Opioid Use Disorder

Opioid use disorder is a medical condition characterized by a problematic pattern of opioid use that causes clinically significant impairment or distress.[3] It often includes a strong desire to use opioids, increased tolerance to opioids, and withdrawal syndrome when opioids are abruptly discontinued.[4][8] Addiction and dependence are components of a substance use disorder and addiction represents the most severe form of the disorder Opioid dependence can manifest as physical dependence, psychological dependence, or both.[4][10]

Opioids include substances such as morphine, heroin, codeine and oxycodone. These can be bought illegally or prescribed. The diagnosis of OPIOID ADDICTION AND DEPENDENCE use disorder is often based on criteria by the American Psychiatric Association in the DSM-5.[4] These include a preoccupation with a desire to obtain and take opioids, as well as using more than intended despite social and professional consequences due to these behaviors.
Opioid use disorder can be treated with opioid replacement therapy using methadone or buprenorphine.[5] Being on such treatment reduces the risk of death.[5] Additionally, individuals with opioid use disorder may benefit from twelve-step programs, other peer support, and support from mental health professionals such as individual or group therapy.[6] The medication naltrexone may also be useful to prevent relapse. Naloxone is useful for the treatment of an opioid overdose.[11]

In 2013 opioid use disorders affects about 0.4% of people.[4] About 16 million people have been affected at one point in time.[12] It resulted in 122,000 deaths worldwide in 2015,[13] up from 18,000 deaths in 1990.[14] In the United States in 2015 there were 33,000 deaths due to drug overdose involving opioids.[15] Of those 33,000 deaths, about 15,000 were from prescribed opioids and 13,000 from heroin.

Addiction[edit]
Addiction is a brain disorder characterized by compulsive drug use despite adverse consequences.[9][24][25][26] Addiction is a component of a substance use disorder and represents the most severe form of the disorder.[9]

Overexpression of the gene transcription factor "ΔFosB" in the nucleus accumbens 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.[24][27][28][29] Like other addictive drugs, overuse of opiates leads to increased ΔFosB expression in the nucleus accumbens.[27][28][29][30] Opiates affect dopamine neurotransmission in the nucleus accumbens via the disinhibition of dopaminergic pathways as a result of inhibiting the GABA-based projections to the ventral tegmental area (VTA) from the rostromedial tegmental nucleus (RMTg), which negatively modulate dopamine neurotransmission.[31][32] In other words, opiates 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.[31][32]

Neuroimaging has shown functional and structural alterations in the brain.[33] A 2017 study showed that chronic intake of opiate, such as heroin, may cause long-term effect in the orbitofrontal area (OFC), which is essential for regulating reward-related behaviors, emotional responses, and anxiety.[34][non-primary source needed] Moreover, neuroimaging and neuropsychological studies demonstrated dysregulation of circuits associated with emotion, stress and high impulsivity.[35]

Dependence[edit]
Drug dependence is an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake).[24][25][26] Dependence is a component of a substance use disorder.[9][36] Opioid dependence can manifest as physical dependence, psychological dependence, or both.[36][10][25]

Increased brain-derived neurotrophic factor (BDNF) signaling in the ventral tegmental area (VTA) has been shown to mediate opiate-induced withdrawal symptoms via downregulation of insulin receptor substrate 2 (IRS2), protein kinase B (AKT), and mechanistic target of rapamycin complex 2 (mTORC2).[24][37] 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).[24] It has been shown that when an opiate-naive person begins using opiates in concentrations that induce euphoria, BDNF signaling increases in the VTA.[38]

Upregulation of the cyclic adenosine monophosphate (cAMP) signal transduction pathway by cAMP response element binding protein (CREB), a gene transcription factor, in the nucleus accumbens is a common mechanism of psychological dependence among several classes of drugs of abuse.[10][24] Upregulation of the same pathway in the locus coeruleus is also a mechanism responsible for certain aspects of opioid-induced physical dependence Via WIKI