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Medicine

Therapeutic infusions of ketamine: Do the psychoactive effects matter?

February 18, 2014 / Addiction, Consciousness, Ketamine, Medicine, Neuroscience, Other disciplines, Other subjects, Papers, Personal development, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , , , , ,

Abstract

Background

Sub-anesthetic ketamine infusions may benefit a variety of psychiatric disorders, including addiction. Though ketamine engenders transient alterations in consciousness, it is not known whether these alterations influence efficacy. This analysis evaluates the mystical-type effects of ketamine, which may have therapeutic potential according to prior research, and assesses whether these effects mediate improvements in dependence-related deficits, 24 h postinfusion.

Methods

Eight cocaine dependent individuals completed this double-blind, randomized, inpatient study. Three counter-balanced infusions separated by 48 h were received: lorazepam (2 mg) and two doses of ketamine (0.41 mg/kg and 0.71 mg/kg, with the former dose always preceding the latter). Infusions were followed within 15 min by measures of dissociation (Clinician Administered Dissociative Symptoms Scale: CADSS) and mystical-type effects (adapted from Hood’s Mysticism Scale: HMS). At baseline and 24 h postinfusion, participants underwent assessments of motivation to stop cocaine (University of Rhode Island Change Assessment) and cue-induced craving (by visual analogue scale for cocaine craving during cue exposure).

Results

Ketamine led to significantly greater acute mystical-type effects (by HMS) relative to the active control lorazepam; ketamine 0.71 mg/kg was associated with significantly higher HMS scores than was the 0.41 mg/kg dose. HMS score, but not CADSS score, was found to mediate the effect of ketamine on motivation to quit cocaine 24 h postinfusion.

Conclusions

These findings suggest that psychological mechanisms may be involved in some of the anti-addiction benefits resulting from ketamine. Future research can evaluate whether the psychoactive effects of ketamine influence improvements in larger samples.

Dakwar, E., Anerella, C., Hart, C. L., Levin, F. R., Mathew, S. J., & Nunes, E. V. (2014). Therapeutic infusions of ketamine: Do the psychoactive effects matter?. Drug and alcohol dependence, 136, 153-157. http://dx.doi.org/10.1016/j.drugalcdep.2013.12.019

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Do the dissociative side effects of ketamine mediate its antidepressant effects?

February 18, 2014 / Depression, Ketamine, Medicine, Neuroscience, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , , , , , , ,

Abstract

Background

The N-methyl-d-aspartate receptor antagonist ketamine has rapid antidepressant effects in major depression. Psychotomimetic symptoms, dissociation and hemodynamic changes are known side effects of ketamine, but it is unclear if these side effects relate to its antidepressant efficacy.

Methods

Data from 108 treatment-resistant inpatients meeting criteria for major depressive disorder and bipolar disorder who received a single subanesthetic ketamine infusion were analyzed. Pearson correlations were performed to examine potential associations between rapid changes in dissociation and psychotomimesis with the Clinician-Administered Dissociative States Scale (CADSS) and Brief Psychiatric Rating Scale (BPRS), respectively, manic symptoms with Young Mania Rating Scale (YMRS), and vital sign changes, with percent change in the 17-item Hamilton Depression Rating scale (HDRS) at 40 and 230 min and Days 1 and 7.

Results

Pearson correlations showed significant association between increased CADSS score at 40 min and percent improvement with ketamine in HDRS at 230 min (r=−0.35, p=0.007) and Day 7 (r=−0.41, p=0.01). Changes in YMRS or BPRS Positive Symptom score at 40 min were not significantly correlated with percent HDRS improvement at any time point with ketamine. Changes in systolic blood pressure, diastolic blood pressure, and pulse were also not significantly related to HDRS change.

Limitations

Secondary data analysis, combined diagnostic groups, potential unblinding.

Conclusions

Among the examined mediators of ketamine׳s antidepressant response, only dissociative side effects predicted a more robust and sustained antidepressant. Prospective, mechanistic investigations are critically needed to understand why intra-infusion dissociation correlates with a more robust antidepressant efficacy of ketamine.

Luckenbaugh, D. A., Niciu, M. J., Ionescu, D. F., Nolan, N. M., Richards, E. M., Brutsche, N. E., … & Zarate, C. A. (2014). Do the dissociative side effects of ketamine mediate its antidepressant effects?. Journal of affective disorders, 159, 56-61. http://dx.doi.org/10.1016/j.jad.2014.02.017

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IJTS Special Topic Section: Ketamine ● Ketamine (IM) Assisted Psychotherapy (KAP): A Model for Informed Consent

January 1, 2014 / Ketamine, Medicine, Other subjects, Papers, Psychiatry, Psychopharmacology, Publications, Safety / By /

Abstract

Informed consent is important for every medical intervention, and the unique nature of ketamine assisted psychotherapy (KAP) calls for a particularly thoughtful and detailed informed consent document. The following is an informed consent form developed for the author’s use in his own private practice. No representations are made concerning its adequacy or appropriateness for use by other practitioners, or in any other contexts; author, editors, and publisher disclaim liability for any use of or reliance on this document. However, as a document created by a psychiatrist with experience in KAP, this form may serve to illustrate the range of issues that an informed consent document might address.

Wolfson, P. E. (2015). Ketamine (IM) Assisted Psychotherapy (KAP): A Model for Informed Consent. International Journal of Transpersonal Studies.
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IJTS Special Topic Section: Ketamine ● Psychedelic Experiential Pharmacology: Pioneering Clinical Explorations with Salvador Roquet

January 1, 2014 / Addiction, History, LSD, MDMA, Medicine, Other disciplines, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By /

Abstract

Richard Yensen was a research fellow at the Maryland Psychiatric Research Center from 1972 to 1976. He studied psychedelic psychotherapy with Stanislav Grof, M.D. and other senior staff. During this time he treated patients with substance abuse disorders, cancer, neurosis, and other health professionals seeking a training experience. Dr. Yensen did his Ph.D. dissertation on the use of MDA in psychotherapy with neurotic outpatients and conducted his research at the MPRC. Through many years of experience in governmentsanctioned psychedelic research, he has evolved a non-drug shamanistic psychotherapy called Perceptual Affective Therapy. In the 1990’s Richard was co-holder of IND 3250, an investigational new drug permit issued by the U.S. Food and Drug Administration to study LSD and psychotherapy until 2006. He is currently a licensed psychologist in California and director of the Orenda Institute in Vancouver and Cortes Island, British Columbia, Canada and president of the Salvador Roquet Psychosynthesis Association. He has served on the faculties of Harvard Medical School, Johns Hopkins University and the University of Maryland Medical School in Baltimore.

Wolfson, P. E. (2015). Psychedelic Experiential Pharmacology: Pioneering Clinical Explorations with Salvador Roquet. International Journal of Transpersonal Studies.
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IJTS Special Topic Section: Ketamine ● Regarding the Transpersonal Nature of Ketamine Therapy: An Approach to the Work

January 1, 2014 / Ketamine, Medicine, Mystical experiences, Other disciplines, Papers, Personal development, Personality, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications, Religious studies / 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 / Depression, History, Ketamine, Medicine, Other disciplines, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, 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, Medicine, Other subjects, Papers, Phenomenology, Psychiatry, Psychology, Psychopharmacology, 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 / Depression, Ketamine, Medicine, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, 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 / Depression, Ketamine, Medicine, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, 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, Ayahuasca, Ethnobotany, Medicine, Other subjects, Papers, 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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7 May - Psychedelics, Nature & Mental Health with Sam Gandy

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