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Noribogaine reduces nicotine self-administration in rats

May 20, 2015 / Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / , , ,

Abstract

Noribogaine, a polypharmacological drug with activities at opioid receptors, ionotropic nicotinic receptors, and serotonin reuptake transporters, has been investigated for treatment of substance abuse-related disorders. Smoking cessation has major benefits for both individuals and society, therefore the aim of this study was to evaluate the potential of noribogaine for use as a treatment for nicotine dependence. Adult male Sprague-Dawley rats were trained to self-administer nicotine intravenous. After initial food pellet training, followed by 26 sessions of nicotine self-administration training, the rats were administered noribogaine (12.5, 25 or 50 mg/kg orally), noribogaine vehicle, varenicline or saline using a within-subject design with a Latin square test schedule. Noribogaine dose-dependently decreased nicotine self-administration by up to 64% of saline-treated rats’ levels and was equi-effective to 1.7 mg/kg intraperitoneal varenicline. Noribogaine was less efficient at reducing food pellets self-administration than at nicotine self-administration, inhibiting the nondrug reinforcing effects of palatable pellets by 23% at the highest dose. These results suggest that noribogaine dose-dependently attenuates drug-taking behavior for nicotine, attenuates the reinforcing effects of nicotine and is comparable to varenicline power in that regard. The findings from the present study hold promise for a new therapy to aid smoking cessation.

Chang, Q., Hanania, T., Mash, D. C., & Maillet, E. L. (2015). Noribogaine reduces nicotine self-administration in rats. Journal of Psychopharmacology, 29(6), 704-711. http://dx.doi.org/10.1177/0269881115584461
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Ketamine induces a robust whole-brain connectivity pattern that can be differentially modulated by drugs of different mechanism and clinical profile

May 19, 2015 / Ketamine, Neuroscience, Papers, Publications / By / , , , , , ,

Abstract

Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has been studied in relation to the glutamate hypothesis of schizophrenia and increases dissociation, positive and negative symptom ratings. Ketamine effects brain function through changes in brain activity; these activity patterns can be modulated by pre-treatment of compounds known to attenuate the effects of ketamine on glutamate release. Ketamine also has marked effects on brain connectivity; we predicted that these changes would also be modulated by compounds known to attenuate glutamate release. Here, we perform task-free pharmacological magnetic resonance imaging (phMRI) to investigate the functional connectivity effects of ketamine in the brain and the potential modulation of these effects by pre-treatment of the compounds lamotrigine and risperidone, compounds hypothesised to differentially modulate glutamate release. Connectivity patterns were assessed by combining windowing, graph theory and multivariate Gaussian process classification. We demonstrate that ketamine has a robust effect on the functional connectivity of the human brain compared to saline (87.5 % accuracy). Ketamine produced a shift from a cortically centred, to a subcortically centred pattern of connections. This effect is strongly modulated by pre-treatment with risperidone (81.25 %) but not lamotrigine (43.75 %). Based on the differential effect of these compounds on ketamine response, we suggest the observed connectivity effects are primarily due to NMDAR blockade rather than downstream glutamatergic effects. The connectivity changes contrast with amplitude of response for which no differential effect between pre-treatments was detected, highlighting the necessity of these techniques in forming an informed view of the mechanistic effects of pharmacological compounds in the human brain.

Joules, R., Doyle, O. M., Schwarz, A. J., O’Daly, O. G., Brammer, M., Williams, S. C., & Mehta, M. A. (2015). Ketamine induces a robust whole-brain connectivity pattern that can be differentially modulated by drugs of different mechanism and clinical profile. Psychopharmacology, 1-14. https://dx.doi.org/10.1007/s00213-015-3951-9

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Recreational 3,4-methylenedioxy-N-methylamphetamine (MDMA) or ‘ecstasy’ and self-focused compassion: Preliminary steps in the development of a therapeutic psychopharmacology of contemplative practices.

