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Ketamine and other potential glutamate antidepressants

November 12, 2014 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , ,

Abstract

The need for rapid acting antidepressants is widely recognised. There has been much interest in glutamate mechanisms in major depressive disorder (MDD) as a promising target for the development of new antidepressants. A single intravenous infusion of ketamine, a N-methyl-d–aspartate (NMDA) receptor antagonist anaesthetic agent, can alleviate depressive symptoms in patients within hours of administration. The mechanism of action appears to be in part through glutamate release onto non-NMDA receptors including α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and metabotropic receptors. However these are also reported effects on 5-HT, dopamine and intracellular effects on the mammalian target of rapamycin (mTOR) pathway. The effects of SSRI (Selective Serotonin Reuptake Inhibitor) antidepressants may also involve alterations in NMDA function. The article reviews the effect of current antidepressants on NMDA and examines the efficacy and mechanism of ketamine. Response to ketamine is also discussed and comparison with other glutamate drugs including lamotrigine, amantadine, riluzole, memantine, traxoprodil, GLYX-13, MK-0657, RO4917523, AZD2066 and Coluracetam. Future studies need to link the rapid antidepressant effects seen with ketamine to inflammatory theories in MDD.

Dutta, A., McKie, S., & Deakin, J. W. (2014). Ketamine and other potential glutamate antidepressants. Psychiatry research, 225(1-2), 1-13. https://dx.doi.org/10.1016/j.psychres.2014.10.028

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Psilocybin and Obsessive Compulsive Disorder

November 11, 2014 / Anxiety Disorders / PTSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

Obsessive Compulsive Disorder (OCD) is a psychiatric disorder with considerable morbidity and mortality. This condition disables many individuals and is often refractory to treatment. Research suggests that serotonin plays a role in OCD symptom reduction. We present a case of an individual who successfully used psilocybin, a serotonergic agent, to reduce the core symptoms of OCD for several years. Although not endorsing this form of treatment, we feel that the successful use of this agent highlights the role of serotonergic factors in OCD and the need for further, legitimate research into the value of psilocybin in the treatment of anxiety disorders.

Wilcox, J. A. (2014). Psilocybin and Obsessive Compulsive Disorder. Journal of psychoactive drugs, 46(5), 393-395. https://dx.doi.org/10.1080/02791072.2014.963754

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LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects

November 11, 2014 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, Papers, Psychology, Publications / By / , ,

Abstract

Objective: A recently published study showed the safety and efficacy of LSD-assisted psychotherapy in patients with anxiety associated with life-threatening diseases. Participants of this study were included in a prospective follow-up.

Method: 12 months after finishing LSD psychotherapy, 10 participants were tested for anxiety (STAI) and participated in a semi-structured interview. A Qualitative Content Analysis (QCA) was carried out on the interviews to elaborate about LSD effects and lasting psychological changes.

Results: None of the participants reported lasting adverse reactions. The significant benefits as measured with the STAI were sustained over a 12-month period. In the QCA participants consistently reported insightful, cathartic and interpersonal experiences, accompanied by a reduction in anxiety (77.8%) and a rise in quality of life (66.7%). Evaluations of subjective experiences suggest facilitated access to emotions, confrontation of previously unknown anxieties, worries, resources and intense emotional peak experiences à la Maslow as major psychological working mechanisms. The experiences created led to a restructuring of the person’s emotional trust, situational understanding, habits and world view.

Conclusions: LSD administered in a medically supervised psychotherapeutic setting can be safe and generate lasting benefits in patients with a life-threatening disease. Explanatory models for the therapeutic effects of LSD warrant further study.

Gasser, P., Kirchner, K., & Passie, T. (2014). LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects. Journal of Psychopharmacology. https://dx.doi.org/10.1177/0269881114555249
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Improvement in suicidal ideation after ketamine infusion: Relationship to reductions in depression and anxiety

November 8, 2014 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Objective

Suicide is a psychiatric emergency. Currently, there are no approved pharmacologic treatments for suicidal ideation. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that rapidly reduces suicidal ideation as well as depression and anxiety, but the dynamic between these symptoms is not known. The aim of this analysis was to evaluate whether ketamine has an impact on suicidal thoughts, independent of depressive and anxiety symptoms.

