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Acharya B, Sahu PK, Behera A, Feehan J, Mishra DP, Apostolopoulos V. Cannabinoids and the male reproductive system: Implications of endocannabinoid signaling pathways. Maturitas 2025; 192:108156. [PMID: 39602858 DOI: 10.1016/j.maturitas.2024.108156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 10/29/2024] [Accepted: 11/13/2024] [Indexed: 11/29/2024]
Abstract
The escalating use and legalization of cannabis (marijuana) in the United States reflect shifting societal attitudes and growing awareness of its potential therapeutic benefits. Historically viewed as a harmful psychoactive substance, contemporary research has shown the intricate pharmacology of cannabis, with its diverse array of cannabinoids and their interactions with the endocannabinoid system. Among these cannabinoids, Δ9-tetrahydrocannabinol is the primary psychoactive component, characterized by its activation of cannabinoid receptors. The discovery of endocannabinoids, including anandamide and 2-arachidonoylglycerol, illuminated the body's innate cannabinoid signaling pathways and their involvement in several physiological processes. Endocannabinoids exert both positive and negative effects on the male reproductive system. They facilitate erectile function by modulating neurotransmission and vasodilation, offering potential therapeutic avenues for conditions like erectile dysfunction and prostatitis. However, chronic exogenous cannabinoid use, mainly of tetrahydrocannabinol, poses risks to male reproductive health by disrupting spermatogenesis, causing hormonal imbalances, and potentially influencing cancer cell proliferation. Understanding endocannabinoid signaling in the male reproductive system is essential to fully comprehend both the therapeutic benefits and potential drawbacks of cannabis use. Further research is required on these mechanisms, to provide insights that can guide clinical practice and policy-making regarding cannabis use. In this narrative review, we highlight the need for additional research into how cannabinoids affect male reproductive health, particularly with prolonged use. Investigating cannabinoids' impacts on spermatogenesis, hormonal balance, and cancer cell proliferation can provide valuable insights for healthcare professionals.
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Affiliation(s)
- Biswajeet Acharya
- School of Pharmacy and Life Sciences, Centurion University of Technology and Management, Odisha, India.
| | - Prafulla Kumar Sahu
- School of Pharmacy and Life Sciences, Centurion University of Technology and Management, Odisha, India; Department of Pharmacy, Keonjhar Institute of Medical Science & Research, Keonjhar, Odisha, India; IndQuench Life Science Innovations (OPC) Pvt. Ltd., Plot No: 31/761, Devika Bihar, Dasabatia, Tamando (P), Khurda (Dist), Bhubaneswar, Odisha-751028, India.
| | | | - Jack Feehan
- School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, Victoria 3000, Australia.
| | - Durga Prasad Mishra
- School of Pharmacy and Life Sciences, Centurion University of Technology and Management, Odisha, India.
| | - Vasso Apostolopoulos
- School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, Victoria 3000, Australia.
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Nikvarz N, Sedighi B, Ansari M, Shahdizade S, Shojaei R, Sharififar F. Medicinal plants used in multiple sclerosis patients, prevalence and associated factors: a descriptive cross-sectional study. BMC Complement Med Ther 2024; 24:278. [PMID: 39039480 PMCID: PMC11265095 DOI: 10.1186/s12906-024-04587-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 07/10/2024] [Indexed: 07/24/2024] Open
Abstract
INTRODUCTION Multiple sclerosis (MS) is a chronic and debilitating disease that not only leads to disability and associated condition but also impacts one's ability to maintain a professional life. People's acceptance and utilization of medicinal plants (MPs) play an important role in managing their treatment process. As a result, this study aims to investigate the use of medicinal herbs among patients with MS. METHODS A descriptive cross-sectional study was conducted on 150 MS patients who visited a private clinic and the MS Association in Kerman, Iran in 2021. A questionnaire comprising questions about sociodemographic information, disease variables, and aspects of MPs usage was utilized for data collection. Statistical analysis was performed using SPSS version 20 (SPSS Inc., Chicago, IL). The Chi-square test was employed to identify any association between demographic characteristics and MPs usage. To determine the prevalence of plant use in a specific area and the consensus among informants, the use value (UV) and Informant consensus factor (Fic) were calculated. RESULTS The study revealed a high prevalence of MPs usage among MS patients. Chamomile (66.6%) and golegavzaban (62.0%) were the most commonly used plants with the highest UV indices (0.88 and 0.82 respectively), while St. John's wort and licorice were rarely used (0.67% and 4% respectively). Participants cited pursuing a healthier lifestyle as the primary reason for using MPs (24%). St. John's wort, lavender, and chamomile were the most satisfying plants (100%, 100%, and 53.0% respectively). Chamomile had the highest Fic too. Most patients were motivated to get MPs from their relatives. CONCLUSIONS Given the widespread use of MPs among MS patients, neurologists should enhance their knowledge in this area to guide patients away from seeking advice from non-professionals. Providing standardized formulations can help prevent potential interactions between MPs and mainstream drugs, thereby improving patients safety and outcomes.
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Affiliation(s)
- Naemeh Nikvarz
- Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Behnaz Sedighi
- Neurology Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Mehdi Ansari
- Pharmaceutical Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Shirin Shahdizade
- Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Reyhane Shojaei
- Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran.
| | - Fariba Sharififar
- Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran.
- Pharmaceutical Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
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Javid FA, Alam A, Williams E, Malik SS, Mohayuddin U, Hasan SS. Trends in prescription and cost of Sativex, a cannabinoid-based medicine, in treating patients with multiple sclerosis in England. J Pharm Policy Pract 2024; 17:2342318. [PMID: 38726319 PMCID: PMC11080669 DOI: 10.1080/20523211.2024.2342318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/12/2024] Open
Abstract
Aim Cannabis-based medication has recently been made available in the NHS for reducing pain and spasticity in patients with multiple sclerosis (MS). The currently available preparation of Sativex (nabiximols) contains a combination of botanical cannabis extracts with cannabidiol (CBD) and tetrahydrocannabinol (THC) with almost equal amounts in addition to minor cannabinoids and terpenoids and is delivered via an oro-mucosal spray. The present study aims to examine the use and trends in prescribing cannabinoid-based Sativex to control pain in patients diagnosed with MS. Methods Primary care prescribing data for cannabinoid-based Sativex (2013-2022) from the Prescription Cost Analysis were extracted and analysed. Linear regression analyses were performed to examine prescription trends and prescription costs (average change per year). Results There was a general increasing trend in the number of prescriptions each year, from 4.42 items dispensed per 100,000 people in 2013 to 5.15 in 2022. Overall, prescription items for cannabinoid-based Sativex increased by 0.34% per year (95% CI:-3.98, 4.67, p = 0.860) on average between 2013 and 2022. On average, a 2.43% (95% CI: -5.78, 0.92, p = 0.133) increase per year was observed for the costs of cannabinoid-based Sativex from 2013 to 2022. Conclusion The results suggested that cannabinoid-based Sativex should be considered an option due to its effectiveness, acceptable tolerance, and safety profile in the prescribing of Sativex.
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Affiliation(s)
- Farideh A. Javid
- Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, UK
| | - Anam Alam
- Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, UK
| | - Emily Williams
- Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, UK
| | - Sidhra Sajid Malik
- Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, UK
| | - Usama Mohayuddin
- Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, UK
| | - Syed Shahzad Hasan
- Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, UK
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Chen H, Hoi MPM, Lee SMY. Medicinal plants and natural products for treating overactive bladder. Chin Med 2024; 19:56. [PMID: 38532487 DOI: 10.1186/s13020-024-00884-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 01/02/2024] [Indexed: 03/28/2024] Open
Abstract
BACKGROUND Overactive bladder (OAB) presents a high prevalence of 16-18% worldwide. The pathophysiology of OAB is still poorly understood while effective therapy or countermeasure are very limited. On the other hand, medicinal plants and herbal remedies have been utilized for treating lower urinary tract symptoms (LUTS) in both Eastern and Western cultures since ancient times. In recent years, accumulating progress has also been made in OAB treatment research by using medicinal plants. METHODS Relevant literature on the studies of medicinal plants and herbs used to treat OAB was reviewed. The medicinal plants were summarized and categorized into two groups, single-herb medications and herbal formulations. RESULTS The present review has summarized current understanding of OAB's pathophysiology, its available treatments and new drug targets. Medicinal plants and natural products which have been used or have shown potential for OAB treatment were updated and comprehensively categorized. Studies on a wide variety of medicinal plants showed promising results, although only a few phytochemicals have been isolated and identified. Until now, none of these herbal compounds have been further developed into clinical therapeutics for OAB. CONCLUSIONS This review provides the basis for discovering and designing new phytopharmaceutical candidates with effective and well-tolerated properties to treat OAB. Increasing evidences indicate new strategies with alternative herbal treatment for OAB have high efficacy and safety, showing great promise for their clinical use. Future studies in a rigorously designed controlled manner will be beneficial to further support the eligibility of herbal treatment as OAB therapeutics.
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Affiliation(s)
- Huanxian Chen
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macao, China
| | - Maggie Pui Man Hoi
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macao, China
- Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macao, China
| | - Simon Ming Yuen Lee
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macao, China.
- Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macao, China.
- Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hong Kong, China.
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Salehi N, Nourbakhsh M, Noori S, Rezaeizadeh H, Zarghi A. Tehranolid and Artemisinin Effects on Ameliorating Experimental Autoimmune Encephalomyelitis by Modulating Inflammation and Remyelination. Mol Neurobiol 2023; 60:5975-5986. [PMID: 37391648 DOI: 10.1007/s12035-023-03449-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 06/19/2023] [Indexed: 07/02/2023]
Abstract
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. Artemisinin (ART) is a natural sesquiterpene lactone with an endoperoxide bond that is well-known for its anti-inflammatory effects in experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS. Tehranolide (TEH) is a novel compound with structural similarity to ART. In this study, we aimed to investigate the ameliorating effect of TEH on EAE development by targeting proteins and genes involved in this process and compare its effects with ART. Female C57BL/6 mice were immunized with MOG35-55. Twelve days post-immunization, mice were treated with 0.28 mg/kg/day TEH and 2.8 mg/kg/day ART for 18 consecutive days, and the clinical score was measured daily. The levels of pro-inflammatory and anti-inflammatory cytokines were assessed in mice serum and splenocytes by ELISA. We also evaluated the mRNA expression level of cytokines, as well as genes involved in T cell differentiation and myelination in the spinal cord tissue by qRT-PCR. Administration of TEH and ART significantly alleviated EAE signs. A significant reduction in IL-6 and IL-17 secretion and IL-17 and IL-1 gene expression in spinal cord were observed in the TEH-treated group. ART had similar or less significant effects. Moreover, TGF-β, IL-4, and IL-10 genes were stimulated by ART and TEH in the spinal cord, while the treatments did not affect IFN-γ expression. Both treatments dramatically increased the expression of FOXP3, GATA3, MBP, and AXL. Additionally, the T-bet gene was reduced after TEH administration. The compounds made no changes in RORγt, nestin, Gas6, Tyro3, and Mertk mRNA expression levels in the spinal cord. The study revealed that both TEH and ART can effectively modulate the genes responsible for inflammation and myelination that play a crucial role in EAE. Interestingly, TEH demonstrated a greater potency compared to ART and hence may have the potential to be evaluated in interventions for the management of MS.
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Affiliation(s)
- Niloufar Salehi
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mitra Nourbakhsh
- Finetech in Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Shokoofe Noori
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Hossein Rezaeizadeh
- Department of Traditional Medicine, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Afshin Zarghi
- School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Michel MC, Cardozo L, Chermansky CJ, Cruz F, Igawa Y, Lee KS, Sahai A, Wein AJ, Andersson KE. Current and Emerging Pharmacological Targets and Treatments of Urinary Incontinence and Related Disorders. Pharmacol Rev 2023; 75:554-674. [PMID: 36918261 DOI: 10.1124/pharmrev.121.000523] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 01/23/2023] [Accepted: 01/24/2023] [Indexed: 03/16/2023] Open
Abstract
Overactive bladder syndrome with and without urinary incontinence and related conditions, signs, and disorders such as detrusor overactivity, neurogenic lower urinary tract dysfunction, underactive bladder, stress urinary incontinence, and nocturia are common in the general population and have a major impact on the quality of life of the affected patients and their partners. Based on the deliberations of the subcommittee on pharmacological treatments of the 7th International Consultation on Incontinence, we present a comprehensive review of established drug targets in the treatment of overactive bladder syndrome and the aforementioned related conditions and the approved drugs used in its treatment. Investigational drug targets and compounds are also reviewed. We conclude that, despite a range of available medical treatment options, a considerable medical need continues to exist. This is largely because the existing treatments are symptomatic and have limited efficacy and/or tolerability, which leads to poor long-term adherence. SIGNIFICANCE STATEMENT: Urinary incontinence and related disorders are prevalent in the general population. While many treatments have been approved, few patients stay on long-term treatment despite none of them being curative. This paper provides a comprehensive discussion of existing and emerging treatment options for various types of incontinence and related disorders.
