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Lezing: Psilocybin in the treatment of end-of-life anxiety

/ Mushrooms / Psilocybin /

flashback-psychedelic-research-returns

Dr. Charles Grob komt speciaal uit Los Angeles om een lezing te geven over zijn onderzoek naar psilocybine, het actieve bestandsdeel in ‘paddo’s’. De lezing zal zich vooral focussen op zijn onderzoek naar de veiligheid en effectiviteit van psilocybine als therapeutisch hulpmiddel binnen de behandeling van angst bij patiënten met vergevorderde kanker. Daarnaast zal er ook aandacht worden besteed aan zijn eerdere onderzoeken met middelen als MDMA en ayahuasca. Er zal ruim tijd zijn voor vragen en discussie. Studenten, therapeuten, wetenschappers, en gezondheidszorgmedewerkers worden aangemoedigd om te komen.

Dr. Charles Grob is hoogleraar Psychiatrie & Biogedragswetenschappen aan de UCLA, Los Angeles (VS). Hij heeft veel gepubliceerd over onderwerpen als drugsmisbruik en de geschiedenis van hallucinogenen in de psychiatrie. Hij leidde onder andere de eerste door de FDA goedgekeurde studie naar de fysiologische en psychologische effecten van MDMA; een multinationale studie naar het gebruik van ayahuasca in Brazilië en een pilotstudie naar de veiligheid en effectiviteit van psilocybine bij de behandeling van angst in patiënten met vergevorderde kanker.

De lezing (in het Engels) vindt plaats op vrijdag 14 juni 2013, van 16:00 tot 18:00 uur.

LOCATIE: CREA (Muziekzaal), Nieuwe Achtergracht 170 Amsterdam.

KOSTEN: €5,- algemeen / studenten en alumni gratis

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A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity

/ DMT, Papers, Psychiatry & Medicine, Publications / / , , , ,

Abstract

N,N-dimethyltryptamine (DMT) is classified as a naturally occurring serotonergic hallucinogen of plant origin. It has also been found in animal tissues and regarded as an endogenous trace amine transmitter. The vast majority of research on DMT has targeted its psychotropic/psychedelic properties with less focus on its effects beyond the nervous system. The recent discovery that DMT is an endogenous ligand of the sigma-1 receptor may shed light on yet undiscovered physiological mechanisms of DMT activity and reveal some of its putative biological functions. A three-step active uptake process of DMT from peripheral sources to neurons underscores a presumed physiological significance of this endogenous hallucinogen. In this paper, we overview the literature on the effects of sigma-1 receptor ligands on cellular bioenergetics, the role of serotonin, and serotoninergic analogues in immunoregulation and the data regarding gene expression of the DMT synthesizing enzyme indolethylamine-N-methyltransferase in carcinogenesis. We conclude that the function of DMT may extend central nervous activity and involve a more universal role in cellular protective mechanisms. Suggestions are offered for future directions of indole alkaloid research in the general medical field. We provide converging evidence that while DMT is a substance which produces powerful psychedelic experiences, it is better understood not as a hallucinogenic drug of abuse, but rather an agent of significant adaptive mechanisms that can also serve as a promising tool in the development of future medical therapies.

Frecska, E., Szabo, A., Winkelman, M. J., Luna, L. E., & McKenna, D. J. (2013). A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity. Journal of Neural Transmission, 120(9), 1295-1303. http://dx.doi.org/10.1007/s00702-013-1024-y
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NMDA Receptor Antagonists for Treatment of Depression

