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Ketamine as a Rapid-Acting Antidepressant: Promising Clinical and Basic Research

/ Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology / / ,

Abstract

Suicidal ideation and attempts are a common medical emergency, accounting for about 650,000 adult evaluations per year in emergency settings (1). Depressive disorders are a major driving force behind this, but first-line antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), can take months to work, making them of limited use in acutely suicidal patients. Potentially safe and fast-acting interventions would be invaluable in acute situations until standard antidepressants have time to take effect.
Ketamine, best known as an N-methyl-d-aspartate receptor (NMDAR) antagonist commonly used as an anesthetic, has recently drawn attention for possibly filling the role. At lower doses it exhibits strong antidepressant effects in many patients, and it acts on the order of minutes. Despite these promising effects, its use as an antidepressant has been controversial, as ketamine is also a Schedule III controlled substance that is used recreationally for its dissociative and hallucinogenic effects. Furthermore, the full mechanism of action regarding its antidepressant effects has long remained unclear.
In the present article, we review research surrounding ketamine’s potential as a fast-acting antidepressant from a “two-pronged” approach: first, summarizing established and new knowledge on its mechanism of action and second, reviewing clinical research addressing its potential to quickly reduce depression and suicidality.
Tuck, A. N., & Ghazali, D. H. (2017). Ketamine as a Rapid-Acting Antidepressant: Promising Clinical and Basic Research. American Journal of Psychiatry Residents’ Journal, 12(3), 3-5. 10.1176/appi.ajp-rj.2017.120302
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Examination of the Phenomenology of the Ibogaine Treatment Experience: Role of Altered States of Consciousness and Psychedelic Experiences

/ Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / / , ,

Abstract

Psychedelic drugs have historically been used for ritualistic purposes and to help individuals gain insight. Ibogaine, a naturally occurring psychoactive substance, has been reported to have anti-addictive properties that aid in the treatment of substance use disorders. An online survey obtained retrospective data from individuals who used ibogaine in the past. Individuals who used ibogaine tended to describe thematically similar experiences post-treatment. This study adds to the literature by using the 5d-ASC, a psychometrically sound measure of altered states of consciousness (ASCs), to examine the ASCs induced by ibogaine and discusses the demographic characteristics of those who seek ibogaine treatment (N = 27). The study also examined several aspects of ibogaine treatment experience, including reasons for seeking treatment, course of treatment, and treatment outcome. Results indicated a positive correlation between the various dimensions of the ASCs and the outcome (ability to make changes in one’s life, cravings, and how changed the person was as a result of ibogaine treatment). While this study is limited in generalizability due to high attrition and low sample size, it deepens the understanding of the phenomenological experience of ibogaine and explores the possible utility of ibogaine in the treatment of substance use disorders.

Heink, A., Katsikas, S., & Lange-Altman, T. (2017). Examination of the Phenomenology of the Ibogaine Treatment Experience: Role of Altered States of Consciousness and Psychedelic Experiences. Journal of Psychoactive Drugs, 1-8. 10.1080/02791072.2017.1290855
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Conducting Qualitative Research With Psychedelic Psychopharmacologists: Challenges of Co-Production in an Era of Interdisciplinarity

/ Mushrooms / Psilocybin, Papers, Psychology, Substance Use Disorder / /

Abstract

From 2013 to 2015, I worked as a postdoctoral research fellow with a team of pharmacologists experimenting with psilocybin, an illegal psychoactive compound found in psychedelic mushrooms. The team had conducted an open-label clinical trial with long-term cigarette smokers, using psilocybin-assisted psychotherapy to help them quit. The smoking outcomes were very promising, occurring alongside many other profound positive life-changes. The team wanted to investigate further the mechanisms of change by which the study led to its effects. With my PhD training in qualitative research but little knowledge of psychopharmacology, I spearheaded a retrospective qualitative research project to identify participants’ perceptions of the mechanisms of change. This case study describes the challenges I experienced through my involvement with the pharmacology team and some of the solutions that emerged. The distance between collaborating physical scientists and social scientists ebbs and flows, and I begin by situating our interdisciplinary project in the context of the recent intellectual history of psychopharmacology. I then offer a twin analysis of working on the topic as a qualitative researcher and working in a team with pharmacologists. The case study ends with practical suggestions for getting the most out of interdisciplinary co-production.

