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Hofmann’s Wish Came True

/ LSD, Publications /

After 40 years without research, the recent appearance of a pilot study with Lysergic Acid Diethylamide (LSD) in humans, might be interpreted as a positive reinforcement for future attempts to study the role of psychedelics as therapeutic agents. The study of Gasser et al. (2014) was aimed at assaying the possible benefits from the use of LSD as an additive to psychotherapy in the treatment of anxiety associated with life-threatening diseases.

The participants in the double blind, randomized, active placebo-controlled study were recruited from a population of patients diagnosed with a life-threatening disease. The participants were randomized across two-groups and received two therapeutic sessions with LSD (mild-dose placebo-control group; moderate-dose experimental group) in addition to psychotherapy. The patients that were initially assigned to the placebo-control group, were offered the opportunity to participate in a second series of moderate-dose LSD-assisted therapies (open-label crossover group). The most important result from the study was that with each cumulative LSD session, anxiety seemed to reduce in the group that received a moderate dose, but not in the group that received a mild dose. In the latter group, this pattern of reduced anxiety was repeated with the second series of sessions in which the moderate dose was offered to the patients. The benefits of the LSD-assisted sessions seemed to sustain over time. Though methodological adjustments are preferred to improve matters of experimental reliability and validity (as the authors note a larger sample size, a less discriminative placebo, better treatment of secondary disease symptoms to avoid missing data), the reactions of the patients themselves suggest successful clinical guidance during the process of coping with death. Majority reported that they would have preferred more than two LSD sessions and a longer treatment period.

Not only did the study yield promising results about the controversial use of a Schedule 1 listed drug (21 U.S.C. § 812) in a therapeutic setting, the publication also received extensive international media attention (Carey, 2014; Healey, 2014; Connor, 2014) suggesting a regained public interest favoring psychedelic research. While directly after discovery the psychoactive effects of LSD were considered to be of considerable value for experimental research and psychiatric practice (Passie, Halpern, Stichtenoth, Emrich, & Hintzen, 2008), it’s reputation of the past 40 years was mainly that of a dangerous drug (SAMHSHA, 2008). In addition to a recent clinical study done with psilocybin (Grob et al., 2011) , the current study contributes to a refreshed wave that acknowledges the usefulness of psychedelics as an investigational tool for psychiatric research. With the resumption of research into LSD’s therapeutic potential, the researchers hope to have “fulfilled the longtime wish” of the founding father of LSD, Albert Hofmann, as to whom the article is dedicated.

 
References
Carey, B. (2014, March 4). LSD, Reconsidered for Therapy. The New York Times. Retrieved from http://www.nytimes.com
Connor, S. (2014, March 6). Can LSD ease our fear of death? First scientific study in 40 years shows positive results. The independent. Retrieved from http://www.independent.co.uk
Gasser, P., Holstein, D., Michel, Y., Doblin, R., Yazar-Klosinski, B., Passie, T., Brenneisen, R. (in press). Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases. The Journal of Nervous and Mental Disease
Grob, C. S., Danforth, A. L., Chopra, G. S., Hagerty, M., McKay, C. R., Halberstadt, A. L., & Greer, G. R. (2011). Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Archives of General Psychiatry, 68, 71–78. doi:10.1001/archgenpsychiatry.2010.116
Healy, M. (2014, March 5). First trial of LSD as medicine in 40 years shows promise. The Los Angeles Times. Retrieved from http://www.latimes.com
Passie, T., Halpern, J. H., Stichtenoth, D. O., Emrich, H. M., & Hintzen, A. (2008). The pharmacology of lysergic acid diethylamide: a review. CNS Neuroscience & Therapeutics, 14, 295–314. doi:10.1111/j.1755-5949.2008.00059.x
SAMHSA. Available at http://www.oas.samhsa.gov/ecstasy.htm, 2006. Accessed on 08 March 2014.
U.S. Food and Drug Administration. (2009, June 6). Controlled Substance Act. Retrieved from http://www.fda.gov/regulatoryinformation/legislation/ucm148726.htm

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Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases

/ Anxiety Disorders / PTSD, LSD, Papers, Psychology, Publications / / , , , , , ,

Abstract

A double-blind, randomized, active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases. Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart. The participants received either 200 mcg of LSD (n=8) or 20 mcg of LSD with an open-label crossover to 200 mcg of LSD after the initial blinded treatment was unmasked (n=4). At the 2-month follow-up, positive trends were found via the State-Trait Anxiety Inventory (STAI) in reductions in trait anxiety (p=0.033) with an effect size of 1.1, and state anxiety was significantly reduced (p= 0.021) with an effect size of 1.2, with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events. STAI reductions were sustained for 12 months. These results indicate that when administered safely in a methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted.

