Biological Psychiatry
November 29, 2014
Yasmin Schmid, Florian Enzler, Peter Gasser et al.
425 citations
Lysergic acid diethylamide (LSD), a well-known hallucinogen, significantly influenced mood and perception in a recent crossover study involving 60 participants. Those receiving LSD reported a 70% reduction in feelings of derealization and depersonalization compared to a placebo. Additionally, serotonin receptor activity was linked to improved prepulse inhibition, suggesting potential benefits for psychosis and schizophrenia. While heart rate increased by 15% and blood pressure rose moderately, adverse effects remained minimal, highlighting the need for further exploration of psychedelics in clinical psychology and psychiatry.
Social Cognitive and Affective Neuroscience
October 4, 2013
Cédric M. Hysek, Yasmin Schmid, Linda D. Simmler et al.
356 citations
MDMA (ecstasy) enhances emotional empathy and prosocial behavior in men but impairs recognition of negative emotions like fear, anger, and sadness, especially in women. In a placebo-controlled, double-blind crossover trial with 32 healthy volunteers, MDMA increased explicit and implicit emotional empathy on the Multifaceted Empathy Test and boosted prosocial choices on the Social Value Orientation test in men. It did not affect cognitive empathy but worsened identification of negative facial expressions on the Face Emotion Recognition Task, particularly in women. MDMA also raised plasma cortisol, prolactin, and oxytocin levels, markers linked to social behavior. These effects may explain MDMA's recreational sociability and its potential therapeutic use in psychotherapy for social dysfunction or PTSD.
Neuropsychopharmacology
June 1, 2016
Patrick C. Dolder, Yasmin Schmid, Felix Müller et al.
249 citations
LSD acutely enhances feelings of happiness, trust, and closeness to others, increases explicit and implicit emotional empathy, impairs recognition of sad and fearful faces, and boosts prosocial behavior and desire for social interaction. These effects were observed in two placebo-controlled, double-blind, crossover studies with 24 participants receiving 100 μg and 16 receiving 200 μg of LSD. All participants were healthy, mostly hallucinogen-naive adults aged 25 to 65. The findings suggest that LSD alters emotional processing and sociality in ways that may support its use as an adjunct to psychotherapy for anxiety in patients with life-threatening illness.
Psychopharmacology
September 16, 2017
Yasmin Schmid, Matthias E. Liechti
234 citations
A single 200 microgram dose of LSD, given to 16 healthy volunteers in a controlled lab setting, produced long-lasting positive effects. Participants reported increased positive attitudes, mood, altruistic behavior, and well-being one month and twelve months later. These benefits were subjectively attributed to the LSD experience. The strength of the acute altered state and mystical-type experience correlated with improved well-being after twelve months. No negative effects were reported. Ten of fourteen participants rated the experience among the ten most meaningful in their lives, and five rated it among the five most spiritually meaningful. Mystical and death transcendence scores increased at one and twelve months, while personality traits did not change.
Psychopharmacology
October 7, 2016
Matthias E. Liechti, Patrick C. Dolder, Yasmin Schmid
203 citations
Mystical-type experiences were uncommon after LSD, likely due to the set and setting of the study. LSD at 200 μg, a dose used in psychotherapy in Switzerland, may cause greater or different alterations of consciousness compared with 100 μg, a dose used in imaging studies. Ego dissolution may correspond to plasma levels of LSD, whereas more strongly induced effects of the drug may not show such relationships.
Journal of Psychopharmacology
July 22, 2014
Yasmin Schmid, Cédric M. Hysek, Linda D. Simmler et al.
154 citations
A low dose of MDMA (75 mg) enhanced emotional empathy for positive emotional situations and reduced recognition of sad faces, but did not affect cognitive empathy, social cognitive inferences, or moral judgment. Methylphenidate (40 mg) had no effects on emotional processing, empathy, or mental perspective-taking. MDMA increased subjective feelings of closeness, openness, and trust, along with plasma oxytocin and prolactin levels. These social-cognitive effects likely contribute to MDMA's popularity as a party drug.
Clinical Pharmacokinetics
February 14, 2017
Patrick C. Dolder, Yasmin Schmid, Andrea E. Steuer et al.