Noorani, T. (2017). Conducting Qualitative Research With Psychedelic Psychopharmacologists: Challenges of Co-Production in an Era of Interdisciplinarity. 10.4135/9781526404862
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Peyote as Commodity: An Examination of Market Actors and Access Mechanisms

/ Mescaline / Cacti, Papers, Publications, Scientific Discipline / /

Abstract

Access to the peyote cactus, a religious sacrament of the Native American Church (NAC), has been regulated by the federal government and the state of Texas since the 1960s. Over the last forty years, the number of licensed distributors has declined, a trend accompanied by rising prices and a diminishing market supply of the psychoactive cactus. Distributors are recognized as the primary NAC peyote source; consequently, their disappearance would be devastating for the 250,000-plus adherents of this distinctive indigenous tradition. Based on interviews with current and former peyote distributors, peyote pickers, landowners, and NAC members, a map of the various commodity chains that make up the peyote supply network is constructed. This research applies Access Mapping and Access Analysis of the supply network to identify the primary factors driving the decline of the regulated peyote trade. Focusing on the distributors’ and NAC members’ rights-based, structural, and relational access mechanisms, avenues for increasing access are identified, including amendment of distributor licensing fees.

Feeney, K. (2017). Peyote as Commodity: An Examination of Market Actors and Access Mechanisms. Human Organization, 76(1), 59-72. 10.17730/0018-7259.76.1.59
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Intranasal Ketamine and Cognitive-Behavioral Therapy for Treatment-Refractory Obsessive-Compulsive Disorder

/ Ketamine, Papers, Psychology, Publications / / , ,

Adams, T. G., Bloch, M. H., & Pittenger, C. (2017). Intranasal Ketamine and Cognitive-Behavioral Therapy for Treatment-Refractory Obsessive-Compulsive Disorder. Journal of clinical psychopharmacology, 37(2), 269-271. 10.1097/JCP.0000000000000659
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Psychedelics and the science of self-experience

/ Neuroscience, Papers, Psychology, Publications, Scientific Discipline / / ,

Abstract

Altered self-experiences arise in certain psychiatric conditions, and may be induced by psychoactive drugs and spiritual/religious practices. Recently, a neuroscience of self-experience has begun to crystallise, drawing upon findings from functional neuroimaging and altered states of consciousness occasioned by psychedelic drugs. This advance may be of great importance for psychiatry.

Nour, M. M., & Carhart-Harris, R. L. (2017). Psychedelics and the science of self-experience. 10.1192/bjp.bp.116.194738
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Synthesis of New Harmine Isoxazoles and Evaluation of their Potential Anti-Alzheimer, Anti-inflammatory, and Anticancer Activities

/ Ayahuasca, Neuroscience, Papers, Pharmacology & Chemistry, Publications / / , , , ,

Abstract

Harmine 1 was extracted from the seeds of Peganum harmala. From this natural molecule, a new series of isoxazole derivatives with complete regiospecificity were prepared using 1,3-dipolar cycloaddition reactions with various arylnitrile oxides. Harmine and its derivatives were characterized by (1)H NMR, (13)C NMR and HRMS. The evaluation of their anti-acetylcholinesterase (AChE), anti-5-lipoxygenase (5-LOX), anti-xanthine oxidase (XOD) and anticancer activities were studied in vitro against AChE, 5-LOX and XOD enzymes, respectively, and in HTC-116, MCF7 and OVCAR-3 cancer cell lines. The prepared derivatives were shown to be inactive against the XOD enzyme (0-38.3 ± 1.9% at 100 µM). Compound 2 exhibited the best anti-AChE activity (IC50=1.9 ± 1.5 µM). Derivatives 3a, 3b and 3d had moderate cytotoxic activities (IC50=5.0 ± 0.3 µM (3a) and IC50=6.3 ± 0.4 µM (3b) against HCT 116 cells, IC50=5.0 ± 1.0 µM (3d) against MCF7 cells).