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Affiliation(s)
- Martin C Michel
- Department of Pharmacology, University Medical Center, Johannes Gutenberg University, Mainz, Germany (M.C.M.); Department of Urogynaecology, King's College Hospital, London, UK (L.C.); Department of Urology, Magee Women's Hospital, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania (C.J.C.); Department of Urology, Faculty of Medicine of University of Porto, Hospital São João and i3S Institute for Innovation and Investigation in Health, Porto, Portugal (F.C.); Department of Urology, Nagano Prefectural Shinshu Medical Center, Suzaka, Japan (Y.I.); Department of Urology Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (K-S.L.); Guy's Hospital and King's College London, London, UK (A.S.); Dept. of Urology, Perlman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.J.W.); Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina (A.J.W.); and Institute for Laboratory Medicine, Lund University, Lund, Sweden (K-E.A.)
| | - Linda Cardozo
- Department of Pharmacology, University Medical Center, Johannes Gutenberg University, Mainz, Germany (M.C.M.); Department of Urogynaecology, King's College Hospital, London, UK (L.C.); Department of Urology, Magee Women's Hospital, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania (C.J.C.); Department of Urology, Faculty of Medicine of University of Porto, Hospital São João and i3S Institute for Innovation and Investigation in Health, Porto, Portugal (F.C.); Department of Urology, Nagano Prefectural Shinshu Medical Center, Suzaka, Japan (Y.I.); Department of Urology Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (K-S.L.); Guy's Hospital and King's College London, London, UK (A.S.); Dept. of Urology, Perlman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.J.W.); Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina (A.J.W.); and Institute for Laboratory Medicine, Lund University, Lund, Sweden (K-E.A.)
| | - Christopher J Chermansky
- Department of Pharmacology, University Medical Center, Johannes Gutenberg University, Mainz, Germany (M.C.M.); Department of Urogynaecology, King's College Hospital, London, UK (L.C.); Department of Urology, Magee Women's Hospital, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania (C.J.C.); Department of Urology, Faculty of Medicine of University of Porto, Hospital São João and i3S Institute for Innovation and Investigation in Health, Porto, Portugal (F.C.); Department of Urology, Nagano Prefectural Shinshu Medical Center, Suzaka, Japan (Y.I.); Department of Urology Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (K-S.L.); Guy's Hospital and King's College London, London, UK (A.S.); Dept. of Urology, Perlman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.J.W.); Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina (A.J.W.); and Institute for Laboratory Medicine, Lund University, Lund, Sweden (K-E.A.)
| | - Francisco Cruz
- Department of Pharmacology, University Medical Center, Johannes Gutenberg University, Mainz, Germany (M.C.M.); Department of Urogynaecology, King's College Hospital, London, UK (L.C.); Department of Urology, Magee Women's Hospital, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania (C.J.C.); Department of Urology, Faculty of Medicine of University of Porto, Hospital São João and i3S Institute for Innovation and Investigation in Health, Porto, Portugal (F.C.); Department of Urology, Nagano Prefectural Shinshu Medical Center, Suzaka, Japan (Y.I.); Department of Urology Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (K-S.L.); Guy's Hospital and King's College London, London, UK (A.S.); Dept. of Urology, Perlman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.J.W.); Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina (A.J.W.); and Institute for Laboratory Medicine, Lund University, Lund, Sweden (K-E.A.)
| | - Yasuhiko Igawa
- Department of Pharmacology, University Medical Center, Johannes Gutenberg University, Mainz, Germany (M.C.M.); Department of Urogynaecology, King's College Hospital, London, UK (L.C.); Department of Urology, Magee Women's Hospital, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania (C.J.C.); Department of Urology, Faculty of Medicine of University of Porto, Hospital São João and i3S Institute for Innovation and Investigation in Health, Porto, Portugal (F.C.); Department of Urology, Nagano Prefectural Shinshu Medical Center, Suzaka, Japan (Y.I.); Department of Urology Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (K-S.L.); Guy's Hospital and King's College London, London, UK (A.S.); Dept. of Urology, Perlman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.J.W.); Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina (A.J.W.); and Institute for Laboratory Medicine, Lund University, Lund, Sweden (K-E.A.)
| | - Kyu-Sung Lee
- Department of Pharmacology, University Medical Center, Johannes Gutenberg University, Mainz, Germany (M.C.M.); Department of Urogynaecology, King's College Hospital, London, UK (L.C.); Department of Urology, Magee Women's Hospital, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania (C.J.C.); Department of Urology, Faculty of Medicine of University of Porto, Hospital São João and i3S Institute for Innovation and Investigation in Health, Porto, Portugal (F.C.); Department of Urology, Nagano Prefectural Shinshu Medical Center, Suzaka, Japan (Y.I.); Department of Urology Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (K-S.L.); Guy's Hospital and King's College London, London, UK (A.S.); Dept. of Urology, Perlman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.J.W.); Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina (A.J.W.); and Institute for Laboratory Medicine, Lund University, Lund, Sweden (K-E.A.)
| | - Arun Sahai
- Department of Pharmacology, University Medical Center, Johannes Gutenberg University, Mainz, Germany (M.C.M.); Department of Urogynaecology, King's College Hospital, London, UK (L.C.); Department of Urology, Magee Women's Hospital, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania (C.J.C.); Department of Urology, Faculty of Medicine of University of Porto, Hospital São João and i3S Institute for Innovation and Investigation in Health, Porto, Portugal (F.C.); Department of Urology, Nagano Prefectural Shinshu Medical Center, Suzaka, Japan (Y.I.); Department of Urology Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (K-S.L.); Guy's Hospital and King's College London, London, UK (A.S.); Dept. of Urology, Perlman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.J.W.); Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina (A.J.W.); and Institute for Laboratory Medicine, Lund University, Lund, Sweden (K-E.A.)
| | - Alan J Wein
- Department of Pharmacology, University Medical Center, Johannes Gutenberg University, Mainz, Germany (M.C.M.); Department of Urogynaecology, King's College Hospital, London, UK (L.C.); Department of Urology, Magee Women's Hospital, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania (C.J.C.); Department of Urology, Faculty of Medicine of University of Porto, Hospital São João and i3S Institute for Innovation and Investigation in Health, Porto, Portugal (F.C.); Department of Urology, Nagano Prefectural Shinshu Medical Center, Suzaka, Japan (Y.I.); Department of Urology Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (K-S.L.); Guy's Hospital and King's College London, London, UK (A.S.); Dept. of Urology, Perlman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.J.W.); Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina (A.J.W.); and Institute for Laboratory Medicine, Lund University, Lund, Sweden (K-E.A.)
| | - Karl-Erik Andersson
- Department of Pharmacology, University Medical Center, Johannes Gutenberg University, Mainz, Germany (M.C.M.); Department of Urogynaecology, King's College Hospital, London, UK (L.C.); Department of Urology, Magee Women's Hospital, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania (C.J.C.); Department of Urology, Faculty of Medicine of University of Porto, Hospital São João and i3S Institute for Innovation and Investigation in Health, Porto, Portugal (F.C.); Department of Urology, Nagano Prefectural Shinshu Medical Center, Suzaka, Japan (Y.I.); Department of Urology Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (K-S.L.); Guy's Hospital and King's College London, London, UK (A.S.); Dept. of Urology, Perlman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.J.W.); Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina (A.J.W.); and Institute for Laboratory Medicine, Lund University, Lund, Sweden (K-E.A.)
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Flores VA, Kisiolek JN, Ramani A, Townsend R, Rodriguez E, Butler B, Stewart LK. Effects of Oral Cannabidiol on Health and Fitness in Healthy Adults: An 8-Week Randomized Trial. Nutrients 2023; 15:2664. [PMID: 37375567 PMCID: PMC10301202 DOI: 10.3390/nu15122664] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/03/2023] [Accepted: 06/05/2023] [Indexed: 06/29/2023] Open
Abstract
BACKGROUND There is a lack of research on the effects of cannabidiol (CBD) on health-related fitness, physical activity, cognitive health, psychological wellbeing, and concentrations of C-reactive protein (CRP) in healthy individuals. CBD has potential anti-inflammatory and neuroprotective effects. METHODS This study aimed to investigate the effects of 8 weeks of CBD on the above-mentioned measures in healthy individuals. Forty-eight participants were randomized into two groups receiving either oral capsules of 50 mg of CBD or a calorie-matched placebo daily. Participants completed pre- and post-intervention assessments, including blood draws, body composition, fitness, physical activity, and self-reported surveys. RESULTS There were no significant differences between groups regarding body composition, aerobic fitness, muscular strength, physical activity, cognitive health, psychological wellbeing, and resting CRP concentrations. However, the placebo group experienced a decline in mean peak power and relative peak power compared to the CBD group. CONCLUSIONS The results suggest that 8 weeks of CBD supplementation may prevent declines in anaerobic fitness over time. However, long-term CBD supplementation may not be beneficial for altering measures of health-related fitness, mental health, and inflammation in healthy individuals.
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Affiliation(s)
- Victoria A. Flores
- Department of Kinesiology, Nutrition, and Dietetics, University of Northern Colorado, Greeley, CO 80639, USA; (J.N.K.); (A.R.); (R.T.); (E.R.); (B.B.)
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Jacob N. Kisiolek
- Department of Kinesiology, Nutrition, and Dietetics, University of Northern Colorado, Greeley, CO 80639, USA; (J.N.K.); (A.R.); (R.T.); (E.R.); (B.B.)
- Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, UT 84112, USA
| | - Arjun Ramani
- Department of Kinesiology, Nutrition, and Dietetics, University of Northern Colorado, Greeley, CO 80639, USA; (J.N.K.); (A.R.); (R.T.); (E.R.); (B.B.)
| | - Ryland Townsend
- Department of Kinesiology, Nutrition, and Dietetics, University of Northern Colorado, Greeley, CO 80639, USA; (J.N.K.); (A.R.); (R.T.); (E.R.); (B.B.)
| | - Edwin Rodriguez
- Department of Kinesiology, Nutrition, and Dietetics, University of Northern Colorado, Greeley, CO 80639, USA; (J.N.K.); (A.R.); (R.T.); (E.R.); (B.B.)
| | - Blake Butler
- Department of Kinesiology, Nutrition, and Dietetics, University of Northern Colorado, Greeley, CO 80639, USA; (J.N.K.); (A.R.); (R.T.); (E.R.); (B.B.)
| | - Laura K. Stewart
- Department of Kinesiology, Nutrition, and Dietetics, University of Northern Colorado, Greeley, CO 80639, USA; (J.N.K.); (A.R.); (R.T.); (E.R.); (B.B.)
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Torri Clerici V, Brambilla L, Politi PL, Viggiani F, Mercurio S, Tonietti S, Ronzoni M, Crisafulli SG, Antozzi C, Tramacere I, Redemagni C, Confalonieri P. Nabiximols oromucosal spray in patients with multiple sclerosis-related bladder dysfunction: A prospective study. Mult Scler Relat Disord 2023; 74:104711. [PMID: 37062198 DOI: 10.1016/j.msard.2023.104711] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 03/31/2023] [Accepted: 04/08/2023] [Indexed: 04/18/2023]
Abstract
BACKGROUND Spasticity and urinary disturbances can profoundly impact the daily lives of persons with multiple sclerosis (pwMS). Cannabis has been associated with improvement in sphincteric disturbances. To our knowledge, few studies have evaluated the effect of nabiximols oromucosal spray (Sativex®) on urinary disturbances by instrumental methods. OBJECTIVES This longitudinal study was conducted to assess the effect of nabiximols oromucosal spray on urinary disturbances by clinical and urodynamic evaluation in pwMS. MATERIALS AND METHODS Neurological, spasticity, and quality of life (QoL) assessments were performed before (T0), and at one (T1) and six (T6) months after the start of nabiximols treatment. At these same time points, patients were assessed for urinary disturbances by the International Prostatic Symptoms Score (IPSS) and a urodynamic test evaluating maximum detrusor pressure (Pdet), bladder filling capacity (CCmax), uninhibited detrusor contractions (UDC), bladder volume at first desire (BVFD), post-void residual volume (PVR) and voluntary abdominal pressure (PA). RESULTS Of 31 pwMS enrolled in the study, 25 reached T1 and 18 reached T6. Mean IPSS total score, its subscores, and IPSS QoL decreased significantly from T0 to T6 (p = 0.000), with no differences according to sex, age, MS type, disease duration and disability at baseline. Pdet improved significantly from T0 to T6 (p = 0.0171), and CCmax changed only marginally (p = 0.0494); results were similar in patient subgroups naïve to or previously exposed to urological treatment. All patients with overactive bladder showed improvement in their urodynamic assessment based on significant reduction of Pdet (p = 0.0138). In patients with mainly hypotonic bladder, mean Pdet decreased from T0 to T6 without reaching statistical significance; most urodynamic parameters showed a trend to improve. Mean numerical scale scores for MS spasticity, and for spasms, pain and tremors, decreased significantly from T0 to T6. The mean 'physical health composite' score of the MS Quality of Life-54 questionnaire increased significantly from T0 to T6 (p = 0.0126). DISCUSSION AND CONCLUSION Our data suggest that nabiximols has an appreciable effect on ameliorating subjective perception of urinary disturbances and appears to have a positive effect on objective urodynamic parameters, particularly in patients with hyperactive bladder.
