question: Biologically, how does opiate use diminish a person's ability to feel stress?
comment: Well, you have opioid receptors. These are intended as "docking stations" for endorphines (= endogenous morphine - > "your body's morphine"), but by chance, opioids and opiates have a very similar structure, so they can bind to them as well. The opioid receptors are responsible for hindering nerve signals, mainly pain, and thus cause you to feel "comfortably numb". It's essentially the same process your body goes through when suppressing pain from an injury, but way stronger due to the larger dosage and longer half-life of synthetic opioids and opiates. EDIT: Totally forgot to mention the biggest cause of the good feeling, which is dopamine, basically the go to drug for your brain when it wants to reward itself (and you) with good feelings.
passages: The nucleus raphes dorsalis has also been implicated in naloxone-induced morphine withdrawal. It is known that endogenous opioid receptors exist on the nucleus raphes dorsalis, and that it is a focal point as an ascending and descending regulator. Pourshanazari et al. showed in their 2000 paper that electrical stimulation of the nucleus raphes dorsalis can partially alleviate morphine withdrawal symptoms via electrical stimulation of the raphe nucleus in question.
   KOR agonists have recently been investigated for their therapeutic potential in the treatment of addiction and evidence points towards dynorphin, the endogenous KOR agonist, to be the body's natural addiction control mechanism. Childhood stress/abuse is a well known predictor of drug abuse and is reflected in alterations of the MOR and KOR systems. In experimental "addiction" models the KOR has also been shown to influence stress-induced relapse to drug seeking behavior. For the drug-dependent individual, risk of relapse is a major obstacle to becoming drug-free. Recent reports demonstrated that KORs are required for stress-induced reinstatement of cocaine seeking.
   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 demonstrated dysregulation of circuits associated with emotion, stress and high impulsivity.
  
  Section::::Mechanism.:Dependence.
   Mandenoff et al. proposed that, although endogenous opioids are not necessary to maintain body weight and energy expenditure under predictable circumstances, they become activated under stressful conditions. They found that endogenous opioids, such as dynorphin, stimulate appetite and decrease energy expenditure. Taken together, the studies above suggest an important evolutionary mechanism in which more food is eaten, more nutrients are stored, and less energy is expended by an organism during times of stress.
  
  Section::::Temperature regulation.
   Opiates decrease spine density and dendrite complexity in the nucleus accumbens (NAc). Morphine decreases spine density regardless of the treatment paradigm. Either chronic or intermittent administration of morphine will produce the same effect. The only case where opiates increase dendritic density is with chronic morphine exposure, which increases spine density on pyramidal neurons in the orbitofrontal cortex. Stimulants increase spinal density and dendritic complexity in the nucleus accumbens (NAc), ventral tegmental area (VTA), and other structures in the reward circuit.
  
  Section::::The reward pathway.:Ventral tegmental area.
   Studies have also shown that ingesting a high-fat diet increases the gene expression of dynorphin in the hypothalamus. Thus, dynorphin may cause overeating when a high-fat diet is available. Morley & Levine were the first to describe the role of opioid peptides in stress-related eating. In their study, mice had their tails pinched (causes stress), which induced eating. Stress-related eating was reduced by injecting naloxone, an opioid peptide antagonist.
   When under stress the brain is unable to achieve homeostasis. As a result, the brain reverts to allostasis, which in turn alters the brains ability to process pleasure, which is experienced at the hedonic “set point” (see figures one). Thus, previous pleasures may become no longer pleasurable. This is also known as anhedonia, or “pleasure deafness.” When stressed, the addict may experience extreme craving—an intense, emotional, obsessive experience.
  
