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Psychedelics, Personality and Political Perspectives

April 26, 2017 / Papers, Psychology, Publications / By / , ,

Abstract

The psychedelic experience (including psychedelic-induced ego dissolution) can effect lasting change in a person’s attitudes and beliefs. Here, we aimed to investigate the association between naturalistic psychedelic use and personality, political perspectives, and nature relatedness using an anonymous internet survey. Participants (N = 893) provided information about their naturalistic psychedelic, cocaine, and alcohol use, and answered questions relating to personality traits of openness and conscientiousness (Ten-Item Personality Inventory), nature relatedness (Nature-Relatedness Scale), and political attitudes (one-item liberalism-conservatism measure and five-item libertarian-authoritarian measure). Participants also rated the degree of ego dissolution experienced during their “most intense” recalled psychedelic experience (Ego-Dissolution Inventory). Multivariate linear regression analysis indicated that lifetime psychedelic use (but not lifetime cocaine use or weekly alcohol consumption) positively predicted liberal political views, openness and nature relatedness, and negatively predicted authoritarian political views, after accounting for potential confounding variables. Ego dissolution experienced during a participant’s “most intense” psychedelic experience positively predicted liberal political views, openness and nature relatedness, and negatively predicted authoritarian political views. Further work is needed to investigate the nature of the relationship between the peak psychedelic experience and openness to new experiences, egalitarian political views, and concern for the environment.

Nour, M. M., Evans, L., & Carhart-Harris, R. L. (2017). Psychedelics, Personality and Political Perspectives. Journal of Psychoactive Drugs, 1-10. 10.1080/02791072.2017.1312643
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Anxiety, panic, and hopelessness during and after ritual ayahuasca intake in a woman with generalized anxiety disorder: A case report

April 24, 2017 / Anxiety Disorders / PTSD, Ayahuasca, Papers, Psychology / By / , , ,

Abstract

Background and aims

Ayahuasca is a dimethyltryptamine- and β-carboline-rich hallucinogenic beverage traditionally used by indigenous groups of Northwest Amazonian for ritual and therapeutic purposes. Animal and human studies suggest that ayahuasca has antidepressant and anxiolytic potentials and has a good safety profile. However, anxiety-like reactions may also occur after ayahuasca intake, although they are rare.

Methods

Case report.

Results

Here, we describe a case of a non-medicated, symptom-free young female with generalized anxiety disorder, who experienced intense anxiety, panic, and hopelessness during and for 3 days after participating in an ayahuasca ritual. The symptoms appeared in the first hours after ayahuasca intake and were gradually reducing in the following hours/days, but were intense enough to cause significant suffering to her, who needed to seek psychiatric help and restarted pharmacological treatment.

Conclusions

Although “bad/horror trips” with anxiety features may occur during the acute effects of ayahuasca and other hallucinogens, to the best of our knowledge, this is the first report of a subacute/prolonged anxiety-like reaction to this substance. Ayahuasca should be used with caution in people with a history of anxiety disorders.

dos Santos, R. G., Osório, F. L., Crippa, J. A. S., & C. Hallak, J. E. (2017). Anxiety, panic, and hopelessness during and after ritual ayahuasca intake in a woman with generalized anxiety disorder: A case report. Journal of Psychedelic Studies, 1(1), 35-39. 10.1556/2054.01.2017.004
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Prefrontal Connectivity and Glutamate Transmission: Relevance to Depression Pathophysiology and Ketamine Treatment

April 23, 2017 / Depressive Disorders, Ketamine, Neuroscience, Papers / By / , , , , , ,

Abstract

Background

Prefrontal global brain connectivity with global signal regression (GBCr) was proposed as a robust biomarker of depression and was associated with ketamine’s mechanism of action. Here, we investigated prefrontal GBCr in treatment-resistant depression (TRD) at baseline and following treatment. Then, we conducted a set of pharmacological challenges in healthy subjects to investigate the glutamate neurotransmission correlates of GBCr.

Methods

In the cohort A study, we used functional magnetic resonance imaging to compare GBCr between 22 patients with TRD and 29 healthy control subjects. Then, we examined the effects of ketamine and midazolam on GBCr in patients with TRD 24 hours posttreatment. In the cohort B study, we acquired repeated functional magnetic resonance imaging in 18 healthy subjects to determine the effects of lamotrigine (a glutamate release inhibitor), ketamine, and lamotrigine-by-ketamine interaction.

