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Antidepressant, anxiolytic and procognitive effects of subacute and chronic ketamine in the chronic mild stress model of depression

October 18, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , ,

Abstract

Ketamine is the prototype of a new generation of antidepressant drugs, which is reported in clinical studies to be effective in treatment-resistant patients, with an effect that appears within hours and lasts for a few days. Chronic mild stress (CMS) is a well-established and widely used animal model of depression, in which anhedonia, anxiogenesis and cognitive dysfunction can be observed reliably. Studies using acute or brief ketamine treatment following withdrawal from CMS have replicated the clinical finding of a rapid onset of antidepressant action. However, there have been no CMS studies of chronic daily ketamine treatment or continued stress following ketamine treatment, which would have greater translational potential in relation to the long-term maintenance of antidepressant effects. Wistar rats were drug treated following an initial 2 weeks of CMS exposure, which continued alongside daily drug treatment. A first experiment tested a range of chronic (5 weeks) ketamine doses (5-30 mg/kg); a second compared the effects of subacute (3-5 days) and chronic (5 weeks) treatment. CMS-induced anhedonic, anxiogenic and dyscognitive effects, as measured, respectively, by decreased sucrose intake, avoidance of open arms in the elevated plus maze and loss of discrimination in the novel object recognition test. A sustained antidepressant-like effect of ketamine in the sucrose intake test was observed in both experiments, with an onset at around 1 week, faster than imipramine, and an optimum dose of 10 mg/kg. Anxiogenic and dyscognitive effects of CMS, in the elevated plus maze and novel object recognition test, respectively, were fully reversed by both subacute and chronic ketamine treatment. Daily treatment with ketamine in the CMS model causes sustained long-term antidepressant, anxiolytic and procognitive effects. The demonstration of a procognitive effect of ketamine may have particular translational value.

Papp, M., Gruca, P., Lason-Tyburkiewicz, M., & Willner, P. (2016). Antidepressant, anxiolytic and procognitive effects of subacute and chronic ketamine in the chronic mild stress model of depression. Behavioural Pharmacology. 10.1097/FBP.0000000000000259

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Development of a Psychotherapeutic Model for Psilocybin-Assisted Treatment of Alcoholism

October 16, 2016 / Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Research activity on the potential clinical value of classic hallucinogens and other psychedelics has increased markedly in the past two decades, and promises to continue to expand. Experimental study of hallucinogen-assisted treatment, and any future clinical use, requires the development of psychotherapeutic models that are appropriate to the disorder being treated and effectively integrated with the pharmacologic component of the treatment. To provide a framework for thinking about possible treatment models, we provide an overview of the history of psychedelic-assisted treatment, review what is known about the therapeutic mechanisms of these treatments, and consider the various purposes of psychotherapy in the context of both research and clinical use of psychedelic-assisted treatment. We then provide a description of a therapy model we have developed and are currently using in a trial of psilocybin-assisted treatment for alcoholism. Finally, we discuss advantages and disadvantages of a range of alternative models, emphasizing the need for research to determine the most effective treatment models for any indications for which efficacy becomes established.

Bogenschutz, M. P., & Forcehimes, A. A. (2016). Development of a Psychotherapeutic Model for Psilocybin-Assisted Treatment of Alcoholism. Journal of Humanistic Psychology, 0022167816673493.
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Alterations of consciousness and mystical-type experiences after acute LSD in humans

October 7, 2016 / LSD, Papers, Psychology, Publications / By / , ,

Abstract

Rationale: Lysergic acid diethylamide (LSD) is used recreationally and in clinical research. Acute mystical-type experiences that are acutely induced by hallucinogens are thought to contribute to their potential therapeutic effects. However, no data have been reported on LSD-induced mystical experiences and their relationship to alterations of consciousness. Additionally, LSD dose- and concentration-response functions with regard to alterations of consciousness are lacking.

Methods: We conducted two placebo-controlled, double-blind, cross-over studies using oral administration of 100 and 200 μg LSD in 24 and 16 subjects, respectively. Acute effects of LSD were assessed using the 5 Dimensions of Altered States of Consciousness (5D-ASC) scale after both doses and the Mystical Experience Questionnaire (MEQ) after 200 μg.

