OPEN Foundation

Menu
Search
Close this search box.

Scienitific Discipline

The Non-Peptide Arginine-Vasopressin v1a Selective Receptor Antagonist, SR49059, Blocks the Rewarding, Prosocial, and Anxiolytic Effects of 3,4-Methylenedioxymethamphetamine and Its Derivatives in Zebra Fish

August 14, 2017 / MDMA, Neuroscience, Papers, Psychology, Publications / By / , , ,

Abstract

3,4-Methylenedioxymethamphetamine (MDMA) and its derivatives, 2,5-dimethoxy-4-bromo-amphetamine hydrobromide (DOB) and para-methoxyamphetamine (PMA), are recreational drugs whose pharmacological effects have recently been attributed to serotonin 5HT2A/C receptors. However, there is growing evidence that the oxytocin (OT)/vasopressin system can modulate some the effects of MDMA. In this study, MDMA (2.5–10 mg/kg), DOB (0.5 mg/kg), or PMA (0.005, 0.1, or 0.25 mg/kg) were administered intramuscularly to adult zebra fish, alone or in combination with the V1a vasopressin antagonist, SR49059 (0.01–1 ng/kg), before carrying out conditioned place preference (CPP), social preference, novel tank diving, and light–dark tests in order to evaluate subsequent rewarding, social, and emotional-like behavior. The combination of SR49059 and each drug progressively blocked: (1) rewarding behavior as measured by CPP in terms of time spent in drug-paired compartment; (2) prosocial effects measured on the basis of the time spent in the proximity of a nacre fish picture; and (3) anxiolytic effects in terms of the time spent in the upper half of the novel tank and in the white compartment of the tank used for the light–dark test. Antagonism was obtained at SR49059 doses which, when given alone, did not change motor function. In comparison with a control group, receiving vehicle alone, there was a three to five times increase in the brain release of isotocin (the analog of OT in fish) after treatment with the most active doses of MDMA (10 mg/kg), DOB (0.5 mg/kg), and PMA (0.1 mg/kg) as evaluated by means of bioanalytical reversed-phase high-performance liquid chromatography. Taken together, these findings show that the OT/vasopressin system is involved in the rewarding, prosocial, and anxiolytic effects of MDMA, DOB, and PMA in zebra fish and underline the association between this system and the behavioral alterations associated with disorders related to substance abuse.
Ponzoni, L., Braida, D., Bondiolotti, G., & Sala, M. (2017). The Non-Peptide Arginine-Vasopressin v1a Selective Receptor Antagonist, SR49059, Blocks the Rewarding, Prosocial, and Anxiolytic Effects of 3, 4-Methylenedioxymethamphetamine and Its Derivatives in Zebra Fish. Frontiers in psychiatry, 8, 146. 10.3389/fpsyt.2017.00146
Link to full text

Psychedelics and connectedness

August 10, 2017 / LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

Psychedelic drugs are creating ripples in psychiatry as evidence accumulates of their therapeutic potential. An important question remains unresolved however: how are psychedelics effective? We propose that a sense of connectedness is key, provide some preliminary evidence to support this, and suggest a roadmap for testing it further.
Carhart-Harris, R. L., Erritzoe, D., Haijen, E., Kaelen, M., & Watts, R. (2017). Psychedelics and connectedness. Psychopharmacology, 1-4. 10.1007/s00213-017-4701-y
Link to full text

Entheogenesis: Toward an Expanded Worldview for Our Time

August 9, 2017 / Papers, Philosophy & Religious Studies, Psychology / By /

Abstract

Whereas the terminology of psychedelics has acquired spurious cultural associations of “tripping,” the historically primal concept of consciousness expansion has two advantages. One, it connects psychedelic drugs with other modes of consciousness expansion, such as meditation and creative visioning; and two, it suggests contrasting comparison with the consciousness contraction involved in concentration and focus. Both expansions and contractions can be observed at the level of an individual’s states of consciousness and also at the level of the shared worldview of society. Contemporary world culture is moving toward an expanded worldview that recognizes both the material and the spiritual dimensions of our existence.
Metzner, R. (2017). Entheogenesis: Toward an Expanded Worldview for Our Time. Journal of Humanistic Psychology, 57(5), 443-449. 10.1177/0022167817723405
Link to full text

MDMA and brain activity during neurocognitive performance: An overview of neuroimaging studies with abstinent ‘Ecstasy’ users

August 8, 2017 / MDMA, Papers, Psychology, Publications / By / , , ,

Abstract

MDMA/Ecstasy has had a resurgence in popularity, with recent supplies comprising higher strength MDMA, potentially leading to increased drug-related harm. Neurocognitive problems have been widely reported in ecstasy users, equally some studies report null findings, and it remains unclear which factors underlie the development of neurocognitive impairments. This review covers the empirical research into brain activity during neurocognitive performance, using fMRI, fNIRS, and EEG. Our main conclusion is that chronic repeated use of recreational ecstasy can result in haemodynamic and electrophysiological changes that reflect recruitment of additional resources to perform cognitive tasks.