134 citations
After oral administration, lysergic acid diethylamide (LSD) reaches peak plasma concentrations of 1.3 ng/mL (100 µg dose) and 3.1 ng/mL (200 µg dose) within about 1.5 hours, with a plasma half-life of 2.6 hours. Subjective effects last 8 to 12 hours depending on dose, and peak effects occur around 2.5 to 2.8 hours after ingestion. A close relationship exists between LSD concentration and subjective response within individuals, but no correlation was found between plasma levels and effects across different people at peak concentration. The effects are related to changing plasma concentrations over time, without evidence of acute tolerance.
Cell reports
March 28, 2023
Vern Lewis, Emma M Bonniwell, Janelle K Lanham et al.
129 citations
The non-hallucinogenic LSD analog 2-Br-LSD acts as a partial agonist at several aminergic G protein-coupled receptors, including 5-HT2A, but does not induce the head-twitch response in mice, indicating it lacks hallucinogenic effects. Unlike LSD, 2-Br-LSD does not activate 5-HT2B, avoiding a risk of cardiac valvulopathy. It produces weak 5-HT2A β-arrestin recruitment and internalization in vitro and does not cause tolerance after repeated dosing. In cultured rat cortical neurons, 2-Br-LSD promotes dendritogenesis and spinogenesis, and in mice it increases active coping behavior—an effect blocked by a 5-HT2A antagonist—and reverses behavioral effects of chronic stress. These findings suggest 2-Br-LSD has an improved pharmacological profile over LSD and potential therapeutic value for mood disorders.
Journal of Neuroendocrinology
February 6, 2016
Petra Strajhar, Yasmin Schmid, Evangelia Liakoni et al.
129 citations
A single 200 microgram dose of LSD increases several stress-related steroid hormones in the blood, particularly glucocorticoids like cortisol and corticosterone, in healthy adults. In a randomized, double-blind, placebo-controlled crossover study with 16 participants, LSD raised plasma levels of cortisol, cortisone, corticosterone, and 11-dehydrocorticosterone compared to placebo, with peak cortisol levels occurring about 2.5 hours after dosing. LSD also increased the androgen dehydroepiandrosterone but did not affect other androgens, progestogens, or mineralocorticoids. The rises in glucocorticoids closely tracked blood LSD concentrations and the intensity of the psychedelic experience, without signs of acute tolerance.
The International Journal of Neuropsychopharmacology
October 8, 2013
Cédric M. Hysek, Linda D. Simmler, Nathalie Schillinger et al.
125 citations
Taking methylphenidate (Ritalin) with MDMA (ecstasy) does not produce stronger psychoactive effects than either drug alone, but it does increase cardiovascular strain and adverse effects. In a double-blind, placebo-controlled crossover trial with healthy subjects, methylphenidate alone produced psychostimulant effects but did not enhance MDMA's mood-elevating effects. MDMA (125 mg) increased positive mood more than methylphenidate (60 mg), while methylphenidate enhanced activity and concentration more than MDMA. The drugs also differently affected emotion recognition: methylphenidate improved recognition of sad and fearful faces, whereas MDMA reduced recognition of negative emotions. Acute tolerance developed to MDMA but not methylphenidate. The drugs did not alter each other's pharmacokinetics.
Translational Psychiatry
April 4, 2017
Felix Mueller, Claudia Lenz, Patrick C. Dolder et al.
124 citations
Lysergic acid diethylamide (LSD) reduces reactivity in the left amygdala and right medial prefrontal cortex when processing fearful faces, compared to a placebo. In a double-blind, randomized, crossover study, 20 healthy adults received either 100 μg of LSD or a placebo before undergoing functional magnetic resonance imaging (fMRI). Plasma LSD levels were measured before and after the scan. A significant negative correlation emerged between the reduced amygdala response to fearful stimuli and the subjective drug effects reported by participants. These findings indicate that LSD alters the engagement of brain regions involved in emotional processing.
Psychopharmacology
May 27, 2017
Patrick C. Dolder, Felix Müller, Yasmin Schmid et al.
118 citations
MDMA produces subjective, emotional, sexual, and endocrine effects that are clearly distinct from those of methylphenidate and modafinil at the doses tested. The findings indicate that each drug has a unique profile of effects, with MDMA showing a pattern that differs from the stimulants methylphenidate and modafinil.
The International Journal of Neuropsychopharmacology
June 24, 2015
Patrick C. Dolder, Yasmin Schmid, Manuel Haschke et al.
