Cannabinoids: an Effective Treatment for Chemotherapy-Induced Peripheral Neurotoxicity?

AbstractChemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most frequent side effects of antineoplastic treatment, particularly of lung, breast, prostate, gastrointestinal, and germinal cancers, as well as of different forms of leukemia, lymphoma, and multiple myeloma. Currently, no effective therapies are available for CIPN prevention, and symptomatic treatment is frequently ineffective; thus, several clinical trials are addressing this unmet clinical need. Among possible pharmacological treatments of CIPN, modulation of the endocannabinoid system might be particularly promising, especially in those CIPN types where analgesia and neuroinflammation modulation might be beneficial. In fact, several clinical trials are ongoing with the specific aim to better investigate the changes in endocannabinoid levels induced by systemic chemotherapy and the possible role of endocannabinoid system modulation to provide relief from CIPN symptoms, a hypothesis supported by preclinical evidence but never consistently demonstrated in patients. Interestingly, endocannabinoid system modulation might be one of the mechanisms at the basis of the reported efficacy of exercise and physical therapy in CIPN patients. This possible virtuous interplay will be discussed in this review.

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An update on the role of daratumumab in the treatment of multiple myeloma

Therapeutic Advances in Hematology ◽

10.1177/2040620716677523 ◽

2016 ◽

Vol 8 (1) ◽

pp. 28-37 ◽

Cited By ~ 16

Author(s):

Caitlin Costello

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Blood Compatibility ◽

Daily Practice ◽

Combination Strategies ◽

Heavily Pretreated ◽

Pretreated Patients ◽

Phase Ii And Iii ◽

Future Plans

Monoclonal antibodies (mAbs) have emerged as a promising new drug class for the treatment of multiple myeloma (MM). Daratumumab (DARA), a CD38 mAb, has demonstrated safety, tolerability and activity in a range of clinical trials, both as monotherapy and in combination strategies for MM. The favorable efficacy results in heavily pretreated patients with advanced MM have provided the rationale for the investigation of DARA in a number of ongoing and future phase II and III trials. The general tolerability of mAbs has allowed for widespread investigation and use of DARA among a variety of MM patients, however their use requires special consideration. Infusion-related reactions (IRRs), interference with blood compatibility assays and response assessments are all unique factors related to the use of DARA. This review provides an update of the results from the DARA clinical trials conducted to date, its future plans for investigation, and practical management considerations for the use of DARA in daily practice.

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The role of erenumab in the treatment of migraine

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286420927119 ◽

2020 ◽

Vol 13 ◽

pp. 175628642092711 ◽

Cited By ~ 1

Author(s):

Anna P. Andreou ◽

Matteo Fuccaro ◽

Giorgio Lambru

Keyword(s):

Clinical Trials ◽

Side Effects ◽

European Medicines Agency ◽

Human Antibody ◽

Subcutaneous Injections ◽

Calcitonin Gene ◽

The Us ◽

Different Doses

Calcitonin gene related peptide (CGRP) monoclonal antibodies (mAbs) have been the first class of specifically developed preventive treatments for migraine. Clinical trials data suggest superiority of the CGRP mAbs to placebo in terms of prevention of migraine symptoms, migraine-specific quality of life and headache related disability. Treatment-related side effects overall did not differ significantly from placebo and discontinuation rate due to side effects has been low across the clinical trials, perhaps in view of their peripheral mode of action. Along with their route and frequency of administration, these novel class of drugs may constitute an improvement compared with the established arsenal of migraine treatments. Erenumab is a fully human antibody and the only mAb acting on the CGRP pathway by blocking its receptor. It is the first of the CGRP mAb class approved by the US Food and Drug Administration (May 2018) and the European Medicines Agency (July 2018). Erenumab exists in two different doses (70 mg and 140 mg) and it is administered with monthly subcutaneous injections. This review summarises erenumab pharmacological characteristics, clinical trials data, focusing on the potential role of this treatment in clinical practice.

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Disease and outcome disparities in multiple myeloma: exploring the role of race/ethnicity in the Cooperative Group clinical trials

Blood Cancer Journal ◽

10.1038/s41408-018-0102-7 ◽

2018 ◽

Vol 8 (7) ◽

Cited By ~ 22

Author(s):

Sikander Ailawadhi ◽

Susanna Jacobus ◽

Rachael Sexton ◽

Alexander K. Stewart ◽

Angela Dispenzieri ◽

...

