Clinical Pharmacology & Therapeutics
May 28, 2026
Gia Han Le, Sabrina Wong, Danica E. Johnson et al.
Major depressive disorder (MDD) and treatment-resistant depression (TRD) remain leading causes of disability, providing the impetus for receptor-level treatment strategies beyond monoamine reuptake. The serotonin 5-HT2B receptor (5-HT2BR) is uniquely positioned at the interface of central-antidepressant mechanisms and peripheral cardiac risks. Herein, we reviewed preclinical, translational and...
Clinical Pharmacology & Therapeutics
February 28, 2025
Lorenz Mueller, Alen Jelusic, Avram Tolev et al.
15 citations
Psychedelics, such as psilocybin and lysergic acid diethylamide (LSD), are being investigated for the treatment of depressive and anxiety disorders, for which concomitant treatment with selective serotonin reuptake inhibitors (SSRIs) is prevalent. The present study investigated the acute response to single doses of LSD (100 μg) after daily administration of paroxetine (10 mg for 7 days,...
Clinical Pharmacology & Therapeutics
September 30, 2024
Andreas Halman, Rachel Conyers, Claire Moore et al.
13 citations
Psychedelics have recently re‐emerged as potential treatments for various psychiatric conditions that impose major public health costs and for which current treatment options have limited efficacy. At the same time, personalized medicine is increasingly being implemented in psychiatry to provide individualized drug dosing recommendations based on genetics. This review brings together these...
Clinical Pharmacology & Therapeutics
October 5, 2023
Robert H. Dworkin, Michael Mcdermott, Sandeep M. Nayak et al.
16 citations
Clinical trials of psychedelics have provided support for their potential efficacy and safety. Although most combined a psychedelic with psychological support akin to psychotherapy, providing psychotherapy is costlier and more difficult to scale than providing only support to reduce harms. Trials with factorial designs can evaluate the individual effects of a psychedelic and psychotherapy and...
Clinical Pharmacology & Therapeutics
May 30, 2023
Pablo Mallaroni, Riccardo Paci, Sabrina Ritscher et al.
34 citations
2,5‐dimethoxy‐4‐bromophenethylamine (2C‐B) is a hallucinogenic phenethylamine derived from mescaline. Observational and preclinical data have suggested it to be capable of producing both subjective and emotional effects on par with other classical psychedelics and entactogens. Whereas it is the most prevalently used novel serotonergic hallucinogen to date, it's acute effects and distinctions...
Clinical Pharmacology & Therapeutics
March 15, 2023
Piet H. van der Graaf
1 citation
In the televised fictional drama "Nine Perfect Strangers," based on a novel with the same name,1 nine people gather for a retreat in a wellness resort which promises to heal and transform them. The guests discover that as part of the program the charismatic owner of "Tranquillum" has been feeding them smoothies spiked with psilocybin-containing mush room extract without their knowledge. After...
Clinical Pharmacology & Therapeutics
December 12, 2022
Friederike Holze, Urs Duthaler, Anna M Becker et al.
116 citations
Psilocybin is being investigated as a potential treatment for psychiatric and neurological disorders. Only a few studies have evaluated the pharmacokinetics (PKs) of psilocybin and have used body weight‐adjusted dosing. Data on PKs and the PK‐pharmacodynamic (PD) relationship of fixed doses that are commonly used are unavailable. The present study characterized the PKs and PK‐PD relationship of...
Clinical Pharmacology & Therapeutics
November 7, 2021
Anna M Becker, Friederike Holze, Tanja Grandinetti et al.
177 citations
The psychedelic psilocybin is being investigated for the treatment of depression and anxiety. Unclear is whether antidepressant treatments interact with psilocybin. The present study used a double‐blind, placebo‐controlled, crossover design with two experimental test sessions to investigate the response to psilocybin (25 mg) in healthy subjects after pretreatment with escitalopram or placebo....
Clinical Pharmacology & Therapeutics
September 25, 2020
Friederike Holze, Matthias E. Liechti, Nadia R. P. W. Hutten et al.
63 citations
“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 pharmacokinetic‐pharmacodynamic 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...
Clinical Pharmacology & Therapeutics
August 29, 2020
Eva G. Katz, David Hough, Teodora Doherty et al.
35 citations
This post hoc analysis assessed the benefit-risk profile of esketamine nasal spray + oral antidepressant (AD) induction and maintenance treatment in patients with treatment-resistant depression (TRD). The Benefit-Risk Action Team framework was utilized to assess the benefit-risk profile using data from three induction studies and one maintenance study. Benefits were proportion of remitters or...
Clinical Pharmacology & Therapeutics
August 24, 2017
Edward M. Sellers, Deborah B. Leiderman
27 citations
Interest in the potential therapeutic benefits of psychedelic agents has recently increased. In addition to psilocybin, a wide variety of agents with psychedelic properties have been proposed and partially tested. However, the challenges of obtaining approval to market a restricted psychotomimetic agent are formidable.
Clinical Pharmacology & Therapeutics
May 26, 2017
EM Sellers
18 citations
Much of the history of pharmacology and therapeutics involves finding new uses for old drugs. The latest rediscovery is that of psychedelic drugs. Since they can cause profound distortions of perception and were once used as part of religious ceremonies, such research may seem unusual at this time.
Clinical Pharmacology & Therapeutics
January 13, 2017
M Huestis, Rachel F. Tyndale
12 citations
This “Designer Drugs 2.0” issue of Clinical Pharmacology & Therapeutics focuses on novel psychoactive substances, primarily cannabinoids and cathinones, and the repurposing of established psychoactive compounds (e.g., modafinil, psilocybin, lysergic acid diethylamide, and 3,4‐methylenedioxymethamphetamine) that simultaneously offer new pharmacotherapies and pose serious health problems. Novel...