May 18, 2015 / MDMA, Papers, Psychology, Publications / By / , , , , , ,

Abstract

3,4-methylenedioxy-N-methylamphetamine (MDMA) produces diverse pro-social effects. Cognitive training methods rooted in Eastern contemplative practices also produce these effects through the development of a compassionate mindset. Given this similarity, we propose that one potential mechanism of action of MDMA in psychotherapy is through enhancing effects on intrapersonal attitudes (i.e. pro-social attitudes towards the self). We provide a preliminary test of this idea. Recreational MDMA (ecstasy) users were tested on two occasions, having consumed or not consumed ecstasy. Self-critical and self-compassionate responses to self-threatening scenarios were assessed before (T1) and after (T2) ecstasy use (or non-use), and then after compassionate imagery (T3). Moderating roles of dispositional self-criticism and avoidant attachment were examined. Separately, compassionate imagery and ecstasy produced similar sociotropic effects, as well as increases in self-compassion and reductions in self-criticism. Higher attachment-related avoidance was associated with additive effects of compassionate imagery and ecstasy on self-compassion. Findings were in line with MDMA’s neuropharmacological profile, its phenomenological effects and its proposed adjunctive use in psychotherapy. However, although conditions were balanced, the experiment was non-blind and MDMA dose/purity was not determined. Controlled studies with pharmaceutically pure MDMA are still needed to test these effects rigorously.

Kamboj, S. K., Kilford, E. J., Minchin, S., Moss, A., Lawn, W., Das, R. K., … & Freeman, T. P. (2015). Recreational 3, 4-methylenedioxy-N-methylamphetamine (MDMA) or ‘ecstasy’and self-focused compassion: Preliminary steps in the development of a therapeutic psychopharmacology of contemplative practices. Journal of Psychopharmacology, 0269881115587143.
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Immunomodulatory activity of ketamine in human astroglial A172 cells: Possible relevance to its rapid antidepressant activity.

May 15, 2015 / Depressive Disorders, Ketamine, Neuroscience, Papers, Publications / By / , , ,

Abstract

To determine if the immunomodulatory effect of ketamine is relevant to its rapid antidepressant activity, cultured human astroglial cells were incubated with ketamine, cytokine mix, or both. At 24h, ketamine dose-dependently (100-500 μM) decreased IL-6 and TNFα production and gene expression and, at clinically relevant concentration (100 μM), augmented IL-β release and gene expression in both unstimulated and cytokine-stimulated cells. In unstimulated cells, ketamine also increased IL-8 production and mRNA expression. The reduction in IL-6 mRNA was significant within 1h in unstimulated cells and at 4h after stimulation. Ketamine suppressed the production of the only established depression-relevant proinflammatory cytokines, IL-6 and TNFα.

Yuhas, Y., Ashkenazi, S., Berent, E., & Weizman, A. (2015). Immunomodulatory activity of ketamine in human astroglial A172 cells: Possible relevance to its rapid antidepressant activity. Journal of neuroimmunology, 282, 33-38. https://dx.doi.org/10.1016/j.jneuroim.2015.03.012
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Ketamine-induced state models schizophrenia

February 7, 2022 / Ketamine, Psychology, Psychotic Disorders / By

In the 1950’s, research on the psychoactive properties of lysergic acid diethylamide (LSD) led scientists to the serotonin hypothesis of schizophrenia, a theory still used to explain the neurochemical roots of schizophrenia. Today, Höflich et al. (2015) have used ketamine to explore the role of neurotransmitter glutamate in this mental disorder [3].

Since neuroimaging studies indicated dysfunctional glutamate pathways in schizophrenia, glutamate is thought to play a key role in its aetiology. These abnormalities are specifically apparent in the thalamus, a brain region regarded as the information integration system of the brain. By measuring brain activity in healthy volunteers after ketamine administration, Höflich et al. (2015) explored ketamine as a model for schizophrenia to further investigate the link between glutamate and schizophrenia. Ketamine is a glutamate antagonist, which means that it prevents neurotransmission by blocking the activity of glutamate on N-methyl-D-aspartate (NMDA) receptors. The effects of ketamine resemble some of the positive, negative, and cognitive symptoms of schizophrenia.