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

Abstract

Depression is a psychiatric disorder that affects millions of people worldwide. Individuals battling this disorder commonly experience high rates of relapse, persistent residual symptoms, functional impairment, and diminished well-being. Medications have important utility in stabilizing moods and daily functions of many individuals. However, only one third of patients had considerable improvement with a standard antidepressant after 2 months and all patients had to deal with numerous side effects. The N-methyl-d-aspartate (NMDA) receptor family has received special attention because of its critical role in psychiatric disorders. Direct targeting of the NMDA receptor could result in more rapid antidepressant effects. Antidepressant-like effects of NMDA receptor antagonists have been demonstrated in different animal models. MK-801 (a use-dependent channel blocker), and CGP 37849 (an NMDA receptor antagonist) have shown antidepressant properties in preclinical studies, either alone or combined with traditional antidepressants. A recent development is use of ketamine clinically for refractory depression. The purpose of this review is to examine and analyze current literature on the role of NMDA receptor antagonists for treatment of depression and whether this is a feasible route in drug discovery.

Ates-Alagoz, Z., & Adejare, A. (2013). NMDA Receptor Antagonists for Treatment of Depression. Pharmaceuticals, 6(4), 480-499. http://dx.doi.org/10.3390/ph6040480
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The Ketamine Analogue Methoxetamine and 3- and 4-Methoxy Analogues of Phencyclidine Are High Affinity and Selective Ligands for the Glutamate NMDA Receptor

/ Ketamine, Neuroscience, Papers, Publications / / , , , , , ,

Abstract

In this paper we determined the pharmacological profiles of novel ketamine and phencyclidine analogues currently used as ‘designer drugs’ and compared them to the parent substances via the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. The ketamine analogues methoxetamine ((RS)–2-(ethylamino)-2-(3-methoxyphenyl)cyclohexanone) and 3-MeO-PCE (N-ethyl-1-(3-methoxyphenyl)cyclohexanamine) and the 3- and 4-methoxy analogues of phencyclidine, (1-[1-(3-methoxyphenyl)cyclohexyl]piperidine and 1-[1-(4-methoxyphenyl)cyclohexyl]piperidine), were all high affinity ligands for the PCP-site on the glutamate NMDA receptor. In addition methoxetamine and PCP and its analogues displayed appreciable affinities for the serotonin transporter, whilst the PCP analogues exhibited high affinities for sigma receptors. Antagonism of the NMDA receptor is thought to be the key pharmacological feature underlying the actions of dissociative anaesthetics. The novel ketamine and PCP analogues had significant affinities for the NMDA receptor in radioligand binding assays, which may explain their psychotomimetic effects in human users. Additional actions on other targets could be important for delineating side-effects.

Roth, B. L., Gibbons, S., Arunotayanun, W., Huang, X. P., Setola, V., Treble, R., & Iversen, L. (2013). The ketamine analogue methoxetamine and 3-and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor. PLoS One, 8(3), e59334. http://dx.doi.org/10.1371%2Fjournal.pone.0059334
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Hallucinogen persisting perception disorder: what do we know after 50 years?

/ DMT, Ketamine, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Salvia / Salvinorin A / / ,

Abstract

‘Flashbacks’ following use of hallucinogenic drugs have been reported for decades; they are recognized in DSM-IV as ‘Hallucinogen Persisting Perception Disorder (Flashbacks)’, or HPPD. We located and analyzed 20 quantitative studies between 1955 and 2001 examining this phenomenon. However, many of these studies were performed before operational criteria for HPPD were published in DSM-III-R, so they are difficult to interpret in the light of current diagnostic criteria. Overall, current knowledge of HPPD remains very limited. In particular (1) the term ‘flashbacks’ is defined in so many ways that it is essentially valueless; (2) most studies provide too little information to judge how many cases could meet DSM-IV criteria for HPPD; and consequently (3) information about risk factors for HPPD, possible etiologic mechanisms, and potential treatment modalities must be interpreted with great caution. At present, HPPD appears to be a genuine but uncommon disorder, sometimes persisting for months or years after hallucinogen use and causing substantial morbidity. It is reported most commonly after illicit LSD use, but less commonly with LSD administered in research or treatment settings, or with use of other types of hallucinogens. There are case reports, but no randomized controlled trials, of successful treatment with neuroleptics, anticonvulsants, benzodiazepines, and clonidine. Although it may be difficult to collect large samples of HPPD cases, further studies are critically needed to augment the meager data presently available regarding the prevalence, etiology, and treatment of HPPD.