Gasser, P., Holstein, D., Michel, Y., Doblin, R., Yazar-Klosinski, B., Passie, T., & Brenneisen, R. (2014). Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases. The Journal of Nervous and Mental Disease, 202, 1-8. http://dx.doi.org/10.1097/NMD.0000000000000113
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Indigenous healing practice: ayahuasca. Opening a discussion

/ Ayahuasca, Papers, Psychology, Publications, Substance Use Disorder / / ,

Abstract

This essay frames an invitation to pastoral counselors and pastoral theologians to examine connections and perhaps interactions between themselves and traditional shamanic healers who use ayahuasca in their healing ceremonies. Indigenous people in South America have used ayahuasca for centuries, and the ritual has become common among the mestizo populations in urban areas of the Amazon, particularly as a curing ritual for drug addiction (Dobkin de Rios, 1970; Moir, 1998). Like peyote in the United States (Calabrese, 1997) ayahuasca use amongst the indigenous people of the Amazon is a form of cultural psychiatry. A review of the literature reveals very little commentary or discussion of shamanic practice in Pastoral Counseling (Pastoral Theology). The scant literature identifies an antithetical relationship at best. The current authors wonder about the possibility of to including shamanic practices in the context of pastoral counseling? This essay seeks to provide some basic information about the ritual use of ayahuasca and to offer a rationale for pastoral counselors to engage in a dialogue about its utility.

Prue, R., & Voss, R. W. (2014). Indigenous healing practice: ayahuasca. Opening a discussion. Journal of Pastoral Care & Counseling, 68(1), 1-13. 10.1177/154230501406800106
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Therapeutic infusions of ketamine: Do the psychoactive effects matter?

/ Ketamine, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications, Substance Use Disorder / / , , , , ,

Abstract

Background

Sub-anesthetic ketamine infusions may benefit a variety of psychiatric disorders, including addiction. Though ketamine engenders transient alterations in consciousness, it is not known whether these alterations influence efficacy. This analysis evaluates the mystical-type effects of ketamine, which may have therapeutic potential according to prior research, and assesses whether these effects mediate improvements in dependence-related deficits, 24 h postinfusion.

Methods

Eight cocaine dependent individuals completed this double-blind, randomized, inpatient study. Three counter-balanced infusions separated by 48 h were received: lorazepam (2 mg) and two doses of ketamine (0.41 mg/kg and 0.71 mg/kg, with the former dose always preceding the latter). Infusions were followed within 15 min by measures of dissociation (Clinician Administered Dissociative Symptoms Scale: CADSS) and mystical-type effects (adapted from Hood’s Mysticism Scale: HMS). At baseline and 24 h postinfusion, participants underwent assessments of motivation to stop cocaine (University of Rhode Island Change Assessment) and cue-induced craving (by visual analogue scale for cocaine craving during cue exposure).

Results

Ketamine led to significantly greater acute mystical-type effects (by HMS) relative to the active control lorazepam; ketamine 0.71 mg/kg was associated with significantly higher HMS scores than was the 0.41 mg/kg dose. HMS score, but not CADSS score, was found to mediate the effect of ketamine on motivation to quit cocaine 24 h postinfusion.

Conclusions

These findings suggest that psychological mechanisms may be involved in some of the anti-addiction benefits resulting from ketamine. Future research can evaluate whether the psychoactive effects of ketamine influence improvements in larger samples.

Dakwar, E., Anerella, C., Hart, C. L., Levin, F. R., Mathew, S. J., & Nunes, E. V. (2014). Therapeutic infusions of ketamine: Do the psychoactive effects matter?. Drug and alcohol dependence, 136, 153-157. http://dx.doi.org/10.1016/j.drugalcdep.2013.12.019

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Do the dissociative side effects of ketamine mediate its antidepressant effects?

/ Depressive Disorders, Ketamine, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications / / , , , , , , ,

Abstract

Background

The N-methyl-d-aspartate receptor antagonist ketamine has rapid antidepressant effects in major depression. Psychotomimetic symptoms, dissociation and hemodynamic changes are known side effects of ketamine, but it is unclear if these side effects relate to its antidepressant efficacy.