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Affiliation(s)
- Valentina Torri Clerici
- Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Via Celoria n° 11, Milan 20133, Italy.
| | - Laura Brambilla
- Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Via Celoria n° 11, Milan 20133, Italy
| | - Paolo Luca Politi
- Urology Unit - ASST NORD Milano - E. Bassini Hospital, Cinisello Balsamo, Milan, Italy
| | - Federica Viggiani
- Urology Unit - ASST NORD Milano - E. Bassini Hospital, Cinisello Balsamo, Milan, Italy
| | - Simone Mercurio
- Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Via Celoria n° 11, Milan 20133, Italy
| | | | - Marco Ronzoni
- Neurology Unit-ASST Garbagnate Milanese, Milan, Italy
| | - Sebastiano Giuseppe Crisafulli
- Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Via Celoria n° 11, Milan 20133, Italy
| | - Carlo Antozzi
- Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Via Celoria n° 11, Milan 20133, Italy
| | - Irene Tramacere
- Department of Research and Clinical Development, Scientific Directorate, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Chiara Redemagni
- Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Via Celoria n° 11, Milan 20133, Italy
| | - Paolo Confalonieri
- Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Via Celoria n° 11, Milan 20133, Italy
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9
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The association between recent cannabis use and urinary incontinence in women: a population-based analysis of the NHANES from 2009 to 2018. World J Urol 2022; 40:3099-3105. [DOI: 10.1007/s00345-022-04193-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 09/06/2022] [Indexed: 10/31/2022] Open
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10
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Ranum RM, Whipple MO, Croghan I, Bauer B, Toussaint LL, Vincent A. Use of Cannabidiol in the Management of Insomnia: A Systematic Review. Cannabis Cannabinoid Res 2022; 8:213-229. [PMID: 36149724 DOI: 10.1089/can.2022.0122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Background: Cannabidiol (CBD), one of the major cannabinoids derived from the cannabis plant, is available over the counter. CBD is often used by patients for the management of insomnia, yet research supporting CBDs effectiveness as a treatment for insomnia is inadequate. Objective: The objective of this review was to critically evaluate the literature regarding the therapeutic benefits of CBD in the management of insomnia. Methods: A comprehensive search of the following databases from inception to December 29, 2021, was conducted: Ovid MEDLINE® and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. The search included randomized controlled trials, nonrandomized experimental studies, cross-sectional studies, cohort studies, case series, and case reports. Risk of bias was assessed with the Agency for Healthcare Research and Quality design-specific recommended criteria. Results: Thirty-four studies were eligible for inclusion. All studies reported improvement in the insomnia symptoms of at least a portion of their participants. Of the 34 studies, 19 studies used CBD predominant therapy and 21 studies used nearly equal ratios of CBD to Δ9-tetrahydrocannabinol (THC). Of the studies that performed hypothesis testing, 4 of 7 studies with a CBD predominant arm and 12 of 16 studies with a nearly equal ratio of CBD to THC arm reported significant improvement in insomnia outcomes. However, only 2 of the 34 studies focused on patients with insomnia, of which 1 study was a case report. Additionally, several studies used nonvalidated subjective measures, and most studies failed to include objective measures for symptom assessment. Conclusions: The results of our systematic review suggest that CBD alone or with equal quantities of THC may be beneficial in alleviating the symptoms of insomnia. Nevertheless, future research assessing CBDs effectiveness in population of patients specifically with insomnia utilizing validated subjective and objective measures is necessary before definitive inferences can be made.
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Affiliation(s)
- Rylea M Ranum
- Department of Psychology, Luther College, Decorah, Iowa, USA
| | - Mary O Whipple
- Department of Adult and Gerontological Health Cooperative, School of Nursing, University of Minnesota, Minneapolis, Minnesota, USA
| | - Ivana Croghan
- Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Brent Bauer
- Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Ann Vincent
- Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
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Abstract
INTRODUCTION Current drug treatment of lower urinary tract disorders, for example, overactive bladder syndrome and lower urinary tract symptoms associated with benign prostatic hyperplasia, is moderately effective, has a low treatment persistence and some short- and long-term adverse events. Even if combination therapy with approved drugs may offer advantages in some patients, there is still a need for new agents. AREAS COVERED New b3-adrenoceptor agonists, antimuscarinics, the naked Maxi-K channel gene, a novel 5HT/NA reuptake inhibitor and soluble guanylate cyclase activators are discussed. Focus is given to P2X3 receptor antagonists, small molecule blockers of TRP channels, the roles of cannabis on incontinence in patients with multiple sclerosis, and of drugs acting directly on CB1 and CB2 receptor or indirectly via endocannabinoids by inhibition of fatty acid aminohydrolase. EXPERT OPINION New potential alternatives to currently used drugs/drug principles are emerging, but further clinical testing is required before they can be evaluated as therapeutic alternatives. It seems that for the near future individualized treatment with approved drugs and their combinations will be the prevailing therapeutic approach.
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Affiliation(s)
- Karl-Erik Andersson
- Wake Forest Institute for Regenerative Medicine, Wake Forest University, Winston Salem, NC, USA.,Department of Laboratory Medicine, Lund University, Lund, Sweden
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12
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Birke R, Meister S, Winkelmann A, Hinz B, Walther UI. Correlation of Nabiximols Dose to Steady-State Concentrations of Cannabinoids in Urine Samples from Patients with Multiple Sclerosis. J Clin Med 2022; 11:jcm11133717. [PMID: 35807001 PMCID: PMC9267351 DOI: 10.3390/jcm11133717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 06/02/2022] [Accepted: 06/14/2022] [Indexed: 11/16/2022] Open
Abstract
Therapeutic drug monitoring of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is based on a complex procedure and is therefore not possible in most laboratories, especially in emergency cases. This work addresses the question of whether therapeutic drug monitoring of nabiximols can be performed using an immunological urine-based test system for cannabinoid abuse. Seventeen patients with multiple sclerosis were included in this study. Administered doses of nabiximols were correlated with immunologically determined urine concentrations of cannabinoids using the DRITM Cannabinoid (THC) Assay. Significant correlations with the administered nabiximols doses were found for creatinine-normalized urine concentrations of cannabinoids without (r = 0.675; p = 0.0015) and after (r = 0.650; p = 0.0044) hydrolysis, as well as for gas-chromatography-coupled mass spectrometry (GC/MS)-measured concentrations of the THC metabolite 11-nor-9-carboxy-Δ9-THC (THC-COOH) in urine samples (r = 0.571; p = 0.0084) by Pearson’s correlation. In addition, doses were significantly correlated with plasma THC-COOH concentrations (r = 0.667; p = 0.0017) measured by GC/MS. Simple immunological cannabinoid measurements in urine samples could provide an estimate of nabiximols dosage, although the correlations obtained here were weak because of the small number of patients observed. Longitudinal monitoring of individual patients is expected to exhibit good results of therapeutic drug monitoring of nabiximols.
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Affiliation(s)
- Rüdiger Birke
- Institute of Pharmacology and Toxicology, Rostock University Medical Center, 18057 Rostock, Germany; (R.B.); (B.H.)
| | - Stefanie Meister
- Department of Neurology, Rostock University Medical Center, 18147 Rostock, Germany; (S.M.); (A.W.)
| | - Alexander Winkelmann
- Department of Neurology, Rostock University Medical Center, 18147 Rostock, Germany; (S.M.); (A.W.)
| | - Burkhard Hinz
- Institute of Pharmacology and Toxicology, Rostock University Medical Center, 18057 Rostock, Germany; (R.B.); (B.H.)
| | - Udo I. Walther
- Institute of Pharmacology and Toxicology, Rostock University Medical Center, 18057 Rostock, Germany; (R.B.); (B.H.)
- Correspondence: ; Tel.: +49-381-494-5786
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13
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Longoria V, Parcel H, Toma B, Minhas A, Zeine R. Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination. Biomedicines 2022; 10:539. [PMID: 35327341 PMCID: PMC8945692 DOI: 10.3390/biomedicines10030539] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 02/20/2022] [Accepted: 02/21/2022] [Indexed: 12/22/2022] Open
Abstract
Despite current therapeutic strategies for immunomodulation and relief of symptoms in multiple sclerosis (MS), remyelination falls short due to dynamic neuropathologic deterioration and relapses, leading to accrual of disability and associated patient dissatisfaction. The potential of cannabinoids includes add-on immunosuppressive, analgesic, neuroprotective, and remyelinative effects. This study evaluates the efficacy of medical marijuana in MS and its experimental animal models. A systematic review was conducted by a literature search through PubMed, ProQuest, and EBSCO electronic databases for studies reported since 2007 on the use of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) in MS and in experimental autoimmune encephalomyelitis (EAE), Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), and toxin-induced demyelination models. Study selection and data extraction were performed by 3 reviewers, and 28 studies were selected for inclusion. The certainty of evidence was appraised using the Cochrane GRADE approach. In clinical studies, there was low- and moderate-quality evidence that treatment with ~1:1 CBD/THC mixtures as a nabiximols (Sativex®) oromucosal spray reduced numerical rating scale (NRS) scores for spasticity, pain, and sleep disturbance, diminished bladder overactivity, and decreased proinflammatory cytokine and transcription factor expression levels. Preclinical studies demonstrated decreases in disease severity, hindlimb stiffness, motor function, neuroinflammation, and demyelination. Other experimental systems showed the capacity of cannabinoids to promote remyelination in vitro and by electron microscopy. Modest short-term benefits were realized in MS responders to adjunctive therapy with CBD/THC mixtures. Future studies are recommended to investigate the cellular and molecular mechanisms of cannabinoid effects on MS lesions and to evaluate whether medical marijuana can accelerate remyelination and retard the accrual of disability over the long term.
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Affiliation(s)
- Victor Longoria
- Basic Medical Sciences, St. Vincent Campus, Saint James School of Medicine, 1480 Renaissance Drive, Park Ridge, IL 60068, USA; (V.L.); (H.P.); (B.T.); (A.M.)
| | - Hannah Parcel
- Basic Medical Sciences, St. Vincent Campus, Saint James School of Medicine, 1480 Renaissance Drive, Park Ridge, IL 60068, USA; (V.L.); (H.P.); (B.T.); (A.M.)
| | - Bameelia Toma
- Basic Medical Sciences, St. Vincent Campus, Saint James School of Medicine, 1480 Renaissance Drive, Park Ridge, IL 60068, USA; (V.L.); (H.P.); (B.T.); (A.M.)
| | - Annu Minhas
- Basic Medical Sciences, St. Vincent Campus, Saint James School of Medicine, 1480 Renaissance Drive, Park Ridge, IL 60068, USA; (V.L.); (H.P.); (B.T.); (A.M.)
| | - Rana Zeine
- School of Natural Sciences, Kean University, 1000 Morris Ave., Union, NJ 07083, USA
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14
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Kim J, Choi H, Kang EK, Ji GY, Kim Y, Choi IS. In Vitro Studies on Therapeutic Effects of Cannabidiol in Neural Cells: Neurons, Glia, and Neural Stem Cells. Molecules 2021; 26:molecules26196077. [PMID: 34641624 PMCID: PMC8512311 DOI: 10.3390/molecules26196077] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 09/28/2021] [Accepted: 09/30/2021] [Indexed: 11/25/2022] Open
Abstract
(‒)-Cannabidiol (CBD) is one of the major phytocannabinoids extracted from the Cannabis genus. Its non-psychoactiveness and therapeutic potential, partly along with some anecdotal—if not scientific or clinical—evidence on the prevention and treatment of neurological diseases, have led researchers to investigate the biochemical actions of CBD on neural cells. This review summarizes the previously reported mechanistic studies of the CBD actions on primary neural cells at the in vitro cell-culture level. The neural cells are classified into neurons, microglia, astrocytes, oligodendrocytes, and neural stem cells, and the CBD effects on each cell type are described. After brief introduction on CBD and in vitro studies of CBD actions on neural cells, the neuroprotective capability of CBD on primary neurons with the suggested operating actions is discussed, followed by the reported CBD actions on glia and the CBD-induced regeneration from neural stem cells. A summary section gives a general overview of the biochemical actions of CBD on neural cells, with a future perspective. This review will provide a basic and fundamental, but crucial, insight on the mechanistic understanding of CBD actions on neural cells in the brain, at the molecular level, and the therapeutic potential of CBD in the prevention and treatment of neurological diseases, although to date, there seem to have been relatively limited research activities and reports on the cell culture-level, in vitro studies of CBD effects on primary neural cells.