Clinical Pharmacology & Therapeutics
November 10, 2016
Bb Yazar‐klosinski, Mc Mithoefer
81 citations
Phase II trials of 3,4‐methylenedioxymethamphetamine (MDMA)‐assisted psychotherapy have demonstrated initial safety and efficacy for treatment of posttraumatic stress disorder (PTSD), with potential for expansion to depression and anxiety disorders. In these trials, single doses of MDMA are administered in a model of medication‐assisted psychotherapy, differing from trials involving daily drug...
Clinical Pharmacology & Therapeutics
November 4, 2016
De Nichols, Mw Johnson, Cd Nichols
366 citations
Scientific interest in serotonergic psychedelics (e.g., psilocybin and LSD; 5‐HT 2A receptor agonists) has dramatically increased within the last decade. Clinical studies administering psychedelics with psychotherapy have shown preliminary evidence of robust efficacy in treating anxiety and depression, as well as addiction to tobacco and alcohol. Moreover, recent research has suggested that...
Clinical Pharmacology & Therapeutics
August 10, 2011
Kazuya Maeda, Yasumasa Ikeda, Tomoe Fujita et al.
207 citations
Clearance of atorvastatin occurs through hepatic uptake by organic anion transporting polypeptides (OATPs) and subsequent metabolism by cytochrome P450 (CYP) 3A4. To demonstrate the relative importance of OATPs and CYP3A4 in the hepatic elimination of atorvastatin in vivo, a clinical cassette microdose study was performed. A cocktail consisting of a microdose of atorvastatin along with probe...
Clinical Pharmacology & Therapeutics
July 20, 2011
Thomas F. Newton
9 citations
In this issue, Hysek and colleagues present new data describing the impact of treatment with reboxetine on the effects produced by 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in human volunteers. They demonstrate that several effects of MDMA are mediated by reboxetine's actions on norepinephrine (NE) transporters, an unexpected finding. Building on earlier work, their new data provide...
Clinical Pharmacology & Therapeutics
June 29, 2011
Kazuya Maeda, Junichi Takano, Yasumasa Ikeda et al.
50 citations
Microdosing studies are effective in enabling the early identification of the pharmacokinetic properties of compounds administered to humans. However, the nonlinearity of the pharmacokinetics between microdose and therapeutic dose, attributable to the saturation of metabolic enzymes and transporters, is a major concern. Verapamil and quinidine are good substrates of both the multidrug...
Clinical Pharmacology & Therapeutics
June 15, 2011
Cédric M. Hysek, Linda D. Simmler, M. Ineichen et al.
153 citations
This study assessed the pharmacodynamic and pharmacokinetic effects of the interaction between the selective norepinephrine (NE) transporter inhibitor reboxetine and 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in 16 healthy subjects. The study used a double-blind, placebo-controlled crossover design. Reboxetine reduced the effects of MDMA including elevations in plasma levels of NE,...
Clinical Pharmacology & Therapeutics
December 19, 2007
WT Robinson
37 citations
The Food and Drug Administration (FDA) Critical Path Initiative as well as the European Medicines Agency Road Map to 2010 (ref. 2) call for opportunities for more efficient drug development. One of the initiatives that has emerged in this context is the elaboration through guidance of exploratory investigational new drugs (INDs)/clinical trial applications (CTAs). This article reviews the...
Clinical Pharmacology & Therapeutics
September 1, 2006
Graham Lappin, W. Kuhnz, R. Jochemsen et al.
242 citations
OBJECTIVES: A volunteer trial was performed to compare the pharmacokinetics of 5 drugs--warfarin, ZK253 (Schering), diazepam, midazolam, and erythromycin--when administered at a microdose or pharmacologic dose. Each compound was chosen to represent a situation in which prediction of pharmacokinetics from either animal or in vitro studies (or both) was or is likely to be problematic. METHODS: In...
Clinical Pharmacology & Therapeutics
November 1, 1968
Leo E. Hollister, R. K. Richards, H. K. Gillespie
195 citations
A synthetic isomer of tetrahydrocannabinol (1‐Δ'‐3,4‐transtetrahydrocannabinol), believed to be identical to the most active naturally occurring THC, was compared with a semisynthetic THC‐like compound, synhexyl. Sixteen volunteer subiects received THC in doses ranging from 341 to 946 p.g per kilo gram (median 581). Thirteen subjects received synhexyl in doses ranging from 633 to 2,666 µg per...
Clinical Pharmacology & Therapeutics
September 1, 1968
John G. Wagner, George K. Aghajanian, O. Bing
61 citations
Previously published plasma concentrations of LSD‐25, observed following intravenous iniection of 2 mcg. per kilogram of LSD‐25, have been found to be explained by the two‐compartment open model. Performance scores on arithmetic tests were shown to be highly linearly correlated with the concentration in the “tissue” (outer) compartment. The estimated volume of the plasma (inner) compartment was...
Clinical Pharmacology & Therapeutics
March 1, 1965
A. Hoffer
83 citations
This is a review of an important but controversial subject, written by one of the important figures involved in the controversy. It was not possible to get a review in depth by someone who was not also involved in the controversy. With this in mind, this review was accepted for publication because it was written by an authority actively engaged in the problem and because it was thought...
Clinical Pharmacology & Therapeutics
September 1, 1964
George K. Aghajanian, O. Bing
118 citations
Two micrograms per kilogram of LSD‐25 was administered intravenously to five normal human subjects. The concentration of drug in plasma was determined serially over the subsequent 8 hours. LSD‐25 was found to be present in human plasma in relatively large quantities during the period of peak effect. The half‐life of LSD‐25 in human plasma was calculated to be 175 minutes.