  Choice
   It has also been reported that the KOR system is critical for stress-induced drug-seeking. In animal models, stress has been demonstrated to potentiate cocaine reward behavior in a kappa opioid-dependent manner. These effects are likely caused by stress-induced drug craving that requires activation of the KOR system. Although seemingly paradoxical, it is well known that drug taking results in a change from homeostasis to allostasis. It has been suggested that withdrawal-induced dysphoria or stress-induced dysphoria may act as a driving force by which the individual seeks alleviation via drug taking. The rewarding properties of drug are altered, and it is clear KOR activation following stress modulates the valence of drug to increase its rewarding properties and cause potentiation of reward behavior, or reinstatement to drug seeking. The stress-induced activation of KORs is likely due to multiple signaling mechanisms. The effects of KOR agonism on dopamine systems are well documented, and recent work also implicates the mitogen-activated protein kinase cascade and pCREB in KOR-dependent behaviors.
   This learning process has two parts. First, opiate users must connect their drug withdrawal to their use of the drug, which is something that individuals exposed to opiates in hospital settings are more likely to do. When withdrawal is interpreted as a form of addiction, the perceived (and felt) need for more drugs grows. More recent research has shown that, because hospital patients often associate opiate analgesia with an illness and/or hospital care, and because the drugs cause sedation and other mind-altering effects, patients rarely experience any withdrawal.
   In terms of cognitive abilities, one study has shown that morphine may have a negative impact on anterograde and retrograde memory, but these effects are minimal and transient. Overall, it seems that acute doses of opioids in non-tolerant subjects produce minor effects in some sensory and motor abilities, and perhaps also in attention and cognition. It is likely that the effects of morphine will be more pronounced in opioid-naive subjects than chronic opioid users.
   A six-year study on 51 Vietnam veterans who were drug abusers of either mainly stimulants (11 people), mainly opiates (26 people), or mainly benzodiazepines (14 people) was carried out to assess psychiatric symptoms related to the specific drugs of abuse. After six years, opiate abusers had little change in psychiatric symptomatology; five of the stimulant users had developed psychosis, and eight of the benzodiazepine users had developed depression. Therefore, long-term benzodiazepine abuse and dependence seems to carry a negative effect on mental health, with a significant risk of causing depression. Benzodiazepines are also sometimes abused intra-nasally.
   Chronic stress or trauma has been shown to have neuroadaptive effects such that the brain can essentially physically “rewire” itself to accommodate for the increase in cortisol produced by the stressors. Evidence has also shown that a great amount of stress hinders your prefrontal functioning as well causes an increased limbic-stratal level responding. This can lead to low behavioral and cognitive control. Additionally, when the brain is put under severe stress due to repeated drug use, it has been shown to be physiologically altered. This compromised neural state plays a large role in perpetuating addiction and in making recovery more difficult.
   Dihydrocodeine 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.
  
  An extended-release morphine 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.
  
  Section::::Management.:Medications.:Naltrexone.
   Section::::Treatment.
  
  If cessation or decreasing of doses of opioids is possible, endocrinopathy can be reversed. If the treatment with opioid cannot be disrupted due to the serious reasons, for example in substitution program or due to the severe pain or cancer, the hormonal substitution should be considered. It seems like opioids with partial antagonistic action, like buprenorphine, effect hormonal levels less.
   The neurochemical, glutamate is the most abundant neurochemical in the brain. It is critical in memory consolidation. When an addict discovers an addicting behavior, glutamate plays a role by creating the drug cues. It is the neurochemical in motivation which initiates the drug seeking, thus creating the addiction.
  
  Stress
   Changes in receptor expression has also been linked to withdrawal. For example, in rats suffering from nicotine withdrawal it could be observed a down regulation of α6β2*n-icotinic acetylcholine receptors in the mesostriatal dopaminergic pathways has been observed .
  
  Section::::Methods for reducing dependence.
  