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Cooperative Group ◽

Race Ethnicity

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Mathematical modelling of the role of GADD45β in the pathogenesis of multiple myeloma

Royal Society Open Science ◽

10.1098/rsos.192152 ◽

2020 ◽

Vol 7 (5) ◽

pp. 192152

Author(s):

Yao Zhang ◽

Changqing Zhen ◽

Qing Yang ◽

Bing Ji

Keyword(s):

Multiple Myeloma ◽

Side Effects ◽

Bone Cells ◽

Specific Treatment ◽

Underlying Mechanism ◽

High Morbidity ◽

Jnk Pathway ◽

Incurable Disease ◽

Targeted Treatments

Multiple myeloma (MM) is an incurable disease with relatively high morbidity and mortality rates. Great efforts were made to develop nuclear factor-kappa B (NF-κB)-targeted therapies against MM disease. However, these treatments influence MM cells as well as normal cells, inevitably causing serious side effects. Further research showed that NF-κB signalling promotes the survival of MM cells by interacting with JNK signalling through growth arrest and DNA damage-inducible beta (GADD45β), the downstream module of NF-κB signalling. The GADD45β-targeted intervention was suggested to be an effective and MM cell-specific treatment. However, the underlying mechanism through which GADD45β promotes the survival of MM cells is usually ignored in the previous models. A mathematical model of MM is built in this paper to investigate how NF-κB signalling acts along with JNK signalling through GADD45β and MKK7 to promote the survival of MM cells. The model cannot only mimic the variations in bone cells, the bone volume and MM cells with time, but it can also examine how the NF-κB pathway acts with the JNK pathway to promote the development of MM cells. In addition, the model also investigates the efficacies of GADD45β - and NF-κB-targeted treatments, suggesting that GADD45β-targeted therapy is more effective but has no apparent side effects. The simulation results match the experimental observations. It is anticipated that this model could be employed as a useful tool to initially investigate and even explore potential therapies involving the NF-κB and JNK pathways in the future.

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Daratumumab in untreated newly diagnosed multiple myeloma

Therapeutic Advances in Hematology ◽

10.1177/2040620719894871 ◽

2019 ◽

Vol 10 ◽

pp. 204062071989487 ◽

Cited By ~ 8

Author(s):

Nadine Abdallah ◽

Shaji K. Kumar

Keyword(s):

Multiple Myeloma ◽

Monoclonal Antibody ◽

Clinical Trials ◽

High Risk ◽

Human Monoclonal Antibody ◽

Proteasome Inhibitors ◽

Immunomodulatory Drugs ◽

Newly Diagnosed ◽

Infusion Reactions

The treatment of multiple myeloma has evolved markedly in the last decade, but mortality remains high, emphasizing the need for more effective therapies. Daratumumab, a fully human monoclonal antibody targeting CD38, has shown clinical efficacy in relapsed/refractory multiple myeloma both as monotherapy and in combination with other drugs, including novel agents. More recently, promising results have been reported in patients with untreated newly diagnosed multiple myeloma (NDMM). Clinical trials thus far have shown enhanced efficacy and tolerability of several daratumumab-based combinations in both transplant ineligible and eligible patients, without compromising transplant ability. However, benefit in high-risk subpopulations is still unclear. A subcutaneous formulation of daratumumab has been introduced to decrease the risk of infusion reactions, with preliminary results showing non-inferior efficacy. The antimyeloma activity of daratumumab is achieved through multiple mechanisms including direct, Fc-dependent, and immunomodulatory mechanisms. Enhanced efficacy of daratumumab in combination with immunomodulatory drugs and proteasome inhibitors is supported by preclinical data showing synergism. This review will focus on the role of daratumumab in untreated NDMM patients, highlighting the results of major clinical trials, and listing ongoing trials that are evaluating various daratumumab-based combinations in this setting.

