Article
Chemistry, Analytical
Hongyi Zhang, Jiajie Luo, Zhen Qiao, Baoshuai An, Ningning Wei, Yanru Zhang
Summary: Diacylglycerol lipase (DAGL) is an important biosynthetic enzyme involved in various biological processes. However, the lack of an effective method to detect DAGL activity has hindered our understanding of its role in neurophysiological and pathological processes. In this study, a novel activatable fluorescence probe was designed to detect DAGL activity, and its application in studying changes in DAGL activity after brain injury was demonstrated.
SENSORS AND ACTUATORS B-CHEMICAL
(2022)
Article
Biochemistry & Molecular Biology
Berend Gagestein, Anna F. Stevens, Domenico Fazio, Bogdan Florea, Tom van der Wel, Alexander T. Bakker, Filomena Fezza, Hans den Dulk, Herman S. Overkleeft, Mauro Maccarrone, Mario van der Stelt
Summary: A study found that WOBE437 can inhibit the uptake of a specific signaling lipid in the brain, but unlike the commonly used inhibitor OMMD-1, WOBE437 actually increases the uptake of the signaling lipid in cells. Further research also identified three proteins, SCCPDH, VAT1, and FECH, that interact with WOBE437 in neuronal cells.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jiangyinzi Shang, Sophie Hines, Meagan J. Makarczyk, Hang Lin, MaCalus V. Hogan, Alan Yan
Summary: Studies on human chondrocytes indicate that the effects of marijuana derivatives on normal cartilage are concentration-dependent, with potential protective effects on cartilage degradation associated with osteoarthritis. However, further research is needed to understand the extent of these effects.
Review
Medicine, General & Internal
Klaudia Berk, Wiktor Bzdega, Karolina Konstantynowicz-Nowicka, Tomasz Charytoniuk, Hubert Zywno, Adrian Chabowski
Summary: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in adults in developed countries, with a global prevalence reaching one billion. The endocannabinoid system (ECS) plays a significant role in NAFLD development, but the effects and impacts of plant-derived cannabinoids in NAFLD pathophysiology still require further understanding.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Family Studies
Kerry A. Lee, Sharon Rose Priestley, Kevin K. Hylton
Summary: This study highlights the importance of addressing adverse childhood experiences to disrupt the sequalae of negative mental and behavioral outcomes.
CHILDREN AND YOUTH SERVICES REVIEW
(2022)
Article
Psychology, Clinical
Natania A. Crane, Scott A. Langenecker, Robin J. Mermelstein
Summary: The study found that depression, anxiety, negative mood regulation expectancies, and lower GPA were associated with increased poly-substance use over time. Interaction effects of gender and developmental stage moderated these relationships, highlighting the importance of early identification and treatment of mental health issues and academic struggles in preventing substance use among youth.
ADDICTIVE BEHAVIORS
(2021)
Article
Pharmacology & Pharmacy
Michaela Dvorakova, Agnieszka Kubik-Zahorodna, Alex Straiker, Radislav Sedlacek, Alena Hajkova, Ken Mackie, Jaroslav Blahos
Summary: SGIP1 interacts with CB1 receptors and may modulate affect, anxiety, pain processing, and other physiological processes. SGIP1(-/-) mice show decreased anxiety-like behaviors and increased sensitivity to nociception/analgesics in behavioral tests.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Clinical Neurology
Zitong Wang, Rebekah van Bruggen, Thaisa Sandini, Ethan Hagen, Xin-Min Li, Yanbo Zhang
Summary: The interaction of social, psychological, and biological stresses can lead to mental health conditions such as major depressive disorder (MDD), adjustment disorder, and posttraumatic stress disorder (PTSD). The endocannabinoid system (ECS), consisting of endocannabinoids and cannabinoid receptors, plays a crucial role in responding to stress stimuli. This study examined the impact of the ECS on chronic social instability stress (SIS) and found that both stressed Wistar (WIS) rats and endogenously depressed Wistar-Kyoto (WKY) rats exhibited similar behavioral changes in anxiety, behavioral despair, and cognitive impairment, with WKY rats showing higher resilience in cortisol (CORT) modulation towards chronic SIS.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2023)
Article
Pharmacology & Pharmacy
Lesley D. O'Brien, Terry L. Smith, Giulia Donvito, Benjamin F. Cravatt, Jason Newton, Sarah Spiegel, Thomas M. Reeves, Linda L. Phillips, Aron H. Lichtman
Summary: The research reveals that DAGL-beta is not essential for TBI-induced cognitive and neurological functions, but it does have an impact on the vulnerability of male mice to TBI-induced mortality, while female mice show high survival rates regardless of DAGL-beta expression.
