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Article ; Online: Role of Cannabinoid Signaling in Cardiovascular Function and Ischemic Injury.

Rorabaugh, Boyd R / Guindon, Josée / Morgan, Daniel J

The Journal of pharmacology and experimental therapeutics

2023 Volume 387, Issue 3, Page(s) 265–276

Abstract: Cardiovascular disease represents a leading cause of death, morbidity, and societal economic burden. The prevalence of cannabis use has significantly increased due to legalization and an increased societal acceptance of cannabis. Therefore, it is ... ...

Abstract	Cardiovascular disease represents a leading cause of death, morbidity, and societal economic burden. The prevalence of cannabis use has significantly increased due to legalization and an increased societal acceptance of cannabis. Therefore, it is critically important that we gain a greater understanding of the effects and risks of cannabinoid use on cardiovascular diseases as well as the potential for cannabinoid-directed drugs to be used as therapeutics for the treatment of cardiovascular disease. This review summarizes our current understanding of the role of cannabinoid receptors in the pathophysiology of atherosclerosis and myocardial ischemia and explores their use as therapeutic targets in the treatment of ischemic heart disease. Endocannabinoids are elevated in patients with atherosclerosis, and activation of cannabinoid type 1 receptors (CB
MeSH term(s)	Humans ; Cannabinoids/pharmacology ; Cannabinoids/therapeutic use ; Endocannabinoids/therapeutic use ; Cannabinoid Receptor Agonists/therapeutic use ; Receptors, Cannabinoid ; Myocardial Infarction/drug therapy ; Atherosclerosis/drug therapy
Chemical Substances	Cannabinoids ; Endocannabinoids ; Cannabinoid Receptor Agonists ; Receptors, Cannabinoid
Language	English
Publishing date	2023-09-22
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	3106-9
ISSN	1521-0103 ; 0022-3565
ISSN (online)	1521-0103
ISSN	0022-3565
DOI	10.1124/jpet.123.001665
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Article ; Online: A novel inhibitor of endocannabinoid catabolic enzymes sheds light on behind the scene interplay between chronic pain, analgesic tolerance, and heroin dependence.

Guindon, Josée

Neuropharmacology

2016 Volume 114, Page(s) 168–171

Abstract: From the Aristotelian ancient Greece, pain has been associated with appetites or emotions and is opposite to pleasure. Reward and addiction is also linked to pleasure and compulsive drug seeking reinstates pleasure. Alleviation of chronic pain can induce ...

Abstract	From the Aristotelian ancient Greece, pain has been associated with appetites or emotions and is opposite to pleasure. Reward and addiction is also linked to pleasure and compulsive drug seeking reinstates pleasure. Alleviation of chronic pain can induce a euphoric phase similar to what is found in addiction. Both chronic pain and addiction are recognized as a disease of the central nervous system. They share many characteristics and brain regions/mechanisms. Evidence points to the usefulness of cannabinoids as a new class of agents to add to the pharmaceutical toolbox in the management of chronic pain. Wilkerson and colleagues, in this issue, examine SA-57, an inhibitor of two different endocannabinoid catabolic enzymes FAAH and MAGL, demonstrating its analgesic effectiveness and morphine-sparing properties in a chronic pain model, as well as its ability to reduce heroin seeking behavior in a self-administration paradigm in mice. This timely study emphasizes the need for development of more efficacious chronic pain therapeutics with minimized abuse potential and/or reinforcing properties. It also highlights the need for better understanding of the overlapping circuitry of chronic pain, reward, and addiction.
MeSH term(s)	Amidohydrolases ; Analgesics ; Animals ; Chronic Pain ; Endocannabinoids ; Heroin Dependence ; Mice ; Monoacylglycerol Lipases ; Piperidines
Chemical Substances	Analgesics ; Endocannabinoids ; Piperidines ; Monoacylglycerol Lipases (EC 3.1.1.23) ; Amidohydrolases (EC 3.5.-)
Language	English
Publishing date	2016-11-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2016.11.018
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Article ; Online: Role of sex hormones in modulating breast and ovarian cancer associated pain.