Halpern, J. H., & Harrison, G. P. Jr. (2003). Hallucinogen persisting perception disorder: what do we know after 50 years? Drug and Alcohol Dependence, 69(2), 109-119. http://dx.doi.org/10.1016/S0376-8716(02)00306-X
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Studying the Effects of Classic Hallucinogens in the Treatment of Alcoholism: Rationale, Methodology, and Current Research with Psilocybin

/ LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / /

Abstract

Recent developments in the study of classic hallucinogens, combined with a re-appraisal of the older literature, have led to a renewal of interest in possible therapeutic applications for these drugs, notably their application in the treatment of addictions. This article will first provide a brief review of the research literature providing direct and indirect support for the possible therapeutic effects of classic hallucinogens such as psilocybin and lysergic acid diethylamide (LSD) in the treatment of addictions. Having provided a rationale for clinical investigation in this area, we discuss design issues in clinical trials using classic hallucinogens, some of which are unique to this class of drug. We then discuss the current status of this field of research and design considerations in future randomized trials.

Bogenschutz, M. P. (2013). Studying the Effects of Classic Hallucinogens in the Treatment of Alcoholism: Rationale, Methodology, and Current Research with Psilocybin. Current Drug Abuse Reviews, 6(1), 17-29.
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Ibogaine in the Treatment of Substance Dependence

/ Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / /

Abstract

Ibogaine is a psychoactive alkaloid derived from Tabernanthe iboga, a plant used in initiatory rituals in West Central Africa. Largely because of ibogaine’s status as a Schedule I substance in the U.S., the development of ibogaine’s use in the treatment of drug addiction took place outside conventional clinical and medical settings. This article reviews the history of ibogaine’s use in the treatment of drug addiction, and discusses progress made towards, and obstacles blocking, the establishment of controlled clinical trials of ibogaine’s efficacy. Preclinical research has generally supported anecdotal claims that ibogaine attenuates withdrawal symptoms and reduces drug cravings. Concerns about ibogaine’s safety, as well as a dearth of solid data from human studies, have hampered progress in its development as an approved medication. This article outlines major findings from preclinical studies, discusses concerns about ibogaine’s safety, and details previous and ongoing research on ibogaine’s use as an anti-addictive treatment for humans.

Brown, T. K. (2013). Ibogaine in the Treatment of Substance Dependence. Current Drug Abuse Reviews, 6(1), 3-16.
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Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada

/ Ayahuasca, Papers, Psychology, Publications, Substance Use Disorder / / , , , ,

Abstract

Introduction: This paper reports results from a preliminary observational study of ayahuasca-assisted treatment for problematic substance use and stress delivered in a rural First Nations community in British Columbia, Canada.

Methods: The “Working with Addiction and Stress” retreats combined four days of group counselling with two expert-led ayahuasca ceremonies. This study collected pre-treatment and six months follow-up data from 12 participants on several psychological and behavioral factors related to problematic substance use, and qualitative data assessing the personal experiences of the participants six months after the retreat.

Findings: Statistically significant (p < 0.05) improvements were demonstrated for scales assessing hopefulness, empowerment, mindfulness, and quality of life meaning and outlook subscales. Self-reported alcohol, tobacco and cocaine use declined, although cannabis and opiate use did not; reported reductions in problematic cocaine use were statistically significant. All study participants reported positive and lasting changes from participating in the retreats.

Conclusions: This form of ayahuasca-assisted therapy appears to be associated with statistically significant improvements in several factors related to problematic substance use among a rural aboriginal population. These findings suggest participants may have experienced positive psychological and behavioral changes in response to this therapeutic approach, and that more rigorous research of ayahuasca-assisted therapy for problematic substance use is warranted.

