Herbal highs: review on psychoactive effects and neuropharmacology

Background: A new trend among users of new psychoactive substances’ the consumption of “herbal highs”: plant parts containing psychoactive substances. Most of the substances extracted from herbs, in old centuries were at the centre of religious ceremonies of ancient civilizations. Currently, these herbal products are mainly sold by internet web sites and easily obtained since some of them have no legal restriction. Objective: We reviewed psychoactive effects and neuropharmacology of the most used “herbal highs” with characterized active principles, with studies reporting mechanisms of action, pharmacological and subjective effects, eventual secondary effects including intoxications and/or fatalities Method: The PubMed database was searched using the following key.words: herbal highs, Argyreia nervosa, Ipomoea violacea and Rivea corymbosa; Catha edulis; Datura stramonium; Piper methysticum; Mitragyna speciosa. Results: Psychoactive plants here reviewed have been known and used from ancient times, even if for some of them limited information still exist regarding subjective and neuropharmacological effects and consequent eventual toxicity when plants are used alone or in combination with “classical” drugs of abuse. Conclusion: Some “herbal highs” should be classified as harmful drugs since chronic administration has been linked with addiction and cognitive impairment; for some others taking into consideration only the recent trends of abuse, studies investigating these aspects are lacking

Tako-tsubo Syndrome as First Manifestation in a Case of Pheochromocytoma Developed From a Non-functional Adrenal Incidentaloma

Abstract Background: Pheochromocytoma is a catecholamine secreting tumor that, in extremely rare cases, may develop over time from a non-functional adrenal adenoma. Catecholamine excess can lead to a kind of cardiomyopathy similar to that seen in tako-tsubo syndrome (TTS). Case report: A 69 years old female with a history of type 2 diabetes, hypertension, and a non-functional right adrenal adenoma diagnosed 3 years earlier was referred to our center for further investigations. During the evaluation, she had a hypertensive crisis with chest pain, tachycardia, and diaphoresis. Suspecting an acute coronary syndrome, she underwent coronary angiography, which showed the typical features of TTS. The high 24 h-urinary metanephrines excretion and abdominal MRI findings were suggestive of pheochromocytoma. Right laparoscopic adrenalectomy was performed, with the resolution of all symptoms. Pathology findings confirmed the diagnosis of pheochromocytoma. After 12 months, the patient was still asymptomatic, with the echocardiography displaying a complete recovery of the left-ventricular function. Conclusions: The development of a pheochromocytoma from an adrenal non functional adenoma is an extremely rare event, but potentially life-threating because of the catecholamine-associated cardiovascular toxicity. In particular, TTS is a form of cardiomyopathy that has been increasingly described as associated with catecholamine-secreting tumors. The exclusion of pheochromocytoma in a patient with TTS has important therapeutic implications, since the administration of β-blockers may be extremely harmful in patients with catecholamine surge in the absence of adequate α-blockage. Keywords: adrenal incidentaloma; catecholamine; infarction; pheochromocytoma; tako-tsubo syndrome; ventricular dysfunction

The FDA “black box” warning on antidepressant suicide risk in young adults: More harm than benefits?

The decision made in the year 2004 by the U.S. Food and Drug Administration (FDA) to require a boxed warning on antidepressants regarding the risk of suicidality in young adults still represents a matter of controversy. The FDA warning was grounded on industry-sponsored trials carried one decade ago or earlier. However, within the past decade, an increasing number of reports have questioned the actual validity of the FDA warning, especially considering a decline in the prescription of the antidepressant drugs associated with an increase in the rate of suicidal events among people with severe depression. The present report provides an overview of the FDA black box warning, also documenting two Major Depressive Disorder patients whose refusal to undergo a pharmacological antidepressant treatment possibly led to an increased risk for suicidal behaviors. The concerns raised by the FDA black box warning need to be considered in real-world clinical practice, stating the associated clinical and public health implications

Lurasidone in the Treatment of Bipolar Depression: Systematic Review of Systematic Reviews

Introduction. A burgeoning number of systematic reviews considering lurasidone in the treatment of bipolar depression have occurred since its Food and Drug Administration extended approval in 2013. While a paucity of available quantitative evidence still precludes preliminary meta-analysis on the matter, the present quality assessment of systematic review of systematic reviews, nonetheless, aims at highlighting current essential information on the topic. Methods. Both published and unpublished systematic reviews about lurasidone mono- or adjunctive therapy in the treatment of bipolar depression were searched by two independent authors inquiring PubMed/Cochrane/Embase/Scopus from inception until October 2016. Results. Twelve included systematic reviews were of moderate-to-high quality and consistent in covering the handful of RCTs available to date, suggesting the promising efficacy, safety, and tolerability profile of lurasidone. Concordance on the drug profile seems to be corroborated by a steadily increasing number of convergent qualitative reports on the matter. Limitations. Publication, sponsorship, language, citation, and measurement biases. Conclusions. Despite being preliminary in nature, this overview stipulates the effectiveness of lurasidone in the acute treatment of Type I bipolar depression overall. As outlined by most of the reviewed evidence, recommendations for future research should include further controlled trials of extended duration

Celecoxib Adjunctive Treatment to Antipsychotics in Schizophrenia: A Review of Randomized Clinical Add-On Trials

