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Psychiatry & Medicine

Banisteriopsis caapi, a Forgotten Potential Therapy for Parkinson's Disease?

October 6, 2015 / Neuroscience, Papers, Psychiatry & Medicine, Publications / By / , , ,

Abstract

Banisteriopsis caapi, a liana indigenous to the Amazon basin with metagnomigenic properties and possible anti-depressant effects is one of the natural sources of harmala alkaloids. A summary of early trials with extracts of Banisteriopsis caapi and Peganum harmala (from which harmine was first isolated) in the 1920s and 1930s on various forms of parkinsonism is given as well as a brief overview of the known pharmacological properties of harmine. Despite its earlier abandonment because of perceived weaker efficacy than solanaceous alkaloids like scopolamine and hyoscine we propose that harmine should be reconsidered as a potential rapidly acting anti-Parkinsonian agent.

Djamshidian, A., Bernschneider‐Reif, S., Poewe, W., & Lees, A. J. (2015). Banisteriopsis caapi, a Forgotten Potential Therapy for Parkinson’s Disease?. Movement Disorders Clinical Practice. http://dx.doi.org/10.1002/mdc3.12242
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Harmine blocks herpes simplex virus infection through downregulating cellular NF-κB and MAPK pathways induced by oxidative stress

September 5, 2015 / Neuroscience, Papers, Psychiatry & Medicine, Publications / By / , , , , , ,

Abstract

Herpes simplex virus types 1 and 2 (HSV-1 and -2) are highly prevalent in many populations and therapeutic options are limited. Both viruses can establish latency by maintaining viral genomes in neurons of sensory ganglia. Primary or recurrent HSV infections may lead to deleterious outcomes: HSV-1 infection may result in corneal blindness and encephalitis and HSV-2 infection leads to herpes genitalis. While no effective vaccine is available, acyclovir is widely used for therapy, which targets and inhibits viral DNA polymerase. Although acyclovir is of low toxicity, resistant strains arise due to persistent use, mainly in immune compromised patients. In our effort to identify new HSV inhibitory molecules, harmine was found to potently inhibit HSV infection. Harmine, a beta-carbon alkaloid with an indole core structure and a pyridine ring, is widely distributed in plants. Earlier studies showed that harmine exhibited pharmacological activities such as antifungal, antimicrobial, antitumor, antiplasmodial and antioxidants. In the current study, we showed that harmine was a potent inhibitor of HSV-2 infection in vitro assays with EC50 value at around 1.47μM and CC50 value at around 337.10μM. The HSV RNA transcription, protein synthesis, and virus titers were reduced by the presence of harmine in a dose dependent manner. Further study on the mechanism of the anti-HSV activity showed that harmine blocked HSV-induced ROS production and the upregulated cytokine/chemokine expression, but our evidence showed that the inhibition of viral replication was unlikely mediated by the blocking of ROS production. We demonstrated that harmine significantly reduced HSV-2-induced NF-κB activation, as well as IκB-α degradation and p65 nuclear translocation. We found that harmine also inhibited HSV-2-mediated p38 kinase and c-Jun N-terminal kinases (JNK) phosphorylation.

Chen, D., Su, A., Fu, Y., Wang, X., Lv, X., Xu, W., … & Wu, Z. (2015). Harmine blocks herpes simplex virus infection through downregulating cellular NF-κB and MAPK pathways induced by oxidative stress. Antiviral research, 123, 27-38. 10.1016/j.antiviral.2015.09.003
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The potential utility of some legal highs in CNS disorders

July 29, 2015 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychiatry & Medicine, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Over the last decade there has been an explosion of new drugs of abuse, so called legal highs or novel psychoactive substances (NPS). Many of these abused drugs have unknown pharmacology, but their biological effects can be anticipated from their molecular structure and possibly also from online user reports. When considered with the findings that some prescription medications are increasingly abused and that some abused drugs have been tested clinically one could argue that there has been a blurring of the line between drugs of abuse and clinically used drugs. In this review we examine these legal highs/NPS and consider whether, based on their known or predicted pharmacology, some might have the potential to be clinically useful in CNS disorders.