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Affiliation(s)
- Jungnam Kim
- Department of Chemistry, KAIST, Daejeon 34141, Korea; (J.K.); (H.C.); (E.K.K.)
| | - Hyunwoo Choi
- Department of Chemistry, KAIST, Daejeon 34141, Korea; (J.K.); (H.C.); (E.K.K.)
| | - Eunhye K. Kang
- Department of Chemistry, KAIST, Daejeon 34141, Korea; (J.K.); (H.C.); (E.K.K.)
| | - Gil Yong Ji
- Cannabis Medical, Inc., Sandong-ro 433-31, Eumbong-myeon, Asan-si 31418, Korea; (G.Y.J.); (Y.K.)
| | - Youjeong Kim
- Cannabis Medical, Inc., Sandong-ro 433-31, Eumbong-myeon, Asan-si 31418, Korea; (G.Y.J.); (Y.K.)
| | - Insung S. Choi
- Department of Chemistry, KAIST, Daejeon 34141, Korea; (J.K.); (H.C.); (E.K.K.)
- Correspondence:
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15
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Kim-Fine S, Greenfield J, Chaput KH, Robert M, Metz LM. Cannabinoids and bladder symptoms in multiple sclerosis. Mult Scler Relat Disord 2021; 54:103105. [PMID: 34216995 DOI: 10.1016/j.msard.2021.103105] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 06/04/2021] [Accepted: 06/16/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Research on the health benefits of cannabis has been limited because use remains restricted or illegal in most countries. Medical cannabis has been legal in Canada since 2001 and recreational use became legal in October 2018. While there are data that support a biological mechanism by which cannabinoids can impact various other symptoms of MS, the evidence of effectiveness of cannabis as a treatment for bladder symptoms remains unsettled. We conducted an exploratory study to describe the current trends of cannabis product consumption among people with MS (PwMS) and their association with perceived benefits on MS symptoms. METHODS A cross-sectional survey study of PwMS, recruited from the MS Clinic in Calgary, Alberta, Canada was undertaken. Logistic regression analyses were performed to assess the associations between cannabis consumption and improvement in bladder function symptoms. RESULTS There were 775 respondents out of 2899 PwMS contacted by email. Among respondents, 734 reported cannabis use in the past 3 months. There were 275 (37.5%) respondents who reported cannabis use in the prior 3 months, and 73.8% of these reported at least weekly use of cannabis. Among all users, 78.1% reported a primary medical or therapeutic indication for consumption. The most common modes of cannabis consumption were oral-edible (69.0%) and smoked (57.1%), while 59.3% used more than one mode of consumption and 2.6% used five different modes. The most common reasons for cannabis use were for sleep (58.3%), pain (51.5%), relaxation (44.4%), muscle spasms (40.2%), anxiety (33.8%) and depression (22.9%). Among the 19 participants who reported bladder symptoms as a main reason for cannabis use, 89.5% reported "better" bladder symptoms when using cannabis. Cannabis consumption in the past 3 months was associated with a two-fold increased odds of reporting improvement in urinary frequency, urinary urgency, bladder leakage and wetness, pad use and bladder emptying. CONCLUSIONS Cannabis is commonly used in this survey study of personal cannabis use among PwMS. Patterns of use, dosing, frequency and mode of delivery are diverse among survey respondents. This pilot study provides some initial glimpses into real world therapeutic use of cannabinoids among PwMS for bladder symptoms.
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Affiliation(s)
- Shunaha Kim-Fine
- Section of Pelvic Medicine and Reconstructive Surgery, Dept OBGYN, Cumming School of Medicine, University of Calgary.
| | - Jamie Greenfield
- Dept of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary
| | - Kathleen H Chaput
- Dept of Obstetrics and Gynecology and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary
| | - Magali Robert
- Section of Pelvic Medicine and Reconstructive Surgery, Dept OBGYN, Cumming School of Medicine, University of Calgary
| | - Luanne M Metz
- Dept of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary
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Stairs J, Maguire F, Lehmann C, Cox A. Cannabinoid Therapy in Female Pelvic Medicine and Reconstructive Surgery: Current Evidence and Future Directions. CURRENT BLADDER DYSFUNCTION REPORTS 2021. [DOI: 10.1007/s11884-021-00632-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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The endocannabinoid system, cannabis, and cannabidiol: Implications in urology and men's health. Curr Urol 2021; 15:95-100. [PMID: 34168527 PMCID: PMC8221009 DOI: 10.1097/cu9.0000000000000023] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 03/16/2020] [Indexed: 01/09/2023] Open
Abstract
Background: The endocannabinoid system is a neuromodulatory system responsible for partial regulation of cognitive and emotional processes in the human central nervous system such as behavior, mood disorders, and neurologic disorders such as epilepsy. The endocannabinoid system is also prevalent throughout the peripheral nervous system and human body and its receptors and signaling pathways are present and active in areas including the male and female reproductive tracts and organ systems such as the urologic and gastrointestinal system. Summary: The purpose of this article is to provide the reader with a brief background on the endocannabinoid system and to discuss the implications of the endocannabinoid system in urology as it applies to the male reproductive system, risk of urologic malignancy, and impact on the lower urinary tract, voiding, and urologic pain. It also summaries and discusses the epidemiology and research on cannabis and cannabidiol products. Key message: The endocannabinoid system affects the urologic and reproductive systems. Cannabis products and inhibitors targeting endocannabinoid pathways are being studied for their potential use as treatments for lower urinary tract symptoms and other urologic symptoms. Cannabis use adversely affects spermatogenesis and semen parameters and may be a risk factor for testicular germ cell tumors, however, it may be useful as a potential treatment for urologic symptoms. Cannabidiol products are popular in the consumer marketplace but there is still a paucity of scientific data on their potential medicinal use.
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Shakil SSM, Gowan M, Hughes K, Azam MNK, Ahmed MN. A narrative review of the ethnomedicinal usage of Cannabis sativa Linnaeus as traditional phytomedicine by folk medicine practitioners of Bangladesh. J Cannabis Res 2021; 3:8. [PMID: 33741060 PMCID: PMC7980557 DOI: 10.1186/s42238-021-00063-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 03/05/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND There is a worldwide interest in the use of Cannabis sativa for biomedicine purposes. Cannabis has ethnomedicinal usage as a natural medicine in Bangladesh and cultivated during the British Empire period for revenues. OBJECTIVE Folk medicine practitioners (FMPs) from different districts of Bangladesh have been using Cannabis sativa, but until now there have not been any compiled studies particularly regarding this practice. Hence, this review is an effort to retrieve the traditional usage of Cannabis sativa as a phytomedicine from published ethnomedicinal studies. METHODS AND MATERIALS Information was searched by using the search terms "ethnomedicinal Cannabis sativa and Bangladesh"; "Bangladesh cannabaceae and ethnomedicinal survey"; "ganja, bhang and folk medicine Bangladesh"; "tetrahydrocannabinol (THC), cannabinoid and therapeutic, clinical trial"; and "cannabis and pharmacological/biological" and retrieved from ethnobotanical articles available on PubMed, Scopus, Science Direct, and Google Scholar databases. A search of the relevant scientific literature also was conducted to assess the efficacy of the ethnomedicinal usage of Cannabis sativa. RESULTS While reviewing over 200 ethnomedicinal plants' survey articles, we found that FMPs of Bangladesh from 12 different districts used Cannabis sativa to treat cited ailments like sleep-associated problems (n=5), neuropsychiatric and CNS problems (n=5), and infections and respiratory problems (n=5) followed by rheumatism, gastrointestinal, gynecological (n=4 each), cancer, sexual, and other ailments including hypertension, headache, itch, increases bile secretion, abortifacient, dandruff, fever, and urinary problems (n=1 each). There are a total of 15 formulations identified from the 11 out of 18 ethnomedicinal plant survey reports. The leaf was the main plant part used (53.8%), followed by root (23%), seed (7.7%) and flower, inflorescence, resin, and all parts 3.8% respectively. CONCLUSIONS Sales and cultivation of Cannabis are illegal at present in Bangladesh, but the use of Cannabis sativa as a natural phytomedicine has been practiced traditionally by folk medicine practitioners of Bangladesh for many years and validated through relevant pharmacological justification. Although Cannabis sativa possesses ethnomedicinal properties in the folk medicine of Bangladesh, it is, furthermore, needed to conduct biological research to consolidate pharmacological justification about the prospects and challenges of Cannabis and cannabinoids' use in Bangladesh as safer biomedicine in the future.
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Affiliation(s)
| | - Matt Gowan
- The Canadian College of Naturopathic Medicine, Toronto, Ontario Canada
| | | | - Md. Nur Kabidul Azam
- Department of Genetic Engineering & Biotechnology, Jashore University of Science & Technology, Jashore, Bangladesh
| | - Md. Nasir Ahmed
- Biotechnology & Natural Medicine Division, TechB Nutrigenomics, Dhaka, Bangladesh
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The Effect of Cannabis on the Clinical and Cytokine Profiles in Patients with Multiple Sclerosis. Mult Scler Int 2021; 2021:6611897. [PMID: 33628507 PMCID: PMC7884151 DOI: 10.1155/2021/6611897] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 01/28/2021] [Accepted: 02/01/2021] [Indexed: 02/08/2023] Open
Abstract
Background Multiple studies have reported that cannabis administration in multiple sclerosis patients is associated with decreased symptom severity. This study was conducted to evaluate the prevalence of cannabis abuse in multiple sclerosis cases and to evaluate the effect of cannabis on serum cytokines in such cases. Patients and Methods. A total of 150 multiple sclerosis cases along with 150 healthy controls were included during the study period. All cases were subjected to history taking, neurological examination, and routine investigations. Cases were asked about cannabis intake which was confirmed by a urine test. Serum cytokines including IL-1, IL-2, IL-4, IL-10, IL-12, IL-17, IL-22, IFN-γ, IFN-β1, and TNF-α were ordered for all cases and controls. Results Twenty-eight cases were cannabis abusers (MS/cannabis group, 18.67%). The remaining 122 cases represented the MS group. There was no significant difference between the three groups regarding age, disease duration, or MS type. Male gender was more predominant in the MS/cannabis group, and the number of relapses was significantly lower in the same group. Fifteen cases (53.6%) reported that their symptoms were improved by cannabis. Proinflammatory cytokines were significantly elevated in the MS group compared to the MS/cannabis and control groups. Additionally, anti-inflammatory cytokines had significantly lower values in the MS group compared to the MS/cannabis and control groups. Most clinical symptoms were significantly improved in the MS/cannabis group compared to the MS group apart from sexual dysfunction, bladder symptoms, and visual disturbances. Mild side effects of cannabis were also reported. Conclusion Cannabis may have a positive impact on the cytokine and clinical profiles in cases with multiple sclerosis.
