OPEN Foundation

T. Passie

Reviewing the Potential of Psychedelics for the Treatment of PTSD.

Abstract

There are few medications with demonstrated efficacy for the treatment of posttraumatic stress disorder (PTSD). Treatment guidelines have unequivocally designated psychotherapy as a first line treatment for PTSD. Yet, even after psychotherapy, PTSD often remains a chronic illness, with high rates of psychiatric and medical comorbidity. Meanwhile, the search and development of drugs with new mechanisms of action has stalled. Therefore, there is an urgent need to explore not just novel compounds, but novel approaches for the treatment of PTSD. A promising new approach involves the use of psychedelic drugs. Within the past few years, two psychedelics have received breakthrough designations for psychiatric indications from the US Food and Drug Administration, and several psychedelics are currently being investigated for the treatment of PTSD. This review discusses four types of compounds: 3,4-methylenedioxymethamphetamine (MDMA), ketamine, classical psychedelics (e.g. psilocybin and LSD) and cannabinoids. We describe the therapeutic rationale, the setting in which they are being administered, and their current state of evidence in the treatment of PTSD. Each compound provides unique qualities for the treatment of PTSD, from their use to rapidly target symptoms, to their use as adjuncts to facilitate psychotherapeutic treatments. Several questions are formulated that outline an agenda for future research.
Krediet, E., Bostoen, T., Breeksema, J., van Schagen, A., Passie, T., & Vermetten, E. (2020). Reviewing the Potential of Psychedelics for the Treatment of PTSD. International Journal of Neuropsychopharmacology., https://doi.org/10.1093/ijnp/pyaa018
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Self-Experiments with Psychoactive Substances: A Historical Perspective

Abstract

The purpose of this chapter is to highlight the rich tradition of self-experiments (SEs) with psychoactive substances carried out by scientists and therapists for more than a century. Scientifically inspired controlled SEs dominated until the end of the twentieth century, when ethical requirements minimized controlled SEs and “wild” SEs expanded particularly with the emergence of new psychoactive substances. The review focuses on laughing gas (nitrous oxide), cannabis, cocaine, hallucinogens, entactogens, and dissociative hallucinogens. This is due to the fact that substances that induce “complex” effects such as alteration of space/time experience, ego dissolution, and increased feelings and insights (e.g., hallucinogens, entactogens) represent by far the majority of SEs, whereas SEs with substances inducing “simple” effects such as euphoria, anxiolysis, dissociation, or emotional blunting (e.g., cocaine, opioids) are much rarer or even absent (e.g., benzodiazepines). Complex drug effects are much harder to describe, thus allowing SEs to fulfill a more important function.

SEs with psychoactive drugs appeared to emerge in the mid-eighteenth century, which triggered a long-standing tradition throughout the nineteenth and early twentieth century. SEs have been de facto performed for a variety of reasons, ranging from establishing scientific knowledge and gaining philosophical insights to compensating for personal deficits. Self-experimenters can be divided into two general types. Besides their scientific intentions, “exploratory” self-experimenters intend to expand awareness and insight, whereas “compensatory” self-experimenters might aim for coping with psychiatric symptoms or personality deficits. Scientific limitations of SEs are obvious when compared to double-blind, randomized, placebo-controlled trials. Whereas the former might lead to more “realistic” detailed description of subjective effects, the latter lead to more solid results in respect to objectively measurable “average” effects. Possible adverse effects of SEs were identified that resulted in loss of scientific objectivity and decreased control over substance use and addiction, development of isolation, problematic group dynamics, and “social autism.”

Passie, T., & Brandt, S. D. (2018). Self-Experiments with Psychoactive Substances: A Historical Perspective., 10.1007/164_2018_177
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The early use of MDMA (‘Ecstasy’) in psychotherapy (1977–1985)

3,4-Methylenedioxymethamphetamine (MDMA), also known as ecstasy, was first synthesized in 1912 but first reached widespread popularity as a legal alternative after the much sought-after recreational drug 3,4-methylenedioxy-amphetamine (MDA) was made illegal in 1970. Because of its benign, feeling-enhancing, and nonhallucinatory properties, MDMA was used by a few dozen psychotherapists in the United States between 1977 and 1985, when it was still legal. This article looks into the contexts and practices of its psychotherapeutic use during these years. Some of the guidelines, recommendations, and precautions developed then are similar to those that apply to psychedelic drugs, but others are specific for MDMA. It is evident from this review that the therapists pioneering the use of MDMA were able to develop techniques (and indications/counterindications) for individual and group therapy that laid the groundwork for the use of MDMA in later scientific studies. In retrospect, it appears that the perceived beneficial effects of MDMA supported a revival of psycholytic/psychedelic therapy on an international scale.
Passie, T. (2018). The early use of MDMA (‘Ecstasy’) in psychotherapy (1977–1985). Drug Science, Policy and Law4, 2050324518767442., 10.1177/2050324518767442
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MDA, MDMA and other mescaline-like substances in the US military's search for a truth drug (1940s to 1960s)