Findings are consistent with serotonergic system changes, although whether this reflects neurotoxicity or neuroadaptation, cannot be answered from these data. There is a degree of heterogeneity in the methodologies and findings, limiting the strengths of current conclusions. Future research with functional neuroimaging paired with molecular imaging, genetics or pharmacological challenges of the serotonin system may help to decipher the link between serotonergic and cognitive changes in ecstasy users.

Roberts, C. A., Quednow, B. B., Montgomery, C., & Parrott, A. C. (2017). MDMA and brain activity during neurocognitive performance: An overview of neuroimaging studies with abstinent ‘Ecstasy’users. Neuroscience & Biobehavioral Reviews. 10.1016/j.neubiorev.2017.07.015
Link to full text

Shannon entropy of brain functional complex networks under the influence of the psychedelic Ayahuasca

August 7, 2017 / Ayahuasca, Neuroscience, Papers, Psychology, Publications / By / , , , ,

Abstract

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.
Viol, A., Palhano-Fontes, F., Onias, H., de Araujo, D. B., & Viswanathan, G. M. (2016). Shannon entropy of brain functional complex networks under the influence of the psychedelic Ayahuasca. arXiv preprint arXiv:1611.00358. 10.1038/s41598-017-06854-0
Link to full text

Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) psychotherapy prolong the therapeutic effects of single ketamine infusion on post-traumatic stress disorder and comorbid depression: a pilot randomized, placebo-controlled, crossover clinical trial

August 2, 2017 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, Papers, Psychology / By / , , , , , ,

Abstract

Background and objectives: Trauma memories lay at the core in etiopathogenesis of post-traumatic stress disorder (PTSD). Using pharmacological and cognitive behavioral treatments that specifically target trauma memories can improve the outcome. Ketamine has been shown to rapidly improve symptoms in PTSD and comorbid depression, but unfortunately these effects are short-lived. Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) psychotherapy is a type of mindfulness based cognitive behavioral therapy that targets the trauma memories. TIMBER psychotherapy in combination with (R,S)-ketamine are increasingly used to treat PTSD and comorbid depression. This study aims to determine if the combination of (R,S)-ketamine chemotherapy and TIMBER psychotherapy would produce a positive synergistic response in patients with PTSD.
Design: This is a randomized, placebo-controlled, cross-over clinical study.
Methods: Because response to ketamine alone is short-lived, this study combined TIMBER with a single infusion of 0.5 mg/kg (R,S)-ketamine to sustain its therapeutic effects. Ten patients with chronic and refractory PTSD were randomly assigned to two groups (n = 5 each): TIMBER-K group patients received ketamine infusion in combination with 12 TIMBER sessions (3 sessions in the first week followed by 9 sessions conducted on a weekly basis) and TIMBER-P group patients received placebo (normal saline infusion) in combination with 12 TIMBER sessions. The patients in the TIMBER-P group were switched to those in the TIMBER-K group after they experienced a sustained relapse.
Outcome measures: PTSD Checklist (PCL), Clinician Administered PTSD Scale for DSM-IV (CAPS), the 17-item Hamilton Rating Scale for Depression (Ham-D-17, clinician rated), Beck Anxiety Inventory (BAI), and Montreal Cognitive Assessment (MoCA) at baseline and 8 hours after infusion were used to investigate if ketamine selectively affected trauma memories leaving the general memory intact. The mindfulness interventions in TIMBER were personalized based on subject’s scores on Assessment Scale for Mindfulness Interventions which was administered at baseline, and after 5 sessions and 9 sessions (completion) of TIMBER. In this study, scores on CAPS and PCL scales were the primary outcome measures.
Results: In the acute phase trial ( first 3 months after infusion), nine out of 10 subjects showed robust response in primary outcome measures (PCL and CAPS scores for PTSD) and in the secondary outcome measures (Ham-D-17 and Beck Anxiety Inventory for depression and anxiety respectively) with a sustained response of 31.78 ± 18.29 days. The TIMBER-K group had a more sustained response (33 ± 22.98 days) compared to the TIMBER-P group (25 ± 16.8 days, P = 0.545). After switch from TIMBER-P group to TIMBER-K, patients experienced significantly prolonged response (49 vs. 25 days, P = 0.028). There were no intolerable side effects or dropouts during the 18-month follow-up period.
Conclusion: TIMBER psychotherapy augmented with low dose (R,S)-ketamine prolongs the therapeutic effects of the later and may be a valuable treatment option for PTSD.
Pradhan, B. K., Wainer, I. W., Moaddel, R., Torjman, M. C., Goldberg, M., Sabia, M., … & Pumariega, A. J. (2017). Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) psychotherapy prolong the therapeutic effects of single ketamine infusion on post-traumatic stress disorder and comorbid depression: a pilot randomized, placebo-controlled, crossover clinical trial. Asia Pacific Journal of Clinical Trials: Nervous System Diseases, 2(3), 80. 10.4103/2542-3932.211589
Link to full text

