The Journal of Nervous and Mental Disease
March 4, 2014
Peter Gasser, Dominique Holstein, Yvonne Michel et al.
752 citations
In a small pilot study, 12 patients with anxiety related to life-threatening diseases underwent two sessions of LSD-assisted psychotherapy, receiving either a full 200-microgram dose or a low 20-microgram active placebo, with the placebo group later crossing over to the full dose. At a 2-month follow-up, trait anxiety decreased with a large effect size, and state anxiety also dropped significantly. These anxiety reductions persisted for 12 months. No serious adverse effects occurred beyond one day after treatment. The findings suggest that, under careful medical supervision, LSD can reduce anxiety, supporting the need for larger controlled trials.
Addiction Biology
October 1, 2002
Torsten Passie, Juergen Seifert, Udo Schneider et al.
465 citations
Psilocybin, the main psychoactive alkaloid in certain mushrooms found worldwide, is increasingly abused as a hallucinogenic drug. Although it was used experimentally in medicine during the 1960s, pharmacological information about it remained scarce until recently. This review compiles all available pharmacological data on psilocybin, addressing the ongoing abuse potential and the need for comprehensive knowledge.
CNS Neuroscience & Therapeutics
November 11, 2008
Torsten Passie, John H. Halpern, Dirk O. Stichtenoth et al.
459 citations
Lysergic acid diethylamide (LSD) was synthesized in 1938 and its psychoactive effects discovered in 1943. It was used in psychiatric research during the 1950s and 1960s to produce experimental psychosis and in psycholytic and psychedelic therapy. After becoming an illegal drug of abuse from the mid-1960s, scientific interest has resumed with new methods and oversight. This review covers all aspects of LSD's pharmacology and psychopharmacology, based on nearly 10,000 scientific papers. LSD is physiologically well tolerated and psychological reactions can be controlled in a medical setting, but uncontrolled use risks complications. New interest focuses on LSD as a tool for studying consciousness and potential treatments for cluster headache and terminally ill patients.
Journal of Psychopharmacology
November 11, 2014
Peter Gasser, Katharina Kirchner, Torsten Passie
458 citations
In patients with anxiety linked to life-threatening diseases, LSD-assisted psychotherapy produced lasting benefits. Twelve months after treatment, none of the ten participants reported adverse reactions, and significant reductions in anxiety (measured by the STAI) were sustained. Qualitative interviews revealed that most participants experienced insightful, cathartic, and interpersonal encounters; 77.8% reported reduced anxiety and 66.7% reported improved quality of life. Subjective accounts pointed to facilitated access to emotions, confrontation of unknown anxieties and resources, and intense peak experiences as key psychological mechanisms. These experiences helped restructure emotional trust, situational understanding, habits, and worldview. The findings suggest that medically supervised LSD therapy can be safe and yield enduring benefits.
The International Journal of Neuropsychopharmacology
March 12, 2020
Erwin Krediet, Tijmen Bostoen, Joost J. Breeksema et al.
262 citations
Posttraumatic stress disorder (PTSD) often remains chronic after psychotherapy, and few effective medications exist. A promising new approach involves psychedelic drugs. This review discusses four compound types: MDMA, ketamine, classical psychedelics (psilocybin, LSD), and cannabinoids. It describes each compound's therapeutic rationale, administration setting, and current evidence for treating PTSD. Each offers unique qualities, from rapidly targeting symptoms to facilitating psychotherapy. The review outlines questions for future research.
Drug Science Policy and Law
January 1, 2018
Torsten Passie
115 citations
MDMA, also known as ecstasy, was first made in 1912 but became popular as a legal substitute for the illegal recreational drug MDA in 1970. Between 1977 and 1985, while still legal, a few dozen psychotherapists in the United States used MDMA for its benign, feeling-enhancing, and nonhallucinatory properties. This article examines the contexts and practices of that psychotherapeutic use. Some guidelines and precautions developed then are similar to those for psychedelic drugs, while others are specific to MDMA. The pioneering therapists developed techniques for individual and group therapy that laid the groundwork for later scientific studies, and the perceived beneficial effects of MDMA helped revive psycholytic/psychedelic therapy internationally.
Drug Testing and Analysis
June 26, 2012
Torsten Passie, H. M. Emrich, Matthias Karst et al.