Davidson, C., & Schifano, F. (2015). The potential utility of some legal highs in CNS disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry. https://dx.doi.org/10.1016/j.pnpbp.2015.07.010
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Antidepressant mechanism of ketamine: perspective from preclinical studies

July 21, 2015 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications / By / , , ,

Abstract

A debilitating mental disorder, major depressive disorder is a leading cause of global disease burden. Existing antidepressant drugs are not adequate for the majority of depressed patients, and large clinical studies have demonstrated their limited efficacy and slow response onset. Growing evidence of low-dose ketamine’s rapid and potent antidepressant effects offers strong potential for future antidepressant agents. However, ketamine has considerable drawbacks such as its abuse potential, psychomimetic effects, and increased oxidative stress in the brain, thus limiting its widespread clinical use. To develop superior antidepressant drugs, it is crucial to better understand ketamine’s antidepressant mechanism of action. Recent preclinical studies indicate that ketamine’s antidepressant mechanism involves mammalian target of rapamycin pathway activation and subsequent synaptogenesis in the prefrontal cortex, as well as glycogen synthase kinase-3 beta (GSK-3β) inactivation. Adjunct GSK-3β inhibitors, such as lithium, can enhance ketamine’s efficacy by augmenting and prolonging its antidepressant effects. Given the potential for depressive relapses, lithium in addition to ketamine is a promising solution for this clinical issue.

Scheuing, L., Chiu, C. T., Liao, H. M., & Chuang, D. M. (2015). Antidepressant mechanism of ketamine: perspective from preclinical studies. Frontiers in Neuroscience, 9. http://dx.doi.org/10.3389/fnins.2015.00249
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Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities

July 14, 2015 / DMT, LSD, MDMA, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications / By /

Abstract

Classical psychedelics are psychoactive substances, which, besides their psychopharmacological activity, have also been shown to exert significant modulatory effects on immune responses by altering signaling pathways involved in inflammation, cellular proliferation, and cell survival via activating NF-κB and mitogen-activated protein kinases. Recently, several neurotransmitter receptors involved in the pharmacology of psychedelics, such as serotonin and sigma-1 receptors, have also been shown to play crucial roles in numerous immunological processes. This emerging field also offers promising treatment modalities in the therapy of various diseases including autoimmune and chronic inflammatory conditions, infections, and cancer. However, the scarcity of available review literature renders the topic unclear and obscure, mostly posing psychedelics as illicit drugs of abuse and not as physiologically relevant molecules or as possible agents of future pharmacotherapies. In this paper, the immunomodulatory potential of classical serotonergic psychedelics, including N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-iodoamphetamine, and 3,4-methylenedioxy-methamphetamine will be discussed from a perspective of molecular immunology and pharmacology. Special attention will be given to the functional interaction of serotonin and sigma-1 receptors and their cross-talk with toll-like and RIG-I-like pattern-recognition receptor-mediated signaling. Furthermore, novel approaches will be suggested feasible for the treatment of diseases with chronic inflammatory etiology and pathology, such as atherosclerosis, rheumatoid arthritis, multiple sclerosis, schizophrenia, depression, and Alzheimer’s disease.

Szabo, A. Psychedelics and immunomodulation: Novel approaches and therapeutic opportunities. Frontiers in Immunology, 0. https://dx.doi.org/10.3389/fimmu.2015.00358
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Ayahuasca Alters Structural Parameters of the Rat Aorta

July 1, 2015 / Ayahuasca, Papers, Psychiatry & Medicine, Publications / By / , , , , , ,

Abstract

Ayahuasca is a hallucinogenic brew traditionally used by Northwestern Amazonian indigenous groups for therapeutic purposes. It is prepared by the decoction of Banisteriopsis caapi with the leaves of Psychotria viridis. Banisteriopsis caapi contains β-carbolines that are inhibitors of monoamine oxidase and P. viris is rich in dimethyltryptamine, a 5-HT1A/2A/2C agonist. Acute ayahuasca administration produces moderate cardiovascular effects in healthy volunteers, but information regarding long-term use is lacking. This study investigated the effects of ayahuasca (2–4 mL/kg) in the rat aorta after acute and chronic (14 days) administration. Ayahuasca caused flattening and stretching of vascular smooth muscle cells and changes in the arrangement and distribution of collagen and elastic fibers. Chronic treatment with the higher dose significantly increased media thickness and the ratio of media thickness to lumen diameter. More research is needed on the cardiovascular function of long-term ayahuasca consumers.

