The symptom cluster with substantial evidence of CEDS is present for migraine, fibromyalgia, and irritable bowel syndrome. The endocannabinoid system regulates gut function, the CNS, and has a communicative relationship with the microbiome. Therefore, many other disorders and diseases are linked to a deficiency and dysfunction of the endocannabinoid system. Dysregulation of the endocannabinoids and CB2 receptors lead to many disorders affecting the liver, kidneys, CNS,neuromuscular, GI, immune system, lungs, bone, and mental health. Deficiency of endocannabinoids disrupts homeostasis. This provides an opportunity for the additional assessment of the therapeutic potential of phytocannabinoids, naturally-occurring cannabinoids in the cannabis, or hemp plants. These phytocannabinoids interact with the endocannabinoid system in the same way as endocannabinoids. There was a reduction in expression of the tight junction proteins occludin and claudin-5 on brain microvascular endothelial cells in germ-free mice . Expression of these proteins and BBB integrity was restored after gut colonization with the butyrate producing species, Clostridium tyrobutyricum or by administration of butyrate. Probiotics improved gut integrity and enhanced endocannabinoid signaling. Zebrafish were treated with a probiotic formulation for 30 days. Compared to untreated animals, histological analysis of gut Thissue from treated animals showed an intact epithelial barrier with increases in enterocyte length, villus length, and crypt depth. There was a reduction in epithelial and mesenchymal apoptotic cells, microgreen grow rack confirming molecular level changes of the pro-apoptotic factors casp3 and BCL2 associated X , and an increase in antiapoptotic signals such as B cell lymphoma 2 . Probiotics also decreased the gene expression for fatty acid amide hydrolase and monoacylglycerol lipase , which are involved in the degradation of endocannabinoids AEA and 2-AG.

One must take into consideration these metabolism pathways. Thus, probiotic treatment improved gut integrity and enhanced endocannabinoid signaling. The influence of cannabis on host Thissues, particularly gut permeability and its subsequent indirect effects on the gut microbiome, suggests significant potential therapeutic applications in HIV. Cannabis has been used for its medicinal properties for thousands of years in ancient cultures. Being a novice to cannabis use can be an intimidating issue for providers making recommendations to their patients. There are hundreds of strains that have names that are not based on structured nomenclature that clinicians are normally familiar with. Only recently, in the 1960s have scienThists begun to explore the properties of cannabis and even more recently the medicinal application in conjunction with Western medicine. Understanding the general physiological mechanism of endocannabinoids will support the framework in forming strategies to strain selection for symptom management. Despite suppressive ART, PWH maintain a high symptom burden with GI disorders, HAND, depression/ anxiety, pain, and fatigue. In addition, CD4 + T cell depletion and gut microbiota dysbiosis promote dysfunction of the gut epithelial barrier, resulting in a positive feedback loop sustained by increased microbial translocation of pro-inflammatory antigens such as LPS and subsequent immune activation and chronic inflammation. Consequences of these events in PWH are associated with poor health outcomes, including organ damage, cognitive decline, and decreased quality of life. Phytocannabinoids may be a viable supplement to accommodate for deficiencies in the endocannabinoid system. Components of cannabis have an anti inflammatory and antioxidant effect addressing problems on a molecular and cellular level. Responsibly used, cannabis can be given as an antidepressant and for relief of post-traumatic stress disorder, sedative, and anticancer benefits and relief of obsessive behaviors. Benefits extend to symptomatic relief for symptoms like fatigue, poor appetite, depression,anxiety, insomnia, pain, nausea/vomiting, and cognitive changes.

Clinicians will find confidence in educating themselves on the effects of cannabis to support a conversation with patients during office visits. One caveat to widespread adoption by the medical community is that as of 2019, the Department of Justice Drug Enforcement Agency holds that cannabis is a controlled substance with no evidence of medical benefit and high potential of abuse, even with 33 of 50 states and the District of Columbia currently having state-legislated approval to dispense cannabis for medical purposes. Furthermore, the federal government enforces barriers and restrictions on studies investigating the benefits of cannabis due to federal restrictions.104 Regardless of the discordance of laws between federal and state governments, patients are in fact using or interested in using cannabis to manage aspects of their health. Providers should have a working understanding of cannabis and its various effects on the body, including benefits and potential risks. While effects of cannabis on gut barrier function have been studied in pre-clinical models, the translation to humans is uncertain. Evaluation of the gut microbiome in both PWH and HIV transgenic animals exposed to chronic cannabis is necessary to begin to test beneficial effects to correct gut permeability and dysbiosis. The additive effect of probiotics and cannabis may result in synergistic effects in terms of supporting healing of the gut and also the reduction of inflammation, immune activation, and neuropsychiatric disorders within the context of ART.Modern agriculture faces environmental concerns about the use of pesticides. Organic agriculture is an alternative production method that limits the use of synthetic pesticides and fertilizers. The literature has documented that organic crop production does has a lower environmental impact per unit of land than conventional agriculture . However, previous studies often concentrate on a small geographic or crop variety scoop. In essay 1, I use the California Pesticide Use Report database to examine the environmental impacts in conventional and organic crop production at a full scale. It includes all pesticide use in commercial production. I examine the period 1995 to 2015 and find that pesticides used in organic production had smaller negative environmental impacts on surface water, groundwater, soil, air, and pollinators than pesticides used in conventional production.

