OPEN Foundation

Menu

Author name: OPEN Foundation

Rapid effectiveness of intravenous ketamine for ultraresistant depression in a clinical setting and evidence for baseline anhedonia and bipolarity as clinical predictors of effectiveness

/ Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications / / , , ,

Abstract

BACKGROUND:

Intravenous ketamine has been established as an efficacious and safe treatment, with transient effect, for treatment-resistant depression. However, the effectiveness of intravenous ketamine in non-research settings and with ultraresistant depression patients remains understudied.

AIMS:

This study aims to measure the response and remission rates in ultraresistant depression patients in a clinical setting by means of a retrospective, open label, database study. Secondarily, the study will attempt to support previous findings of clinical predictors of effectiveness with intravenous ketamine treatment.

METHODS:

Fifty patients with ultraresistant depression were treated between May 2015-December 2016, inclusive, in two community hospitals in Edmonton using six ketamine infusions of 0.5 mg/kg over 40 min over 2-3 weeks. Data were collected retrospectively from inpatient and outpatient charts. Statistical analysis to investigate clinical predictors of effectiveness included logistic regression analysis using a dependent variable of a 50% reduction in rating scale score at any point during treatment.

RESULTS:

At baseline, the average treatment resistance was severe, with a Maudsley Staging Method score of 12.1 out of 15, 90.0% were resistant to electroconvulsive therapy, and the average Beck Depression Inventory score was 34.2. The response rate was 44% and remission rate was 16%. As a single predictor, moderate or severe anhedonia at baseline predicted a 55% increased likelihood of response. As a combined predictor, this level of anhedonia at baseline with a diagnosis of bipolar depression predicted a 73% increase in likelihood of response.

CONCLUSION:

In a clinical setting, intravenous ketamine showed effectiveness in a complex, severely treatment-resistant, depressed population on multiple medication profiles concurrently. This study gave support to anhedonia and bipolar depression as clinical predictors of effectiveness.

Thomas, R. K., Baker, G., Lind, J., & Dursun, S. (2018). Rapid effectiveness of intravenous ketamine for ultraresistant depression in a clinical setting and evidence for baseline anhedonia and bipolarity as clinical predictors of effectiveness. Journal of psychopharmacology, 32(10), 1110-1117., 10.1177/0269881118793104
Link to full text

Rapid effectiveness of intravenous ketamine for ultraresistant depression in a clinical setting and evidence for baseline anhedonia and bipolarity as clinical predictors of effectiveness Read More »

A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus

/ Depressive Disorders, DMT, Neuroscience, Papers, Psychology, Publications / / , , ,

Abstract

The subgranular zone (SGZ) of dentate gyrus (DG) is one of the few regions in which neurogenesis is maintained throughout adulthood. It is believed that newborn neurons in this region encode temporal information about partially overlapping contextual memories. The 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring compound capable of inducing a powerful psychedelic state. Recently, it has been suggested that DMT analogs may be used in the treatment of mood disorders. Due to the strong link between altered neurogenesis and mood disorders, we tested whether 5-MeO-DMT is capable of increasing DG cell proliferation. We show that a single intracerebroventricular (ICV) injection of 5-MeO-DMT increases the number of Bromodeoxyuridine (BrdU+) cells in adult mice DG. Moreover, using a transgenic animal expressing tamoxifen-dependent Cre recombinase under doublecortin promoter, we found that 5 Meo-DMT treated mice had a higher number of newborn DG Granule cells (GC). We also showed that these DG GC have more complex dendritic morphology after 5-MeO-DMT. Lastly, newborn GC treated with 5-MeO-DMT, display shorter afterhyperpolarization (AHP) potentials and higher action potential (AP) threshold compared. Our findings show that 5-MeO-DMT affects neurogenesis and this effect may contribute to the known antidepressant properties of DMT-derived compounds.

Lima, R. V., Moulin, T., Lintzmaier, L. P., & Leão, R. N. (2018). A single dose of 5-MeO-DMT stimulates cell proliferation, neuronal survivability, morphological and functional changes in adult mice ventral dentate gyrus. Frontiers in molecular neuroscience, 11, 312., 10.3389/fnmol.2018.00312

Link to full text

A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus Read More »

d-Lysergic acid diethylamide, psilocybin, and other classic hallucinogens: Mechanism of action and potential therapeutic applications in mood disorders.

/ Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications / / , , , ,

Abstract

Depression and anxiety are psychiatric diagnoses commonly associated with low quality of life and low percentage of responsiveness by patients treated with currently available drugs. Thus, research into alternative compounds to treat these disorders is essential to guarantee a patient’s remission. The last decade has witnessed a revamped interest for the application of psychedelic medicine for the treatment of mental disorders due to anecdotal reports and clinical studies which show that low doses of d-lysergic acid diethylamide (LSD) and psilocybin may have antidepressant effects. LSD and psilocybin have demonstrated mood-modulating properties likely due to their capacity to modulate serotonergic (5-HT), dopaminergic (DA) and glutamatergic systems. LSD, belonging to the category of “classic halluginogens,” interacts with the 5-HT system through 5HT1A, and 5HT2A receptors, with the DA system through D2 receptors, and indirectly also the glutamatergic neurotransmission thought the recruitment of N-methyl-d-aspartate (NMDA) receptors. Randomized clinical studies have confirmed its antidepressant and anxiolytic effects in humans. Thus, in this chapter, we will review the pharmacology of psychedelic drugs, report the most striking clinical evidence which substantiate the therapeutic potentials of these fascinating compounds in mood disorders, and look into the horizon of where psychedelic medicine is heading.
De, D. G., Enns, J. P., Nuñez, N. A., Posa, L., & Gobbi, G. (2018). d-Lysergic acid diethylamide, psilocybin, and other classic hallucinogens: Mechanism of action and potential therapeutic applications in mood disorders. Progress in brain research, 242, 69-96., 10.1016/bs.pbr.2018.07.008
Link to full text

d-Lysergic acid diethylamide, psilocybin, and other classic hallucinogens: Mechanism of action and potential therapeutic applications in mood disorders. Read More »

LSD Administered as a Single Dose Reduces Alcohol Consumption in C57BL/6J Mice.

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

Abstract

There is a substantive clinical literature on classical hallucinogens, most commonly lysergic acid diethylamide (LSD) for the treatment of alcohol use disorder. However, there has been no published research on the effect of LSD on alcohol consumption in animals. This study evaluated the effect of LSD in mice using a two-bottle choice alcohol drinking paradigm. Adult male C57BL/6J mice were exposed to ethanol to develop preference and divided into three groups of equal ethanol consumption, and then treated with single intraperitoneal injection of saline or 25 or 50 μg/kg LSD and offered water and 20% ethanol. The respective LSD-treated groups were compared to the control group utilizing a multilevel model for repeated measures. In mice treated with 50 μg/kg LSD ethanol consumption was reduced relative to controls (p= 0.0035), as was ethanol preference (p = 0.0024), with a group mean reduction of ethanol consumption of 17.9% sustained over an interval of 46 days following LSD administration. No significant effects on ethanol consumption or preference were observed in mice treated with 25 μg/kg LSD. Neither total fluid intake nor locomotor activity in the LSD-treated groups differed significantly from controls. These results suggest that classical hallucinogens in the animal model merit further study as a potential approach to the identification of targets for drug discovery and investigation of the neurobiology of addiction.
Alper, K., Dong, B., Shah, R., Sershen, H., & Vinod, K. Y. (2018). LSD administered as a single dose reduces alcohol consumption in C57BL/6J mice. Frontiers in pharmacology, 9, 994., 10.3389/fphar.2018.00994
Link to full text

LSD Administered as a Single Dose Reduces Alcohol Consumption in C57BL/6J Mice. Read More »

Therapeutic Potential Ascribed to Ayahuasca by Users in the Czech Republic

/ Ayahuasca, Papers, Psychiatry & Medicine, Psychology, Publications, Substance Use Disorder / / , ,

ABSTRACT

This article focuses on the therapeutic potential ascribed to ayahuasca by users in the Czech Republic. Following an online survey, the fieldwork among users of ayahuasca was carried out from November 2015 to December 2016. The research sample consisted of 46 persons (23 women and 23 men), who took part at least once in some type of ayahuasca ritual and/or were the facilitators of the ayahuasca sessions. We held semi-structured interviews with participants in order to discover the therapeutic potential of ayahuasca. Transcribed recordings were analyzed using the Grounded Theory Method. The results suggest that the intensity of effects produced by ayahuasca is not directly proportional to its therapeutic effect. According to the informants, ayahuasca is applicable in the treatment of drug addiction. They consider it to have a broad spectrum of therapeutic potential. This therapeutic potential could be based on memory recall.
Horák, M., Hasíková, L., & Verter, N. (2018). Therapeutic Potential Ascribed to Ayahuasca by Users in the Czech Republic. Journal of psychoactive drugs, 50(5), 430-436., 10.1080/02791072.2018.1511878
Link to full text
 

Therapeutic Potential Ascribed to Ayahuasca by Users in the Czech Republic Read More »

The influence of therapists’ first-hand experience with psychedelics on psychedelic-assisted psychotherapy research and therapist training

/ MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / / ,

Abstract

Clinical research on psychedelic-assisted psychotherapy is rapidly advancing in the USA, with two drugs, psilocybin and MDMA, progressing through a structure of FDA-approved trials on a trajectory toward Drug Enforcement Agency rescheduling for therapeutic use. Researcher’s and clinician’s personal use of psychedelics was cited as a potential confound in psychedelic research studies conducted in the 1950s and 1960s, a concern which contributed to the cessation of this research for some 20 years. Currently, there is no empirical research on personal use of psychedelics by current academic researchers and clinicians; its influence is undocumented, unknown, and undertheorized. This paper explores the history of personal use of psychedelics by clinicians and researchers, the potential impact of personal use on psychedelic-assisted psychotherapy and research, and the rationale for opening an academic discussion and program of research to investigate the role of personal use. We propose that there are factors unique to psychedelic-assisted therapy such that training for it cannot neatly fit into the framework of modern psychopharmacology training, nor be fully analogous to psychotherapy training in contemporary psychological and psychiatric settings. We argue that scientific exploration of the influence of therapists’ first-hand experience of psychedelics on psychedelic-assisted therapy outcomes is feasible, timely, and necessary for the future of clinical research.
Nielson, E. M., & Guss, J. (2018). The influence of therapists’ first-hand experience with psychedelics on psychedelic-assisted psychotherapy research and therapist training. Journal of Psychedelic Studies, 1-10. 10.1556/2054.2018.009
Link to full text

The influence of therapists’ first-hand experience with psychedelics on psychedelic-assisted psychotherapy research and therapist training Read More »

Legitimate Medicine in the Age of Consumerism

/ Anthropology & Sociology, Papers, Psychiatry & Medicine, Psychology, Publications / /

Abstract

From the opioid epidemic and medical marijuana to abortion restrictions and physician-assisted suicide, disputes over the proper uses of medicine loom large in American life. Nowhere is this conflict more apparent than in federal drug control policy, which is premised on a clear distinction between legitimate “medical” uses and illicit “abuse.” Yet the Controlled Substances Act defines neither of these foundational concepts. While it is tempting to imagine medicine’s scope is limited to treating or preventing disease – rendering nontherapeutic drug use “abuse” – in fact medical practice has always included interventions that are not aimed at healing. This trend has only accelerated as medical practice has become increasingly consumer-oriented. From Adderall to Xanax, patients now routinely seek prescriptions not to treat diagnosable illnesses, but to relieve stress, improve productivity, and otherwise enhance quality of life.

As physicians increasingly prescribe psychoactive drugs to help healthy people obtain desirable mental states, distinguishing legitimate drug use from recreational abuse becomes ever more difficult. Having failed to acknowledge this challenge, the DEA, courts, and scholars have not offered a principled way to make this distinction, rendering drug control policy increasingly incoherent. As a result, doctors face criminal prosecution without clear standards governing prescribing, potentially valuable interventions are arbitrarily barred from the market, and millions seek the benefits of drugs without professional medical guidance to mitigate their risks.

Rather than being limited to therapeutic aims, medicine is better understood as the application of a loosely-defined set of knowledge and interventions that the law entrusts to specific professionals, with accompanying duties to use these tools to benefit patients. Medical practice includes treating and preventing illnesses, but can also include enhancing social and cognitive functioning and promoting the well-being of people whose challenges do not rise to the level of disorders. Discarding a narrow conception of medicine does not require abandoning the enforcement of drug laws or the policing of doctors. But acknowledging the expansiveness of medicine’s domain does argue for clarifying the scope of physicians’ criminal liability and pursuing new strategies for harnessing drugs’ benefits while mitigating their risks.

Lamkin, M. (2018). Legitimate Medicine in the Age of Consumerism., 10.2139/ssrn.3228692
Link to full text

Legitimate Medicine in the Age of Consumerism Read More »

Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews

/ Ayahuasca, Depressive Disorders, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / / , , ,

Abstract

Mood, anxiety, and substance-use disorders are among the most prevalent psychiatric disorders in the population. Although several pharmacological treatments are available, they are not effective for a significant proportion of patients and are associated with several adverse reactions. Therefore, new treatments should be explored. Recent studies suggest that serotonergic hallucinogens/psychedelics including ayahuasca, psilocybin, and lysergic acid diethylamide (LSD) have anxiolytic, antidepressive, and antiaddictive effects. Areas Covered: A systematic review of systematic reviews assessing the efficacy, safety, and tolerability of serotonergic hallucinogens/psychedelic was performed using the PubMed data base until 11 April 2018. Systematic reviews with or without meta-analysis were analyzed, but only reviews that described at least one randomized controlled trial (RCT) were included. Expert Commentary: Psilocybin and LSD reduced anxiety and depression in cancer patients and symptoms of alcohol and tobacco dependence, and ayahuasca reduced depression symptoms in treatment-resistant depression. Although the results are promising, several studies were open label, and only few were RCTs, and most had small sample sizes and a short duration. Single or few doses of these drugs seem to be well tolerated, but long-term studies are lacking. New RCTs with bigger samples and longer duration are needed to replicate these findings.