114 citations
A 19-year-old male with severe PTSD symptoms, including flashbacks, panic attacks, and self-mutilation, experienced dramatic symptom reduction after smoking cannabis resin. This review examines clinical and preclinical neurobiological evidence for cannabis's effects on PTSD. Cannabis may reduce the strength and emotional impact of traumatic memories through synergistic mechanisms, potentially aiding sleep, reducing anxiety, and lessening flashback involvement. Endocannabinoid signaling systems in stress-sensitive brain regions like the hypothalamus and amygdala suggest their role in regulating stress responses. Evidence increasingly indicates cannabinoids may play a role in fear extinction and have antidepressive effects. Further studies are needed to evaluate cannabinoids' therapeutic potential in PTSD.
Cephalalgia
March 26, 2010
Matthias Karst, John H. Halpern, Michael Bernateck et al.
104 citations
Cluster headache is a severe, one-sided headache condition affecting 0.1% of people. Standard treatments like oxygen and sumatriptan can fail, and surgical options carry serious risks. An internet survey of 53 patients suggested that the hallucinogens psilocybin and LSD may abort attacks and extend remission better than standard drugs, but these substances are criminalized. To test whether a non-hallucinogenic LSD analog could also help, researchers investigated 2-bromo-LSD (BOL-148). Past studies found BOL-148 non-toxic and non-hallucinogenic, with only mild side effects at the dose used, and no long-term effects in over 300 healthy subjects or in schizophrenic women given 30mg daily for weeks.
Frontiers in Psychiatry
December 2, 2022
Torsten Passie, Jeffrey Guss, Rainer Krähenmann
71 citations
Lysergic acid diethylamide (LSD) and similar psychoactive drugs have been used in psychotherapy since 1949, when the first clinical study with lower-dose LSD showed therapeutically relevant effects. Psycholytic therapy, named in 1960, involved serial lower-dose LSD or psilocybin sessions within a psychoanalytical framework, conducted in clinical settings on both inpatient and outpatient bases. Over 15 years, it was established at 30 clinical treatment centers and by more than 100 outpatient psychotherapists in Europe, while North America favored high-dose psychedelic therapy. Professor Hanscarl Leuner in Germany was the leading figure, providing a detailed analysis of the LSD reaction in a 1962 monograph. The article reviews evidence for psycholytic therapy's efficacy and argues for its inclusion in substance-assisted psychotherapy.
Addiction
August 1, 2010
Udo Benzenhöfer, Torsten Passie
69 citations
Alexander Shulgin is often called the 'father' of MDMA, but a re-assessment of his original publications and laboratory notebook shows he did not synthesize or try MDMA in 1965 as his book PIHKAL suggests. He learned of its special effects in the mid-1970s, re-synthesized it, and first tried it in September 1976. In 1977 he gave MDMA to psychotherapist Leo Zeff, who then introduced it to other therapists. Shulgin also co-authored the first paper on MDMA's pharmacological action in humans in 1978. These contributions explain why he is sometimes erroneously called the 'father' of MDMA, though he was not the first to synthesize it.
Journal of Psychoactive Drugs
March 3, 2016
Torsten Passie, Udo Benzenhöfer
56 citations
MDMA, also known as ecstasy, was first synthesized in 1912 and later resynthesized for pharmaceutical reasons before becoming a popular recreational drug. Drawing on previously overlooked U.S. government documents, this article traces MDMA's early recreational history in the U.S. from 1960 to 1979. MDMA appeared as a street drug in the late 1960s, with the first forensic detection in 1970 in Chicago. Underground chemists likely synthesized it as a legal alternative to MDA, which was scheduled under the Controlled Substances Act in 1970. Until 1974, nearly all seized MDMA street samples came from the U.S. Midwest, the first hot region of use. In Canada, MDMA was first detected in 1974 and scheduled in 1976.
Drug Testing and Analysis
August 29, 2017
Torsten Passie, Udo Benzenhöfer
43 citations
From the 1940s to the 1960s, the United States military explored mescaline and related compounds such as MDA, MDMA, and MDE as potential truth drugs for interrogation and behavior manipulation, following earlier German tests with mescaline. After animal testing, some derivatives were given to patients at the New York State Psychiatric Institute. During tests in 1952–53, an unwitting patient died, a fact kept secret. Subsequent secret animal studies in 1953–54 identified several mescaline derivatives for further human testing. By 1955, military focus shifted to LSD, though interest in mescaline-like compounds persisted for their ability to alter mood and habit without disrupting cognition. Whether any were used operationally remains unclear but probable.
Journal of Psychedelic Studies
March 29, 2019
Tom Wolff, Simon Ruffell, Nigel Netzband et al.
