OPEN Foundation

Psychology

Comparative phenomenology of psilocybin experiences in research and non-research settings

Abstract

This study sought to compare questionnaire ratings of subjective experiences after psilocybin when administered in controlled research settings vs. uncontrolled, non-research settings.

Carbonaro, T. M., Klinedinst, M., Johnson, M. W., & Griffiths, R. R. (2015). Comparative phenomenology of psilocybin experiences in research and non-research settings. Drug and Alcohol Dependence, 156, e36-e37.  http://dx.doi.org/10.1016/j.drugalcdep.2015.07.1017
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Long-term follow-up of psilocybin-facilitated smoking cessation: Abstinence outcomes and qualitative analysis of participant accounts

Abstract

We assessed long-term (>12 months) outcomes of psilocybin-facilitated smoking cessation, and qualitatively analyzed participants’ accounts to inform potential psychological mechanisms of treatment efficacy.

Garcia-Romeu, A. P., Noorani, T., Griffiths, R. R., Johnson, M. W., Garey, L., Zvolensky, M. J., & Schmidt, N. B. (2015). Long-term follow-up of psilocybin-facilitated smoking cessation: Abstinence outcomes and qualitative analysis of participant accounts. Drug and Alcohol Dependence, 156, e78.  http://dx.doi.org/10.1016/j.drugalcdep.2015.07.1130
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Meta-analysis of short- and mid-term efficacy of ketamine in unipolar and bipolar depression

Abstract

Among treatments currently assessed in major depression, ketamine, has been proposed of great interest, especially because of its very rapid action. However, the time-course of the antidepressive action of ketamine remained unclear. In the present meta-analysis, we provided a clear and objective view regarding the putative antidepressive effect of ketamine and its time-course. We searched the MEDLINE and PsycINFO databases through December 2013, without limits on year of publication, using the key words ketamine and synonyms for mood disorder or episode. Six randomized, double-blind and placebo-controlled trials of ketamine in major depression (n=103 patients) were thus identified. Authors were contacted and they all provided original data necessary for this meta-analysis. Standardized mean differences (SMD) were calculated between the depression scores in ketamine and placebo groups at days 1, 2, 3–4, 7 and 14. Ketamine showed an overall antidepressive efficacy from day 1 to day 7. However, the maintenance of its efficacy over time failed to reach significance in bipolar depression after day 3–4. Significant SMDs were not explained by demographic or clinical characteristics of included samples. The present meta-analysis provides a high level of evidence that ketamine has a rapid antidepressive action during one week, especially in unipolar disorder.

Romeo, B., Choucha, W., Fossati, P., & Rotge, J. Y. (2015). Meta-analysis of short-and mid-term efficacy of ketamine in unipolar and bipolar depression. Psychiatry research.  http://dx.doi.org/10.1016/j.psychres.2015.10.032
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Ayahuasca Tourism: Participants in Shamanic Rituals and their Personality Styles, Motivation, Benefits and Risks

Abstract

Ayahuasca continues to attract tourists to South America, where there has been a growth in the number of centers offering hallucinogenic ayahuasca experiences. The aims of this study were to (1) discover the reasons foreigners seek this type of experience; (2) define what an ayahuasca experience entails; (3) discover subjective perceptions of ayahuasca’s benefits and risks; and (4) describe personality styles of participants using the personality questionnaire (PSSI). Participants (N = 77) were persons who had travelled to South America to use ayahuasca. Among the most frequent motivations were curiosity, desire to treat mental health problems, need for self-knowledge, interest in psychedelic medicine, spiritual development, and finding direction in life. Frequently mentioned benefits included self-knowledge, change in the way one relates to oneself, spiritual development, improved interpersonal relations, overcoming mental and physical problems, and gaining a new perspective on life. Stated potential risks included lack of trust in the shaman or organizer, inaccurate information provided by the shaman or organizer, and exposure to dangerous situations. PSSI results showed that people using ayahuasca scored significantly above the norm on the scales of intuition, optimism, ambition, charm, and helpfulness and significantly lower on the scales of distrust and quietness.