  A study examined how rats experienced morphine withdrawal in different surroundings. The rats was either placed in an standard environment (SE) or in an enriched environment (EE). The study concluded that EE reduced depression and anxiety withdrawal symptoms.
   Fear induced hypoalgesia is another example of a mechanism controlled by opioids. It is postulated that fear is a defense mechanism that has evolved over time to provide protection. In the case of hypoalgesia, a decreased response to pain would be very beneficial in a situation where an organism's life was at stake, since feeling pain would be a hindrance rather than a help. It has been well documented that fear does cause a decrease in pain response, however much like the exercise induced hypoalgesia, the exact mechanisms of action are not well understood. Studies have shown that opioids are definitely involved in the process, yet opiates alone do not completely explain the analgesic response. What the other mechanisms of action are is still unknown.
   The concurrent use of opioids with other depressant drugs such as benzodiazepines or ethanol increases the rates of adverse events and overdose. As with an overdose of opioid alone, the combination of an opioid and another depressant may precipitate respiratory depression often leading to death. These risks are lessened with close monitoring by a physician, who may conduct ongoing screening for changes in patient behavior and treatment compliance.
  
  Section::::Interactions.:Opioid antagonist.
   Clinical studies consistently conclude that morphine, like other opioids, often causes hypogonadism and hormone imbalances in chronic users of both sexes. This side effect is dose-dependent and occurs in both therapeutic and recreational users. Morphine can interfere with menstruation in women by suppressing levels of luteinizing hormone. Many studies suggest the majority (perhaps as many as 90%) of chronic opioid users have opioid-induced hypogonadism. This effect may cause the increased likelihood of osteoporosis and bone fracture observed in chronic morphine users. Studies suggest the effect is temporary. , the effect of low-dose or acute use of morphine on the endocrine system is unclear.
   Sapolsky has also studied stress in rats and his results indicate that early experiences in young rats have strong, lasting effects. Rats that were exposed to human handling (a stressful situation) had finely-tuned stress responses that may have lowered their lifetime exposure to stress hormones compared to those that were not handled. In short: stress can be adaptive. The more exposure to stressful situations, the better the rat can handle that situation.
  
  Section::::Behavioral disorders.:Stereotypies.
   Section::::Research.:Opioids.
  
  Isbell and associates published a number of studies on morphine, methadone and assorted analgesics; much of this work was motivated by the search for a "nonaddicting analgesic" (that is, a compound with the pain-relieving capabilities of morphine, but without the opioid dependence issues). 
  
  Many opiate derivatives and synthetic opioids were tested for addiction and abuse potential.
   Opiates are a class of sedative with the capacity for pain relief. Morphine is an opiate that is commonly used in animal testing of addiction. Opiates stimulate dopamine neurons in the brain indirectly by inhibiting GABA release from modulatory interneurons that synapse onto the dopamine neurons. GABA is an inhibitory neurotransmitter that decreases the probability that the target neuron will send a subsequent signal.
  
  Section::::Research methodologies.:Types of drugs.:Stimulants.
   The magnitude of this LTD is comparable to that which results from low frequency stimulation, but with fewer stimulation pulses (40 PPS for 900 low frequency stimulations). It is suggested that the effect of NE is to control the gain of NMDA receptor-dependent homosynaptic LTD. Like norepinephrine, acetylcholine is proposed to control the gain of NMDA receptor-dependent homosynaptic LTD, but it is likely to be a promoter of additional LTD mechanisms as well.
  
  Section::::Mechanisms that weaken synapses.:Prefrontal cortex.
   Drugs of abuse change the complexity of dendritic branching as well as the number and size of the branches in both the VTA and the NAc. [7] By correlation, these structural changes have been linked to addictive behaviors. The effect of these structural changes on behavior is uncertain and studies have produced conflicting results. Two studies have shown that an increase in dendritic spine density due to cocaine exposure facilitates behavioral sensitization, while two other studies produce contradicting evidence.
   - Endone 
  
  - Norspan 
  
  - Oxynorm 
  
  - Oxycontin 
  
  These analgesic drugs bind and acts on opioid receptors in both the gastrointestinal and central nervous system to alleviate moderate to severe pain. This sedating medication acts on receptors known as mu-receptors to reduce pain radiation across the body. These can come in the form of extended release medication or immediate release depending on the condition and type of medication being consumed. 
  
  Section::::Effect of opioid.
  