Buprenorphine: prospective novel therapy for depression and PTSD

2020 ◽  
Vol 50 (6) ◽  
pp. 881-893
Author(s):  
Caitlin A. Madison ◽  
Shoshana Eitan

AbstractBackgroundDepression and post-traumatic stress disorder (PTSD) are leading causes of disability and loss of life by suicide. Currently, there are less than satisfactory medical solutions to treat these mental disorders. Here, we explore recent preclinical and clinical studies demonstrating the potential of using buprenorphine to treat major depressive disorder, treatment-resistant depression, and PTSD.MethodBibliographic databases were searched to include preclinical and clinical studies demonstrating the therapeutic potential of buprenorphine and the involvement of the kappa opioid receptor (KOR) in mediating these effects.ResultsOriginal clinical studies examining the effectiveness of buprenorphine to treat depression were mixed. The majority of participants in the PTSD studies were males and suffer from chronic pain and/or substance use disorders. Nonetheless, these recent studies and analyses established proof of concept warranting farther investigations. Additionally, KOR likely mediates the antidepressant and some of the anxiolytic effects of buprenorphine. Still, it appears that the full spectrum of buprenorphine's beneficial effects might be due to activity at other opioid receptors as well.ConclusionsPharmaceuticals' abilities to treat medical conditions directly relates to their ability to act upon the endogenous biological systems related to the conditions. Thus, these recent findings are likely a reflection of the central role that the endogenous opioid system has in these mental illnesses. Further studies are necessary to study the involvement of endogenous opioid systems, and specifically KOR, in mediating buprenorphine's beneficial effects and the ability to treat these medical conditions while minimizing risks for misuse and diversion.

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Sara Assadpour ◽  
Mohammad Reza Shiran ◽  
Peyman Asadi ◽  
Javad Akhtari ◽  
Amirhossein Sahebkar

Sumatriptan (ST) is a commonly prescribed drug for treating migraine. The efficiency of several routes of ST administration has been investigated. Recently, the intranasal route with different delivery systems has gained interest owing to its fast-acting and effectiveness. The present study is aimed at reviewing the available studies on novel delivery systems for intranasal ST administration. The oral route of ST administration is common but complicated with some problems. Gastroparesis in patients with migraine may reduce the absorption and effectiveness of ST upon oral use. Furthermore, the gastrointestinal (GI) system and hepatic metabolism can alter the pharmacokinetics and clinical effects of ST. The bioavailability of conventional nasal liquids is low due to the deposition of a large fraction of the delivered dose of a drug in the nasal cavity. Several delivery systems have been utilized in a wide range of preclinical and clinical studies to enhance the bioavailability of ST. The beneficial effects of the dry nasal powder of ST (AVP-825) have been proven in clinical studies. Moreover, other delivery systems based on microemulsions, microspheres, and nanoparticles have been introduced, and their higher bioavailability and efficacy were demonstrated in preclinical studies. Based on the extant findings, harnessing novel delivery systems can improve the bioavailability of ST and enhance its effectiveness against migraine attacks. However, further clinical studies are needed to approve the safety and efficacy of employing such systems in humans.