Results: On the MEQ, 200 μg LSD induced mystical experiences that were comparable to those in patients who underwent LSD-assisted psychotherapy but were fewer than those reported for psilocybin in healthy subjects or patients. On the 5D-ASC scale, LSD produced higher ratings of blissful state, insightfulness, and changed meaning of percepts after 200 μg compared with 100 μg. Plasma levels of LSD were not positively correlated with its effects, with the exception of ego dissolution at 100 μg.

Conclusions: Mystical-type experiences were infrequent after LSD, possibly because of the set and setting used in the present study. LSD may produce greater or different alterations of consciousness at 200 μg (i.e., a dose that is currently used in psychotherapy in Switzerland) compared with 100 μg (i.e., a dose used in imaging studies). Ego dissolution may reflect plasma levels of LSD, whereas more robustly induced effects of LSD may not result in such associations.

Liechti, M. E., Dolder, P. C., & Schmid, Y. (2016). Alterations of consciousness and mystical-type experiences after acute LSD in humans. Psychopharmacology, 1-12. 10.1007/s00213-016-4453-0

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Activation of 5-HT2A/2C receptors reduces the excitability of cultured cortical neurons

October 6, 2016 / Neuroscience, Papers, Publications / By / , , , , ,

Abstract

The abundant forebrain serotonergic projections are believed to modulate the activities of cortical neurons. 5-HT2 receptor among multiple subtypes of serotonin receptors contributes to the modulation of excitability, synaptic transmissions and plasticity. In the present study, whole-cell patch-clamp recording was adopted to examine whether activation of 5-HT2A/2C receptors would have any impact on the excitability of cultured cortical neurons. We found that 2,5-Dimethoxy-4-iodoamphetamine (DOI), a selective 5-HT2A/2C receptor agonist, rapidly and reversibly depressed spontaneous action potentials mimicking the effect of serotonin. The decreased excitability was also observed for current-evoked firing. Additionally DOI increased neuronal input resistance. Hyperpolarization-activated cyclic nucleotide-gated cationic channels (HCN) did not account for the inhibition of spontaneous firing. The synaptic contribution was ruled out in that DOI augmented excitation and attenuated inhibition to actually favor an increase in the excitability. Our findings revealed that activation of 5-HT2A/2C receptors reduces neuronal excitability, which would deepen our understanding of serotonergic modulation of cortical activities.
Hu, L., Liu, C., Dang, M., Luo, B., Guo, Y., & Wang, H. (2016). Activation of 5-HT 2A/2C receptors reduces the excitability of cultured cortical neurons. Neuroscience letters, 632, 124-129. 10.1016/j.neulet.2016.08.052
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Psychological effects of MDMA

October 4, 2016 / MDMA, Papers, Psychology, Publications / By /

Abstract

Zinberg’s Interaction Model implies that the content of a drug-induced experience is a function of the pharmacological properties of the drug, the set (the user’s characteristics e.g. motivation and personality), and the setting (the physical and social context). The current research investigated the function of the set and setting and their role in shaping the psychological effects of 3,4-methylenedioxmethamphetamine (MDMA), as well as their role in reducing the risk of drug abuse.
An online survey was distributed among adult MDMA polydrug users (n = 158) and MDMA-naïve controls (alcohol, nicotine and cannabis users, n = 138). Participants answered questions regarding their pattern of drug use, their motivation for MDMA use and the setting (e.g. clubbing, home with friends), as well as the subjective effects of MDMA. Participants also completed a range of self-report measures of self-reflection and insight, emotional intelligence, and personality, as well as a drug dependency measure.
MDMA users displayed higher levels of self-reflection and insight, openness to new experience and lower levels of neuroticism and conscientiousness, in comparison to the control group. The significant predictors of self-reflection and insight were openness, emotional intelligence, MDMA use, extraversion and neuroticism. When the analysis was rerun only for the MDMA group, the significant predictors of self-reflection and insight were openness, emotional intelligence and self-insight effects of MDMA. High levels of self-reported negative effects of MDMA were predictors of a problematic drug use.
These findings suggest that there might be a relationship between MDMA use and higher levels of self-reflection and insight; however, longitudinal studies are required to further investigate the causality of this relationship. The results add to existing evidence that MDMA has potential for altering emotional experiences. Further research utilising a prospective design is warranted.

