment programs (OTPs) and issues buprenorphine waivers to practitioners.
The driving principle behind ORT is the patient's reclamation of a self-directed life. ORT facilitates this process by reducing symptoms of drug withdrawal
Drug withdrawal, drug withdrawal syndrome, or substance withdrawal syndrome, is the group of symptoms that occur upon the abrupt discontinuation or decrease in the intake of pharmaceutical or recreational drugs.
In order for the symptoms of wit ...
and drug cravings; a strong euphoric effect is not experienced as a result of the treatment drug. In some countries (not the U.S. or Australia), regulations enforce a limited time for people on ORT programs that conclude when a stable economic and psychosocial situation is achieved. (People with HIV/AIDS
Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...
or hepatitis C
Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...
are usually excluded from this requirement.) In practice, 40–65% of patients maintain abstinence from additional opioids while receiving opioid replacement therapy and 70–95% can reduce their use significantly. Medical (improper diluent
A diluent (also referred to as a filler, dilutant or thinner) is a Concentration, diluting agent. Certain fluids are too Viscosity, viscous to be pumped easily or too density, dense to flow from one particular point to the other. This can be prob ...
s, non- sterile injecting equipment), psychosocial (mental health
Mental health encompasses emotional, psychological, and social well-being, influencing cognition, perception, and behavior. It likewise determines how an individual handles stress, interpersonal relationships, and decision-making. Mental health ...
, relationships), and legal (arrest
An arrest is the act of apprehending and taking a person into custody (legal protection or control), usually because the person has been suspected of or observed committing a crime. After being taken into custody, the person can be questi ...
and imprisonment
Imprisonment is the restraint of a person's liberty, for any cause whatsoever, whether by authority of the government, or by a person acting without such authority. In the latter case it is "false imprisonment". Imprisonment does not necessari ...
) issues that can arise from the use of illegal opioids are concurrently eliminated or reduced. Clonidine
Clonidine, sold under the brand name Catapres among others, is an α2-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal ( alcohol, opioids, or nicotine), menopausal flushing, diarrhea, spasticity, and c ...
or lofexidine
Lofexidine, sold under the brand name Lucemyra among others, is a medication historically used to treat high blood pressure; today, it is more commonly used to help with the physical symptoms of opioid withdrawal. It is taken by mouth. It is an ...
can help treat the symptoms of withdrawal.
The period when initiating methadone and the time immediately after discontinuing treatment with both drugs are periods of particularly increased mortality risk, which should be dealt with by both public health and clinical strategies. ORT has proven to be the most effective treatment for improving the health and living condition of people experiencing illegal opiate use or dependence, including mortality reduction and overall societal costs, such as the economic loss from drug-related crime
A drug-related crime is a crime to possess, manufacture, or distribute drugs classified as having a potential for abuse (such as cocaine, heroin, morphine and amphetamines). Drugs are also related to crime as drug trafficking and drug produc ...
and healthcare expenditure. A review of UK hospital policies found that local guidelines delayed access to substitute opioids, for instance by requiring lab tests to demonstrate recent use or input from specialist drug teams before prescribing. Delays to access can increase people's risk of discharging themselves early against medical advice. ORT is endorsed by the World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
, United Nations Office on Drugs and Crime
The United Nations Office on Drugs and Crime (UNODC; French: ''Office des Nations unies contre la drogue et le crime'') is a United Nations office that was established in 1997 as the Office for Drug Control and Crime Prevention by combining the ...
and UNAIDS
The Joint United Nations Programme on HIV and AIDS (UNAIDS) (, ONUSIDA) is the main advocate for accelerated, comprehensive and coordinated global action on the HIV/AIDS pandemic.
The mission of UNAIDS is to lead, strengthen and support an ...
as effective at reducing injection, lowering risk for HIV/AIDS, and promoting adherence to antiretroviral therapy.
Buprenorphine and methadone work by reducing opioid cravings, easing withdrawal symptoms, and blocking the euphoric effects of opioids via cross-tolerance, and in the case of buprenorphine, a high-affinity partial opioid agonist, also due to opioid receptor saturation. It is this property of buprenorphine that can induce acute withdrawal when administered before other opioids have left the body.
Methadone
''Important considerations when initiating methadone include the patient's opioid tolerance, the time since last opioid use, the type of opioid used (long-acting vs. short-acting), and the risk of methadone toxicity.''