Pitol, D. L., Siéssere, S., Dos Santos, R. G., Nunes, M. R. M., Cecilio, H. J., Scalize, P. H., … & Hallak, R. S. (2015). Ayahuasca alters structural parameters of the rat aorta. Journal of cardiovascular pharmacology. http://dx.doi.org/10.1097/FJC.0000000000000243
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Paclitaxel combined with harmine inhibits the migration and invasion of gastric cancer cells through downregulation of cyclooxygenase‑2 expression

June 25, 2015 / Papers, Psychiatry & Medicine, Publications / By / , ,

Abstract

Cyclooxygenase‑2 (COX‑2) has a critical role in the invasiveness and metastasis of gastric cancer. In addition, paclitaxel (PTX) and harmine (HM) were reported to be potential therapeutic drug candidates for cancer therapy; however, the synergistic antitumor effect of PTX and HM combined treatment on the human gastric cancer cells remains to be elucidated. The aim of the present study was to evaluate the effects of PTX and/or HM on the cell migration and invasion in two human gastric cancer cell lines, SGC‑7901 and MKN‑45. MTT assay was used to detect the growth inhibition induced by PTX and HM . The Transwell assay was employed to assess the effects of PTX and HM on the cell migration and invasion. The expression levels of COX-2 and matrix metalloproteinase-9 (MMP-9) were analyzed by western blot analysis. The results demonstrated that PTX and HM inhibited cell proliferation in a dose‑dependent manner. Individually PTX and HM were able to inhibit the migration and invasion of two human gastric cancer cells; however, the combination of PTX and HM exerted synergistic effects on migration and invasion inhibition, with downregulation of COX‑2 and matrix metalloproteinase (MMP)‑9. In conclusion, the results of the present study indicated that combination chemotherapy using PTX with HM exerted an antitumor effect, which may be implicated for the treatment of gastric cancer. Of note, the combination of the two drugs inhibited migration and invasion more effectively compared with each drug alone, the mechanism of which proceeded via the downregulation of COX‑2 expression.

Sun, K., Tang, X. H., & Xie, Y. K. (2015). Paclitaxel combined with harmine inhibits the migration and invasion of gastric cancer cells through downregulation of cyclooxygenase‑2 expression. Oncology Letters, 10(3), 1649-1654. https://dx.doi.org/10.3892/ol.2015.3425
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Pharmacokinetics and concentration-effect relationship of oral LSD in humans

June 24, 2015 / LSD, Neuroscience, Papers, Psychiatry & Medicine, Publications / By / , , , ,

Abstract

Background: The pharmacokinetics of oral lysergic acid diethylamide (LSD) are unknown, despite its common recreational use and renewed interest in its use in psychiatric research and practice.

Methods: We characterized the pharmacokinetic profile, pharmacokinetic-pharmacodynamic relationship, and urine recovery of LSD and its main metabolite after administration of a single oral dose of LSD (200 μg) in eight male and eight female healthy subjects.

Results: Plasma LSD concentrations were quantifiable (> 0.1 ng/ml) in all of the subjects up to 12 h after administration. Maximal concentrations of LSD (mean ± SD: 4.5 ± 1.4 ng/ml) were reached (median, range) 1.57 (0.5-4) h after administration. Concentrations then decreased following first-order kinetics with a half-life of 3.6 ± 0.9 h up to 12 h and slower elimination thereafter with a terminal half-life of 8.9 ± 5.9 h. One percent of the orally administered LSD was eliminated in urine as LSD, and 14% was eliminated as 2-oxo-3-hydroxy-LSD within 24 h. No sex differences were observed in the pharmacokinetic profiles of LSD. The acute subjective and sympathomimetic responses to LSD lasted up to 12 h and were closely associated with the concentrations in plasma over time and exhibited no acute tolerance.

