scholarly journals Psychosocial and Biological Aspects of Synthetic and Natural FAAH Inhibitors

Author(s):  
David A Dawson

Molecular engineers are studying FAAH as a target for pharmaceuticals as controlling levels of FAAH may produce some of the same health effects that excite clinicians about the potential for phytocannabinoid-based medicines. Synthetic cannabinoids work by flooding the system with molecules structurally similar to THC and other phytocannabinoids. Medicines that inhibit the body’s production of FAAH are theorized to have a similar effect by maximizing the concentration of deficient endocannabinoids in the nervous system. Technological limitations coupled with a suppression of research of biologic cannabinoids at many major research universities have limited our understanding of the endocannabinoid system. Questions still need to be answered to provide a comprehensive comparison of biologic with synthetic FAAH inhibitors. Advancement and research aimed at understanding of endogenous and exogenous cannabinoids, and particularly the medicinal properties of the Trans-Δ⁹-Tetrahydrocannabinol (THC) molecule and its endocannabinoid equivalent anandamide are hindered by prohibitive restrictions resulting from the Food and Drug Administration (FDA), Drug Enforcement Administration (DEA), National Institute of Health (NIH), and the National Institute on Drug Abuse (NIDA). The mission statements of each of these entities effectively integrate to ensure research and utilization of the medicinal properties of THC will be nearly impossible to attain.

Author(s):  
Rebekah E Wharton ◽  
Jerry Casbohm ◽  
Ryan Hoffmaster ◽  
Bobby N Brewer ◽  
M G Finn ◽  
...  

Abstract Health-care workers, laboratorians and overdose prevention centers rely on commercial immunoassays to detect the presence of fentanyl; however, the cross-reactivity of fentanyl analogs with these kits is largely unknown. To address this, we conducted a pilot study evaluating the detection of 30 fentanyl analogs and metabolites by 19 commercially available kits (9 lateral flow assays, 7 heterogeneous immunoassays and 3 homogenous immunoassays). The analogs selected for analysis were compiled from the Drug Enforcement Administration and National Forensic Laboratory Information System reports from 2015 to 2018. In general, the immunoassays tested were able to detect their intended fentanyl analog and some closely related analogs, but more structurally diverse analogs, including 4-methoxy-butyryl fentanyl and 3-methylfentanyl, were not well detected. Carfentanil was only detected by kits specifically designed for its recognition. In general, analogs with group additions to the piperidine, or bulky rings or long alkyl chain modifications in the N-aryl or alkyl amide regions, were poorly detected compared to other types of modifications. This preliminary information is useful for screening diagnostic, forensic and unknown powder samples for the presence of fentanyl analogs and guiding future testing improvements.


2020 ◽  
Vol 21 (12) ◽  
pp. 4221
Author(s):  
Tomasz Charytoniuk ◽  
Hubert Zywno ◽  
Karolina Konstantynowicz-Nowicka ◽  
Klaudia Berk ◽  
Wiktor Bzdega ◽  
...  

The worldwide prevalence of neurological and neurodegenerative disorders, such as depression or Alzheimer’s disease, has spread extensively throughout the last decades, becoming an enormous health issue. Numerous data indicate a distinct correlation between the altered endocannabinoid signaling and different aspects of brain physiology, such as memory or neurogenesis. Moreover, the endocannabinoid system is widely regarded as a crucial factor in the development of neuropathologies. Thus, targeting those disorders via synthetic cannabinoids, as well as phytocannabinoids, becomes a widespread research issue. Over the last decade, the endocannabinoid system has been extensively studied for its correlation with physical activity. Recent data showed that physical activity correlates with elevated endocannabinoid serum concentrations and increased cannabinoid receptor type 1 (CB1R) expression in the brain, which results in positive neurological effects including antidepressant effect, ameliorated memory, neuroplasticity development, and reduced neuroinflammation. However, none of the prior reviews presented a comprehensive correlation between physical activity, the endocannabinoid system, and neuropathologies. Thus, our review provides a current state of knowledge of the endocannabinoid system, its action in physical activity, as well as neuropathologies and a possible correlation between all those fields. We believe that this might contribute to finding a new preventive and therapeutic approach to both neurological and neurodegenerative disorders.


2021 ◽  
Vol 27 ◽  
Author(s):  
Alenabi Aylar ◽  
Malekinejad Hassan

Objective: In this review we discuss the emerging evidence for the effectiveness of cannabinoids in the treatment of cancer and inflammation. The remarkable effects complete the traditional evidence for their successful application in the treatment of pain and cancer-related side effects. Methods: we searched Pub Med (132 articles) and Google scholar (9 articles) databases and gathered the clinical (4 articles), preclinical (28 articles) studies, reports on cell culture models (30 articles) and other original and review articles (78 articles) related to inflammation, cancer and cannabinoids. Results: Cannabinoids are described in three different forms, comprising endo- phyto- and synthetic compounds that exert biological effects. The molecular and cellular pathways of endogenous cannabinoids in the maintenance of homeostasis are well documented. In addition to classical cannabinoid receptors type 1 and 2, Vanilloid receptors and G protein-coupled receptor 55 were identified as common receptors. Subsequently, the effectiveness of phyto- and synthetic cannabinoids mediated by cannabinoid receptors has been demonstrated in the treatment of inflammatory diseases including neurodegenerative diseases as well as gastrointestinal and respiratory inflammations. Another accepted property of cannabinoids is their anti-cancer effects. Cannabinoids were found to be effective in the treatment of lung, colorectal, prostate, breast, pancreas and hepatic cancers. The anticancer effects of cannabinoids were characterized by their anti-proliferative property, inhibition of cancer cells migration, suppression of vascularization and induction of apoptosis. Conclusion: The current review provides and overview the role of endocannabinoid system in the mediation of physiological functions, the type and expression of cannabinoids receptors under physiological and pathological conditions. In additions, the molecular pathways involved in the effects of cannabinoids and the effectiveness of cannabinoids in the treatment of inflammations and cancers are highlighted.


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