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Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens

May 20, 2016 / Neuroscience, Papers, Publications / By / , , ,

Abstract

The present study investigated interactions between the novel psychoactive tryptamines DiPT, 4-OH-DiPT, 4-OH-MET, 5-MeO-AMT, and 5-MeO-MiPT at monoamine receptors and transporters compared with the classic hallucinogens lysergic acid diethylamide (LSD), psilocin, N,N-dimethyltryptamine (DMT), and mescaline. We investigated binding affinities at human monoamine receptors and determined functional serotonin (5-hydroxytryptamine [5-HT]) 5-HT2A and 5-HT2B receptor activation. Binding at and the inhibition of human monoamine uptake transporters and transporter-mediated monoamine release were also determined. All of the novel tryptamines interacted with 5-HT2A receptors and were partial or full 5-HT2A agonists. Binding affinity to the 5-HT2A receptor was lower for all of the tryptamines, including psilocin and DMT, compared with LSD and correlated with the reported psychoactive doses in humans. Several tryptamines, including psilocin, DMT, DiPT, 4-OH-DiPT, and 4-OH-MET, interacted with the serotonin transporter and partially the norepinephrine transporter, similar to 3,4-methylenedioxymethamphetamine but in contrast to LSD and mescaline. LSD but not the tryptamines interacted with adrenergic and dopaminergic receptors. In conclusion, the receptor interaction profiles of the tryptamines predict hallucinogenic effects that are similar to classic serotonergic hallucinogens but also MDMA-like psychoactive properties.

Rickli, A., Moning, O. D., Hoener, M. C., & Liechti, M. E. (2016). Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology. http://dx.doi.org/10.1016/j.euroneuro.2016.05.001

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Ego-Dissolution and Psychedelics: Validation of the Ego-Dissolution Inventory (EDI)

May 20, 2016 / Papers, Psychology, Publications / By / , , ,

Abstract

Aims: The experience of a compromised sense of ‘self’, termed ego-dissolution, is a key feature of the psychedelic experience and acute psychosis. This study aimed to validate the Ego-Dissolution Inventory (EDI), a new 8-item self-report scale designed to measure ego-dissolution. Additionally, we aimed to investigate the specificity of the relationship between psychedelics and ego-dissolution.

Method: Sixteen items relating to altered ego-consciousness were included in an internet questionnaire; 8 relating to the experience of ego-dissolution (comprising the EDI), and 8 relating to the antithetical experience of increased self-assuredness. Items were rated using a visual analogue scale. Participants answered the questionnaire for experiences with classical psychedelic drugs, cocaine or alcohol. They also answered the 7 questions from the Mystical Experiences Questionnaire (MEQ) relating to the experience of unity with one’s surroundings.
Results: 691 participants completed the questionnaire, providing data for 1828 drug experiences (1043 psychedelics. 377 cocaine. 408 alcohol). Exploratory factor analysis demonstrated that the 8 EDI items loaded exclusively onto a single common factor, which was orthogonal to a second factor comprised of the items relating to increased self-assuredness (rho= -.110), demonstrating discriminant validity. The EDI correlated strongly with our measure of unitive experience (rho = .735), demonstrating convergent validity. EDI internal consistency was excellent (Cronbach’s alpha 0.93). Three analyses confirmed the specificity of ego-dissolution for experiences occasioned by psychedelic drugs. Firstly, EDI score correlated with drug-dose for psychedelic drugs (rho=.371), but not for cocaine (rho=.115) or alcohol (rho=-0.055). Secondly, the linear regression line relating the subjective intensity of the experience to EDI was significantly steeper for psychedelics (unstandardized B coefficient= 0.701) compared with cocaine (0.135) or alcohol (0.144). Finally, a binary support vector machine classifier identified experiences occasioned by psychedelic drugs vs. cocaine or alcohol with over 85% accuracy using ratings of ego-dissolution and ego-inflation alone.
Conclusions: Our results demonstrate the psychometric structure, internal consistency and construct validity of the EDI. Moreover, we demonstrate the close relationship between ego-dissolution and the psychedelic experience. The EDI will facilitate the study of the neuronal correlates of ego-dissolution, which is relevant for psychedelic-assisted psychotherapy and our understanding of psychosis.
Nour, M. M., Evans, L., Nutt, D., & Carhart-Harris, R. L. (2016). Ego-Dissolution and Psychedelics: Validation of the Ego-Dissolution Inventory (EDI). Frontiers in Human Neuroscience, 10, 269. http://dx.doi.org/10.3389/fnhum.2016.00269
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Ketamine for Treatment of Suicidal Ideation and Reduction of Risk for Suicidal Behavior