2018 ◽  
Vol 2 (2) ◽  
Author(s):  
Silvia Menendez Cepero

Ozone has been used as a therapeutical agent for the treatment of different diseases and beneficial effects have been observed. However, ozone biological effects remain controversial due to the scarce knowledge of its biochemical and pharmacodynamic mechanisms. Taking into account that ozone therapy is gathering more interest, day by day, and it has been used in apparently nonrelated diseases with beneficial effects, the National Center for Scientific Research (Havana, Cuba) in collaboration with different research centers and health institutions have studied the ozone toxicology and its pharmacological actions as well as its biochemical mechanisms. The most remarkable experiences, in preclinical and clinical studies, developed in Cuba during the last 30 years, in order to prove unequivocally ozone therapy validity, are presented in this lecture. On the basis of the oxidant properties of ozone, we postulate that controlled ozone administration (named as ozone oxidative pre-/postconditioning mechanism) is able to promote a slight and transient oxidative stress which in turn re-establishes the signalling pathways which have been lost in pathological conditions, preserving the cellular redox balance (increasing antioxidant endogenous system), mitochondrial function as well as the regulation of transcription factors and the modulation of the immunological system. It is evident that membrane-associated ozone peroxides, 4-hydroxialkenals, superoxide anion, nitric oxide, among others, are going to play an important role in cellular signals as well as in the pathology of different diseases. Regulation of these biomolecules by ozone preconditioning has been demonstrated in several preclinical and clinical studies as ischaemia-reperfusion phenomenom, parkinson, senile dementia, disk herniation, retinitis pigmentosa, ischemic cardiopathy, arterial insufficiencies, diabetes, osteoarthritis, asthma, vestibulocochlear syndrome, among others. Nitric oxide modulation, as well as the increase in A1 adenosine receptors achieved with this therapy has an important role in brain blood flux, in the formation of memory, in the release of neurotransmitters and in the inflammatory processes. Ozone therapy seems to induce a simultaneous resuscitation of functions that had gone wrong, reactivating and re-equilibrating physiological activities. This lecture contributes to clarify the ozone mechanism of action and its different pharmacology effects. It is concluded that ozone therapy can be useful in the treatment of several diseases, either as adjuvant of ortodox medicine or taking part positively in those where conventional therapy has had no success, all this with a common purpose: to favour the patients and contribute to a better quality of life.


CNS Spectrums ◽  
2020 ◽  
pp. 1-6
Author(s):  
Funda Akkus ◽  
Sylvia Terbeck ◽  
Connor J. Haggarty ◽  
Valerie Treyer ◽  
Janan J. Dietrich ◽  
...  

Abstract This review summarizes the evidence for the potential involvement of metabotropic glutamate receptor 5 (mGluR5) in the development of nicotine addiction. Nicotine is consumed worldwide and is highly addictive. Previous research has extensively investigated the role of dopamine in association with reward learning and addiction, which has provided strong evidence for the involvement of dopaminergic neuronal circuitry in nicotine addiction. More recently, researchers focused on glutamatergic transmission after nicotine abuse, and its involvement in the reinforcing and rewarding effects of nicotine addiction. A number of robust preclinical and clinical studies have shown mGluR5 signaling as a facilitating mechanism of nicotine addiction and nicotine withdrawal. Specifically, clinical studies have illustrated lower cortical mGluR5 density in smokers compared to nonsmokers in the human brain. In addition, mGluR5 might selectively regulate craving and withdrawal. This suggests that mGluR5 could be a key receptor in the development of nicotine addiction and therefore clinical trials to examine the therapeutic potential of mGluR5 agents could help to contribute to reduce nicotine addiction in society.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Seahyoung Lee ◽  
Eunhyun Choi ◽  
Min-Ji Cha ◽  
Ki-Chul Hwang

The literature provides abundant evidence that mesenchymal stem cells (MSCs) are an attractive resource for therapeutics and have beneficial effects in regenerating injured tissues due to their self-renewal ability and broad differentiation potential. Although the therapeutic potential of MSCs has been proven in both preclinical and clinical studies, several questions have not yet been addressed. A major limitation to the use of MSCs in clinical applications is their poor viability at the site of injury due to the harsh microenvironment and to anoikis driven by the loss of cell adhesion. To improve the survival of the transplanted MSCs, strategies to regulate apoptotic signaling and enhance cell adhesion have been developed, such as pretreatment with cytokines, growth factors, and antiapoptotic molecules, genetic modifications, and hypoxic preconditioning. More appropriate animal models and a greater understanding of the therapeutic mechanisms of MSCs will be required for their successful clinical application. Nevertheless, the development of stem cell therapies using MSCs has the potential to treat degenerative diseases. This review discusses various approaches to improving MSC survival by inhibiting anoikis.


2021 ◽  
Vol 11 ◽  
Author(s):  
Bahare Salehi ◽  
Cristina Quispe ◽  
Imane Chamkhi ◽  
Nasreddine El Omari ◽  
Abdelaali Balahbib ◽  
...  