41 citations
In a study of nine foreign tourists at an ayahuasca retreat in Peru, the typical structure of spontaneously reported experiences included personal preparation, physical symptoms, visual phenomena, cognitive and emotional phenomena, reactions within the psychedelic world and ordinary reality, and appraisal of the process. Emotional reactions ranged from pleasant (psychotherapeutic target emotions and hedonistic emotions) to unpleasant. For most participants, the presence of psychotherapeutic target emotions seemed to involve unpleasant emotions in the same session, possibly as transitional emotional states. This suggests psychodynamic processes, such as activation of emotional conflicts, can occur spontaneously during ayahuasca intake in this setting. Some participants attributed symbolic meaning to visionary content, more likely among psychotherapeutically motivated clients. The setting and expectations about native wisdom may influence experiences and interpretations.
Drug Testing and Analysis
March 16, 2020
Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal et al.
38 citations
1-Cylopropanoyl-LSD (1CP-LSD), a new lysergamide-based designer drug, was analyzed using multiple chemical and spectroscopic methods. Incubation with human serum converted 1CP-LSD into LSD, suggesting it may act as a prodrug for LSD in the body. In mice, 1CP-LSD induced a head-twitch response (HTR) with an ED50 of 430.0 nmol/kg, comparable to 1P-LSD (ED50 = 349.6 nmol/kg), indicating an LSD-like behavioral profile. The study includes analysis of blotters and pellets, and detected artificially induced degradation products during GC-MS analysis. Clinical studies are needed to determine its potency and effects in humans.
Neuropsychobiology
January 1, 2005
Torsten Passie, Matthias Karst, Birgitt Wiese et al.
35 citations
The first neuropsychological study of the S-enantiomer of ketamine, a noncompetitive NMDA antagonist, found that low and high subanaesthetic doses produced only nonsignificant impairment on most cognitive tasks in 12 healthy male volunteers. However, tasks involving divided and sustained attention, along with objective and subjective psychopathology scores, showed significant impairment that increased with dose. These results suggest that ketamine's effects on attention may model aspects of schizophrenia.
Journal of Pharmaceutical and Biomedical Analysis
May 28, 2019
Christina Grumann, Kerstin Henkel, Alexander Stratford et al.
27 citations
1-propionyl-LSD (1P-LSD), an uncontrolled derivative of LSD, requires sensitive detection methods due to its high potency. A validated LC-MS/MS method quantified 1P-LSD and LSD in urine and serum with a calibration range of 0.015-0.4 ng mL⁻¹ and limits of detection and quantification at 0.005 and 0.015 ng mL⁻¹, respectively. Stability tests showed 1P-LSD remained stable in samples stored at -20 °C, 5 °C, or room temperature for up to five days, but LSD formed at room temperature (up to 21% in serum), likely from enzymatic hydrolysis. Sodium fluoride prevented this conversion. In an intoxication case, only LSD was detected: 0.51 ng mL⁻¹ in urine and 3.4 ng mL⁻¹ in serum, suggesting rapid in-vivo hydrolysis of 1P-LSD to LSD.
Journal of Psychopharmacology
January 1, 2003
Torsten Passie, Matthias Karst, Mathias Borsutzky et al.
27 citations
The NMDA neurotransmitter system's role in psychoses is not fully understood, but NMDA antagonists like phencyclidine and ketamine induce psychotic states similar to schizophrenia. Binocular depth inversion, a visual illusion impaired in psychotic states, was tested in 12 healthy male volunteers using stereoscopic pictures of natural and artificial objects. Two subanaesthetic doses of the psychotomimetic S-enantiomer of ketamine were compared with placebo. Despite dose-dependent subjective and objective psychopathology, no significant impairment of binocular depth perception occurred with (S)-ketamine. The findings suggest implications for memory, perception formation, and bottom-up processing in ketamine model psychosis and schizophrenia.
Drug Testing and Analysis
May 16, 2020
Christina Grumann, Kerstin Henkel, Simon D. Brandt et al.
23 citations
1P-LSD, a non-controlled alternative to LSD, acts as a prodrug that converts almost entirely into LSD in the human body. In two volunteers, oral and intravenous doses of 100 μg 1P-LSD were administered. After oral intake, only LSD was detected in serum and urine, with a terminal elimination half-life of about 6.4 hours. Intravenous 1P-LSD was detectable for only a few hours, while LSD persisted much longer. The bioavailability of LSD from oral 1P-LSD was nearly 100%. Subjective drug effects and altered states of consciousness scores were comparable to those from LSD, supporting the prodrug hypothesis. Oral administration produced higher 5D-ASC scores than intravenous.
Frontiers in Psychology
January 1, 2013
Janina Nielsen, Tillmann H. C. Krüger, Uwe Hartmann et al.