May 19, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / ,

Abstract

Ketamine, an NMDA receptor antagonist with efficacy as a rapid anti-depressant, has early evidence for action to reduce suicidal ideation. This review will explore several important questions that arise from these studies. First, how do we measure reductions in suicidal ideation that occur over minutes to hours? Second, are the reductions in suicidal ideation after ketamine treatment solely a result of its rapid anti-depressant effect? Third, is ketamine only effective in reducing suicidal ideation in patients with mood disorders? Fourth, could ketamine’s action lead us to a greater understanding of the neurobiology of suicidal processes? Last, do the reductions in depression and suicidal ideation after ketamine treatment translate into decreased risk for suicidal behavior? Our review concludes that ketamine treatment can be seen as a double-edged sword, clinically to help provide treatment for acutely suicidal patients and experimentally to explore the neurobiological nature of suicidal ideation and suicidal behavior.

Mallick, F., & McCullumsmith, C. B. (2016). Ketamine for Treatment of Suicidal Ideation and Reduction of Risk for Suicidal Behavior. Current psychiatry reports, 18(6), 1-14. http://dx.doi.org/10.1007/s11920-016-0680-7
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Prohibited or regulated? LSD psychotherapy and the United States Food and Drug Administration

May 18, 2016 / Humanities & Art, LSD, Papers, Psychology, Publications / By /

Abstract

Over the 1950s and early 1960s, the use of the hallucinogenic drug lysergic acid diethylamide (LSD) to facilitate psychotherapy was a promising field of psychiatric research in the USA. However, during the 1960s, research began to decline, before coming to a complete halt in the mid-1970s. This has commonly been explained through the increase in prohibitive federal regulations during the 1960s that aimed to curb the growing recreational use of the drug. However, closely examining the Food and Drug Administration’s regulation of LSD research in the 1960s will reveal that not only was LSD research never prohibited, but that the administration supported research to a greater degree than has been recognized. Instead, the decline in research reflected more complex changes in the regulation of pharmaceutical research and development.

Oram, M. (2016). Prohibited or regulated? LSD psychotherapy and the United States Food and Drug Administration. History of psychiatry, 0957154X16648822.
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Remission of Severe Opioid Use Disorder with Ibogaine: A Case Report

May 18, 2016 / Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / , , , ,

Abstract

BACKGROUND: Opioid use disorders (OUD) translate into major health, social, and economic consequences. Opioid agonist medications, which generally require long-term administration, are the mainstay pharmacological treatment of OUD. However, a large proportion of individuals with OUD either refuse or fail to respond to these therapies. Ibogaine, a naturally occurring substance found in the Tabernanthe iboga plant, has shown potential to bring about transformative or spiritual experiences that have reportedly been associated with long-term abstinece. Although research on ibogaine is limited, an ibogaine subculture persists, offering unregulated ibogaine preparations for the treatment of addiction.

CASE PRESENTATION: We describe the case of a 37-year-old female with a 19-year history of severe OUD achieving an ongoing 18-month period of abstinence following a four-day ibogaine treatment. Her previous longest period of continuous abstinence from opioids was two months while on methadone. No safety issues associated with ibogaine were observed.

CONCLUSIONS: A four-day treatment with ibogaine was succesful in achieving long-term remission of a previously treatment-refractory patient with severe OUD. While rigorous trials are required to establish safety and efficacy, future studies should seek to delineate the potential role of ibogaine or other molecules that may produce transformative experiences for individuals with substance use disorder.