Methods

133 patients with treatment-resistant depression (major depressive disorder or bipolar I/II disorder) received a single subanesthetic infusion of ketamine (0.5 mg/kg over 40 min). Post-hoc correlations and linear mixed models evaluated the relationship between suicidal ideation and depression and anxiety symptoms using the Hamilton Depression Rating Scale (HAMD), Scale for Suicidal Ideation (SSI), Beck Depression Inventory (BDI), and Hamilton Anxiety Rating Scale (HAMA) focusing on 230 min post-infusion.

Results

At 230 min post-infusion, correlations between changes in suicidal ideation and depression ranged from 0.23 to 0.44 (p < .05), accounting for up to 19% in the variance of ideation change. Correlations with anxiety ranged from 0.23 to 0.40 (p < .05), accounting for similar levels of variance. Ketamine infusion was associated with significant reductions in suicidal ideation compared to placebo, when controlling for the effects of ketamine on depression (F1,587 = 10.31, p = .001) and anxiety (F1,567 = 8.54, p = .004).

Conclusions

Improvements in suicidal ideation after ketamine infusion are related to, but not completely driven by, improvements in depression and anxiety. Investigation of the specific effects of ketamine on suicidal thoughts is warranted.

Ballard, E. D., Ionescu, D. F., Voort, J. L. V., Niciu, M. J., Richards, E. M., Luckenbaugh, D. A., … & Zarate, C. A. (2014). Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depression and anxiety. Journal of psychiatric research, 58, 161-166. https://dx.doi.org/10.1016/j.jpsychires.2014.07.027

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Effects of ecstasy on cooperative behaviour and perception of trustworthiness: A naturalistic study

November 8, 2014 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Background: Acute recreational use of 3,4-methylenedioxymethamphetamine (MDMA; ‘ecstasy’) can promote pro-social effects which may alter interpersonal perceptions.

Aims: To explore such effects, this study investigated whether acute recreational use of ecstasy was associated with changes in individual perception of trustworthiness of people’s faces and co-operative behaviours.

Method: An independent group, repeated measures design was used in which 17 ecstasy users were tested on the night of drug use (day 0) and again three days later (day 3); 22 controls were tested on parallel days. On each day, participants rated the trustworthiness of 66 faces, carried out three co-operative behaviour tasks (public good; dictator; ultimatum game) and completed mood self-ratings.

Results: Acute ecstasy use was associated with increased face trustworthiness ratings and increased cooperative behaviour on the dictator and ultimatum games; on day 3 there were no group differences on any task. Self-ratings showed the standard acute ecstasy effects (euphoria, energy, jaw clenching) with negative effects (less empathy, compassion, more distrust, hostility) emerging on day 3.

Conclusions: Our findings of increased perceived trustworthiness and co-operative behaviours following use of ecstasy suggest that a single dose of the drug enhances aspects of empathy. This may in turn contribute to its popularity as a recreational drug and potentially to its enhancement of the therapeutic alliance in psychotherapy.

Stewart, L. H., Ferguson, B., Morgan, C. J. A., Swaboda, N., Jones, L., Fenton, R., … & Curran, H. V. (2014). Effects of ecstasy on cooperative behaviour and perception of trustworthiness: A naturalistic study. Journal of Psychopharmacology, 28(11), 1001-1008. https://dx.doi.org/10.1177/0269881114544775

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M1 and M2 Muscarinic Receptor Subtypes Regulate Antidepressant-Like Effects of the Rapidly Acting Antidepressant Scopolamine