Methadone
Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid agonist used for chronic pain and also for opioid dependence. It is used to treat chronic pain, and it is also used to treat addiction to heroin ...
is a full-opioid agonist used for both opioid overuse treatment and for chronic pain. It is the most commonly prescribed medication for addiction. Methadone comes in a different forms: tablet, oral solution, or an injection.
One of methadone's benefits is that it can last up to 56 hours in the body, so if a patient misses one of their daily doses (~24 hrs.), they will not typically struggle with withdrawal symptoms. Other advantages of methadone include reduction in infectious disease related to injection drug use and reduced mortality. When patients taking MAT improve and want to refrain from taking methadone, they must be properly weaned off the medication, which must be done under medical observation. Methadone has a number of serious side effects, including slowed breathing, nausea, vomiting, restlessness, and headache.
Dosages can be adjusted after 1–2 days, or another medication may be recommended for your situation if you experience side effects. Lung and breathing complications are possible long-term side effects of methadone use. Methadone, as an opiate, has the potential to be addictive. Many opponents believe that replacement drugs only substitute one addiction with another, and that methadone can be manipulated and exploited in some cases.
Buprenorphine
''Important considerations when initiating buprenorphine include withdrawal symptom severity, the time since last opioid use, and the type of opioid used (long-acting vs. short-acting). Initiating buprenorphine too soon can lead to rapidly-triggered withdrawal symptoms (i.e., precipitated withdrawal). This is because buprenorphine has a high affinity for opioid receptors and is only a partial opioid agonist, meaning that as buprenorphine displaces full opioid agonists, a much weaker analgesic and euphoric effect is produced.''
Buprenorphine
Buprenorphine is an opioid used to treat opioid use disorder, acute pain, and chronic pain. It can be used under the tongue (sublingual), in the cheek (buccal), by injection (intravenous and subcutaneous), as a skin patch (transdermal ...
is a partial opioid receptor agonist. Unlike methadone and other full opioid receptor agonists, buprenorphine is less likely to cause respiratory depression due to its ceiling effect. This is because buprenorphine's effects do not increase linearly past moderate doses. Buprenorphine is known to be more at a risk of misuse or overdose compared to buprenorphine-naloxone and methadone, but treatment with buprenorphine may be associated with reduced mortality. Buprenorphine under the tongue is often used to manage opioid dependence. Preparations were approved for this use in the United States in 2002. A month-long injectable version of buprenorphine was approved by the FDA in 2017.
Buprenorphine/Naloxone
''Important considerations when initiating buprenorphine/naloxone include withdrawal symptom severity, the time since last opioid use, and the type of opioid used (long-acting vs. short-acting).'' ''Though not standard practice, clinicians are exploring micro-induction protocols for buprenorphine/naloxone that prioritizes rapid induction with small, increasing doses.'' ''The theoretical benefit of this form of induction is that treatment can be initiated irrespective of withdrawal symptoms.''
Some formulations of buprenorphine incorporate the opiate antagonist naloxone
Naloxone, sold under the brand names Narcan (4 mg) and Kloxxado (8 mg) among others, is a medication used to reverse or reduce the effects of opioids. It is commonly used to counter decreased breathing in opioid overdose. Effects begin withi ...
during the production of the pill
Pill or The Pill may refer to:
Drugs
* Pill (pharmacy), referring to anything small for a specific dose of medicine
* "The Pill", a general nickname for the combined oral contraceptive pill
Film and television
* ''The Pill'' (film), a 2011 fil ...
form to prevent people from crushing the tablets and injecting them, instead of using the sublingual (under the tongue) route of administration. Buprenorphine/naloxone formulations are available as tablets and films. The combined tablet works via sublingual administration because buprenorphine maintains adequate bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...
(35-55%) while naloxone doesn't (~10%). When injected, naloxone has higher bioavailability, thereby blocking the pain and craving-reducing effects of buprenorphine.
Naltrexone
Naltrexone
Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been found t ...
is an opioid receptor antagonist used for the treatment of opioid addiction. Naltrexone is not as widely used as buprenorphine or methadone for OUD due to low rates of patient acceptance, non-adherence due to daily dosing, and difficulty achieving abstinence from opioids before beginning treatment. Additionally, dosing naltrexone after recent opioid use could lead to precipitated withdrawal. Conversely, naltrexone antagonism at the opioid receptor can be overcome with higher doses of opioids. Naltrexone monthly IM injections received FDA approval in 2010, for the treatment of opioid dependence in abstinent opioid users.
