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Effect of Ritualistic Consumption of Ayahuasca on Hepatic Function in Chronic Users.

/ Ayahuasca, Papers, Psychology, Publications / / , , , , , ,

Abstract

Ayahuasca is a beverage obtained from decoctions of the liana Banisteriopsis caapi plus the shrub Psychotria viridis. This beverage contains a combination of monoamine oxidase inhibitors (harmine, harmaline, and tetrahydroharmine) and N,N-dimethyltryptamine, the main substance responsible for its visionary effect. The ritualistic use of ayahuasca is becoming a global phenomenon. Most members of ayahuasca churches consume this beverage throughout their life, and many reports have discussed the therapeutic potential of this beverage. Ayahuasca is consumed orally, and the liver, as the major organ for the metabolism and detoxification of xenobiotics absorbed from the alimentary tract, may be susceptible to injury by compounds present in the ayahuasca decoction. In this study, we evaluated biochemical parameters related to hepatic damage in the serum of 22 volunteers who consumed ayahuasca twice a month or more for at least one year. There was no significant alteration in the following parameters: alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine, urea, lactate dehydrogenase, alkaline phosphatase, and gamma glutamyl transferase. These findings indicate that chronic ayahuasca consumption in a religious context apparently does not affect hepatic function.
Mello, S. M., Soubhia, P. C., Silveira, G., Corrêa-Neto, N. F., Lanaro, R., Costa, J. L., & Linardi, A. (2018). Effect of Ritualistic Consumption of Ayahuasca on Hepatic Function in Chronic Users. Journal of psychoactive drugs, 1-9., 10.1080/02791072.2018.1557355
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Ketamine interactions with gut-microbiota in rats: relevance to its antidepressant and anti-inflammatory properties.

/ Depressive Disorders, Ketamine, Papers, Psychiatry & Medicine, Psychology, Publications / / , , , , ,

Abstract

BACKGROUND:
Appreciable evidence suggest that dysbiosis in microbiota, reflected in gut microbial imbalance plays a key role in the pathogenesis of neuropsychiatric disorders including depression and inflammatory diseases. Recently, the antidepressant properties of ketamine have gained prominence due to its fast and long lasting effects. Additional uses for ketamine in inflammatory disorders such as irritable bowel syndrome have been suggested. However, ketamine’s exact mechanism of action and potential effects on microbiome is not known. Here, we examined the effects of low dose ketamine, known to induce antidepressant effects, on stool microbiome profile in adult male Wistar rats. Animals (5/group) were injected intraperitoneally with ketamine (2.5 mg/kg) or saline, daily for 7 days and sacrificed on day 8 when intestinal stools were collected and stored at - 80 °C. DNA was extracted from the samples and the 16 S rRNA gene-based microbiota analysis was performed using 16S Metagenomics application.
RESULTS:
At genus-level, ketamine strikingly amplified Lactobacillus, Turicibacter and Sarcina by 3.3, 26 and 42 fold, respectively. Conversely, opportunistic pathogens Mucispirillum and Ruminococcus were reduced by approximately 2.6 and 26 fold, respectively, in ketamine group. Low levels of Lactobacillus and Turicibacter are associated with various disorders including depression and administration of certain species of Lactobacillus ameliorates depressive-like behavior in animal models. Hence, some of the antidepressant effects of ketamine might be mediated through its interaction with these gut bacteria. Additionally, high level of Ruminococcus is positively associated with the severity of irritable bowel syndrome (IBS), and some species of Mucispirillum have been associated with intestinal inflammation. Indirect evidence of anti-inflammatory role of Sarcina has been documented. Hence, some of the anti-inflammatory effects of ketamine and its usefulness in specific inflammatory diseases including IBS may be mediated through its interaction with these latter bacteria.
CONCLUSION:
Our data suggest that at least some of the antidepressant and anti-inflammatory effects of daily ketamine treatment for 7 days may be mediated via its interaction with specific gut bacteria. These findings further validate the usefulness of microbiome as a target for therapeutic intervention and call for more detailed investigation of microbiome interaction with central mediators of mood and/or inflammatory disorders.
Getachew, B., Aubee, J. I., Schottenfeld, R. S., Csoka, A. B., Thompson, K. M., & Tizabi, Y. (2018). Ketamine interactions with gut-microbiota in rats: relevance to its antidepressant and anti-inflammatory properties. BMC microbiology, 18(1), 222., 10.1186/s12866-018-1373-7
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DARK Classics in Chemical Neuroscience: Atropine, Scopolamine, and Other Anticholinergic Deliriant Hallucinogens

/ Neuroscience, Papers, Publications / / , , , , , ,

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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A Jamesian Response to Reductionism in the Neuropsychology of Religious Experience

/ Papers, Philosophy & Religious Studies, Publications, Scienitific Discipline / / ,

Abstract

The neuroscience revolution has revived interpretations of religious experiences as wholly dependent on biological conditions. William James cautioned against allowing such neurological reductionism to overwhelm other useful perspectives. Contemporary psychologists of religion have raised similar cautions, but have failed to engage James as a full conversation partner. In this article, we present a contemporary, applied version of James’s perspective. We clarify the problem by reviewing specific James-like contemporary concerns about reductionism in the neuropsychological study of religion. Then, most centrally, we employ three of James’s conceptual tools—pragmatism, pluralism, and radical empiricism—to moderate contemporary reductionism. Finally, we point to a constructive approach through which neuroscientists might collaborate with scholars in the humanities and psychosocial sciences, which is consistent with our conclusion that it is often no longer fruitful to separate neurobiological studies from studies that are psychosocial or sociocultural.

