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The Psychedelic Personality: Personality Structure and Associations in a Sample of Psychedelics Users

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Abstract

Research on the relationship between personality and psychedelics use has found evidence of a two-way influence where the personality structure predicts individual responses to psychedelics, and psychedelics use results in lasting changes to the individual’s personality structure. This study used brief personality measures in the form of the Ten-Item Personality Inventory (TIPI) and a simplified version of the Risk Taking Index (RTI) in order to measure personality traits in a sample of psychedelics users (N = 319). The participants in the study scored consistently higher than norms on each of the Big Five traits except Extraversion, and on every dimension of risk taking in the RTI. In multivariate logistic regression analyses, personality structure was associated with characteristics of the psychedelic experience that included the feelings of fear, love, and peace as well as states of perceived contact with non-ordinary beings and transcendent forces.

Johnstad P. G. (2021). The Psychedelic Personality: Personality Structure and Associations in a Sample of Psychedelics Users. Journal of psychoactive drugs, 53(2), 97–103. https://doi.org/10.1080/02791072.2020.1842569

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Evaluation of the Cytotoxicity of Ayahuasca Beverages

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Abstract

Ayahuasca is a beverage consumed at shamanic ceremonies and currently has gained popularity on recreational scenarios. It contains beta-carboline alkaloids and N,N-dimethyltryptamine, which possesses hallucinogenic effects. Only a few studies have elicited the psychoactive effects and the dose of such compounds on neurological dopaminergic cells or animals. In this work, we aimed to study the cytotoxic effects of these compounds present in ayahuasca beverages and on five different teas (Banisteriopsis caapi, Psychotria viridis, Peganum harmala, Mimosa tenuiflora and Dc Ab (commercial name)) preparations on dopaminergic immortalized cell lines. Moreover, a characterization of the derivative alkaloids was also performed. All the extracts were characterized by chromatographic systems and the effect of those compounds in cell viability and total protein levels were analyzed in N27 dopaminergic neurons cell line. This is the first article where cytotoxicity of ayahuasca tea is studied on neurological dopaminergic cells. Overall, results showed that both cell viability and protein contents decreased when cells were exposed to the individual compounds, as well as to the teas and to the two mixtures based on the traditional ayahuasca beverages.

Simão, A. Y., Gonçalves, J., Gradillas, A., García, A., Restolho, J., Fernández, N., Rodilla, J. M., Barroso, M., Duarte, A. P., Cristóvão, A. C., & Gallardo, E. (2020). Evaluation of the Cytotoxicity of Ayahuasca Beverages. Molecules (Basel, Switzerland), 25(23), 5594. https://doi.org/10.3390/molecules25235594

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Psychedelics as an emerging novel intervention in the treatment of substance use disorder: a review

/ Papers, Substance Use Disorder / Leave a Comment / / ,

Abstract

Classical psychedelics are a group of drugs characterized by their activation of the serotonin-2A (5-hydroxytryptamine-2A; 5-HT2A) receptor and the unique hallucinogenic and mystical-type experiences that result. After a substantial period of restrictions limiting investigations into the therapeutic potential of psychedelics, a relatively recent recommencement of interest has sparked the burgeoning possibility for these drugs to play a part in the treatment of a wide array of psychopathologies. One of the most promising is in the study of addiction. Evidence has emerged that psychedelic agents may provide a novel avenue for the clinical treatment of patients dealing with substance use disorders (SUD). These serotonergic hallucinogens have displayed remarkable and enduring positive outcomes in this area, even when administered as one or two doses. The neural targets for these psychedelics are varied and underlie a complex mechanism of action-modulating multiple neural networks. It is believed that these agents allow for the reorganization of disordered neural pathways in the default mode network and attenuate maladaptive signaling in mesolimbic reward circuitry. The aim of this review is to examine the current standing of evidence regarding psychedelic psychopharmacology and to provide an overview of the use and effectiveness of these drugs in the treatment of SUD, alcohol use disorder, and for smoking cessation.

