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OPEN Foundation

Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV)

Abstract

This paper describes a refinement of Dittrich’s Altered States of Consciousness questionnaire. This questionnaire is among the most widely used self-report questionnaires for retrospectively assessing subjective experiences induced by psychedelics and other psychoactive drugs. Using data collected over many years from 591 human volunteers, they factored the original four subscales developed by Dittrich into 11 new subscales. This new improved instrument will play an important role in more precisely defining the qualitative subjective experiences in research with psychedelics.

Background: The OAV questionnaire has been developed to integrate research on altered states of consciousness (ASC). It measures three primary and one secondary dimensions of ASC that are hypothesized to be invariant across ASC induction methods. The OAV rating scale has been in use for more than 20 years and applied internationally in a broad range of research fields, yet its factorial structure has never been tested by structural equation modeling techniques and its psychometric properties have never been examined in large samples of experimentally induced ASC.

Methodology/Principal Findings: The present study conducted a psychometric evaluation of the OAV in a sample of psilocybin (n = 327), ketamine (n = 162), and MDMA (n = 102) induced ASC that was obtained by pooling data from 43 experimental studies. The factorial structure was examined by confirmatory factor analysis, exploratory structural equation modeling, hierarchical item clustering (ICLUST), and multiple indicators multiple causes (MIMIC) modeling. The originally proposed model did not fit the data well even if zero-constraints on non-target factor loadings and residual correlations were relaxed. Furthermore, ICLUST suggested that the ‘‘oceanic boundlessness’’ and ‘‘visionary restructuralization’’ factors could be combined on a high level of the construct hierarchy. However, because these factors were multidimensional, we extracted and examined 11 new lower order factors. MIMIC modeling indicated that these factors were highly measurement invariant across drugs, settings, questionnaire versions, and sexes. The new factors were also demonstrated to have improved homogeneities, satisfactory reliabilities, discriminant and convergent validities, and to differentiate well among the three drug groups.

Conclusions/Significance: The original scales of the OAV were shown to be multidimensional constructs. Eleven new lower order scales were constructed and demonstrated to have desirable psychometric properties. The new lower order scales are most likely better suited to assess drug induced ASC.

Studerus, E., Gamma, A., & Vollenweider, F. X. (2010). Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV). PLoS ONE, 5(8). http://dx.doi.org/10.1371/journal.pone.0012412
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A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression

Abstract

Context: Existing therapies for bipolar depression have a considerable lag of onset of action. Pharmacological strategies that produce rapid antidepressant effects—for instance, within a few hours or days—would have an enormous impact on patient care and public health.

Objective: To determine whether an N-methyl-Daspartate–receptor antagonist produces rapid antidepressant effects in subjects with bipolar depression.

Design: A randomized, placebo-controlled, doubleblind, crossover, add-on study conducted from October 2006 to June 2009.

Setting: Mood Disorders Research Unit at the National Institute of Mental Health, Bethesda, Maryland.

Patients: Eighteen subjects with DSM-IV bipolar depression (treatment-resistant).

Interventions: Subjects maintained at therapeutic levels of lithium or valproate received an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days 2 weeks apart. The Montgomery- Asberg Depression Rating Scale was used to rate subjects at baseline and at 40, 80, 110, and 230 minutes and on days 1, 2, 3, 7, 10, and 14 postinfusion.

Results: Within 40 minutes, depressive symptoms significantly improved in subjects receiving ketamine compared with placebo (d=0.52, 95% confidence interval [CI], 0.28-0.76); this improvement remained significant through day 3. The drug difference effect size was largest at day 2 (d=0.80, 95% CI, 0.55-1.04). Seventy-one percent of subjects responded to ketamine and 6% responded to placebo at some point during the trial. One subject receiving ketamine and 1 receiving placebo developed manic symptoms. Ketamine was generally well tolerated; the most common adverse effect was dissociative symptoms, only at the 40-minute point.