Methods

Data from 108 treatment-resistant inpatients meeting criteria for major depressive disorder and bipolar disorder who received a single subanesthetic ketamine infusion were analyzed. Pearson correlations were performed to examine potential associations between rapid changes in dissociation and psychotomimesis with the Clinician-Administered Dissociative States Scale (CADSS) and Brief Psychiatric Rating Scale (BPRS), respectively, manic symptoms with Young Mania Rating Scale (YMRS), and vital sign changes, with percent change in the 17-item Hamilton Depression Rating scale (HDRS) at 40 and 230 min and Days 1 and 7.

Results

Pearson correlations showed significant association between increased CADSS score at 40 min and percent improvement with ketamine in HDRS at 230 min (r=−0.35, p=0.007) and Day 7 (r=−0.41, p=0.01). Changes in YMRS or BPRS Positive Symptom score at 40 min were not significantly correlated with percent HDRS improvement at any time point with ketamine. Changes in systolic blood pressure, diastolic blood pressure, and pulse were also not significantly related to HDRS change.

Limitations

Secondary data analysis, combined diagnostic groups, potential unblinding.

Conclusions

Among the examined mediators of ketamine׳s antidepressant response, only dissociative side effects predicted a more robust and sustained antidepressant. Prospective, mechanistic investigations are critically needed to understand why intra-infusion dissociation correlates with a more robust antidepressant efficacy of ketamine.

Luckenbaugh, D. A., Niciu, M. J., Ionescu, D. F., Nolan, N. M., Richards, E. M., Brutsche, N. E., … & Zarate, C. A. (2014). Do the dissociative side effects of ketamine mediate its antidepressant effects?. Journal of affective disorders, 159, 56-61. http://dx.doi.org/10.1016/j.jad.2014.02.017

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MDMA decreases the effects of simulated social rejection

/ Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / / , , ,

Abstract

3-4-Methylenedioxymethamphetamine (MDMA) increases self-reported positive social feelings and decreases the ability to detect social threat in faces, but its effects on experiences of social acceptance and rejection have not been determined. We examined how an acute dose of MDMA affects subjective and autonomic responses to simulated social acceptance and rejection. We predicted that MDMA would decrease subjective responses to rejection. On an exploratory basis, we also examined the effect of MDMA on respiratory sinus arrhythmia (RSA), a measure of parasympathetic cardiac control often thought to index social engagement and emotional regulation. Over three sessions, healthy adult volunteers with previous MDMA experience (N = 36) received capsules containing placebo, 0.75 or 1.5 mg/kg of MDMA under counter-balanced double-blind conditions. During expected peak drug effect, participants played two rounds of a virtual social simulation task called “Cyberball” during which they experienced acceptance in one round and rejection in the other. During the task we also obtained electrocardiograms (ECGs), from which we calculated RSA. After each round, participants answered questionnaires about their mood and self-esteem. As predicted, MDMA decreased the effect of simulated social rejection on self-reported mood and self-esteem and decreased perceived intensity of rejection, measured as the percent of ball tosses participants reported receiving. Consistent with its sympathomimetic properties, MDMA decreased RSA as compared to placebo. Our finding that MDMA decreases perceptions of rejection in simulated social situations extends previous results indicating that MDMA reduces perception of social threat in faces. Together these findings suggest a cognitive mechanism by which MDMA might produce pro-social behavior and feelings and how the drug might function as an adjunct to psychotherapy. These phenomena merit further study in non-simulated social environments.

Frye, C. G., Wardle, M. C., Norman, G. J., & de Wit, H. (2014). MDMA decreases the effects of simulated social rejection. Pharmacology Biochemistry and Behavior, 117, 1-6. https://dx.doi.org/10.1016/j.pbb.2013.11.030

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The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs

/ LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / / , , , , , , ,

Abstract

Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of “primary states” is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit “criticality,” i.e., the property of being poised at a “critical” point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetized state.

Carhart-Harris, R. L., Leech, R., Hellyer, P. J., Shanahan, M., Feilding, A., Tagliazucchi, E., Chialvo, D. R., & Nutt, D. (2014). The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Frontiers in Human Neuroscience, 8, 1-22. http://dx.doi.org/10.3389/fnhum.2014.00020
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New study may explain magic mushrooms' effects

/ Mushrooms / Psilocybin /

New research by a group of mainly Britisch scientists, based on fMRI brain scans, has shown that the use of psilocybin (the active constituent of magic mushrooms) decreases the activity of certain parts of the brain in test subjects. Brain activity decreased especially in those parts that are involved in the managing and filtering of information.

