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3,4-Methylenedioxymethamphetamine facilitates fear extinction learning

/ Anxiety Disorders / PTSD, MDMA, Neuroscience, Papers, Psychology, Publications / / , , ,

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.

/ LSD, Papers, Psychology, Publications / / , , ,

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

/ Ayahuasca, DMT, Humanities & Art, LSD, MDMA, Mushrooms / Psilocybin, Papers, Publications / / ,

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”][…]
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Yensen, R., & Johnson, M. W. (2015). Psychedelic medicine: a re-emerging therapeutic paradigm. https://dx.doi.org/10.1503/cmaj.141124
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Psychedelic medicine: A re-emerging therapeutic paradigm

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

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

/ Biology & Ethnobotany, Neuroscience, Papers, Psychology, Publications, Salvia / Salvinorin A / / ,

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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Harmine blocks herpes simplex virus infection through downregulating cellular NF-κB and MAPK pathways induced by oxidative stress

/ Neuroscience, Papers, Psychiatry & Medicine, Publications / / , , , , , ,

Abstract

Herpes simplex virus types 1 and 2 (HSV-1 and -2) are highly prevalent in many populations and therapeutic options are limited. Both viruses can establish latency by maintaining viral genomes in neurons of sensory ganglia. Primary or recurrent HSV infections may lead to deleterious outcomes: HSV-1 infection may result in corneal blindness and encephalitis and HSV-2 infection leads to herpes genitalis. While no effective vaccine is available, acyclovir is widely used for therapy, which targets and inhibits viral DNA polymerase. Although acyclovir is of low toxicity, resistant strains arise due to persistent use, mainly in immune compromised patients. In our effort to identify new HSV inhibitory molecules, harmine was found to potently inhibit HSV infection. Harmine, a beta-carbon alkaloid with an indole core structure and a pyridine ring, is widely distributed in plants. Earlier studies showed that harmine exhibited pharmacological activities such as antifungal, antimicrobial, antitumor, antiplasmodial and antioxidants. In the current study, we showed that harmine was a potent inhibitor of HSV-2 infection in vitro assays with EC50 value at around 1.47μM and CC50 value at around 337.10μM. The HSV RNA transcription, protein synthesis, and virus titers were reduced by the presence of harmine in a dose dependent manner. Further study on the mechanism of the anti-HSV activity showed that harmine blocked HSV-induced ROS production and the upregulated cytokine/chemokine expression, but our evidence showed that the inhibition of viral replication was unlikely mediated by the blocking of ROS production. We demonstrated that harmine significantly reduced HSV-2-induced NF-κB activation, as well as IκB-α degradation and p65 nuclear translocation. We found that harmine also inhibited HSV-2-mediated p38 kinase and c-Jun N-terminal kinases (JNK) phosphorylation.

Chen, D., Su, A., Fu, Y., Wang, X., Lv, X., Xu, W., … & Wu, Z. (2015). Harmine blocks herpes simplex virus infection through downregulating cellular NF-κB and MAPK pathways induced by oxidative stress. Antiviral research, 123, 27-38. 10.1016/j.antiviral.2015.09.003
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Darwin’s Pharmacy: Sex, Plants, and the Evolution of the Noösphere (In Vivo)

/ Uncategorized /

Darwin's pharmacyDarwin’s Pharmacy: Sex, Plants, and the Evolution of the Noösphere (In Vivo) door Richard M. Doyle, University of Washington Press, 2011.

In zijn boek ‘Darwin’s Pharmacy: Sex, Plants, and the Evolution of the Noösphere (In Vivo)’ draait Richard Doyle, professor Engels aan de Penn State University, een ingewikkelde stelling in elkaar die een aantal van onze wetenschappelijke vooronderstellingen, zoals intentionaliteit, evolutie en taal, uitdaagt. Zorgvuldig analyseert hij de invloed die psychedelica kunnen hebben op de waarneming, en suggereert hij zodoende een bijna Copernicaanse revolutie. Als we bepalen dat de spirituele piekervaringen die door planten en paddenstoelen worden teweeggebracht functioneren als “spraakbevorderaars”, en we in ruil daarvoor deze “brengers van schoonheid” helpen zich voort te planten, hoe kunnen we dan zeggen welke intelligentie de andere beïnvloedt?