November 8, 2014 / Depressive Disorders, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Scopolamine produces rapid and significant symptom improvement in patients with depression, and most notably in patients who do not respond to current antidepressant treatments. Scopolamine is a nonselective muscarinic acetylcholine receptor antagonist, and it is not known which one or more of the five receptor subtypes in the muscarinic family are mediating these therapeutic effects. We used the mouse forced-swim test, an antidepressant detecting assay, in wild-type and transgenic mice in which each muscarinic receptor subtype had been genetically deleted to define the relevant receptor subtypes. Only the M1 and M2 knockout (KO) mice had a blunted response to scopolamine in the forced-swim assay. In contrast, the effects of the tricyclic antidepressant imipramine were not significantly altered by gene deletion of any of the five muscarinic receptors. The muscarinic antagonists biperiden, pirenzepine, and VU0255035 (N-[fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][3-oxo-3-[4-(4-pyridinyl)-1-piper azinyl]propyl]-2,1,3-benzothiadiazole-4-sulfonamide) with selectivity for M1 over M2 receptors also demonstrated activity in the forced-swim test, which was attenuated in M1 but not M2 receptor KO mice. An antagonist with selectivity of M2 over M1 receptors (SCH226206 [(2-amino-3-methyl-phenyl)-[4-[4-[[4-(3 chlorophenyl)sulfonylphenyl]methyl]-1-piperidyl]-1-piperidyl]methanone]) was also active in the forced-swim assay, and the effects were deleted in M2−/− mice. Brain exposure and locomotor activity in the KO mice demonstrated that these behavioral effects of scopolamine are pharmacodynamic in nature. These data establish muscarinic M1 and M2 receptors as sufficient to generate behavioral effects consistent with an antidepressant phenotype and therefore as potential targets in the antidepressant effects of scopolamine.

Witkin, J. M., Overshiner, C., Li, X., Catlow, J. T., Wishart, G. N., Schober, D. A., … & Felder, C. C. (2014). M1 and M2 Muscarinic Receptor Subtypes Regulate Antidepressant-Like Effects of the Rapidly Acting Antidepressant Scopolamine. Journal of Pharmacology and Experimental Therapeutics, 351(2), 448-456. https://dx.doi.org/10.1124/jpet.114.216804
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Synesthesias in the context of hallucinogen-induced persistent perception disorder following the use of lsd

November 7, 2014 / LSD, Papers, Psychology, Publications / By / ,

Abstract

The hallucinogen-induced persistent perception disorder (hppd) is a disturbing complication resulting from the use of hallucinogens. We report on a case-study in which an artist suffering from visual, auditory and olfactory hallucinations also experienced chromatic-phonemic synesthesias that had persisted for two years after he had stopped using lysergic acid diethylamide (lsd). The case described demonstrates that individuals suffering from hppd can also experience synesthesias that may in fact differ phenomenologically from ‘coloured hearing’, which is a symptom known to occur in the context of substance abuse.

Neven, A., & Blom, J. D. (2013). [Synesthesias in the context of hallucinogen-induced persistent perception disorder following the use of lsd]. Tijdschrift voor psychiatrie, 56(11), 748-752.
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Harmine mediated neuroprotection via evaluation of glutamate transporter 1 in a rat model of global cerebral ischemia.

November 7, 2014 / Neuroscience, Papers, Publications / By / , , ,

Abstract

Global cerebral ischemia (GCI) causes energy deficiency results in excessive release of glutamate from neurons. Astrocytic glutamate transporters play a predominant role in keeping extracellular glutamate concentrations below excitotoxic levels. Glutamate transporter 1 (GLT-1) may account for more than 90% of glutamate uptake in adult forebrain. Preclinical findings implicate that Harmine present neuroprotection effects in a rat model of amyotrophic lateral sclerosis disease, and the beneficial effects were specifically due to up-regulation of GLT-1. However, no experiments have explored the potential of Harmine to provide neuroprotection in the setting of GCI. The current study was designed to determine whether Harmine could attenuate cerebral infarction as well as improve neuronal survival after GCI. Furthermore, to test whether the mechanisms were associated with up-regulating of GLT-1, we used a GLT-1 specific inhibitor dihydrokainate (DHK) and analysis the expression of GLT-1 mRNA and protein in cortex of brain. We also examined whether Harmine treatment affected astrocytes activation via immunofluorescence. Our results showed that post-GCI administration of Harmine could attenuate cerebral infarct volume and decrease neurons death. It also caused significantly elevation of GLT-1 mRNA and protein and remarkably attenuation of astrocyte activation. We provide novel clues in understanding the mechanisms of which Harmine exerts its neuroprotective activity in neurological disorders.