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Lloyd GL, Wiesen B, Atwell M, Malykhina A. Marijuana, Alcohol, and ED: Correlations with LUTS/BPH. Curr Urol Rep 2021; 22:21. [PMID: 33554319 PMCID: PMC8054558 DOI: 10.1007/s11934-020-01031-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2020] [Indexed: 10/22/2022]
Abstract
PURPOSE OF REVIEW Benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) is a disease complex with enormous societal burden and yet the pathogenesis of LUTS/BPH is poorly understood. We set out to review the literature on the relationship between depression, marijuana usage, and erectile dysfunction (ED) to LUTS/BPH. RECENT FINDINGS LUTS/BPH has independent associations with depression as well as with ED. In each case, the causality and mechanistic relationship is unknown. The impact of marijuana, as it increasingly pervades the general population, on the disease complex of LUTS/BPH is not well studied but recent results support short-term benefit and long-term caution. Depression, a form of central nervous dysfunction, and ED, which is likely mediated via endothelial dysfunction, are independently associated with LUTS/BPH. The presence of cannabinoid receptors in urologic organs, coupled with recent population studies, supports a modulatory effect of marijuana on voiding although an enormous knowledge gap remains.
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Affiliation(s)
- Granville L Lloyd
- Rocky Mountain Regional Veterans Hospital, Aurora, CO, USA.
- Department of Surgery/Urology, University of Colorado Anschutz School of Medicine, Aurora, CO, 80045, USA.
| | - Brett Wiesen
- University of Colorado Anschutz School of Medicine, Aurora, CO, 80045, USA
| | - Mike Atwell
- Division of Urology, Department of Surgery, University of Colorado Anschutz School of Medicine, Aurora, CO, 80045, USA
| | - Anna Malykhina
- Department of Surgery, University of Colorado Anschutz School of Medicine, Aurora, CO, 80045, USA
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21
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Nabata KJ, Tse EK, Nightingale TE, Lee AH, Eng JJ, Querée M, Walter M, Krassioukov AV. The Therapeutic Potential and Usage Patterns of Cannabinoids in People with Spinal Cord Injuries: A Systematic Review. Curr Neuropharmacol 2021; 19:402-432. [PMID: 32310048 PMCID: PMC8033968 DOI: 10.2174/1570159x18666200420085712] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 03/12/2020] [Accepted: 04/15/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND People with spinal cord injuries (SCI) commonly experience pain and spasticity; limitations of current treatments have generated interest in cannabis as a possible therapy. OBJECTIVES We conducted this systematic review to: 1) examine usage patterns and reasons for cannabinoid use, and 2) determine the treatment efficacy and safety of cannabinoid use in people with SCI. METHODS PubMed, Embase, Web of Science and Cumulative Index to Nursing and Allied Health Literature databases were queried for keywords related to SCI and cannabinoids. RESULTS 7,232 studies were screened, and 34 were included in this systematic review. Though 26 studies addressed cannabinoid usage, only 8 investigated its therapeutic potential on outcomes such as pain and spasticity. The most common method of use was smoking. Relief of pain, spasticity and recreation were the most common reasons for use. A statistically significant reduction of pain and spasticity was observed with cannabinoid use in 83% and 100% of experimental studies, respectively. However, on examination of randomized control trials (RCTs) alone, effect sizes ranged from - 0.82 to 0.83 for pain and -0.95 to 0.09 for spasticity. Cannabinoid use was associated with fatigue and cognitive deficits. CONCLUSION Current evidence suggests that cannabinoids may reduce pain and spasticity in people with SCI, but its effect magnitude and clinical significance are unclear. Existing information is lacking on optimal dosage, method of use, composition and concentration of compounds. Long-term, double-blind, RCTs, assessing a wider range of outcomes should be conducted to further understand the effects of cannabinoid use in people with SCI.
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Affiliation(s)
| | | | | | | | | | | | | | - Andrei V. Krassioukov
- Address correspondence to this author at the International Collaboration On Repair Discoveries (ICORD), University of British Columbia (UBC), Vancouver, Canada; E-mail:
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22
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Lopez SR, Mangır N. Current standard of care in treatment of bladder pain syndrome/interstitial cystitis. Ther Adv Urol 2021; 13:17562872211022478. [PMID: 34178118 PMCID: PMC8202321 DOI: 10.1177/17562872211022478] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 05/15/2021] [Indexed: 12/30/2022] Open
Abstract
Bladder pain syndrome/interstitial cystitis (BPS/IC) is a debilitating, systemic pain syndrome with a cardinal symptom of bladder related pain with associated systemic symptoms. It is characterized by an inflammation that partially or completely destroys the mucus membrane and can extend into the muscle layer; however, the etiology and pathogenesis is still enigmatic. It has been suggested that mast cell activation, defects in the glycosaminoglycan layer, non-functional proliferation of bladder epithelial cells, neurogenic inflammation, microvascular abnormalities in the submucosal layer, autoimmunity and infectious causes may cause BPS/IC. Available treatment options include general relaxation techniques, patient education, behavioral treatments, physical therapy, multimodal pain therapy, oral (amitriptyline, cimetidine, hydroxyzine) and intravesical treatments (heparin, lidocaine, hyaluronic acid and chondroitin sulfate), hydrodistension and other more invasive treatments. Available treatments are mostly not based on a high level of evidence. Lack of understanding of disease mechanisms has resulted in lack of targeted therapies on this area and a wealth of empirical approaches with usually inadequate efficacy. The aim of this article is to review the available evidence on the pathophysiological mechanisms of BPS/IC as they relate to available treatment options.
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Affiliation(s)
| | - Naşide Mangır
- Department of Urology, Consultant Urologist and Clinical Lecturer in Urology, Hacettepe University School of Medicine, Sıhhiye, Ankara 06100, Turkey
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Dash R, Ali MC, Jahan I, Munni YA, Mitra S, Hannan MA, Timalsina B, Oktaviani DF, Choi HJ, Moon IS. Emerging potential of cannabidiol in reversing proteinopathies. Ageing Res Rev 2021; 65:101209. [PMID: 33181336 DOI: 10.1016/j.arr.2020.101209] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Revised: 10/22/2020] [Accepted: 11/04/2020] [Indexed: 12/14/2022]
Abstract
The aberrant accumulation of disease-specific protein aggregates accompanying cognitive decline is a pathological hallmark of age-associated neurological disorders, also termed as proteinopathies, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and multiple sclerosis. Along with oxidative stress and neuroinflammation, disruption in protein homeostasis (proteostasis), a network that constitutes protein surveillance system, plays a pivotal role in the pathobiology of these dementia disorders. Cannabidiol (CBD), a non-psychotropic phytocannabinoid of Cannabis sativa, is known for its pleiotropic neuropharmacological effects on the central nervous system, including the ability to abate oxidative stress, neuroinflammation, and protein misfolding. Over the past years, compelling evidence has documented disease-modifying role of CBD in various preclinical and clinical models of neurological disorders, suggesting the potential therapeutic implications of CBD in these disorders. Because of its putative role in the proteostasis network in particular, CBD could be a potent modulator for reversing not only age-associated neurodegeneration but also other protein misfolding disorders. However, the current understanding is insufficient to underpin this proposition. In this review, we discuss the potentiality of CBD as a pharmacological modulator of the proteostasis network, highlighting its neuroprotective and aggregates clearing roles in the neurodegenerative disorders. We anticipate that the current effort will advance our knowledge on the implication of CBD in proteostasis network, opening up a new therapeutic window for aging proteinopathies.
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A Critical Review of the Role of the Cannabinoid Compounds Δ 9-Tetrahydrocannabinol (Δ 9-THC) and Cannabidiol (CBD) and their Combination in Multiple Sclerosis Treatment. Molecules 2020; 25:molecules25214930. [PMID: 33113776 PMCID: PMC7663366 DOI: 10.3390/molecules25214930] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 10/02/2020] [Accepted: 10/07/2020] [Indexed: 02/07/2023] Open
Abstract
Many people with MS (pwMS) use unregulated cannabis or cannabis products to treat the symptoms associated with the disease. In line with this, Sativex, a synthetic combination of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) has been approved to treat symptoms of spasticity. In animals, CBD is effective in reducing the amounts of T-cell infiltrates in the spinal cord, suggesting CBD has anti-inflammatory properties. By doing this, CBD has shown to delay symptom onset in animal models of multiple sclerosis and slow disease progression. Importantly, combinations of CBD and Δ9-THC appear more effective in treating animal models of multiple sclerosis. While CBD reduces the amounts of cell infiltrates in the spinal cord, Δ9-THC reduces scores of spasticity. In human studies, the results are less encouraging and conflict with the findings in animals. Drugs which deliver a combination of Δ9-THC and CBD in a 1:1 ratio appear to be only moderately effective in reducing spasticity scores, but appear to be almost as effective as current front-line treatments and cause less severe side effects than other treatments, such as baclofen (a GABA-B receptor agonist) and tizanidine (an α2 adrenergic receptor agonist). The findings of the studies reviewed suggest that cannabinoids may help treat neuropathic pain in pwMS as an add-on therapy to already established pain treatments. It is important to note that treatment with cannabinoid compounds may cause significant cognitive dysfunction. Long term double-blind placebo studies are greatly needed to further our understanding of the role of cannabinoids in multiple sclerosis treatment.
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Affiliation(s)
- Yara Dadalti Fragoso
- Post-Graduate Program on Health and Environment, Universidade Metropolitana De Santos, Santos, Brazil
- Department of Neurology, MS & Headache Research, Santos, Brazil
| | - Adriana Carra
- MS Section, Hospital Británico De CABA, Buenos Aires, Argentina
| | - Miguel Angel Macias
- Departamento De Neurociencias Y Doctorado De Farmacologia, CUCS, Universidad De Guadalajara, Mexico
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Inglet S, Winter B, Yost SE, Entringer S, Lian A, Biksacky M, Pitt RD, Mortensen W. Clinical Data for the Use of Cannabis-Based Treatments: A Comprehensive Review of the Literature. Ann Pharmacother 2020; 54:1109-1143. [DOI: 10.1177/1060028020930189] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Objective: To compile and synthesize the available literature describing medical cannabis use across various disease states. Data Sources: PubMed, EBSCO, and Google Scholar searches were conducted using MeSH and/or keywords. Study Selection and Data Extraction: Studies were included if they described the use of cannabis-based products and medications in the treatment of a predefined list of disease states in humans and were published in English. The extraction period had no historical limit and spanned through April 2019. Data Synthesis: Evidence was compiled and summarized for the following medical conditions: Alzheimer disease, amyotrophic lateral sclerosis, autism, cancer and cancer-associated adverse effects, seizure disorders, human immunodeficiency virus, inflammatory bowel disease, multiple sclerosis (MS), nausea, pain, posttraumatic stress disorder, and hospice care. Relevance to Patient Care and Clinical Practice: Based on identified data, the most robust evidence suggests that medical cannabis may be effective in the treatment of chemotherapy-induced nausea and vomiting, seizure disorders, MS-related spasticity, and pain (excluding diabetic neuropathy). Overall, the evidence is inconsistent and generally limited by poor quality. The large variation in cannabis-based products evaluated in studies limits the ability to make direct comparisons. Regardless of the product, a gradual dose titration was utilized in most studies. Cannabis-based therapies were typically well tolerated, with the most common adverse effects being dizziness, somnolence, dry mouth, nausea, and euphoria. Conclusions: As more states authorize medical cannabis use, there is an increasing need for high-quality clinical evidence describing its efficacy and safety. This review is intended to serve as a reference for clinicians, so that the risks and realistic benefits of medical cannabis are better understood.
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Affiliation(s)
| | | | | | | | - Anh Lian
- Intermountain Healthcare, Taylorsville, UT, USA
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A Novel Alternative in the Treatment of Detrusor Overactivity? In Vivo Activity of O-1602, the Newly Synthesized Agonist of GPR55 and GPR18 Cannabinoid Receptors. Molecules 2020; 25:molecules25061384. [PMID: 32197469 PMCID: PMC7144400 DOI: 10.3390/molecules25061384] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 03/15/2020] [Accepted: 03/17/2020] [Indexed: 02/07/2023] Open
Abstract
The aim of the research was to assess the impact of O-1602—novel GPR55 and GPR18 agonist—in the rat model of detrusor overactivity (DO). Additionally, its effect on the level of specific biomarkers was examined. To stimulate DO, 0.75% retinyl acetate (RA) was administered to female rats’ bladders. O-1602, at a single dose of 0.25 mg/kg, was injected intra-arterially during conscious cystometry. Furthermore, heart rate, blood pressure, and urine production were monitored for 24 h, and the impact of O-1602 on the levels of specific biomarkers was evaluated. An exposure of the urothelium to RA changed cystometric parameters and enhanced the biomarker levels. O-1602 did not affect any of the examined cystometric parameters or levels of biomarkers in control rats. However, the O-1602 injection into animals with RA-induced DO ameliorated the symptoms of DO and caused a reversal in the described changes in the concentration of CGRP, OCT3, BDNF, and NGF to the levels observed in the control, while the values of ERK1/2 and VAChT were significantly lowered compared with the RA-induced DO group, but were still statistically higher than in the control. O-1602 can improve DO, and may serve as a promising novel substance for the pharmacotherapy of bladder diseases.