DiVito, A. J., & Leger, R. F. (2020). Psychedelics as an emerging novel intervention in the treatment of substance use disorder: a review. Molecular biology reports, 47(12), 9791–9799. https://doi.org/10.1007/s11033-020-06009-x

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MDMA-assisted psychotherapy for treatment of anxiety and other psychological distress related to life-threatening illnesses: a randomized pilot study

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Abstract

The success of modern medicine creates a growing population of those suffering from life-threatening illnesses (LTI) who often experience anxiety, depression, and existential distress. We present a novel approach; investigating MDMA-assisted psychotherapy for the treatment of anxiety in people with an LTI. Participants with anxiety from an LTI were randomized in a double-blind study to receive MDMA (125 mg, n = 13) or placebo (n = 5) in combination with two 8-h psychotherapy sessions. The primary outcome was change in State-Trait Anxiety Inventory (STAI) Trait scores from baseline to one month post the second experimental session. After unblinding, participants in the MDMA group had one open-label MDMA session and placebo participants crossed over to receive three open-label MDMA sessions. Additional follow-up assessments occurred six and twelve months after a participant’s last experimental session. At the primary endpoint, the MDMA group had a greater mean (SD) reduction in STAI-Trait scores, – 23.5 (13.2), indicating less anxiety, compared to placebo group, – 8.8 (14.7); results did not reach a significant group difference (p = .056). Hedges’ g between-group effect size was 1.03 (95% CI: – 5.25, 7.31). Overall, MDMA was well-tolerated in this sample. These preliminary findings can inform development of larger clinical trials to further examine MDMA-assisted psychotherapy as a novel approach to treat individuals with LTI-related anxiety.Trial Registration: clinicaltrials.gov Identifier: NCT02427568, first registered April 28, 2015.

Wolfson, P. E., Andries, J., Feduccia, A. A., Jerome, L., Wang, J. B., Williams, E., Carlin, S. C., Sola, E., Hamilton, S., Yazar-Klosinski, B., Emerson, A., Mithoefer, M. C., & Doblin, R. (2020). MDMA-assisted psychotherapy for treatment of anxiety and other psychological distress related to life-threatening illnesses: a randomized pilot study. Scientific reports, 10(1), 20442. https://doi.org/10.1038/s41598-020-75706-1

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Increased signal diversity/complexity of spontaneous EEG, but not evoked EEG responses, in ketamine-induced psychedelic state in humans

/ Ketamine, Neuroscience, Papers / Leave a Comment / / , , , ,

Abstract

How and to what extent electrical brain activity reflects pharmacologically altered states and contents of consciousness, is not well understood. Therefore, we investigated whether measures of evoked and spontaneous electroencephalographic (EEG) signal diversity are altered by sub-anaesthetic levels of ketamine compared to normal wakefulness, and how these measures relate to subjective experience. High-density 62-channel EEG was used to record spontaneous brain activity and responses evoked by transcranial magnetic stimulation (TMS) in 10 healthy volunteers before and during administration of sub-anaesthetic doses of ketamine in an open-label within-subject design. Evoked signal diversity was assessed using the perturbational complexity index (PCI), calculated from EEG responses to TMS perturbations. Signal diversity of spontaneous EEG, with eyes open and eyes closed, was assessed by Lempel Ziv complexity (LZc), amplitude coalition entropy (ACE), and synchrony coalition entropy (SCE). Although no significant difference was found in TMS-evoked complexity (PCI) between the sub-anaesthetic ketamine condition and normal wakefulness, all measures of spontaneous EEG signal diversity (LZc, ACE, SCE) showed significantly increased values in the sub-anaesthetic ketamine condition. This increase in signal diversity correlated with subjective assessment of altered states of consciousness. Moreover, spontaneous signal diversity was significantly higher when participants had eyes open compared to eyes closed, both during normal wakefulness and during influence of sub-anaesthetic ketamine. The results suggest that PCI and spontaneous signal diversity may reflect distinct, complementary aspects of changes in brain properties related to altered states of consciousness: the brain’s capacity for information integration, assessed by PCI, might be indicative of the brain’s ability to sustain consciousness, while spontaneous complexity, as measured by EEG signal diversity, may be indicative of the complexity of conscious content. Thus, sub-anaesthetic ketamine may increase the complexity of the conscious content and the brain activity underlying it, while the level or general capacity for consciousness remains largely unaffected.

