Matthieu Conroy

Bio: Matthieu Conroy is an academic researcher from Colorado State University–Pueblo. The author has contributed to research in topics: Medicine & CYP3A4. The author has an hindex of 2, co-authored 2 publications receiving 30 citations.

Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects.

Abstract: This review aims to present completed clinical trial data surrounding the medicinal benefits and potential side effects of the increasingly popular cannabidiol (CBD)-based drug products, specifically Epidiolex. The article is divided into two sections based on if the ailment being treated by this cannabinoid is classified as either physiological or neurological conditions. In addition to describing the current status, we also examined the different primary and secondary outcomes recorded for each study, which varies greatly depending on the funding source of the clinical trial. With the recent FDA-approval of Epidiolex, this review mainly focused on trials involving this specific formulation since it is the only CBD-based drug currently available to clinicians, although all other clinically trialed CBD(A) drugs were also examined. We hope this review will help guide future research and clinical trials by providing the various outcomes measured in a single review.

Cannabis Contaminants Limit Pharmacological Use of Cannabidiol.

Abstract: For nearly a century, Cannabis has been stigmatized and criminalized across the globe, but in recent years, there has been a growing interest in Cannabis due to the therapeutic potential of phytocannabinoids. With this emerging interest in Cannabis, concerns have arisen about the possible contaminations of hemp with pesticides, heavy metals, microbial pathogens, and carcinogenic compounds during the cultivation, manufacturing, and packaging processes. This is of particular concern for those turning to Cannabis for medicinal purposes, especially those with compromised immune systems. This review aims to provide types of contaminants and examples of Cannabis contamination using case studies that elucidate the medical consequences consumers risk when using adulterated Cannabis products. Thus, it is imperative to develop universal standards for cultivation and testing of products to protect those who consume Cannabis.

Methylene Blue – A Potential Therapeutic Treatment for Sodium Fluoroacetate Poisoning

Abstract: Sodium fluoroacetate (1080) is a toxic metabolic poison with no known antidote. Its use is strictly regulated within the United States, but it is commonly used as a pesticide in Australia, Israel, Japan, Mexico, New Zealand, and South Korea. 1080 has been identified as a possible terrorist weapon, and exposure is extremely difficult to diagnose given its overlapping symptoms with other common diseases. An abandoned U.S. patent indicated that methylene blue (MB) could be used as a potential countermeasure to 1080 poisoning when combined with monosodium glutamate (MSG). In this study, MB was used as a stand‐alone treatment to determine if it is capable of rescuing cellular metabolism or decreasing 1080 lethality.

Metabolic clearance of select opioids and opioid antagonists using hepatic spheroids and recombinant cytochrome P450 enzymes

Abstract: The opioid crisis is a pressing public health issue, exacerbated by the emergence of more potent synthetic opioids, particularly fentanyl and its analogs. While competitive antagonists exist, their efficacy against synthetic opioids is largely unknown. Furthermore, due to the short durations of action of current antagonists, renarcotization remains a concern. In this study, metabolic activity was characterized for fentanyl‐class opioids and common opioid antagonists using multiple in vitro systems, namely, cytochrome P450 (CYP) enzymes and hepatic spheroids, after which an in vitro‐in vivo correlation was applied to convert in vitro metabolic activity to predictive in vivo intrinsic clearance. For all substrates, intrinsic hepatic metabolism was higher than the composite of CYP activities, due to fundamental differences between whole cells and single enzymatic reactions. Of the CYP isozymes investigated, 3A4 yielded the highest absolute and relative metabolism across all substrates, with largely negligible contributions from 2D6 and 2C19. Comparative analysis highlighted elevated lipophilicity and diminished CYP3A4 activity as potential considerations for the development of more efficacious opioid antagonists. Finally, antagonists with a high degree of molecular similarity exhibited comparable clearance, providing a basis for structure‐metabolism relationships. Together, these results provide multiple screening criteria for early stage drug discovery involving opioid countermeasures.

Medical cannabis use in the Australian community following introduction of legal access: the 2018–2019 Online Cross-Sectional Cannabis as Medicine Survey (CAMS-18)

Abstract: In 2016, the Australian federal government passed legislation enabling a range of cannabis-based products to be prescribed to patients by registered healthcare professionals. An online survey conducted immediately prior to these legislative changes found that the vast majority of respondents at the time were illicitly sourcing cannabis plant matter, smoking was the preferred route of administration and mental health, chronic pain, and sleep conditions were the most frequently cited reasons for medical cannabis use. This manuscript reports the results of a follow-up survey conducted in 2018–2019, the Cannabis As Medicine Survey (CAMS-18). The goal of this second questionnaire was to examine patterns of use and consumer perspectives regarding medical cannabis use in Australia, 2 years after the introduction of legal access pathways. Anonymous online cross-sectional survey with convenience sample, recruited mainly through online media between September 2018 and March 2019. Participants were adults (18 years or over) residing in Australia who reported using a cannabis product for self-identified therapeutic reasons during the preceding 12 months. The survey measured consumer characteristics, indications and patterns of medical cannabis use, routes and frequency of administration, perceived benefits and harms, experiences and preferred models of access to medical cannabis. Data were available for 1388 respondents. The main categories of condition being treated with medical cannabis were pain (36.4%), mental health (32.8%), sleep (9.2%), neurological (5.2%) and cancer (3.8%). Respondents reported using medical cannabis on 15.8 (11.2) days in the past 28, by inhaled (71.4%) or oral (26.5%) routes and spending AUD$82.27 ($101.27) per week. There were high levels of self-reported effectiveness, but also high rates of side effects. There was uncertainty regarding the composition of illicit cannabinoid products and concerns regarding their possible contamination. Few respondents (2.7%) had accessed legally prescribed medical cannabis, with the main perceived barriers being cost, disinterest from the medical profession and stigma regarding cannabis use. Chronic pain, mental health and sleep remain the main clinical conditions for which consumers report using medical cannabis. Despite 2 years of legal availability, most consumers in Australia reported accessing illicit cannabis products, with uncertainty regarding the quality or composition of cannabis products.

