How have cannabis use and related indicators changed since legalization of cannabis for non-medical purposes? Results of the Canadian Cannabis Survey 2018-2022.

Background: Cannabis use for non-medical purposes was legalized and regulated in Canada through the Cannabis Act in October 2018. This paper examined trends in use of cannabis for non-medical purposes and related indicators from pre- to post-legalization in Canada (2018-2022).

Methods: Data from 5 years of the Canadian Cannabis Survey, an annual web-based survey administered to Canadians 16 years of age or older, were used in the analysis (n=12,952; n=11,922; n=10,821; n=10,733; n=10,048).

Evidence That Metal Particles in Cannabis Vape Liquids Limit Measurement Reproducibility.

Cannabis vaping involves the vaporization of a cannabis vaping liquid or solid via a vaping accessory such as a vape pen constructed of various metals or other parts. An increasing number of reports advocate for expansion of the testing and regulation of metal contaminants in cannabis vape liquids beyond the metals typically tested such as arsenic, cadmium, mercury, and lead to reflect the possibility of consumers' exposure to other metal contaminants. Metal contaminants may originate not only from the cannabis itself but also from the vape devices in which the cannabis vape liquid is packaged.

Modulation of type 1 cannabinoid receptor activity by cannabinoid by-products from and non-cannabis phytomolecules.

contains more than 120 cannabinoids and 400 terpene compounds (i.e., phytomolecules) present in varying amounts.

In-situ TD-GCMS measurements of oxidative products of monoterpenes at typical vaping temperatures: implications for inhalation exposure to vaping products.

Vaping is gaining in popularity. However, there is still much that remains unknown about the potential risk and harms of vaping. Formation of oxidative products is one of such areas that are not well understood.

Assessing the bioactivity of cannabis extracts in larval zebrafish.

Background: Whole-plant cannabis extracts are consumed by the public for medical and non-medical ("recreational") purposes but are poorly researched compared to pure cannabinoids. There is emerging evidence that cannabis extracts comprising complex mixtures of cannabinoids may have different biological effects from that of pure cannabinoids. In the current study, we sought to assess the effect of whole-plant cannabis extracts produced from different chemotypes of cannabis on the normal behavior of zebrafish larvae.

Increasing Cannabis Use Is Associated With Poorer Cigarette Smoking Cessation Outcomes: Findings From the ITC Four Country Smoking and Vaping Surveys, 2016-2018.

Introduction: Concurrent use of tobacco and cannabis may impede successful cigarette smoking cessation. This study examined whether changes in cannabis use frequency were associated with smoking cessation.

Aims And Methods: Nationally representative samples of adult cigarette smokers from Canada (n = 1455), the United States (n = 892), England (n = 1416), and Australia (n = 717) were surveyed in 2016 and 2018.

Cannabis and Cannabinoids: Kinetics and Interactions.

Cannabis sativa and related products are widely used, but their potential to cause significant clinical interactions remains unclear, particularly for cannabinoid-enriched or otherwise concentrated products. The pharmacokinetics of most cannabis products is not known. Where information is known, there is wide variation.

The lows of getting high: sentinel surveillance of injuries associated with cannabis and other substance use.

Objectives: Cannabis is a widely used illicit substance that has been associated with acute injuries. This study seeks to provide near real-time injury estimates related to cannabis and other substance use from the electronic Canadian Hospitals Injury Reporting and Prevention Program (eCHIRPP) database.

Methods: Data from the eCHIRPP database, years 2011 to 2016, were analyzed via data mining, descriptive, logistic regression, and sensitivity analyses.

Diacylglycerol kinase ζ regulates RhoA activation via a kinase-independent scaffolding mechanism.

Rho GTPases share a common inhibitor, Rho guanine nucleotide dissociation inhibitor (RhoGDI), which regulates their expression levels, membrane localization, and activation state. The selective dissociation of individual Rho GTPases from RhoGDI ensures appropriate responses to cellular signals, but the underlying mechanisms are unclear. Diacylglycerol kinase ζ (DGKζ), which phosphorylates diacylglycerol to yield phosphatidic acid, selectively dissociates Rac1 by stimulating PAK1-mediated phosphorylation of RhoGDI on Ser-101/174.

Diacylglycerol kinases as sources of phosphatidic acid.

There are ten mammalian diacylglycerol kinases (DGKs) whose primary role is to terminate diacylglycerol (DAG) signaling. However, it is becoming increasingly apparent that DGKs also influence signaling events through their product, phosphatidic acid (PA). They do so in some cases by associating with proteins and then modifying their activity by generating PA.

Diacylglycerol kinase zeta regulates actin cytoskeleton reorganization through dissociation of Rac1 from RhoGDI.

Activation of Rac1 GTPase signaling is stimulated by phosphorylation and release of RhoGDI by the effector p21-activated kinase 1 (PAK1), but it is unclear what initiates this potential feed-forward mechanism for regulation of Rac activity. Phosphatidic acid (PA), which is produced from the lipid second messenger diacylglycerol (DAG) by the action of DAG kinases (DGKs), is known to activate PAK1. Here, we investigated whether PA produced by DGKzeta initiates RhoGDI release and Rac1 activation.

Morphological changes and spatial regulation of diacylglycerol kinase-zeta, syntrophins, and Rac1 during myoblast fusion.

The fusion of mononuclear myoblasts into multinucleated myofibers is essential for the formation and growth of skeletal muscle. Myoblast fusion follows a well-defined sequence of cellular events, from initial recognition and adhesion, to alignment, and finally plasma membrane fusion. These processes depend upon coordinated remodeling of the actin cytoskeleton.

Regulation of neurite outgrowth in N1E-115 cells through PDZ-mediated recruitment of diacylglycerol kinase zeta.

Syntrophins are scaffold proteins that regulate the subcellular localization of diacylglycerol kinase zeta (DGK-zeta), an enzyme that phosphorylates the lipid second-messenger diacylglycerol to yield phosphatidic acid. DGK-zeta and syntrophins are abundantly expressed in neurons of the developing and adult brain, but their function is unclear. Here, we show that they are present in cell bodies, neurites, and growth cones of cultured cortical neurons and differentiated N1E-115 neuroblastoma cells.

Diacylglycerol kinase-zeta localization in skeletal muscle is regulated by phosphorylation and interaction with syntrophins.

Syntrophins are scaffolding proteins that link signaling molecules to dystrophin and the cytoskeleton. We previously reported that syntrophins interact with diacylglycerol kinase-zeta (DGK-zeta), which phosphorylates diacylglycerol to yield phosphatidic acid. Here, we show syntrophins and DGK-zeta form a complex in skeletal muscle whose translocation from the cytosol to the plasma membrane is regulated by protein kinase C-dependent phosphorylation of the DGK-zeta MARCKS domain.

Generation and functional characterization of arylamine N-acetyltransferase Nat1/Nat2 double-knockout mice.

Arylamine N-acetyltransferases (NATs) catalyze the biotransformation of a variety of arylamine drugs and carcinogens and may play diametrically opposing roles in enhancing either the detoxification of these chemicals or their metabolic activation into DNA-binding electrophiles. To facilitate the study of these processes, we have generated a Nat1/Nat2 double-knockout mouse model by gene targeting in embryonic stem cells. Nat1/2(-/-) mice were born at the expected frequency and seemed normal and viable with no overt phenotype, indicating that these genes are not critical for development or physiological homeostasis.