Diazgranados, N.,  Ibrahim, L. Brutsche, N. E., Newberg, A., Kronstein, P.,  Khalife, S., … Zarate Jr., Z. A. (2010). A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression. Archives of General Psychiatry, 67(8). http://dx.doi.org/10.1001/archgenpsychiatry.2010.90
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Shamanism: A Biopsychosocial Paradigm of Consciousness and Healing

ShamanismWhat does the brain do during “soul journeys”? How do shamans alter consciousness and why is this important for healing? Are shamans different from other kinds of healers? Is there a connection between the rituals performed by chimpanzees and traditional shamanistic practices? All of these questions-and many more-are answered in Shamanism, Second Edition: A Biopsychosocial Paradigm of Consciousness and Healing. This text contains crosscultural examinations of the nature of shamanism, biological perspectives on alterations of consciousness, mechanisms of shamanistic healing, as well as the evolutionary origins of shamanism. It presents the shamanic paradigm within a biopsychosocial framework for explaining successful human evolution through group rituals. In the final chapter,”the author compares shamanistic rituals with chimpanzee displays to identify homologies that point to the ritual dynamics of our ancient hominid ancestors.

Shamanism: A Biopsychosocial Paradigm of Consciousness and Healing, door Michael J. Winkelman, Praeger, 309 pagina’s.

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The Pharmacology of LSD: A critical review

PharmacologyLSDLSD has a controversial and extraordinary reputation, due to the special effects it can induce on human consciousness. Its experimental use lead to some groundbreaking discoveries about the brain and the deeper layers of the human psyche. After its application in neuroscience, and as a tool within psychotherapy, it was increasingly used by laymen for producing euphoria and religious experiences. Today, there is a resurgence of interest in LSD, including its possible uses in psychotherapy and for the treatment of some headache disorders. This book represents the first ever comprehensive review of the psychological and pharmacological effects of LSD. It draws on data from more than 3000 experimental and clinical studies. The Pharmacology of LSD provides a unique and valuable resource for anyone interested in better understanding this controversial hallucinogenic drug – including brain scientists, psychopharmacologists, addiction researchers, and psychiatrists.

The Pharmacology of LSD: A critical review, door Annelie Hintzen & Torsten Passie, Oxford University Press, 150 pagina’s.

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Eerste MDMA/PTSS trial afgerond

Uit de eerste afgeronde klinische trial op het gebied van de behandeling van PTSS (posttraumatische stressstoornis) met MDMA is gebleken dat MDMA bij patiënten voor een verlichting van hun klachten kan zorgen: meer dan 80 procent van de deelnemers voldeden na de behandeling niet meer aan de voorwaarden voor PTSS zoals deze in de DSM-IV (het meest recente ‘handboek’ voor mentale stoornissen) zijn vermeld.

Het onderzoek richtte zich op twee psychotherapie-sessies van acht uur met een tussenperiode van drie tot vijf weken. Een deel van de proefpersonen kreeg MDMA, de rest kreeg een placebo. Ook ondergingen alle deelnemers wekelijks ‘normale’ psychotherapie. Tien van de twaalf mensen die MDMA kregen, reageerden positief op de behandeling.

Na twee maanden kregen de mensen uit de controlegroep de mogelijkheid om alsnog deel te nemen aan de behandeling, waarin ze nu wel MDMA zouden krijgen. Zeven van de acht mensen uit de controlegroep kozen hiervoor, met positieve resultaten. Het lijkt er dus op dat er een doorbraak is geweest in het onderzoek naar psychotherapie met behulp van MDMA, waardoor er ruimte is voor nieuwe onderzoeken – dat is goed nieuws!

First MDMA/PTSD trial finished

The first finished clinical trial regarding PTSD (post-traumatic stress disorder) and the treatment of that disorder with MDMA has indicated that MDMA can relieve PTSD symptoms: over 80 percent of the participants no longer met the requirements for PTSD as they are defined in DSM-IV (the most recent ‘handbook’ for mental disorders).

The study focused on two therapy sessions of eight hours with a period of three to five weeks in between. Some of the participants were given MDMA, the others were given a placebo. All participants also took part in weekly ‘normal’ psychotherapy sessions. Ten out of the twelve people that were given MDMA reacted positively on the treatment.

After two months, the people from the control group were given the opportunity to take part in the real treatment, where they would be given MDMA this time. Seven out of eight people from the control group chose to do this, with positive results. It seems as if there has been a breakthrough in researching psychotherapy with the aid of MDMA, making room for new studies – which is good news!

