Drug liking and wanting, not impulsive action or reflection is increased by 4-fluoroamphetamine

Kuypers, Kim P. C.; Perna, Elizabeth B. de Sousa Fernandes; Dolder, Patrick C.; Toennes, Stefan W.; Theunissen, Eef L.; Mason, Natasha L.; Hutten, Nadia R. P. W.; Ramaekers, Johannes G.

doi:10.1007/s00213-018-4931-7

Cited by 8 publications

(17 citation statements)

References 38 publications

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“…Visual analog scales (VASs) were repeatedly used to assess subjective effects over time 20–23 . The VASs included separate measures for “under the influence” (any drug effect), “good drug effect,” and “bad drug effect,” and were presented as 10 cm horizontal lines (0–10), marked from “not at all” on the left to “extremely” on the right.…”

Section: Methodsmentioning

confidence: 99%

“…Visual analog scales (VASs) were repeatedly used to assess subjective effects over time. [20][21][22][23] The VASs included separate measures for "under the influence" (any drug effect), "good drug effect," and "bad drug effect," and were presented as 10 cm horizontal lines (0-10), marked from "not at all" on the left to "extremely" on the right. These VASs have been shown to be sensitive and reliable measures of the effects of LSD and other psychoactive substances and suitable for pharmacokinetic-pharmacodynamic (PK-PD) analyses.…”

Section: Methodsmentioning

confidence: 99%

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Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants

Holze

Liechti

Hutten

et al. 2020

Clin Pharma and Therapeutics

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Microdoses" of lysergic acid diethylamide (LSD) are used recreationally to enhance mood and cognition. Increasing interest has also been seen in developing LSD into a medication. Therefore, we performed a pharmacokineticpharmacodynamic study using very low doses of LSD. Single doses of LSD base (5, 10, and 20 µg) and placebo were administered in a double-blind, randomized, placebo-controlled crossover study in 23 healthy participants. Test days were separated by at least 5 days. Plasma levels of LSD and subjective effects were assessed up to 6 hours after administration. Pharmacokinetic parameters were determined using compartmental modeling. Concentrationsubjective effect relationships were described using pharmacokinetic-pharmacodynamic modeling. Mean (95% confidence interval) maximal LSD concentrations were 151 pg/mL (127-181), 279 pg/mL (243-320), and 500 pg/ mL (413-607) after 5, 10, and 20 µg LSD administration, respectively. Maximal concentrations were reached after 1.1 hours. The mean elimination half-life was 2.7 hours (1.5-6.2). The 5 µg dose of LSD elicited no significant acute subjective effects. The 10 µg dose of LSD significantly increased ratings of "under the influence" and "good drug effect" compared with placebo. These effects began an average of 1.1 hours after 10 µg LSD administration, peaked at 2.5 hours, and ended at 5.1 hours. The 20 µg dose of LSD significantly increased ratings of "under the influence," "good drug effects," and "bad drug effects." LSD concentrations dose-proportionally increased at doses as low as 5-20 µg and decreased with a half-life of 3 hours. The threshold dose of LSD base for psychotropic effects was 10 µg. Lysergic acid diethylamide (LSD) is a well-known classic serotonergic psychedelic that is widely used for recreational purposes. 1 LSD is well-absorbed, 2,3 and maximal LSD concentrations are reached 1.5-2 hours after oral administration. 4 LSD is mainly metabolized to inactive O-H-LSD, which is renally eliminated. 3 The plasma half-life of LSD is 3-4 hours. 3,4 Increasing interest has been seen in using LSD for the treatment of various disorders, including depression and anxiety, 5 substance use, 6 and cluster headache, 7 among others. 8 LSD "microdosing" has recently become popular. 9,10 The practice of microdosing refers to the use of very low doses of LSD that are taken at 2-to-5-day intervals to improve cognitive function and mood. 11-13 However, little is known about the effects of very low doses of LSD. More data are needed to

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants

Holze

Liechti

Hutten

et al. 2020

Clin Pharma and Therapeutics

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“…As expected for an oral ingestion, it took at least 1 hour (typically 2 hours, range 1−3 hours) to reach maximum concentrations. This was known from oral amphetamine dosing and respected in the design of the time scheme of the psychomotoric tests . It appeared that maximal concentrations were reached sooner in the higher dosing condition (Figure ) but this might be a consequence of the lower subject number.…”