Over time, this difference has declined. I also investigate how farm size and farming experience are correlated with pesticide use. I find that farmers with more acreage use pesticides that have larger environmental impacts. Specifically, more experienced farmers use pesticides that have greater impact on surface water and groundwater, and less impact on soil, air, and pollinators. The environmental impacts of pesticide use in organic agriculture increased over my study period, which is an interesting observations that requires further investigation. In essay 2, I focus on organic crop production and try to quantify the change in pesticide use. I find that the pesticide portfolio has changed dramatically for organic crop growers, as illustrated by the decline in sulfur use and the increase in spinosad use. Pesticide use is correlated with farm size. The consolidation of organic cropland is another trend documented in essay 2. Historically, ebb and flow flood table consolidation in agriculture as a whole has manifested as an decrease in the number of farms while the total cropland remains stable . In the organic sector, in contrast, both the number of farms and acreage have grown significantly for the last two decades. Nonetheless, consolidation has occurred because the share of large farms in total acreage had increased. In 2015, 56% of organic cropland was operated by growers with at least 500 acres of organic cropland, up from 15% in 1995. At the other end of the spectrum, growers with 10-50 acres accounted for 18% of organic cropland in 1995, which dropped to 8% in 2015. The average organic farm size increased from 46 acres in 1995 to 103 acres in 2015. The median organic farm size increased from 15 to 17 from 1995 to 2015. Farms with larger organic acreage, holding other variables constant, applied sulfur and fixed copper pesticides more frequently than those with smaller acreage. As a result, they had greater impacts on surface water and smaller impacts on soil and air because those ingredients are more toxic to fish and algae, and less toxic to earthworms and have lower Volatile Organic Compound emissions than other ingredients used in organic fields. The composition of organic crop has changed in California with the acreage share of vegetables increasing from 30% in 1995 to 50% in 2015. However, pesticide use patterns and the correlation with farm size do not differ between vegetables and other crops. The consolidation of cropland has not been limited to the organic sector. MacDonald et al. documented that the consolidation of acreage and value of production into a smaller number of larger operations has characterized U.S. agriculture for decades. In essay 3, I adapt and extent the endogenous growth model introduced in Lucas to explain changes in the size distribution of farms and specialization over time. In the theoretical model, farmers have knowledge regarding the production of each crop, and this knowledge grows only through learning from other farmers. Increased knowledge increases the profitability and knowledge can be apply across crops to various degrees. In my modeling framework, the opportunity cost of producing crops that farmers know less about increases as specialized knowledge accumulates, which reduces the number of crops produced by each farmer. The evolution of the farm size distribution in equilibrium and simulation results are presented to demonstrate how model parameters including learning rate, budget share, and elasticity of substitution alter the distribution of farm size and specialization.

The food system has faced concerns about its use of pesticides since even before Rachel Carson published Silent Spring . Today, concerns about environmental impacts from pesticide applications continue to grow . In this context, organic agriculture is proposed as an alternative farming system as it prohibits the use of most synthetic substances . With strict modeling assumptions, Muller et al. presents sim- ulation results that support organic agriculture as an alternative production system capable of providing food for the world population by 2050. Consumers’ perception that organic agriculture is more environmentally friendly has facilitated its growth . According to the Organic Trade Association, U.S. organic food commodity sales reached $39 billion in 2015 in real terms, up from $4 billion in 1997, the base year. The share of organic food sales in total food commodity sales increased from less than 1% to 5% during the same time period . In 2002, the National Organic Program was launched. It established national standards for organic certification and took enforcement actions if there were violations of the standards. Organic growers are prohibited from using certain production practices that have significant negative environmental impacts. However, the regulation of organic agriculture is process-based, not outcome-based, and the regulatory agency does not monitor or enforce standards on environmental outcomes such as biodiversity and soil fertility . Another source of concern comes from the way organic farming practices may change as the sector grows. As pointed out by Läpple and Van Rensburg , late adopters of organic agriculture are more likely to be profit driven and care less about the environment than early adopters. And, the prices of organic products remained at least 20% higher than their conventional counterparts in 2010 , which could encourage additional entry. Therefore, unintended consequences might emerge and organic agriculture could be less environmentally friendly than commonly perceived. There is some evidence of this in the scientific literature. Organic agriculture has been reported to have higher nitrogen leaching and larger nitrous oxide emissions per unit of output than conventional agriculture . Certain pesticide active ingredients used in organic agriculture have been found to be more toxic than conventional AIs in laboratory environments and field experiments . For example, Racke reviewed the discovery and development of spinosad, a natural substance used to control a wide variety of pests, and observed that spinosad was approved based on its low mammalian toxicity. However, Biondi et al. found that spinosad is more harmful to natural predators than pesticides used commonly in conventional agriculture. As the case of spinosad demonstrates, pesticide use in organic agriculture could impose more environmental impact than conventional agriculture in one or more dimensions. Therefore more evidence is needed to evaluate the environmental impact of organic farming practices and its determinants. In this essay, I provide novel evidence regarding the impact of pesticide use in organic and conventional agriculture on different dimensions of environmental quality, and quantify the difference between the environmental impacts of pesticide use in the two production systems in California. In addition, I examine the relationships between farmers’ pesticide-use decisions and their experience and farm size. California is the leading state for organic agriculture in the U.S., accounting for 12% of certified organic cropland and 51% of certified organic crop value nationally in 2016 .