McHann, Melissa C / Blanton, Henry L / Guindon, Josée

Molecular and cellular endocrinology

2021 Volume 533, Page(s) 111320

Abstract: According to the National Cancer Institute in 2020 there will be an estimated 21,750 new ovarian cancer cases and 276,480 new breast cancer cases. Both breast and ovarian cancer are hormone dependent cancers, meaning they cannot grow without the presence ...

Abstract	According to the National Cancer Institute in 2020 there will be an estimated 21,750 new ovarian cancer cases and 276,480 new breast cancer cases. Both breast and ovarian cancer are hormone dependent cancers, meaning they cannot grow without the presence of hormones. The two most studied hormones in these two cancers are estrogen and progesterone, which are also involved in the modulation of pain. The incidence of pain in breast and ovarian cancer is very high. Research about mechanisms involved in modulation of pain by hormones are still being debated, as some studies find estrogen to be anti-nociceptive and others pro-nociceptive in pain studies. Moreover, analgesic treatments for breast and ovarian cancer-associated pain are limited and often ineffective. In this review, we will focus on estrogen and progesterone mechanisms of action in modulation of pain and cancer. We will also discuss new treatment options for these types of cancer and associated-pain.
MeSH term(s)	Analgesics/therapeutic use ; Breast Neoplasms/complications ; Breast Neoplasms/metabolism ; Cancer Pain/drug therapy ; Cancer Pain/epidemiology ; Cancer Pain/metabolism ; Estrogens/metabolism ; Female ; Humans ; Incidence ; Molecular Targeted Therapy ; Ovarian Neoplasms/complications ; Ovarian Neoplasms/metabolism ; Progesterone/metabolism
Chemical Substances	Analgesics ; Estrogens ; Progesterone (4G7DS2Q64Y)
Language	English
Publishing date	2021-05-24
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	187438-x
ISSN	1872-8057 ; 0303-7207
ISSN (online)	1872-8057
ISSN	0303-7207
DOI	10.1016/j.mce.2021.111320
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Article ; Online: Nabilone in inflammatory pain: to be or not to be.

Guindon, Josée

Clinical and experimental pharmacology & physiology

2012 Volume 39, Issue 4, Page(s) 327–328

MeSH term(s)	Capsaicin/toxicity ; Central Nervous System/drug effects ; Dronabinol/analogs & derivatives ; Dronabinol/therapeutic use ; Humans ; Male ; Pain/chemically induced ; Pain/drug therapy ; Pain Measurement/drug effects
Chemical Substances	nabilone (2N4O9L084N) ; Dronabinol (7J8897W37S) ; Capsaicin (S07O44R1ZM)
Language	English
Publishing date	2012-04
Publishing country	Australia
Document type	Comment ; Editorial
ZDB-ID	189277-0
ISSN	1440-1681 ; 0305-1870 ; 0143-9294
ISSN (online)	1440-1681
ISSN	0305-1870 ; 0143-9294
DOI	10.1111/j.1440-1681.2012.05687.x
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Article ; Online: Sex and dose-dependent antinociceptive effects of the JNK (c-Jun N-terminal kinase) inhibitor SU 3327 are mediated by CB

Blanton, Henry L / Pietrzak, Agata / McHann, Melissa C / Guindon, Josée

Brain research bulletin

2021 Volume 177, Page(s) 39–52

Abstract: Activation of c-Jun N-terminal kinases (JNKs) has been implicated in the development and persistence of inflammatory and neuropathic pain in animal models. Moreover, JNKs have been involved in the maintenance of chronic pain, as well as development of ... ...