Thomas, G., Lucas, P., Capler, N.R., Tupper, K. W., & Martin, G. (2013). Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada. Current Drug Abuse Reviews, 6(1), 30-42.
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Salvia divinorum: A Psychopharmacological Riddle and a Mind-Body Prospect

/ Biology & Ethnobotany, Papers, Pharmacology & Chemistry, Psychology, Publications, Salvia / Salvinorin A / /

Abstract

The multidisciplinary research on Salvia divinorum and its chemical principles is analyzed concerning whether the ethnobotany, phytochemistry, mental effects, and neuropharmacology of this sacred psychoactive plant and main principle clarify its experienced effects and divinatory uses. The scientific pursuit spans from the traditional practices, continues with the botanical identification, isolation of active molecules, characterization of mental and neural effects, possible therapeutic applications, and impinges upon the mind-body problem. The departure point is ethnopharmacology and therefore the traditional beliefs, ritual uses, and mental effects of this Mazatec sacred mint recorded during a 1973-1983 field research project are described. A water potion of crushed leaves produced short-lasting light-headedness, dysphoria, tactile and proprioceptive sensations, a sense of depersonalization, amplified sound perception, and an increase visual and auditory imagery, but not actual hallucinations. Similar effects were described using questionnaires and are attributable to salvinorin A, but cannot be explained solely by its specific and potent brain kappa-opioid receptor agonist activity. Some requirements for a feasible classification and mechanism of action of consciousness-altering products are proposed and include the activation of neural networks comprising several neurochemical systems. Top-down analyses should be undertaken in order to characterize such neural networks and eventually allowing to explore the differential ethnic effects. As is the case for other consciousness-altering preparations, a careful and encompassing research on this plant and principle can be consequential to endeavors ranging from the mind-body problem, a better understanding of shamanic ecstasy, to the potential generation of analgesic, antidepressant, and drug-abuse attenuating products.

Diaz, J-L (2013) Salvia divinorum: A Psychopharmacological Riddle and a Mind-Body Prospect. Current Drug Abuse Reviews, 6(1), 43-53.
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Can MDMA Play a Role in the Treatment of Substance Abuse?

/ MDMA, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / / , ,

Abstract

A wider array of treatments are needed for people with substance abuse disorders. Some psychedelic compounds have been assessed as potential substance abuse treatments with promising results. MDMA may also help treat substance abuse based on shared features with psychedelic compounds and recent reports indicating that MDMA-assisted psychotherapy can reduce symptoms of PTSD. Narrative reports and data from early investigations found that some people reduced or eliminated their substance use after receiving MDMA, especially in a therapeutic setting. MDMA is a potent monoamine releaser with sympathomimetic effects that may indirectly activate 5-HT2A receptors. It increases interpersonal closeness and prosocial feelings, potentially through oxytocin release. Findings suggest that ecstasy, material represented as containing MDMA, is associated with deleterious long-term effects after heavy lifetime use, including fewer serotonin transporter sites and impaired verbal memory. Animal and human studies demonstrate moderate abuse liability for MDMA, and this effect may be of most concern to those treating substance abuse disorders. However, subjects who received MDMA-assisted psychotherapy in two recent clinical studies were not motivated to seek out ecstasy, and tested negative in random drug tests during follow-up in one study. MDMA could either directly treat neuropharmacological abnormalities associated with addiction, or it could indirectly assist with the therapeutic process or reduce symptoms of comorbid psychiatric conditions, providing a greater opportunity to address problematic substance use. Studies directly testing MDMA-assisted psychotherapy in people with active substance abuse disorder may be warranted.

Jerome, L, Schuster, S., & Yazar-Klosinski, B. B. (2013) Can MDMA Play a Role in the Treatment of Substance Abuse? Current Drug Abuse Reviews, 6(1), 54-62.
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Peer Perspectives: How Psychedelics Induce Neuroplasticity - February 26

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