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Neuroscience

The effects of ketamine on suicidality across various formulations and study settings

January 4, 2019 / Anxiety Disorders / PTSD, Ketamine, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications / By / ,

Abstract

INTRODUCTION:

Suicidality and self-injurious behavior afflict patients with a wide variety of psychiatric illnesses. Currently, there are few pharmacologic treatments for suicidality and self-injurious behavior and none that treat these conditions emergently. Recently, ketamine has demonstrated efficacy in treating both depression and acute suicidal ideation. An increasing usage of ketamine, of a variety of formulations, has been studied for these indications. This article reviews the evidence for use of ketamine in self-injurious behavior and suicidality.

METHODS:

A review of the MEDLINE database for articles relating to ketamine, self-injurious behavior, suicidality, and self-harm was conducted. Additional articles were assessed via cross-reference.

RESULTS:

A total of 24 articles that included clinical trials, meta-analyses, case series, and case reports were analyzed. The majority of studies of ketamine for suicidal ideation include the intravenous route using a dose of 0.5 mg/kg over 40 minutes. These studies suggest that intravenous ketamine may be effective at reducing suicidal ideation acutely. Data on use of ketamine in the intramuscular, intranasal, and oral forms are limited and of poorer quality. Studies on these formulations contain greater variability of positive and negative results of ketamine for reducing suicidality and self-injurious behavior. The durability of the antisuicidal effects across all formulations is limited.

DISCUSSION:

Ketamine may be an effective option for the treatment of suicidal ideation in patients across inpatient, outpatient, or emergent settings. At this time, more research is needed on the efficacy of ketamine across all formulations being used in clinical practice.

Dadiomov, D., & Lee, K. (2019). The effects of ketamine on suicidality across various formulations and study settings. Mental Health Clinician, 9(1), 48-60., 10.9740/mhc.2019.01.048
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Transformative Psychopharmacology: the Case of 5-Methoxy-N,N-Dimethyltryptamine

January 2, 2019 / DMT, Neuroscience, Papers, Publications / By /

Abstract

Since the 2nd part of last century neo-shamanic rituals using mind-altering extracts from plants or animals have become increasingly popular in Europe and the USA. The first rituals coming to the west were based on drinking a special Amazonian tea, Ayahuasca, based on 2 different plants, with active compounds belonging to the class of the beta-carbolines (harmala alkaloids) and tryptamines. The use of such compounds will be described from the perspective of the transformative psychopharmacology: that part of psychopharmacology studying the use of psychoactive compounds to achieve a new balance, a transformation or healing and sometimes even leading to a cure. Examples of curing are meanwhile well documented, for instance the positive influence on drug abuse and addiction, alcoholism. The importance of the healing aspects of these rituals however are often neglected or overlooked. For users, these are key however. As medicine becomes more and more personalized and postmodern, it will be relevant to understand why patients and healthy people decide to participate in healing rituals based on psycho-active compounds. We will present the pharmacology, the transformative psychopharmacology, the effects and adverse events of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) and its place in postmodern medicine.

Jan M Keppel Hesselink (2019) Transformative Psychopharmacology: the Case of 5-Methoxy-N,N-Dimethyltryptamine. International Journal of Psychotherapy Practice and Research – 1(3):9-15., 10.14302/issn.2574-612X.ijpr-18-2503
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Microdosing psychedelics: personality, mental health, and creativity differences in microdosers

January 2, 2019 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

RATIONALE:

Microdosing psychedelics-the regular consumption of small amounts of psychedelic substances such as LSD or psilocybin-is a growing trend in popular culture. Recent studies on full-dose psychedelic psychotherapy reveal promising benefits for mental well-being, especially for depression and end-of-life anxiety. While full-dose therapies include perception-distorting properties, microdosing mayprovide complementary clinical benefits using lower-risk, non-hallucinogenic doses.

OBJECTIVES:

This pre-registered study aimed to investigate whether microdosing psychedelics is related to differences in personality, mental health, and creativity.

METHODS:

In this observational study, respondents recruited from online forums self-reported their microdosing behaviors and completed questionnaires concerning dysfunctional attitudes, wisdom, negative emotionality, open-mindedness, and mood. Respondents also performed the Unusual Uses Task to assess their creativity.

RESULTS:

Current and former microdosers scored lower on measures of dysfunctional attitudes (p < 0.001, r = – 0.92) and negative emotionality (p = 0.009, r = – 0.85) and higher on wisdom (p < 0.001, r = 0.88), openmindedness(p = 0.027, r = 0.67), and creativity (p < 0.001, r = 0.15) when compared to non-microdosing controls.

