Changes in brain metabolites related to stress resilience: Metabolomic analysis of the hippocampus in a rat model of depression

Akimoto, Hayato; Oshima, Shinji; Sugiyama, Tomohide; Negishi, Akio; Nemoto, Tadashi; Kobayashi, Daisuke

doi:10.1016/j.bbr.2018.11.017

Cited by 32 publications

(28 citation statements)

References 58 publications

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“…The plasma levels of BDNF were measured at baseline and 3 and 5 h after drug administration. Plasma BDNF levels were measured using an ELISA kit (Biosensis Mature BDNF Rapid ELISA kit: human, mouse, rat; Thebarton, Australia) as previously described [64]. Analyses were performed at the end of the study in one batch.…”

Section: Methodsmentioning

confidence: 99%

Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects

Holze

Vizeli

Müller

et al. 2019

Neuropsychopharmacol.

172

181

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Lysergic acid diethylamide (LSD) is a classic psychedelic, 3,4-methylenedioxymethamphetamine (MDMA) is an empathogen, and D-amphetamine is a classic stimulant. All three substances are used recreationally. LSD and MDMA are being investigated as medications to assist psychotherapy, and D-amphetamine is used for the treatment of attention-deficit/hyperactivity disorder. All three substances induce distinct acute subjective effects. However, differences in acute responses to these prototypical psychoactive substances have not been characterized in a controlled study. We investigated the acute autonomic, subjective, and endocrine effects of single doses of LSD (0.1 mg), MDMA (125 mg), D-amphetamine (40 mg), and placebo in a randomized, doubleblind, cross-over study in 28 healthy subjects. All of the substances produced comparable increases in hemodynamic effects, body temperature, and pupil size, indicating equivalent autonomic responses at the doses used. LSD and MDMA increased heart rate more than D-amphetamine, and D-amphetamine increased blood pressure more than LSD and MDMA. LSD induced significantly higher ratings on the 5 Dimensions of Altered States of Consciousness scale and Mystical Experience Questionnaire than MDMA and D-amphetamine. LSD also produced greater subjective drug effects, ego dissolution, introversion, emotional excitation, anxiety, and inactivity than MDMA and D-amphetamine. LSD also induced greater impairments in subjective ratings of concentration, sense of time, and speed of thinking compared with MDMA and D-amphetamine. MDMA produced greater ratings of good drug effects, liking, high, and ego dissolution compared with D-amphetamine. D-Amphetamine increased ratings of activity and concentration compared with LSD. MDMA but not LSD or D-amphetamine increased plasma concentrations of oxytocin. None of the substances altered plasma concentrations of brain-derived neurotrophic factor. These results indicate clearly distinct acute effects of LSD, MDMA, and D-amphetamine and may assist the dose-finding in substance-assisted psychotherapy research.

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Section: Methodsmentioning

confidence: 99%

Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects

Holze

Vizeli

Müller

et al. 2019

Neuropsychopharmacol.

172

181

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show abstract

“…Plasma BDNF levels were measured at baseline and 6, 12, and 24 h after drug administration using the Biosensis Mature BDNF Rapid ELISA Kit (Thebarton, Australia) [30].…”

Section: Plasma Bdnf Levelsmentioning

confidence: 99%

Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects

Holze

Vizeli

Ley

et al. 2020

Neuropsychopharmacol.

143

223

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Growing interest has been seen in using lysergic acid diethylamide (LSD) in psychiatric research and therapy. However, no modern studies have evaluated subjective and autonomic effects of different and pharmaceutically well-defined doses of LSD. We used a double-blind, randomized, placebo-controlled, crossover design in 16 healthy subjects (eight women, eight men) who underwent six 25 h sessions and received placebo, LSD (25, 50, 100, and 200 µg), and 200 µg LSD 1 h after administration of the serotonin 5-hydroxytryptamine-2A (5-HT2A) receptor antagonist ketanserin (40 mg). Test days were separated by at least 10 days. Outcome measures included self-rating scales that evaluated subjective effects, autonomic effects, adverse effects, plasma brain-derived neurotrophic factor levels, and pharmacokinetics up to 24 h. The pharmacokinetic-subjective response relationship was evaluated. LSD showed dose-proportional pharmacokinetics and first-order elimination and dose-dependently induced subjective responses starting at the 25 µg dose. A ceiling effect was observed for good drug effects at 100 µg. The 200 µg dose of LSD induced greater ego dissolution than the 100 µg dose and induced significant anxiety. The average duration of subjective effects increased from 6.7 to 11 h with increasing doses of 25–200 µg. LSD moderately increased blood pressure and heart rate. Ketanserin effectively prevented the response to 200 µg LSD. The LSD dose–response curve showed a ceiling effect for subjective good effects, and ego dissolution and anxiety increased further at a dose above 100 µg. These results may assist with dose finding for future LSD research. The full psychedelic effects of LSD are primarily mediated by serotonin 5-HT2A receptor activation.

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“…Blood samples were collected every 2 h over 6 h, and BDNF levels were determined afterward in blood plasma using ELISA. 18 Previously, it has been demonstrated that blood plasma BDNF concentrations reflect mammalian brain-tissue BDNF levels. 19 …”

mentioning

confidence: 99%

Low Doses of LSD Acutely Increase BDNF Blood Plasma Levels in Healthy Volunteers

Hutten

Mason

Dolder

et al. 2020

ACS Pharmacol. Transl. Sci.

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Despite preclinical evidence for psychedelic-induced neuroplasticity, confirmation in humans is grossly lacking. Given the increased interest in using low doses of psychedelics for psychiatric indications and the importance of neuroplasticity in the therapeutic response, this placebo-controlled within-subject study investigated the effect of single low doses of LSD (5, 10, and 20 μg) on circulating BDNF levels in healthy volunteers. Blood samples were collected every 2 h over 6 h, and BDNF levels were determined afterward in blood plasma using ELISA. The findings demonstrated an increase in BDNF blood plasma levels at 4 h (5 μg) and 6 h (5 and 20 μg) compared to that for the placebo. The finding that LSD acutely increases BDNF levels warrants studies in patient populations.

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Changes in brain metabolites related to stress resilience: Metabolomic analysis of the hippocampus in a rat model of depression

Cited by 32 publications

References 58 publications

Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects

Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects

Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects

Low Doses of LSD Acutely Increase BDNF Blood Plasma Levels in Healthy Volunteers

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