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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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Microdosing psychedelics: personality, mental health, and creativity differences in microdosers.

January 2, 2019 / LSD, Mushrooms / Psilocybin, 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. (2019). Microdosing Psychedelics: Personality, mental health, and creativity differences in microdosers. Psychopharmacology, 236(2), 731-740., https://doi.org/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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Effect of Ritualistic Consumption of Ayahuasca on Hepatic Function in Chronic Users.

December 22, 2018 / Ayahuasca, Papers, Psychology, Publications / By / , , , , , ,

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.

December 22, 2018 / Depressive Disorders, Ketamine, Papers, Psychiatry & Medicine, Psychology, Publications / By / , , , , ,

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

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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A Jamesian Response to Reductionism in the Neuropsychology of Religious Experience

September 10, 2024 / Papers, Philosophy & Religious Studies, Publications, Scienitific Discipline / By / ,

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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