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(Hoe) werken psychedelica?

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From psychology to pharmacology and back: in this lecture, we discuss both subjectively and ’objectively’ what it means to be tripping. Two prominent scientists offer an overview of the actual research regarding psychedelics, clinical health care trials and neural mechanisms.

Are psychedelics of any use? And what are the risks? What are the possibilities? What do we know about the effects of psychedelics on the brain? To what degree can techniques such as fMRI, PET and neuroimaging contribute to psychedelic research? And what does this tell us about research regarding our consciousness? These and other interesting questions will be discussed in our series of lectures “(How) do psychedelics work?”

(This lecture is in Dutch)

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The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: An open, non-randomized case series

/ Headache Pain and Neurological Disorders, LSD, Neuroscience, Papers, Pharmacology & Chemistry, Psychiatry & Medicine, Publications / / , , ,

Introduction

Cluster headache (CH) is a stereotyped primary headache characterized by strictly unilateral severe orbital or periorbital pain and categorized as either episodic or chronic (1,2). Its prevalence is 0.1% (3). Oxygen and sumatriptan are the treatments of choice for individual attacks, whereas verapamil, lithium, corticosteroids and other neuromodulators can suppress attacks during cluster periods (1). All standard medication treatments may be ineffective. Surgical treatment may be an option for medication non-responders, including deep brain (4) or occipital nerve stimulation (5). However, serious complications from brain surgery, including death, can occur (6).

An Internet survey of 53 CH patients reported on claims that psilocybin is better at aborting acute attacks than either oxygen or sumatriptan and that LSD and psilocybin are both better at triggering and extending remission than standard drugs (7). However, due to hallucinogenicity and the absence of established medical indication, these drugs are criminalized and placed within the most restrictive Schedule I of the Controlled Substances Act, which sanctions only limited research use. Although the hallucinogenic properties of LSD and psilocybin are undesirable from both regulatory and patient safety perspectives, it was unclear to us at the outset whether a non-hallucinogenic analog could also provide meaningful relief to CH patients. To address the question of whether the CH relief associated with these two structurally diverse compounds is related to the mechanisms triggering intoxication, we decided to investigate the efficacy of a non-hallucinogenic analog of LSD. LSD’s hallucinogenic effects are completely lost when the double bond in the D ring is saturated and with substitution at R2 (e.g. by bromination in 2-bromo-LSD) (BOL-148) (8). BOL-148 has been studied in volunteers (up to 20 mg per os) (9) and in patients suffering from vascular headaches but not, apparently, in patients with CH (9,10). These past studies [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”][…]

Karst, M., Halpern, J. H., Bernateck, M., & Passie, T. (2010). The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: An open, non-randomized case series. Cephalalgia, 30(9), 1140-1144. https://dx.doi.org/10.1177/0333102410363490
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The persistence of the subjective in neuropsychopharmacology: observations of contemporary hallucinogen research

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

Abstract

The elimination of subjectivity through brain research and the replacement of so-called ‘folk psychology’ by a neuroscientifically enlightened worldview and self-conception has been both hoped for and feared. But this cultural revolution is still pending. Based on nine months of fieldwork on the revival of hallucinogen research since the ‘Decade of the Brain,’ this paper examines how subjective experience appears as epistemic object and practical problem in a psychopharmacological laboratory. In the quest for neural correlates of (drug-induced altered states of) consciousness, introspective accounts of test subjects play a crucial role in neuroimaging studies. Firsthand knowledge of the drugs’ flamboyant effects provides researchers with a personal knowledge not communicated in scientific publications, but key to the conduct of their experiments. In many cases, the ‘psychedelic experience’ draws scientists into the field and continues to inspire their self-image and way of life. By exploring these domains the paper points to a persistence of the subjective in contemporary neuropsychopharmacology.

