OPEN Foundation

Day: 5 February 2016

Modification of 5-methoxy-N,N-dimethyltryptamine-induced hyperactivity by monoamine oxidase A inhibitor harmaline in mice and the underlying serotonergic mechanisms

February 5, 2016 / Neuroscience, Other subjects, Other substances, Papers, Psychopharmacology, Publications / By / , ,

Abstract

BACKGROUND: 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and harmaline are indolealkylamine (IAA) drugs often abused together. Our recent studies have revealed the significant effects of co-administered harmaline, a monoamine oxidase inhibitor (MAOI), on 5-MeO-DMT pharmacokinetics and thermoregulation. This study was to delineate the impact of harmaline and 5-MeO-DMT on home-cage activity in mouse models, as well as the contribution of serotonin (5-HT) receptors.

METHODS: Home-cage activities of individual animals were monitored automatically in the home cages following implantation of telemetry transmitters and administration of various doses of IAA drugs and 5-HT receptor antagonists. Area under the effect curve (AUEC) of mouse activity values were calculated by trapezoidal rule.

RESULTS: High dose of harmaline (15mg/kg, ip) alone caused an early-phase (0-45min) hypoactivity in mice that was fully attenuated by 5-HT1A receptor antagonist WAY-100635, whereas a late-phase (45-180min) hyperactivity that was reduced by 5-HT2A receptor antagonist MDL-100907. 5-MeO-DMT (10 and 20mg/kg, ip) alone induced biphasic effects, an early-phase (0-45min) hypoactivity that was completely attenuated by WAY-100635, and a late-phase (45-180min) hyperactivity that was fully suppressed by MDL-100907. Interestingly, co-administration of MAOI harmaline (2-15mg/kg) with a subthreshold dose of 5-MeO-DMT (2mg/kg) induced excessive hyperactivities at late phase (45-180min) that could be abolished by either WAY-100635 or MDL-100907.

CONCLUSIONS: Co-administration of MAOI with 5-MeO-DMT provokes excessive late-phase hyperactivity, which involves the activation of both 5-HT1A and 5-HT2A receptors.

Jiang, X. L., Shen, H. W., & Yu, A. M. (2016). Modification of 5-methoxy-N, N-dimethyltryptamine-induced hyperactivity by monoamine oxidase A inhibitor harmaline in mice and the underlying serotonergic mechanisms. Pharmacological Reports, 68(3), 608-615. http://dx.doi.org/10.1016/j.pharep.2016.01.008

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Should ketamine be used for the clinical treatment of depression?

February 5, 2016 / Depression, Ketamine, Papers, Psychiatry, Psychology, Publications / By / , ,

Abstract

OBJECTIVE: There has been widespread interest from the public and media in the potential of ketamine as a novel treatment for depression. This paper reviews whether current evidence supports the use of ketamine for the clinical treatment of depression.

CONCLUSIONS: Clinical trials have investigated the use of intravenous ketamine for the treatment of depressive symptoms over the past 15 years. However, there remain many unanswered questions regarding its effectiveness, safety, and the route, dose and regimen for repeated administration. Experts have also raised concerns regarding ketamine’s adverse effects, abuse potential and the risk of addiction. At this stage, the use of ketamine in the treatment of depression remains in the realm of research settings.

Arunogiri, S., Keks, N. A., & Hope, J. (2016). Should ketamine be used for the clinical treatment of depression?. Australasian Psychiatry, http://dx.doi.org/10.1177/1039856216629839.

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The paradoxical psychological effects of lysergic acid diethylamide (LSD).

February 5, 2016 / Consciousness, LSD, Other subjects, Papers, Personality, Psychiatry, Psychology, Publications / By / , , , , ,

Abstract

BACKGROUND: Lysergic acid diethylamide (LSD) is a potent serotonergic hallucinogen or psychedelic that modulates consciousness in a marked and novel way. This study sought to examine the acute and mid-term psychological effects of LSD in a controlled study.

METHOD: A total of 20 healthy volunteers participated in this within-subjects study. Participants received LSD (75 µg, intravenously) on one occasion and placebo (saline, intravenously) on another, in a balanced order, with at least 2 weeks separating sessions. Acute subjective effects were measured using the Altered States of Consciousness questionnaire and the Psychotomimetic States Inventory (PSI). A measure of optimism (the Revised Life Orientation Test), the Revised NEO Personality Inventory, and the Peter’s Delusions Inventory were issued at baseline and 2 weeks after each session.

RESULTS: LSD produced robust psychological effects; including heightened mood but also high scores on the PSI, an index of psychosis-like symptoms. Increased optimism and trait openness were observed 2 weeks after LSD (and not placebo) and there were no changes in delusional thinking.

CONCLUSIONS: The present findings reinforce the view that psychedelics elicit psychosis-like symptoms acutely yet improve psychological wellbeing in the mid to long term. It is proposed that acute alterations in mood are secondary to a more fundamental modulation in the quality of cognition, and that increased cognitive flexibility subsequent to serotonin 2A receptor (5-HT2AR) stimulation promotes emotional lability during intoxication and leaves a residue of ‘loosened cognition’ in the mid to long term that is conducive to improved psychological wellbeing.

Carhart-Harris, R. L., Kaelen, M., Bolstridge, M., Williams, T. M., Williams, L. T., Underwood, R., … & Nutt, D. J. (2016). The paradoxical psychological effects of lysergic acid diethylamide (LSD). Psychological medicine, 1-12. http://dx.doi.org/10.1017/S0033291715002901

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30 April - Q&A with Rick Strassman

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