In the study of Höflich et al. (2015), thirty healthy volunteers completed a double-blind, placebo-controlled, randomized, crossover study in which each volunteer was scanned using fMRI on two separate days. Brain network activation under ketamine was compared to placebo. The brain images revealed higher functional connectivity in the thalamus hub network in the ketamine condition compared to placebo. Furthermore, ketamine induced higher connectivity between thalamic regions and somatosensory and temporal cortices. Connectivity between the thalamus and prefrontal, motor, posterior parietal, and occipital cortices did not differ significantly.

The authors conclude that ketamine temporarily triggers alterations in functional connectivity in healthy volunteers that resemble structural brain connectivity patterns in schizophrenic patients. They infer that the ketamine-induced state might function as a model of schizophrenia, especially relative to characteristic sensory filtering problems. However, their results did not reveal a decrease of prefrontal-thalamic connectivity typical for schizophrenic patients [4] suggesting that other neurotransmitters also account for the manifestation of schizophrenia. Using ketamine and other drug models [5] to investigate the relationship between neurotransmitter systems and the symptomatology of schizophrenia could yield valuable information about the neural underpinnings of this mental disorder.

[1] Gaddum, J. H., Hebb, C. O., Silver, A., & Swan, A. A. B. (1953). 5-Hydroxytryptamine. Pharmacological action and destruction in perfused lungs. Quart. J. Exper. Physiol., 38, 255.
[2] Woolley, D. W., & Shaw, E. (1954). a Biochemical and Pharmacological Suggestion About Certain Mental Disorders. Proceedings of the National Academy of Sciences of the United States of America, 40(4), 228–231. doi:10.1073/pnas.40.4.228
[3] Höflich, A., Hahn, A., Küblböck, M., Kranz, G. S., Vanicek, T., Windischberger, C., …Lanzenberger, R. (2015). Ketamine-Induced Modulation of the Thalamo- Cortical Network in Healthy Volunteers As a Model for Schizophrenia. International Journal of Neuropsychopharmacology, 1–11. doi:10.1093/ijnp/pyv040 [Abstract]
[4] Leitman DI, Sehatpour P, Higgins BA, Foxe JJ, Silipo G, Javitt DC (2010) Sensory deficits and distributed hierarchical dysfunction in schizophrenia. Am J Psychiatry 167:818–827
[5] Steeds, H., Carhart-Harris, R. L., & Stone, J. M. (2014). Drug models of schizophrenia. Therapeutic Advances in Psychopharmacology, 5(1), 43–58. doi:10.1177/2045125314557797 [Abstract][/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]

Ketamine geïnduceerde staat als model voor schizofrenie

December 2, 2021 / Uncategorized / By

Onderzoek naar de psychoactieve eigenschappen van lysergeenzuurdi-ethyladmide (LSD) in de jaren ’50 bracht wetenschappers op de serotonine hypothese van schizofrenie [1][2], een theorie die nog steeds wordt gebruikt om de neurochemische oorsprong van schizofrenie te verklaren. Recentelijk hebben Höflich et al. (2015) ketamine gebruikt om de rol van neurotransmitter glutamaat in deze psychische stoornis te onderzoeken [3].