CANNABIS AND CANNABINOID RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Rafie Belali, Seyyed Ali Mard, Seyed Esmaeil Khoshnam, Kowsar Bavarsad, Alireza Sarkaki, Yaghoob Farbood
Summary: In this study, the anti-anxiety and anti-depressant effects of the endocannabinoid anandamide (AEA) were investigated in a chronic sleep deprivation (SD) model in rats. AEA administration showed anxiolytic-like effects by increasing the time spent, distance traveled, and climbing behavior in the open-field test, and also modulated CB1R mRNA expression, cortical EEG, and inflammatory response. However, it did not exhibit anti-depressant effects in the forced swimming test.
NEUROCHEMICAL RESEARCH
(2023)
Article
Surgery
Sharven Taghavi, Saul Ramirez, Juan Duchesne, Danielle Tatum
Summary: Although preinjury use of marijuana does not improve survival in trauma patients, it may provide some improvement in outcomes in patients with traumatic brain injury and those that are more severely injured (Injury Severity Score >16). This finding provides valuable insights for future research.
JOURNAL OF SURGICAL RESEARCH
(2021)
Article
Obstetrics & Gynecology
Noga Fuchs Weizman, Brandon A. Wyse, Peter Szaraz, Miranda Defer, Sahar Jahangiri, Clifford L. Librach
Summary: Exposure to phytocannabinoids increases endocannabinoid receptor expression, reduces DNA methylation enzyme expression, and decreases global DNA methylation in granulosa cells.
HUMAN REPRODUCTION
(2021)
Review
Biochemistry & Molecular Biology
Henry Lowe, Ngeh Toyang, Blair Steele, Joseph Bryant, Wilfred Ngwa
Summary: The Endocannabinoid System (ECS) plays a crucial role in maintaining internal balance in biological systems and is implicated in various diseases. In recent years, there has been significant interest in manipulating the ECS for medical purposes, offering promising opportunities for developing novel cannabinoid-based therapeutic drugs for the treatment of a range of diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Food Science & Technology
Xiaoxue Sun, Shuo Zou, Xiaodong Xie, Yong Wang, Zhen Zhang
Summary: Lecitase & REG; Ultra (LU) was immobilized on a macroporous resin by adsorption and characterized. The obtained immobilized lipase LXTE-1000-LU was used in the preparation of diacylglycerol (DAG), and the catalytic stability during glycerolysis was investigated. An immobilization efficiency (IE) of 89.98% was achieved at pH 7.0, with a resin amount of 2.5 g and an adsorption time of 2 h. After storage for 60 days at 4 degrees C and 25 degrees C, the lipase activity remained over 85% compared to the initial state. Furthermore, the glycerolysis reaction using LXTE-1000-LU as the catalyst yielded 41.31% flaxseed oil-based DAG. However, prolonged reaction led to a decrease in lipase protein content and changes in the protein's secondary confirmation, resulting in reduced catalytic activity.
LWT-FOOD SCIENCE AND TECHNOLOGY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Thomas P. Sakmar
Summary: This study reveals that the increased cardiovascular risks associated with cannabis use are caused by proinflammatory signaling of the cannabinoid 1 (CB1) receptor, which can be alleviated by the natural antioxidant genistein.
