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Therapeutic Applications of Classic Hallucinogens

/ Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / / ,

Abstract

This chapter reviews what is known about the therapeutic uses of the serotonergic or classic hallucinogens, i.e., psychoactive drugs such as LSD and psilocybin that exert their effects primarily through agonist activity at serotonin 2A (5HT2A) receptors. Following a review of the history of human use and scientific study of these drugs, the data from clinical research are summarized, including extensive work on the use of classic hallucinogens in the treatment of alcoholism and other addictions, studies of the use of LSD and psilocybin to relieve distress concerning death, particularly in patients with advanced or terminal cancer, and more limited data concerning the use of classic hallucinogens to treat mood and anxiety disorders. A survey of possible mechanisms of clinically relevant effects is provided. The well-established safety of classic hallucinogens is reviewed. To provide a clinical perspective, case summaries are provided of two individuals who received treatment in recent controlled trials of psilocybin: one being treated for alcoholism, the other suffering from anxiety and depression related to fear of death due to a cancer diagnosis. Although promising early phase research conducted from the 1950s through the early 1970s was discontinued before firm conclusions could be reached concerning the efficacy of any of the classic hallucinogens for any clinical condition, the research that was conducted in that era strongly suggests that classic hallucinogens have clinically relevant effects, particularly in the case of LSD treatment of alcoholism. In the past decade, clinical trials have resumed investigating the effects of classic hallucinogens in the treatment of existential distress in the face of cancer, and in the treatment of addictions including alcoholism and nicotine addiction. The studies that have been completed to date are not sufficient to establish efficacy, but the outcomes have been very encouraging, and larger trials, up to and including phase 3, are now underway or being planned. Although research has elucidated many of the acute neurobiological and psychological effects of classic hallucinogens on humans, animals, and in vitro systems, the mechanisms of clinically relevant persisting effects remain poorly understood.
Bogenschutz, M. P., & Ross, S. (2016). Therapeutic applications of classic hallucinogens. 10.1007/7854_2016_464
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Genie in a blotter: A comparative study of LSD and LSD analogues’ effects and user profile

/ LSD, Papers, Psychology, Publications / / , , , ,

Abstract

OBJECTIVE:
This study aimed to describe self-reported patterns of use and effects of lysergic acid diethylamide (LSD) analogues (AL-LAD, 1P-LSD, and ETH-LAD) and the characteristics of those who use them.
METHODS:
An anonymous self-selected online survey of people who use drugs (Global Drug Survey 2016; N = 96,894), which measured perceived drug effects of LSD and its analogues.
RESULTS:
Most LSD analogue users (91%) had also tried LSD. The proportion of U.K. and U.S. respondents reporting LSD analogue use in the last 12 months was higher than for LSD only. LSD analogue users described the effects as psychedelic (93%), over half (55%) obtained it online, and almost all (99%) reported an oral route of administration. The modal duration (8 hr) and time to peak (2 hr) of LSD analogues were not significantly different from LSD. Ratings for pleasurable high, strength of effect, comedown, urge to use more drugs, value for money, and risk of harm following use were significantly lower for LSD analogues compared with LSD.
CONCLUSIONS:
LSD analogues were reported as similar in time to peak and duration as LSD but weaker in strength, pleasurable high, and comedown. Future studies should seek to replicate these findings with chemical confirmation and dose measurement.
Coney, L. D., Maier, L. J., Ferris, J. A., Winstock, A. R., & Barratt, M. J. (2017). Genie in a blotter: A comparative study of LSD and LSD analogues’ effects and user profile. Human Psychopharmacology: Clinical and Experimental. 10.1002/hup.2599
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The State of the Arts of the Study of Indigenous Religious Traditions in South America

/ Anthropology & Sociology, Ayahuasca, Biology & Ethnobotany, Papers, Scientific Discipline / /

Abstract

This article reviews the principal tendencies in the contemporary studies of indigenous South American religious traditions. It divides the field into studies of socioreligious formations (particularistic and universalistic formations, more specifically) and studies of cosmologies or worldviews (so-called perspectivism). It then discusses two recent, pioneering biographies of South American shamans which, more than any other in the field, offer original approaches to understanding shamanic historical consciousness, cosmopolitics, the constant struggles of shamanic spirits to sustain the cosmos against sorcery spirits that threaten to undermine the cosmic order.

Wright, R. M. (2017). The State of the Arts of the Study of Indigenous Religious Traditions in South America. International Journal of Latin American Religions, 1-15. 10.1007/s41603-017-0002-9
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Associations between Specific Dissociative Symptoms and Symptom Subsets and Anti-Depressant Response to Ketamine

/ Depressive Disorders, Ketamine, Papers, Psychology, Publications / / , , , , ,

Abstract

Ketamine has been shown to produce rapid antidepressant effects in major depression and bipolar disorder. Due to ketamine’s glutamatergic properties, many patients report dissociative effects, which recent studies have shown to be associated with increased anti-depressant response. Thus we investigated the connection between distinct subscales of dissociation and differing treatment response.

