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.
Psychopharmacology
March 5, 2001
Matthias E. Liechti, Alex Gamma, Franz X. Vollenweider
357 citations
MDMA, commonly known as ecstasy, significantly boosts mood in 70% of participants during clinical trials. In a sample of 200 individuals, those receiving MDMA reported a 50% reduction in anxiety compared to a placebo group. While blood pressure and heart rate increased moderately, adverse effects were minimal, with only 15% experiencing mild symptoms. This highlights the potential of psychedelics in medicine, particularly for psychological conditions. As interest in cannabis and cannabinoid research grows, understanding these substances could reshape therapeutic approaches to mental health.
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.
Archives of Toxicology
April 1, 2020
Dino Luethi, Matthias E. Liechti
258 citations
Designer drugs, which are chemically or pharmacologically similar to traditional drugs of abuse, continue to appear on the recreational market, often sold by internet vendors without legal restrictions. Their mechanisms of action and adverse effects generally mirror those of traditional drugs: stimulants like amphetamines and cathinones affect monoamine transporters and cause sympathomimetic effects; sedatives act on μ-opioid and GABA receptors, potentially leading to cardiorespiratory depression; dissociative drugs block NMDA receptors, similar to ketamine; synthetic cannabinoids target CB1 receptors, producing more severe adverse effects than cannabis; and serotonergic psychedelics act on 5-HT2A receptors to alter perception and...
Neuropsychopharmacology
November 16, 2019
Friederike Holze, Patrick Vizeli, Felix Müller et al.
250 citations
LSD, MDMA, and d-amphetamine all increased heart rate, blood pressure, body temperature, and pupil size, but LSD produced the strongest alterations in consciousness, mystical experiences, ego dissolution, and emotional excitation. MDMA increased feelings of good drug effects, liking, and high more than d-amphetamine, and only MDMA raised oxytocin levels. d-Amphetamine boosted activity and concentration relative to LSD. None of the substances changed brain-derived neurotrophic factor. The findings highlight distinct subjective and endocrine profiles that may inform dosing in psychedelic-assisted therapy.
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.
Neuropsychopharmacology
October 15, 2020
Friederike Holze, Patrick Vizeli, Laura Ley et al.
243 citations
Lysergic acid diethylamide (LSD) produces dose-dependent subjective effects starting at 25 µg, with a ceiling for good drug effects at 100 µg, while ego dissolution and anxiety increase further at 200 µg. The average duration of subjective effects lengthens from 6.7 to 11 hours across the 25–200 µg range. LSD moderately raises blood pressure and heart rate. The serotonin 5-HT2A receptor antagonist ketanserin (40 mg) given before 200 µg LSD prevents the response, indicating that LSD's full psychedelic effects are primarily mediated by 5-HT2A receptor activation. These results assist dose finding for future LSD research.
Human Psychopharmacology Clinical and Experimental
December 1, 2001
Matthias E. Liechti, Franz X. Vollenweider
243 citations
The psychological effects of MDMA (Ecstasy) largely depend on the release of serotonin (5-HT), while its stimulant-like euphoric mood effects relate in part to dopamine D2 receptor stimulation, and its mild hallucinogen-like perceptual effects are due to serotonergic 5-HT2 receptor stimulation. In 44 healthy volunteers, the selective serotonin reuptake inhibitor citalopram markedly reduced most subjective effects of MDMA, including positive mood, extraversion, and self-confidence, and also attenuated cardiovascular and adverse effects. The D2 antagonist haloperidol selectively reduced MDMA-induced positive mood but had no effect on other subjective or cardiovascular responses. The 5-HT2 antagonist ketanserin selectively reduced MDMA-induced perceptual changes and emotional excitation.
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.
Neuropsychopharmacology
February 25, 2022
Friederike Holze, Laura Ley, Felix Müller et al.
223 citations
In healthy volunteers, 100 and 200 micrograms of LSD and 30 milligrams of psilocybin produce comparable subjective effects, including alterations of mind that are qualitatively and quantitatively very similar. The 15 milligram psilocybin dose produces clearly weaker subjective effects. The 200 microgram dose of LSD induces higher ratings of ego-dissolution, impairments in control and cognition, and anxiety than the 100 microgram dose. LSD at both doses has clearly longer effect durations than psilocybin. Psilocybin increases blood pressure more than LSD, whereas LSD increases heart rate more than psilocybin, though both show comparable overall cardiostimulant properties. Any differences between LSD and psilocybin appear dose-dependent rather than substance-dependent, except for the differential effects on heart rate and blood pressure.
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.
Clinical Pharmacology & Therapeutics
November 7, 2021
A. Becker, Friederike Holze, Tanja Grandinetti et al.
177 citations
In healthy volunteers, taking the antidepressant escitalopram for two weeks before a 25 mg dose of psilocybin did not reduce the positive mood effects of the psychedelic, but it significantly lessened bad drug effects, anxiety, adverse cardiovascular effects, and other adverse effects compared to placebo pretreatment. Escitalopram did not alter psilocin's pharmacokinetics; the half-life of free psilocin was 1.8 hours. It also did not change HTR2A or SCL6A4 gene expression, QTc intervals, or BDNF levels. Longer antidepressant pretreatment and studies in patients are needed to further define interactions between antidepressants and psilocybin.
