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Psychiatry & Medicine

Isolated non-cardiogenic pulmonary edema – A rare complication of MDMA toxicity

June 27, 2017 / MDMA, Papers, Psychiatry & Medicine, Publications / By / , , , ,

Abstract

This is a case of a 19-year-old male who presented to the medical tent at an outdoor electronic dance music festival (EDMF) due to an altered mental state in the setting of acute 3,4-methylenedioxymethamphetamine (MDMA) intoxication. He was noted to be in severe respiratory distress, required endotracheal intubation in the field and subsequently developed Acute Respiratory Distress Syndrome (ARDS) without other acute organ dysfunction. He was hospitalized for 5days requiring endotracheal intubation and mechanical ventilation. By presenting this case, we will explore and discuss the cardiopulmonary effects of MDMA intoxication that can lead to a rare, deleterious complication of MDMA intoxication other than previously reported adverse outcomes.
Haaland, A., Warman, E., Pushkar, I., Likourezos, A., & Friedman, M. S. (2017). Isolated non-cardiogenic pulmonary edema—A rare complication of MDMA toxicity. The American journal of emergency medicine, 35(9), 1385-e3. 10.1016/j.ajem.2017.06.040
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Psilocybin-assisted therapy for anxiety and depression: implications for euthanasia

June 19, 2017 / Anxiety Disorders / PTSD, Mushrooms / Psilocybin, Papers, Psychiatry & Medicine, Psychology, Publications / By /

Abstract

Despite their stigmatisation, psychedelic drugs are once again being clinically researched in Europe and North America. This long-awaited renaissance is showing very promising results and, unlike the pioneering research that occurred before these drugs were outlawed over 30 years ago, the current methodology is rigorous and of a very high standard.
Strauss, N. (2017). Psilocybin-assisted therapy for anxiety and depression: implications for euthanasia. The Medical Journal of Australia, 206(11), 468-469. 10.5694/mja17.00081
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In vitro antiviral effects of Peganum harmala seed extract and its total alkaloids against Influenza virus

June 16, 2017 / Papers, Psychiatry & Medicine, Publications / By / , , ,

Abstract

This research was aimed to evaluate the in vitro antiviral effect and the mechanism of the effect of Peganum. harmala seeds extract against influenza A virus infection using Madin-Darby canine kidney (MDCK) cells. In this research, ethyl alcohol extract of P. harmala seeds and its total alkaloids was prepared. The potential antiviral activity of the extract and its total alkaloids against influenza A/Puerto Rico/8/34 (H1N1; PR8) virus was assessed. The mode of action of the extract to inhibit influenza replication was investigated using virucidal activity, hemagglutination inhibition assay, time of addition assays, RNA replication, western blot analysis and RNA polymerase blocking assay. The crud extract of P. harmala seed and its total alkaloids showed the best inhibitory effect against influenza A virus replication in MDCK cells using MTT assay, TCID50 method and hemagglutination assay. Our results indicated that the extract inhibits viral RNA replication and viral polymerase activity but did not effect on hemagglutination inhibition and virucidal activity. This study showed that, in vitro antiviral activity of P. harmala seed extract against influenza virus is most probably associated with inhibiting viral RNA transcription. Therefore, this extract and its total alkaloid should be further characterized to be developed as anti-influenza A virus agent.

Moradi, M. T., Karimi, A., Rafieian-Kopaei, M., & Fotouhi, F. (2017). In vitro antiviral effects of Peganum harmala seed extract and its total alkaloids against Influenza virus. Microbial Pathogenesis. 10.1016/j.micpath.2017.06.014
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Neuropathic and inflammatory antinociceptive effects and electrocortical changes produced by Salvia divinorum in rats

May 11, 2017 / Papers, Psychiatry & Medicine, Publications, Salvia / Salvinorin A / By / , , , , , ,

