scholarly journals The paradoxical psychological effects of lysergic acid diethylamide (LSD)

2016 ◽  
Vol 46 (7) ◽  
pp. 1379-1390 ◽  
Author(s):  
R. L. Carhart-Harris ◽  
M. Kaelen ◽  
M. Bolstridge ◽  
T. M. Williams ◽  
L. T. Williams ◽  
...  
Keyword(s):  
Subjective Effects ◽  
Lysergic Acid ◽  
Psychological Effects ◽  
Lysergic Acid Diethylamide ◽  
Psychological Wellbeing ◽  
Controlled Study ◽  
Life Orientation Test ◽  
Neo Personality Inventory ◽  
Within Subjects

BackgroundLysergic acid diethylamide (LSD) is a potent serotonergic hallucinogen or psychedelic that modulates consciousness in a marked and novel way. This study sought to examine the acute and mid-term psychological effects of LSD in a controlled study.MethodA total of 20 healthy volunteers participated in this within-subjects study. Participants received LSD (75 µg, intravenously) on one occasion and placebo (saline, intravenously) on another, in a balanced order, with at least 2 weeks separating sessions. Acute subjective effects were measured using the Altered States of Consciousness questionnaire and the Psychotomimetic States Inventory (PSI). A measure of optimism (the Revised Life Orientation Test), the Revised NEO Personality Inventory, and the Peter's Delusions Inventory were issued at baseline and 2 weeks after each session.ResultsLSD produced robust psychological effects; including heightened mood but also high scores on the PSI, an index of psychosis-like symptoms. Increased optimism and trait openness were observed 2 weeks after LSD (and not placebo) and there were no changes in delusional thinking.ConclusionsThe present findings reinforce the view that psychedelics elicit psychosis-like symptoms acutely yet improve psychological wellbeing in the mid to long term. It is proposed that acute alterations in mood are secondary to a more fundamental modulation in the quality of cognition, and that increased cognitive flexibility subsequent to serotonin 2A receptor (5-HT2AR) stimulation promotes emotional lability during intoxication and leaves a residue of ‘loosened cognition’ in the mid to long term that is conducive to improved psychological wellbeing.

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

2020 ◽  
Author(s):  
Friederike Holze ◽  
Patrick Vizeli ◽  
Laura Ley ◽  
Felix Müller ◽  
Patrick Dolder ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Rating Scales ◽  
Subjective Effects ◽  
Receptor Activation ◽  
Lysergic Acid ◽  
Ceiling Effect ◽  
Lysergic Acid Diethylamide ◽  
Psychiatric Research ◽  
Controlled Study ◽  
Double Blind

Abstract 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.

Alleviation of the Psychological Effects of LSD in Man by 5-Hydroxytryptophan

1958 ◽  
Vol 104 (437) ◽  
pp. 1237-1244 ◽  
Author(s):  
J. C. Brengelmann ◽  
C. M. B. Pare ◽  
M. Sandler
Keyword(s):  
Psychological Tests ◽  
Lysergic Acid ◽  
Psychological Effects ◽  
Lysergic Acid Diethylamide ◽  
Placebo Controls

In the investigation described, the hypothesis was tested that 5-hydroxytryptamine (5HT) acts to reduce the psychological effects of lysergic acid diethylamide (LSD). The method was to inject 5-hydroxytryptophan (5HTP) prior to LSD and to compare the results of psychological tests performed after these injections. Placebo controls were used.

Serotonin type 5A receptor antagonists inhibit D-lysergic acid diethylamide discriminatory cue in rats

2019 ◽  
Vol 33 (11) ◽  
pp. 1447-1455 ◽  
Author(s):  
Piotr Popik ◽  
Martyna Krawczyk ◽  
Agata Kuziak ◽  
Ryszard Bugno ◽  
Adam Hogendorf ◽  
...  
Keyword(s):  
Serotonin Receptors ◽  
Subjective Effects ◽  
Lysergic Acid ◽  
Lysergic Acid Diethylamide ◽  
Sprague Dawley ◽  
Receptor Antagonists ◽  
Training Dose ◽  
Behavioural Effects ◽  
Sprague Dawley Rats ◽  
Agonistic Activity

Purpose: Like other psychedelics, D-lysergic acid diethylamide (LSD) affects numerous serotonin receptors, and according to the current dogma, the 5-HT2A receptors are considered the main target for its hallucinogenic effects. LSD, however, also displays agonistic activity at the 5-HT5A receptors, which mediate some of LSD-induced behavioural effects. Methods: Using male Sprague Dawley rats, we examined the effects of 5-HT2A and 5-HT5A receptor antagonists on LSD-induced stimulus control in the two-lever drug discrimination test using a FR10 schedule of reinforcement. Results: In animals trained to discriminate 0.08 mg/kg LSD from vehicle 15 minutes after injection, LSD produced dose-related increases in response, with an ED50 (±95% confidence limits) of 0.0384 (± 0.025–0.051) mg/kg). LSD-like responses were observed when the training dose of LSD was given 5–30 but not 90 minutes before the test. Confirming earlier reports, the 5-HT antagonist ketanserin (2 mg/kg) attenuated the LSD response in 50% of rats, and due to pretreatment with 0.2 and 2 mg/kg MDL 100907, 63% and 67% of animals, respectively, failed to select the LSD lever. We then investigated the effects of two 5-HT5A receptor antagonists, and we found that 56% and 60% of rats pretreated with 3 and 10 mg/kg SB 699551, respectively, failed to select the LSD lever. Due to pretreatment with 0.01 mg/kg ASP 5736, 58% of rats did not select the LSD lever. This dose also reduced the response rate but not the number of rats failing to complete the test. Conclusions: The present results suggest that antagonists of the 5-HT5A receptor may inhibit subjective effects of LSD in rats.

Effects of 5-Hydroxytryptophan on Schizophrenia

1959 ◽  
Vol 105 (440) ◽  
pp. 770-776 ◽  
Author(s):  
J. C. Brengelmann ◽  
C. M. B. Pare ◽  
M. Sandler
Keyword(s):  
Previous Experiment ◽  
Psychological Tests ◽  
Lysergic Acid ◽  
Psychological Effects ◽  
Lysergic Acid Diethylamide ◽  
Functional Abnormality ◽  
Psychotomimetic Effects

The present investigation represents a logical continuation of a previous experiment where it was shown that the injection of 5-hydroxytryptophan (5HTP) alleviates the psychological effects of lysergic acid diethylamide (LSD-25) (Brengelmann, Pare and Sandler, 1958). LSD is of interest in psychiatry because the psychotomimetic effects of the drug bear a resemblance to schizophrenia clinically, in psychological tests and, according to Hoagland, Rinkel and Hyde (1955), in their abnormal excretion of urinary phosphate. The possibility presents itself that, in some cases of schizophrenia, the functional abnormality is similar to that produced by LSD.

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