dos Santos, R. G., Bouso, J. C., Alcázar-Córcoles, M. Á., & Hallak, J. E. (2018). Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: A systematic review of systematic reviews. Expert review of clinical pharmacology, 11(9), 889-902., 10.1080/17512433.2018.1511424
Link to full text

Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews Read More »

Therapeutic use of classic psychedelics to treat cancer-related psychiatric distress

/ Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychiatry & Medicine, Psychology, Publications / /

Abstract

Cancer is highly prevalent and one of the leading causes of global morbidity and mortality. Psychological and existential suffering is common in cancer patients, associated with poor psychiatric and medical outcomes. Promising early-phase clinical research (1960s to early 1970s) suggested a therapeutic signal for serotoninergic psychedelics (e.g. psilocybin, LSD) in treating cancer-related psychiatric distress. After several decades of quiescence, research on psychedelic-assisted therapy to treat psychiatric disorders in cancer patients has resumed within the last 2 decades in the US and Europe. This review article is based on a systematic search of clinical trials from 1960–2018 researching the therapeutic use of psychedelic treatment in patients with serious or terminal illnesses and related psychiatric illness. The search found 10 eligible clinical trials, with a total of 445 participants, with the vast majority of the patients having advanced or terminal cancer diagnoses. Six open label trials, published between 1964 and 1980 (n = 341), suggested that psychedelic therapy (mostly with LSD) may improve cancer-related depression, anxiety, and fear of death. Four RCTs trials were published between 2011 and 2016 (n = 104), mostly with psilocybin treatment (n = 92), and demonstrated that psychedelic-assisted treatment can produce rapid, robust, and sustained improvements in cancer-related psychological and existential distress.
Ross, S. (2018). Therapeutic use of classic psychedelics to treat cancer-related psychiatric distress. International Review of Psychiatry, 30(4), 317-330., 10.1080/09540261.2018.1482261
Link to full text

Therapeutic use of classic psychedelics to treat cancer-related psychiatric distress Read More »

Sub-acute and long-term effects of ayahuasca on affect and cognitive thinking style and their association with ego dissolution

/ Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychology, Publications / / , , , , , ,

Abstract

Rationale

Ayahuasca is a psychotropic plant tea from South America used for religious purposes by indigenous people of the Amazon. Increasing evidence indicates that ayahuasca may have therapeutic potential in the treatment of mental health disorders and can enhance mindfulness-related capacities. Most research so far has focused on acute and sub-acute effects of ayahuasca on mental health-related parameters and less on long-term effects.

Objectives

The present study aimed to assess sub-acute and long-term effects of ayahuasca on well-being and cognitive thinking style. The second objective was to assess whether sub-acute and long-term effects of ayahuasca depend on the degree of ego dissolution that was experienced after consumption of ayahuasca.

Results

Ayahuasca ceremony attendants (N = 57) in the Netherlands and Colombia were assessed before, the day after, and 4 weeks following the ritual. Relative to baseline, ratings of depression and stress significantly decreased after the ayahuasca ceremony and these changes persisted for 4 weeks. Likewise, convergent thinking improved post-ayahuasca ceremony up until the 4 weeks follow-up. Satisfaction with life and several aspects of mindfulness increased the day after the ceremony, but these changes failed to reach significance 4 weeks after. Changes in affect, satisfaction with life, and mindfulness were significantly correlated to the level of ego dissolution experienced during the ayahuasca ceremony and were unrelated to previous experience with ayahuasca.

Conclusion

It is concluded that ayahuasca produces sub-acute and long-term improvements in affect and cognitive thinking style in non-pathological users. These data highlight the therapeutic potential of ayahuasca in the treatment of mental health disorders, such as depression.

Uthaug, M. V., van Oorsouw, K., Kuypers, K. P. C., van Boxtel, M., Broers, N. J., Mason, N. L., … & Ramaekers, J. G. (2018). Sub-acute and long-term effects of ayahuasca on affect and cognitive thinking style and their association with ego dissolution. Psychopharmacology, 235(10), 2979-2989., 10.1007/s00213-018-4988-3
Link to full text

Sub-acute and long-term effects of ayahuasca on affect and cognitive thinking style and their association with ego dissolution Read More »

Breath and Body: Scientific and Experiential Perspectives on Breathwork - September 23rd

REGISTER NOW