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.
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.
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.
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.
The International Journal of Neuropsychopharmacology
May 30, 2019
Nadia R. P. W. Hutten, Natasha L. Mason, Patrick C. Dolder et al.
132 citations
A survey of 1,116 people who microdose psychedelics found that performance enhancement was the main motive (37%), with LSD (10 mcg) and psilocybin (0.5 g) used 2-4 times per week. Most users were unaware of their exact dose. Negative effects were mostly psychological and occurred acutely while under the influence, but the primary reason for stopping microdosing was that it was not effective. The authors call for placebo-controlled studies to quantify performance effects and assess longer-term negative effects.
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.
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.
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
August 25, 2020
Johannes G. Ramaekers, Nadia R. P. W. Hutten, Natasha L. Mason et al.
95 citations
A low dose of LSD (20 micrograms) that does not cause a psychedelic experience can increase pain tolerance and reduce the unpleasantness of pain in healthy volunteers. In a controlled experiment with 24 participants, those given 20 µg of LSD kept their hand in cold (3°C) water longer and reported less pain than when given a placebo. Smaller doses (5 and 10 µg) did not produce the same effect. The 20 µg dose caused slight increases in blood pressure, anxiety, and dissociation, but no profound mind-altering effects. These findings suggest that very low doses of LSD may offer a new approach to pain management without the intense psychological effects of higher doses.
Journal of Psychopharmacology
April 3, 2017
Kim P. C. Kuypers, Patrick C. Dolder, Johannes G. Ramaekers et al.
88 citations
A pooled analysis of six placebo-controlled studies with 118 participants confirmed that a single dose of MDMA (75 or 125 mg) increases emotional empathy—the ability to share and understand others' feelings—without affecting cognitive empathy, which involves recognizing others' emotions. The empathy boost was strongest for positive emotions and was linked to higher MDMA blood levels before testing. The effect was consistent across different labs and doses, and was not influenced by sex, prior drug use, or participants' baseline trait empathy. Although MDMA raised oxytocin levels, those increases did not explain the empathy changes.
Frontiers in Psychiatry
September 13, 2019
Nadia R. P. W. Hutten, Natasha L. Mason, Patrick C. Dolder et al.
78 citations
People who microdose psychedelics report that it relieves symptoms of mental and physiological disorders more effectively than conventional treatments, especially for ADHD/ADD and anxiety disorders. However, regular (full) doses of psychedelics are rated as more effective than microdoses for mental disorders like anxiety and depression, while for physiological disorders there is no difference in effectiveness between microdoses and regular doses. These findings come from an online survey of 410 adults diagnosed with at least one disorder by a medical professional. The authors call for future randomized controlled trials to objectively test these claims.
Neuroscience & Biobehavioral Reviews
December 30, 2015
Felix Mueller, Claudia Lenz, Markus Steiner et al.
68 citations
Moderate use of MDMA (ecstasy) shows no convincing evidence of structural or functional brain alterations in neuroimaging studies. A review of 19 studies, each involving subjects with fewer than 50 lifetime episodes or under 100 tablets consumed, found no significant harmful effects. However, the lack of results is linked to high methodological variability in dosages and co-consumption of other drugs, low study quality, and small sample sizes.
Clinical Pharmacology & Therapeutics
September 25, 2020
Friederike Holze, Matthias E. Liechti, Nadia R. P. W. Hutten et al.
63 citations
Very low doses of LSD (5, 10, and 20 µg) were given to 23 healthy participants in a double-blind, placebo-controlled crossover trial. LSD concentrations in the blood increased in proportion to dose, with maximal levels reached after about 1.1 hours and an average elimination half-life of 2.7 hours. The 5 µg dose produced no significant subjective effects. The 10 µg dose significantly increased feelings of being under the influence and good drug effect, starting at 1.1 hours, peaking at 2.5 hours, and lasting until 5.1 hours. The 20 µg dose also increased bad drug effects. The threshold for psychotropic effects was 10 µg.
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.
Neuropsychopharmacology
November 20, 2020
Felix Müller, Friederike Holze, Patrick C. Dolder et al.
43 citations
The non-hallucinogenic drug MDMA reduces functional connectivity within several resting-state brain networks, including the default mode network, visual networks, and the sensorimotor network. These decreases closely match those previously reported for hallucinogenic drugs like LSD. The findings suggest that such connectivity changes are not specific to serotonergic hallucinogens but can be induced by monoaminergic stimulation without marked subjective drug effects. However, alterations within the default mode network may help explain the antidepressant effects of some of these substances.
Journal of Clinical Laboratory Analysis
May 26, 2017
Patrick C. Dolder, Matthias E. Liechti, Katharina Rentsch
31 citations
A liquid chromatography tandem mass spectrometry method was developed and validated to measure lysergic acid diethylamide (LSD) and several of its metabolites in human plasma. After controlled administration of 100 μg LSD to 24 healthy subjects, the method accurately and precisely quantified LSD in all plasma samples, with a quantification limit of 0.05 ng/mL. Other compounds—iso-LSD, 2-oxo-3-hydroxy LSD, nor-LSD, lysergic acid monoethylamide, lysergic acid ethyl-2-hydroxyethylamide, 2-oxo-LSD, trioxylated-LSD, and 13/14-hydroxy-LSD—were only sporadically detected at levels too low for quantification.
Drug Science Policy and Law
January 1, 2020
Natasha L. Mason, Patrick C. Dolder, Kim P. C. Kuypers
15 citations
Psychedelics like LSD and psilocybin are most often used at home, while MDMA is more common at parties or festivals. Most people take these substances when already in a positive mood, and their mood stays positive or shifts to positive afterward. Individuals with low psychological well-being are more likely to experience a positive mood change after using LSD, psilocybin, or MDMA compared to those with normal well-being. Higher neuroticism scores are linked to both a greater likelihood of positive mood change and a greater likelihood of negative side effects. The findings suggest that psychedelic use can yield positive outcomes even in people with lower well-being and higher neuroticism.