The safety and efficacy of ±3,4-methylenedioxymethamphetamineassisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder

Abstract

Case reports indicate that psychiatrists administered 3,4-methylenedioxymethamphetamine (MDMA) as a catalyst to psychotherapy before recreational use of MDMA as ‘Ecstasy’ resulted in its criminalization in 1985. Over two decades later, this study is the first completed clinical trial evaluating MDMA as a therapeutic adjunct. Twenty patients with chronic posttraumatic stress disorder, refractory to both psychotherapy and psychopharmacology, were randomly assigned to psychotherapy with concomitant active drug (n¼12) or inactive placebo (n¼8) administered during two 8-h experimental psychotherapy sessions. Both groups received preparatory and follow-up non-drug psychotherapy. The primary outcome measure was the Clinician- Administered PTSD Scale, administered at baseline, 4 days after each experimental session, and 2 months after the second session. Neurocognitive testing, blood pressure, and temperature monitoring were performed. After 2-month follow-up, placebo subjects were offered the option to re-enroll in the experimental procedure with open-label MDMA. Decrease in Clinician-Administered PTSD Scale scores from baseline was significantly greater for the group that received MDMA than for the placebo group at all three time points after baseline. The rate of clinical response was 10/12 (83%) in the active treatment group versus 2/8 (25%) in the placebo group. There were no drug-related serious adverse events, adverse neurocognitive effects or clinically significant blood pressure increases. MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory to other treatments.

Mithoefer, M. C., Wagner, M. T., Mithoefer, A. T., Jerome, L., & Doblin, R. (2010). The safety and efficacy of ±3,4-methylenedioxymethamphetamineassisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Journal of Psychopharmacology, 25(4), 439-452. http://dx.doi.org/10.1177/0269881110378371
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Rediscovering MDMA (ecstasy): the role of the American chemist Alexander T. Shulgin

Abstract

Aims: Alexander T. Shulgin is widely thought of as the ‘father’ of +/-3,4-methylenedioxymethamphetamine (MDMA). This paper re-assesses his role in the modern history of this drug.

Methods: We analysed systematically Shulgin’s original publications on MDMA, his publications on the history of MDMA and his laboratory notebook.

Results: According to Shulgin’s book PIHKAL (1991), he synthesized MDMA in 1965, but did not try it. In the 1960s Shulgin also synthesized MDMA-related compounds such as 3,4-methylenedioxyamphetamine (MDA), 3-methoxy- 4,5-methylenedioxyamphetamine (MMDA) and 3,4-methylenedioxyethylamphetamine (MDE), but this had no impact on his rediscovery of MDMA. In the mid-1970s Shulgin learned of a ‘special effect’ caused by MDMA, whereupon he re-synthesized it and tried it himself in September 1976, as confirmed by his laboratory notebook. In 1977 he gave MDMA to Leo Zeff PhD, who used it as an adjunct to psychotherapy and introduced it to other psychotherapists.

Conclusion: Shulgin was not the first to synthesize MDMA, but he played an important role in its history. It seems plausible that he was so impressed by its effects that he introduced it to psychotherapist Zeff in 1977. This, and the fact that in 1978 he published with David Nichols the first paper on the pharmacological action of MDMA in humans, explains why Shulgin is sometimes (erroneously) called the ‘father’ of MDMA.

Benzenhöfer, U., & Passie, T. (2010). Rediscovering MDMA (ecstasy): the role of the American chemist Alexander T. Shulgin. Addiction, 105(8), 1355–1361. http://dx.doi.org/10.1111/j.1360-0443.2010.02948.x
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qNMR: An applicable method for the determination of dimethyltryptamine in ayahuasca, a psychoactive plant preparation

Abstract

Ayahuasca is an Amazonian plant beverage obtained by infusing the pounded stems of Banisteriopsis caapi in combination with the leaves of Psychotria viridis. P. viridis contains the psychedelic indole N,N-dimethyltryptamine (DMT). This association has a wide range of use in religious rituals around the world. In the present work, an easy, fast and non-destructive method by Nuclear Magnetic Resonance of proton (1H NMR) for quantification of DMT in ayahuasca samples was developed and validated. 2,5-Dimethoxybenzaldehyde (DMBO) was used as internal standard (IS). For this purpose, the area ratios produced by protons of DMT (N(CH3)2) at 2.70 ppm, singlet, (6H) and for DMBO (Ar(OCH3)2) at 3.80 and 3.89 ppm, doublet, (6H) were used for quantification. The lower limit of quantification (LLOQ) was 12.5 μg/mL and a good intra-assay precision was also obtained (relative standard deviation < 5.1%). The present 1H NMR method is not time consuming and can be readily applied to monitor this tryptamine in plant preparations. We believe that qNMR can be used for identification and quantification of many plant-based products and metabolites with important advantages, while comparing with other analytical techniques.