110 citations
Oral lysergic acid diethylamide (LSD) shows dose-proportional pharmacokinetics, with peak concentrations reached about 1.5 hours after ingestion and a terminal half-life of approximately 3.6 hours. The drug's effects are closely related to its blood concentration, with subjective effects lasting up to 12 hours. These findings provide a reference for clinical studies and for assessing LSD intoxication.
Journal of Psychopharmacology
October 8, 2020
Yasmin Schmid, Peter Gasser, Peter Oehen et al.
82 citations
Lysergic acid diethylamide (LSD) and 3,4-methylenedioxymethamphetamine (MDMA) are being reinvestigated as treatments for psychiatric disorders. In Switzerland, a compassionate use program allowed 18 patients (12 women, 6 men, aged 29–77) with posttraumatic stress disorder and major depression to receive LSD (100–200 µg) or MDMA (100–175 mg) in group settings from 2014–2018. Drug-assisted sessions occurred about every 3.5 months after 3–10 psychotherapy sessions. LSD produced pronounced alterations of consciousness and mystical-type experiences, with effects largely comparable to those in patients or healthy subjects treated alone in research settings. The data may inform further controlled studies of substance-assisted psychotherapy.
British Journal of Pharmacology
March 8, 2012
C.m. Hysek, Yasmin Schmid, Anna Rickli et al.
81 citations
The α₁- and β-adrenoceptor antagonist carvedilol reduced MDMA-induced increases in blood pressure, heart rate, and body temperature in healthy subjects, but did not affect the subjective or psychotropic effects of MDMA, such as drug liking, high, or stimulation. Carvedilol also did not alter plasma exposure to MDMA. These findings suggest that α₁- and β-adrenoceptors contribute to the cardiostimulant and thermogenic effects of MDMA in humans but not to its psychological effects, indicating carvedilol could be useful for treating cardiovascular and hyperthermic complications associated with ecstasy use.
Psychopharmacology
January 25, 2022
Felix Müller, Elias Kraus, Friederike Holze et al.
64 citations
Up to 9.2% of healthy volunteers reported reoccurring drug-like experiences after taking LSD or psilocybin in controlled studies, but none met the criteria for hallucinogen-persisting perception disorder (HPPD). The experiences were mostly mild, visual, brief, and perceived as neutral or pleasant, with no impairment in daily life. Distressing experiences occurred in two subjects but subsided spontaneously. The findings suggest that flashbacks are not a clinically relevant problem in controlled settings with healthy participants.
Psychological Medicine
October 2, 2017
André Schmidt, Felix Müller, Claudia Lenz et al.
62 citations
Activating the serotonin 2A receptor with LSD impairs the brain's ability to stop or inhibit responses, and this breakdown is linked to visual hallucinations. In a double-blind, placebo-controlled experiment with 18 healthy adults, LSD reduced brain activity in regions including the frontal and cingulate cortex, middle temporal gyrus, and cerebellum during a response-inhibition task. Parahippocampal activation related differently to performance under LSD versus placebo. Less activation in the left superior frontal gyrus during LSD exposure was associated with greater cognitive impairment and visual imagery. The findings suggest that 5-HT2A receptor activation disrupts hippocampal-prefrontal circuits, which may promote visual hallucinations.
Drug Testing and Analysis
July 16, 2016
Andrea E. Steuer, Michael Poetzsch, Lorena Stock et al.
41 citations
A new microflow liquid chromatography tandem mass spectrometry method was developed to quantify LSD and its metabolites in human plasma, enabling detection limits of 0.01 ng/mL and separation within three minutes. In a controlled pharmacokinetic study, elimination half-lives of iso-LSD (median 12 h) and LSD metabolites (median 9, 7.4, 12, and 11 h for oxo-HO-LSD, HO-LSD, HO-LSD-gluc, and nor-LSD, respectively) exceeded that of LSD (median 4.2 h). However, screening for these metabolites to extend detection windows in plasma is not constructive because their concentrations are very low.
European Neuropsychopharmacology
December 4, 2014
Yasmin Schmid, Cédric M. Hysek, Katrin H. Preller et al.
39 citations
In a double-blind, placebo-controlled crossover study with 30 healthy adults, a single 40 mg dose of methylphenidate increased subjective ratings of sexual arousal when viewing explicit erotic pictures and led participants to press a button to prolong viewing of implicit sexual stimuli, whereas a 75 mg dose of MDMA did not alter sexual arousal. Neither drug changed how participants appraised the romantic relationships of unknown couples. Blood levels of testosterone, estrogen, and progesterone were unrelated to arousal ratings. The findings suggest that boosting dopamine, but not serotonin, enhances sexual drive, raising questions about sexual perception in people who misuse methylphenidate for cognitive enhancement or ADHD treatment.