Abstract

This article describes the broader context in which 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and other mescaline-like compounds were explored as hallucinogens for military and intelligence purposes during the 1940s to the 1960s. Germans first tested mescaline as a “truth drug” in a military context. Since the 1940s, the United States military tested hallucinogenic drugs as “truth drugs” for the purpose of interrogation and behavior manipulation. After tests carried out using mescaline and other drugs in 1950, some derivatives of mescaline were synthesized by the Army for the exploration of possible „speech-inducing“ effects. After insufficient animal testing, the substances were given to patients at the New York State Psychiatric Institute (NYSPI). 3,4-Methylenedioxy-N-ethylamphetamine (MDE), a compound almost identical to MDMA, was among the mescaline derivatives delivered for testing at the NYSPI. During tests with other derivatives (3,4-dimethoxyphenethylamine (DMA), 3,4-methylenedioxyphenethylamine (MDPEA), MDA) in 1952-53, an unwitting patient died in these tests, which was kept secret from the public. Research was interrupted and toxicological animal testing procedures were initiated. The secret animal studies run in 1953/54 revealed that some of the “mescaline derivatives” tested (e.g. MDA, MDE, DMA, 3,4,5-trimethoxyamphetamine (TMA), MDMA) were considered for further testing in humans. Since 1955, the military changed focus to LSD, but some interest in mescaline-like compounds remained for their ability to change mood and habit without interefing with cognition and sensory perception. Based on the known documents, it remains unclear (but probable) wether any of the mescaline derivatives tested were being used operationally.
Passie, T., & Benzenhöfer, U. (2017). MDA, MDMA and other mescaline‐like substances in the US military’s search for a truth drug (1940s to 1960s). Drug testing and analysis. 10.1002/dta.2292
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MDA, MDMA and other mescaline-like substances in the US military’s search for a truth drug (1940s to 1960s)

Abstract

This article describes the broader context in which 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and other mescaline-like compounds were explored as hallucinogens for military and intelligence purposes during the 1940s to the 1960s. Germans first tested mescaline as a “truth drug” in a military context. Since the 1940s, the United States military tested hallucinogenic drugs as “truth drugs” for the purpose of interrogation and behavior manipulation. After tests carried out using mescaline and other drugs in 1950, some derivatives of mescaline were synthesized by the Army for the exploration of possible „speech-inducing“ effects. After insufficient animal testing, the substances were given to patients at the New York State Psychiatric Institute (NYSPI). 3,4-Methylenedioxy-N-ethylamphetamine (MDE), a compound almost identical to MDMA, was among the mescaline derivatives delivered for testing at the NYSPI. During tests with other derivatives (3,4-dimethoxyphenethylamine (DMA), 3,4-methylenedioxyphenethylamine (MDPEA), MDA) in 1952-53, an unwitting patient died in these tests, which was kept secret from the public. Research was interrupted and toxicological animal testing procedures were initiated. The secret animal studies run in 1953/54 revealed that some of the “mescaline derivatives” tested (e.g. MDA, MDE, DMA, 3,4,5-trimethoxyamphetamine (TMA), MDMA) were considered for further testing in humans. Since 1955, the military changed focus to LSD, but some interest in mescaline-like compounds remained for their ability to change mood and habit without interefing with cognition and sensory perception. Based on the known documents, it remains unclear (but probable) wether any of the mescaline derivatives tested were being used operationally.
Passie, T., & Benzenhöfer, U. (2017). MDA, MDMA and other mescaline‐like substances in the US military’s search for a truth drug (1940s to 1960s). Drug testing and analysis. 10.1002/dta.2292
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The History of MDMA as an Underground Drug in the United States, 1960-1979