Other opioids
Evidence of effects of heroin maintenance compared to methadone are unclear as of 2010. A Cochrane review found some evidence in opioid users who had not improved with other treatments. In Switzerland, Germany, the Netherlands, and the United Kingdom, long-term injecting drug users
Injection or injected may refer to:
Science and technology
* Injective function, a mathematical function mapping distinct arguments to distinct values
* Injection (medicine), insertion of liquid into the body with a syringe
* Injection, in broad ...
who do not benefit from methadone
Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid agonist used for chronic pain and also for opioid dependence. It is used to treat chronic pain, and it is also used to treat addiction to heroin ...
and other medication options may be treated with injectable heroin
Heroin, also known as diacetylmorphine and diamorphine among other names, is a potent opioid mainly used as a recreational drug for its euphoric effects. Medical grade diamorphine is used as a pure hydrochloride salt. Various white and brow ...
that is administered under the supervision of medical staff. Other countries where it is available include Spain, Denmark, Belgium, Canada, and Luxembourg.
Dihydrocodeine
Dihydrocodeine is a semi-synthetic opioid analgesic prescribed for pain or severe dyspnea, or as an antitussive, either alone or compounded with paracetamol (acetaminophen) (as in co-dydramol) or aspirin. It was developed in Germany in 1908 a ...
in both extended-release and immediate-release form are also sometimes used for maintenance treatment as an alternative to methadone or buprenorphine in some European countries. Dihydrocodeine is an opioid agonist. It may be used as a second line treatment. A 2020 systematic review found low quality evidence that dihydrocodeine may be no more effective than other routinely used medication interventions in reducing illicit opiate use.
An extended-release morphine
Modified-release dosage is a mechanism that (in contrast to immediate-release dosage) delivers a drug with a delay after its administration (delayed-release dosage) or for a prolonged period of time (extended-release R, XR, XLdosage) or to a sp ...
confers a possible reduction of opioid use and with fewer depressive symptoms but overall more adverse effects when compared to other forms of long-acting opioids. Retention in treatment was not found to be significantly different. It is used in Switzerland and more recently in Canada.
Behavioral therapy
Cognitive behavioral therapy
Cognitive behavioral therapy
Cognitive behavioral therapy (CBT) is a psycho-social intervention that aims to reduce symptoms of various mental health conditions, primarily depression and anxiety disorders. CBT focuses on challenging and changing cognitive distortions (suc ...
(CBT), a form of psychosocial intervention that is used to improve mental health, may not be as effective as other forms of treatment. CBT primarily focuses on an individual's coping strategies to help change their cognition, behaviors and emotions about the problem. This intervention has demonstrated success in many psychiatric conditions (e.g., depression) and substance use disorders (e.g., tobacco). However, the use of CBT alone in opioid dependence has declined due to the lack of efficacy, and many are relying on medication therapy or medication therapy with CBT, since both were found to be more efficacious than CBT alone. A form of CBT therapy known as motivational interviewing (MI) is often used opioid use disorder. MI leverages a person intrinsic motivation to recover through education, formulation of relapse prevention strategies, reward for adherence to treatment guidelines, and positive thinking to keep motivation high—which are based on a person's socioeconomic status, gender, race, ethnicity, sexual orientation, and their readiness to recover.
Twelve-step programs
While medical treatment may help with the initial symptoms of opioid withdrawal, once the first stages of withdrawal are through, a method for long-term preventative care is attendance at 12-step groups such as Narcotics Anonymous
Narcotics Anonymous (NA), founded in 1953, describes itself as a "nonprofit fellowship or society of men and women for whom drugs had become a major problem." Narcotics Anonymous uses a 12-step model developed for people with varied subst ...
. Narcotics Anonymous is a global service that provides multilingual recovery information and public meetings free of charge. Some evidence supports the use of these programs in adolescents as well.
The 12-step program is an adapted form of the Alcoholics Anonymous
Alcoholics Anonymous (AA) is an international mutual aid fellowship of alcoholics dedicated to abstinence-based recovery from alcoholism through its spiritually-inclined Twelve Step program. Following its Twelve Traditions, AA is non-professi ...
program. The program strives to help create behavioural change by fostering peer-support and self-help programs. The model helps assert the gravity of addiction by enforcing the idea that addicts must surrender to the fact that they are addicted and be able to recognize the problem. It also helps maintain self-control and restraint to help promote one's capabilities.