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:
Salvia divinorum is a medicinal plant traditionally used in hallucinogenic ethnopharmacological practices and for its analgesic and antinflammatory properties. Its active compounds include diterpenes known as salvinorins which act as potent κ opioid receptor agonists.
AIM OF THE STUDY:
Given its effects in acute animal models of pain, as well as its antinflammatory attributes, we decided to investigate the analgesic effects of an SD extract in neuropathic (sciatic loose nerve ligature) and inflammatory (intra plantar carrageenan) pain models in rats. We also determined in this study the electrocorticographic changes to correlate similar hallucinogenic state and behavior as those produced in humans.
MATERIAL AND METHODS:
Mechanical and thermonociceptive responses, plantar test and von Frey assay, respectively, were measured in adult Wistar rats 30min, 3h and 24h after the intraperitoneal administration of saline or an hydroponic SD extract. We also evaluated carbamazepine and celecoxib, as gold reference drugs, to compare its antinociceptive effects.
RESULTS:
Our results showed that administration of SD extract induced antialgesic effects in both neuropathic and inflammatory pain models. All those effects were blocked by nor-binaltorphimine (a Kappa opioid receptor antagonist). Moreover, it was observed an increase of the anterior power spectral density and a decrease in the posterior region as electrocorticographic changes.
CONCLUSION:
The present investigation give evidence that SD is capable to reduce algesic response associated to neuropathic and inflammatory nociception. This study support therapeutic alternatives for a disabling health problem due to the long term pain with high impact on population and personal and social implications.
Simón-Arceo, K., González-Trujano, M. E., Coffeen, U., Fernández-Mas, R., Mercado, F., Almanza, A., … & Pellicer, F. (2017). Neuropathic and inflammatory antinociceptive effects and electrocortical changes produced by Salvia divinorum in rats. Journal of Ethnopharmacology, 206, 115-124. 10.1016/j.jep.2017.05.016
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A review on traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology of the genus Peganum

May 5, 2017 / Ayahuasca, Biology & Ethnobotany, Papers, Psychiatry & Medicine / By / , ,

Abstract

Ethnopharmacological relevance

The plants of the genus Peganum have a long history as a Chinese traditional medicine for the treatment of cough, hypertension, diabetes, asthma, jaundice, colic, lumbago, and many other human ailments. Additionally, the plants can be used as an amulet against evil-eye, dye and so on, which have become increasingly popular in Asia, Iran, Northwest India, and North Africa.

Aim of the review

The present paper reviewed the ethnopharmacology, phytochemistry, analytical methods, biological activities, metabolism, pharmacokinetics, toxicology, and drug interaction of the genus Peganum in order to assess the ethnopharmacological use and to explore therapeutic potentials and future opportunities for research.

Materials and methods

Information on studies of the genus Peganum was gathered via the Internet (using Google Scholar, Baidu Scholar, Elsevier, ACS, Pudmed, Web of Science, CNKI and EMBASE) and libraries. Additionally, information was also obtained from some local books, PhD and MS’s dissertations.

Results

The genus Peganum has played an important role in traditional Chinese medicine. The main bioactive metabolites of the genus include alkaloids, flavonoids, volatile oils, etc. Scientific studies on extracts and formulations revealed a wide range of pharmacological activities, such as cholinesterase and monoamine oxidase inhibitory activities, antitumor, anti-hypertension, anticoagulant, antidiabetic, antimicrobial, insecticidal, antiparasidal, anti-leishmaniasis, antioxidant, and anti-inflammatory.

Conclusions

Based on this review, there is some evidence for extracts’ pharmacological effects on Alzheimer’s and Parkinson’s diseases, cancer, diabetes, hypertension. Some indications from ethnomedicine have been confirmed by pharmacological effects, such as the cholinesterase, monoamine oxidase and DNA topoisomerase inhibitory activities, hypoglycemic and vasodilation effects of this genus. The available literature showed that most of the activities of the genus Peganum can be attributed to the active alkaloids. Data regarding many aspects of the genus such as mechanisms of actions, metabolism, pharmacokinetics, toxicology, potential drug interactions with standard-of-care medications is still limited which call for additional studies particularly in humans. Further assessments and clinical trials should be performed before it can be integrated into medicinal practices.

Li, S., Cheng, X., & Wang, C. (2017). A review on traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology of the genus Peganum. Journal of Ethnopharmacology. 10.1016/j.jep.2017.03.049
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Population scale data reveals the antidepressant effects of ketamine and other therapeutics approved for non-psychiatric indications.