Chalcones are among the leading bioactive flavonoids with a therapeutic potential implicated to an array of bioactivities investigated by a series of preclinical and clinical studies. In this article, different scientific databases were searched to retrieve studies depicting the biological activities of chalcones and their derivatives. This review comprehensively describes preclinical studies on chalcones and their derivatives describing their immense significance as antidiabetic, anticancer, anti-inflammatory, antimicrobial, antioxidant, antiparasitic, psychoactive, and neuroprotective agents. Besides, clinical trials revealed their use in the treatment of chronic venous insufficiency, skin conditions, and cancer. Bioavailability studies on chalcones and derivatives indicate possible hindrance and improvement in relation to its nutraceutical and pharmaceutical applications. Multifaceted and complex underlying mechanisms of chalcone actions demonstrated their ability to modulate a number of cancer cell lines, to inhibit a number of pathological microorganisms and parasites, and to control a number of signaling molecules and cascades related to disease modification. Clinical studies on chalcones revealed general absence of adverse effects besides reducing the clinical signs and symptoms with decent bioavailability. Further studies are needed to elucidate their structure activity, toxicity concerns, cellular basis of mode of action, and interactions with other molecules.


2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Carmen Mannucci ◽  
Fabrizio Calapai ◽  
Luigi Cardia ◽  
Giuseppina Inferrera ◽  
Giovanni D’Arena ◽  
...  

Objective. The aim of this review is to analyze preclinical and clinical studies investigating the anxiety effects ofCitrus aurantiumorCitrus sinensisessential oils (EOs).Design. The bibliographic research was made on the major scientific databases. Analysis included only articles written in English and published on peer-reviewed scientific journals describing preclinical experiments and clinical trials carried out to investigate the antianxiety effects ofCitrus aurantium or Citrus sinensisEOs on anxiety disorders. Clinical studies reporting the antianxiety effects of products containingCitrus aurantiumorCitrus sinensisEOs in combination with other active substances, including medicinal plants, were excluded. Nine clinical studies fulfilled the criteria adopted for analysis.Results. Data show thatCitrus aurantiumorCitrus sinensisEOs produce anxiolytic effects both in preclinical experiments and in different clinical conditions.Citrus aurantiumEO aromatherapy reduced anxiety level in the great part of stress conditions studied (subjects affected by chronic myeloid leukemia and preoperative patients) except for a sample of patients subjected to colonoscopy. Exposition toCitrus sinensisEO in clinical studies shows to be positive in reducing anxiety level in patients waiting for dental treatment as well as in healthy volunteers submitted to an anxiogenic situation.Conclusions. Overview of clinical trials conducted withCitrus aurantiumorCitrus sinensison people with anxiety showed that inhalation or oral administration ofCitrus aurantiumand inhalation ofCitrus sinensiscan exert beneficial effects on anxiety; however, because of incomplete accuracy in the reporting of methodology, further more complete clinical studies are warranted.


2019 ◽  
Vol 20 (9) ◽  
pp. 2313 ◽  
Author(s):  
Stephanie Andrade ◽  
Maria João Ramalho ◽  
Joana Angélica Loureiro ◽  
Maria do Carmo Pereira

Alzheimer’s Disease (AD) is a neurodegenerative disorder related with the increase of age and it is the main cause of dementia in the world. AD affects cognitive functions, such as memory, with an intensity that leads to several functional losses. The continuous increase of AD incidence demands for an urgent development of effective therapeutic strategies. Despite the extensive research on this disease, only a few drugs able to delay the progression of the disease are currently available. In the last years, several compounds with pharmacological activities isolated from plants, animals and microorganisms, revealed to have beneficial effects for the treatment of AD, targeting different pathological mechanisms. Thus, a wide range of natural compounds may play a relevant role in the prevention of AD and have proven to be efficient in different preclinical and clinical studies. This work aims to review the natural compounds that until this date were described as having significant benefits for this neurological disease, focusing on studies that present clinical trials.


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