Wieliczko, M. J. (2016). Psychological effects of MDMA (Doctoral dissertation, Canterbury Christ Church University).

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A Double-Blinded, Randomized, Placebo-Controlled Sub-Dissociative Dose Ketamine Pilot Study in the Treatment of Acute Depression and Suicidality in a Military Emergency Department Setting

October 1, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Background: Rates of completed suicide in the military have increased. Options are limited for acute relief of depression and suicidal ideation. Traditional treatments’ effects take weeks to months. A novel, rapid, therapeutic target has emerged with the N-methyl-D-aspartate antagonist ketamine. Previous studies suggest that a single dose of intravenous (IV) ketamine rapidly alleviates depression and suicidality.

Methods: In this proof of concept study, an active duty convenience sample population presenting to the emergency department (ED) meeting criteria for inpatient psychiatric admission as a result of depression and suicidal thinking were randomized to receive either a subdissociative dose (0.2 mg/kg) of IV ketamine or equivalent volume of normal saline (placebo). Subjects were evaluated for symptoms throughout a 4-hour ED course, at hospital discharge, and 2 weeks postdischarge.

Results: Methodological problems limited analyzable data to 10 subjects. Two of three who received ketamine experienced dramatic decreases in suicidality and hopelessness within 40 minutes. No such improvements were seen in any of seven controls over the 4-hour observation in the ED. At discharge from the hospital, there was no clinically significant difference. No subjects described adverse symptoms.

Conclusion: Despite methodology difficulties noted in this pilot study, there was statistical improvement in intervention group versus controls.

Burger, J., Capobianco, M., Lovern, R., Boche, B., Ross, E., Darracq, M. A., & McLay, R. (2016). A Double-Blinded, Randomized, Placebo-Controlled Sub-Dissociative Dose Ketamine Pilot Study in the Treatment of Acute Depression and Suicidality in a Military Emergency Department Setting. Military Medicine, 181(10), 1195-1199. 10.7205/MILMED-D-15-00431
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Psychedelics in the treatment of unipolar mood disorders: A systematic review

October 1, 2016 / Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

Unipolar mood disorders, including major depressive disorder and persistent depressive disorder (dysthymia), confer high rates of disability and mortality and a very high socioeconomic burden. Current treatment is suboptimal in most cases and there is little of note in the pharmaceutical development pipeline. The psychedelic drugs, including lysergic acid diethylamide and psilocybin, were used extensively in the treatment of mood disorders, and other psychiatric conditions, before their prohibition in the late 1960s. They are relatively safe when used in medically controlled environments, with no reported risk of dependence. Here, we present a systematic review of published clinical treatment studies using psychedelics in patients with broadly defined unipolar mood disorder, and consider their place in psychiatry. Whilst all the included studies have methodological shortcomings, of 423 individuals in 19 studies, 335 (79.2%) showed clinician-judged improvement after treatment with psychedelics. A recently completed pilot study in the UK favours the use of psilocybin with psychological support in treatment resistant depressive disorder. The evidence overall strongly suggests that psychedelics should be re-examined in modern clinical trials for their use in unipolar mood disorders and other non-psychotic mental health conditions.

Rucker, J. J., Jelen, L. A., Flynn, S., Frowde, K. D., & Young, A. H. Psychedelics in the Treatment of Unipolar Mood Disorders: A Systematic Review.
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Lysergic Acid Diethylamide and mystical experiences