Moura, S., Carvalhoa, F. G., Rodrigues de Oliveiraa, C. D., Pintoa, E., & Yonaminea, M. (2010). qNMR: An applicable method for the determination of dimethyltryptamine in ayahuasca, a psychoactive plant preparation. Phytochemistry, 3(2), 79–83. http://dx.doi.org/10.1016/j.phytol.2009.12.004
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Composition, Standardization and Chemical Profiling of Banisteriopsis caapi, a Plant for the Treatment of Neurodegenerative Disorders Relevant to Parkinson’s Disease

Abstract

Ethnopharmacological relevance

Banisteriopsis caapi, a woody vine from the Amazonian basin, is popularly known as an ingredient of a sacred drink ayahuasca, widely used throughout the Amazon as a medicinal tea for healing and spiritual exploration. The usefulness of Banisteriopsis caapi has been established for alleviating symptoms of neurological disorders including Parkinson’s disease.

Aim of the study

Primary objective of this study was to develop the process for preparing standardized extracts of Banisteriopsis caapi to achieve high potency for inhibition of human monoamine oxidases (MAO) and antioxidant properties. The aqueous extracts prepared from different parts of the plant collected from different geographical locations and seasons were analyzed by HPLC for principal bioactive markers. The extracts were simultaneously tested in vitro for inhibition of human MAOs and antioxidant activity for analysis of correlation between phytochemical composition of the extracts and bioactivities.

Materials and methods

Reversed-phase HPLC with photodiode array detection was employed to profile the alkaloidal and non-alkaloidal components of the aqueous extract of Banisteriopsis caapi. The Banisteriopsis caapi extracts and standardized compositions were tested in vitro for inhibition of recombinant preparations of human MAO-A and MAO-B. In vitro cell-based assays were employed for evaluation of antioxidant property and mammalian cell cytotoxicity of these preparations.

Results

Among the different aerial parts, leaves, stems/large branches and stem bark of Banisteriopsis caapi, 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. A library of HPLC chromatograms has also been generated as a tool for fingerprinting and authentication of the studied Banisteriopsis caapi species. The correlation between potency of MAO inhibition and antioxidant activity with the content of the main active constituents of the aqueous Banisteriopsis caapi extracts and standardized compositions was established. Phytochemical analysis of regular/commercial Banisteriopsis caapi dried stems, obtained from different sources, showed a similar qualitative HPLC profile, but relatively low content of dominant markers 1, 2, 7, and 9, which led to decreased MAO inhibitory and antioxidant potency compared to Banisteriopsis caapi Da Vine.

Conclusion

The ethnopharmacological use of bark of matured stem/large branch of Banisteriopsis caapi as well as whole matured stem is supported by the results obtained in this investigation. Among various constituents of Banisteriopsis caapi, harmine (7), harmaline (6) and tetrahydroharmine (5) are responsible for MAO-A inhibition, while two major proanthocyanidines, epicatechin (8) and procyanidine B2 (9) produce antioxidant effects. The compounds 1–9 can serve as reliable markers for identification and standardization of Banisteriopsis caapi aerial parts, collected in different seasons and/or from different geographical regions.

Wang, Y. H., Samoylenko, V., Tekwani, B. L., Khan, I. A., Miller, L. S., Chaurasiya, N. D., … & Muhammad, I. (2010). Composition, standardization and chemical profiling of Banisteriopsis caapi, a plant for the treatment of neurodegenerative disorders relevant to Parkinson’s disease. Journal of ethnopharmacology, 128(3), 662-671. http://dx.doi.org/10.1016/j.jep.2010.02.013
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