The Role of Ghrelin/GHS-R1A Signaling in Nonalcohol Drug Addictions

Drug addiction causes constant serious health, social, and economic burden within the human society. The current drug dependence pharmacotherapies, particularly relapse prevention, remain limited, unsatisfactory, unreliable for opioids and tobacco, and even symptomatic for stimulants and cannabinoids, thus, new more effective treatment strategies are researched. The antagonism of the growth hormone secretagogue receptor type A (GHS-R1A) has been recently proposed as a novel alcohol addiction treatment strategy, and it has been intensively studied in experimental models of other addictive drugs, such as nicotine, stimulants, opioids and cannabinoids. The role of ghrelin signaling in these drugs effects has also been investigated. The present review aims to provide a comprehensive overview of preclinical and clinical studies focused on ghrelin’s/GHS-R1A possible involvement in these nonalcohol addictive drugs reinforcing effects and addiction. Although the investigation is still in its early stage, majority of the existing reviewed experimental results from rodents with the addition of few human studies, that searched correlations between the genetic variations of the ghrelin signaling or the ghrelin blood content with the addictive drugs effects, have indicated the importance of the ghrelin’s/GHS-R1As involvement in the nonalcohol abused drugs pro-addictive effects. Further research is necessary to elucidate the exact involved mechanisms and to verify the future potential utilization and safety of the GHS-R1A antagonism use for these drug addiction therapies, particularly for reducing the risk of relapse.

An Overview of Appetite-Regulatory Peptides in Addiction Processes; From Bench to Bed Side

There is a substantial need for new pharmacological treatments of addiction, and appetite-regulatory peptides are implied as possible candidates. Appetite regulation is complex and involves anorexigenic hormones such as glucagon-like peptide-1 (GLP-1) and amylin, and orexigenic peptides like ghrelin and all are well-known for their effects on feeding behaviors. This overview will summarize more recent physiological aspects of these peptides, demonstrating that they modulate various aspects of addiction processes. Findings from preclinical, genetic, and experimental clinical studies exploring the association between appetite-regulatory peptides and the acute or chronic effects of addictive drugs will be introduced. Short or long-acting GLP-1 receptor agonists independently attenuate the acute rewarding properties of addictive drugs or reduce the chronic aspects of drugs. Genetic variation of the GLP-1 system is associated with alcohol use disorder. Also, the amylin pathway modulates the acute and chronic behavioral responses to addictive drugs. Ghrelin has been shown to activate reward-related behaviors. Moreover, ghrelin enhances, whereas pharmacological or genetic suppression of the ghrelin receptor attenuates the responses to various addictive drugs. Genetic studies and experimental clinical studies further support the associations between ghrelin and addiction processes. Further studies should explore the mechanisms modulating the ability of appetite-regulatory peptides to reduce addiction, and the effects of combination therapies or different diets on substance use are warranted. In summary, these studies provide evidence that appetite-regulatory peptides modulate reward and addiction processes, and deserve to be investigated as potential treatment target for addiction.

Dopamine, behavior, and addiction

Addictive drugs are habit-forming. Addiction is a learned behavior; repeated exposure to addictive drugs can stamp in learning. Dopamine-depleted or dopamine-deleted animals have only unlearned reflexes; they lack learned seeking and learned avoidance. Burst-firing of dopamine neurons enables learning—long-term potentiation (LTP)—of search and avoidance responses. It sets the stage for learning that occurs between glutamatergic sensory inputs and GABAergic motor-related outputs of the striatum; this learning establishes the ability to search and avoid. Independent of burst-firing, the rate of single-spiking—or “pacemaker firing”—of dopaminergic neurons mediates motivational arousal. Motivational arousal increases during need states and its level determines the responsiveness of the animal to established predictive stimuli. Addictive drugs, while usually not serving as an external stimulus, have varying abilities to activate the dopamine system; the comparative abilities of different addictive drugs to facilitate LTP is something that might be studied in the future.

Adolescent Cannabis Users Who Have Never Smoked A Combustible Cigarette: Trends and Level of Addictive Drug Use from 1976 to 2020

Background. Adolescents cannabis users are at a substantially elevated risk for use of highly addictive drugs such as cocaine, heroin, and nonmedical use of prescription drugs. Unknown is whether this elevated risk applies to adolescent cannabis users who have never smoked a combustible cigarette, a group that has grown considerably in size in recent years. This study documents the recent growth in the proportion of adolescent cannabis users who abstain from combustible cigarette use, and examines their probability for use of addictive drugs. Methods. Data are annual, cross-sectional, nationally-representative Monitoring the Future surveys of 607,932 U.S. 12th grade students from 1976-2020. Results. Among ever cannabis users, the percentage who had never smoked a combustible cigarette grew from 11% in 2000 to 58% in 2020. This group had levels of addictive drug use that were 8% higher than their peers. In comparison, adolescents who had ever used cannabis – regardless of whether they had ever smoked a cigarette – had levels of addictive drug use 500% higher than their peers.Conclusions. Adolescent cannabis users who have not smoked a combustible cigarette have much lower levels of addictive drug use than the group of cannabis users as a whole. These results suggest policies and laws aimed at reducing adolescent prevalence of addictive drugs may do better to focus on cigarette use of adolescent cannabis users rather than cannabis use per se.