Article
Chemistry, Analytical
Zheng Ao, Hongwei Cai, Zhuhao Wu, Jonathan Krzesniak, Chunhui Tian, Yvonne Y. Lai, Ken Mackie, Feng Guo
Summary: The study introduces a human spinal organoid-on-a-chip device for modeling the biology and electrophysiology of human nociceptive neurons and dorsal horn interneurons. The device allows for testing nociceptive modulators and is cost-efficient, scalable, and easy to use. By integrating human sensory-spinal-cord organoids, the method shows promise for screening and validating novel therapeutics for human pain medicine discovery.
ANALYTICAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Ming Tatt Lee, Ken Mackie, Lih-Chu Chiou
Summary: This review explores the potential and contributions of activating the endocannabinoid system and peripheral neuromodulation in opioid tolerance.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Lawrence M. Carey, Zhili Xu, Gabriela Rajic, Alexandros Makriyannis, Julian Romero, Cecilia Hillard, Ken Mackie, Andrea G. Hohmann
Summary: This study suggests that CB2 activation may alleviate HIV-associated antiretroviral neuropathy and identifies a previously unreported mechanism through which CB2 activation produces antinociceptive efficacy. The study also demonstrates that a CB2 agonist can reverse established morphine tolerance and shows that CB2 localized to peripheral sensory neurons mediates the opioid tolerance sparing efficacy of CB2 agonists.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Toni Kline, Cong Xu, Faith R. Kreitzer, Dow P. Hurst, Khalil M. Eldeeb, Jim Wager-Miller, Kathleen Olivas, Seon A. Hepburn, John W. Huffman, Ken Mackie, Allyn C. Howlett, Patricia Reggio, Nephi Stella
Summary: The author synthesized fourteen novel alkylindole analogues and evaluated their activities at alkylindole-sensitive GPCRs. They found three characteristics that favor binding to alkylindole-sensitive GPCRs versus CB1R/CB2R and identified novel chemical tools for studying alkylindole-sensitive GPCRs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Toxicology
Jinhwan Lim, Hye-Lim Lee, Julie Nguyen, Joyce Shin, Samantha Getze, Caitlin Quach, Erica Squire, Kwang-Mook Jung, Stephen Mahler, Ken Mackie, Daniele Piomelli, Ulrike Luderer
Summary: Adolescent exposure to THC may cause aberrant activation of the ovarian endocannabinoid system in female mice, resulting in substantial loss of ovarian reserve in adulthood. Further investigation is needed to understand the relevance of these findings to women who frequently used cannabis during adolescence.
TOXICOLOGICAL SCIENCES
(2023)
Article
Engineering, Biomedical
Hongwei Cai, Zheng Ao, Chunhui Tian, Zhuhao Wu, Connor Kaurich, Zi Chen, Mingxia Gu, Andrea G. Hohmann, Ken Mackie, Feng Guo
Summary: Opioids may induce tolerance and hyperalgesia, but the human mechanisms underlying these effects are not well understood. Researchers have developed a novel human spinal microphysiological system (MPS) to model human nociception and opioid-induced tolerance. This system shows promising potential for studying pain etiology, screening new treatments, and validating novel therapeutics for human pain medicine.
BIOACTIVE MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Jonah E. Zarrow, Abdul-Musawwir Alli-Oluwafuyi, Cristina M. Youwakim, Kwangho Kim, Andrew N. Jenkins, Isabelle C. Suero, Margaret R. Jones, Zahra Mashhadi, Ken Mackie, Alex G. Waterson, Amanda C. Doran, Gary A. Sulikowski, Sean S. Davies
Summary: N-Acyl-phosphatidylethanolamine hydrolyzing phospholipase D (NAPE-PLD) is an enzyme that hydrolyzes N-acyl-phosphatidylethanolamines (NAPEs) to produce N-acyl-ethanolamines (NAEs) and phosphatidic acid. Reduced NAPE-PLD activity is associated with cardiometabolic diseases, and small molecule activators of NAPE-PLD could be a potential therapeutic treatment. A series of benzothiazole phenylsulfonyl-piperidine carboxamides were identified as NAPE-PLD activators, which increased efferocytosis by macrophages. These findings suggest the importance of NAPE-PLD in regulating efferocytosis and the potential use of NAPE-PLD activators for treating cardiometabolic diseases.
