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
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.
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.
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.
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.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
October 1, 2023
Laura Ley, Friederike Holze, Denis Arikci et al.
127 citations
At equally strong doses, the classic psychedelics mescaline, LSD, and psilocybin produce comparable subjective experiences, with no evidence of qualitative differences in altered states of consciousness. Autonomic effects were moderate; psilocybin increased diastolic blood pressure more than LSD, while LSD showed a trend toward higher heart rate than psilocybin. Mescaline had the longest effect duration (mean 11.1 hours), followed by LSD (8.2 hours) and psilocybin (4.9 hours). Mescaline and LSD, but not psilocybin, raised circulating oxytocin. None altered brain-derived neurotrophic factor. Tolerability was similar, though mescaline caused slightly more subacute adverse effects 12–24 hours later.
The International Journal of Neuropsychopharmacology
November 4, 2022
Aaron Klaiber, Friederike Holze, Ioanna Istampoulouoglou et al.
100 citations
Lysergic acid diethylamide (LSD) produces its acute psychedelic effects by stimulating the serotonin 5-HT2A receptor. In a double-blind, randomized, placebo-controlled, crossover study with 24 healthy participants, the 5-HT2A antagonist ketanserin (40 mg orally) was given one hour after LSD (100 µg orally). Ketanserin reversed the acute response to LSD, reducing the duration of subjective effects from 8.5 hours with placebo to 3.5 hours. It also reversed LSD-induced alterations of mind, including visual and acoustic alterations and ego dissolution, and reduced adverse cardiovascular effects and mydriasis. Ketanserin did not alter LSD's pharmacokinetics or its elevation of brain-derived neurotrophic factor levels. The findings indicate that LSD produces its psychedelic effects only when occupying 5-HT2A receptors, and ketanserin can shorten and attenuate the LSD experience for research and therapy.
Translational psychiatry
May 23, 2023
Severin B Vogt, Laura Ley, Livio Erne et al.
85 citations
Intravenous DMT can produce a psychedelic state that is short-lasting and controllable. A double-blind, placebo-controlled crossover trial with 27 healthy participants tested five DMT regimens: low infusion (0.6 mg/min), high infusion (1 mg/min), low bolus plus low infusion (15 mg + 0.6 mg/min), and high bolus plus high infusion (25 mg + 1 mg/min). Bolus doses induced very intense effects within 2 minutes, with more negative feelings and anxiety than infusions. Infusions produced slowly increasing, dose-dependent effects that plateaued after 30 minutes. All effects subsided within 15 minutes of stopping the infusion. Acute tolerance developed, with stable subjective effects from 30 to 90 minutes despite rising plasma concentrations. Intravenous DMT infusion is a promising tool for tailored psychedelic therapy.
Frontiers in Pharmacology
July 13, 2021
Friederike Holze, Isidora Avedisian, Nimmy Varghese et al.
66 citations
Lysergic acid diethylamide (LSD) dose-dependently increased both implicit and explicit emotional empathy in 16 healthy subjects, with the highest 200 µg dose producing a significant effect compared with placebo. The 200 µg dose also moderately increased plasma oxytocin levels. Blocking the serotonin 5-HT2A receptor with ketanserin reduced the LSD-induced oxytocin release but did not reduce the increases in emotional empathy. These results indicate that LSD enhances empathy through mechanisms that may be partially independent of its primary action on 5-HT2A receptors, whereas the oxytocin release depends on 5-HT2A receptor stimulation and aligns with the psychedelic effect of LSD.
Frontiers in Pharmacology
July 13, 2022
Patrick Vizeli, Isabelle Straumann, Urs Duthaler et al.
43 citations
A single 125 mg dose of MDMA, given to 30 healthy men after fear conditioning and two hours before extinction learning, reduced skin conductance responses to a conditioned fear cue during both extinction learning and its recall the next day, compared with placebo. The drug did not affect fear-potentiated startle responses. Subjective feelings of trust and openness during extinction learning were linked to poorer discrimination between danger and safety cues during recall. MDMA raised oxytocin levels fourfold, but this increase did not correlate with fear extinction outcomes. The findings suggest MDMA can accelerate fear extinction learning and retention, at least for some physiological measures of fear, which may help explain its therapeutic benefit in PTSD.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
December 1, 2023
Isabelle Straumann, Laura Ley, Friederike Holze et al.
41 citations
Co-administering MDMA (100 mg) with LSD (100 µg) does not improve the quality of the acute subjective effects compared with LSD alone in healthy adults. The combination prolongs the duration of subjective effects and increases blood pressure, heart rate, and pupil size more than LSD alone. Oxytocin levels rise more with MDMA alone or the combination than with LSD alone. The findings suggest that combining MDMA with LSD offers no relevant benefits over LSD alone for psychedelic-assisted therapy.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
December 1, 2024
Isabelle Straumann, Isidora Avedisian, Aaron Klaiber et al.
20 citations
The two mirror-image forms of MDMA, S-MDMA and R-MDMA, produce different acute effects in humans. S-MDMA (125 mg) caused stronger feelings of stimulation, happiness, and openness, and larger increases in blood pressure than R-MDMA (125 or 250 mg) or racemic MDMA (125 mg). R-MDMA did not produce more psychedelic-like effects than S-MDMA. S-MDMA also increased plasma prolactin, cortisol, and oxytocin more than the other forms. The body eliminated S-MDMA faster (half-life 4.1 hours) than R-MDMA (half-life 12-14 hours). The findings suggest that S-MDMA's stronger stimulant effects are due to its higher potency rather than a qualitative difference, and that equivalent effects may occur at doses of 100 mg S-MDMA, 125 mg racemic MDMA, and 300 mg R-MDMA.
Neuropsychopharmacology
December 19, 2024
Livio Erne, Severin B Vogt, Lorenz Müller et al.
14 citations
Continuous intravenous infusions of DMT produce dose-dependent subjective effects that plateau after 30 minutes, with a ceiling effect for good drug effect at 1.8 mg/min. The highest dose tested (2.4 mg/min) caused greater anxious ego dissolution and significant anxiety compared to placebo. DMT showed dose-proportional pharmacokinetics and moderate acute tolerance. When participants could self-titrate their dose, they chose moderate to strong psychedelic effects comparable to the 1.8 mg/min rate. These findings can guide dose selection in future DMT research and show that subjective effects can be rapidly adjusted through dose titration.