Section: Discussionmentioning

confidence: 95%

“…This was known from oral amphetamine dosing 14,15 and respected in the design of the time scheme of the psychomotoric tests. 2,16,17 It appeared that maximal concentrations were reached sooner in the higher dosing condition (Figure 1) but this might be a consequence of the lower subject number.…”

Section: Pharmacokinetic Properties Of 4-fa and Amphetamine In Serummentioning

confidence: 96%

Pharmacokinetic properties of 4‐fluoroamphetamine in serum and oral fluid after oral ingestion

Toennes

Schneider

Pogoda

et al. 2019

Drug Testing and Analysis

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Introduction Each year, synthetic drugs occur in high numbers on the illicit drug market. But data on their pharmacology and toxicology are scarce. Therefore, a controlled study was performed to evaluate pharmacokinetic parameters of 4‐fluoroamphetamine (4‐FA) in humans and to compare it with effects. Methods Twelve subjects ingested 100 mg and five subjects also received 150 mg 4‐FA in a bitter lemon drink. Blood and oral fluid samples were taken during the following 12 hours and analyzed for 4‐FA and traces of amphetamine as impurity by liquid chromatography−tandem mass spectrometry (LC–MS/MS). Results For 12 hours after ingestion, the concentration‐time course of 4‐FA was similar to that of amphetamine with maximal concentrations appearing in serum after about 2 hours (in median 195 ng/mL after the 100 mg dose, range 155–316 ng/mL). The elimination half‐life was approximately 8–9 hours and shorter than that of amphetamine but it exhibited a marked variation (5.5–16.8 hours). In oral fluid, 4‐FA could also be detected for 12 hours and concentrations were higher than in serum. During the first 3 hours after ingestion concentrations were higher, most probably due to oral contamination. Serum concentrations in forensic cases were in the range of those observed in the present study suggesting dosages in recreational use in the range of those tested here. Conclusions The pharmacokinetic properties of 4‐FA are similar to that of amphetamine including a marked variation in elimination. However, recreational dosages may already exhibit prominent adverse effects and may even have life‐threatening consequences.

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“…The data presented in the current paper are a part of a larger project called Predicting Risk of Emerging Drugs with In silico and Clinical Toxicology. Additional data of the present study including the safety profile and neurocognitive effects of 4-FA are published in separate papers Kuypers et al, 2018).…”

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confidence: 99%

Independent elevation of peripheral oxytocin concentrations and reduction in cognitive empathy during 4‐fluoroamphetamine intoxication

Dolder

Perna

Mason

et al. 2018

Human Psychopharmacology

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Objectives 4‐Fluoroamphetamine (4‐FA) is a novel psychoactive substance with a pharmacological profile and reported subjective effects (e.g., empathy) intermediate between 3,4‐methylenedioxymethamphetamine (MDMA) and amphetamine. Studies have shown that MDMA and amphetamine increase emotional empathy without affecting cognitive empathy; MDMA simultaneously leads to elevated levels of oxytocin, unrelated to its behavioral effects. The aim of the present study was to assess the reported enhancement of empathy by 4‐FA, to assess its effects on oxytocin, and to test potential associations between both. Methods Twelve healthy poly‐drug users were included in a double‐blind placebo‐controlled two‐way crossover study. Treatments were 4‐FA (100 mg) and placebo; empathy was assessed by means of the multifaceted empathy test, and blood samples were taken before and after treatment administration to determine oxytocin concentrations. Results 4‐FA reduced cognitive empathy, whereas emotional empathy was left unaffected. One hour after treatment, plasma oxytocin levels were significantly increased compared with placebo. Behavioral and hormonal effects were unrelated. Conclusion Although 4‐FA shares its pharmacological mechanism with MDMA and amphetamine, current findings seem to indicate that it affects empathy differently. The 4‐FA‐induced increase in oxytocin levels was independent of behavioral effects, which confirms previous findings that drug‐induced effects on peripheral oxytocin levels are not associated with empathy.

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Drug liking and wanting, not impulsive action or reflection is increased by 4-fluoroamphetamine

Cited by 8 publications

References 38 publications

Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants

Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants

Pharmacokinetic properties of 4‐fluoroamphetamine in serum and oral fluid after oral ingestion

Independent elevation of peripheral oxytocin concentrations and reduction in cognitive empathy during 4‐fluoroamphetamine intoxication

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