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Psychiatry & Medicine

IJTS Special Topic Section: Ketamine ● Regarding the Transpersonal Nature of Ketamine Therapy: An Approach to the Work

January 1, 2014 / Ketamine, Papers, Psychiatry & Medicine, Psychology, Publications / By /

Abstract

Recent evidence has shown that ketamine treatment can facilitate psychological insight and symptom resolution in various psychiatric disorders. To aid this process, psychotherapeutic support should be considered a fundamental aspect of treatment. The psychedelic experience produced by ketamine can be a deeply meaningful source of enduring change and personal growth. The author has repeatedly observed a rapid realignment of self-perception away from shame, fear, and dread toward authentic self-acceptance and gratitude, offering patients opportunity for insight and the consideration of new potentialities. The experience produced by ketamine is similar in quality to transpersonal experiences described by Jung and induced by various religious practices and near-death experiences. As such, therapists working with these patients may wish to understand and incorporate the concepts of the Psychic Life Cycle, Restitution of the ego-Self Axis, and the Encounter with the Self described within Jungian and Transpersonal Psychology. The author discusses broad themes and practical therapeutic considerations regarding the transpersonal themes identified while overseeing this treatment process. Case studies are provided for illustration.

Becker, J. (2014). Regarding the Transpersonal Nature of Ketamine Therapy: An Approach to the Work. International Journal of Transpersonal Studies, 33(2).
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IJTS Special Topic Section: Ketamine ● Making Ketamine Work in the Long Run

January 1, 2014 / Depressive Disorders, Humanities & Art, Ketamine, Papers, Psychiatry & Medicine, Psychology, Publications / By /

Abstract

Treatments such as ketamine psychotherapy face substantial financial and regulatory obstacles to dissemination into widespread use. Newly patented medications are able to generate enough capital to pay for studies required for FDA approval, personnel to apply for coverage on insurance plans, and marketing to establish a successful launch. Ketamine is an older drug with considerable evidence of efficacy for treatment resistant depression, and almost 50 years of data concerning safety as an anesthetic agent. However, it can no longer be patented, so there is no incentive for pharmaceutical companies to help get it into widespread use. In this paper we discuss some of the complex issues surrounding use of ketamine in the outpatient setting and share information and practice pearls that have been gathered through communication with other practitioners and through direct experience with over 1000 treatments involving 120 patients in the last eight years. The safety and appropriateness of intramuscular ketamine treatment in the outpatient psychiatric office is discussed. We hope to help proponents of effective mental health interventions navigate the actual and potential challenges involved in safe application of this treatment option outside of hospital-based programs.

Early, T. S. (2014). Making Ketamine Work in the Long Run. International Journal of Transpersonal Studies, 33(2).
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IJTS Special Topic Section: Ketamine ● Ketamine Psychedelic Psychotherapy: Focus on its Pharmacology, Phenomenology, and Clinical Applications

January 1, 2014 / Ketamine, Papers, Psychiatry & Medicine, Psychology, Publications / By / , , , , , ,

Abstract

Meant to be an authoritative guide for psychiatrists and others interested in understanding and applying ketamine psychedelic psychotherapy (KPP), this paper focuses on its pharmacology, phenomenology, and clinical applications. Ketamine is a dissociative anesthetic widely used by physicians and veterinarians in the United States. In addition to its anesthetic and dissociative properties, ketamine also has a multitude of other psychological and pharmacological properties, which include analgesic, sedative, neuroprotective, anxiolytic, antidepressant, stimulant, euphoriant, and hallucinogenic effects. The literature on the clinical application of KPP is comprehensively reviewed, practical advice for using KPP is given, and the pharmacology and phenomenology of ketamine-induced psychedelic experiences are explored, including in relationship to transpersonal healing and possible iatrogenic consequences of misuse of KPP.

Kolp, E., Krupitsky, E., Sylvester, M., Kolp, A., Friedman, H. L., Jansen, K., & Young, M. S. (2014). Ketamine Psychedelic Psychotherapy: Focus on its Pharmacology, Phenomenology, and Clinical Applications. International Journal of Transpersonal Studies, 33(2).
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IJTS Special Topic Section: Ketamine ● Ketamine for Depression: A Mixed-Methods Study

January 1, 2014 / Depressive Disorders, Ketamine, Papers, Psychiatry & Medicine, Psychology, Publications / By /

Abstract

Prior studies have reported variously on the presence or absence of dissociative effects at subanesthtetic doses of ketamine administered for treatment-resistant depression. This mixedmethods study emulated the protocol used for the studies in question, with IV administration of 0.5mg/kg over 40 minutes with eight experienced ketamine users. Quantitative measures were generally insignificant since this was not a population reporting depression; blood pressure increased as expected by 20-30mm systolic and 6-20mm diastolic, falling rapidly by 20 minutes after completion of the infusion. Individual qualitative reports reports of relaxation, pleasant sensation, decreased cognitive function, and some disabling of ordinary capacities. As experienced users, subjects commented freely on what was characterized as the triviality of the experience, and typically expressed skepticism that ketamine could have antidepressant properties when administered at this dose or in this manner, as well as disbelief that it could be beneficial except perhaps as a period of relaxation, or as a partial break from ordinary states of mind in naïve subjects. Group discussion produced a consensus recommendation in favor of threshold- and higher-dosage transformative work beginning with a 40-50mg IM bolus, potentially in a series of sessions with higher dosages if indicated, with the number of sessions to be determined by clinical practice; such work should occur in a closely monitored psychotherapeutic setting.