May 3, 2017 / Depressive Disorders, Ketamine, Papers, Psychiatry & Medicine, Psychology, Publications / By / , , ,

Abstract

Current therapeutic approaches to depression fail for millions of patients due to lag in clinical response and non-adherence. Here we provide new support for the antidepressant effect of an anesthetic drug, ketamine, by Inverse-Frequency Analysis of eight million reports from the FDA Adverse Effect Reporting System. The results of the examination of population scale data revealed that patients who received ketamine had significantly lower frequency of reports of depression than patients who took any other combination of drugs for pain. The analysis also revealed that patients who took ketamine had significantly lower frequency of reports of pain and opioid induced side effects, implying ketamine’s potential to act as a beneficial adjunct agent in pain management pharmacotherapy. Further, the Inverse-Frequency Analysis methodology provides robust statistical support for the antidepressant action of other currently approved therapeutics including diclofenac and minocycline.
Cohen, I. V., Makunts, T., Atayee, R., & Abagyan, R. (2017). Population scale data reveals the antidepressant effects of ketamine and other therapeutics approved for non-psychiatric indications. Scientific Reports, 7. 10.1038/s41598-017-01590-x
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Psychedelics As A New Anti-Inflammatory Therapeutic For Atherosclerosis

April 1, 2017 / Neuroscience, Papers, Psychiatry & Medicine / By / , ,

Abstract

Background and Objective We previously discovered that serotonin 5-HT2A receptor activation with psychedelics has potent anti-inflammatory activity in both cell culture and whole animals, which indicated potent anti-inflammatory effects in vascular tissues among others. More recently we found that the psychedelic (R)-DOI potently prevents the development of allergic asthma in a mouse model. The effects of (R)-DOI were found to not result from a generalized anti-inflammatory process, but due to specific inflammatory pathways inhibition in both innate and Th2 cells. In this work, we have examined the therapeutic effects of the psychedelic (R)-DOI in the ApoE −/− high-fat model of atherosclerosis.

Methods Osmotic minipumps were used to deliver very low doses of (R)-DOI to male ApoE −/− mice that were divided into four treatment groups [Saline, normal chow; (R)-DOI, normal chow; Saline, hi-fat diet; (R)-DOI, hi-fat diet]. After 16 weeks, mice were euthanized and tissues collected for analysis

Results Calculated steady state levels of ~0.0013 mg/kg (R)-DOI resulted in a significant reduction of mRNA expression for inflammatory markers like Il6 in vascular tissue, reduced levels of glucose, and a reduction in circulating cholesterol in the high fat fed animals. Additional ongoing studies are examining arterial plaque size and heart pathology.

Summary Extremely low levels of the psychedelic (R)-DOI were sufficient to significantly block the development of vascular inflammation, normalize glucose homeostasis, and prevent the increase in cholesterol associated with a hi-fat ‘western’ high diet. Activation of serotonin 5-HT2A receptor therefore represents a powerful new strategy to treat inflammatory-related vascular disease.

Nichols, C. D., Sebastian, M., & Flanagan, T. (2017). Psychedelics As A New Anti-Inflammatory Therapeutic For Atherosclerosis. The FASEB Journal, 31(1 Supplement), 825-3.
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Psychoactive Drugs as a Route to Development of Novel Anti-parasitic Agents

April 1, 2017 / LSD, Papers, Psychiatry & Medicine / By / ,

Abstract

Over a third of the world’s population is infected with parasitic worms. One of the most burdensome infections underpins the neglected tropical disease schistosomiasis (Bilharzia) caused by parasitic flatworms of the genus Schistosoma, which afflicts ~200 million people worldwide. Consequently, there is a need to discover and develop next generation anthelmintics, active against a broad spectrum of parasitic helminths.

Flatworm musculature is regulated by bioaminergic signalling: addition of exogenous 5-HT to isolated flatworm muscle fibres causes contraction. This effect is likely mediated by engagement of serotonergic G protein coupled receptors (GPCRs). For example, in free living planarians, knockdown of a serotonergic GPCR (S7.1) impairs worm motility. Here, we demonstrate that the psychoactive agent, lysergic acid diethylamide (LSD) acts as a agonist at the planarian S7.1 receptor (EC50 = 1.3±0.5nM, Emax 99±5% of 5-HT response). LSD evoked contraction inhibited the motility of free living planarian worms (distance moved 16±2% versus control worms) and potently blocked bipolar regeneration evoked by praziquantel (IC50 = 0.5±0.2nM). These data raises the possibility that other psychoactive drugs, including psychotropics with known activity at human 5-HT2 receptors, could serve as efficacious lead compounds to disrupt flatworm mobility.