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A review on five medicinal plants considering the therapeutic potentials in the management of COVID-19

10.31219/osf.io/ekf8n ◽

2020 ◽

Author(s):

Fahad Jubayer ◽

Shahidullah Kayshar ◽

Anisur Rahman Mazumder ◽

Syeda Sabrina Akter

Keyword(s):

Clinical Trials ◽

Side Effects ◽

Medicinal Plants ◽

Therapeutic Option ◽

Pharmacological Properties ◽

Specific Effects ◽

Control Options ◽

Life Threatening ◽

Working Mechanisms

The spread of pandemic coronavirus disease-2019 has become a health emergency worldwide. Since the unprecedented outbreak, attention has been raised worldwide to develop and research for control options and treatments. Although several clinical trials are ongoing, no registered drugs or vaccines are available yet. As situation warrants for the exploration of a successful antiviral, there should be a search for the remedies in nature also. Medicinal plants and their metabolites have long been used as a treatment option for various life-threatening diseases with minimal or no side effects. Thus this review aims to summarize previous outcomes concerning the role of medicinal plants in treating several life-threatening diseases. Above all, this work intends to find the constituents of five selected medicinal plants and their possible working mechanisms in the management of COVID-19. Constituents of the presented medicinal plants possess excellent pharmacological properties, including significant antiviral and antimicrobial potential. Based on the traditional uses, pharmacological properties, and previous studies, these medicinal plants mentioned in this review can be considered as a possible therapeutic option for the management and treatment of COVID-19. However, further extensive researches and trials are suggested to discover specific effects and dosage for this pathogenic outbreak.

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Herbal Home Remedies for Toothache during the COVID-19 Pandemic: A Review

Himalayan Journal of Health Sciences ◽

10.22270/hjhs.v6i3.104 ◽

2021 ◽

pp. 18-29

Author(s):

Abhishek Kumar ◽

Akash Kumar Giri ◽

Bibek Kattel

Keyword(s):

Clinical Trials ◽

Side Effects ◽

Dental Care ◽

Symptomatic Treatment ◽

Dental Pain ◽

The Other ◽

Commercial Products ◽

Plant Products ◽

Home Remedies ◽

The World

The COVID-19 pandemic resulted in the halt of proper dental care in most of the world, except for emergency cases. And, this resulted in a lot of people seek some home remedies for relieve in dental pain. So, this article aims to list down herbal home remedies which can be very helpful in such conditions. The use of medicinal herbs for dental pain can be traced back to history in some form or the other in almost every country. These herbal home remedies have no significant side effects as compared to other chemical-based alternatives, are also easy to obtain and cheaper as well. Clove, Olive, Miswak, Babool and other herbs listed in the article have significant dental properties which have been validated scientifically through various researches. These plant products can be hence used in commercial products as well but only after proper clinical trials. Further research should be encouraged in this field as herbal alternatives can be very beneficial with no such side effects. However, these home remedies are only useful for symptomatic treatment and undergoing proper dental care is advised.

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Immunotherapeutic Approaches for the Treatment of Neurodegenerative Diseases: Challenges and Outcomes

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527321666211228100955 ◽

2021 ◽

Vol 21 ◽

Author(s):

Sushma ◽

Amal Chandra Mondal

Keyword(s):

Clinical Trials ◽

Side Effects ◽

Neurodegenerative Diseases ◽

Prion Proteins ◽

Amyloid Β ◽

Corticobasal Degeneration ◽

Amyloid Β Peptide ◽

Neuronal Function ◽

Literature Study

Background: Neurodegenerative diseases, being rapidly increasing disorders and the seventh leading cause of death worldwide, have been a great challenge for researchers, affecting cognition, motor activity and other body functioning due to neurodegeneration. Several neurodegenerative diseases are caused by aggregation of proteins which induce the alteration of neuronal function leading to cell death. These proteins are amyloid-β peptide, tau, α-synuclein, and mHTT, which cause Alzheimer’s disease, Frontotemporal dementia, Corticobasal degeneration, Progressive supranuclear palsy, Parkinson’s disease, Multiple system atrophy, Dementia with Lewy-body and Huntington’s disease. Currently available treatments only reduce symptoms and increase life sustainability; however, they possess side effects and are ineffective in curing the diseases. Objectives: Literature survey of neurodegenerative diseases and immunotherapeutic approaches used to evaluate their pharmacological effects and future endeavours. Methods: A literature search was performed to find the relevant articles related to neurodegenerative diseases and immunotherapies. Clinical trials data were analysed from clinicaltrial.com. Result: According to literature study, it was found that researchers have explored the effect of active and passive vaccines generated against amyloid-β, tau, α-synuclein and mHTT. Few clinical trials have shown severe side effects and terminated, despite of that, few of them produced desirable effects for the treatment of AD and PD. Conclusion: Several immunotherapeutic trials have shown promising outcomes against amyloid-β, tau and α-synuclein. In addition, various preclinical studies against mHTT and prion proteins are under scrutinization. These clinical outcomes indicate promising role of immunotherapies against neurodegenerative diseases.

