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Psychology

Acute Biphasic Effects of Ayahuasca

September 30, 2015 / Ayahuasca, DMT, Neuroscience, Papers, Psychology, Publications / By / , , , , ,

Abstract

Ritual use of ayahuasca, an amazonian Amerindian medicine turned sacrament in syncretic religions in Brazil, is rapidly growing around the world. Because of this internationalization, a comprehensive understanding of the pharmacological mechanisms of action of the brew and the neural correlates of the modified states of consciousness it induces is important. Employing a combination of electroencephalogram (EEG) recordings and quantification of ayahuasca’s compounds and their metabolites in the systemic circulation we found ayahuasca to induce a biphasic effect in the brain. This effect was composed of reduced power in the alpha band (8–13 Hz) after 50 minutes from ingestion of the brew and increased slow- and fast-gamma power (30–50 and 50–100 Hz, respectively) between 75 and 125 minutes. Alpha power reductions were mostly located at left parieto-occipital cortex, slow-gamma power increase was observed at left centro-parieto-occipital, left fronto-temporal and right frontal cortices while fast-gamma increases were significant at left centro-parieto-occipital, left fronto-temporal, right frontal and right parieto-occipital cortices. These effects were significantly associated with circulating levels of ayahuasca’s chemical compounds, mostly N,N-dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine and some of their metabolites. An interpretation based on a cognitive and emotional framework relevant to the ritual use of ayahuasca, as well as it’s potential therapeutic effects is offered.

Schenberg E.E., Alexandre J.F.M., Filev R., Cravo A.M., Sato J.R., Muthukumaraswamy S.D., et al. (2015) Acute Biphasic Effects of Ayahuasca. PLoS ONE 10(9): e0137202. http://dx.doi.org/10.1371/journal.pone.0137202
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Ketamine for depression: evidence, challenges and promise

September 25, 2015 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

Major depressive disorder and bipolar depression are among the most prevalent and disabling mental disorders worldwide. Real-world effectiveness trials in major depressive disorder have underscored that most pharmacological options target monoamines, which are involved in a minority (15-20%) of synaptic contacts in the mammalian brain.

Most synapses (∼50%) use the amino acid glutamate as their primary neurotransmitter, and preclinical models of depression have implicated aberrant glutamatergic neurotransmission for 25 years. More recently, the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine was shown to produce rapid and robust antidepressant effects in patients with treatment-resistant major depressive disorder and bipolar depression.

Zarate, C. A., & Niciu, M. J. (2015). Ketamine for depression: evidence, challenges and promise. World Psychiatry, 14(3), 348-350. http://dx.doi.org/10.1002/wps.20269
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The Prosocial Effects of 3,4-methylenedioxymethamphetamine (MDMA): Controlled Studies in Humans and Laboratory Animals

September 25, 2015 / MDMA, Papers, Psychology, Publications / By / ,

Abstract

Users of ±3,4-Methylenedioxymethamphetamine (MDMA; ‘ecstasy’) report prosocial effects such as sociability and empathy. Supporting these apparently unique social effects, data from controlled laboratory studies indicate that MDMA alters social feelings, information processing, and behavior in humans, and social behavior in rodents. Here, we review this growing body of evidence. In rodents, MDMA increases passive prosocial behavior (adjacent lying) and social reward while decreasing aggression, effects that may involve serotonin 1A receptor mediated oxytocin release interacting with vasopressin receptor 1A. In humans, MDMA increases plasma oxytocin and produces feelings of social affiliation. It decreases identification of negative facial expressions (cognitive empathy) and blunts responses to social rejection, while enhancing responses to others’ positive emotions (emotional empathy) and increasing social approach. Thus, consistent with drug folklore, laboratory administration of MDMA robustly alters social processing in humans and increases social approach in humans and animals. Effects are consistent with increased sociability, with mixed evidence about enhanced empathy. These neurobiologically-complex prosocial effects likely motivate recreational ecstasy use.

