Background:
Ayahuasca is a traditional Amazon brew and its potential antidepressant properties have recently been explored in scientific settings. We conducted a double-blind placebo-controlled trial ...of ayahuasca with treatment-resistant depression patients (n = 28) and healthy controls (n = 45).
Aims:
We are evaluating the blood inflammatory biomarkers: C-reactive protein and interleukin 6, as a potential consequence of ayahuasca intake and their correlation with serum cortisol and brain-derived neurotrophic factor levels. Blood samples were collected at pre-treatment and 48 hours after substance ingestion to assess the concentration of inflammatory biomarkers, together with administration of the Montgomery-Åsberg Depression Rating Scale.
Results:
At pre-treatment, patients showed higher C-reactive protein levels than healthy controls and a significant negative correlation between C-reactive protein and serum cortisol levels was revealed (rho = –0.40, n = 14). C-reactive protein in those patients was not correlated with Montgomery-Åsberg Depression Rating Scale scores. We observed a significant reduction of C-reactive protein levels across time in both patients and controls treated with ayahuasca, but not with placebo. Patients treated with ayahuasca showed a significant correlation (rho = + 0.57) between larger reductions of C-reactive protein and lower depressive symptoms at 48 hours after substance ingestion (Montgomery-Åsberg Depression Rating Scale). No significant result with respect to interleukin 6 and brain-derived neurotrophic factor was found. Furthermore, these biomarkers did not predict the antidepressant response or remission rates observed.
Conclusions:
These findings enhance the understanding of the biological mechanisms behind the observed antidepressant effects of ayahuasca and encourage further clinical trials in adults with depression.
The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase ...in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN). Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The entropic brain hypothesis holds that the key facts concerning psychedelics are partially explained in terms of increased entropy of the brain's functional connectivity. Ayahuasca is a psychedelic ...beverage of Amazonian indigenous origin with legal status in Brazil in religious and scientific settings. In this context, we use tools and concepts from the theory of complex networks to analyze resting state fMRI data of the brains of human subjects under two distinct conditions: (i) under ordinary waking state and (ii) in an altered state of consciousness induced by ingestion of Ayahuasca. We report an increase in the Shannon entropy of the degree distribution of the networks subsequent to Ayahuasca ingestion. We also find increased local and decreased global network integration. Our results are broadly consistent with the entropic brain hypothesis. Finally, we discuss our findings in the context of descriptions of "mind-expansion" frequently seen in self-reports of users of psychedelic drugs.
Background:
Controversy surrounds psychedelics and their potential to boost creativity. To date, psychedelic studies lack a uniform conceptualization of creativity and methodologically rigorous ...designs.
Aims:
This study aimed at addressing previous issues by examining the effects of lysergic acid diethylamide (LSD) on creativity using multimodal tasks and multidimensional approaches.
Methods:
In a randomized, double-blind, placebo-controlled, crossover study, 24 healthy volunteers received 50 μg of LSD or inactive placebo. Near drug peak, a creativity task battery was applied, including pattern meaning task (PMT), alternate uses task (AUT), picture concept task (PCT), creative metaphors task (MET) and figural creativity task (FIG). Creativity was assessed by scoring creativity criteria (novelty, utility, surprise), calculating divergent thinking (fluency, originality, flexibility, elaboration) and convergent thinking, computing semantic distances (semantic spread, semantic steps) and searching for data-driven special features.
Results:
LSD, compared to placebo, changed several creativity measurements pointing to three overall LSD-induced phenomena: (1) ‘pattern break’, reflected by increased novelty, surprise, originality and semantic distances; (2) decreased ‘organization’, reflected by decreased utility, convergent thinking and, marginally, elaboration; and (3) ‘meaning’, reflected by increased symbolic thinking and ambiguity in the data-driven results.
Conclusion:
LSD changed creativity across modalities and measurement approaches. Three phenomena of pattern break, disorganization and meaning seemed to fundamentally influence creative cognition and behaviour pointing to a shift of cognitive resources ‘away from normal’ and ‘towards the new’. LSD-induced symbolic thinking might provide a tool to support treatment efficiency in psychedelic-assisted therapy.