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The role of cannabinoids and endocannabinoid system in the treatment of epilepsy

Journal of Epileptology ◽

10.1515/joepi-2015-0034 ◽

2015 ◽

Vol 23 (2) ◽

pp. 131-138

Author(s):

Monika Pędracka ◽

Jacek Gawłowicz

Keyword(s):

Side Effects ◽

Animal Studies ◽

Endocannabinoid System ◽

Seizure Threshold ◽

Gamma Aminobutyric Acid ◽

Double Blind ◽

Model Studies ◽

Treatment Of Epilepsy ◽

New Antiepileptic Drugs

Summary Introduction. The treatment of epilepsy is still a major challenge. Despite the introduction of many new antiepileptic drugs, approximately 30% of patients still remain drug resistant. In the absence of a satisfactory therapy outcome, which is sometimes associated with numerous side effects, there is a need for new and effective drugs with low toxicity. Cannabinoids have been shown in preliminary animal model studies and in studies of patients with epilepsy to have antiepileptic activity. Aim. The aim of this paper is to review current reports on the role of the endocannabinoid system and cannabinoids in the treatment of epilepsy. Methods. Articles from PubMed and Scopus published up to 2015 concerning the role of cannabinoids and the endocannabinoid system in the treatment of epilepsy are reviewed. Review and Discussion. Cannabis has been used for thousands of years in the treatment of various diseases. They contain cannabinoids, which act on the endocannabinoid system which regulates many biochemical and physiological processes. By affecting glutamate and gamma-aminobutyric acid (GABA) neurotransmission cannabinoids have the ability to affect seizure threshold. The best known cannabinoid is cannabidiol, which inhibits the occurrence of seizures without causing significant side effects in humans and animals. However, only a small number of double blind, randomized and placebo controlled studies have been published to date. Conclusions. The role of cannabinoids in the treatment of epilepsy is not well defined because these substances have shown pro-convulsive actions in some animal studies and also there are not many randomized trials performed to date. The existing human data do not support the conclusion that cannabinoids are effective and safe in the treatment of epilepsy, but do encourage further studies on a larger group of patients.

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Prospects for the Use of Cannabinoids in Psychiatric Disorders

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.620073 ◽

2021 ◽

Vol 12 ◽

Author(s):

Michał Graczyk ◽

Małgorzata Łukowicz ◽

Tomasz Dzierzanowski

Keyword(s):

Clinical Trials ◽

Psychiatric Disorders ◽

Cognitive Abilities ◽

Young Patients ◽

Endocannabinoid System ◽

Cannabis Use ◽

Depression Symptoms ◽

Opioid Use ◽

Psychoactive Effects

Increasing evidence suggests an essential role of the endocannabinoid system in modulating cognitive abilities, mood, stress, and sleep. The psychoactive effects of cannabis are described as euphoric, calming, anxiolytic, and sleep-inducing and positively affect the mood, but can also adversely affect therapy. The responses to cannabinoid medications depend on the patient's endocannabinoid system activity, the proportion of phytocannabinoids, the terpenoid composition, and the dose used. There is some evidence for a therapeutic use of phytocannabinoids in psychiatric conditions. THC and CBD may have opposing effects on anxiety. Current guidelines recommend caution in using THC in patients with anxiety or mood disorders. In a small number of clinical trials, cannabinoids used to treat cancer, HIV, multiple sclerosis, hepatitis C, Crohn's disease, and chronic neuropathic pain report decreases in anxiety or depression symptoms and presented sedative and anxiolytic effects. Several studies have investigated the influence of potential genetic factors on psychosis and schizophrenia development after cannabis use. THC may increase the risk of psychosis, especially in young patients with an immature central nervous system. There is limited evidence from clinical trials that cannabinoids are effective therapy for sleep disorders associated with concomitant conditions. There is evidence for a possible role of cannabis as a substitute for alcohol and drugs, also in the context of the risks of opioid use (e.g., opioid-related mortality). In this narrative review of the recent evidence, we discuss the prospects of using the psychoactive effects of cannabinoids in treating mental and psychiatric disorders. However, this evidence is weak for some clinical conditions and well-designed randomized controlled trials are currently lacking. Furthermore, some disorders may be worsened by cannabis use.

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