Kavenská, V., & Simonová, H. (2015). Ayahuasca Tourism: Participants in Shamanic Rituals and their Personality Styles, Motivation, Benefits and Risks. Journal of psychoactive drugs, 1-9. http://dx.doi.org/10.1080/02791072.2015.1094590

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The Ups and Downs of 3,4-Methylenedioxymethamphetamine: Linking Subjective Effects to Spontaneous Brain Function

Abstract

Psychoactive drugs, especially drugs with so-called psychedelic properties, exert profound effects on sensory perception, cognition, and emotion by modulating target neurotransmitter systems. The compound 3,4-methylenedioxymethamphetamine (MDMA) exerts stimulant and psychedelic effects through its actions on dopamine, norepinephrine, and serotonin (5-hydroxytryptamine, [5-HT]) transporters, by inhibiting their reuptake and stimulating their release. In addition to producing euphoria and positive mood, MDMA appears to produce unique “prosocial” or “empathogenic” feelings.

de Wit, H., Gorka, S. M., & Phan, K. L. (2015). The Ups and Downs of 3, 4-Methylenedioxymethamphetamine: Linking Subjective Effects to Spontaneous Brain Function. Biological psychiatry, 78(8), 519-521. http://dx.doi.org/10.1016/j.biopsych.2015.08.015
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The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level-Dependent Resting State Functional Connectivity

Abstract

BACKGROUND:

The compound 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals.

METHODS:

In a double-blind, placebo-controlled, balanced-order study, MDMA was orally administered to 25 physically and mentally healthy individuals. Arterial spin labeling and seed-based resting state functional connectivity (RSFC) were used to produce spatial maps displaying changes in cerebral blood flow (CBF) and RSFC after MDMA administration. Participants underwent two arterial spin labeling and two blood oxygen level-dependent scans in a 90-minute scan session; MDMA and placebo study days were separated by 1 week.

RESULTS:

Marked increases in positive mood were produced by MDMA. Decreased CBF only was observed after MDMA, and this was localized to the right medial temporal lobe (MTL), thalamus, inferior visual cortex, and the somatosensory cortex. Decreased CBF in the right amygdala and hippocampus correlated with ratings of the intensity of global subjective effects of MDMA. The RSFC results complemented the CBF results, with decreases in RSFC between midline cortical regions, the medial prefrontal cortex, and MTL regions, and increases between the amygdala and hippocampus. There were trend-level correlations between these effects and ratings of intense and positive subjective effects.

CONCLUSIONS:

The MTLs appear to be specifically implicated in the mechanism of action of MDMA, but further work is required to elucidate how the drug’s characteristic subjective effects arise from its modulation of spontaneous brain activity.

Carhart-Harris, R. L., Murphy, K., Leech, R., Erritzoe, D., Wall, M. B., Ferguson, B., … & Tanner, M. (2014). The Effects of Acutely Administered 3, 4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level–Dependent Resting State Functional Connectivity. Biological psychiatry. http://dx.doi.org/10.1016/j.biopsych.2013.12.015

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Return of the lysergamides. Part I: Analytical and behavioural characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD)

Abstract

1-Propionyl-d-lysergic acid diethylamide hemitartrate (1P-LSD) has become available as a ‘research chemical’ in the form of blotters and powdered material. This non-controlled derivative of d-lysergic acid diethylamide (LSD) has previously not been described in the published literature despite being closely related to 1-acetyl-LSD (ALD-52), which was developed in the 1950s. This study describes the characterization of 1P-LSD in comparison with LSD using various chromatographic and mass spectrometric methods, infrared and nuclear magnetic resonance spectroscopy. An important feature common to LSD and other serotonergic hallucinogens is that they produce 5-HT2A-receptor activation and induce the head-twitch response (HTR) in rats and mice. In order to assess whether 1P-LSD displays LSD-like properties and activates the 5-HT2A receptor, male C57BL/6 J mice were injected with vehicle (saline) or 1P-LSD (0.025–0.8 mg/kg, IP) and HTR assessed for 30 min using magnetometer coil recordings. It was found that 1P-LSD produced a dose-dependent increase in HTR counts, and that it had ~38% (ED50 = 349.6 nmol/kg) of the potency of LSD (ED50 = 132.8 nmol/kg). Furthermore, HTR was abolished when 1P-LSD administration followed pretreatment with the selective 5-HT2A receptor antagonist M100907 (0.1 mg/kg, SC), which was consistent with the concept that the behavioural response was mediated by activation of the 5-HT2A receptor. These results indicate that 1P-LSD produces LSD-like effects in mice, consistent with its classification as a serotonergic hallucinogen. Nevertheless, the extent to which 1P-LSD might show psychoactive effects in humans similar to LSD remains to be investigated.