Psychotherapy with Adjuvant use of Serotonergic Psychoactive Substances: Possibilities and Challenges

August 2, 2017 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Substance Use Disorder / By / , , , , ,

Abstract

Background Recently, scientific interest in the therapeutic potential of serotonergic and psilocybin hallucinogens (psychedelics) such as lysergic acid diethylamide (LSD) and entactogens like 3,4-methylendioxymethamphetamine (MDMA) within the framework of psychotherapy has resumed. The present article provides an overview on the current evidence on substance-assisted psychotherapy with these substances.
Method A selective search was carried out in the PubMed and Cochrane Library including studies investigating the clinical use of serotonergic psychoactive substances since 2000.
Results Studies were found investigating the following indications: alcohol (LSD and psilocybin) and tobacco addiction (psilocybin), anxiety and depression in patients suffering from life-threatening somatic illness (LSD and psilocybin), obsessive-compulsive disorder (OCD) (psilocybin), treatment-resistant major depression (psilocybin), and posttraumatic stress disorder (PTSD) (MDMA).
Discussion Substance use disorders, PTSD and anxiety and depression in patients suffering from life-threatening somatic illness belong to the indications with the best evidence for substance-assisted psychotherapy with serotonergic psychoactive agents. To date, studies indicate efficacy and relatively good tolerability. Further studies are needed to determine whether these substances may represent suitable and effective treatment options for some treatment-resistant psychiatric disorders in the future.
Majić, T., Jungaberle, H., Schmidt, T. T., Zeuch, A., Hermle, L., & Gallinat, J. (2017). Psychotherapy with Adjuvant use of Serotonergic Psychoactive Substances: Possibilities and Challenges. Fortschritte der Neurologie-Psychiatrie, 85(7), 383. 10.1055/s-0043-103085
Link to full text

Oral Ketamine in Treatment-Resistant Depression: A Clinical Effectiveness Case Series

August 1, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , ,

Abstract

PURPOSE:
The aim of the study was to assess the effectiveness, tolerability, and safety of oral ketamine as an antidepressant treatment in adults with treatment-resistant depression.
METHODS:
We reviewed retrospective data on 22 patients with treatment-resistant depression, who failed at least 3 adequate antidepressant treatment trials and 1 adequate trial of repetitive transcranial magnetic stimulation; subsequently, they received open-label treatment with oral ketamine, commenced at a dose of 50 mg every 3 days, titrated up by 25 mg every 3 days, according to response and tolerability. The primary outcome measure was the Beck Depression Inventory II, which was used to rate subjective mood improvement at baseline and then at each follow-up visit. Data about adverse effects related to ketamine and a self-harm risk assessment were also obtained.
FINDINGS:
Over the course of treatment, 18% of the patients showed greater than 50% reduction in the Beck Depression Inventory II scores, 14% reported partial improvement in mood symptoms, while 45% had no response to ketamine and 23% showed a mild worsening in their depressive symptoms. The most frequent adverse effects were acute dissociation, dizziness, blurred vision, numbness and sedation. Neither serious adverse effects, nor any cases of abuse or dependence were observed.
CONCLUSIONS:
Although this case series found oral ketamine to be safe and well tolerated, the findings also showed rather modest effectiveness of oral ketamine in treatment-resistant depression, with only approximately 30% reporting some benefit and approximately 70% reporting no change or worsening of mood. However, bearing in mind the limitations of this small, open-label case series, further exploration of the effectiveness of oral ketamine is warranted.
Al Shirawi, M. I., Kennedy, S. H., Ho, K. T., Byrne, R., & Downar, J. (2017). Oral Ketamine in Treatment-Resistant Depression: A Clinical Effectiveness Case Series. Journal of Clinical Psychopharmacology, 37(4), 464. 10.1097/JCP.0000000000000717
Link to full text