CONCLUSIONS:

These findings provide promising initial evidence that warrants controlled experimental research to directly test safety and clinical efficacy. As microdoses are easier to administer than full-doses, this new paradigm has the exciting potential to shape future psychedelic research.

Anderson, T., Petranker, R., Rosenbaum, D., Weissman, C. R., Dinh-Williams, L. A., Hui, K., … & Farb, N. A. (2018). Microdosing Psychedelics: Personality, mental health, and creativity differences in microdosers. Psychopharmacology, 1-10., 10.1007/s00213-018-5106-2
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How do psychedelics work?

January 1, 2019 / Neuroscience, Papers, Publications / By /

Abstract

Purpose of review

Psychedelics are reawakening interest from psychiatry, cognitive neuroscience and the general public with impressive outcomes in small-scale clinical trials, intriguing human brain imaging work and high-impact journalism.

Recent findings

This brief opinion piece offers a perspective on how psychedelics work in the brain that may help contextualize these developments. It attempts to link various scales of action, from the molecular (serotonin 2A receptor agonism) through to the anatomical and functional (heightened plasticity) and up to the dynamic (increased brain entropy), systems level (network disintegration and desegregation) and experiential.

Summary

It is proposed that psychedelics initiate a cascade of neurobiological changes that manifest at multiple scales and ultimately culminate in the relaxation of high-level beliefs. The purpose of psychedelic therapy is to harness the opportunity afforded by this belief-relaxation to achieve a healthy revision of pathological beliefs.

Carhart-Harris, R. L. (2019). How do psychedelics work?. Current opinion in psychiatry, 32(1), 16-21.,  10.1097/YCO.0000000000000467
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Role of serotonin transporter and receptor gene variations in the acute effects of MDMA in healthy subjects

December 27, 2018 / MDMA, Neuroscience, Papers, Publications / By / , ,

Abstract

Methylenedioxymethamphetamine (MDMA; ecstasy) is used recreationally and has been investigated as an adjunct to psychotherapy. Most acute effects of MDMA can be attributed to activation of the serotonin (5-hydroxytryptamine [5-HT]) system. Genetic variants, such as single-nucleotide polymorphisms (SNPs) and polymorphic regions in 5-HT system genes, may contribute to interindividual differences in the acute effects of MDMA. We characterized the effects of common genetic variants within selected genes that encode the 5-HT system (TPH1 [tryptophan 5-hydroxylase 1] rs1800532 and rs1799913, TPH2 [tryptophan 5-hydroxylase 2] rs7305115, HTR1A [5-HT1A receptor] rs6295, HTR1B [5-HT1B receptor] rs6296, HTR2A [5-HT2A receptor] rs6313, and SLC6A4 [serotonin transporter] 5-HTTLPR and rs25531) on the physiological and subjective response to 125 mg MDMA compared with placebo in 124 healthy subjects. Data were pooled from eight randomized, double-blind, placebo-controlled studies that were conducted in the same laboratory. TPH2 rs7305115, HTR2A rs6313, and SLC6A4 5-HTTLPR polymorphisms tended to moderately alter some effects of MDMA. However, after correcting for multiple comparisons, none of the tested genetic polymorphisms significantly influenced the response to MDMA. Variations in genes that encode key targets in the 5-HT system did not significantly influence the effects of MDMA in healthy subjects. Interindividual differences in the 5-HT system may thus play a marginal role when MDMA is used recreationally or therapeutically.

Vizeli, P., Meyer zu Schwabedissen, H. E., & Liechti, M. E. (2018). Role of serotonin transporter and receptor gene variations in the acute effects of MDMA in healthy subjects. ACS chemical neuroscience., 10.1021/acschemneuro.8b00590
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DARK Classics in Chemical Neuroscience: Atropine, Scopolamine, and Other Anticholinergic Deliriant Hallucinogens

December 19, 2018 / Neuroscience, Papers, Publications / By / , , , , , ,

Abstract

Anticholinergic drugs based on tropane alkaloids, including atropine, scopolamine, and hyoscyamine, have been used for various medicinal and toxic purposes for millennia. These drugs are competitive antagonists of acetylcholine muscarinic (M-) receptors that potently modulate the central nervous system (CNS). Currently used clinically to treat vomiting, nausea, and bradycardia, as well as alongside other anesthetics to avoid vagal inhibition, these drugs also evoke potent psychotropic effects, including characteristic delirium-like states with hallucinations, altered mood, and cognitive deficits. Given the growing clinical importance of anti-M deliriant hallucinogens, here we discuss their use and abuse, clinical importance, and the growing value in preclinical (experimental) animal models relevant to modeling CNS functions and dysfunctions.