Farnes, N., Juel, B. E., Nilsen, A. S., Romundstad, L. G., & Storm, J. F. (2020). Increased signal diversity/complexity of spontaneous EEG, but not evoked EEG responses, in ketamine-induced psychedelic state in humans. PloS one, 15(11), e0242056. https://doi.org/10.1371/journal.pone.0242056

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The Effects of Ketamine on Cognition in Treatment-Resistant Depression: A Systematic Review and Priority Avenues for Future Research

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Abstract

Replicated evidence has documented cognitive deficits in populations with treatment-resistant depression (TRD). Approximately 40 % of patients with MDD present with impairment of one or more cognitive domains. As such, there is an unmet need to discover treatments that have pro-cognitive effects in TRD patients. Ketamine has demonstrated efficacy as a rapid-onset intervention for the treatment of depression. The objective of the current review was to assess the effects of ketamine on cognition in TRD patients. We systematically searched PubMed, Google Scholar and PsycINFO between database inception to March 24th, 2020. We identified five studies that evaluated cognition in TRD populations following ketamine treatment. All studies included a 0.5 mg/kg subanesthetic intravenous (IV) administration of ketamine. One study found significant improvements in complex (p = .008) and simple (p = .027) working memory and one study found improvements in visual learning memory following IV ketamine infusions (p = .014). Improvements in speed of processing and verbal learning memory were observed in anxious TRD participants only. Importantly, a subanesthetic dose of IV ketamine does not worsen cognitive function.

Gill, H., Gill, B., Rodrigues, N. B., Lipsitz, O., Rosenblat, J. D., El-Halabi, S., Nasri, F., Mansur, R. B., Lee, Y., & McIntyre, R. S. (2021). The Effects of Ketamine on Cognition in Treatment-Resistant Depression: A Systematic Review and Priority Avenues for Future Research. Neuroscience and biobehavioral reviews, 120, 78–85. https://doi.org/10.1016/j.neubiorev.2020.11.020

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Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapy

/ Anxiety Disorders / PTSD, Depressive Disorders, MDMA, Papers / Leave a Comment / / , , ,

Abstract

Rationale: MDMA-assisted psychotherapy is under investigation as a novel treatment for posttraumatic stress disorder (PTSD). The primary mechanism of action of MDMA involves the same reuptake transporters targeted by antidepressant medications commonly prescribed for PTSD.

Objectives: Data were pooled from four phase 2 trials of MDMA-assisted psychotherapy. To explore the effect of tapering antidepressant medications, participants who had been randomized to receive active doses of MDMA (75-125 mg) were divided into two groups (taper group (n = 16) or non-taper group (n = 34)).

Methods: Between-group comparisons were made for PTSD and depression symptom severity at the baseline and the primary endpoint, and for peak vital signs across two MDMA sessions.

Results: Demographics, baseline PTSD, and depression severity were similar between the taper and non-taper groups. At the primary endpoint, the non-taper group (mean = 45.7, SD = 27.17) had a significantly (p = 0.009) lower CAPS-IV total scores compared to the taper group (mean = 70.3, SD = 33.60). More participants in the non-taper group (63.6%) no longer met PTSD criteria at the primary endpoint than those in the taper group (25.0%). The non-taper group (mean = 12.7, SD = 10.17) had lower depression symptom severity scores (p = 0.010) compared to the taper group (mean = 22.6, SD = 16.69). There were significant differences between groups in peak systolic blood pressure (p = 0.043) and diastolic blood pressure (p = 0.032).

Conclusions: Recent exposure to antidepressant drugs that target reuptake transporters may reduce treatment response to MDMA-assisted psychotherapy.

Feduccia, A. A., Jerome, L., Mithoefer, M. C., & Holland, J. (2021). Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapy. Psychopharmacology, 238(2), 581–588. https://doi.org/10.1007/s00213-020-05710-w

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Quantum chemical (QM:MM) investigation of the mechanism of enzymatic reaction of tryptamine and N,N-dimethyltryptamine with monoamine oxidase A