Abstract	Activation of c-Jun N-terminal kinases (JNKs) has been implicated in the development and persistence of inflammatory and neuropathic pain in animal models. Moreover, JNKs have been involved in the maintenance of chronic pain, as well as development of tolerance to antinociceptive agents in the opioid and cannabinoid class of compounds. In this study, we evaluated the antinociceptive effects of the JNK inhibitor SU 3327 (0.3-30 mg/kg) in the formalin pain model with an emphasis on the sex-specific actions of this compound. In wild-type C57BL6J mice, SU 3327 produced strong antinociceptive effects in the formalin pain model which were mediated by CB
MeSH term(s)	Analgesics/pharmacology ; Animals ; Female ; JNK Mitogen-Activated Protein Kinases ; Male ; Mice ; Mice, Inbred C57BL ; Neuralgia ; Receptor, Cannabinoid, CB1/genetics ; Receptor, Cannabinoid, CB2 ; Thiadiazoles
Chemical Substances	Analgesics ; Receptor, Cannabinoid, CB1 ; Receptor, Cannabinoid, CB2 ; SU 3327 ; Thiadiazoles ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2021-09-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	197620-5
ISSN	1873-2747 ; 0361-9230
ISSN (online)	1873-2747
ISSN	0361-9230
DOI	10.1016/j.brainresbull.2021.09.004
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Article ; Online: Sex differences in acute delta-9-tetrahydrocannabinol (Δ

Lulek, Courtney F / Maulik, Malabika / Mitra, Swarup / Guindon, Josée / Morgan, Daniel J / Henderson-Redmond, Angela N

Psychopharmacology

2023 Volume 240, Issue 9, Page(s) 1987–2003

Abstract: Cannabinoids are increasingly used to alleviate pain; however, tolerance to their antinociceptive effects, including those of delta-9-tetrahydrocannabinol ( ... ...

Abstract	Cannabinoids are increasingly used to alleviate pain; however, tolerance to their antinociceptive effects, including those of delta-9-tetrahydrocannabinol (Δ
MeSH term(s)	Mice ; Rats ; Female ; Male ; Animals ; Dronabinol/pharmacology ; Sex Characteristics ; Mice, Inbred CBA ; Mice, Inbred DBA ; Mice, Inbred C57BL ; Cannabinoids/pharmacology ; Analgesics/pharmacology ; Dose-Response Relationship, Drug
Chemical Substances	Dronabinol (7J8897W37S) ; Cannabinoids ; Analgesics
Language	English
Publishing date	2023-07-29
Publishing country	Germany
Document type	Journal Article
ZDB-ID	130601-7
ISSN	1432-2072 ; 0033-3158
ISSN (online)	1432-2072
ISSN	0033-3158
DOI	10.1007/s00213-023-06421-8
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Article ; Online: Cannabinoid Tolerance in S426A/S430A x

Piscura, Mary K / Sepulveda, Diana E / Maulik, Malabika / Guindon, Josée / Henderson-Redmond, Angela N / Morgan, Daniel J

The Journal of pharmacology and experimental therapeutics

2023 Volume 385, Issue 1, Page(s) 17–34

Abstract: Tolerance to compounds that target G protein-coupled receptors (GPCRs), such as the cannabinoid type-1 receptor ( ... ...

Abstract	Tolerance to compounds that target G protein-coupled receptors (GPCRs), such as the cannabinoid type-1 receptor (CB
MeSH term(s)	Mice ; Male ; Female ; Animals ; Cannabinoids/pharmacology ; Dronabinol/pharmacology ; beta-Arrestin 2/genetics ; Mice, Knockout ; Receptors, Cannabinoid ; Analgesics/pharmacology ; Receptor, Cannabinoid, CB1/genetics
Chemical Substances	Cannabinoids ; 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol (83003-12-7) ; Dronabinol (7J8897W37S) ; beta-Arrestin 2 ; Receptors, Cannabinoid ; Analgesics ; Receptor, Cannabinoid, CB1
Language	English
Publishing date	2023-01-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	3106-9
ISSN	1521-0103 ; 0022-3565
ISSN (online)	1521-0103
ISSN	0022-3565
DOI	10.1124/jpet.122.001367
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Article ; Online: Mechanisms of cannabinoid tolerance.