Kime, K. G., & Snarey, J. R. (2018). A Jamesian Response to Reductionism in the Neuropsychology of Religious Experience. Archive for the Psychology of Religion, 40(2-3), 307-325., 10.1163/15736121-12341357
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Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions.

/ Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / / ,

Abstract

BACKGROUND:
For a number of mental health disorders, including posttraumatic stress disorders (PTSD), there are not many available treatment options. Recently, there has been renewed interest in the potential of methylenedioxymethamphetamine (MDMA) to restore function for patients with these disorders. The primary hypothesis is that MDMA, via prosocial effects, increases the ability of patients to address the underlying psychopathology of the disorder. However, the use of MDMA poses potential problems of neurotoxicity, in addition to its own potential for misuse.
METHODS:
In this article, the proposed potential of MDMA as an adjunct to psychotherapy for PTSD is evaluated. The rationale for the use of MDMA and the positive results of studies that have administered MDMA in the treatment of PTSD are provided (pros). A description of potential adverse effects of treatment is also presented (cons). An overview of MDMA pharmacology and pharmacokinetics and a description of potential adverse effects of treatments are also presented. Methylenedioxymethamphetamine-produced oxytocin release and decreased expression of fear conditioning as well as one of the MDMA enantiomers (the n R- entaniomer) are suggested as potential mechanisms for the beneficial effects of MDMA in PTSD (suggestions).
RESULTS:
There is some evidence that MDMA facilitates recovery of PTSD. However, the significant adverse effects of MDMA raise concern for its adoption as a pharmacotherapy. Alternative potential treatments with less adverse effects and that are based on the ubiquitous pharmacology of MDMA are presented.
CONCLUSIONS:
We suggest that additional research investigating the basis for the putative beneficial effects of MDMA might reveal an effective treatment with fewer adverse effects. Suggestions of alternative treatments based on the behavioral pharmacology and toxicology of MDMA and its enantiomers are presented.
Schenk, S., & Newcombe, D. (2018). Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions. Journal of clinical psychopharmacology, 38(6), 632-638., 10.1097/JCP.0000000000000962
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Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study

/ DMT, Papers, Psychology, Publications / / , , , , , ,

Abstract

5-MeO-DMT is a psychoactive substance found in high concentrations in the bufotoxin of the Colorado River Toad (Bufo alvarius). Emerging evidence suggests that vaporized 5-MeO-DMT may occasion mystical experiences of comparable intensity to those occasioned by more widely studied psychedelics such as psilocybin, but no empirical study has tested this hypothesis. Data was obtained from 20 individuals (Mage = 38.9, ± 10.7; male = 55%, Caucasian = 85%) who were administered 5-MeO-DMT as part of a psychospiritual retreat program in Mexico. All participants received 50 mg of inhaled vaporized toad bufotoxin which contains 5-MeO-DMT and completed the Mystical Experience Questionnaire (MEQ30) approximately 4–6 h after their session. Administration of 5-MeO-DMT occasioned strong mystical experiences (MEQ30 Overall Mintensity = 4.17, ± 0.64, range 0–5) and the majority (n = 15, 75%) had “a complete mystical experience” (≥60% on all MEQ30 subscales). Compared to a prior laboratory-based psilocybin study, there were no differences in the intensity of mystical effects between 5-MeO-DMT and a high dose (30 mg/70 kg) of psilocybin, but the intensity of mystical effects was significantly higher in the 5-MeO-DMT sample compared to moderate/high dose (20 mg/70 kg) of psilocybin (MEQ30 Total Score: p = 0.02, d = 0.81). Administration of vaporized 5-MeO-DMT reliably occasioned complete mystical experiences in 75% of individuals and was similar in intensity to high dose psilocybin administered in a laboratory setting. The short duration of action may be advantageous for clinical interventions and for studying mystical-type experiences.
Barsuglia, J. P., Davis, A. K., Palmer, R., Lancelotta, R., Windham-Herman, A. M., Peterson, K., … & Griffiths, R. R. (2018). Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study. Frontiers in psychology, 9, 2459., 10.3389/fpsyg.2018.02459
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Classic Psychedelics: An integrative review of epidemiology, mystical experience, brain network function, and therapeutics

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

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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Psychiatry might need some psychedelic therapy

/ Papers, Psychology, Publications / /

Abstract

In historical and modern-day studies, psychedelic drugs have shown promise in managing a variety of psychiatric disorders, but their medical use has often raised controversies. The controversies have related to social, political, and legal challenges.
Johnson, M. (2018). Psychiatry might need some psychedelic therapy. International Review of Psychiatry, 30(4), pp.285-290.,10.1080/09540261.2018.1509544
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Hallucinogen Persisting Perception Disorder After Ibogaine Treatment for Opioid Dependence

/ Iboga / Ibogaine, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications, Substance Use Disorder / / , , , , ,

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

/ Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychiatry & Medicine, Publications / / , , , , , ,

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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