Sun, P., Zhang, S., Li, Y., & Wang, L. (2014). Harmine mediated neuroprotection via evaluation of glutamate transporter 1 in a rat model of global cerebral ischemia. Neuroscience letters, 583, 32-36. http://dx.doi.org/10.1016/j.neulet.2014.09.023
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Dictyonema huaorani (Agaricales: Hygrophoraceae), a new lichenized basidiomycete from Amazonian Ecuador with presumed hallucinogenic properties

November 7, 2014 / Biology & Ethnobotany, Papers, Pharmacology & Chemistry, Publications / By / , , , , ,

Abstract

Dictyonema huaorani, a new species represented by a well-developed specimen found in the Ecuadorian Amazon region, is described in this paper. The material was collected during a Harvard ethnobotanical expedition in 1981 and originally determined by Mason E. Hale Jr. as belonging in the genus Dictyonema (D. sericeum s.lat.) and possibly representing an undescribed species. The species is morphologically distinctive in forming densely woven, semicircular thalli, closely resembling those of the paleotropical D. ligulatum but lacking clamps and with hyphal sheath around the photobiont filaments that resembles those of Cyphellostereum species. The species was reported to have hallucinogenic properties and chemical analyses suggest certain substances present that are shared with the hallucinogenic mushroom Psilocybe cubensis. Due to our inability to use pure reference compounds and scarce amount of sample for compound identification, however, our analyses were not able to determine conclusively the presence of hallucinogenic substances.

Schmull, M., Dal-Forno, M., Lücking, R., Cao, S., Clardy, J., & Lawrey, J. D. (2014). Dictyonema huaorani (Agaricales: Hygrophoraceae), a new lichenized basidiomycete from Amazonian Ecuador with presumed hallucinogenic properties. The Bryologist, 117(4), 386-394. http://dx.doi.org/10.1639/0007-2745-117.4.386

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Toxicities Associated With NBOMe Ingestion—A Novel Class of Potent Hallucinogens: A Review of the Literature

November 6, 2014 / Papers, Publications / By / , , , , , ,

Abstract

Background

A new class of synthetic hallucinogens called NBOMe has emerged as drugs of abuse.

Objective

Our aim was to conduct a systematic review of published reports of toxicities associated with NBOMe ingestion.

Methods

We searched PubMed for relevant English-language citations that described adverse effects from analytically confirmed human NBOMe ingestion. Demographic and clinical data were extracted.

Results

A total of 10 citations met the criteria for inclusion, representing 20 individual patients. 25I-NBOMe was the most common analogue identified, followed by 25B-NBOMe and 25C-NBOMe. Fatalities were reported in 3 (15%) cases. Of all the patients, 7 (35%) were discharged after a period of observation, whereas 8 (40.0%) required admission to an intensive care unit. The most common adverse effects were agitation (85.0%), tachycardia (85.0%), and hypertension (65.0%). Seizures were reported in 8 (40.0%) patients. The most common abnormalities reported on laboratory tests were elevated level of creatinine kinase (45.0%), leukocytosis (25.0%), and hyperglycemia (20.0%).

Conclusion

NBOMe ingestion is associated with severe adverse effects. Clinicians need to have a high index of suspicion for NBOMe ingestion in patients reporting the recent use of hallucinogens.

Suzuki, J., Dekker, M. A., Valenti, E. S., Cruz, F. A. A., Correa, A. M., Poklis, J. L., & Poklis, A. (2014). Toxicities associated with NBOMe Ingestion, a Novel Class of Potent Hallucinogens: a Review of the Literature. Psychosomatics. http://dx.doi.org/10.1016/j.psym.2014.11.002
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