Neuroendocrinology of Stress and Addiction

The stress response evolved as a series of neural and endocrine mechanisms that protect the host organism from threats to homeostasis. Repeated use of psychotropic drugs can lead to the development of tolerance (i.e., decreased drug activity at a given dose) and drug dependence, as indicated by withdrawal syndromes following drug abstinence. Drug withdrawal is often overtly stressful, although acute drug exposure may also represent a threat to homeostasis. This article explores the neuroendocrine effects of drugs of abuse and some of the ways in which stress and appetitive mechanisms interact.

Full Opioid Agonists and Tramadol: Pharmacological and Clinical Considerations

: Opioids are mu receptor agonists and have been an important part of pain treatment for thousands of years. In order to use these drugs appropriately and successfully in patients, whether to control pain, to treat opiate-induced side effects, or opiate withdrawal syndromes, a solid understanding of the pharmacology of such drugs is crucial. The most recognized full agonist opioids are heroin, morphine, codeine, oxycodone, meperidine, and fentanyl. Phenanthrenes refer to a naturally occurring plant-based compound that includes three or more fused rings. The opioids derived from the opium plant are phenanthrene derivatives, whereas most synthetic opioids are simpler molecules that do not have multiple rings. Methadone acts as a synthetic opioid analgesic similar to morphine in both quality and quantity; however, methadone lasts longer and in oral form, has higher efficacy, and is considered a diphenylheptane. Fentanyl is a strong synthetic phenylpiperdine derivative that exhibits activity as a mu-selective opioid agonist approximately 50 to 100 times more potent than morphine. Meperidine is another medication which is a phenylpiperdine. Tramadol is considered a mixed-mechanism opioid drug, as it is a centrally acting analgesic that exerts its effects via binding mu receptors and blocking the reuptake of monoamines. Some of the most common adverse effects shared among all opioids are nausea, vomiting, pruritus, addiction, respiratory depression, constipation, sphincter of Oddi spasm, and miosis (except in the case of meperidine). Chronic opioid usage has also established a relationship to opioid-induced hypogonadism and adrenal suppression. Physicians must be stewards of opioid use and use opioids only when necessary.

Psychomotor Agitation Non-responsive to Treatment: A Case Report of Phenibut Withdrawal Syndrome

Background and Objectives: Phenibut (4-amino-3-phenyl-butyric acid), acting as a GABA-B receptor agonist, has a beneficial effect on anxiety. Although its medical use is not approved in western countries, it can be easily obtained worldwide via the Internet, so it spread as a substance of abuse. In recent years, some case reports have, therefore, highlighted episodes of acute toxicity or withdrawal, but it is still a largely unknown phenomenon.Methods: In this case report, a 50-year-old woman was admitted to the emergency room with psychomotor agitation, psychotic symptoms, and insomnia, and was non-responsive to treatment. She was hospitalized at the psychiatry ward for 25 days and gave her consent for the publication of the present case report.Results: The suspicion of phenibut withdrawal allowed to establish the appropriate management, leading to the restitutio ad integrum of the psychopathological case.Conclusions: In the face of an incoercible psychomotor agitation case, the knowledge of the so-called novel psychoactive substances allows for more appropriate clinical management of intoxication and withdrawal syndromes. This is a scientifically significant report as it provides therapeutic and outcome data concerning a syndrome that is still quite unfamiliar.

Characterization of the GHB Withdrawal Syndrome

The gamma-hydroxybutyric acid (GHB) withdrawal syndrome can have a fulminant course, complicated by severe complications such as delirium or seizures. Detoxification by tapering with pharmaceutical GHB is a safe way to manage GHB withdrawal. However, a detailed description of the course of the GHB withdrawal syndrome is currently lacking. This study aimed to (1) describe the course of GHB withdrawal symptoms over time, (2) assess the association between vital signs and withdrawal symptoms, and (3) explore sex differences in GHB withdrawal. In this observational multicenter study, patients with GHB use disorder (n = 285) were tapered off with pharmaceutical GHB. The most reported subjective withdrawal symptoms (SWS) were related to cravings, fatigue, insomnia, sweating and feeling gloomy. The most prevalent objective withdrawal symptoms (OWS) were related to cravings, fatigue, tremors, sweating, and sudden cold/warm feelings. No association between vital signs and SWS/OWS was found. Sex differences were observed in the severity and prevalence of specific withdrawal symptoms. Our results suggest that the GHB withdrawal syndrome under pharmaceutical GHB tapering does not strongly differ from withdrawal syndromes of other sedative drugs. The lack of association between vital signs and other withdrawal symptoms, and the relative stability of vitals over time suggest that vitals are not suitable for withdrawal monitoring. The reported sex differences highlight the importance of a personalized approach in GHB detoxification.

Can Deep Brain Stimulation Withdrawal Syndromes Be Avoided by Removing Infected Implanted Pulse Generator and Cables with Contralateral Replacement in the Same Session?

Objective: Infections are feared complications following deep brain stimulation in 1.9 to 17.6% of cases. These infections can necessitate the removal of implants, which carries the risk of life-threatening withdrawal syndromes, especially in patients suffering from Parkinson’s disease. In this report, we describe our procedure of removing an infected implanted pulse generator (IPG) and cables with contralateral replacement in the same session. Methods: We retrospectively analysed all patients with transpositions of an IPG and cables between 2017 and 2020 in a single-centre, university hospital setting. Medical records of all patients undergoing this particular surgical procedure were systematically reviewed. The shortest follow-up time was 12 months. Results: Between 2017 and 2020, we had 6 patients with a high risk of withdrawal syndrome in whom an infected IPG with cables was removed and replaced on the opposite side in the same session. There were postoperative complications in 2 patients: in one, the generator had to be re-affixed, and in the second, a skin transplant was required over one electrode because of skin necrosis. No case of invasive infection was seen, and the stimulation therapy was not interrupted. Conclusion: One-session removal of an IPG and cables with contralateral replacement seems to be an effective therapy for patients at high risk of withdrawal syndrome.

Alcohol and Drug Withdrawal Syndromes and Their Clinical Management

Withdrawal syndromes are clusters of signs and symptoms that occur with cessation or decrease in use of a substance. All substance withdrawal syndromes are classified and diagnosed based on criteria published in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). All withdrawal syndromes range in their ability to cause significant medical and/or psychiatric consequences. Alcohol withdrawal remains a medically serious syndrome that can occur within hours to days of decreased use and result in hallucinations, delirium, seizures, and death. Despite increasing research into the type, frequency, dose, and route of administration, benzodiazepines remain the first-line treatment in preventing alcohol withdrawal complications. Although typically not medically severe, opioid withdrawal is often associated with relapse even after successful detoxification. Opioid-agonist therapy, including methadone and buprenorphine, remains the treatment of choice for both opioid withdrawal and relapse prevention. Stimulant withdrawal from cocaine or amphetamines can cause significant psychiatric symptoms within minutes to hours of cessation and may require psychiatric hospitalization for suicidal ideation or attempts. There are no current medications approved by the Food and Drug Administration (FDA) for treatment of stimulant withdrawal. Cannabis withdrawal, although not medically dangerous, has recently been adopted as a discrete syndrome in the DSM-5. Its severity correlates significantly with the amount of cannabis used, functional impairment, and ability to achieve sustained remission. There are no current medications approved by the FDA for treatment of cannabis withdrawal. This review contains 6 figures, 13 tables, and 101 references. Key words: alcohol, amphetamine, benzodiazepines, buprenorphine, cannabis, clonidine, cocaine, dexmedetomidine, methadone, opioid, phenobarbital, stimulant, withdrawal