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Haddad R, Denys P, Arlandis S, Giannantoni A, Del Popolo G, Panicker JN, De Ridder D, Pauwaert K, Van Kerrebroeck PE, Everaert K. Nocturia and Nocturnal Polyuria in Neurological Patients: From Epidemiology to Treatment. A Systematic Review of the Literature. Eur Urol Focus 2020; 6:922-934. [PMID: 32192920 DOI: 10.1016/j.euf.2020.02.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 01/12/2020] [Accepted: 02/10/2020] [Indexed: 12/12/2022]
Abstract
CONTEXT Nocturia is among the most common and bothersome lower urinary tract symptoms (LUTS), but there is no clear consensus on how to identify and manage this symptom in the neurological population. OBJECTIVE To systematically review the literature about nocturia in neurological patients. EVIDENCE ACQUISITION Studies were identified by electronic search of Cochrane and Medline databases. The studies were included if their participants had acquired neurological pathology among multiple sclerosis (MS), Parkinson's disease (PD), stroke, spinal cord injury (SCI), and reported data on the epidemiology, aetiology, diagnosis, or treatment of nocturia. An independent extraction of the articles was performed by two authors using predetermined datasets, including quality-of-study indicators. EVIDENCE SYNTHESIS A total of 132 studies were included; 46 evaluated the epidemiology of nocturia, 28 the possible aetiologies, 10 the diagnostic tools, and 60 the treatments. Nocturia prevalence ranged from 15% to 96% depending on the pathology and definition used. It was one of the most frequently reported LUTS in PD and stroke patients. Several validated questionnaires were found to screen for nocturia in this population. Causalities were numerous: LUT, renal, sleep, cardiovascular dysfunctions, etc. Treatments targeted these mechanisms, with an overall risk of bias assessed as high or serious. The highest level of evidence was seen in MS patients: pelvic floor muscle training, cannabinoids, and desmopressin were effective, but not melatonin. In stroke patients, transcutaneous sacral and transcutaneous tibial nerve stimulation (TTNS) improved nocturia; in PD patients, TTNS, solifenacin, and rotigotine did not. CONCLUSIONS Nocturia is highly prevalent in patients with neurological disorders. Causalities and treatments are not different from the general population, but are poorly studied in neurological patients. PATIENT SUMMARY In this report, we looked at the published studies about nocturia-the fact of waking to void during the hours of sleep-in patients with neurological diseases. We found that nocturia is very frequent in this population, that the causes are the same as in the general population but may be combined, and that treatments are also the same but have an overall weak level of evidence. We conclude that more research is needed on this topic.
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Affiliation(s)
- Rebecca Haddad
- Urology Department, Ghent University Hospital, Ghent, Belgium.
| | - Pierre Denys
- Neuro-Urology Unit, PMR Department, Université de Versailles Saint Quentin, APHP, Raymond Poincaré Hospital, Garches, France
| | - Salvador Arlandis
- Urology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - Antonella Giannantoni
- Department of Medical and Surgical Sciences and Neurosciences, Functional and Surgical Urology Unit, University of Siena, Siena, Italy
| | - Giulio Del Popolo
- Neuro-Urology & Spinal Unit Department, Careggi University Hospital, Firenze, Italy
| | - Jalesh N Panicker
- Department of Uro-Neurology, The National Hospital for Neurology and Neurosurgery and UCL Queen Square Institute of Neurology, London, UK
| | - Dirk De Ridder
- Urology, University Hospitals KU Leuven, Leuven, Belgium
| | - Kim Pauwaert
- Urology Department, Ghent University Hospital, Ghent, Belgium
| | | | - Karel Everaert
- Urology Department, Ghent University Hospital, Ghent, Belgium
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Sznitman SR, Shochat T, Greene T. Is time elapsed between cannabis use and sleep start time associated with sleep continuity? An experience sampling method. Drug Alcohol Depend 2020; 208:107846. [PMID: 31954953 DOI: 10.1016/j.drugalcdep.2020.107846] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2019] [Revised: 12/26/2019] [Accepted: 01/01/2020] [Indexed: 11/28/2022]
Abstract
BACKGROUND A substantial proportion of people using cannabis report using it to improve sleep. Yet, little research exists on the associations between the timing of cannabis use and sleep. This study examines the time elapsed between cannabis use and sleep start time and its association with two of the main indicators of sleep continuity: (1) sleep onset latency (SOL) and (2) number of awakenings (NOA) throughout the night. METHODS Each morning, for 7 consecutive days, daily cannabis users (n = 54) reported on the timing of previous night's cannabis use and sleep indicators on their smartphones. Mixed effects models examined the relations of within- and between-subjects' time elapsed between previous night cannabis use and sleep start time, with (1) SOL and (2) NOA. RESULTS Within subjects, shorter time elapsed between cannabis use and sleep start time was associated with shorter SOL (β = 0.519, p = 0.010), but not NOA (β = -0.030, p = 0.535). Furthermore, between individuals, the time gap between the previous night cannabis use and sleep start time was not associated with SOL or NOA (p > 0.05). CONCLUSIONS It is possible that cannabis use proximal to bedtime is associated with shorted sleep onset latency but not nighttime awakenings. Cannabis users should be informed about both the potential sleep aid effects of cannabis and its limitations. Pending further evidence of the effects of cannabis on sleep, cannabis users experiencing sleep problems should be provided with evidence-based alternatives to improve sleep, e.g., pharmacological and behavioral treatments.
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Affiliation(s)
- Sharon R Sznitman
- School of Public Health, University of Haifa, Aba Houshy Ave, Haifa, 3498838, Israel.
| | - Tamar Shochat
- The Cheryl Spencer Department of Nursing, University of Haifa, Aba Houshy Ave, Haifa, 3498838, Israel
| | - Talya Greene
- Department of Community Mental Health, University of Haifa, Aba Houshy Ave, Haifa, 3498838, Israel
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Pham MN, Hudnall MT, Nadler RB. Marijuana, Lower Urinary Tract Symptoms, and Pain in the Urologic Patient. Urology 2020; 139:8-13. [PMID: 32027882 DOI: 10.1016/j.urology.2020.01.029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 01/19/2020] [Accepted: 01/21/2020] [Indexed: 10/25/2022]
Abstract
OBJECTIVE To describe marijuana's clinical role for urologic symptoms. METHODS Studies related to marijuana, voiding dysfunction, lower urinary tract symptoms (LUTS), and pain through January 2019 from PubMed were evaluated for relevance and quality. RESULTS Forty-eight studies were reviewed. Cannabinoids have mixed efficacy for neurogenic LUTS and little evidence for non-neurogenic LUTS, chronic non-cancer-related and perioperative pain. For cancer-related pain, high-level studies demonstrate cannabinoids are well-tolerated with unclear benefit. CONCLUSION Cannabinoids appear well-tolerated in the short-term, but their efficacy and long-term impact is unproven and unknown in urologic discomfort. Cannabinoids for urologic symptoms should be further explored with well-designed randomized controlled trials.
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Affiliation(s)
- Minh N Pham
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Matthew T Hudnall
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Robert B Nadler
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL.
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Abstract
Cannabinoid receptors, endocannabinoids and the enzymes responsible for their biosynthesis and degradation constitute the endocannabinoid system. In recent decades, the endocannabinoid system has attracted considerable interest as a potential therapeutic target in numerous pathological conditions. Its involvement in several physiological processes is well known, such as in energy balance, appetite stimulation, blood pressure, pain modulation, embryogenesis, nausea and vomiting control, memory, learning and immune response, among others, as well as in pathological conditions where it exerts a protective role in the development of certain disorders. As a result, it has been reported that changes in endocannabinoid levels may be related to neurological diseases such as Parkinson's disease, Huntington's disease, Alzheimer's disease and multiple sclerosis, as well as anorexia and irritable bowel syndrome. Alterations in the endocannabinoid system have also been associated with cancer, affecting the growth, migration and invasion of some tumours. Cannabinoids have been tested in several cancer types, including brain, breast and prostate cancers. Cannabinoids have shown promise as analgesics for the treatment of both inflammatory and neuropathic pain. There is also evidence for a role of the endocannabinoid system in the control of emotional states, and cannabinoids could prove useful in decreasing and palliating post-traumatic stress disorder symptoms and anxiolytic disorders. The role of the endocannabinoid system in addictions has also been examined, and cannabinoids have been postulated as alternative and co-adjuvant treatments in some abuse syndromes, mainly in ethanol and opioid abuses. The expression of the endocannabinoid system in the eye suggests that it could be a potential therapeutic target for eye diseases. Considering the importance of the endocannabinoid system and the therapeutic potential of cannabinoids in this vast number of medical conditions, several clinical studies with cannabinoid-based medications are ongoing. In addition, some cannabinoid-based medications have already been approved in various countries, including nabilone and dronabinol capsules for the treatment of nausea and vomiting associated with chemotherapy, dronabinol capsules for anorexia, an oral solution of dronabinol for both vomiting associated with chemotherapy and anorexia, a Δ9-tetrahydrocannabinol/cannabidiol oromucosal spray for pain related to cancer and for spasticity and pain associated with multiple sclerosis, and an oral solution of cannabidiol for Dravet and Lennox-Gastaut syndromes. Here, we review the available efficacy, safety and tolerability data for cannabinoids in a range of medical conditions.
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Affiliation(s)
- Ana Isabel Fraguas-Sánchez
- Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Plaza Ramón y Cajal s/n, 28040 , Madrid, Spain
| | - Ana Isabel Torres-Suárez
- Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Plaza Ramón y Cajal s/n, 28040 , Madrid, Spain. .,Institute of Industrial Pharmacy, Complutense University of Madrid, 28040 , Madrid, Spain.
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Nielsen S, Murnion B, Campbell G, Young H, Hall W. Cannabinoids for the treatment of spasticity. Dev Med Child Neurol 2019; 61:631-638. [PMID: 30680713 DOI: 10.1111/dmcn.14165] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/05/2018] [Indexed: 12/19/2022]
Abstract
This review summarizes studies that examined the effectiveness of cannabinoids in treating spasticity, with a focus on understanding the relevance of the existing evidence to paediatric populations. MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched to identify studies that examined the use of cannabinoids in spasticity. We identified 32 studies in adult and paediatric populations. Results were summarized by condition, with adult and paediatric studies considered separately. There is evidence from randomized controlled clinical trials that cannabinoids are more effective than placebo in reducing symptoms of spasticity in adults with multiple sclerosis. Most positive effects were based on patient-rated rather than clinician-rated measures, were modest in size, and should be considered in the context of the narrow therapeutic index of cannabinoids for spasticity and adverse effects. There were comparatively few, and no large studies, of spasticity in conditions other than multiple sclerosis. Few studies have been conducted in paediatric populations. Paediatric studies of spasticity provide low quality evidence and are inadequate to inform clinical practice. Cannabinoids have modest efficacy in reducing muscle spasticity in adults with multiple sclerosis. There is limited evidence of efficacy for cannabinoid use in other conditions, particularly in paediatric populations. Studies in paediatric populations have been of low quality and are insufficient to inform clinical practice.
