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The Heffter Research Institute: Past and Hopeful Future

/ Anxiety Disorders / PTSD, Mushrooms / Psilocybin, Papers, Publications, Substance Use Disorder / /

Abstract

This essay describes the founding of the Heffter Research Institute in 1993 and its development up to the present. The Institute is the only scientific research organization dedicated to scientific research into the medical value of psychedelics, and it has particularly focused on the use of psilocybin. The first clinical treatment study was of the value of psilocybin in obsessive-compulsive disorder. Next was a UCLA study of psilocybin to treat end-of-life distress in end-stage cancer patients. While that study was ongoing, a trial was started at Johns Hopkins University (JHU) to study the efficacy of psilocybin in treating anxiety and depression resulting from a cancer diagnosis. Following the successful completion of the UCLA project, a larger study was started at New York University, which is near completion. A pilot study of the value of psilocybin in treating alcoholism at the University of New Mexico also is nearing completion, with a larger two-site study being planned. Other studies underway involve the use of psilocybin in a smoking cessation program and a study of the effects of psilocybin in long-term meditators, both at JHU. The institute is now planning for a Phase 3 clinical trial of psilocybin to treat distress in end-stage cancer patients.

Nichols, D. E. (2014). The Heffter Research Institute: Past and Hopeful Future. Journal of Psychoactive Drugs, 46(1), 20–26. http://dx.doi.org/10.1080/02791072.2014.873688
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Self-Experimentations with Psychedelics Among Mental Health Professionals: LSD in the Former Czechoslovakia

/ LSD, Papers, Psychology, Publications / / ,

Abstract

This article enquires into auto-experiments with psychedelics. It is focused on the experiences and current attitudes of mental health professionals who experimented with LSD in the era of legal research of this substance in the former Czechoslovakia. The objective of the follow-up study presented was to assess respondents’ long-term views on their LSD experience(s). A secondary objective was to capture the attitude of the respondents toward the use of psychedelics within the mental health field. A total of 22 individuals participated in structured interviews. None of the respondents reported any long-term negative effect and all of them except two recorded enrichment in the sphere of self-awareness and/or understanding to those with mental disorder(s). Although there were controversies with regard to the ability of preventing possible negative consequences, respondents were supportive towards self-experiments with LSD in mental health sciences. This article is the first systematic examination of the self-experimentation with psychedelics that took place east of the Iron Curtain.

Winkler, P., & Csémy, L. (2014). Self-Experimentations with Psychedelics Among Mental Health Professionals: LSD in the Former Czechoslovakia. Journal of Psychoactive Drugs, 46(1), 11–19. http://dx.doi.org/10.1080/02791072.2013.873158
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From Hofmann to the Haight Ashbury, and into the Future: The Past and Potential of Lysergic Acid Diethlyamide

/ LSD, Papers, Psychology, Publications / / , ,

Abstract

Since the discovery of its psychedelic properties in 1943, lysergic acid diethylamide (LSD) has been explored by psychiatric/therapeutic researchers, military/intelligence agencies, and a significant portion of the general population. Promising early research was halted by LSD’s placement as a Schedule I drug in the early 1970s. The U.S. Army and CIA dropped their research after finding it unreliable for their purposes. NSDUH estimates that more than 22 million (9.1% of the population) have used LSD at least once in their lives. Recently, researchers have been investigating the therapeutic use of LSD and other psychedelics for end-of-life anxiety, post-traumatic stress disorder (PTSD), cancer, and addiction treatment. Adverse psychedelic reactions can be managed using talkdown techniques developed and in use since the 1960s.

Smith, D. E., Raswyck, G. E., & Leigh Dickerson Davidson, L. (2014). From Hofmann to the Haight Ashbury, and into the Future: The Past and Potential of Lysergic Acid Diethlyamide. Journal of Psychoactive Drugs, 46(1), 3–10. http://dx.doi.org/10.1080/02791072.2014.873684
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Hofmann’s wens komt uit

/ Uncategorized /

Na 40 jaar zonder onderzoek, lijken de resultaten van een recente pilotstudie vervolgonderzoek naar het gebruik van lyserginezuurdiëthylamide (LSD) als hulpmiddel bij psychotherapie te rechtvaardigen. Gasser et al. (2014) onderzochten of LSD in combinatie met psychotherapie doodsangst, gerelateerd aan een levensbedreigende ziekte, kon verminderen.

De participanten in de dubbel-blinde, gerandomiseerde, actieve placebo-gecontroleerde studie werden geselecteerd uit een populatie van patiënten die gediagnosticeerd waren met een levensbedreigende ziekte. De participanten werden willekeurig verdeeld over twee groepen (milde-dosis placebo-gecontroleerd, matige-dosis experimentele groep) en ondergingen twee therapeutische sessies met LSD ter aanvulling op de psychotherapeutische sessies. Aan degenen die aanvankelijk waren ingedeeld bij de milde-dosis placebo gecontroleerde groep, werd aangeboden om deel te nemen in een tweede serie sessies met matige dosis LSD (open-label crossover groep). Het belangrijkste resultaat uit het onderzoek was dat, met elke cumulatieve LSD sessie, de mate van angst afnam bij de participanten in de groep die een matige dosis ontving, maar niet in de groep met de lage dosis. In laatstgenoemde groep herhaalde dit patroon zich tijdens de deelname aan de tweede serie sessies waarin de matige dosis werd aangeboden aan de patiënten. De voordelen van de met LSD-gecombineerde psychotherapie leken zich langdurig te manifesteren. Hoewel er volgens de onderzoekers nog een hoop te winnen is wat betreft de wetenschappelijke betrouwbaarheid en validiteit (zoals zij zelf al aangeven een grotere steekproef en een minder eenvoudig te discrimineren placebo), kan er op basis van de reacties van de patiënten gesteld worden dat het klinische onderzoek geslaagd is. Het merendeel gaf aan dat ze de voorkeur zouden hebben voor meer dan twee LSD sessies en een langere behandelperiode.

Niet alleen leverde het onderzoek veelbelovende resultaten op over het controversiële gebruik van een als Schedule 1 geclassificeerd middel (21 U.S.C. § 812) in een therapeutische setting, de publicatie ontving ook internationale media-aandacht (Carey, 2014; Healey, 2014; Connor, 2014), wat een toename van de publieke interesse in onderzoek naar psychedelica suggereert. Hoewel de psychoactieve effecten van LSD al snel na ontdekking als zeer waardevol werden beschouwd voor experimenteel onderzoek en psychiatrische behandeling (Passie, Halpern, Stichtenoth, Emrich, & Hintzen, 2008), was de reputatie van dit middel de afgelopen 40 jaar vooral dat van een gevaarlijke drug (SAMHSHA, 2008). In navolging van een recent klinisch onderzoek met psilocybine (Grob et al., 2011), draagt de huidige studie bij aan een heropleving van een wetenschappelijke stroming die het belang van psychedelica als instrument voor psychiatrisch onderzoek erkent. Met de hervatting van onderzoek naar het therapeutisch potentieel van LSD, hopen de onderzoekers een ‘levenslange wens te hebben vervuld’ van zijn schepper, Albert Hofmann, aan wie het artikel van dit onderzoek is opgedragen.

 
Referenties
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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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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Psyche & Praxis Forum: Working at the Edge of Medicine and Mysticism - January 29

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