Kamilar-Britt, P., & Bedi, G. (2015). The Prosocial Effects of 3, 4-methylenedioxymethamphetamine (MDMA): Controlled Studies in Humans and Laboratory Animals. Neuroscience & Biobehavioral Reviews. http://dx.doi.org/10.1016/j.neubiorev.2015.08.016
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[Psychedelics and quasi-psychedelics in the light of contemporary research: medical cannabis, MDMA, salvinorin A, ibogaine and ayahuasca]

September 17, 2015 / Ayahuasca, Iboga / Ibogaine, MDMA, Papers, Psychology, Publications, Salvia / Salvinorin A / By / , , ,

Abstract

In lack of professional research and appropriate concepts our scientific knowledge of psychedelic agents is limited. According to the long-held official view these drugs are entirely harmful and have no medical use. However, a recent surge of clinical and pharmacological studies in the field indicates that many psychedelic-like agents have therapeutic potentials under proper circumstances. In this paper, from a biomedical and psychological perspective, we provide a brief review of the general effects and promising treatment uses of medical cannabis, 3,4-methylenedioxy-methamphetamine (MDMA), salvinorin A, ibogaine and the dimethyltryptamine-(DMT)-containing ayahuasca. In Hungary – similarly to many other countries – these compounds are classified as “narcotic drugs” and their research is difficult due to strict regulations.

Szabo, A., Kazai, A., Frecska, E., & Brys, Z. (2015). [Psychedelics and quasi-psychedelics in the light of contemporary research: medical cannabis, MDMA, salvinorin A, ibogaine and ayahuasca]. Neuropsychopharmacologia Hungarica: a Magyar Pszichofarmakologiai Egyesulet lapja= official journal of the Hungarian Association of Psychopharmacology, 17(3), 120-128.
Link to full text [Article in Hungarian]

3,4-Methylenedioxymethamphetamine facilitates fear extinction learning

September 15, 2015 / Anxiety Disorders / PTSD, MDMA, Neuroscience, Papers, Psychology, Publications / By / , , ,

Abstract

Acutely administered 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) has been proposed to have long-term positive effects on post-traumatic stress disorder (PTSD) symptoms when combined with psychotherapy. No preclinical data support a mechanistic basis for these claims. Given the persistent nature of psychotherapeutic gains facilitated by MDMA, we hypothesized that MDMA improves fear extinction learning, a key process in exposure-based therapies for PTSD. In these experiments, mice were first exposed to cued fear conditioning and treated with drug vehicle or MDMA before extinction training 2 days later. MDMA was administered systemically and also directly targeted to brain structures known to contribute to extinction. In addition to behavioral measures of extinction, changes in mRNA levels of brain-derived neurotrophic factor (Bdnf) and Fos were measured after MDMA treatment and extinction. MDMA (7.8 mg kg−1) persistently and robustly enhanced long-term extinction when administered before extinction training. MDMA increased the expression of Fos in the amygdala and medial prefrontal cortex (mPFC), whereas increases in Bdnf expression were observed only in the amygdala after extinction training. Extinction enhancements were recapitulated when MDMA (1  μg) was infused directly into the basolateral complex of the amygdala (BLA), and enhancement was abolished when BDNF signaling was inhibited before extinction. These findings suggest that MDMA enhances fear memory extinction through a BDNF-dependent mechanism, and that MDMA may be a useful adjunct to exposure-based therapies for PTSD and other anxiety disorders characterized by altered fear learning.

Young, M. B., Andero, R., Ressler, K. J., & Howell, L. L. (2015). 3, 4-Methylenedioxymethamphetamine facilitates fear extinction learning. Translational Psychiatry, 5(9), e634. http://dx.doi.org/10.1038/tp.2015.138

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LSD Flashbacks – The Appearance of New Visual Imagery Not Experienced During Initial Intoxication: Two Case Reports.