Digital care programs
Digital care programs (see telehealth
Telehealth is the distribution of health-related services and information via electronic information and telecommunication technologies. It allows long-distance patient and clinician contact, care, advice, reminders, education, intervention, mon ...
or digital health
Digital health is a discipline that includes digital care programs, technologies with health, healthcare, living, and society to enhance the efficiency of healthcare delivery and to make medicine more personalized and precise. It uses informat ...
) have increased in number since the Coronavirus pandemic mandated the increased usage of remote healthcare options. These programs offer treatment and continuing care remotely, via smartphone and desktop applications. This often includes remote substance testing, access to peer support meetings, recovery coaching or therapy, and self-guided learning modules. Examples of digital care programs for opioid use disorder include: Chess, Pear Therapeutics, DynamiCare Health, Kaden Health and WeConnect.
Epidemiology
Globally, the number of people with opioid dependence increased from 10.4 million in 1990 to 15.5 million in 2010. In 2016, the numbers rose to 27 million people who experienced this disorder. Opioid use disorders resulted in 122,000 deaths worldwide in 2015, up from 18,000 deaths in 1990. Deaths from all causes rose from 47.5 million in 1990 to 55.8 million in 2013.[
]
United States
The current epidemic of opioid abuse is the most lethal drug epidemic in American history. In 2008, there were four times as many deaths due to overdose than there were in 1999. In 2017, in the US, "the age-adjusted drug poisoning death rate involving opioid analgesics increased from 1.4 to 5.4 deaths per 100,000 population between 1999 and 2010, decreased to 5.1 in 2012 and 2013, then increased to 5.9 in 2014, and to 7.0 in 2015. The age-adjusted drug poisoning death rate involving heroin doubled from 0.7 to 1.4 deaths per 100,000 resident population between 1999 and 2011 and then continued to increase to 4.1 in 2015."
In 2017, the U.S. Department of Health and Human Services (HHS) announced a public health emergency due to an increase in the misuse of opioids. The administration introduced a strategic framework called the Five-Point Opioid Strategy, which includes providing access recovery services, increasing the availability of reversing agents for overdose, funding opioid misuse and pain research, changing treatments of people managing pain, and updating public health reports related to combating opioid drug misuse.
The US epidemic in the 2000s is related to a number of factors.[ Rates of opioid use and dependency vary by age, sex, race, and socioeconomic status.][ With respect to race the discrepancy in deaths is thought to be due to an interplay between physician prescribing and lack of access to healthcare and certain prescription drugs.][ Men are at higher risk for opioid use and dependency than women,] and men also account for more opioid overdoses than women, although this gap is closing. Women are more likely to be prescribed pain relievers, be given higher doses, use them for longer durations, and may become dependent upon them faster.
Deaths due to opioid use also tend to skew at older ages than deaths from use of other illicit drugs. This does not reflect opioid use as a whole, which includes individuals in younger age demographics. Overdoses from opioids are highest among individuals who are between the ages of 40 and 50, in contrast to heroin overdoses, which are highest among individuals who are between the ages of 20 and 30. 21- to 35-year-olds represent 77% of individuals who enter treatment for opioid use disorder, however, the average age of first-time use of prescription painkillers was 21.2 years of age in 2013. Among the middle class means of acquiring funds have included Elder financial abuse
Elder financial abuse is a type of elder abuse in which misappropriation of financial resources or abusive use of financial control, in the context of a relationship where there is an expectation of trust, causes harm to an older person.
The Old ...
through a vulnerability of financial transactions of selling items and international dealers noticing a lack of enforcement in their transaction scams throughout the Caribbean.
Since 2018, with the US federal government's passing of the SUPPORT (Substance Use-Disorder Prevention That Promotes Opioid Recovery and Treatment for Patients and Communities Act) Act, federal restrictions on methadone use for patients receiving Medicare have been lifted. Since March 2020, as a result of the COVID-19 pandemic
The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel virus was first identif ...
, buprenorphine may be dispensed via telemedicine in the U.S.