Brandt, S. D., Kavanagh, P. V., Westphal, F., Stratford, A., Elliott, S. P., Hoang, K., … & Halberstadt, A. L. (2015). Return of the lysergamides. Part I: Analytical and behavioural characterization of 1‐propionyl‐d‐lysergic acid diethylamide (1P‐LSD). Drug Testing and Analysis. http://dx.doi.org/10.1002/dta.1884
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Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin

Abstract

The 30-item revised Mystical Experience Questionnaire (MEQ30) was previously developed within an online survey of mystical-type experiences occasioned by psilocybin-containing mushrooms. The rated experiences occurred on average eight years before completion of the questionnaire. The current paper validates the MEQ30 using data from experimental studies with controlled doses of psilocybin. Data were pooled and analyzed from five laboratory experiments in which participants (n=184) received a moderate to high oral dose of psilocybin (at least 20 mg/70 kg). Results of confirmatory factor analysis demonstrate the reliability and internal validity of the MEQ30. Structural equation models demonstrate the external and convergent validity of the MEQ30 by showing that latent variable scores on the MEQ30 positively predict persisting change in attitudes, behavior, and well-being attributed to experiences with psilocybin while controlling for the contribution of the participant-rated intensity of drug effects. These findings support the use of the MEQ30 as an efficient measure of individual mystical experiences. A method to score a “complete mystical experience” that was used in previous versions of the mystical experience questionnaire is validated in the MEQ30, and a stand-alone version of the MEQ30 is provided for use in future research.

Barrett, F. S., Johnson, M. W., & Griffiths, R. R. (2015). Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin. Journal of psychopharmacology (Oxford, England). http://dx.doi.org/10.1177/0269881115609019
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Kappa Opioids, Salvinorin A and Major Depressive Disorder

Abstract

Opioids are traditionally associated with pain, analgesia and drug abuse. It is now clear, however, that the opioids are central players in mood. The implications for mood disorders, particularly clinical depression, suggest a paradigm shift from the monoamine neurotransmitters to the opioids either alone or in interaction with monoamine neurons. We have a special interest in dynorphin, the last of the major endogenous opioids to be isolated and identified. Dynorphin is derived from the Greek word for power, dynamis, which hints at the expectation that the neuropeptide held for its discoverers. Yet, dynorphin and its opioid receptor subtype, kappa, has always taken a backseat to the endogenous b – endorphin and the exogenous morphine that both bind the mu opioid receptor subtype. That may be changing as the dynorphin/ kappa system has been shown to have different, often opposite, neurophysiological and behavioral influences. This includes major depressive disorder (MDD). Here, we have undertaken a review of dynorphin/ kappa neurobiology as related to behaviors, especially MDD. Highlights include the unique features of dynorphin and kappa receptors and the special relation of a plant- based agonist of the kappa receptor salvinorin A. In addition to acting as a kappa opioid agonist, we conclude that salvinorin A has a complex pharmacologic profile , with potential additional mechanisms of action. Its unique neurophysiological effects make Salvinorina A an ideal candidate for MDD treatment research.

T Taylor and Francesca Manzella, G. Kappa Opioids, Salvinorin A and Major Depressive Disorder. Current Neuropharmacology, 13. http://dx.doi.org/10.2174/1570159X13666150727220944
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Current Status of Ketamine and Related Therapies for Mood and Anxiety Disorders

Abstract

Major depressive disorder (MDD) is a leading cause of disability worldwide. Despite a plethora of established treatments, less than one third of individuals with MDD achieve stable remission of symptoms. Given limited efficacy and significant lag time to onset of therapeutic action among conventional antidepressants, interest has shifted to treatments that act outside of the monoamine neurotransmitter systems (e.g., serotonin, norepinephrine, and dopamine). Preclinical and clinical research on the glutamate system has been particularly promising in this regard. Accumulating evidence shows support for a rapid antidepressant effect of ketamine—a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist. The present article reviews the pharmacology, safety, and efficacy of ketamine as a novel therapeutic agent for mood and anxiety disorders. The majority of clinical trials using ketamine have been conducted in patients with treatment-resistant forms of MDD; recent work has begun to examine ketamine in bipolar disorder, post-traumatic stress disorder, and obsessive–compulsive disorder. The impact of ketamine on suicidal ideation is also discussed. The current status and prospects for the identification of human biomarkers of ketamine treatment response and hurdles to treatment development are considered. We conclude by considering modulators of the glutamate system other than ketamine currently in development as potential novel treatment strategies for mood and anxiety disorders.

Costi, S., Van Dam, N. T., & Murrough, J. W. (2015). Current Status of Ketamine and Related Therapies for Mood and Anxiety Disorders. Current Behavioral Neuroscience Reports, 1-10. https://dx.doi.org/10.1007/s40473-015-0052-3
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