Langlitz, N. (2010). The persistence of the subjective in neuropsychopharmacology: observations of contemporary hallucinogen research. History of Human Sciences, 23(1), 37-57. http://dx.doi.org/10.1177/0952695109352413
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Psychedelics and the Human Receptorome

/ DMT, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry, Publications / /

Abstract

We currently understand the mental effects of psychedelics to be caused by agonism or partial agonism of 5-HT2A (and possibly 5-HT2C) receptors, and we understand that psychedelic drugs, especially phenylalkylamines, are fairly selective for these two receptors. This manuscript is a reference work on the receptor affinity pharmacology of psychedelic drugs. New data is presented on the affinity of twenty-five psychedelic drugs at fifty-one receptors, transporters, and ion channels, assayed by the National Institute of Mental Health – Psychoactive Drug Screening Program (NIMH-PDSP). In addition, comparable data gathered from the literature on ten additional drugs is also presented (mostly assayed by the NIMH-PDSP). A new method is introduced for normalizing affinity (Ki) data that factors out potency so that the multi-receptor affinity profiles of different drugs can be directly compared and contrasted. The method is then used to compare the thirty-five drugs in graphical and tabular form. It is shown that psychedelic drugs, especially phenylalkylamines, are not as selective as generally believed, interacting with forty-two of forty-nine broadly assayed sites. The thirty-five drugs of the study have very diverse patterns of interaction with different classes of receptors, emphasizing eighteen different receptors. This diversity of receptor interaction may underlie the qualitative diversity of these drugs. It should be possible to use this diverse set of drugs as probes into the roles played by the various receptor systems in the human mind.

Ray, T. S. (2010). Psychedelics and the Human Receptorome. PLoS ONE, 5(2). http://dx.doi.org/10.1371/journal.pone.0009019
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Cannabis and Ecstasy/MDMA: Empirical Measures of Creativity in Recreational Users

/ MDMA, Papers, Psychology, Publications / / , ,

Abstract

This study investigated the associations between chronic cannabis and Ecstasy/MDMA use and one objective and two subjective measure of creativity. Fifteen abstinent Ecstasy users, 15 abstinent cannabis users, and 15 nondnig-user controls, completed three measures of creativity: the Consequences behavioral test of creativity, self-assessed performance on the Consequences test, and Gough’s Trait Self-Report Creative Adjective Checklist. The Consequences test involved five scenarios where possible consequences had to be devised; scoring was conducted by the standard blind rating (by two independent judges) for “remoteness” and “rarity,” and by a frequency and rarity of responses method. Cannabis users had significantly more “rare-creative” responses than controls (Tukey, p < 0.05); this effect remained significant with gender as a covariate. There were no significant differences between the groups on the number of standard scoring “remote-creative” ideas or for fluency of responses. On self-rated creativity, there was a significant ANOVA group difference (p < 0.05), with Ecstasy users tending to rate their answers as more creative than controls (Tukey comparison; p = 0.058, two-tailed). Ecstasy users did not differ from controls on the behavioral measures of creativity, although there was a borderline trend for self-assessment of greater creativity. Cannabis users produced significantly more “rare-creative” responses, but did not rate themselves as more creative.

Jones, K. A., Blagrove, M., & Parrott, A. C. Cannabis and Ecstasy/MDMA: Empirical Measures of Creativity in Recreational Users. Journal of Psychoactive Drugs, 41(4), 323-329. http://dx.doi.org/10.1080/02791072.2009.10399769
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Experiences of Encounters with Ayahuasca – “the Vine of the Soul”

/ Ayahuasca, Papers, Psychology, Publications / / , ,

Abstract

Ayahuasca is a psychoactive brew used by the indigenous populations of the Amazon. The aim of this qualitative study was to gain insight into the experiences of western users of ayahuasca, as well as to ascertain the experienced meaning that participants felt by their participation. Twenty-five people from Northern Europe with experiences of group sessions with ayahuasca wrote anonymous descriptions of their experiences. The Empirical Phenomenological Psychological method was used for this analysis. The analysis resulted in 33 c^egories which weie assembled into six getieral themes: (a) motivation and aim, (h) contractile frightening state (c) sudden transformation of the experience, (d) limitless expansive states with transcendental experiences, (f) reflections, and (g) changed woridview and new orientation to life. These themes provided a new structure, called the transcendental circle. Participants reponed many positive psychological and physical improvements that indicate that ayahuasca could be of potential interest in the development of new medicines and therapies.

