Evidence of Dopaminergic Processing of Executive Inhibition

Inhibition of unwanted response is an important function of the executive system. Since the inhibitory system is impaired in patients with dysregulated dopamine system, we examined dopamine neurotransmission in the human brain during processing of a task of executive inhibition. The experiment used a recently developed dynamic molecular imaging technique to detect and map dopamine released during performance of a modified Eriksen's flanker task. In this study, young healthy volunteers received an intravenous injection of a dopamine receptor ligand (11C-raclopride) after they were positioned in the PET camera. After the injection, volunteers performed the flanker task under Congruent and Incongruent conditions in a single scan session. They were required to inhibit competing options to select an appropriate response in the Incongruent but not in the Congruent condition. The PET data were dynamically acquired during the experiment and analyzed using two variants of the simplified reference region model. The analysis included estimation of a number of receptor kinetic parameters before and after initiation of the Incongruent condition. We found increase in the rate of ligand displacement (from receptor sites) and decrease in the ligand binding potential in the Incongruent condition, suggesting dopamine release during task performance. These changes were observed in small areas of the putamen and caudate bilaterally but were most significant on the dorsal aspect of the body of left caudate. The results provide evidence of dopaminergic processing of executive inhibition and demonstrate that neurochemical changes associated with cognitive processing can be detected and mapped in a single scan session using dynamic molecular imaging

Pilot clinical observations between food and drug seeking derived from fifty cases attending an eating disorder clinic

Background The reward deficiency syndrome hypothesis posits that genes are responsible for reward dependence and related behaviors. There is evidence that both bulimia and anorexia nervosa, especially in women, have been linked to a lifetime history of substance use disorder (SUD). There are difficulties in accepting food as an addiction similar to drugs; however, increasingly neuroimaging studies favor such an assertion. Case presentations We are reporting the evidence of comorbidity of eating disorders with SUD found within these case presentations. We show 50 case reports derived from two independent treatment centers in Florida that suggest the commonality between food and drug addictions. In an attempt to provide data from this cohort, many participants did not adequately respond to our questionnaire. Discussion We propose that dopamine agonist therapy may be of common benefit. Failure in the past may reside in too powerful D2 agonist activity leading to D2 receptor downregulation, while the new methodology may cause a reduction of “dopamine resistance” by inducing “dopamine homeostasis.” While this is not a definitive study, it does provide some additional clinical evidence that these two addictions are not mutually exclusive. Conclusion Certainly, it is our position that there is an overlap between food- and drug-seeking behavior. We propose that the studies focused on an effort to produce natural activation of dopaminergic reward circuitry as a type of common therapy may certainly be reasonable. Additional research is warranted

Neurogenetic and epigenetic aspects of cannabinoids

Cannabis is one of the most commonly used and abused illicit drugs in the world today. The United States (US) currently has the highest annual prevalence rate of cannabis consumption in the world, 17.9% in individuals aged 12 or older, and it is on the rise. With increasing cannabis use comes the potential for an increase in abuse, and according to the Substance Abuse and Mental Health Services Administration (SAMHSA), approximately 5.1% of Americans had Cannabis Use Disorder (CUD) in 2020. Research has shown that genetics and epigenetics play a significant role in cannabis use and CUD. In fact, approximately 50-70% of liability to CUD and 40-48% of cannabis use initiation have been found to be the result of genetic factors. Cannabis usage and CUD have also been linked to an increased risk of psychiatric disorders and Reward Deficiency Syndrome (RDS) subsets like schizophrenia, depression, anxiety, and substance use disorder. Comprehension of the genetic and epigenetic aspects of cannabinoids is necessary for future research, treatment plans, and the production of pure cannabinoid compounds, which will be essential for FDA approval. In conclusion, having a better understanding of the epigenetic and genetic underpinnings of cannabis use, CUD, and the endocannabinoid system as a whole will aid in the development of effective FDA-approved treatment therapies and the advancement of personalized medicine

Co-occurrences of substance use and other potentially addictive behaviors: epidemiological results from the Psychological and Genetic Factors of the Addictive Behaviors (PGA) Study

