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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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Psilocybin, psychological distress, and suicidality

/ Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / / , ,

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

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

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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Psychedelics and Acceptance and Commitment Therapy (ACT): A Process-Based Approach - September 15th

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