Kjellgren, A., Eriksson, A., & Norlander, T. (2009). Experiences of Encounters with Ayahuasca – ‘the Vine of the Soul. Joumal of Psychoactive Drugs, 41(4), 309-315. http://dx.doi.org/10.1080/02791072.2009.10399767
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Ayahuasca–From Dangerous Drug to National Heritage: An Interview with Antonio A. Arantes

/ Anthropology & Sociology, Ayahuasca, Papers, Publications / / ,

Abstract

This interview with Antonio A. Arantes, Brazilian anthropology professor and recognized specialist on the topics of intellectual property and traditional knowledge, addresses the 2008 request by Brazilian ayahuasca groups to be recognized as part of the immaterial cultural heritage of Brazil. In the first portion of the interview, Arantes reflects on the challenges of the new conceptions of the Brazilian national immaterial policy program. He discusses several examples of cultural goods recognized by the Brazilian state, such as the candomblé and the samba, and analyzes the controversial issues involving authenticity and tradition in these and other similar cases. In the second portion, Arantes reflects on the specific case of ayahuasca, the relationship of this cultural heritage request to legal issues, the challenges to define exactly what aspects should be recognized, and speculates on the chances that these religious groups will come to be recognized as a national symbol of Brazil.

Labate, B. C., & Goldstein, I. (2009). Ayahuasca–From Dangerous Drug to National Heritage: An Interview with Antonio A. Arantes. International Journal of Transpersonal Studies, 28, 53-64.
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LSD: The highway to mental health

/ Publications /

HighwaytomentalhealthThe book describes the work of Dr. Milan Hausner at his clinic at Sadska, near Prague, where as Medical Director of the psychiatric clinic he supervised over 3,000 LSD therapeutic sessions from 1954 to 1980. As Grof says on a back cover blurb, “He has amassed information that is invaluable for the theory and practice of psychotherapy.”

Hausner attributes emotional disorders to the patients’ lack of understanding of hidden thought processes which occur from a combination of disfunctional social learning processes and faulty parenting. His method of bringing these thought processes to consciousness is a system he calls Pathogenic Confrontation Model within a system of Multigroup Community Therapy. In order to reset patients’ irrational attachments to faulty ideas and emotions, psychotherapy confronts patients’ own past illness-producing experiences and replaces their dysfunctional reactions during the more congenial atmosphere of the therapeutic relationship between patient and therapist.

After 10 chapters of theory and description of Hausner’s model, Highway presents 11 chapters of case histories and back-matter enrichments. Enriched with excerpts from transcripts of sessions, these chapters focus on depression, schizophrenia, double bind, archetypes, sexuality, and other presenting problems.

As well as filling in the gap about treatment that continued in Czechoslovakia,  LSD: The Highway to Mental Health presents its psycholytic methods of treating inpatients, a way to use group processes, and social learning as adjuncts on the way to mental health. As in addition to a place in university, medical school, and city libraries, Highway deserves a place in the library of anyone doing LSD-based therapy or investigating it, on the shelves of psychedelic book collectors, and of historians of the 60s and of the history of psychotherapy.

LSD: The Highway to Mental Health, door Milan Hausner, vertaald door Erna Segal, ASC Books, 300 pagina’s, ascbooks.com.

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LSD but not lisuride disrupts prepulse inhibition in rats by activating the 5-HT2A receptor

/ LSD, Papers, Publications / / ,

Abstract

Rationale: Compounds that activate the 5-HT2A receptor, such as lysergic acid diethylamide (LSD), act as hallucinogens in humans. One notable exception is the LSD congener lisuride, which does not have hallucinogenic effects in humans even though it is a potent 5-HT2A agonist. LSD and other hallucinogens have been shown to disrupt prepulse inhibition (PPI), an operational measure of sensorimotor gating, by activating 5-HT2A receptors in rats.

Objective: We tested whether lisuride disrupts PPI in male Sprague–Dawley rats. Experiments were also conducted to identify the mechanism(s) responsible for the effect of lisuride on PPI and to compare the effects of lisuride to those of LSD.

Results: Confirming a previous report, LSD (0.05, 0.1, and 0.2 mg/kg, s.c.) reduced PPI, and the effect of LSD was blocked by pretreatment with the selective 5-HT2A antagonist MDL 11,939. Administration of lisuride (0.0375, 0.075, and 0.15 mg/kg, s.c.) also reduced PPI. However, the PPI disruption induced by lisuride (0.075 mg/kg) was not blocked by pretreatment with MDL 11,939 or the selective 5-HT1A antagonist WAY-100635 but was prevented by pretreatment with the selective dopamine D2/D3 receptor antagonist raclopride (0.1 mg/kg, s.c).