13 citations
People with synaesthesia who experience sensory crossovers during sex—such as seeing colors or feeling textures from arousal—report deeper states of sexual trance but lower sexual satisfaction than those without synaesthesia. Among 19 synaesthetes and 36 controls, synaesthetes scored higher on measures of oceanic boundlessness and visionary restructuralization, indicating more intense altered states during intercourse. They also showed better overall sexual function, particularly in sexual appetite, yet felt less satisfied. Qualitative interviews revealed that the idiosyncratic perceptions can create a sense of isolation. The findings suggest that sexual synaesthesia amplifies trance-like immersion without improving satisfaction.
Journal of Psychedelic Studies
November 9, 2018
Tom Wolff, Torsten Passie
10 citations
Western ayahuasca drinkers who are active in online forums are typically 28–50 years old, hold higher education degrees, have prior experience with other psychedelic drugs and psychospiritual methods, and are motivated to drink ayahuasca again, usually in organized events like shamanic ceremonies or retreats. Their motivation is composed of four main elements: self-exploration, spiritual purposes, physical health issues, and sensation seeking. Self-exploration and spiritual purposes are the dominant reasons, while physical health and sensation seeking are minor. This motivational structure differs from that of local ayahuasca shaman clients in the upper Amazonas region.
Psychology Health & Medicine
November 27, 2012
Torsten Passie, Udo Schneider, Mathias Borsutzky et al.
7 citations
The binocular depth inversion test (BDIT) measures a visual illusion in which implausible objects, such as a hollow face, are perceived as normal and convex. This illusion is common and influenced by familiarity, with cognitive factors overriding binocular disparity cues. The internal mechanism balancing top-down and bottom-up perceptual processes appears disturbed in pro-psychotic states. In this pilot study, patients with anxiety disorders scored significantly higher on the BDIT than matched controls, in a range comparable to pro-psychotic conditions. The findings suggest anxiety patients may have abnormalities in central perceptual processing, top-down processing, and reality testing similar to those seen in pro-psychotic conditions.
Drug testing and analysis
September 1, 2024
Verena Angerer, Yasmin Schmid, Florian Franz et al.
6 citations
In six healthy volunteers, the new psychoactive substance MDAI at 3.0 mg/kg produced subjective effects comparable to 125 mg of MDMA, including increased blood pressure, but did not raise heart rate or body temperature. MDAI increased cortisol and prolactin levels, appeared in serum about 20 minutes after ingestion, and remained detectable for at least 4 days in serum and 6 days in urine. The drug was well tolerated. Further research is needed to evaluate whether MDAI might have medicinal applications.
Journal of psychopharmacology (Oxford, England)
June 10, 2025
Torsten Passie, Anja Loizaga-Velder, Alicia Danforth et al.
4 citations
A consensus-based model curriculum for education and training in substance-assisted psychotherapy (SAP) covers theoretical topics and practical components including apprenticeship observation, ongoing clinical supervision, and self-experience for trainees. The model, developed by authors with extensive SAP experience, also addresses peer and conventional supervision, respect for intercultural differences, and teachings about indigenous use of related substances. It is largely adapted to western industrialized countries with established graduate-level psychotherapy training. The curriculum may be valuable for psychedelic researchers, those training therapists for research studies, and those preparing for clinical work outside research settings.
Drug Science Policy and Law
January 1, 2024
Torsten Passie
4 citations
The so-called psychedelic renaissance has revived interest in therapies using drugs like LSD and psilocybin. In 1960s and 1970s Europe, the dominant approach was psycholytic therapy, which used serial low-dose sessions embedded in long-term psychotherapy, grounded in psychoanalysis. Today, this method is largely neglected in favor of high-dose psychedelic peak therapy with minimal psychotherapy. The European Medical Society for Psycholytic Therapy (EPT), founded in 1965, coordinated LSD therapists, promoted professional exchange, and aimed to develop treatment and training standards, yet its history has been virtually undocumented. The author reconstructs the EPT's history from unique archival resources to inform future standards.
June 29, 2023
Torsten Passie
4 citations
MDMA's history is a mosaic of parallel developments across research, politics, recreational use, and medicine, not a simple linear story. The book traces MDMA from its early pharmaceutical origins after 1900, through its studied military potential and early psychotherapeutic use, to its spread as a recreational drug in Europe and the United States. Later chapters address debates over its toxicity, its global distribution as a dance drug since the 1990s, and recent research into its therapeutic potentials. The account integrates multiple narratives and levels of interaction to make this complex history more intelligible.