Abstract

MDMA (3,4-methylenedioxy-methylamphetamine, a.k.a. “ecstasy”) was first synthesized in 1912 and resynthesized more than once for pharmaceutical reasons before it became a popular recreational drug. Partially based on previously overlooked U.S. government documentation, this article reconstructs the early history of MDMA as a recreational drug in the U.S. from 1960 to 1979. According to the literature, MDMA was introduced as a street drug at the end of the 1960s. The first forensic detection of MDMA “on the street” was reported in 1970 in Chicago. It appears that MDMA was first synthesized by underground chemists in search of “legal alternatives” for the closely related and highly sought-after drug MDA, which was scheduled under the Controlled Substances Act (CSA) in 1970. Until 1974, nearly all MDMA street samples seized came from the U.S. Midwest, the first “hot region” of MDMA use. In Canada, MDMA was first detected in 1974 and scheduled in 1976. From 1975 to 1979, MDMA was found in street samples in more than 10 U.S. states, the West Coast becoming the major “hot region” of MDMA use. Recreational use of MDMA spread across the U.S. in the early 1980s, and in 1985 it was scheduled under the CSA.

Passie, T., & Benzenhöfer, U. (2016). The history of MDMA as an underground drug in the United States, 1960–1979. Journal of psychoactive drugs48(2), 67-75., 10.1080/02791072.2015.1128580

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LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects

Abstract

Objective: A recently published study showed the safety and efficacy of LSD-assisted psychotherapy in patients with anxiety associated with life-threatening diseases. Participants of this study were included in a prospective follow-up.

Method: 12 months after finishing LSD psychotherapy, 10 participants were tested for anxiety (STAI) and participated in a semi-structured interview. A Qualitative Content Analysis (QCA) was carried out on the interviews to elaborate about LSD effects and lasting psychological changes.

Results: None of the participants reported lasting adverse reactions. The significant benefits as measured with the STAI were sustained over a 12-month period. In the QCA participants consistently reported insightful, cathartic and interpersonal experiences, accompanied by a reduction in anxiety (77.8%) and a rise in quality of life (66.7%). Evaluations of subjective experiences suggest facilitated access to emotions, confrontation of previously unknown anxieties, worries, resources and intense emotional peak experiences à la Maslow as major psychological working mechanisms. The experiences created led to a restructuring of the person’s emotional trust, situational understanding, habits and world view.

Conclusions: LSD administered in a medically supervised psychotherapeutic setting can be safe and generate lasting benefits in patients with a life-threatening disease. Explanatory models for the therapeutic effects of LSD warrant further study.

Gasser, P., Kirchner, K., & Passie, T. (2014). LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects. Journal of Psychopharmacology. https://dx.doi.org/10.1177/0269881114555249
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Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases

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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Research on psychedelic substances

Introduction

The term psychedelic (i.e. mind-manifesting) was coined by Humphrey Osmond to characterize a grou p of substances that are capable of liberating human perception from cultural conditioning, providing an op ening to the transcendent qualities of being human. Osmond claimed that LSD and similar drugs may give people insightful experiences that enable them to better understand themselves and their relationships with the world. Psychedelic substances have the potential to show mindmanifesting properties under appropriate internally and externally supported conditions. They can offer lucid insights into ones psychological make-up and functioning. They are also capable of inducing a spectrum of inner experiences, sometimes
referred to as religious or mystical. Another commonly used term for these substances is hallucinogens, although this synonym is viewed as controversial because of the implication that they somehow cause hallucinations, which they do very rarely. Most psychedelic substances produce visual alterations of perceived objects and pseudohallucinations which are understood by the subject to be illusionary in character […]
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Brandt, S. D., & Passie, T. (2012). Research on psychedelic substances. Drug testing and analysis4(7-8), 539-542. https://dx.doi.org/10.1002/dta.1389
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Genuine and drug-induced synesthesia: a comparison

Abstract

Despite some principal similarities, there is no systematic comparison between the different types of synesthesia (genuine, acquired and drug-induced). This comprehensive review compares the three principal types of synesthesia and focuses on their phenomenological features and their relation to different etiological models. Implications of this comparison for the validity of the different etiological models are discussed.

Comparison of the three forms of synesthesia show many more differences than similarities. This is in contrast to their representation in the literature, where they are discussed in many respects as being virtually similar. Noteworthy is the much broader spectrum and intensity with the typical drug-induced synesthesias compared to genuine and acquired synesthesias. A major implication of the phenomenological comparison in regard to the etiological models is that genuine and acquired synesthesias point to morphological substrates, while drug-induced synesthesia appears to be based on functional changes of brain activity.

Sinke, C., Halpern, J. H., Zedler, M., Neufeld, J., Emrich, H. M., & Passie, T. (2012). Genuine and drug-induced synesthesia: a comparison. Consciousness and cognition, 21(3), 1419-1434. http://dx.doi.org/10.1016/j.concog.2012.03.009
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13 June - Near Death Experiences & Psychedelic Experiences

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