Vanwege het feit dat er in eerder neuroimaging onderzoek verstoorde glutamaterge hersennetwerken zijn gevonden bij schizofrene patiënten, wordt er gedacht dat glutamaat een sleutelrol speelt in de etiologie van schizofrenie. Deze afwijkingen doen zich vooral voor in de thalamus, het hersengebied dat betrokken is bij het integreren en doorgeven van informatie uit andere hersengebieden. Door de hersenactiviteit te meten bij gezonde vrijwilligers die ketamine toegediend kregen, onderzochten Höflich e.a. (2015) of ketamine gebruikt kan worden als een model voor schizofrenie om zo de link tussen glutamaat en schizofrenie verder te bestuderen. Ketamine is een glutamaat antagonist. Dit betekent dat ketamine de glutamaterge neurotransmissie verhindert door de overdracht van glutamaat te blokkeren op de N-methyl-D-aspartaat (NMDA) receptor. De effecten van ketamine lijken op een aantal van de positieve, negatieve en cognitieve symptomen van schizofrenie.

In het onderzoek van Höflich e.a. (2015) voltooiden dertig gezonde vrijwilligers het dubbelblinde, placebogecontroleerde, gerandomiseerde crossover onderzoek, waarbij iedere vrijwilliger op twee verschillende dagen werd gescand in een fMRI-scanner. Hersenactiviteit werd vergeleken tussen degenen die ketamine toegediend kregen en degenen die een placebo ontvingen. De hersenscans van degenen in de ketamineconditie vertoonden, in vergelijking met de placeboconditie, een hogere functionele activiteit van de thalamus. Ook veroorzaakte ketamine een hogere connectiviteit tussen de thalamische gebieden en de somatosensorische en temporale cortexen. Er werd geen significant verschil in connectiviteit gevonden tussen de thalamus en de prefrontale, motorische, posteriore pariëtale en occipitale cortexen.

De auteurs concluderen dat ketamine tijdelijk een veranderde functionele connectiviteit teweeg kan brengen in gezonde hersenen die lijkt op de structurele hersenconnectiviteit bij schizofrene patiënten. Ze leiden hieruit af dat de neurochemische toestand die wordt veroorzaakt door ketamine als model zou kunnen fungeren voor schizofrenie, vooral wanneer het om het verklaren van de karakteristieke problemen inzake zintuiglijke filtering betreft. In het onderzoek werd echter geen afname van de connectiviteit tussen prefrontale cortex en thalamus gevonden, hetgeen wel voorkomt bij schizofrene patiënten [4]. Deze bevinding suggereert dat andere neurotransmitters ook verantwoordelijk zijn voor de manifestatie van schizofrenie. Het gebruik van ketamine en andere drugsmodellen [5] om de relatie tussen neurotransmittersystemen en de symptomatologie van schizofrenie te onderzoeken kan waardevolle informatie opleveren over de neurale fundamenten van deze mentale stoornis.

 
[1] Gaddum, J. H., Hebb, C. O., Silver, A., & Swan, A. A. B. (1953). 5-Hydroxytryptamine. Pharmacological action and destruction in perfused lungs. Quart. J. Exper. Physiol., 38, 255.
[2] Woolley, D. W., & Shaw, E. (1954). A Biochemical and Pharmacological Suggestion About Certain Mental Disorders. Proceedings of the National Academy of Sciences of the United States of America, 40(4), 228–231. doi:10.1073/pnas.40.4.228
[3] Höflich, A., Hahn, A., Küblböck, M., Kranz, G. S., Vanicek, T., Windischberger, C., …Lanzenberger, R. (2015). Ketamine-Induced Modulation of the Thalamo-Cortical Network in Healthy Volunteers As a Model for Schizophrenia. International Journal of Neuropsychopharmacology, 1–11. doi:10.1093/ijnp/pyv040 [Abstract]
[4] Leitman DI, Sehatpour P, Higgins BA, Foxe JJ, Silipo G, Javitt DC (2010). Sensory deficits and distributed hierarchical dysfunction in schizophrenia. Am J Psychiatry 167: 818-827
[5] Steeds, H., Carhart-Harris, R. L., & Stone, J. M. (2014). Drug models of schizophrenia. Therapeutic Advances in Psychopharmacology, 5(1), 43–58. doi:10.1177/2045125314557797 [Abstract]

Acid Hype: American News Media and the Psychedelic Experience

May 4, 2015 / Publications / By

acid hypeNow synonymous with Sixties counterculture, LSD actually entered the American consciousness via the mainstream. Time and Life, messengers of lumpen-American respectability, trumpeted its grand arrival in a postwar landscape scoured of alluring descriptions of drug use while lesser outlets piggybacked on their coverage with stories by turns sensationalised and glowing.