Serotonergic psychedelics are emerging as potential antidepressant therapeutic tools, as suggested in a recent randomized controlled trial with ayahuasca for treatment-resistant depression. ...Preclinical and clinical studies have suggested that serum brain-derived neurotrophic factor (BDNF) levels increase after treatment with serotoninergic antidepressants, but the exact role of BDNF as a biomarker for diagnostic and treatment of major depression is still poorly understood. Here we investigated serum BDNF levels in healthy controls (
= 45) and patients with treatment-resistant depression (
= 28) before (baseline) and 48 h after (D2) a single dose of ayahuasca or placebo. In our sample, baseline serum BDNF levels did not predict major depression and the clinical characteristics of the patients did not predict their BDNF levels. However, at baseline, serum cortisol was a predictor of serum BDNF levels, where lower levels of serum BDNF were detected in a subgroup of subjects with hypocortisolemia. Moreover, at baseline we found a negative correlation between BDNF and serum cortisol in volunteers with eucortisolemia. After treatment (D2) we observed higher BDNF levels in both patients and controls that ingested ayahuasca (
= 35) when compared to placebo (
= 34). Furthermore, at D2 just patients treated with ayahuasca (
= 14), and not with placebo (
= 14), presented a significant negative correlation between serum BDNF levels and depressive symptoms. This is the first double-blind randomized placebo-controlled clinical trial that explored the modulation of BDNF in response to a psychedelic in patients with depression. The results suggest a potential link between the observed antidepressant effects of ayahuasca and changes in serum BDNF, which contributes to the emerging view of using psychedelics as an antidepressant. This trial is registered at http://clinicaltrials.gov (NCT02914769).
Suicide is a major public health problem. Given increasing suicide rates and limitations surrounding current interventions, there is an urgent need for innovative interventions for suicidality. ...Although ayahuasca has been shown to target mental health concerns associated with suicidality (i.e., depression and hopelessness), research has not yet explored the impact of ayahuasca on suicidality. Therefore, we conducted secondary analyses of a randomized placebo-controlled trial in which individuals with treatment-resistant depression were administered one dose of ayahuasca (
n
= 14) or placebo (
n
= 15). Suicidality was assessed by a trained psychiatrist at baseline, as well as 1 day, 2 days, and 7 days after the intervention. A fixed-effects linear mixed model, as well as between and within-groups Cohen's
d
effect sizes were used to examine changes in suicidality. Controlling for baseline suicidality, we found a significant effect for time (
p
< .05). The effect of the intervention (i.e., ayahuasca vs. placebo) trended toward significance (
p
= .088). At all time points, we found medium between-group effect sizes (i.e., ayahuasca vs. placebo; day 1 Cohen’s
d
= 0.58; day 2 d = 0.56; day 7 d = 0.67), as well as large within-group (ayahuasca; day 1 Cohen's
d
= 1.33; day 2 d = 1.42; day 7 d = 1.19) effect sizes, for decreases in suicidality. Conclusions: This research is the first to explore the impact of ayahuasca on suicidality. The findings suggest that ayahuasca may show potential as an intervention for suicidality. We highlight important limitations of the study, potential mechanisms, and future directions for research on ayahuasca as an intervention for suicidality.
Clinical Trial Registration:
www.ClinicalTrials.gov
, identifier NCT02914769.
Pranayama
refers to a set of yoga breathing exercises. Recent evidence suggests that the practice of
pranayama
has positive effects on measures of clinical stress and anxiety. This study explored the ...impact of a
Bhastrika pranayama
training program on emotion processing, anxiety, and affect. We used a randomized controlled trial design with thirty healthy young adults assessed at baseline and after 4 weeks of
pranayama
practices. Two functional magnetic resonance imaging (MRI) protocols were used both at baseline and post-intervention: an emotion task as well as a resting-state acquisition. Our results suggest that
pranayama
significantly decreased states of anxiety and negative affect. The practice of
pranayama
also modulated the activity of brain regions involved in emotional processing, particularly the amygdala, anterior cingulate, anterior insula, and prefrontal cortex. Resting-state functional MRI (fMRI) showed significantly reduced functional connectivity involving the anterior insula and lateral portions of the prefrontal cortex. Correlation analysis revealed that changes in connectivity between the ventrolateral prefrontal cortex and the right anterior insula were associated with changes in anxiety. Although it should be noted that these analyses were preliminary and exploratory, it provides the first evidence that 4 weeks of
B. pranayama
significantly reduce the levels of anxiety and negative affect, and that these changes are associated with the modulation of activity and connectivity in brain areas involved in emotion processing, attention, and awareness. The study was registered at
https://www.ensaiosclinicos.gov.br/rg/RBR-2gv5c2/(RBR-2gv5c2)
.