Results

In the cohort A study, patients with TRD showed significant reduction in dorsomedial and dorsolateral prefrontal GBCr compared with healthy control subjects. In patients with TRD, GBCr in the altered clusters significantly increased 24 hours following ketamine (effect size = 1.0, confidence interval = 0.3 to 1.8) but not following midazolam (effect size = 0.5, confidence interval = −0.6 to 1.3). In the cohort B study, oral lamotrigine reduced GBCr 2 hours postadministration, while ketamine increased medial prefrontal GBCr during infusion. Lamotrigine significantly reduced the ketamine-induced GBCr surge. Exploratory analyses showed elevated ventral prefrontal GBCr in TRD and significant reduction of ventral prefrontal GBCr during ketamine infusion in healthy subjects.

Conclusions

This study provides the first replication of the ability of ketamine to normalize depression-related prefrontal dysconnectivity. It also provides indirect evidence that these effects may be triggered by the capacity of ketamine to enhance glutamate neurotransmission.

Abdallah, C. G., Averill, C. L., Salas, R., Averill, L. A., Baldwin, P. R., Krystal, J. H., … & Mathalon, D. H. (2017). Prefrontal Connectivity & Glutamate Transmission: Relevance to Depression Pathophysiology and Ketamine Treatment. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 10.1016/j.bpsc.2017.04.006
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MDMA does not alter responses to the Trier Social Stress Test in humans

April 21, 2017 / MDMA, Papers, Philosophy & Religious Studies / By / , ,

Abstract

Rationale

±3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) is a stimulant-psychedelic drug with unique social effects. It may dampen reactivity to negative social stimuli such as social threat and rejection. Perhaps because of these effects, MDMA has shown promise as a treatment for post-traumatic stress disorder (PTSD). However, the effect of single doses of MDMA on responses to an acute psychosocial stressor has not been tested.

Objectives

In this study, we sought to test the effects of MDMA on responses to stress in healthy adults using a public speaking task. We hypothesized that the drug would reduce responses to the stressful task.

Methods

Volunteers (N = 39) were randomly assigned to receive placebo (N = 13), 0.5 mg/kg MDMA (N = 13), or 1.0 mg/kg MDMA (N = 13) during a stress and a no-stress session. Dependent measures included subjective reports of drug effects and emotional responses to the task, as well as salivary cortisol, heart rate, and blood pressure.

Results

The stress task produced its expected increase in physiological responses (cortisol, heart rate) and subjective ratings of stress in all three groups, and MDMA produced its expected subjective and physiological effects. MDMA alone increased ratings of subjective stress, heart rate, and saliva cortisol concentrations, but contrary to our hypothesis, it did not moderate responses to the Trier Social Stress Test.

Conclusions

Despite its efficacy in PTSD and anxiety, MDMA did not reduce either the subjective or objective responses to stress in this controlled study. The conditions under which MDMA relieves responses to negative events or memories remain to be determined.

Bershad, A. K., Miller, M. A., & de Wit, H. (2017). MDMA does not alter responses to the Trier Social Stress Test in humans. Psychopharmacology, 1-8. 10.1007/s00213-017-4621-x
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Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin

April 19, 2017 / Ketamine, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

What is the level of consciousness of the psychedelic state? Empirically, measures of neural signal diversity such as entropy and Lempel-Ziv (LZ) complexity score higher for wakeful rest than for states with lower conscious level like propofol-induced anesthesia. Here we compute these measures for spontaneous magnetoencephalographic (MEG) signals from humans during altered states of consciousness induced by three psychedelic substances: psilocybin, ketamine and LSD. For all three, we find reliably higher spontaneous signal diversity, even when controlling for spectral changes. This increase is most pronounced for the single-channel LZ complexity measure, and hence for temporal, as opposed to spatial, signal diversity. We also uncover selective correlations between changes in signal diversity and phenomenological reports of the intensity of psychedelic experience. This is the first time that these measures have been applied to the psychedelic state and, crucially, that they have yielded values exceeding those of normal waking consciousness. These findings suggest that the sustained occurrence of psychedelic phenomenology constitutes an elevated level of consciousness – as measured by neural signal diversity.
Schartner, M. M., Carhart-Harris, R. L., Barrett, A. B., Seth, A. K., & Muthukumaraswamy, S. D. (2017). Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin. Scientific Reports, 7. 10.1038/srep46421
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Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study

