Lysergic Acid Diethylamide (LSD-25): XVII. Tolerance Development and its Relationship to a Theory of Psychosis

Abramson, Harold A.; Jarvik, Murray E.; Gorin, M.H.; Hirsch, M.

doi:10.1080/00223980.1956.9916206

Cited by 66 publications

(14 citation statements)

References 5 publications

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“…If LSD and DOM are administered repeatedly at daily intervals tolerance is observed after 1-3 days and there is eventually nearly a complete loss of response (Abramson et al, 1956; Isbell et al, 1956, 1961; Angrist et al, 1974). Tolerance occurs with a variety of phenylalkylamine, indolealkylamine, and ergoline hallucinogens, and compounds from these classes exhibit symmetrical cross-tolerance (Abramson et al, 1958, 1960; Balestrieri and Fontanari, 1959; Isbell et al, 1961; Wolbach et al, 1962a; Abramson and Rolo, 1967; Hollister et al, 1969).…”

Section: Evidence That Serotonergic Hallucinogens Belong To a Unitmentioning

confidence: 99%

Recent advances in the neuropsychopharmacology of serotonergic hallucinogens

Halberstadt

2015

Behavioural Brain Research

239

203

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Serotonergic hallucinogens, such as (+)-lysergic acid diethylamide, psilocybin, and mescaline, are somewhat enigmatic substances. Although these drugs are derived from multiple chemical families, they all produce remarkably similar effects in animals and humans, and they show cross-tolerance. This article reviews the evidence demonstrating the serotonin 5-HT2A receptor is the primary site of hallucinogen action. The 5-HT2A receptor is responsible for mediating the effects of hallucinogens in human subjects, as well as in animal behavioral paradigms such as drug discrimination, head twitch response, prepulse inhibition of startle, exploratory behavior, and interval timing. Many recent clinical trials have yielded important new findings regarding the psychopharmacology of these substances. Furthermore, the use of modern imaging and electrophysiological techniques is beginning to help unravel how hallucinogens work in the brain. Evidence is also emerging that hallucinogens may possess therapeutic efficacy.

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Section: Evidence That Serotonergic Hallucinogens Belong To a Unitmentioning

confidence: 99%

Recent advances in the neuropsychopharmacology of serotonergic hallucinogens

Halberstadt

2015

Behavioural Brain Research

239

203

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“…Allen et al, 1991 No micronuclei were induced in mice exposed to 4, 8 or 16 mg psilocybin per kg body weight (Van Went, 1978). Tolerance to psilocybin (or cross-tolerance with LSD) might develop, but physical dependence does not occur (Abramson et al, 1956;Isbel et al, 1961;Abramson and Rolo, 1965;Balestrieri, 1967).…”

Section: Symptomsmentioning

confidence: 99%

Occurrence and use of hallucinogenic mushrooms containing psilocybin alkaloids

Andersson¹,

Gry²,

Kristinsson³

2009

TemaNord

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“…Tolerance to repeated LSD administration reportedly begins with the second daily dose of LSD, and complete tolerance develops within 3–4 days of repeated LSD administration in humans according to older studies (Cholden et al, 1955; Abramson et al, 1956; Belleville et al, 1956; Passie et al, 2008; Nichols, 2016) that need to be replicated. In the present study, we found no evidence of acute pharmacological tolerance within 12 h of acute LSD administration at a dose of 100 μg as documented in detail elsewhere (Dolder et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…The 1.5 h time point was selected to coincide with the peak of the plasma concentration of LSD (Dolder et al, 2015b). The 24 h time point was selected because partial tolerance by that time has been documented (Cholden et al, 1955; Abramson et al, 1956; Belleville et al, 1956). Samples were incubated for 2 h at room temperature, followed by freezing at -80°C until further processing.…”

Section: Methodsmentioning

confidence: 99%

“…However, many aspects of LSD’s pharmacological effects remain unclear, including the phenomenon of the rapid development of tolerance (i.e., tachyphylaxis) to its psychological and physiological effects with repeated administration (Passie et al, 2008). Early studies that employed repeated daily administration of 100 μg LSD in humans described partial tolerance with the second dose and complete tolerance with the third and subsequent doses (Cholden et al, 1955; Abramson et al, 1956; Belleville et al, 1956). The effects of LSD reappeared only after a substance-free interval of 4 days.…”

Section: Introductionmentioning

confidence: 99%

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A Single Dose of LSD Does Not Alter Gene Expression of the Serotonin 2A Receptor Gene (HTR2A) or Early Growth Response Genes (EGR1-3) in Healthy Subjects

et al. 2017

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Rationale: Renewed interest has been seen in the use of lysergic acid diethylamide (LSD) in psychiatric research and practice. The repeated use of LSD leads to tolerance that is believed to result from serotonin (5-HT) 5-HT2A receptor downregulation. In rats, daily LSD administration for 4 days decreased frontal cortex 5-HT2A receptor binding. Additionally, a single dose of LSD acutely increased expression of the early growth response genes EGR1 and EGR2 in rat and mouse brains through 5-HT2A receptor stimulation. No human data on the effects of LSD on gene expression has been reported. Therefore, we investigated the effects of single-dose LSD administration on the expression of the 5-HT2A receptor gene (HTR2A) and EGR1-3 genes.Methods: mRNA expression levels were analyzed in whole blood as a peripheral biomarker in 15 healthy subjects before and 1.5 and 24 h after the administration of LSD (100 μg) and placebo in a randomized, double-blind, placebo-controlled, cross-over study.Results: LSD did not alter the expression of the HTR2A or EGR1-3 genes 1.5 and 24 h after administration compared with placebo.Conclusion: No changes were observed in the gene expression of LSD’s primary target receptor gene or genes that are implicated in its downstream effects. Remaining unclear is whether chronic LSD administration alters gene expression in humans.

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Lysergic Acid Diethylamide (LSD-25): XVII. Tolerance Development and its Relationship to a Theory of Psychosis

Cited by 66 publications

References 5 publications

Recent advances in the neuropsychopharmacology of serotonergic hallucinogens

Recent advances in the neuropsychopharmacology of serotonergic hallucinogens

Occurrence and use of hallucinogenic mushrooms containing psilocybin alkaloids

A Single Dose of LSD Does Not Alter Gene Expression of the Serotonin 2A Receptor Gene (HTR2A) or Early Growth Response Genes (EGR1-3) in Healthy Subjects

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