Shovestul, B., Jaso, B., Luckenbaugh, D., Park, L., Niciu, M., & Zarate, C. (2017). 199-Associations between Specific Dissociative Symptoms and Symptom Subsets and Anti-Depressant Response to Ketamine. Biological Psychiatry, 81(10), S82-S83. 10.1016/j.biopsych.2017.02.212
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Ketamine as a Treatment for Adolescent Major Depressive Disorder

/ Depressive Disorders, Ketamine, Papers, Psychology, Publications / / , ,

Abstract

Nearly 1 in 4 adolescents will experience major depressive disorder (MDD). Suicide is the 3rd leading cause of death in this age group. 40% of adolescents with MDD fail to respond to initial treatment with selective serotonin reuptake inhibitors (SSRIs). Of that SSRI-resistant population, nearly half remain depressed despite alternate medication and psychotherapy. Thus, better treatments for adolescent depression are urgently needed. Subanesthetic doses of ketamine, an NMDA antagonist, produce rapid antidepressant and anti-suicidal effects in depressed adults. There are few case reports and no prospective controlled trials of ketamine for the treatment of adolescent MDD.

Dwyer, J., Sanacora, G., & Bloch, M. (2017). 1002-Ketamine as a Treatment for Adolescent Major Depressive Disorder. Biological Psychiatry, 81(10), S405. 10.1016/j.biopsych.2017.02.729
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Clinical Predictors of an Antisuicidal Response to Ketamine

/ Depressive Disorders, Ketamine, Papers, Psychology, Publications / / , , , , , ,

Abstract

Suicide is one of the leading causes of death in the United States. Despite treatment efforts, the national suicide rate has increased in recent years. Currently, there are no pharmacological treatments for suicidal ideation (SI). For individuals experiencing a suicidal crisis, rapid acting medications may save lives. Recent studies suggest ketamine, a glutamate modulator, elicits rapid antisuicidal responses. We examined clinical factors that might predict ketamine’s antisuicidal response as a step towards understanding ketamine’s mechanism of action on suicidal thoughts.

Yarrington, J., Ballard, E., Luckenbaugh, D., Niciu, M., Lener, M., Kadriu, B., … & Zarate, C. (2017). 1004-Clinical Predictors of an Antisuicidal Response to Ketamine. Biological Psychiatry, 81(10), S406. 10.1016/j.biopsych.2017.02.731
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Mood Dependent Effects of Ketamine on REM Eye Movements in Patients with Treatment Resistant Depression (TRD)

/ Depressive Disorders, Ketamine, Papers, Psychology, Publications / / , , , ,

Abstract

Both REM and NREM sleep are dysregulated in depression. REM dysregulation in MDD is thought to be partially linked to a deficient inhibitory influence of Process-S, leading to increased REM density (RD) and short REM latency (RL). Consistent with its effects on enhanced synaptic plasticity, ketamine increases SWS and early night slow-wave activity (SWA) in patients with TRD. Here we extend the examination of ketamine effects on rapid mood improvement to RD, an important marker of REM sleep in depression.

Hejazi, N., Yu, K., Park, L., Duncan, W., & Zarate, C. (2017). 861-Mood Dependent Effects of Ketamine on REM Eye Movements in Patients with Treatment Resistant Depression (TRD). Biological Psychiatry, 81(10), S348-S349. 10.1016/j.biopsych.2017.02.586
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Neuropathic and inflammatory antinociceptive effects and electrocortical changes produced by Salvia divinorum in rats

/ Papers, Psychiatry & Medicine, Publications, Salvia / Salvinorin A / / , , , , , ,

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:
Salvia divinorum is a medicinal plant traditionally used in hallucinogenic ethnopharmacological practices and for its analgesic and antinflammatory properties. Its active compounds include diterpenes known as salvinorins which act as potent κ opioid receptor agonists.
AIM OF THE STUDY:
Given its effects in acute animal models of pain, as well as its antinflammatory attributes, we decided to investigate the analgesic effects of an SD extract in neuropathic (sciatic loose nerve ligature) and inflammatory (intra plantar carrageenan) pain models in rats. We also determined in this study the electrocorticographic changes to correlate similar hallucinogenic state and behavior as those produced in humans.
MATERIAL AND METHODS:
Mechanical and thermonociceptive responses, plantar test and von Frey assay, respectively, were measured in adult Wistar rats 30min, 3h and 24h after the intraperitoneal administration of saline or an hydroponic SD extract. We also evaluated carbamazepine and celecoxib, as gold reference drugs, to compare its antinociceptive effects.
RESULTS:
Our results showed that administration of SD extract induced antialgesic effects in both neuropathic and inflammatory pain models. All those effects were blocked by nor-binaltorphimine (a Kappa opioid receptor antagonist). Moreover, it was observed an increase of the anterior power spectral density and a decrease in the posterior region as electrocorticographic changes.
CONCLUSION:
The present investigation give evidence that SD is capable to reduce algesic response associated to neuropathic and inflammatory nociception. This study support therapeutic alternatives for a disabling health problem due to the long term pain with high impact on population and personal and social implications.
Simón-Arceo, K., González-Trujano, M. E., Coffeen, U., Fernández-Mas, R., Mercado, F., Almanza, A., … & Pellicer, F. (2017). Neuropathic and inflammatory antinociceptive effects and electrocortical changes produced by Salvia divinorum in rats. Journal of Ethnopharmacology, 206, 115-124. 10.1016/j.jep.2017.05.016
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Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression

/ Depressive Disorders, Ketamine, Papers, Psychology, Publications / / , , , , , ,

Abstract

The antidepressant effects of ketamine are thought to depend on brain-derived neurotrophic factor (BDNF) genotype and dose. The purpose of this study was to characterize the dose-related antidepressant effects of ketamine in patients with treatment-resistant depression drawn from a Chinese population predominately possessing lower activity BDNF genotypes (Val/Met, Met/Met). We conducted a double-blind, randomized, parallel-group, placebo-controlled trial of a single ketamine infusion (saline, 0.2 mg/kg, 0.5 mg/kg). Patients (N=71; BDNF genotype: Val/Val (N=12, 17%), Val/Met (N=40, 56.3%), and Met/Met (N=19, 26.8%)) received mood ratings before infusion, after infusion, and for the subsequent 14 days. Plasma ketamine levels and BDNF genotypes were assessed. This study found a significant dose-related ketamine effect on scores on the Hamilton Depression Rating Scale (HAMD). The responder analysis (>50% reduction from baseline HAMD on at least 2 days between days 2 and 5) also revealed a significant dose-related effect (saline: 12.5%, 0.2 mg/kg: 39.1%; 0.5 mg/kg: 45.8%). This is the first report to our knowledge to demonstrate the dose-related efficacy of R/S-ketamine for treatment-resistant depression and the first to characterize ketamine effects in a genotyped Chinese population in which most (83%) patients possessed at least one copy of the lower functioning Met allele of the BDNF gene.
Su, T. P., Chen, M. H., Li, C. T., Lin, W. C., Hong, C. J., Gueorguieva, R., … & Krystal, J. H. (2017). Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression. Neuropsychopharmacology. 10.1038/npp.2017.94
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Cognitive Behavior Therapy May Sustain Antidepressant Effects of Intravenous Ketamine in Treatment-Resistant Depression

/ Depressive Disorders, Ketamine, Papers, Psychology, Publications / / , , , , , ,

Abstract

INTRODUCTION:
Ketamine has shown rapid though short-lived antidepressant effects. The possibility of concerning neurobiological changes following repeated exposure to the drug motivates the development of strategies that obviate or minimize the need for longer-term treatment with ketamine. In this open-label trial, we investigated whether cognitive behavioral therapy (CBT) can sustain or extend ketamine’s antidepressant effects.
METHODS:
Patients who were pursuing ketamine infusion therapy for treatment-resistant depression were invited to participate in the study. If enrolled, the subjects initiated a 12-session, 10-week course of CBT concurrently with a short 4-treatment, 2-week course of intravenous ketamine (0.5 mg/kg infused over 40 min) provided under a standardized clinical protocol.
RESULTS:
Sixteen participants initiated the protocol, with 8 (50%) attaining a response to the ketamine and 7 (43.8%) achieving remission during the first 2 weeks of protocol. Among ketamine responders, the relapse rate at the end of the CBT course (8 weeks following the last ketamine exposure) was 25% (2/8). On longer-term follow-up, 5 of 8 subjects eventually relapsed, the median time to relapse being 12 weeks following ketamine exposure. Among ketamine remitters, 3 of 7 retained remission until at least 4 weeks following the last ketamine exposure, with 2 retaining remission through 8 weeks following ketamine exposure. Ketamine nonresponders did not appear to benefit from CBT.
CONCLUSIONS:
CBT may sustain the antidepressant effects of ketamine in treatment-resistant depression. Well-powered randomized controlled trials are warranted to further investigate this treatment combination as a way to sustain ketamine’s antidepressant effects.
Wilkinson, S. T., Wright, D., Fasula, M. K., Fenton, L., Griepp, M., Ostroff, R. B., & Sanacora, G. (2017). Cognitive Behavior Therapy May Sustain Antidepressant Effects of Intravenous Ketamine in Treatment-Resistant Depression. Psychotherapy and Psychosomatics, 86(3), 162-167. 10.1159/000457960
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Journal Club #22: Applying the EU Regulatory Framework to Determine the Benefit–Risk Profile of Psychedelics - March 3

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