Therefore, we screened a variety of psychoactive agents on the motility of free living planarian flatworms, as well as the functionality of heterologously expressed S7.1 using a real time cAMP biosensor. Agents were discovered that modulated flatworm movement and regeneration, and efficacy of the screened molecules provided information about structural features necessary for activity at this abundant flatworm serotonergic GPCR. These data also identify features of ligands conveying activity at flatworm 5-HT GPCRs.

Woodhouse, K., Chan, J. D., & Marchant, J. (2017). Psychoactive Drugs as a Route to Development of Novel Anti-parasitic Agents. The FASEB Journal, 31(1 Supplement), 1002-2.
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Anti-inflammatory effects of serotonin 5-HT2A receptor activation in ovalbumin-induced allergic asthma models

April 1, 2017 / Neuroscience, Papers, Psychiatry & Medicine / By / , ,

Abstract

Only recently has the full therapeutic value of serotonin [5-hydroxytryptophan (5-HT)] receptor activation begun to be explored. Currently there are two 5-HT2A receptor agonists in human clinical trials for the treatment of depression and obesity. An exciting new therapeutic avenue in which 5-HT2A agonists might be employed is the modulation of inflammation in allergic airways disease. Our lab has previously used an ovalbumin (OVA)-induced asthma model to demonstrate that administration of (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] prior to allergen challenge prevents many of the symptoms of allergic asthma. Here we have utilized a modified protocol to test the effectiveness of (R)-DOI in treating persistent allergic asthma. We demonstrate that administration of (R)-DOI in a chronic model attenuates the elevated airway hyperresponsiveness (AHR) typically observed in an asthmatic response. We also have probed for the expression of inflammatory markers in the lung and BALF. We concurrently are testing for the impact psilocybin and other tryptamines have on AHR in rodents using our OVA model. Overall our strategy is to develop 5-HT2A receptor agonism as a viable treatment modality against asthma and other inflammatory disorders.
Flanagan, T. W., Sebastian, M. N., & Nichols, C. D. (2017). Anti-inflammatory effects of serotonin 5-HT2A receptor activation in ovalbumin-induced allergic asthma models. The FASEB Journal, 31(1 Supplement), 820-4.
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Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome

March 21, 2017 / Depressive Disorders, Ketamine, Papers, Psychiatry & Medicine, Psychology / By / , , , , , ,

Abstract

A subset of patients with depression have elevated levels of inflammatory cytokines, and some studies demonstrate interaction between inflammatory factors and treatment outcome. However, most studies focus on only a narrow subset of factors in a patient sample. In the current study, we analyzed broad immune profiles in blood from patients with treatment-resistant depression (TRD) at baseline and following treatment with the glutamate modulator ketamine. Serum was analyzed from 26 healthy control and 33 actively depressed TRD patients free of antidepressant medication, and matched for age, sex and body mass index. All subjects provided baseline blood samples, and TRD subjects had additional blood draw at 4 and 24 h following intravenous infusion of ketamine (0.5 mg kg−1). Samples underwent multiplex analysis of 41 cytokines, chemokines and growth factors using quantitative immunoassay technology. Our a priori hypothesis was that TRD patients would show elevations in canonical pro-inflammatory cytokines; analyses demonstrated significant elevation of the pro-inflammatory cytokine interleukin-6. Further exploratory analyses revealed significant regulation of four additional soluble factors in patients with TRD. Several cytokines showed transient changes in level after ketamine, but none correlated with treatment response. Low pretreatment levels of fibroblast growth factor 2 were associated with ketamine treatment response. In sum, we found that patients with TRD demonstrate a unique pattern of increased inflammatory mediators, chemokines and colony-stimulating factors, providing support for the immune hypothesis of TRD. These patterns suggest novel treatment targets for the subset of patients with TRD who evidence dysregulated immune functioning.
Kiraly, D. D., Horn, S. R., Van Dam, N. T., Costi, S., Schwartz, J., Kim-Schulze, S., … & Iosifescu, D. V. (2017). Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome. Translational psychiatry, 7(3), e1065. 10.1038/tp.2017.31
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