Conclusions: The effect of LSD on PPI is mediated by the 5-HT2A receptor, whereas activation of the 5-HT2A receptor does not appear to contribute to the effect of lisuride on PPI. These findings demonstrate that lisuride and LSD disrupt PPI via distinct receptor mechanisms and provide additional support for the classification of lisuride as a non-hallucinogenic 5-HT2A agonist.

Halberstadt, A. L, & Geyer, M. A. (2010). LSD but not lisuride disrupts prepulse inhibition in rats by activating the 5-HT2A receptor. Psychopharmacology, 208(2), 179–189. http://dx.doi.org/10.1007/s00213-009-1718-x
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Banisteriopsis caapi, a unique combination of MAO inhibitory and antioxidative constituents for the activities relevant to neurodegenerative disorders and Parkinson's disease

/ Ayahuasca, Biology & Ethnobotany, Papers, Psychiatry & Medicine, Publications / / , , , , , ,

Abstract

Aim of the study: Parkinson’s disease is a neurological disorder mostly effecting the elder population of the world. Currently there is no definitive treatment or cure for this disease. Therefore, in this study the composition and constituents of the aqueous extract of B. caapi for monoamine oxidases (MAO) inhibitory and antioxidant activities were assessed, which are relevant to the prevention of neurological disorders, including Parkinsonism.

Materials and methods: The aqueous extract of B. caapi stems was standardized and then fractionated using reversed-phase (RP) chromatography. Pure compounds were isolated either by reversed-phase (RP) chromatography or centrifugal preparative TLC, using a Chromatotron®. Structure elucidation was carried out by 1D and 2D NMR, Mass, IR and Circular Dichroism spectroscopy and chemical derivatization. Chemical profiling of the extract was carried out with RP-HPLC. The inhibitory activity of MAO-A, MAO-B, acetylcholinesterase, butyrylcholinesterase and catechol-O-methyl transferase enzymes, as well as antioxidant and cytotoxic activities of both B. caapi extract and isolated compounds were evaluated.

Results: An examination of the aqueous extracts of B. caapi cultivar Da Vine yielded two new alkaloidal glycosides, named banistenoside A (1) and banistenoside B (2), containing “azepino[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”][1,2-a]tetrahydro-β-carboline” unique carbon framework. One additional new natural tetrahydronorharmine (4), four known β-carbolines harmol (3), tetrahydroharmine (5), harmaline (6) and harmine (7), two known proanthocyanidines (−)-epicatechin (8) and (−)-procyanidin B2 (9), and a new disaccharide β-D-fructofuranosyl-(2→5)-fructopyranose (14) together with known sacharose (15) and β-D-glucose (16) were also isolated. In addition, the acetates of 1, 2, 8, 9, 14 and 15 (compounds 10–13, 17, 18) were also prepared. Harmaline (6) and harmine (7) showed potent in vitro inhibitory activity against recombinant human brain monoamine oxidase (MAO) -A and -B enzymes (IC50 2.5 and 2.0 nM, and 25 and 20 µM, respectively), and (−)-epicatechin (8) and (−)-procyanidin B2 (9) showed potent antioxidant and moderate MAO-B inhibitory activities (IC50 <0.13 and 0.57 µg/mL, and 65 and 35 µM). HPLC analysis revealed that most of the dominant chemical and bioactive markers (1, 2, 5, 7–9) were present in high concentrations in dried bark of large branch. Analysis of regular/commercial B. caapi dried stems showed a similar qualitative HPLC pattern, but relatively low content of dominant markers 1, 2, 7, and 9, which led to decreased MAO inhibitory and antioxidant potency.

Conclusion: Collectively, these results give additional basis to the existing claim of B. caapi stem extract for the treatment of Parkinsonism, including other neurodegenerative disorders.

Samoylenko, V., Rahman, M. M., Tekwani, B. L., Tripathi, L. M., Wang, Y. H., Khan, S. I., … & Muhammad, I. (2010). Banisteriopsis caapi, a unique combination of MAO inhibitory and antioxidative constituents for the activities relevant to neurodegenerative disorders and Parkinson’s disease. Journal of ethnopharmacology, 127(2), 357-367. http://dx.doi.org/10.1016%2Fj.jep.2009.10.030

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