Planning of urban green spaces: An ecological perspective on human benefits

Abstract: In the context of urban land-use growth and the consequent impacts on the environment, green spaces provide ecosystem services for human health. The ecosystem services concept synthesises human–environmental interactions through a series of combined components of biodiversity and abiotic elements, linking ecological processes and functions. The concept of green infrastructure (GI) in the urban context emphasises the quality and quantity of urban and peri-urban green spaces and natural areas. In dense urban contexts, the applications of GI are limited and not applied to the potential urban spaces such as roofs and gardens. Often, roofs are characterised by impermeable paved surfaces with negative effects on human well-being, whereas garden designs do not consider social needs and environmental interactions. The role of urban stressors or the urban context as a driving force or pressure of urban green space is not always well understood and employed in the planning of green spaces. This is partly due to a knowledge gap between different science disciplines that operate on different scales, from single processes of the plants (which focus on plant responses to environmental stresses affecting human well-being) to urban ecosystems (which focus on the biodiversity and urban space planning–human well-being relationship). This can create a paradox, as green spaces that are not adequately designed might not produce the expected effects. In this paper, an overview of benefits and limitations of applying the ecosystem services approach when designing green spaces is presented. The focus is on the main urban ecosystem services provided by green roofs and community gardens such as GI that can represent strategies to provide ecological and social multifunctionality to waterproofed surfaces connected to the buildings and low-exploited gardens being the main areas that affect dense urban settlements, and thus, increasing the ecosystem services in the urban environment, such as reducing the Urban Heat Island, as well as flooding events. Specifically, the paper highlights (i) feedback between ecological processes and functions that support ecosystem services, (ii) urban environmental stresses in relation to disservices that these can create for human well-being and (iii) key issues that should be considered in the planning and design of urban ecosystem services. Such a new vision of urban ecosystem services highlights the need to look at GI as an active part of the urban space design in the built environment.

Content versus Label Claims in Cannabidiol (CBD)-Containing Products Obtained from Commercial Outlets in the State of Mississippi.

Abstract: Products containing cannabidiol (CBD) are now available throughout the United States, but their quality is oftentimes questionable. The CBD and Δ9-tetrahydrocannabinol (THC) content of 25 commercia...

Cannabis Contaminants Limit Pharmacological Use of Cannabidiol.

Abstract: For nearly a century, Cannabis has been stigmatized and criminalized across the globe, but in recent years, there has been a growing interest in Cannabis due to the therapeutic potential of phytocannabinoids. With this emerging interest in Cannabis, concerns have arisen about the possible contaminations of hemp with pesticides, heavy metals, microbial pathogens, and carcinogenic compounds during the cultivation, manufacturing, and packaging processes. This is of particular concern for those turning to Cannabis for medicinal purposes, especially those with compromised immune systems. This review aims to provide types of contaminants and examples of Cannabis contamination using case studies that elucidate the medical consequences consumers risk when using adulterated Cannabis products. Thus, it is imperative to develop universal standards for cultivation and testing of products to protect those who consume Cannabis.

Fish Oil, Cannabidiol and the Gut Microbiota: An Investigation in a Murine Model of Colitis.

Abstract: In experimental colitis, administration of fish oil (FO) and the non-psychoactive cannabinoid, cannabidiol (CBD) reduces inflammation and ameliorates behavioural disturbances, two conditions associated with alterations in the gut microbiota (dysbiosis). We investigated the effect of combined FO/CBD administration on inflammation and dysbiosis in the dextran sulphate sodium (DSS) model of mouse colitis, which also causes behavioural disturbances. Colitis was induced in CD1 mice by 4% w/v DSS in drinking water for five consecutive days followed by normal drinking water. FO (20-75 mg/mouse) was administered once a day starting two days after DSS, whereas CBD (0.3-30 mg/kg), alone or after FO administration, was administered once a day starting three days after DSS, until day 8 (d8) or day 14 (d14). Inflammation was assessed at d8 and d14 (resolution phase) by measuring the Disease Activity Index (DAI) score, change in body weight, colon weight/length ratio, myeloperoxidase activity and colonic interleukin (IL)-1β (IL-1β), IL-10 and IL-6 concentrations. Intestinal permeability was measured with the fluorescein isothiocyanate-dextran. Behavioral tests (novel object recognition (NOR) and light/dark box test) were performed at d8. Fecal microbiota composition was determined by ribosomal 16S DNA sequencing of faecal pellets at d8 and d14. DSS-induced inflammation was stronger at d8 and accompanied by anxiety-like behaviour and impaired recognition memory at d8. FO (35, 50, 75 mg/mouse) alone reduced inflammation at d8, whereas CBD alone produced no effect at any of the doses tested; however, when CBD (3,10 mg/kg) was co-administered with FO (75 mg/mouse) inflammation was attenuated. FO (20 mg/mouse) and CBD (1 mg/kg) were ineffective when given alone, but when co-administered reduced all inflammatory markers and the impaired intestinal permeability at both d8 and d14 (but not the behavioural impairments). FO, CBD and their combination affected gut bacteria taxa that were not affected by DSS per se. Akkermansia muciniphila, a species suggested to afford anti-inflammatory action in colitis, was increased by DSS only at d14, but its levels were significantly elevated by all treatments at d8. FO and CBD co-administered at ineffective doses reduce colon inflammation, in a manner potentially strengthened by their independent elevation of Akkermansia muciniphila at d8.