April 12, 2017 / Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / , ,

Abstract

BACKGROUND:
The psychoactive indole alkaloid ibogaine has been associated with encouraging treatment outcomes for opioid dependence. The legal status of ibogaine in New Zealand provides a unique opportunity to evaluate durability of treatment outcomes.
OBJECTIVE:
To examine longitudinal treatment effects over a 12-month period among individuals receiving legal ibogaine treatment for opioid dependence.
METHOD:
This observational study measured addiction severity as the primary outcome in 14 participants (50% female) over 12 months post-treatment using the Addiction Severity Index-Lite (ASI-Lite) following a single ibogaine treatment by either of two treatment providers. Secondary effects on depression were assessed via the Beck Depression Inventory-II (BDI-II). The Subjective Opioid Withdrawal Scale (SOWS) was collected before and immediately after treatment to measure opioid withdrawal symptoms.
RESULTS:
Nonparametric comparisons via Friedman Test between baseline and 12-month follow-up for participants completing all interviews (n = 8) showed a significant reduction for the ASI-Lite drug use (p = 0.002) composite score. Reductions in BDI-II scores from baseline to 12-month follow-up were also significant (p < 0.001). Significant reductions in SOWS scores for all participants (n = 14) were also observed acutely after treatment (p = 0.015). Patients with partial data (n = 4) also showed reductions in ASI-Lite drug use scores and family/social status problems. One patient enrolled in the study died during treatment.
CONCLUSION:
A single ibogaine treatment reduced opioid withdrawal symptoms and achieved opioid cessation or sustained reduced use in dependent individuals as measured over 12 months. Ibogaine’s legal availability in New Zealand may offer improved outcomes where legislation supports treatment providers to work closely with other health professionals.
Noller, G. E., Frampton, C. M., & Yazar-Klosinski, B. (2017). Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study. The American Journal of Drug and Alcohol Abuse, 1-10. 10.1080/00952990.2017.1310218
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New Treatment Strategies of Depression: Based on Mechanisms Related to Neuroplasticity

April 11, 2017 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , ,

Abstract

Major depressive disorder is a severe and complex mental disorder. Impaired neurotransmission and disrupted signalling pathways may influence neuroplasticity, which is involved in the brain dysfunction in depression. Traditional neurobiological theories of depression, such as monoamine hypothesis, cannot fully explain the whole picture of depressive disorders. In this review, we discussed new treatment directions of depression, including modulation of glutamatergic system and noninvasive brain stimulation. Dysfunction of glutamatergic neurotransmission plays an important role in the pathophysiology of depression. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has rapid and lasting antidepressive effects in previous studies. In addition to ketamine, other glutamatergic modulators, such as sarcosine, also show potential antidepressant effect in animal models or clinical trials. Noninvasive brain stimulation is another new treatment strategy beyond pharmacotherapy. Growing evidence has demonstrated that superficial brain stimulations, such as transcranial magnetic stimulation, transcranial direct current stimulation, cranial electrotherapy stimulation, and magnetic seizure therapy, can improve depressive symptoms. The antidepressive effect of these brain stimulations may be through modulating neuroplasticity. In conclusion, drugs that modulate neurotransmission via NMDA receptor and noninvasive brain stimulation may provide new directions of treatment for depression. Furthermore, exploring the underlying mechanisms will help in developing novel therapies for depression in the future.
Huang, Y. J., Lane, H. Y., & Lin, C. H. (2017). New Treatment Strategies of Depression: Based on Mechanisms Related to Neuroplasticity. Neural plasticity, 2017. 10.1155/2017/4605971
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Use of repeated intravenous ketamine therapy in treatment-resistant bipolar depression with suicidal behaviour: a case report from Spain

April 7, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , ,

Abstract

The rapidly-acting antidepressant properties of ketamine are a trend topic in psychiatry. Despite its robust effects, these are ephemeral and can lead to certain adverse events. For this reason, there is still a general concern around the off-label use of ketamine in clinical practice settings. Nonetheless, for refractory depression, it should be an indication to consider. We report the case of a female patient admitted for several months due to a treatment-resistant depressive bipolar episode with chronic suicidal behaviour. After repeated intravenous ketamine infusions without remarkable side effects, the patient experienced a complete clinical recovery during the 4 weeks following hospital discharge. Unfortunately, depressive symptoms reappeared in the 5th week, and the patient was finally readmitted to hospital as a result of a suicide attempt.
López-Díaz, Á., Fernández-González, J. L., Luján-Jiménez, J. E., Galiano-Rus, S., & Gutiérrez-Rojas, L. (2017). Use of repeated intravenous ketamine therapy in treatment-resistant bipolar depression with suicidal behaviour: a case report from Spain. Therapeutic advances in psychopharmacology, 7(4), 137-140. 10.1177/2045125316675578
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Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation

April 7, 2017 / LSD, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

RATIONALE:
Accumulating evidence indicates that the mixed serotonin and dopamine receptor agonist lysergic acid diethylamide (LSD) induces an altered state of consciousness that resembles dreaming.
OBJECTIVES:
This study aimed to test the hypotheses that LSD produces dreamlike waking imagery and that this imagery depends on 5-HT2A receptor activation and is related to subjective drug effects.
METHODS:
Twenty-five healthy subjects performed an audiorecorded guided mental imagery task 7 h after drug administration during three drug conditions: placebo, LSD (100 mcg orally) and LSD together with the 5-HT2A receptor antagonist ketanserin (40 mg orally). Cognitive bizarreness of guided mental imagery reports was quantified as a standardised formal measure of dream mentation. State of consciousness was evaluated using the Altered State of Consciousness (5D-ASC) questionnaire.
RESULTS:
LSD, compared with placebo, significantly increased cognitive bizarreness (p < 0.001). The LSD-induced increase in cognitive bizarreness was positively correlated with the LSD-induced loss of self-boundaries and cognitive control (p < 0.05). Both LSD-induced increases in cognitive bizarreness and changes in state of consciousness were fully blocked by ketanserin.
CONCLUSIONS:
LSD produced mental imagery similar to dreaming, primarily via activation of the 5-HT2A receptor and in relation to loss of self-boundaries and cognitive control. Future psychopharmacological studies should assess the differential contribution of the D2/D1 and 5-HT1A receptors to cognitive bizarreness.
Kraehenmann, R., Pokorny, D., Vollenweider, L., Preller, K. H., Pokorny, T., Seifritz, E., & Vollenweider, F. X. (2017). Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation. Psychopharmacology, 1-16. 10.1007/s00213-017-4610-0
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A proof-of-concept investigation into ketamine as a pharmacological treatment for alcohol dependence: study protocol for a randomised controlled trial

April 4, 2017 / Ketamine, Papers, Psychology, Substance Use Disorder / By / , , , , ,

Abstract

Background

Worldwide, alcohol abuse is a burgeoning problem. Abstinence is key to allow recovery of physical and mental health as well as quality of life, but treatment for alcohol dependence is associated with high relapse rates. Preliminary data have suggested that a combined repeated ketamine and psychological therapy programme may be effective in reducing relapse in severe alcohol use disorder. This non-commercial proof-of-concept trial is aimed at making a preliminary assessment of the effectiveness of this combined treatment in this patient group.

Methods/design

This is a phase II, randomised, double-blind, placebo-controlled, parallel-group clinical trial taking place in two sites in the UK: the South West of England and London. Ninety-six recently detoxified alcoholics, with comorbid depressive symptoms, will be randomised to one of four treatment arms. Patients will receive either three sessions of ketamine (0.8 mg/kg administered intravenously (IV) over 40 minutes) or placebo (50 ml saline 0.9% IV over 40 minutes) plus either seven sessions of manualised psychological therapy or an alcohol education control. Patients will be assessed at 3 and 6 months on a range of psychological and biological variables. The primary endpoints are (1) relapse rates at 6 months and (2) percentage days abstinent at 6 months. Secondary endpoints include 3 and 6 month percentage days abstinence, tolerability (indicated by dropout), adverse events, depressive symptoms, craving and quality of life.

Discussion

This study will provide important information on a new combined psychological and pharmacological intervention aimed at reducing relapse rates in alcoholics. The findings would have broad application given the worldwide prevalence of alcoholism and its associated medical, psychological and social problems.

McAndrew, A., Lawn, W., Stevens, T., Porffy, L., Brandner, B., & Morgan, C. J. (2017). A proof-of-concept investigation into ketamine as a pharmacological treatment for alcohol dependence: study protocol for a randomised controlled trial. Trials, 18(1), 159. 10.1186/s13063-017-1895-6
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