In October 2021, New York Governor Kathy Hochul
Kathleen Hochul ( ; née Courtney; born August 27, 1958) is an American politician serving as the 57th governor of New York since August 24, 2021. A member of the Democratic Party, she is New York's first female governor, as well as the first ...
signed legislation to combat the opioid crisis. This included establishing a program for the use of medication-assisted substance use disorder treatment for incarcerated individuals in state and local correctional facilities, decriminalizing the possession and sale of hypodermic needles and syringes, establishing an online directory for distributors of opioid antagonists, and expanding the number of eligible crimes committed by individuals with a substance use disorder that may be considered for diversion to a substance use treatment program. Until these laws were signed, incarcerated New Yorkers did not reliably have access to medication-assisted treatment and syringe possession was still a class A misdemeanor despite New York authorizing and funding syringe exchange and access programs. This legislation acknowledges the ways New York State laws have contributed to opioid deaths: in 2020 more than 5112 people died from overdoses in New York State, with 2192 deaths in New York City.
File:NIDA overdose deaths.png, US yearly deaths from all opioid drugs. Included in this number are opioid analgesics, along with heroin and illicit synthetic opioids.
File:NIDA overdose all.png, US yearly deaths by drug category.
File:NIDA overdose prescription.png, US yearly opioid overdose deaths involving prescription opioids. Non-methadone synthetics is a category dominated by illegally acquired fentanyl, and has been excluded.[Overdose Death Rates](_blank)
By National Institute on Drug Abuse
The National Institute on Drug Abuse (NIDA) is a United States federal government research institute whose mission is to "advance science on the causes and consequences of drug use and addiction and to apply that knowledge to improve individual a ...
(NIDA).
File:NIDA overdose heroin.png, US yearly opioid overdose deaths involving heroin.
File:NIDA overdose stimulants.png, US yearly opioid overdose deaths involving psychostimulants (primarily methamphetamine).
History
Opiate misuse has been recorded at least since 300 BC. Greek mythology describes Nepenthe
Nepenthe ( grc, νηπενθές, ) is a fictional medicine for sorrow – a "drug of forgetfulness" mentioned in ancient Greek literature and Greek mythology, depicted as originating in Egypt..
The carnivorous plant genus '' Nepenthes'' is ...
(Greek “free from sorrow”) and how it was used by the hero of the ''Odyssey.'' Opioids have been used in the Near East for centuries. The purification of and isolation of opiates occurred in the early 19th century.
Levacetylmethadol
Levacetylmethadol (INN), levomethadyl acetate (USAN), OrLAAM (trade name) or levo-α-acetylmethadol (LAAM) is a synthetic opioid similar in structure to methadone. It has a long duration of action due to its active metabolites.
Medical uses
LAA ...
was previously used to treat opioid dependence. In 2003 the drug's manufacturer discontinued production. There are no available generic versions. LAAM produced long-lasting effects, which allowed the person receiving treatment to visit a clinic only three times per week, as opposed to daily as with methadone. In 2001, levacetylmethadol was removed from the European market due to reports of life-threatening ventricular rhythm disorders. In 2003, Roxane Laboratories, Inc. discontinued Orlaam in the US.US FDA Safety Alerts: Orlaam (levomethadyl acetate hydrochloride)
Page Last Updated: 20 August 2013
See also
*Benzodiazepine withdrawal syndrome
Benzodiazepine withdrawal syndrome often abbreviated to benzo withdrawal or BZD withdrawal is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines, either medically or recreationally develops a p ...
*Doctor shopping Doctor shopping is the practice of visiting multiple physicians to obtain multiple prescriptions. It is a common practice of people with substance use disorders, suppliers of addictive substances, hypochondriacs or patients of factitious disorder an ...
* Hyperkatifeia, hypersensitivity to emotional distress in the context of opioid abuse
*Prescription drug abuse
Substance abuse, also known as drug abuse, is the use of a drug in amounts or by methods which are harmful to the individual or others. It is a form of substance-related disorder. Differing definitions of drug abuse are used in public health, ...
References
Further reading
*
*
* Seabra, P., Sequeira, A., Filipe, F., Amaral, P., Simões, A., & Sequeira, R. (2022). Substance addiction consequences: outpatients severity indicators in a medication-based program. International Journal of Mental Health & Addiction, 20(3), 1837–1853. https://doi.org/10.1007/s11469-021-00485-3
External links
Heroin information from the National Institute on Drug Abuse
Opioid Dependence Treatment and Guidelines
{{DEFAULTSORT:Opioid Dependence
Substance dependence
Dependence
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