ACS CHEMICAL BIOLOGY
(2023)
Article
Neurosciences
Kelsey G. Guenther, Zhili Xu, Julian Romero, Cecilia J. Hillard, Ken Mackie, Andrea G. Hohmann
Summary: CB2 agonists can suppress pathological pain in animal models without unwanted side effects associated with CB1 receptor activation. However, the specific types of pain responsive to CB2 agonists and the cell types underlying therapeutic efficacy are not fully understood.
Article
Pharmacology & Pharmacy
Axel Bernabeu, Anissa Bara, Michelle N. Murphy Green, Antonia Manduca, Jim Wager-Miller, Milene Borsoi, Olivier Lassalle, Anne-Laure Pelissier-Alicot, Pascale Chavis, Ken Mackie, Olivier J. J. Manzoni
Summary: This study reveals sex differences in the maturational trajectories of the rat prefrontal cortex (PFC). The excitability of PFC neurons is lower in adult females compared to other developmental stages. The gene expression of the endocannabinoid/vanilloid systems is sequential and sex-specific.
CANNABIS AND CANNABINOID RESEARCH
(2023)
Correction
Clinical Neurology
Mei Hu, Dexiao Zhu, Jian Zhang, Fei Gao, Jack Hashem, Philip Kingsley, Lawrence J. Marnett, Ken Mackie, Chu Chen
Article
Pharmacology & Pharmacy
Pedro Henrique Gobira, Jacob LaMar, Jade Marques, Ariandra Sartim, Kennia Silveira, Luana Santos, Gregers Wegener, Francisco S. Guimaraes, Ken Mackie, Hui-Chen Lu, Samia Joca
Summary: This study investigates the involvement of cannabinoid type 1 receptors (CB1R) in the antidepressant and psychostimulant effects induced by ketamine. The results suggest that CB1R mediate the psychostimulant side effects of ketamine, but do not play a role in its antidepressant properties. Furthermore, pharmacological blockade of CB1R has similar antidepressant effects, but does not potentiate the effects of ketamine.
CANNABIS AND CANNABINOID RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Joanna Winstone, Hana Shafique, Madeleine E. Clemmer, Ken Mackie, Jim Wager-Miller
Summary: This study found changes in BDNF mRNA expression in the hippocampus of adolescent mice exposed to THC and CBD. THC represses transcript expression for some BDNF variants, and this effect is rescued when CBD is co-administered. Sex differences were observed in specific BDNF isoforms.
CANNABIS AND CANNABINOID RESEARCH
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Joshua L. Rein, Ken Mackie, Thomas R. Kleyman, Lisa M. Satlin
Article
Clinical Neurology
Mei Hu, Dexiao Zhu, Jian Zhang, Fei Gao, Jack Hashem, Philip Kingsley, Lawrence J. Marnett, Ken Mackie, Chu Chen
Summary: Traumatic brain injury is a risk factor for Alzheimer's disease and dementia. In this study, the researchers found that inhibiting monoacylglycerol lipase can reduce neuropathology caused by traumatic brain injury. The neuroprotective effects are mainly due to the inhibition of 2-arachidonoylglycerol metabolism in astrocytes, and not in neurons.
Article
Pharmacology & Pharmacy
Izaque de Sousa Maciel, Gabriel H. D. de Abreu, Claire T. Johnson, Rida Bonday, Heather B. Bradshaw, Ken Mackie, Hui-Chen Lu
Summary: The study using mice found that perinatal cannabinoid exposure affects behaviors in a sex-dependent manner, altering repetitive and hedonic behaviors. Additionally, perinatal exposure to THC or CBD prevents fluoxetine from enhancing coping behavior.
CANNABIS AND CANNABINOID RESEARCH
(2022)