Cloutier-Gill, L., Wood, E., Millar, T., Ferris, C., & Eugenia Socias, M. (2016). Remission of Severe Opioid Use Disorder with Ibogaine: A Case Report. Journal of Psychoactive Drugs, 1-4. http://dx.doi.org/10.1080/02791072.2016.1180467

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Ethical Considerations for Clinical Research and Off-label Use of Ketamine to Treat Mood Disorders: The Balance between Risks and Benefits

May 17, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / ,

Abstract

Tishler & Gordon (1999) highlighted ethical concerns behind challenge studies inducing psychosis with ketamine and made recommendations to enhance ethical standards. Recently, there is a plethora of clinical trials evaluating the efficacy of ketamine to treat mood disorders which lead to complex ethical issues. Pharmaceutical companies and researchers hope to profit by developing patentable variations on ketamine for treating depression. Media has labelled ketamine as a “miracle” antidepressant. Some clinics offer expensive off-label use of ketamine to treat mood disorders. This article examines the ecological validity of ketamine trials, measures to protect patients, informed consent procedures, financial inducements to participants and conflict of interest of researchers, therapeutic misconception, concealment and deception. Further recommendations are purposed to improve ethical standard of clinical research involving ketamine.

Zhang, M. W., & Ho, R. C. (2016). Ethical Considerations for Clinical Research and Off-label Use of Ketamine to Treat Mood Disorders: The Balance between Risks and Benefits. Ethics & Behavior. http://dx.doi.org/10.1080/10508422.2016.1189333
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Psilocybin with psychological support for treatment-resistant depression

May 17, 2016 / Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Background: Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression.

Methods: In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin’s effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797.

Findings: Psilocybin’s acute psychedelic effects typically became detectable 30–60 min after dosing, peaked 2–3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0–1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1 week (mean QIDS difference −11·8, 95% CI −9·15 to −14·35, p=0·002, Hedges’ g=3·1) and 3 months (−9·2, 95% CI −5·69 to −12·71, p=0·003, Hedges’ g=2) after high-dose treatment. Marked and sustained improvements in anxiety and anhedonia were also noted.

Interpretation: This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach.

Carhart-Harris, R. L., Bolstridge, M., Rucker, J., Day, C. M., Erritzoe, D., Kaelen, M., … & Taylor, D. (2016). Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry. http://dx.doi.org/10.1016/S2215-0366(16)30065-7

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Psilocybin with psychological support for treatment-resistant depression: An open-label feasibility study

May 17, 2016 / Depressive Disorders, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Background: Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression.

Methods: In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin’s effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797.

Findings: Psilocybin’s acute psychedelic effects typically became detectable 30–60 min after dosing, peaked 2–3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0–1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1 week (mean QIDS difference −11·8, 95% CI −9·15 to −14·35, p=0·002, Hedges’ g=3·1) and 3 months (−9·2, 95% CI −5·69 to −12·71, p=0·003, Hedges’ g=2) after high-dose treatment. Marked and sustained improvements in anxiety and anhedonia were also noted.

Interpretation: This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach.

Funding: Medical Research Council.

Carhart-Harris, R. L., Bolstridge, M., Rucker, J., Day, C. M., Erritzoe, D., Kaelen, M., … & Taylor, D. (2016). Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry. http://dx.doi.org/10.1016/S2215-0366(16)30065-7
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“Quite a Profoundly Strange Experience”: An Analysis of the Experiences of Salvia divinorum Users

May 13, 2016 / Anthropology & Sociology, Papers, Publications, Salvia / Salvinorin A / By / , ,

Abstract

Salvia divnorum (an intense hallucinogen) is currently illegal in New Zealand under the 2014 Psychoactive Substances Amendment Act. Despite this, there is a scarcity of research surrounding Salvia divinorum and its effects in a New Zealand context. To explore the experiences of Salvia divinorum users, an anonymous questionnaire was advertised through flyers placed in locations where young adults congregate. A total of 393 people took part in the online questionnaire in 2010-2011, while salvia was legally available in New Zealand; 167 respondents had used salvia. Thematic analysis was used to analyze the resulting open-ended questionnaire data and three key themes were identified: the effects of salvia; the importance of set and setting; salvia use and pleasure/not-pleasure. Recreational use of salvia was situated within a broader drug landscape, with participants being drug experienced and “drug wise” (Measham, Aldridge, and Parker 2001). Use of salvia also appeared to be intermittent, with its use referred to as a novel experience. Thus, the recent criminalization of salvia under the 2014 Act may see a significant decline in use as experienced drug users look elsewhere for novel drug experiences.

Hutton, F., Kivell, B., & Boyle, O. (2016). “Quite a Profoundly Strange Experience”: An Analysis of the Experiences of Salvia divinorum Users. Journal of Psychoactive Drugs, 1-8. http://dx.doi.org/10.1080/02791072.2016.1179376

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