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Affiliation(s)
- Suzanne Nielsen
- Monash Addiction Research Centre, Monash University, Melbourne, Victoria, Australia.,National Drug and Alcohol Research Centre, UNSW Sydney, Sydney, New South Wales, Australia
| | - Bridin Murnion
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.,Drug Health Services, Sydney Local Health District, Sydney, New South Wales, Australia.,Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
| | - Gabrielle Campbell
- National Drug and Alcohol Research Centre, UNSW Sydney, Sydney, New South Wales, Australia
| | - Helen Young
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.,Royal North Short Hospital, St Leonards, New South Wales, Australia.,Neurogenetics, The Children's Hospital at Westmead, Westmead, New South Wales, Australia
| | - Wayne Hall
- Centre for Youth Substance Abuse Research, The University of Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
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RABIEI Z. Phytotherapy as a Complementary Medicine for Multiple Sclerosis. Turk J Pharm Sci 2019; 16:246-251. [PMID: 32454721 PMCID: PMC7227963 DOI: 10.4274/tjps.galenos.2018.90522] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 09/06/2018] [Indexed: 12/13/2022]
Abstract
Multiple sclerosis (MS) is the most common cause of neurologic disability in adults worldwide. Two main issues have caused MS patients to face several problems. One issue is that the definite cause of MS has not yet been determined and the other issue is the lack of a definite treatment for this disease. The people with MS, therefore, seek out complementary and alternative medications to manage the symptoms of this disease. Meanwhile, medicinal plants have been demonstrated to have possible positive pharmacological effects in treating MS in different models. The reliable articles indexed in the databases Web of Science, Scopus, PubMed Central, PubMed, Scientific Information Database, and Institute for Scientific Information were retrieved and analyzed to conduct this review. Medicinal plants and plant compounds caused decreases in the neurologic deficits due to MS. Clinical evidence has demonstrated the clinical potential of Cannabis sativa extract, cannabinoids, Ginkgo biloba, beta-phytosterol, and Lippia citriodora extract to improve MS symptoms. These plants and compounds can also improve spasticity, muscle spasm, neuropathic pain, and urinary tract complications in at least some of these patients. Nanocurcumins and Punica granatum L. peel extract have exhibited positive effects in animal models and can decrease neurologic deficits by reducing inflammation. Medicinal plants and their compounds can serve as new sources of MS drugs because they can improve MS symptoms.
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Affiliation(s)
- Zahra RABIEI
- Shahrekord University of Medical Sciences, Basic Health Sciences Institute, Medical Plants Research Center, Shahrekord, Iran
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Fantus RJ, Helfand BT. AUTHOR REPLY. Urology 2019; 123:124-125. [PMID: 30598201 DOI: 10.1016/j.urology.2018.06.056] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 06/11/2018] [Accepted: 06/17/2018] [Indexed: 11/25/2022]
Affiliation(s)
- Richard J Fantus
- Section of Urology, Department of Surgery, University of Chicago Medicine, Chicago, IL
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Mojaverrostami S, Bojnordi MN, Ghasemi-Kasman M, Ebrahimzadeh MA, Hamidabadi HG. A Review of Herbal Therapy in Multiple Sclerosis. Adv Pharm Bull 2018; 8:575-590. [PMID: 30607330 PMCID: PMC6311642 DOI: 10.15171/apb.2018.066] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Revised: 07/30/2018] [Accepted: 08/15/2018] [Indexed: 12/29/2022] Open
Abstract
Multiple sclerosis is a complex autoimmune disorder which characterized by demyelination and axonal loss in the central nervous system (CNS). Several evidences indicate that some new drugs and stem cell therapy have opened a new horizon for multiple sclerosis treatment, but current therapies are partially effective or not safe in the long term. Recently, herbal therapies represent a promising therapeutic approach for multiple sclerosis disease. Here, we consider the potential benefits of some herbal compounds on different aspects of multiple sclerosis disease. The medicinal plants and their derivatives; Ginkgo biloba, Zingiber officinale, Curcuma longa, Hypericum perforatum, Valeriana officinalis, Vaccinium macrocarpon, Nigella sativa,Piper methysticum, Crocus sativus, Panax ginseng, Boswellia papyrifera, Vitis vinifera, Gastrodia elata, Camellia sinensis, Oenothera biennis, MS14 and Cannabis sativa have been informed to have several therapeutic effects in MS patients.
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Affiliation(s)
- Sina Mojaverrostami
- Young Researchers and Elite Club, Behshahr Branch, Islamic Azad University, Behshahr, Iran
| | - Maryam Nazm Bojnordi
- Department of Anatomy & Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.,Cellular and Molecular Research Center, Department of Anatomy & Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Maryam Ghasemi-Kasman
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Mohammad Ali Ebrahimzadeh
- Pharmaceutical Sciences Research Center, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
| | - Hatef Ghasemi Hamidabadi
- Department of Anatomy & Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.,Immunogenetic Research Center, Department of Anatomy & Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
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Russo EB. Cannabis Therapeutics and the Future of Neurology. Front Integr Neurosci 2018; 12:51. [PMID: 30405366 PMCID: PMC6200872 DOI: 10.3389/fnint.2018.00051] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Accepted: 10/01/2018] [Indexed: 12/29/2022] Open
Abstract
Neurological therapeutics have been hampered by its inability to advance beyond symptomatic treatment of neurodegenerative disorders into the realm of actual palliation, arrest or reversal of the attendant pathological processes. While cannabis-based medicines have demonstrated safety, efficacy and consistency sufficient for regulatory approval in spasticity in multiple sclerosis (MS), and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges remain. This review will examine the intriguing promise that recent discoveries regarding cannabis-based medicines offer to neurological therapeutics by incorporating the neutral phytocannabinoids tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), and cannabis terpenoids in the putative treatment of five syndromes, currently labeled recalcitrant to therapeutic success, and wherein improved pharmacological intervention is required: intractable epilepsy, brain tumors, Parkinson disease (PD), Alzheimer disease (AD) and traumatic brain injury (TBI)/chronic traumatic encephalopathy (CTE). Current basic science and clinical investigations support the safety and efficacy of such interventions in treatment of these currently intractable conditions, that in some cases share pathological processes, and the plausibility of interventions that harness endocannabinoid mechanisms, whether mediated via direct activity on CB1 and CB2 (tetrahydrocannabinol, THC, caryophyllene), peroxisome proliferator-activated receptor-gamma (PPARγ; THCA), 5-HT1A (CBD, CBDA) or even nutritional approaches utilizing prebiotics and probiotics. The inherent polypharmaceutical properties of cannabis botanicals offer distinct advantages over the current single-target pharmaceutical model and portend to revolutionize neurological treatment into a new reality of effective interventional and even preventative treatment.
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Affiliation(s)
- Ethan B Russo
- International Cannabis and Cannabinoids Institute (ICCI), Prague, Czechia
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Fantus RJ, Riedinger CB, Chang C, Helfand BT. The Association Between Tetrahydrocannabinol and Lower Urinary Tract Symptoms Utilizing the National Health and Nutrition Examination Survey. Urology 2018; 123:120-125. [PMID: 30142408 DOI: 10.1016/j.urology.2018.06.054] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 06/11/2018] [Accepted: 06/17/2018] [Indexed: 01/06/2023]
Abstract
OBJECTIVE To further define the relationship between tetrahydrocannabinol (THC) and lower urinary tract symptoms (LUTS), specifically how THC use associates with the frequency of LUTS in young community-dwelling men in the United States. MATERIALS AND METHODS The National Health and Nutrition Examination Survey database was queried (2005-2008). Men ages 20-59 who completed the urinary and substance abuse questionnaires were included. The presence of LUTS was defined as having ≥2 of the following: nocturia (≥2), hesitancy, incomplete emptying, or incontinence. THC use was self-reported, and participants were considered regular smokers if they endorsed smoking at least once per month. Multivariable logistic regression was performed to analyze the relationship between THC and LUTS. RESULTS Among 3,037 men who met inclusion criteria, 14.4% (n = 477) of subjects reported THC use. In multivariable analyses, adjusting for clinical variables, regular THC users remained significantly less likely to report LUTS (odds ratio of 0.55; confidence interval 95% 0.408-0.751, P <.01) compared to nonusers. CONCLUSION Obesity, diabetes, and multiple comorbidities are well-established risk factors for LUTS within the National Health and Nutrition Examination Survey. Regular THC use, however, appears to be protective from LUTS in young community-dwelling men.
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Affiliation(s)
- Richard J Fantus
- Section of Urology, Department of Surgery, University of Chicago Medicine, Chicago, IL
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Bailey SM, Rice CM. Symptomatic Treatment for Progressive Multiple Sclerosis. PROGRESSIVE MULTIPLE SCLEROSIS 2018:155-205. [DOI: 10.1007/978-3-319-65921-3_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Kim SD, Cho KJ, Kim JC. Expression of cannabinoid 1 and, 2 receptors and the effects of cannabinoid 1 and, 2 receptor agonists on detrusor overactivity associated with bladder outlet obstruction in rats. BMC Urol 2017; 17:121. [PMID: 29284441 PMCID: PMC5747270 DOI: 10.1186/s12894-017-0313-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2017] [Accepted: 12/20/2017] [Indexed: 12/21/2022] Open
Abstract
Background This study investigated changes in the expression of cannabinoid (CB) receptors and the effects of CB1 and CB2 agonists on detrusor overactivity (DO) associated with bladder outlet obstruction (BOO) in rats. Methods Male Sprague Dawley rats were randomly assigned to four groups (n = 10) in each group. The control group comprised sham-operated rats. A animals in the BOO, CB1 agonist and CB2 agonist groups all underwent BOO surgery. Three weeks postoperatively, cystometrography (CMG) was performed on all rats. After confirming the presence of DO in the CB1 and CB2 agonist groups, a CB1 agonist (WIN 55,212–2) and a CB2 agonist (CB65) were instilled intravesically, and CMG was repeated. CMG parameters, including the contraction interval (CI) and contraction pressure (CP) were then analyzed. The bladders of rats in all four groups were excised following CMG. Immunofluorescence staining and Western blotting were performed to localize CB1 and CB2 and measure their expression levels in the urothelium and detrusor muscle. Results The CI was significantly longer and the CP was significantly lower in the CB1 agonist group than in the BOO group. CI and CP in the CB2 agonist group showed the same results. CB1 receptor immunofluorescence staining signals and immunoreactive bands in Western blotting were increased in the BOO group compared with results in the control group. Similarly, results for the CB2 receptor were also increased in the BOO group, although this difference was not significant. The CMG parameters in the BOO group were significantly improved by the inhibitory effects of CB1 and CB2 agonists on BOO-associated DO. The expression of CB1 was significantly increased in the urothelium and detrusor muscle in BOO-associated DO, but no significant change in CB2 expression was observed. Conclusions CB1 and CB2 receptors, especially CB1, play a role in the pathophysiology of BOO-associated DO, and could serve as therapeutic targets.
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Affiliation(s)
- Sung Dae Kim
- Department of Urology, Graduate School of Medicine, Jeju National University, Jeju, South Korea
| | - Kang Jun Cho
- Department of Urology, Bucheon St. Mary's hospital, College of Medicine, The Catholic University of Korea, Sosa-Ro 327, Wonmi-gu, Bucheon-si, Gyeonggi-do, Seoul, 14647, South Korea
| | - Joon Chul Kim
- Department of Urology, Bucheon St. Mary's hospital, College of Medicine, The Catholic University of Korea, Sosa-Ro 327, Wonmi-gu, Bucheon-si, Gyeonggi-do, Seoul, 14647, South Korea.
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Neues zur symptomatischen MS-Therapie: Teil 3 – Blasenfunktionsstörungen. DER NERVENARZT 2017; 89:184-192. [DOI: 10.1007/s00115-017-0440-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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THC/CBD oromucosal spray in patients with multiple sclerosis overactive bladder: a pilot prospective study. Neurol Sci 2017; 39:97-102. [PMID: 29052091 DOI: 10.1007/s10072-017-3148-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Accepted: 10/06/2017] [Indexed: 12/20/2022]
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Farzaei MH, Shahpiri Z, Bahramsoltani R, Nia MM, Najafi F, Rahimi R. Efficacy and Tolerability of Phytomedicines in Multiple Sclerosis Patients: A Review. CNS Drugs 2017; 31:867-889. [PMID: 28948486 DOI: 10.1007/s40263-017-0466-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disorder of the central nervous system (CNS) that can cause cognition, mobility, and sensory impairments. It is considered one of the most common non-traumatic causes of disability in the world. The aim of the present article was to review the clinical evidence related to medicinal plants in the management of MS symptoms. Electronic databases, including the Cochrane Library, Pubmed, and Scopus, were searched for entries from 1966 to February 2017. Only clinical studies were included in this review. Different medicinal plants have positive effects on MS, including Andrographis paniculata, Boswellia papyrifera, Ruta graveolens, Vaccinium spp., Camellia sinensis, Panax ginseng, Aloysia citrodora, Ginkgo biloba, Oenothera biennis, and Cannabis sativa. C. sativa had the highest level of clinical evidence, supporting its efficacy in MS symptoms. Proanthocyanidins, ginkgo flavone glycosides, ginsenosides, epigallocatechin-3-gallate, cannabinoids (including delta-9-tetrahydrocannabinol and cannabidiol), boswellic acid, and andrographolide were presented as the main bioactive components of medicinal plants with therapeutic benefits in MS. The main complications of MS in which natural drugs were effective include spasticity, fatigue, scotoma, incontinence, urinary urgency, nocturia, memory performance, functional performance, and tremor. Herbal medicines were mostly well tolerated, and the adverse effects were limited to mild to moderate. Further well-designed human studies with a large sample size and longer follow-up period are recommended to confirm the role of medicinal plants and their metabolites in the management of MS.
