Publications by authors named "David W Pate"

6 Publications

  • Page 1 of 1

Phytocannabinoid drug-drug interactions and their clinical implications.

Pharmacol Ther 2020 11 30;215:107621. Epub 2020 Jun 30.

Faculty of Pharmacy & Pharmaceutical Sciences, Katz Centre for Pharmacy & Health Research, University of Alberta, Edmonton, Alberta T6G 2E1, Canada. Electronic address:

Cannabis is a plant with a long history of human pharmacological use, both for recreational purposes and as a medicinal remedy. Many potential modern medical applications for cannabis have been proposed and are currently under investigation. However, its rich chemical content implies many possible physiological actions. As the use of medicinal cannabis has gained significant attention over the past few years, it is very important to understand phytocannabinoid dispositions within the human body, and especially their metabolic pathways. Even though the complex metabolism of phytocannabinoids poses many challenges, a more thorough understanding generates many opportunities, especially regarding possible drug-drug interactions (DDIs). Within this context, computer simulations are most commonly used for predicting substrates and inhibitors of metabolic enzymes. These predictions can assist to identify metabolic pathways by understanding individual CYP isoform specificities to a given molecule, which can help to predict potential enzyme inhibitions and DDIs. The reported in vivo Phase I and Phase II metabolisms of various phytocannabinoids are herein reviewed, accompanied by a parallel in silico analysis of their predicted metabolism, highlighting the clinical importance of such understanding in terms of DDIs and clinical outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pharmthera.2020.107621DOI Listing
November 2020

Cannabis Use, a Self-Management Strategy Among Australian Women With Endometriosis: Results From a National Online Survey.

J Obstet Gynaecol Can 2020 Mar 10;42(3):256-261. Epub 2019 Nov 10.

NICM Health Research Institute, Western Sydney University, Penrith, Australia; Translational Health Research Institute, Western Sydney University, Penrith, Australia. Electronic address:

Objective: This study sought to determine the prevalence, tolerability, and self-reported effectiveness of cannabis in women with endometriosis.

Methods: A cross-sectional online survey was conducted between October and December 2017. Recruitment targeted women with endometriosis through social media postings from endometriosis advocacy groups. Women aged 18 to 45, living in Australia, and with surgically confirmed endometriosis were eligible to participate. Survey questions investigated the types of self-management used, change in symptoms or medication use, costs, and adverse events.

Results: A total of 484 responses were included for analysis, with 76% of the women reporting the use of general self-management strategies within the last 6 months. Of those using self-management, 13% reported using cannabis for symptom management. Self-reported effectiveness in pain reduction was high (7.6 of 10), with 56% also able to reduce pharmaceutical medications by at least half. Women reported the greatest improvements in sleep and in nausea and vomiting. Adverse effects were infrequent (10%) and minor.

Conclusion: Australian law currently requires legal medicinal cannabis use to follow specific, regulated pathways that limit prescription by this method; however, self-reported illicit use of cannabis remains relatively common in Australian women with endometriosis. Women report good efficacy of cannabis in reducing pain and other symptoms, with few adverse effects reported. Further clinical research is warranted to determine the effectiveness of cannabis in managing endometriosis symptoms. In locations where medicinal cannabis is more accessible, there remains a paucity of evidence for its clinical efficacy with endometriosis-associated symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jogc.2019.08.033DOI Listing
March 2020

LC-MS/MS quantitation of phytocannabinoids and their metabolites in biological matrices.

Talanta 2019 Nov 13;204:846-867. Epub 2019 Jun 13.

Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada. Electronic address:

Marijuana (i.e., cannabis) and its derivatives are considered the most commonly used of illicit drugs. Within the last two decades, phytocannabinoids and their synthetic analogues have emerged as potential medicines for the treatment of various disorders via targeting of the endocannabinoid system. Recently, some countries have legalized (medicinal/recreational) cannabis, which now allows for more research to be conducted. Accordingly, sensitive and specific analytical assays are required to identify and quantify these compounds in different human matrices. These analytical approaches were developed using mass spectrometric detection, where LC-MS/MS specifically has become the mainstay for the quantitative analysis of tetrahydrocannabinol and other cannabinoids. This is due to its superior selectivity and sensitivity, and ability to determine free and conjugate analytes within the same analysis. This tabular review of such methods is prefaced by a short overview of the major cannabinoids and some of their physiological actions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.talanta.2019.06.053DOI Listing
November 2019

Anandamide prodrugs. 1. Water-soluble phosphate esters of arachidonylethanolamide and R-methanandamide.