Piscura, Mary K / Henderson-Redmond, Angela N / Barnes, Robert C / Mitra, Swarup / Guindon, Josée / Morgan, Daniel J

Biochemical pharmacology

2023 Volume 214, Page(s) 115665

Abstract: Cannabis has been used recreationally and medically for centuries, yet research into understanding the mechanisms of its therapeutic effects has only recently garnered more attention. There is evidence to support the use of cannabinoids for the treatment ...

Abstract	Cannabis has been used recreationally and medically for centuries, yet research into understanding the mechanisms of its therapeutic effects has only recently garnered more attention. There is evidence to support the use of cannabinoids for the treatment of chronic pain, muscle spasticity, nausea and vomiting due to chemotherapy, improving weight gain in HIV-related cachexia, emesis, sleep disorders, managing symptoms in Tourette syndrome, and patient-reported muscle spasticity from multiple sclerosis. However, tolerance and the risk for cannabis use disorder are two significant disadvantages for cannabinoid-based therapies in humans. Recent work has revealed prominent sex differences in the acute response and tolerance to cannabinoids in both humans and animal models. This review will discuss evidence demonstrating cannabinoid tolerance in rodents, non-human primates, and humans and our current understanding of the neuroadaptations occurring at the cannabinoid type 1 receptor (CB
MeSH term(s)	Animals ; Female ; Humans ; Male ; Cannabinoids/pharmacology ; Cannabinoids/therapeutic use ; Dronabinol/therapeutic use ; Muscle Spasticity/drug therapy ; Cannabinoid Receptor Agonists ; Signal Transduction/physiology ; Receptors, Cannabinoid ; Receptor, Cannabinoid, CB1
Chemical Substances	Cannabinoids ; Dronabinol (7J8897W37S) ; Cannabinoid Receptor Agonists ; Receptors, Cannabinoid ; Receptor, Cannabinoid, CB1
Language	English
Publishing date	2023-06-20
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2023.115665
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Article ; Online: Assessing Dose- and Sex-Dependent Antinociceptive Effects of Cannabidiol and Amitriptyline, Alone and in Combination, and Exploring Mechanism of Action Involving Serotonin 1A Receptors.

Barnes, Robert C / Banjara, Satish / McHann, Melissa C / Almodovar, Sharilyn / Henderson-Redmond, Angela N / Morgan, Daniel J / Castro-Piedras, Isabel / Guindon, Josée

The Journal of pharmacology and experimental therapeutics

2024 Volume 388, Issue 2, Page(s) 655–669

Abstract: Inflammatory pain is caused by tissue hypersensitization and is a component of rheumatic diseases, frequently causing chronic pain. Current guidelines use a multimodal approach to pain and sociocultural changes have renewed interest in cannabinoid use, ... ...