Schizophrenia is a severe, chronic and debilitating mental disorder. Past literature has reported various hypotheses about the psychopathology of schizophrenia. Recently, a growing literature has been trying to explain the role of inflammation in the etiopathogenesis of schizophrenia. In the past, numerous immune modulation and anti-inflammatory treatment options have been proposed for schizophrenia, but sometimes the results were inconsistent. Electronic search was carried out in November 2015. PubMed and Scopus databases have been used to find studies to introduce in this review. Only randomized-placebo-controlled add-on trials were taken into account. In this way, six articles were obtained for the discussion. Celecoxib showed beneficial effects mostly in early stages of schizophrenia. In chronic schizophrenia, the data are controversial, possibly in part for methodological reasons

In vitro and in vivo evaluation of a somatostatin analogue released from PLGA microspheres

The purpose of this study was to design poly(lactide-co-glycolide) (PLGA) microspheres for the continuous delivery of the somatostatin analogue, vapreotide, over 2–4 weeks. The microspheres were produced by spray-drying and the desired characteristics, i.e. high encapsulation efficiency and controlled release over 2–4 weeks, achieved through optimizing the type of polymer, processing solvent, and co-encapsulated additive. The in vitro release was tested in fetal bovine serum preserved with 0.02% of thiomersal. Furthermore, formulations were injected intramuscularly into rats to obtain pharmacokinetic profiles. Encapsulation efficiency was between 34 and 91%, depending on the particular formulation. The initial peptide release (within 6 h) was lowest, i.e. 1 ng/ml) over 21–28 days in rats was the one made with end-group uncapped PLGA 50:50, the solvent acetic acid and the additive polyethyleneglycol. In conclusion, the optimization of formulation parameters allowed us to produce vapreotide-loaded PLGA microspheres of suitable characteristics for therapeutic use

Inflammatory markers and suicidal attempts in depressed patients: A review

Major depressive disorder is a chronic and invalidating psychiatric illness and is associated with a greater risk of suicidal behaviors. In recent decades many data have supported a biological link between depressive states and inflammation. Pro-inflammatory cytokines have been found to rise, first of all TNF-α and IL-6. Suicidal behaviors have been consistently associated with increased levels of IL-6 and decreased levels of IL-2. The aim of this review is to investigate the relationship between inflammatory markers in depressed patients with or without suicidal attempts compared to healthy controls

The role of inhaled loxapine in the treatment of acute agitation in patients with psychiatric disorders: A clinical review

Loxapine is a first generation antipsychotic, belonging to the dibenzoxazepine class. Recently, loxapine has been reformulated at a lower dose, producing an inhaled powder that can be directly administered to the lungs to treat the agitation associated with psychiatric disorders, such as schizophrenia and bipolar disorder. Thus, the aim of this narrative and clinical mini-review was to evaluate the efficacy and tolerability of inhaled loxapine in the treatment of acute agitation in patients with psychiatric disorders. The efficacy of inhaled loxapine has been evaluated in one Phase II trial on patients with schizophrenia, and in two Phase III trials in patients with schizophrenia and bipolar disorder. Moreover, there are two published case series on patients with borderline personality disorder and dual diagnosis patients. Inhaled loxapine has proven to be effective and generally well tolerated when administered to agitated patients with schizophrenia and bipolar disorder. Two case series have suggested that inhaled loxapine may also be useful to treat agitation in patients with borderline personality disorder and with dual diagnosis, but further studies are needed to clarify this point. However, the administration of inhaled loxapine requires at least some kind of patient collaboration, and is not recommended in the treatment of severe agitation in totally uncooperative patients. Moreover, the drug-related risk of bronchospasm must always be kept in mind when planning to use inhaled loxapine, leading to a careful patient assessment prior to, and after, administration. Also, the higher costs of inhaled loxapine, when compared to oral and intramuscular medications, should be taken into account when selecting it for the treatment of agitation

Atmospheric temperature responses to solar irradiance and geomagnetic activity

The relative effects of solar irradiance and geomagnetic activity on the atmospheric temperature anomalies (Ta) are examined from the monthly to interdecadal timescales. Geomagnetic Ap (Ap) signals are found primarily in the stratosphere, while the solar F10.7-cm radio flux (Fs) signals are found in both the stratosphere and troposphere. In the troposphere, 0.1–0.4 K increases in Ta are associated with Fs. Enhanced Fs signals are found when the stratospheric quasi-biennial oscillation (QBO) is westerly. In the extrapolar region of the stratosphere, 0.1–0.6 and 0.1–0.7 K increases in Ta are associated with solar irradiance and with geomagnetic activity, respectively. In this region, Fs signals are strengthened when either the QBO is easterly, or geomagnetic activity is high, while Ap signals are strengthened when either the QBO is westerly, or solar irradiance is high. High solar irradiance and geomagnetic activity tend to enhance each other's signatures either making the signals stronger and symmetric about the equator or extending the signals to broader areas, or both. Positive Ap signals dominate the middle Arctic stratosphere and are two to five times larger than those of Fs. When solar irradiance is low, the signature of Ap in Ta is asymmetric about the equator, with positive signals in the Arctic stratosphere and negative signals at midlatitudes of the NH stratosphere. Weaker stratospheric QBO signals are associated with high Ap and Fs, suggesting possible disturbances on the QBO. The signals of Ap and Fs are distinct from the positive temperature anomalies resulting from volcanic eruptions