Lakstygal, A., Kolesnikova, T., Khatsko, S., Zabegalov, K., Volgin, A., Demin, K., … & Kalueff, A. (2018). DARK classics in chemical neuroscience: atropine, scopolamine and other anticholinergic deliriant hallucinogens. ACS chemical neuroscience., 10.1021/acschemneuro.8b00615
 
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Classic Psychedelics: An integrative review of epidemiology, mystical experience, brain network function, and therapeutics

September 10, 2024 / Anxiety Disorders / PTSD, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Scienitific Discipline / By / , , ,

Abstract

The purpose of this paper is to provide an integrative review and offer novel insights regarding human research with classic psychedelics (classic hallucinogens), which are 5HT2AR agonists such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Classic psychedelics have been administered as sacraments since ancient times. They were of prominent interest within psychiatry and neuroscience in the 1950s to 1960s, and during this time contributed to the emergence of the field of molecular neuroscience. Promising results were reported for treatment of both end-of-life psychological distress and addiction, and classic psychedelics served as tools for studying the neurobiological bases of psychological disorders. Moreover, classic psychedelics were shown to occasion mystical experiences, which are subjective experiences reported throughout different cultures and religions involving a strong sense of unity, among other characteristics. However, the recreational use of classic psychedelics and their association with the counterculture prompted an end to human research with classic psychedelics in the early 1970s. We review recent therapeutic studies suggesting efficacy in treating psychological distress associated with life-threatening diseases, treating depression, and treating nicotine and alcohol addictions. We also describe the construct of mystical experience, and provide a comprehensive review of modern studies investigating classic psychedelic-occasioned mystical experiences and their consequences. These studies have shown classic psychedelics to fairly reliably occasion mystical experiences. Moreover, classic psychedelic-occasioned mystical experiences are associated with improved psychological outcomes in both healthy volunteer and patient populations. We also review neuroimaging studies that suggest neurobiological mechanisms of psychedelics. These studies have also broadened our understanding of the brain, the serotonin system, and the neurobiological basis of consciousness. Finally, we provide the most comprehensive review of epidemiological studies of classic psychedelics to date. Notable among these are a number of studies which have suggested the possibility that nonmedical naturalistic (non-laboratory) use of classic psychedelics is associated with positive mental health and prosocial outcomes, although it is clear that some individuals are harmed by classic psychedelics in non-supervised settings. Overall, these various lines of research suggest that classic psychedelics might hold strong potential as therapeutics, and as tools for experimentally investigating mystical experiences and behavioral-brain function more generally.

Johnson, M. W., Hendricks, P. S., Barrett, F. S., & Griffiths, R. R. (2018). Classic Psychedelics: An integrative review of epidemiology, mystical experience, brain network function, and therapeutics. Pharmacology & therapeutics., 10.1016/j.pharmthera.2018.11.010

 
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Hallucinogen Persisting Perception Disorder After Ibogaine Treatment for Opioid Dependence

December 1, 2018 / Iboga / Ibogaine, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications, Substance Use Disorder / By / , , , , ,

Abstract

Abstract unavailable for this article.
Knuijver, T., Belgers, M., Markus, W., Verkes, R. J., van Oosteren, T., & Schellekens, A. (2018). Hallucinogen persisting perception disorder after ibogaine treatment for opioid dependence. Journal of clinical psychopharmacology, 38(6), 646-648., 10.1097/JCP.0000000000000966
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Possible Interactions Between 5-HT2A Receptors and the Endocannabinoid System in Humans: Preliminary Evidence of Interactive Effects of Ayahuasca and Endocannabinoids in a Healthy Human Subject

December 1, 2018 / Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychiatry & Medicine, Publications / By / , , , , , ,

Excerpt

To the Editors

Ayahuasca is an ethnobotanical hallucinogenic preparation traditionally used for ritual and therapeutic purposes in the Northwestern Amazon Basin. It is prepared by the decoction of the bark of the vine Banisteriopsis caapi with the leaves of the shrub Psychotria viridis. Banisteriopsis caapi contains the β-carbolines harmine, tetrahydroharmine, and harmaline, which are reversible inhibitors of monoamine oxidase type A (MAO-A), whereas P. viridis contains N,N-dimethyltryptamine (DMT), an agonist at 5-HT1A/2A/2C receptors. Pure DMT is not active orally because it is metabolized by MAO-A, but the β-carbolines in ayahuasca inhibit peripheral MAO-A and allow DMT to reach the brain. The β-carbolines also reach the systemic circulation in humans, but their effects are poorly characterized.