A Systematic Review Of Research On N,N-Dimethyltryptamine

August 1, 2017 / DMT, Neuroscience, Papers, Psychology / By / ,

Abstract

Introduction: The effects of the endogenous hallucinogen N,N-dimethyltryptamine are poorly understood and its medical significance is widely unknown. A small number of  studies regarding its biochemical, pharmaceutical and physiological role have been conducted and the efficacy of its therapeutic potential is presently disregarded. How can scientists proceed in gaining insight into DMT and discovering possible medical uses of this substance?
Materials and Methods: Published articles from  1964 to the present year have been reviewed and the outcome of the studies summarized. The results of drug action,  therapeutic use and potential were investigated . Studies that appeared to have little medical purpose or those, which focus on the use of  Ayahuasca, a South American ritual drink containing N,N-dimethyltryptamine and a monoamine oxidase (MAO)  inhibitor of plant origin, have been excluded.
Results: The research conducted between 1964 and 1987 seems to be an approach to understanding general chemical and biochemical properties of the substance (e.g. metabolites, tolerance, distribution, toxicity, etc.). Rick Strassman, who conducted a broad study from 1990 till 1994 has initiated a recurring interest in the field of psychopharmacology towards DMT. Thus, in the following years, the research was focused on the therapeutic gain of N,N-dimethyltryptamine but resulted mostly inconclusively leading to suggestions of further research. The findings have shown contradictions of already established knowledge, especially for receptors like the sigma-1 receptor, the only direct agonist of which is found to be N,N-dimethyltryptamie.
Conclusion: The studies that now need to be conducted should analyze the correlations between psychiatric diseases (e.g. schizophrenia), purpose of the normal endogenous production and exact action, and the already suggested in various studies therapeutic importance. The low amount of knowledge about the drug action (in case of pharmaceutical use), its targets and drug effect should motivate researchers to gain more insight.
Hristova, D., & Zhelyazkova-Savova, M. (2017). A SYSTEMATIC REVIEW OF RESEARCH ON N, N-DIMETHYLTRYPTAMINE. Scripta Scientifica Vox Studentium, 1(1).
Link to full text

Oral Ketamine in Treatment-Resistant Depression: A Clinical Effectiveness Case Series

August 1, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , ,

Abstract

Purpose The aim of the study was to assess the effectiveness, tolerability, and safety of oral ketamine as an antidepressant treatment in adults with treatment-resistant depression.
Methods We reviewed retrospective data on 22 patients with treatment-resistant depression, who failed at least 3 adequate antidepressant treatment trials and 1 adequate trial of repetitive transcranial magnetic stimulation; subsequently, they received open-label treatment with oral ketamine, commenced at a dose of 50 mg every 3 days, titrated up by 25 mg every 3 days, according to response and tolerability. The primary outcome measure was the Beck Depression Inventory II, which was used to rate subjective mood improvement at baseline and then at each follow-up visit. Data about adverse effects related to ketamine and a self-harm risk assessment were also obtained.
Findings Over the course of treatment, 18% of the patients showed greater than 50% reduction in the Beck Depression Inventory II scores, 14% reported partial improvement in mood symptoms, while 45% had no response to ketamine and 23% showed a mild worsening in their depressive symptoms. The most frequent adverse effects were acute dissociation, dizziness, blurred vision, numbness and sedation. Neither serious adverse effects, nor any cases of abuse or dependence were observed.
Conclusions Although this case series found oral ketamine to be safe and well tolerated, the findings also showed rather modest effectiveness of oral ketamine in treatment-resistant depression, with only approximately 30% reporting some benefit and approximately 70% reporting no change or worsening of mood. However, bearing in mind the limitations of this small, open-label case series, further exploration of the effectiveness of oral ketamine is warranted.
Al Shirawi, M. I., Kennedy, S. H., Ho, K. T., Byrne, R., & Downar, J. (2017). Oral Ketamine in Treatment-Resistant Depression: A Clinical Effectiveness Case Series. Journal of clinical psychopharmacology, 37(4), 464. 10.1097/JCP.0000000000000717
Link to full text

interested in becoming a trained psychedelic-assisted therapist?

Psychedelic Care in Recreational Settings - Online Event - Oct 3rd

REGISTER NOW