/ DMT, Papers, Pharmacology & Chemistry / Leave a Comment / / ,

Abstract

The endogenous psychedelic (mind-altering) N,N-dimethyltryptamine (DMT) molecule has an important role in tissue protection, regeneration, and immunity via sigma-1 receptor activation as its natural ligand. The immunologic properties of DMT suggest this biogenic compound should be investigated thoroughly in other aspects as well. In our in silico project, we examined the metabolism of DMT and its primary analogue, the tryptamine (T), by the monoamine oxidase (MAO) flavoenzyme. MAO has two isoforms, MAO-A and MAO-B. MAOs perform the oxidation of various monoamines by their flavin adenine dinucleotide (FAD) cofactor. Two-layer QM:MM calculations at the ONIOM(M06-2X/6-31++G(d,p):UFF=QEq) level were performed including the whole enzyme to explore the potential energy surface (PES) of the reactions. Our findings reinforced that a hybrid mechanism, a mixture of pure H+ and H– transfer pathways, describes precisely the rate-determining step of amine oxidation as suggested by earlier works. Additionally, our results show that the oxidation of tertiary amine DMT requires a lower activation barrier than the primary amine T. This may reflect a general rule, thus we recommend further investigations. Furthermore, we demonstrated that at pH 7.4 the protonated form of these substrates enter the enzyme. As the deprotonation of substrates is crucial, we presumed protonated cofactor, FADH+, may form. Surprisingly, the activation barriers are much lower compared to FAD with both substrates. Therefore, we suggest further investigations in this direction.

Kubicskó, K., , & Farkas, Ö., (2020). Quantum chemical (QM:MM) investigation of the mechanism of enzymatic reaction of tryptamine and N,N-dimethyltryptamine with monoamine oxidase A. Organic & biomolecular chemistry, 18(47), 9660–9674. https://doi.org/10.1039/d0ob01118e

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MDMA-induced changes in within-network connectivity contradict the specificity of these alterations for the effects of serotonergic hallucinogens

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Abstract

It has been reported that serotonergic hallucinogens like lysergic acid diethylamide (LSD) induce decreases in functional connectivity within various resting-state networks. These alterations were seen as reflecting specific neuronal effects of hallucinogens and it was speculated that these shifts in connectivity underlie the characteristic subjective drug effects. In this study, we test the hypothesis that these alterations are not specific for hallucinogens but that they can be induced by monoaminergic stimulation using the non-hallucinogenic serotonin-norepinephrine-dopamine releasing agent 3,4-methylenedioxymethamphetamine (MDMA). In a randomized, placebo-controlled, double-blind, crossover design, 45 healthy participants underwent functional magnetic resonance imaging (fMRI) following oral administration of 125 mg MDMA. The networks under question were identified using independent component analysis (ICA) and were tested with regard to within-network connectivity. Results revealed decreased connectivity within two visual networks, the default mode network (DMN), and the sensorimotor network. These findings were almost identical to the results previously reported for hallucinogenic drugs. Therefore, our results suggest that monoaminergic substances can induce widespread changes in within-network connectivity in the absence of marked subjective drug effects. This contradicts the notion that these alterations can be regarded as specific for serotonergic hallucinogens. However, changes within the DMN might explain antidepressants effects of some of these substances.

Müller, F., Holze, F., Dolder, P., Ley, L., Vizeli, P., Soltermann, A., Liechti, M. E., & Borgwardt, S. (2021). MDMA-induced changes in within-network connectivity contradict the specificity of these alterations for the effects of serotonergic hallucinogens. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 46(3), 545–553. https://doi.org/10.1038/s41386-020-00906-2

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The time course of psychotic symptom side effects of ketamine in the treatment of depressive disorders: a systematic review and meta-analysis

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Abstract

Objective: Ketamine is a potential rapid-acting treatment for depression. Studies have suggested that the side effects are minimal and temporary, but the psychotic symptom side effects have yet to be fully examined. This study investigated whether ketamine infusion in the treatment of mood disorders is associated with increases in positive symptoms and whether these symptom effects endure over time.

Methods: A systematic review and meta-analysis of studies of ketamine in the treatment of depression. Embase and Medline databases were searched for studies including (a) participants with major affective disorders, (b) 0.4 or 0.5 mg intravenously administered ketamine, (c) measurement of positive symptoms using BPRS+, and (d) a within-subject repeated-measures design with participants serving as their own baseline.

Results: Seventeen studies met the inclusion criteria, comprising 458 participants. The meta-analyses examined symptom change occurring within the first 4 h, after 1 day, and after 3 days. Results showed significant BPRS+ increases within the first 30-60 min in 72% of studies, followed by a return to baseline levels.

Conclusion: Peak symptom change occurred within the first hour post infusion. There are limited data to determine if ketamine is safe in the longer term, but there were no indications that psychotic symptoms re-occurred after the first hour and in the days following administration.

Tashakkori, M., Ford, A., Dragovic, M., Gabriel, L., & Waters, F. (2021). The time course of psychotic symptom side effects of ketamine in the treatment of depressive disorders: a systematic review and meta-analysis. Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists, 29(1), 80–87. https://doi.org/10.1177/1039856220961642

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