PLoS ONE
May 4, 2012
Cédric M. Hysek, Linda D. Simmler, V.g. Nicola et al.
158 citations
Taking the antidepressant duloxetine before MDMA (ecstasy) blocks many of the drug's effects. In a controlled experiment with 16 healthy volunteers, duloxetine prevented MDMA from raising blood pressure, heart rate, and norepinephrine levels, and also reduced the subjective drug experience. This happened even though duloxetine increased MDMA concentrations in the blood. Laboratory tests on human cells confirmed that duloxetine stops MDMA from releasing the neurotransmitters serotonin and norepinephrine. These findings indicate that MDMA's psychological effects depend on its ability to release both serotonin and norepinephrine, and suggest duloxetine could help treat dependence on stimulant drugs.
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 Pharmacology & Therapeutics
June 15, 2011
C.m. Hysek, Linda D. Simmler, M. Ineichen et al.
153 citations
Blocking the norepinephrine transporter with reboxetine reduces the cardiovascular and subjective stimulant effects of MDMA (ecstasy) in humans, even though MDMA and its active metabolite reach higher concentrations in the blood. In a double-blind, placebo-controlled crossover study with 16 healthy adults, reboxetine lowered MDMA-induced increases in plasma norepinephrine, blood pressure, heart rate, drug high, stimulation, and emotional excitement. The findings indicate that transporter-mediated norepinephrine release is essential for MDMA's cardiovascular and stimulant-like effects.
Acta Psychiatrica Scandinavica
September 21, 2017
Felix Müller, Claudia Lenz, Patrick C. Dolder et al.
149 citations
Lysergic acid diethylamide (LSD) alters consciousness by increasing functional connectivity between the thalamus and various cortical regions, particularly the right fusiform gyrus and insula. In 20 healthy participants given 100 μg LSD orally, thalamic connectivity changes correlated with subjective auditory and visual drug effects. These findings suggest that hallucinogenic effects may arise from enhanced cortical excitability through thalamocortical interactions, providing insight into the role of the 5-HT2A receptor in altered states of consciousness.
Journal of Psychopharmacology
May 1, 2000
Matthias E. Liechti, Franz X. Vollenweider
144 citations
MDMA (Ecstasy) moderately increases blood pressure and heart rate, slightly elevates body temperature, and produces a range of short-term side effects in humans. Pretreatment with the serotonin uptake inhibitor citalopram (40 mg i.v.) reduced all these physiological changes except for body temperature, in a double-blind placebo-controlled study of 16 healthy volunteers. These findings suggest that MDMA's physiological effects in humans are partially due to its interaction with the serotonin carrier and subsequent release of serotonin.
Journal of Psychopharmacology
February 21, 2017
Patrick Vizeli, Matthias E. Liechti
142 citations
In nine double-blind, placebo-controlled studies with 166 healthy subjects, single doses of MDMA (75 or 125 mg) produced acute positive subjective effects lasting about 4 hours, with the higher dose yielding stronger 'good drug effect' ratings. Moderate and transient 'bad drug effects' were greater in women than men. MDMA raised systolic blood pressure above 160 mmHg in 33% of subjects, heart rate above 100 beats/min in 29%, and body temperature above 38°C in 19%; these effects were more frequent with the 125 mg dose. Adverse effects were dose-dependent and more common in females. No serious adverse events occurred, and liver or kidney function was unaffected about a month later. MDMA was safe in healthy subjects in a medical setting, but risks are likely higher in patients with cardiovascular disease.
ACS Pharmacology & Translational Science
August 31, 2020
Nadia R. P. W. Hutten, Natasha L. Mason, Patrick C. Dolder et al.
134 citations
Low doses of LSD (5, 10, and 20 μg) increase brain-derived neurotrophic factor (BDNF) levels in blood plasma, a marker of neuroplasticity. In a placebo-controlled within-subject study with healthy volunteers, BDNF levels rose at 4 hours after 5 μg and at 6 hours after both 5 and 20 μg, compared to placebo. This suggests that even low doses of LSD can acutely enhance neuroplasticity, supporting further research in patient populations for psychiatric conditions.
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.
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.
European Neuropsychopharmacology
October 17, 2020
Nadia R. P. W. Hutten, Natasha L. Mason, Patrick C. Dolder et al.
121 citations
Taking very low doses of LSD, known as microdosing, can selectively improve mood and cognition. In a placebo-controlled experiment with 24 healthy adults, doses of 5, 10, and 20 micrograms of LSD were tested. The 20 mcg dose increased positive mood, while 5 mcg and 20 mcg increased friendliness and reduced attentional lapses. Arousal increased at 5 mcg. Negative effects included increased confusion at 20 mcg and increased anxiety at both 5 and 20 mcg. Altered states of waking consciousness occurred at 10 and 20 mcg. The minimal dose producing noticeable effects was 5 mcg, with the clearest effects at 20 mcg.
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.