Abstract	Inflammatory pain is caused by tissue hypersensitization and is a component of rheumatic diseases, frequently causing chronic pain. Current guidelines use a multimodal approach to pain and sociocultural changes have renewed interest in cannabinoid use, particularly cannabidiol (CBD), for pain. The tricyclic antidepressant amitriptyline (AT) is approved for use in pain-related syndromes, alone and within a multimodal approach. Therefore, we investigated sex- and dose-dependent effects of CBD and AT antinociception in the 2.5% formalin inflammatory pain model. Male and female C57BL/6J mice were pretreated with either vehicle, CBD (0.3-100 mg/kg), or AT (0.1-30 mg/kg) prior to formalin testing. In the acute phase, CBD induced antinociception after administration of 30-100 mg/kg in males and 100 mg/kg in females and in the inflammatory phase at doses of 2.5-100 mg/kg in males and 10-100 mg/kg in females. In the acute phase, AT induced antinociception at 10 mg/kg for all mice, and at 0.3 mg/kg in males and 3 mg/kg in female mice in the inflammatory phase. Combining the calculated median effective doses of CBD and AT produced additive effects for all mice in the acute phase and for males only in the inflammatory phase. Use of selective serotonin 1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1 piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY-100635) maleate (0.1 mg/kg) before co-administration of CBD and AT reversed antinociception in the acute and partially reversed antinociception in the inflammatory phase. Administration of AT was found to enhance cannabinoid receptor type 1mRNA expression only in female mice. These results suggest a role for serotonin and sex in mediating cannabidiol and amitriptyline-induced antinociception in inflammatory pain. SIGNIFICANCE STATEMENT: Inflammatory pain is an important component of both acute and chronic pain. We have found that cannabidiol (CBD) and amitriptyline (AT) show dose-dependent, and that AT additionally shows sex-dependent, antinociceptive effects in an inflammatory pain model. Additionally, the combination of CBD and AT was found to have enhanced antinociceptive effects that is partially reliant of serotonin 1A receptors and supports the use of CBD within a multimodal approach to pain.
MeSH term(s)	Mice ; Male ; Female ; Animals ; Cannabidiol/pharmacology ; Cannabidiol/therapeutic use ; Serotonin/metabolism ; Amitriptyline/pharmacology ; Amitriptyline/therapeutic use ; Chronic Pain/drug therapy ; Receptor, Serotonin, 5-HT1A ; Mice, Inbred C57BL ; Serotonin Antagonists/pharmacology ; Analgesics/pharmacology ; Analgesics/therapeutic use ; Formaldehyde
Chemical Substances	Cannabidiol (19GBJ60SN5) ; Serotonin (333DO1RDJY) ; Amitriptyline (1806D8D52K) ; Receptor, Serotonin, 5-HT1A (112692-38-3) ; Serotonin Antagonists ; Analgesics ; Formaldehyde (1HG84L3525)
Language	English
Publishing date	2024-01-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3106-9
ISSN	1521-0103 ; 0022-3565
ISSN (online)	1521-0103
ISSN	0022-3565
DOI	10.1124/jpet.123.001855
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Article ; Online: Pain and aging: A unique challenge in neuroinflammation and behavior.

Singh, Shishu Pal / Guindon, Josee / Mody, Prapti H / Ashworth, Gabriela / Kopel, Jonathan / Chilakapati, Sai / Adogwa, Owoicho / Neugebauer, Volker / Burton, Michael D

Molecular pain

2023 Volume 19, Page(s) 17448069231203090

Abstract: Chronic pain is one of the most common, costly, and potentially debilitating health issues facing older adults, with attributable costs exceeding $600 billion annually. The prevalence of pain in humans increases with advancing age. Yet, the contributions ...

Abstract	Chronic pain is one of the most common, costly, and potentially debilitating health issues facing older adults, with attributable costs exceeding $600 billion annually. The prevalence of pain in humans increases with advancing age. Yet, the contributions of sex differences, age-related chronic inflammation, and changes in neuroplasticity to the overall experience of pain are less clear, given that opposing processes in aging interact. This review article examines and summarizes pre-clinical research and clinical data on chronic pain among older adults to identify knowledge gaps and provide the base for future research and clinical practice. We provide evidence to suggest that neurodegenerative conditions engender a loss of neural plasticity involved in pain response, whereas low-grade inflammation in aging increases CNS sensitization but decreases PNS sensitivity. Insights from preclinical studies are needed to answer mechanistic questions. However, the selection of appropriate aging models presents a challenge that has resulted in conflicting data regarding pain processing and behavioral outcomes that are difficult to translate to humans.
MeSH term(s)	Female ; Humans ; Male ; Aged ; Chronic Pain ; Neuroinflammatory Diseases ; Aging ; Inflammation
Language	English
Publishing date	2023-09-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2174252-2
ISSN	1744-8069 ; 1744-8069
ISSN (online)	1744-8069
ISSN	1744-8069
DOI	10.1177/17448069231203090
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