Background and aims: Changes in the nomenclature of addictions suggest a significant shift in the conceptualization of addictions, where non-substance related behaviors can also be classified as addictions. A large amount of data provides empirical evidence that there are overlaps of different types of addictive behaviors in etiology, phenomenology, and in the underlying psychological and biological mechanisms. Our aim was to investigate the co-occurrences of a wide range of substance use and behavioral addictions. Methods: The present epidemiological analysis was carried out as part of the Psychological and Genetic Factors of the Addictive Behaviors (PGA) Study, where data were collected from 3,003 adolescents and young adults (42.6% males; mean age 21 years). Addictions to psychoactive substances and behaviors were rigorously assessed. Results: Data is provided on lifetime occurrences of the assessed substance uses, their co-occurrences, the prevalence estimates of specific behavioral addictions , and co-occurrences of different substance use and potentially addictive behaviors. Associations were found between (i) smoking and problematic Internet use, exercising, eating disorders, and gambling (ii) alcohol consumption and problematic Internet use, problematic online gaming, gambling, and eating disorders, and (iii) cannabis use and problematic online gaming and gambling. Conclusions: The results suggest a large overlap between the occurrence of these addictions and behaviors and underlies the importance of investigating the possible common psychological, genetic and neural pathways. These data further support concepts such as the Reward Deficiency Syndrome and the component model of addictions that propose a common phenomenological and etiological background of different addictive and related behaviors

Pro-dopamine regulator, KB220Z, attenuates hoarding and shopping behavior in a female, diagnosed with SUD and ADHD

Background: Addictive-like behaviors (e.g., hoarding and shopping) may be the result of the cumulative effects of dopaminergic and other neurotransmitter genetic variants as well as elevated stress levels. We, therefore, propose that dopamine homeostasis may be the preferred goal in combating such challenging and unwanted behaviors, when simple dopaminergic activation through potent agonists may not provide any resolution. Case presentation: C.J. is a 38-year-old, single, female, living with her mother. She has a history of substance use disorder as well as attention deficit hyperactivity disorder, inattentive type. She had been stable on buprenorphine/naloxone combination and amphetamine, dextroamphetamine mixed salts for many years when unexpectedly she lost her job for oversleeping and not calling into work. KB200z (a pro-dopamine compound) was added to her regimen for complaints of low drive and motivation. After taking this nutraceutical for 4 weeks, she noticed a marked improvement in her mental status and many behaviors. She noted that her shopping and hoarding addictions had appreciably decreased. Furthermore, her lifelong history of terrifying lucid dreams was eliminated. Finally, she felt more in control; her locus of control shifted from external to more internal. Discussion: The hypothesis is that C.J.’s reported, behavioral, and psychological benefits resulted from the pro-dopamine-regulating effect of KB220Z across the brain reward system. Conclusions: This effect, we surmise, could be the result of a new dopamine balance, across C.J.’s brain reward system. Dopamine homeostasis is an effect of KB220Z seen in both animal and human placebo-controlled fMRI experiments

A flexible sequential learning deficit in patients with Parkinson’s disease: a 2 × 8 button-press task

A 2 × 8 button-press task is a sequential hand movement task in which subjects are required to press eight pairs of buttons as accurately and quickly as possible. The 2 × 8 task allows us to examine flexible sequential learning, more aptly called sequence-unselective learning. Sequence-unselective learning is observed after repeated experiences with the task, when subjects have shown good progress in learning, with new sequences as well as previously learned ones. Although cognitive inflexibility has been reported in patients with Parkinson’s disease (PD), there have been few studies investigating their flexibility in sequential learning. We examined PD patients’ ability for sequence-unselective learning through the use of a 2 × 8 button-press task. In the first session, PD patients and subjects from the control group performed a sequential 2 × 8 task until the learning criterion was fulfilled (Session 1). After 1 month, they participated in other sessions: one involving the learned sequence (Session 2) and another involving the new sequence (Session 3). We found that PD patients made more errors than the normal control subjects only when learning the new sequence (Session 3) (P < 0.01). In Session 3, control subjects reached the learning target with fewer errors than in the Session 1 (normal sequence-unselective learning), whereas the PD patients did not exhibit such an improvement. Our results revealed a sequence-unselective deficit in PD patients. The deficit may help to emphasize the cognitive and physical inflexibility of PD