Eur J Pharm Sci 2003 May;19(1):37-43

Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, FIN-70211, Kuopio, Finland

Phosphate esters of arachidonylethanolamide (AEA) and R-methanandamide were synthesized and evaluated as water-soluble prodrugs. Various physicochemical properties (pK(a), partition coefficient, aqueous solubility) were determined for the synthesized phosphate esters. The chemical stability of phosphate esters was determined at pH 7.4. In vitro enzymatic hydrolysis rates were determined in 10% liver homogenate, and in a pure enzyme-containing (alkaline phosphatase) solution at pH 7.4. The intraocular pressure (IOP) lowering properties of R-methanandamide phosphate ester were tested on normotensive rabbits. The phosphate promoiety increased the aqueous solubility of the parent compounds by more than 16500-fold at pH 7.4. Phosphate esters were stable in buffer solutions, but rapidly hydrolyzed to their parent compounds in alkaline phosphatase solution (t(1/2)<<15 s) and liver homogenate (t(1/2)=8-9 min). The phosphate ester of R-methanandamide reduced IOP in rabbits. These results indicate that the phosphate esters of AEA and R-methanandamide are useful water-soluble prodrugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0928-0987(03)00044-7DOI Listing
May 2003

Cannabinoids in the treatment of glaucoma.

Pharmacol Ther 2002 Aug;95(2):203-20

Department of Pharmaceutical Chemistry, University of Kuopio, Finland.

The leading cause of irreversible blindness is glaucoma, a disease normally characterized by the development of ocular hypertension and consequent damage to the optic nerve at its point of retinal attachment. This results in a narrowing of the visual field, and eventually results in blindness. A number of drugs are available to lower intraocular pressure (IOP), but, occasionally, they are ineffective or have intolerable side-effects for some patients and can lose efficacy with chronic administration. The smoking of marijuana has decreased IOP in glaucoma patients. Cannabinoid drugs, therefore, are thought to have significant potential for pharmaceutical development. However, as the mechanism surrounding their effect on IOP initially was thought to involve the CNS, issues of psychoactivity hindered progress. The discovery of ocular cannabinoid receptors implied an explanation for the induction of hypotension by topical cannabinoid applications, and has stimulated a new phase of ophthalmic cannabinoid research. Featured within these investigations is the possibility that at least some cannabinoids may ameliorate optic neuronal damage through suppression of N-methyl-D-aspartate receptor hyperexcitability, stimulation of neural microcirculation, and the suppression of both apoptosis and damaging free radical reactions, among other mechanisms. Separation of therapeutic actions from side-effects now seems possible through a diverse array of novel chemical, pharmacological, and formulation strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0163-7258(02)00259-0DOI Listing
August 2002

Effect of the enzyme inhibitor, phenylmethylsulfonyl fluoride, on the IOP profiles of topical anandamides.

Invest Ophthalmol Vis Sci 2002 Feb;43(2):393-7

Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland.

Purpose: Earlier studies have suggested that the intraocular pressure (IOP) effects of topical arachidonylethanolamide (AEA) are mediated through its fatty acid metabolite, rather than through AEA, per se. The purpose of this study was to investigate whether the topical anandamides AEA and arachidonyl propionitrileamide (APN) decrease IOP when their enzymatic degradation is prevented by phenylmethylsulfonyl fluoride (PMSF) and whether the neuronal cannabinoid (CB1) receptor mediates the IOP responses of an undegraded AEA, through the use of its specific antagonist SR141716A.

Methods: AEA or APN were each formulated in aqueous 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) solutions and administered unilaterally to the rabbit eye (dose, 62.5 microg per rabbit). To prevent the degradation of AEA or APN, the rabbits were pretreated with a subcutaneous (SC) PMSF injection (0.22-22 mg/kg) 30 minutes before eye drop instillation. To determine whether the neuronal cannabinoid (CB1) receptor mediates the hypotensive IOP effects of undegraded AEA, the rabbits were pretreated with simultaneous SC injections of a CB1 receptor antagonist SR141716A (1.2-2.1 mg/kg) and PMSF (2.2 mg/kg) before the ocularly applied AEA.

Results: In the absence of PMSF, the IOP profiles of AEA and APN showed a biphasic ocular effect--that is, an initial increase of IOP followed by IOP hypotension in the treated eye. In the presence of PMSF (2.2 mg/kg for AEA and 22 mg/kg for APN), IOP profiles showed immediate IOP reduction in the treated eye. SR141716A antagonized the IOP reduction caused by the undegraded AEA.

Conclusions: These results indicate that the apparently undegraded AEA and APN decrease IOP in normotensive rabbits. AEA-induced IOP reduction in the presence of PMSF is probably mediated through a CB1 receptor.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2002
-->