A recent randomized controlled trial (RCT) with 29 patients with treatment-resistant depression showed that, compared with placebo, a single ayahuasca dose induced significant antidepressant effects 7 days after drug intake. The mechanisms behind these effects are not clear but seem to involve agonism at cortical 5-HT2A receptors in brain areas related to emotional processing. 5-HT2A receptor activation also leads to the formation and release of endocannabinoids (ECs), and both the production and release of the EC 2-arachidonoylglycerol (2-AG) are induced by 5-HT2A agonists. Considering that the 5-HT2Areceptor and the EC system (ECS) are coexpressed in brain regions related to emotional processing, they could be involved in the antidepressive effect of ayahuasca. To test the possible interaction between both systems, we administered in an open-label design a single oral ayahuasca dose (1 mL/kg) to a healthy 34-year-old man and assessed subjective effects (Visual Analog Mood Scale [VAMS], Bodily Symptoms Scale, Beck Anxiety Inventory [BAI]), tolerability (blood pressure and heart rate, self-report), and EC plasma levels (anandamide [AEA], 2-AG) at several time points: VAMS, Bodily Symptoms Scale, blood pressure, and heart rate at baseline and 40, 90, 120, 150, and 240 minutes after drug intake; BAI–baseline, 240 minutes after drug intake; AEA, 2-AG (blood samples) at baseline and 90 and 240 minutes after drug intake. Analysis of the ayahuasca sample using gas chromatography with nitrogen-phosphorus detection showed the following alkaloid content (in mg/mL): 0.702 DMT, 1.748 harmine, 0.780 tetrahydroharmine, and 0.039 harmaline. Analysis of plasma ECs was performed using ultrahigh-performance liquid chromatography–tandem mass spectrometry. Detailed information on subjective measures and ayahuasca and EC analyses is described in the Supplemental Digital Content, http://links.lww.com/JCP/A532

The volunteer was not taking any medication and was requested to abstain from alcohol, tobacco, and caffeinated drinks 12 hours before ayahuasca intake. He arrived in the laboratory at 7:00 AM under fasting conditions, and urinalysis for illicit drug use was performed before ayahuasca intake (the test measured cannabis and cocaine and was negative for both drugs). Afterward, a cannula was introduced in his arm for collecting blood samples. Ayahuasca was administered at approximately 8:00 AM, and the experimental session lasted 5 hours. The experimental session consisted in the administration of the drug followed by application of the scales and assessment of tolerability measures at the aforementioned time points. During measurements, the volunteer remained seated in a comfortable reclining chair in a quiet dimly lit room. There was no psychological intervention before, during, or after the session.The volunteer remained in the laboratory under observation to see if the effects had subsided and was discharged around 6 hours after drug intake, which is the approximate duration of the psychoactive effects of ayahuasca.

dos Santos, R. G., Crippa, J. A., de Lima Osório, F., Rocha, J. M., Rossi, G. N., Marchioni, C., … & Hallak, J. E. C. (2018). Possible Interactions Between 5-HT2A Receptors and the Endocannabinoid System in Humans: Preliminary Evidence of Interactive Effects of Ayahuasca and Endocannabinoids in a Healthy Human Subject. Journal of clinical psychopharmacology, 38(6), 644-646., 10.1097/JCP.0000000000000973
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Current perspectives on psychedelic therapy: use of serotonergic hallucinogens in clinical interventions

November 13, 2018 / Humanities & Art, LSD, Mushrooms / Psilocybin, Neuroscience, Psychology / By / ,

Abstract

Humans have used serotonergic hallucinogens (i.e. psychedelics) for spiritual, ceremonial, and recreational purposes for thousands of years, but their administration as part of a structured therapeutic intervention is still a relatively novel practice within Western medical and psychological frameworks. In the mid-20th century, considerable advances were made in developing therapeutic approaches integrating administration of low (psycholytic) and high (psychedelic) doses of serotonergic hallucinogens for treatment of a variety of conditions, often incorporating psychoanalytic concepts prevalent at that time. This work contributed seminal insights regarding how these substances may be employed with efficacy and safety in targeted therapeutic interventions, including the importance of optimizing set (frame of mind) and setting (therapeutic environment). More recently, clinical and pharmacological research has revisited the effects and therapeutic potential of psychedelics utilizing a variety of approaches. The current article provides an overview of past and present models of psychedelic therapy, and discusses important considerations for future interventions incorporating the use of psychedelics in research and clinical practice.

Garcia-Romeu, A., & Richards, W. A. (2018). Current perspectives on psychedelic therapy: use of serotonergic hallucinogens in clinical interventions. International Review of Psychiatry, 30(4), 291-316., 10.1080/09540261.2018.1486289.
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