Wolfson, P. E. (2014). Ketamine for Depression: A Mixed-Methods Study. International Journal of Transpersonal Studies, 33(2).
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IJTS Special Topic Section: Ketamine ● Ketamine and Depression: A Review

January 1, 2014 / Depressive Disorders, Ketamine, Papers, Psychiatry & Medicine, Psychology, Publications / By / , ,

Abstract

Ketamine, via intravenous infusions, has emerged as a novel therapy for treatment-resistant depression, given rapid onset and demonstrable efficacy in both unipolar and bipolar depression. Duration of benefit, on the order of days, varies between these subtypes, but appears longer in unipolar depression. A unique property is reduction in suicidality although data are more limited. Strategies to extend duration, via multiple doses, maintenance treatment, or subsequent augmenting medications have yielded mixed results. There is a relative paucity of data regarding alternate methods of administration such as intramuscular, intranasal, and oral routes, though preliminary results are promising. Adverse effects most reliably include dissociative and sympathomimetic effects, both transient and mild, and suggest good tolerability. Ketamine’s unique effects may represent an opportunity for a paradigm shift in the pharmacologic treatment of depression.

Ryan, W. C., Marta, C. J., & Koek, R. J. (2014). Ketamine and depression: A review. International Journal of Transpersonal Studies, 33(2), 40-74.
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Ayahuasca and cancer treatment

October 21, 2013 / Anthropology & Sociology, Ayahuasca, Biology & Ethnobotany, Papers, Psychiatry & Medicine, Publications / By /

Abstract

Objectives
Comprehensively review the evidence regarding the use of ayahuasca, an Amerindian medicine traditionally used to treat many different illnesses and diseases, to treat some types of cancer.

Methods
An in-depth review of the literature was conducted using PubMed, books, institutional magazines, conferences and online texts in nonprofessional sources regarding the biomedical knowledge about ayahuasca in general with a specific focus in its possible relations to the treatment of cancer.

Results
At least nine case reports regarding the use of ayahuasca in the treatment of prostate, brain, ovarian, uterine, stomach, breast, and colon cancers were found. Several of these were considered improvements, one case was considered worse, and one case was rated as difficult to evaluate. A theoretical model is presented which explains these effects at the cellular, molecular, and psychosocial levels. Particular attention is given to ayahuasca’s pharmacological effects through the activity of N,N-dimethyltryptamine at intracellular sigma-1 receptors. The effects of other components of ayahuasca, such as harmine, tetrahydroharmine, and harmaline, are also considered.

Conclusion
The proposed model, based on the molecular and cellular biology of ayahuasca’s known active components and the available clinical reports, suggests that these accounts may have consistent biological underpinnings. Further study of ayahuasca’s possible antitumor effects is important because cancer patients continue to seek out this traditional medicine. Consequently, based on the social and anthropological observations of the use of this brew, suggestions are provided for further research into the safety and efficacy of ayahuasca as a possible medicinal aid in the treatment of cancer.

Schenberg, E. E. (2013). Ayahuasca and cancer treatment. SAGE Open Medicine, 1, 1-12. http://dx.doi.org/10.1177/2050312113508389
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A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity

April 26, 2013 / DMT, Papers, Psychiatry & Medicine, Publications / By / , , , ,

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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β-Carboline Compounds, Including Harmine, Inhibit DYRK1A and Tau Phosphorylation at Multiple Alzheimer's Disease-Related Sites

May 6, 2011 / Ayahuasca, Papers, Psychiatry & Medicine, Publications / By / , , , , , ,

Abstract

Harmine, a β-carboline alkaloid, is a high affinity inhibitor of the dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) protein. The DYRK1A gene is located within the Down Syndrome Critical Region (DSCR) on chromosome 21. We and others have implicated DYRK1A in the phosphorylation of tau protein on multiple sites associated with tau pathology in Down Syndrome and in Alzheimer’s disease (AD). Pharmacological inhibition of this kinase may provide an opportunity to intervene therapeutically to alter the onset or progression of tau pathology in AD. Here we test the ability of harmine, and numerous additional β-carboline compounds, to inhibit the DYRK1A dependent phosphorylation of tau protein on serine 396, serine 262/serine 356 (12E8 epitope), and threonine 231 in cell culture assays and in vitro phosphorylation assays. Results demonstrate that the β-carboline compounds (1) potently reduce the expression of all three phosphorylated forms of tau protein, and (2) inhibit the DYRK1A catalyzed direct phosphorylation of tau protein on serine 396. By assaying several β-carboline compounds, we define certain chemical groups that modulate the affinity of this class of compounds for inhibition of tau phosphorylation.

Frost, D., Meechoovet, B., Wang, T., Gately, S., Giorgetti, M., Shcherbakova, I., & Dunckley, T. (2011). β-carboline compounds, including harmine, inhibit DYRK1A and tau phosphorylation at multiple Alzheimer’s disease-related sites. PLoS One, 6(5). https://dx.doi.org/10.1371/journal.pone.0019264

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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

April 21, 2010 / Ayahuasca, Biology & Ethnobotany, Papers, Pharmacology & Chemistry, Psychiatry & Medicine, Publications / By / , , , , , ,

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

March 26, 2010 / Headache Pain and Neurological Disorders, LSD, Neuroscience, Papers, Pharmacology & Chemistry, Psychiatry & Medicine, Publications / By / , , ,

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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