October 1, 2016 / Humanities & Art, LSD, Papers, Publications / By /

Abstract

The term psychedelic (“mind-manifesting”) was coined by British psychiatrist Humphry Osmond in 1956 to refer to a unique class of mind-altering chemicals with distinctive effects that set them apart from other drugs with hallucinogenic properties. Some psychedelics come from natural sources that have been traditionally featured in religious, ritual, and healing practices of indigenous cultures of the Americas (Anderson, 1980; Hofmann, 1983; Salak, 2007; Smith, 2000); such drugs include mescaline (from peyote and San Pedro cacti), psilocybin and psilocin (from Psilocybe mushrooms), and dimethyltryptamine or DMT (from the leaves of Psychotria viridis). Many other psychedelics have partly or wholly synthetic origins. The most potent psychedelic agent yet discovered is the semisynthetic ergot derivative lysergic acid diethylamide (LSD), which has distinctive effects at the microscopic dose of 25 μg; a typical psychedelic dose ranges from 50 to 200 μg. There are also a number of purely synthetic psychedelics, many of which are chemically related to both amphetamine and mescaline (Shulgin & Shulgin, 1991). One of the most potent of these is dimethoxymethylamphetamine, or DOM, which was known as “STP” when introduced to the hippie subculture of San Francisco in the late 1960s. More familiar today is methylenedioxymethamphetamine (MDMA, ecstasy), which has only mild or partial psychedelic effects as opposed to full psychedelics such as LSD, psilocybin, and mescaline; MDMA is thus sometimes described as an “entactogen,” meaning “touch within” (Bravo, 2001; Smith, 2000), as opposed to full psychedelics or “entheogens,” meaning “God within.” A newer, extremely potent synthetic psychedelic, 2-(4-iodo-2,5-dimethoxyphenyl)-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”][(2-methoxyphenyl)methyl] ethanamine (2CI-NBOMe, or “N-Bomb”), was invented in 2003 and is useful as a laboratory tool to map brain serotonin receptors (Ettrup et al., 2010). The threshold dose is several hundred micrograms, making this psychedelic second in potency only to LSD. Media reports indicate that 2CI-NBOMe has been sold to drug users on pieces of blotter paper, like LSD, and often misrepresented as the latter drug. Unfortunately 2CI-NBOMe has a much lower therapeutic index than LSD, hence several highly publicized deaths appear to have been caused by this drug (e.g., Hastings, 2013; Poklis et al., 2014) and, in some cases, possibly misattributed to LSD. Some of the deaths resulted from drug-induced seizures, whereas in other cases the individuals killed themselves accidentally or purposefully in a drug-induced psychotic or delirious state. By contrast, fatal reactions are extremely uncommon with the “classic” psychedelics LSD, psilocybin, and mescaline.

Lyvers, M. (2016). Lysergic Acid Diethylamide and mystical experiences. 10.1016/B978-0-12-800212-4.00078-9
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The Relationship between depression and use of ecstasy among adolescents in Taiwan

October 1, 2016 / Depressive Disorders, MDMA, Papers, Psychology, Publications / By / , , ,

Abstract

Introduction: The aim of this cross-sectional study was to examine the relationship between depression and ecstasy use among adolescents in Taiwan by controlling for the effects of demographic characteristics and cannabis use.

Methods: A total of 10,262 adolescents aged 12-18 years completed research questionnaires that assessed their severity of depression, status of ecstasy use, and history of cannabis use. The participants were grouped into non-users, ex-users, and current users. Severity of depression among these three adolescent groups was compared using analysis of covariance (ANCOVA), considering the history of cannabis use and demographic characteristics as covariates.
Results: After controlling for history of cannabis use and age, the study found that current ecstasy users experienced more severe depressive symptoms than ex-users and non-users. The difference between ex-users and non-users was not significant.
Conclusion: This study found that current ecstasy users had more severe depressive symptoms than non-users and ex-users. Psychological health professionals must monitor depressive symptoms among adolescent ecstasy users and provide emotional regulation strategies and psychological intervention for those with significant depression.
Lee, K. H., Su, C. H., Hsiao, R. C., Yen, C. N., & Yen, C. F. (2016). The Relationship between depression and use of ecstasy among adolescents in Taiwan. Neuropsychiatry (London), 6(4), 124-127. 10.4172/Neuropsychiatry.1000130
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The Entheogen Reformation

October 1, 2016 / Ayahuasca, Humanities & Art, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

In addition to promising leads for treating PTSD, addictions, depression, and death anxiety, 21st Century research at medical schools finds that with careful screening, insightful attention to the variables of set, setting, and dosage, psychedelic drug administration often facilitates significant spiritual experiences, meaningfulness, altruism, well-being, and similar prospiritual effects. This article calls for theologians, professors of religious studies, philosophy, sociology, and psychology to update their courses. It challenges leaders of religious organizations, ‘‘How can your institution incorporate these practices and benefit from them?’’

Roberts, T. B. (2016). THE ENTHEOGEN REFORMATION. Association for Transpersonal Psychology, 26.

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