Molecular biomarkers are promising tools to be routinely used in clinical psychiatry. Among psychiatric diseases, major depression disorder (MDD) has gotten attention due to its growing prevalence ...and morbidity.
We tested some peripheral molecular parameters such as serum mature Brain-Derived Neurotrophic Factor (mBDNF), plasma C-Reactive Protein (CRP), serum cortisol (SC), and the salivary Cortisol Awakening Response (CAR), as well as the Pittsburgh sleep quality inventory (PSQI), as part of a multibiomarker panel for potential use in MDD diagnosis and evaluation of disease's chronicity using regression models, and ROC curve.
For diagnosis model, two groups were analyzed: patients in the first episode of major depression (MD: n = 30) and a healthy control (CG: n = 32). None of those diagnosis models tested had greater power than Hamilton Depression Rating Scale-6. For MDD chronicity, a group of patients with treatment-resistant major depression (TRD: n = 28) was tested across the MD group. The best chronicity model (p < 0.05) that discriminated between MD and TRD included four parameters, namely PSQI, CAR, SC, and mBDNF (AUC ROC = 0.99), with 96% of sensitivity and 93% of specificity.
These results indicate that changes in specific biomarkers (CAR, SC, mBDNF and PSQI) have potential on the evaluation of MDD chronicity, but not for its diagnosis. Therefore, these findings can contribute for further studies aiming the development of a stronger model to be commercially available and used in psychiatry clinical practice.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
With the aim of further advancing the understanding of the human brain's functional connectivity, we propose a network metric which we term the
. This metric quantifies the Shannon entropy of the ...distance distribution to a specific node from all other nodes. It allows to characterize the influence exerted on a specific node considering statistics of the overall network structure. The measurement and characterization of this structural information has the potential to greatly improve our understanding of sustained activity and other emergent behaviors in networks. We apply this method to study how the psychedelic infusion Ayahuasca affects the functional connectivity of the human brain in resting state. We show that the geodesic entropy is able to differentiate functional networks of the human brain associated with two different states of consciousness in the awaking resting state: (i) the ordinary state and (ii) a state altered by ingestion of the Ayahuasca. The functional brain networks from subjects in the altered state have, on average, a larger geodesic entropy compared to the ordinary state. Finally, we discuss why the geodesic entropy may bring even further valuable insights into the study of the human brain and other empirical networks.
Major depression is a highly prevalent mood disorder, affecting about 350 million people, and around 30% of the patients are resistant to currently available antidepressant medications. Recent ...evidence from a randomized controlled trial (RCT) supports the rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression. The aim of this study was to explore the effect of ayahuasca on plasma cortisol and awakening salivary cortisol response, in the same group of treatment-resistant patients (MD) and in healthy volunteers (C). Subjects received a single dose of ayahuasca or placebo (dosing session), and both plasma and awakening salivary cortisol response were measured at baseline (before dosing session) and 48 h after the dosing session. Baseline assessment (D0) showed blunted awakening salivary cortisol response and hypocortisolemia in patients, with respect to healthy controls. Salivary cortisol was also measured during dosing session, and we observed higher increases for both C and MD that ingested ayahuasca than placebo. After 48 h from the dosing session with ayahuasca, patients' awakening salivary cortisol response is similar to the ones detected in controls. No significant changes in plasma cortisol levels were observed 48 h after the sessions. Therefore, these findings point to new evidence on the modulation of salivary cortisol levels as a result of an ayahuasca session, both in healthy and depressive volunteers. Considering that cortisol acts in regulation of distinct physiological pathways, emotional and cognitive processes, it is assumed to be critically involved to the etiology of depression and its regulation seems to be important for the treatment and remission of major depression, ayahuasca use as antidepressant should be further investigated. Moreover, this study highlights the importance of psychedelics in the treatment of human mental disorders.
PDF