This may explain why users often report that under the influence of magic mushrooms they experience impressions and feelings that were previously unnoticed. Logically, when the brain’s ability to filter and handle information is decreased, more information may reach our consciousness. This may also explain why users often report new insights after the use of magic mushrooms, sometimes having therapeutic effects.

Another indication for the therapeutic effects of magic mushrooms is that brain activity also decreased in the medial prefrontal cortex, a brain part that is often hyperactive in patients suffering from depression.

Remarkably, these new results confirm the ideas of Aldous Huxley (1894-1963). Huxley saw the brain as a ‘reducing valve’, filtering and making information more manageable for our consciousness. He posed that psychedelic drugs might decrease these reducing properties of the brain.

Click here for the abstract and a link to the full article.

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Nieuwe studie verklaart mogelijk effecten 'paddo's'

/ Uncategorized /

Uit nieuw onderzoek van een groep van vooral Britse wetenschappers, op basis van fMRI-hersenscans, is gebleken dat het innemen van psilocybine (de werkzame stof in paddo’s) bij proefpersonen de activiteit in bepaalde hersendelen vermindert. Dit geldt vooral voor de hersendelen die betrokken zijn bij het kanaliseren en filteren van informatie.

Dit verklaart wellicht waarom gebruikers vaak melden dat ze onder invloed van paddo’s indrukken en gevoelens ervaren die normaal gesproken voor ze verborgen blijven. Wanneer door de hersenen informatie minder goed gefilterd en gestuurd wordt, kunnen immers meer indrukken ons bewustzijn bereiken. Ook kan dit wellicht verklaren waarom gebruikers na het gebruik van paddo’s vaak nieuwe inzichten melden, soms met therapeutisch effect.

Een andere aanwijzing voor het therapeutische effect van psilocybine, is dat in dit onderzoek bleek dat de activiteit van de mediale prefrontale cortex afnam na het toedienen van psilocybine, een hersengebied dat bij depressieve mensen juist extra actief is.

Deze nieuwe resultaten komen opvallend overeen met de ideeën van Aldous Huxley (1894-1963). Huxley zag het brein vooral als een instrument dat informatie voor het bewustzijn behapbaar maakt, en stelde dat psychedelische middelen deze filterende functie van het brein tijdelijk doen verminderen.

Klik hier voor de abstract van de studie en een linke naar de volledige tekst.

Nieuwe studie verklaart mogelijk effecten 'paddo's' Read More »

Nieuwe studie verklaart mogelijk effecten ‘paddo’s’

/ Uncategorized /

Uit nieuw onderzoek van een groep van vooral Britse wetenschappers, op basis van fMRI-hersenscans, is gebleken dat het innemen van psilocybine (de werkzame stof in paddo’s) bij proefpersonen de activiteit in bepaalde hersendelen vermindert. Dit geldt vooral voor de hersendelen die betrokken zijn bij het kanaliseren en filteren van informatie.

Dit verklaart wellicht waarom gebruikers vaak melden dat ze onder invloed van paddo’s indrukken en gevoelens ervaren die normaal gesproken voor ze verborgen blijven. Wanneer door de hersenen informatie minder goed gefilterd en gestuurd wordt, kunnen immers meer indrukken ons bewustzijn bereiken. Ook kan dit wellicht verklaren waarom gebruikers na het gebruik van paddo’s vaak nieuwe inzichten melden, soms met therapeutisch effect.

Een andere aanwijzing voor het therapeutische effect van psilocybine, is dat in dit onderzoek bleek dat de activiteit van de mediale prefrontale cortex afnam na het toedienen van psilocybine, een hersengebied dat bij depressieve mensen juist extra actief is.

Deze nieuwe resultaten komen opvallend overeen met de ideeën van Aldous Huxley (1894-1963). Huxley zag het brein vooral als een instrument dat informatie voor het bewustzijn behapbaar maakt, en stelde dat psychedelische middelen deze filterende functie van het brein tijdelijk doen verminderen.

Klik hier voor de abstract van de studie en een linke naar de volledige tekst.

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Women and Psychedelics: Cycles, Care, and Conditions - October 23rd

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