Acid Hype offers the untold tale of LSD’s wild journey from Brylcreem and Ivory soap to incense and peppermints. As Stephen Siff shows, the early attention lavished on the drug by the news media glorified its use in treatments for mental illness but also its status as a mystical–yet legitimate–gateway to exploring the unconscious mind. Siff’s history takes readers to the center of how popular media hyped psychedelic drugs in a constantly shifting legal and social environment, producing an intricate relationship between drugs and media experience that came to define contemporary pop culture. It also traces how the breathless coverage of LSD gave way to a textbook moral panic, transforming yesterday’s refined seeker of truths into an acid casualty splayed out beyond the fringe of polite society.

Stephen Siff is an assistant professor of journalism at Miami University, Ohio.

Acid Hype: American News Media and the Psychedelic Experience, by Stephen Siff, History of Communication series, University of Illinois Press, 264 pages.

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Acid Hype: American News Media and the Psychedelic Experience

December 24, 2021 / LSD / By

Now synonymous with Sixties counterculture, LSD actually entered the American consciousness via the mainstream. Time and Life, messengers of lumpen-American respectability, trumpeted its grand arrival in a postwar landscape scoured of alluring descriptions of drug use while lesser outlets piggybacked on their coverage with stories by turns sensationalised and glowing.

Acid Hype offers the untold tale of LSD’s wild journey from Brylcreem and Ivory soap to incense and peppermints. As Stephen Siff shows, the early attention lavished on the drug by the news media glorified its use in treatments for mental illness but also its status as a mystical–yet legitimate–gateway to exploring the unconscious mind. Siff’s history takes readers to the center of how popular media hyped psychedelic drugs in a constantly shifting legal and social environment, producing an intricate relationship between drugs and media experience that came to define contemporary pop culture. It also traces how the breathless coverage of LSD gave way to a textbook moral panic, transforming yesterday’s refined seeker of truths into an acid casualty splayed out beyond the fringe of polite society.

Stephen Siff is an assistant professor of journalism at Miami University, Ohio.

Acid Hype: American News Media and the Psychedelic Experience, door Stephen Siff, History of Communication reeks, University of Illinois Press, 264 pagina’s.

Koop dit boek via bookdepository.com en steun daarmee Stichting OPEN.

Intranasal drug delivery in neuropsychiatry: focus on intranasal ketamine for refractory depression.

May 1, 2015 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By /

Abstract

Intranasal drug delivery (INDD) systems offer a route to the brain that bypasses problems related to gastrointestinal absorption, first-pass metabolism, and the blood-brain barrier; onset of therapeutic action is rapid, and the inconvenience and discomfort of parenteral administration are avoided. INDD has found several applications in neuropsychiatry, such as to treat migraine, acute and chronic pain, Parkinson disease, disorders of cognition, autism, schizophrenia, social phobia, and depression. INDD has also been used to test experimental drugs, such as peptides, for neuropsychiatric indications; these drugs cannot easily be administered by other routes. This article examines the advantages and applications of INDD in neuropsychiatry; provides examples of test, experimental, and approved INDD treatments; and focuses especially on the potential of intranasal ketamine for the acute and maintenance therapy of refractory depression.

Andrade, C. (2015). Intranasal drug delivery in neuropsychiatry: focus on intranasal ketamine for refractory depression. The Journal of clinical psychiatry, 76(5), e628-31. https://dx.doi.org/10.4088/JCP.15f10026

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