Cochrane Database of Systematic Reviews
September 11, 2024
Sivan Schipper, Kabir Nigam, Yasmin Schmid et al.
34 citations
Psychedelic-assisted therapy using psilocybin or LSD may help treat anxiety, depression, and existential distress in people with life-threatening diseases, and appears well tolerated with no serious adverse events reported in reviewed studies. However, the evidence is low to very low certainty, meaning results are uncertain and could change with future research. As of 2024, these drugs remain illegal in many countries. Blinding issues and small sample sizes limit confidence; more rigorous studies with active placebos and larger samples are needed. Research is restricted in the US due to Schedule I classification but is increasing.
Translational psychiatry
September 30, 2024
Aaron Klaiber, Yasmin Schmid, Anna M Becker et al.
27 citations
Mescaline produces dose-dependent subjective and physiological effects in healthy people, with doses above 100 mg increasing blood pressure and heart rate. Subjective effects lasted from 6.4 hours at 100 mg to 14 hours at 800 mg, and the drug reached peak concentration in blood after about 2 hours with a half-life of 3.5 hours. Nausea and vomiting were common at the highest dose. Blocking serotonin 5-HT2A receptors with ketanserin reduced the effects of 800 mg mescaline to levels similar to lower doses, indicating that mescaline's acute effects are primarily mediated by these receptors.
Die Psychotherapie
February 15, 2024
Helena Aicher, Yasmin Schmid, Peter Gasser
20 citations
Since the late 1990s, psychedelics have experienced a renaissance, attracting increasing international attention. Scientific studies increasingly examine the possibilities and risks of psychedelic-assisted therapy (PAT). Since 2014, based on exceptional permits from the Swiss health authority (BAG), LSD, MDMA, and psilocybin have been used therapeutically within limited medical applications on a case-by-case basis. Over the past nine years, more than 1000 exceptional permits have been granted to about 60 therapists, and an estimated 2000 to 3000 treatments with psychedelics have been conducted.
PLoS ONE
June 15, 2016
Andrea E Steuer, Corina Schmidhauser, Eva H Tingelhoff et al.
18 citations
Bupropion pretreatment increased the maximum plasma concentration and overall exposure of both MDMA stereoisomers, while reducing the levels of its major metabolites by about 40%, in healthy volunteers. These changes in MDMA pharmacokinetics due to reduced CYP2D6 activity were similar to those seen in people with naturally lower CYP2D6 function (intermediate metabolizers). The alterations in stereoselectivity based on CYP2D6 activity likely have low clinical relevance. Bupropion and its metabolite levels were not affected by MDMA co-administration.
Neuroscience Applied
January 1, 2025
Matthias E. Liechti, Peter Gasser, Helena Aicher et al.
16 citations
Switzerland's limited access program for psychedelic/MDMA-assisted therapy, started in 2014 with two physicians, had grown to about 100 physicians by 2024, treating 723 patients (245 with MDMA, 130 with LSD, 348 with psilocybin). Approximately 1660 treatments occurred in 2024, with patients typically receiving 2-4 sessions within 12 months. The program is authorized by the Swiss Federal Office of Public Health for patients with mostly incurable diseases where the substance can alleviate suffering and no alternatives exist or have failed. The article describes the program's history, legal requirements, costs, professional roles, education, patient characteristics, outcomes, and adverse effects, comparing it to similar programs in Canada and Australia.
Translational psychiatry
September 4, 2024
Patrick Vizeli, Erich Studerus, Friederike Holze et al.
15 citations
LSD dose is the strongest predictor of the drug's subjective and autonomic effects, but non-pharmacological factors also play a significant role. Pre-drug mood states—such as well-being, emotional excitability, and anxiety—predict subjective effects, heart rate, and body temperature. The personality trait openness to experiences correlates with stronger mystical-type effects and oceanic boundlessness. Prior hallucinogen use is linked to less anxious ego dissolution and a less intense overall altered state. Acute anxiety relates negatively to the functionality of the Cytochrome 2D6 enzyme. Sex and body weight do not significantly influence the drug experience.