OPEN Foundation

Day: 1 September 2015

Ketamine for depression: the highs and lows

September 1, 2015 / Depression, Ketamine, Papers, Psychiatry, Psychology, Publications / By /

Abstract

Long used as an anaesthetic and analgesic, most people familiar with ketamine know of it for this purpose. Others know it as a party drug that can give users an out-of-body experience, leaving them completely disconnected from reality. Less well known is its growing off-label use in the USA for depression, in many cases when other options have been exhausted.

Kirby, T. (2015). Ketamine for depression: the highs and lows. The Lancet Psychiatry, 2(9), 783-784. http://dx.doi.org/10.1016/S2215-0366(15)00392-2
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Psilocybin, psychological distress, and suicidality

September 1, 2015 / Depression, Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , ,

Abstract

Hendricks et al. (2015) found that having ever used any classic psychedelic substance—namely, dimethyltryptamine (DMT), ayahuasca, lysergic acid diethylamide (LSD), mescaline, peyote or San Pedro, or psilocybin—was associated with a significantly reduced likelihood of past month psychological distress (weighted OR = .81 (.72–.91)), past year suicidal thinking (weighted OR = .86 (.78–.94)), past year suicidal planning (weighted OR = .71 (.54–.94)), and past year suicide attempt (weighted OR = .64 (.46–.89)) in the United States adult population. Although these findings comport with an emerging literature suggesting classic psychedelics may be effective in the treatment of mental health conditions and prevention of self-harm, they do not speak to the potential risk profile or therapeutic applications of psilocybin in particular, which is the most commonly examined classic psychedelic in contemporary clinical research. Considering that psilocybin may be a candidate for future approved medical use in the United States, the United Kingdom, and other nations (Bogenschutz et al., 2015; Grob et al., 2011; Johnson et al., 2014; see also Nutt et al., 2013), an analysis of the specific relationships of psilocybin use with psychological distress and suicidality may help inform decisions by the United States Food and Drug Administration and regulatory bodies of other nations. The objectives of the current research, therefore, were to extend the analysis of Hendricks et al. (2015) by evaluating the associations of lifetime psilocybin use, per se, with past month psychological distress, past year suicidal thinking, past year suicidal planning, and past year suicide attempt in the United States adult population.

Hendricks, P. S., Johnson, M. W., & Griffiths, R. R. (2015). Psilocybin, psychological distress, and suicidality. Journal of Psychopharmacology, 29(9), 1041-1043. http://dx.doi.org/10.1177/0269881115598338
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R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects

September 1, 2015 / Depression, Ketamine, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , , , , , ,

Abstract

Although the efficacy of racemate ketamine, a rapid onset and sustained antidepressant, for patients with treatment-resistant depression was a serendipitous finding, clinical use of ketamine is limited, due to psychotomimetic side effects and abuse liability. Behavioral and side-effect evaluation tests were applied to compare the two stereoisomers of ketamine. To elucidate their potential therapeutic mechanisms, we examined the effects of these stereoisomers on brain-derived neurotrophic factor (BDNF)-TrkB signaling, and synaptogenesis in selected brain regions. In the social defeat stress and learned helplessness models of depression, R-ketamine showed a greater potency and longer-lasting antidepressant effect than S-ketamine (esketamine). Furthermore, R-ketamine induced a more potent beneficial effect on decreased dendritic spine density, BDNF-TrkB signaling and synaptogenesis in the prefrontal cortex (PFC), CA3 and dentate gyrus (DG) of the hippocampus from depressed mice compared with S-ketamine. However, neither stereoisomer affected these alterations in the nucleus accumbens of depressed mice. In behavioral tests for side effects, S-ketamine, but not R-ketamine, precipitated behavioral abnormalities, such as hyperlocomotion, prepulse inhibition deficits and rewarding effects. In addition, a single dose of S-ketamine, but not R-ketamine, caused a loss of parvalbumin (PV)-positive cells in the prelimbic region of the medial PFC and DG. These findings suggest that, unlike S-ketamine, R-ketamine can elicit a sustained antidepressant effect, mediated by increased BDNF-TrkB signaling and synaptogenesis in the PFC, DG and CA3. R-ketamine appears to be a potent, long-lasting and safe antidepressant, relative to S-ketamine, as R-ketamine appears to be free of psychotomimetic side effects and abuse liability.

Yang, C., Shirayama, Y., Zhang, J. C., Ren, Q., Yao, W., Ma, M., … & Hashimoto, K. (2015). R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects. Translational psychiatry, 5(9), e632. http://dx.doi.org/10.1038/tp.2015.136

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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

September 1, 2015 / MDMA, Papers, Personality, 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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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

September 1, 2015 / MDMA, Papers, Personality, 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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Effects of LSD on grooming behavior in serotonin transporter heterozygous (Sert+/−) mice

September 1, 2015 / LSD, Neuroscience, Other subjects, Papers, Psychology, Psychopharmacology, Publications / By / , ,

Abstract

Serotonin (5-HT) plays a crucial role in the brain, modulating mood, cognition and reward. The serotonin transporter (SERT) is responsible for the reuptake of 5-HT from the synaptic cleft and regulates serotonin signaling in the brain. In humans, SERT genetic variance is linked to the pathogenesis of various psychiatric disorders, including anxiety, autism spectrum disorders (ASD) and obsessive–compulsive disorder (OCD). Rodent self-grooming is a complex, evolutionarily conserved patterned behavior relevant to stress, ASD and OCD. Genetic ablation of mouse Sert causes various behavioral deficits, including increased anxiety and grooming behavior. The hallucinogenic drug lysergic acid diethylamide (LSD) is a potent serotonergic agonist known to modulate human and animal behavior. Here, we examined heterozygous Sert+/− mouse behavior following acute administration of LSD (0.32 mg/kg). Overall, Sert+/− mice displayed a longer duration of self-grooming behavior regardless of LSD treatment. In contrast, LSD increased serotonin-sensitive behaviors, such as head twitching, tremors and backwards gait behaviors in both Sert+/+ and Sert+/− mice. There were no significant interactions between LSD treatment and Sert gene dosage in any of the behavioral domains measured. These results suggest that Sert+/− mice may respond to the behavioral effects of LSD in a similar manner to wild-type mice.

Kyzar, E. J., Stewart, A. M., & Kalueff, A. V. (2016). Effects of LSD on grooming behavior in serotonin transporter heterozygous (Sert+/−) mice. Behavioural brain research, 296, 47-52. http://dx.doi.org/10.1016/j.bbr.2015.08.018
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30 April - Q&A with Rick Strassman

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