Filali, I., Romdhane, A., Znati, M., B Jannet, H., & Bouajila, J. (2016). Synthesis of New Harmine Isoxazoles and Evaluation of their Potential Anti-Alzheimer, Anti-inflammatory, and Anticancer Activities. Medicinal Chemistry, 12(2), 184-190. 10.2174/157340641202160209104115
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Indole Alkaloids from Plants as Potential Leads for Antidepressant Drugs: A Mini Review

/ Ayahuasca, Biology & Ethnobotany, Depressive Disorders, Neuroscience, Papers, Psychology, Publications / / , ,

Abstract

Depression is the most common illness observed in the elderly, adults, and children. Antidepressants prescribed are usually synthetic drugs and these can sometimes cause a wide range of unpleasant side effects. Current research is focussed on natural products from plants as they are a rich source of potent new drug leads. Besides Hypericum perforatum (St. John’s wort), the plants studied include Passiflora incarnata L. (passion flower), Mitragyna speciosa (kratom), Piper methysticum G. Forst (kava) and Valeriana officinalis L. Harman, harmol, harmine, harmalol and harmaline are indole alkaloids isolated from P. incarnata, while mitragynine is isolated from M. speciosa. The structure of isolated compounds from P. methysticum G. Forst and V. officinalis L. contains an indole moiety. The indole moiety is related to the neurotransmitter serotonin which is widely implicated for brain function and cognition as the endogenous receptor agonist. An imbalance in serotonin levels may influence mood in a way that leads to depression. The moiety is present in a number of antidepressants already on the market. Hence, the objective of this review is to discuss bioactive compounds containing the indole moiety from plants that can serve as potent antidepressants.

Hamid, H. A., Ramli, A. N., & Yusoff, M. M. (2017). Indole Alkaloids from Plants as Potential Leads for Antidepressant Drugs: A Mini Review. Frontiers in Pharmacology, 8, 96. 10.3389/fphar.2017.00096
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Anticancer activities of harmine by inducing a pro-death autophagy and apoptosis in human gastric cancer cells

/ Ayahuasca, Papers, Psychiatry & Medicine, Publications / / , , , , ,

Abstract

BACKGROUND:
Harmine, a β-carboline alkaloid from Peganum harmala, has multiple anti-tumor activities, especially for its folk therapy for digestive system neoplasm. However, the underlying mechanism of harmine on gastric cancer remains unclear.
PURPOSE:
To illuminate the potential anti-tumor activity and mechanism of harmine against gastric cancer cells.
METHODS/STUDY DESIGNS:
The anti-proliferative activity of harmine in vitro was evaluated by MTT assay. The autophagic activity induced by harmine was assessed using GFP-LC3 transfection. FITC/PI double staining was applied for the apoptosis inspection. The mitochondrial membrane potential was detected by JC-1 fluorescence probe. The potential mechanisms for proteins level in autophagy and apoptosis were analyzed by Western blot.
RESULTS:
Harmine exhibited potent effects on both autophagy and apoptosis. Treatment with harmine could enhance dots of GFP-LC3 in cells. Meanwhile, the process had connection with Beclin-1, LC3-II, and p62 by the inhibition of Akt/mTOR/p70S6K signaling. However, high concentration of harmine led to apoptosis characterized by the propidium/Annexin V-positive cell pollution, cell shrunk and the collapse of mitochondrial membrane potential. The regulation of Bcl-2, Bax and the gathering of cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 9 contributed to the induction of apoptosis. In addition, 10μM LY294002 (a specific inhibitor of PI3K/Akt) combination with 40μM harmine significantly increased the cytotoxicity to the gastric cancer cells and up-regulated both the apoptosis-related protein (cleaved-PARP, cleaved-caspase-3) and autophagy-related protein (Beclin-1, LC3-II, and p62). Adding the inhibitor of autophagy, 3-MA or BafA1, increased the viability of harmine-exposured gastric cancer cells, which confirmed the role of autophagy played in the gastric cancer cell death induced by harmine.
CONCLUSION:
Harmine might be a potent inducer of apoptosis and autophagy, which offered evidences to therapy of harmine in gastric carcinoma in the folk medicine.
Li, C., Wang, Y., Wang, C., Yi, X., Li, M., & He, X. (2017). Anticancer activities of harmine by inducing a pro-death autophagy and apoptosis in human gastric cancer cells. Phytomedicine, 28, 10-18. 10.1016/j.phymed.2017.02.008
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Journal Club #22: Applying the EU Regulatory Framework to Determine the Benefit–Risk Profile of Psychedelics - March 3

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