The soul of philosophy in a soulless age

In its original Greek conception, philosophy was intended to promote both wisdom and virtue among society; in this sense, the teaching, or presenting, of philosophy is central to its essence. Socrates and Plato famously grappled with the question of how to impart wisdom and virtue to the learner, with mixed results. One of the standard methods—reading and writing—was argued to be misleading and even deceptive, because it deals with static, ‘dead’ words and ideas rather than with the “living discourse” of one person speaking directly to another. This general critique of certain ‘technologies’ of learning is even more relevant today, in our technological age, where the presenting of philosophy often involves computers, laptops, and the Internet. Such things come to function as addictive drugs—much like the pharmakon that Plato warned of. Philosophy would thus be better served by less use of mediating technologies and by a return to live, interactive, living dialogue between student and teacher.

Treatment-resistant Abuse of Oxybutynin With Psychotic Symptoms: A Case Report and Literature Review

BackroundAnticholinergic drugs are the most commonly used addictive drugs among non-prescription drugs. Oxybutynin is one of the anticholinergic drugs widely used for overactive bladder and nocturnal enuresis treatment for both adults and children. Here is a new case of oxybutynin use with high dose and long-term use despite recurrent treatment applications. Case PresentationA 25 years old, unemployed man that was graduated from primary school applied to the inpatient clinic. He reported that he has been using oxybutynin for 8 years. He was taking 500 mg/day of oxybutynin (100 pills in a day), approximately. He stated that he had taken 250-300 pills in some days (1000-1500 mg/day). He described agitation, irritability, anxiety, visual and auditory hallucinations, reference thoughts, and persecution delusions. The patient was diagnosed with Other Substance Use Disorders according to the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria. Carbamazepine 400 mg/day, olanzapine 10 mg/day, and lorazepam 2.5 mg/day treatments were started. At the end of the five weeks, both symptoms improved completely. In the follow-up, he had no psychiatric symptoms two months after the discharge. He was not using any substance or addictive drugs; working regularly in his father’s family business. ConclusionsOxybutynin is one of the non-controlled drugs, so can be obtained easily from pharmacies without a prescription in Turkey. Interestingly, case reports about oxybutynin use are all from Turkey. Oxybutynin should be considered for the potential for addiction due to its anticholinergic properties, easily accessible, and cumulative cases. Psychiatrists and non-psychiatric physicians, especially urologists should be aware of the addiction potential of the drug because of anticholinergic effects, especially between substance users, and oxybutynin may cause some psychotic effects.

Preliminary Analysis of the Effectiveness of Handing Criminal Acts by Children Under the Age

The issue of drug addiction and illegal trafficking continues to plague nations across the globe. Between 153 and 300 million individuals, or 3.4 to 6.6 percent of the world's drug abusers aged 15 to 64 years, having used drugs at least once a year, with almost 12% (15.5 to 38.6 million people) of users being heavy addicts. Initially created for medicinal reasons (therapy), opioids became a political target for those seeking profit by introducing harmful addictive chemicals. Addition of hazardous addictive drugs may precipitate a person's hallucinations and addictions, wreaking havoc on the neurological system and organs of the body and ultimately resulting in death. The risks of drug addiction have prompted many nations to implement laws aimed at protecting citizens and prohibiting drug trafficking. This restriction eventually spawned illegal commerce and the growth of global marketplaces

Use of Alcohol and Addictive Drugs During the COVID-19 Outbreak in Norway: Associations With Mental Health and Pandemic-Related Problems

Background: The outbreak of COVID-19 has had a major impact on people's daily life. This study aimed to examine use of alcohol and addictive drugs during the COVID-19 outbreak in Norway and examine their association with mental health problems and problems related to the pandemic.Methods: A sample of 4,527 persons responded to the survey. Use of alcohol and addictive drugs were cross-tabulated with sociodemographic variables, mental health problems, and problems related to COVID-19. Logistic regression analyses were used to examine the strength of the associations.Results: Daily use of alcohol was associated with depression and expecting financial loss in relation to the COVID-19 outbreak. Use of cannabis was associated with expecting financial loss in relation to COVID-19. Use of sedatives was associated with anxiety, depression, and insomnia. Use of painkillers was associated with insomnia and self-reported risk of complications if contracting the coronavirus.Conclusion: The occurrence of mental health problems is more important for an understanding of the use of alcohol and addictive drugs during the COVID-19 outbreak in Norway, compared to specific pandemic-related worries.

Drive and Instinct—How They Produce Relatedness and Addiction

Addictive drugs are responsible for mass killing. Neither persons with addiction nor the general populace seem conscious of the malevolence of governments and drug dealers working together. How could this be? What is the place of psychoanalysis in thinking about deaths from addiction and in responding to patients with addiction? To answer these questions, we revise concepts of SEEKING, drive, instinct, pleasure, and unpleasure as separable. We review the neurobiological mechanism of cathexis. We discuss how addictive drugs take over the will by changing the SEEKING system. We review how opioid tone in the central nervous system regulates human relationships and how this endogenous hormonal system is modified by external opioid administration. We differentiate the pleasure of relatedness from the unpleasure of urgent need including the urgent need for drugs. We show how addictive drug-induced changes in the SEEKING system diminish dopaminergic tone, reducing the motivation to engage in the pursuit of food, water, sex, sleep, and relationships in favor of addictive drugs. With this neuropsychoanalytic understanding of how drugs work, we become more confidently conscious of our ability to respond individually and socially.