Schrijvend over trip reports, sjamanisme en cannabispornografie probeert Doyle een taal die vinden die, net als de psychedelische ervaring, de subject/object-dichotomie overstijgt. Het is zijn doel om onze normale manier van denken af te breken, zodat we een nieuw perspectief kunnen vormen. Een perspectief waarin bewustzijn steeds al ingebed is in een ecologische context, wat betekent dat alles wat we ervaren afhankelijk is van ‘set en setting.’ Doyle lijkt de nagel op de kop te tikken als hij deze psychoactieve stoffen omdoopt tot ‘ecodelica’ omdat deze planten en stoffen ons helpen onze interconnectie met het ecosysteem van onze te planeet gewaar te worden.

Het resultaat is een rijk en stimulerend boek waarin vorm en inhoud onlosmakelijk verbonden zijn, en de grenzen tussen feiten en interpretaties vervagen. De samenloop van zijn ontelbare ideeën kan alleen in zijn geheel worden begrepen, waarmee het risico gelopen wordt dat een aantal van zijn kerninzichten over het hoofd zullen worden gezien. Maar voor de filosofisch aangelegde lezer met een open geest is het een goed geschreven boek dat veel aannames in vraag stelt, en alleen al om die reden is het de moeite waard om te lezen.

Koop dit boek via bookdepository.com en ondersteun Stichting OPEN

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Boekrecensie: Darwin’s Pharmacy: Sex, Plants, and the Evolution of the Noösphere (In Vivo)

/ Uncategorized /

Darwin's pharmacyDarwin’s Pharmacy: Sex, Plants, and the Evolution of the Noösphere (In Vivo) door Richard M. Doyle, University of Washington Press, 2011.

In zijn boek ‘Darwin’s Pharmacy: Sex, Plants, and the Evolution of the Noösphere (In Vivo)’ draait Richard Doyle, professor Engels aan de Penn State University, een ingewikkelde stelling in elkaar die een aantal van onze wetenschappelijke vooronderstellingen, zoals intentionaliteit, evolutie en taal, uitdaagt. Zorgvuldig analyseert hij de invloed die psychedelica kunnen hebben op de waarneming, en suggereert hij zodoende een bijna Copernicaanse revolutie. Als we bepalen dat de spirituele piekervaringen die door planten en paddenstoelen worden teweeggebracht functioneren als “spraakbevorderaars”, en we in ruil daarvoor deze “brengers van schoonheid” helpen zich voort te planten, hoe kunnen we dan zeggen welke intelligentie de andere beïnvloedt?

Schrijvend over trip reports, sjamanisme en cannabispornografie probeert Doyle een taal die vinden die, net als de psychedelische ervaring, de subject/object-dichotomie overstijgt. Het is zijn doel om onze normale manier van denken af te breken, zodat we een nieuw perspectief kunnen vormen. Een perspectief waarin bewustzijn steeds al ingebed is in een ecologische context, wat betekent dat alles wat we ervaren afhankelijk is van ‘set en setting.’ Doyle lijkt de nagel op de kop te tikken als hij deze psychoactieve stoffen omdoopt tot ‘ecodelica’ omdat deze planten en stoffen ons helpen onze interconnectie met het ecosysteem van onze te planeet gewaar te worden.

Het resultaat is een rijk en stimulerend boek waarin vorm en inhoud onlosmakelijk verbonden zijn, en de grenzen tussen feiten en interpretaties vervagen. De samenloop van zijn ontelbare ideeën kan alleen in zijn geheel worden begrepen, waarmee het risico gelopen wordt dat een aantal van zijn kerninzichten over het hoofd zullen worden gezien. Maar voor de filosofisch aangelegde lezer met een open geest is het een goed geschreven boek dat veel aannames in vraag stelt, en alleen al om die reden is het de moeite waard om te lezen.

Koop dit boek via bookdepository.com en ondersteun Stichting OPEN

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Ketamine for depression: the highs and lows

/ Depressive Disorders, Ketamine, Papers, Psychology, Publications / /

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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