Conclusions: These first data on the pharmacokinetics and concentration-effect relationship of oral LSD are relevant for further clinical studies and serve as a reference for the assessment of intoxication with LSD.

Dolder, P. C., Schmid, Y., Haschke, M., Rentsch, K. M., & Liechti, M. E. (2015). Pharmacokinetics and concentration-effect relationship of oral LSD in humans. International Journal of Neuropsychopharmacology, pyv072.

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Anti-mycobacterial and anti-inflammatory activity of Peganum harmala.

June 1, 2015 / Papers, Psychiatry & Medicine, Publications / By / , , , , ,

Abstract

The aim of this study was to evaluate the antimycobacterial and anti-inflammatory activity of the methanolic extracts of Peganum harmala (Esphand) collected from Golestan province, north of Iran. Methods: Hydroalcoholic extract of seeds of Peganum harmala were obtained and screened for anti-mycobacterial activity by disc diffusion (DD) method. The anti-inflammatory activity of the extract was evaluated by cytokines measurement using ELISA in a model of phagocytized intracellular Mycobacterium tuberculosis, H37Rv strain, in dU937cells. Free radical-scavenging activity, total phenolic, flavonoids and Harmalin concentrations were assessed to investigate phytochemical properties of the extract. Our data showed the inhibitory effect of the extract on growth of all strains of Mycobacterium tuberculosis even on drug resistant strains. Cytokines production in culture media showed the anti-inflammatory activity of the extract. The antioxidant (IC50 (DPPH assay) was 53.6 ± 0.50 mg/L. The amount of total phenolic and flavonoids components was 61.5 ± 0.80 gGAE/kg and 42.20 ± 0.60 respectively. These findings revealed the potential ability of the Peganum harmala s seed as a complementary medicine to treat tuberculosis.

Davoodi, H., Ghaemi, E., Mazandarani, M., Shakeri, F., Javid, S. N., & Klishadi, M. (2015). Anti-mycobacterial and anti-inflammatory activity of Peganum harmala. Journal of Chemical & Pharmaceutical Research, 7(4).
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Ketamine-A Narrative Review of Its Uses in Medicine

April 24, 2015 / Anxiety Disorders / PTSD, Ketamine, Neuroscience, Papers, Pharmacology & Chemistry, Psychiatry & Medicine, Psychology, Publications / By / , , , ,

Abstract

One of the most fascinating drugs in the anesthesiologist’s armament is ketamine, an N-methyl-D-aspartate receptor antagonist with a myriad of uses. The drug is a dissociative anesthetic and has been used more often as an analgesic in numerous hospital units, outpatient pain clinics, and in the prehospital realm. It has been used to treat postoperative pain, chronic pain, complex regional pain syndrome, phantom limb pain, and other neuropathic conditions requiring analgesia. Research has also demonstrated its efficacy as an adjunct in psychotherapy, as a treatment for both depression and posttraumatic stress disorder, as a procedural sedative, and as a treatment for respiratory and neurologic conditions. Ketamine is not without its adverse effects, some of which can be mitigated with certain efforts. Such effects make it necessary for the clinician to use the drug only in situations where it will provide the greatest benefit with the fewest adverse effects. To the best of our knowledge, none of the reviews regarding ketamine have taken a comprehensive look at the drug’s uses in all territories of medicine. This review will serve to touch on its chemical data, pharmacokinetics and pharmacodynamics, medical uses, and adverse effects while focusing specifically on the drugs usage in anesthesia and analgesia.

Radvansky, B. M., Puri, S., Sifonios, A. N., Eloy, J. D., & Le, V. (2015). Ketamine-A Narrative Review of Its Uses in Medicine. American journal of therapeutics. https://dx.doi.org/10.1097/MJT.0000000000000257
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