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Affiliation(s)
- Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Zahra Shahpiri
- Department of Traditional Pharmacy, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, 1417653761, Iran
- PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Roodabeh Bahramsoltani
- Department of Traditional Pharmacy, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, 1417653761, Iran
- PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Marjan Moghaddam Nia
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
- PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Kermanshah, Iran
| | - Fariba Najafi
- Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Roja Rahimi
- Department of Traditional Pharmacy, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, 1417653761, Iran.
- PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
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Nedumaran B, Rudra P, Gaydos J, Kumar S, Meacham RB, Burnham EL, Malykhina AP. Impact of Regular Cannabis Use on Biomarkers of Lower Urinary Tract Function. Urology 2017; 109:223.e9-223.e16. [PMID: 28827195 DOI: 10.1016/j.urology.2017.08.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Revised: 07/31/2017] [Accepted: 08/07/2017] [Indexed: 12/24/2022]
Abstract
OBJECTIVE To evaluate the differences in the composition and quantities of urine peptides in regular cannabis users and nonusers by liquid chromatography tandem mass spectrometry analysis. MATERIALS AND METHODS Urine specimens from healthy control subjects and cannabis users were utilized to identify the differences in the number and quantity of urine proteins by liquid chromatography tandem mass spectrometry analysis. Significantly altered proteins were determined by a permutation testing statistical method. Heat map, dendrogram, pathway, and network analyses were performed to assess the degree of expression and the potential relationships between proteins in both groups. RESULTS A total of 1337 proteins were detected in both groups with 19 proteins being significantly altered in cannabis users. Innate immunity and carbohydrate metabolic pathways were highly linked with upregulated proteins in the cannabis group. Additionally, 91 proteins were present and 46 proteins were absent only in cannabis users in comparison with the control cohort. Our results suggest that regular use of cannabis is associated with significant alterations in a number of urinary peptides, with a large number of proteins present or absent only in cannabis users. Pathway analyses demonstrated an increased immune response in cannabis users compared with controls. CONCLUSION Our observations potentially indicate activation (or inhibition) of specific signaling pathways in the lower urinary tract during chronic exposure to exogenous cannabinoids. Our study provides initial proteomic knowledge for future investigations on the potential role of exocannabinoids in the development of intravesical therapies to treat lower urinary tract disorders.
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Affiliation(s)
- Balachandar Nedumaran
- Division of Urology, Department of Surgery, University of Colorado Denver, Aurora, CO
| | - Pratyaydipta Rudra
- Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, Aurora, CO
| | - Jeanette Gaydos
- Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, Aurora, CO
| | - Sushil Kumar
- Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Denver, Aurora, CO
| | - Randall B Meacham
- Division of Urology, Department of Surgery, University of Colorado Denver, Aurora, CO
| | - Ellen L Burnham
- Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, Aurora, CO
| | - Anna P Malykhina
- Division of Urology, Department of Surgery, University of Colorado Denver, Aurora, CO.
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Aharony SM, Lam O, Corcos J. Treatment of lower urinary tract symptoms in multiple sclerosis patients: Review of the literature and current guidelines. Can Urol Assoc J 2017; 11:E110-E115. [PMID: 28360957 DOI: 10.5489/cuaj.4059] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Multiple sclerosis (MS) is a unique neurological disease with a broad spectrum of clinical presentations that are time- and disease course-related. Lower urinary tract symptoms (LUTS) are highly prevalent in this patient population, with approximately 90% showing some degree of voiding dysfunction and/or incontinence 6-8 years after the initial MS diagnosis. Major therapeutic goals include quality of life improvement and the avoidance of urological complications Owing to the wide divergence of clinical symptoms and disease course, evaluation and treatment differ between patients. Treatment must be customized for each patient based on disease phase, patient independence, manual dexterity, social support, and other medical- or MS-related issues. Ablative or irreversible therapies are indicated only when the disease course is stable. In most cases of "safe" bladder, behavioural treatment is considered first-line defense. Antimuscarinic drugs, alone or in combination with intermittent self-catheterization, are currently the mainstay of conservative treatment, and several other medications may help in specific disease conditions. Second-line treatment includes botulinum toxin A injection, neuromodulation, indwelling catheters, and surgery in well-selected cases.
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Affiliation(s)
| | - Ornella Lam
- Department of Urology, Jewish General Hospital, McGill University, Montreal, QC, Canada
| | - Jacques Corcos
- Department of Urology, Jewish General Hospital, McGill University, Montreal, QC, Canada
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Abo Youssef N, Schneider MP, Mordasini L, Ineichen BV, Bachmann LM, Chartier-Kastler E, Panicker JN, Kessler TM. Cannabinoids for treating neurogenic lower urinary tract dysfunction in patients with multiple sclerosis: a systematic review and meta-analysis. BJU Int 2017; 119:515-521. [DOI: 10.1111/bju.13759] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Nadim Abo Youssef
- Neuro-Urology, Spinal Cord Injury Center and Research; Balgrist University Hospital; University of Zürich; Zürich Switzerland
| | - Marc P. Schneider
- Neuro-Urology, Spinal Cord Injury Center and Research; Balgrist University Hospital; University of Zürich; Zürich Switzerland
- Brain Research Institute; University of Zürich; Zürich Switzerland
- Department of Health Sciences and Technology; Swiss Federal Institute of Technology Zürich; Zürich Switzerland
| | - Livio Mordasini
- Department of Urology; Cantonal Hospital Lucerne; Lucerne Switzerland
| | - Benjamin V. Ineichen
- Brain Research Institute; University of Zürich; Zürich Switzerland
- Department of Health Sciences and Technology; Swiss Federal Institute of Technology Zürich; Zürich Switzerland
| | | | - Emmanuel Chartier-Kastler
- Department of Urology; Academic Hospital Pitié-Salpêtrière; Assistance Publique-Hôpitaux de Paris; Pierre et Marie Curie Medical School; Sorbonne Universités; Paris 6 University; Paris France
| | - Jalesh N. Panicker
- Department of Uro-Neurology; National Hospital for Neurology and Neurosurgery and UCL Institute of Neurology; London UK
| | - Thomas M. Kessler
- Neuro-Urology, Spinal Cord Injury Center and Research; Balgrist University Hospital; University of Zürich; Zürich Switzerland
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Abstract
Although there is a growing literature on the presence of sleep disorders in multiple sclerosis (MS), few studies have specifically addressed the impact of drugs on sleep of these patients. Moreover, even when sleep is considered, quantitative assessment by standardized questionnaires or polysomnography is lacking. The studies that have been done highlight that interferon-beta and some symptomatic medications may affect sleep, thus contributing to fatigue, depression, and poor quality of life; conversely, natalizumab and cannabinoids may improve sleep. Common limitations of the literature reviewed here are small sample size, selection bias, and often a lack of objective outcome measures. Clinicians need to remember to ask about sleep in all MS patients and intervene when appropriate. A systematic approach that takes sleep into account is recommended to enhance recognition and appropriate management of sleep disruption, including disorders related to medication. Consideration of the impact on sleep should also be part of the design of trials of new therapies.
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Affiliation(s)
- Giuseppe Lanza
- Sleep Research Center, Department of Neurology I.C., I.R.C.C.S. Oasi Maria SS., Troina, Italy
| | - Raffaele Ferri
- Sleep Research Center, Department of Neurology I.C., I.R.C.C.S. Oasi Maria SS., Troina, Italy
| | - Rita Bella
- Department of Medical and Surgical Sciences and Advanced Technologies, Section of Neurosciences, University of Catania, Catania, Italy
| | - Luigi Ferini-Strambi
- Department of Clinical Neurosciences, Sleep Disorders Center, Università Vita-Salute San Raffaele, Milan, Italy
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Natural products against Alzheimer's disease: Pharmaco-therapeutics and biotechnological interventions. Biotechnol Adv 2016; 35:178-216. [PMID: 28043897 DOI: 10.1016/j.biotechadv.2016.12.005] [Citation(s) in RCA: 154] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2015] [Revised: 12/19/2016] [Accepted: 12/23/2016] [Indexed: 12/30/2022]
Abstract
Alzheimer's disease (AD) is a severe, chronic and progressive neurodegenerative disease associated with memory and cognition impairment ultimately leading to death. It is the commonest reason of dementia in elderly populations mostly affecting beyond the age of 65. The pathogenesis is indicated by accumulation of the amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFT) in brain tissues and hyperphosphorylation of tau protein in neurons. The main cause is considered to be the formation of reactive oxygen species (ROS) due to oxidative stress. The current treatment provides only symptomatic relief by offering temporary palliative therapy which declines the rate of cognitive impairment associated with AD. Inhibition of the enzyme acetylcholinesterase (AChE) is considered as one of the major therapeutic strategies offering only symptomatic relief and moderate disease-modifying effect. Other non-cholinergic therapeutic approaches include antioxidant and vitamin therapy, stem cell therapy, hormonal therapy, use of antihypertensive or lipid-lowering medications and selective phosphodiesterase (PDE) inhibitors, inhibition of β-secretase and γ-secretase and Aβ aggregation, inhibition of tau hyperphosphorylation and intracellular NFT, use of nonsteroidal anti-inflammatory drugs (NSAIDs), transition metal chelators, insulin resistance drugs, etanercept, brain-derived neurotrophic factor (BDNF) etc. Medicinal plants have been reported for possible anti-AD activity in a number of preclinical and clinical trials. Ethnobotany, being popular in China and in the Far East and possibly less emphasized in Europe, plays a substantial role in the discovery of anti-AD agents from botanicals. Chinese Material Medica (CMM) involving Chinese medicinal plants has been used traditionally in China in the treatment of AD. Ayurveda has already provided numerous lead compounds in drug discovery and many of these are also undergoing clinical investigations. A number of medicinal plants either in their crude forms or as isolated compounds have exhibited to reduce the pathological features associated with AD. In this present review, an attempt has been made to elucidate the molecular mode of action of various plant extracts, phytochemicals and traditional herbal formulations investigated against AD as reported in various preclinical and clinical tests. Herbal synergism often found in polyherbal formulations were found effective to combat disease heterogeneity as found in complex pathogenesis of AD. Finally a note has been added to describe biotechnological improvement, genetic and genomic resources and mathematical and statistical techniques for empirical model building associated with anti-AD plant secondary metabolites and their source botanicals.
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Hedlund P, Gratzke C. The endocannabinoid system — a target for the treatment of LUTS? Nat Rev Urol 2016; 13:463-70. [DOI: 10.1038/nrurol.2016.110] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Wade DT, Makela PM, House H, Bateman C, Robson P. Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis. Mult Scler 2016; 12:639-45. [PMID: 17086911 DOI: 10.1177/1352458505070618] [Citation(s) in RCA: 194] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The object of this study was to monitor the safety and efficacy of long-term use of an oromucosal cannabis-based medicine (CBM) in patients with multiple sclerosis (MS). A total of 137 MS patients with symptoms not controlled satisfactorily using standard drugs entered this open-label trial following a 10-week, placebo-controlled study. Patients were assessed every eight weeks using visual analogue scales and diary scores of main symptoms, and were followed for an average of 434 days (range: 21- 814). A total of 58 patients (42.3%) withdrew due to lack of efficacy (24); adverse events (17); withdrew consent (6); lost to follow-up (3); and other (8). Patients reported 292 unwanted effects, of which 251 (86%) were mild to moderate, including oral pain (28), dizziness (20), diarrhoea (17), nausea (15) and oromucosal disorder (12). Three patients had five ‘serious adverse events’ between them - two seizures, one fall, one aspiration pneumonia, one gastroenteritis. Four patients had first-ever seizures. The improvements recorded and dosage taken in the acute study remained stable. Planned, sudden interruption of CBM for two weeks in 25 patients (of 62 approached) did not cause a consistent withdrawal syndrome, although 11 (46%) patients reported at least one of - tiredness, interrupted sleep, hot and cold flushes, mood alteration, reduced appetite, emotional lability, intoxication or vivid dreams. Twenty-two (88%) patients re-started CBM treatment. We conclude that long-term use of an oromucosal CBM (Sativex) maintains its effect in those patients who perceive initial benefit. The precise nature and rate of risks with long-term use, especially epilepsy, will require larger and longer-term studies.
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Affiliation(s)
- D T Wade
- Oxford Centre for Enablement, Windmill Road, Oxford OX3 7LD, UK.
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