Opiate addiction and cocaine addiction: underlying molecular neurobiology andgenetics PMC

Addictions can also be comorbid with majorinfectious disorders, such as HIV/AIDS (4). In the HPA axis, stress increases both corticotropin-releasing factor (CRF) andarginine-vasopressin (AVP) release into the pituitary portal circulation from terminals ofhypothalamic paraventricular nucleus (PVN). Both CRF-R1 and AVP-V1b receptors are located oncorticotropes in the anterior pituitary and drive the processing and release of ACTH andβ-EP from the pro-opiomelanocortin (POMC) peptide, of particular interest for the fieldof addictive diseases (55, 56). Animaland human studies have demonstrated that β-EP and dynorphin exert tonic inhibition andstimulation of HPA activity acting on MOP-r and KOP-r, respectively. In a rat study, eitheracute morphine or acute stress elevated HPA activity; in contrast, acute morphine blunted theHPA activation by stress, suggesting a counterregulatory role of opiates on the stress response(57). Both ACTH and cortisol levels are significantlydisrupted in active heroin addicts; however, both basal activity and responsivity of the HPAaxis are normalized in steady-state methadone-maintained patients (58).

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Both cocaine and heroin have profound effects on the body, but they differ in terms of the specific physiological and psychological responses they elicit. Cocaine stimulates the central nervous system, leading to increased heart rate, blood pressure, and body temperature. It also produces feelings of euphoria, heightened energy, and increased sociability. However, these effects are short-lived and often followed by a crash, characterized by fatigue, depression, and intense cravings for more cocaine. Heroin addiction treatment often includes medication-assisted treatment (MAT), which combines medications like methadone or buprenorphine with counseling and behavioral therapies. MAT helps to reduce withdrawal symptoms, prevent relapse, and stabilize individuals in recovery.

A typical dose of snorted cocaine is between 30 and 70 milligrams. In a 2021 national survey, about 4.8 million people in the U.S. ages 12 or older said they symptoms of being roofied had used cocaine in the past year. The rate was highest in the age group (1.2 million people or 3.5%), followed by those over age 26 (3.6 million or 1.6%). Comparisons may contain inaccurate information about people, places, or facts.

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Also, one of the major medications approvedfor the treatment of alcoholism, naltrexone, has prominent MOP-r antagonist effects and also hasaffinity for KOP-r receptors (14). Stress-responsivebrain areas and the hypothalamo-pituitary-adrenal (HPA) axis are also involved at particularstages of the addiction trajectory to cocaine, heroin/prescription opioids, and alcohol orrecovery therefrom (15–18). The impact of these stress-related systems on addiction neurobiology willbe discussed separately below.

You could have hallucinations, meaning you see or hear things that aren’t there. These unpleasant effects often make you want to use the drug again. When injected, it goes directly into your bloodstream for a very strong and near-instant effect.

It can affect your heart, brain, lungs, gut, and kidneys as well as your emotional health and daily life — especially if you become addicted. Some of the side effects of cocaine depend on how you take the drug. If you snort it, you might have nosebleeds, loss of smell, hoarseness, nasal irritation, runny nose, or trouble swallowing. If you inject it, you could develop tracks (puncture marks on your arms) and infections, such as HIV or hepatitis C. In humans, stress plays a major role in drug addiction and elevates drug craving.Stress-induced HPA activity predicted relapse to drug use and amounts of subsequent use,indicating that stress not only elicits craving, but also independently predicts relapse (54). Naltrexone (a potent MOP-r antagonist which also has considerable affinity at KOP-r) isapproved for the treatment of alcoholism and has had some effectiveness in reducing cocaine usein alcoholic patients (35).

We also observed increases in KOP-r levels in the caudate-putamen and inother brain regions, including the ventral tegmental area, where the dopaminergic neuronsprojecting to the NAc are located (27). Changes in opioidreceptor levels observed following cocaine use continue to be observed during abstinence,indicating long-term perturbations in the endogenous opioid system (28, 29). In vivo PET imaging in thebrains of cocaine-addicted patients likewise shows an increase in the binding potential of MOP-r(30). The full MOP-r agonist methadone is approved in the chronic maintenance treatment ofaddiction to heroin or prescription opioids, as is the MOP-r partial agonist buprenorphine.Naltrexone, also approved as an i.m.

Such an endogenous activation of KOP-r tone by dynorphins isthought to underlie aversion, dysphoria/anhedonia, and depression-like or anxiety-likeneuropsychiatric states. Such a counterregulatory action by the KOP-r/dynorphin system maytherefore mediate, in part, the negatively reinforcing aspects of withdrawal from drugs of abuseand may exacerbate the chronic relapsing nature of addictive diseases. Drug-induced effects and neuroadaptations, specific genetic variants, and environmentalfactors all contribute to the development of specific addictive diseases.

Neurobiology of addiction to MOP-r agonists or cocaine

Counseling and other types of therapy are the most common treatments for cocaine use disorder. Sessions with a trained therapist can help you make changes to your behaviors and thought processes. You may need to stay in a rehabilitation center (also known as rehab) for intensive therapy and support. If you do attend rehab, continuing treatment afterward (aftercare) is important to help you avoid relapse. If you use cocaine regularly or to excess, you may have long-lasting and serious problems with your physical and mental health.

Your brain covert narcissist and drugs may become less responsive to other natural rewards, such as food and relationships. To make cocaine, the leaves are chemically processed and treated to form a powder. A German chemist named Albert Neiman first isolated the drug from coca leaves in 1860.

1. Drug overdoses are the leading cause of death for Americans ages 18-45.
2. Here, we review the molecular neurobiology andgenetics of opiate addiction, including heroin and prescription opioids, and cocaineaddiction.
3. Such a counterregulatory action by the KOP-r/dynorphin system maytherefore mediate, in part, the negatively reinforcing aspects of withdrawal from drugs of abuseand may exacerbate the chronic relapsing nature of addictive diseases.
4. The opioid peptide β-EP (primarily a MOP-r agonist) is distributed in the hypothalamusand mesocorticolimbic regions, including the NAc.
5. You could have hallucinations, meaning you see or hear things that aren’t there.

These dual-addictiondiagnosis patients may provide a particular challenge, both clinically and for study design andinterpretation. Of interest, naltrexone was effective in reducing use of amphetamine (anotherpsychostimulant compound acting through the dopamine transporter) in patients withoutcooccurring alcoholism (36). In early tests, a vaccine helped reduce the risk of relapse in people who use cocaine. The vaccine activates your immune system to create antibodies that attach to cocaine and stop it from making its way into your brain.

One goal of pharmacogenetics is to develop individualized therapy in response tointerindividual variability in drug response. Methadone is a full MOP-r agonist and a weak NMDAreceptor antagonist (Figure ​(Figure1).1). Predicting individualsensitivity to methadone may help determine the most effective methadone dose. Methadonemetabolism is attributed primarily to cytochrome P450 enzymes CYP3A4, CYP2B6, and CYP2D6.Methadone ween off alcohol is a substrate of the ATP-binding cassette efflux transporter P-glycoprotein.