September 14, 2015 / LSD, Papers, Psychology, Publications / By / , , ,

Abstract

A side effect associated with the use of synthetic hallucinogens such as lysergic acid diethylamide-(LSD) is the partial or total recurrence of perceptual disturbances which previously appeared during intoxication, despite absence of recent use. These are commonly referred to as “flashbacks” or Hallucinogen Persisting Perception Disorder (HPPD). Here we present two cases of patients with a prior history of LSD use who turned to psychiatric consultation following brief episodes of HPPD. Surprisingly, in both cases new visual imagery appeared during episodes of flashbacks which was not experienced during primary LSD use. Both subjects reported the ability to discern between LSD-associated visual disturbances and new visual imagery. This phenomenon did not cause functional impairment and in both cases caused gradual concern due to its persistence. Both patients refused medical treatment and continued psychiatric follow-up. At one year follow-up both patients reported almost complete spontaneous remission. To the best of our knowledge these are the first reported cases of LSD-related benign flashbacks in which new imagery is experienced. Reasons for this reversible and apparently harmless side effect are proposed. Conclusions from case reports should be taken with caution.

Lerner, A. G., Goodman, C., Rudinski, D., & Lev-Ran, S. (2014). LSD flashbacks–the appearance of new visual imagery not experienced during initial intoxication: Two case reports. Isr J Psychiatry Relat Sci, 51(4).
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Psychedelic medicine: A re-emerging therapeutic paradigm

December 6, 2021 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, DMT, Ketamine, LSD, MDMA, Mescaline / Cacti, Papers, Psychology, Publications / By / , , ,

Introduction

In clinical research settings around the world, renewed investigations are taking place on the use of psychedelic substances for treating illnesses such as addiction, depression, anxiety and posttraumatic stress disorder (PTSD). Since the termination of a period of research from the 1950s to the early 1970s, most psychedelic substances have been classified as “drugs of abuse” with no recognized medical value. However, controlled clinical studies have recently been conducted to assess the basic psychopharmacological properties and therapeutic efficacy of these drugs as adjuncts to existing psychotherapeutic approaches. Central to this revival is the re-emergence of a paradigm that acknowledges the importance of set (i.e., psychological expectations), setting (i.e., physical environment) and the therapeutic clinician–patient relationship as critical elements for facilitating healing experiences and realizing positive outcomes [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”][…]

Tupper, K. W., Wood, E., Yensen, R., & Johnson, M. W. (2015). Psychedelic medicine: a re-emerging therapeutic paradigm. CMAJ: Canadian Medical Association journal= journal de l’Association medicale canadienne, 187(14), 1054. https://dx.doi.org/10.1503/cmaj.141124
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Salvinorin A, a kappa-opioid receptor (KOP-r) agonist hallucinogen: Pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders

September 8, 2015 / Biology & Ethnobotany, Neuroscience, Papers, Psychology, Publications, Salvia / Salvinorin A / By / ,

Abstract

Salvinorin A is a potent hallucinogen, isolated from the ethnomedical plant Salvia divinorum. Salvinorin A is a selective high efficacy kappa-opioid receptor (KOPr) agonist, and thus implicates the KOPr system and its endogenous agonist ligands (the dynorphins) in higher functions, including cognition and perceptual effects. Salvinorin A is the only selective KOPr ligand to be widely available outside research or medical settings, and salvinorin A-containing products have undergone frequent non-medical use. KOPr/dynorphin systems in the brain are known to be powerful counter-modulatory mechanisms to dopaminergic function, which is important in mood and reward engendered by natural and chemical reinforcers (including drugs of abuse). KOPr activation (including by salvinorin A) can thus cause aversion and anhedonia in preclinical models. Salvinorin A is also a completely new scaffold for medicinal chemistry approaches, since it is a non-nitrogenous neoclerodane, unlike other known opioid ligands. Ongoing efforts have the goal of discovering novel semi-synthetic salvinorin analogs with potential KOPr-mediated pharmacotherapeutic effects (including partial agonist or biased agonist effects), with a reduced burden of undesirable effects associated with salvinorin A.

Butelman, E., & Kreek, M. J. (2015). Salvinorin A, a kappa-opioid receptor (KOP-r) agonist hallucinogen: Pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders. Frontiers in Pharmacology, 6, 190. http://dx.doi.org/10.3389/fphar.2015.00190
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Ketamine for depression: the highs and lows

September 1, 2015 / Depressive Disorders, Ketamine, Papers, 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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