Mounting clinical evidence could lead to the approval of new psychedelic medicines. The FDA’s draft guidance on psychedelics research includes several recommendations that may be contentious.
BACKGROUND: In treatment-resistant depression, commonly defined as a lack of response to two or more consecutive treatments during the current depressive episode, the percentage of patients with remission is low and the percentage with relapse is high. The efficacy and safety of esketamine nasal spray as compared with extended-release quetiapine augmentation therapy, both in combination with...
BACKGROUND Electroconvulsive therapy (ECT) and subanesthetic intravenous ketamine are both currently used for treatment-resistant major depression, but the comparative effectiveness of the two treatments remains uncertain. METHODS We conducted an open-label, randomized, noninferiority trial involving patients referred to ECT clinics for treatment-resistant major depression. Patients with...
A “nonpsychedelic psychedelic” compound was shown to have anxiolytic and antidepressive effects in a mouse model. This commentary asks whether assumptions implicit in mouse modeling can be trusted to translate to humans.
Psilocybin is being studied for use in treatment-resistant depression. In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the...
Depression ranks first among psychiatric disorders that dominate the global burden of disease, posing a substantial personal strain and economic drain on nations.1 At least 30 drugs are Food and Drug Administration (FDA)–approved to treat depression,2 yet a systematic review and meta-analysis of 22 antidepressants concluded that although they were more effective than placebo in adults with...
On the basis of the change in depression scores on the QIDS-SR-16 at week 6, this trial did not show a significant difference in antidepressant effects between psilocybin and escitalopram in a selected group of patients. Secondary outcomes generally favored psilocybin over escitalopram, but the analyses of these outcomes lacked correction for multiple comparisons. Larger and longer trials are...
In The Doors of Perception, Aldous Huxley described his trial of mescaline as "the most extraordinary and significant experience available to human beings this side of the Beatific Vision." His exegesis was preceded by the synthesis of the hallucinogen lysergic acid diethylamide (LSD) by Sandoz chemist Albert Hoffman in 1938 and was followed by Hoffman's extraction of psilocybin from Psilocybe...
Esketamine for Treatment-Resistant Depression The FDA has approved esketamine, the first antidepressant in a new class, for treatment-resistant depression. The agency weighed the drug’s rapid onset...
A 31-year-old woman was admitted to the emergency department because of a seizure-like attack after a single 3.5-g dose of ibogaine. ECG showed a severe prolonged-QT interval of 548 msec and ventri...
An out-of-body experience was repeatedly elicited during stimulation of the posterior part of the superior temporal gyrus on the right side in a patient in whom electrodes had been implanted to suppress tinnitus. Positron-emission tomographic scanning showed brain activation at the temporoparietal junction--more specifically, at the angular-supramarginal gyrus junction and the superior temporal...
To the Editor: Recreational use of 3,4-methylenedioxymethamphetamine (MDMA, or “ecstasy”), a hallucinogen, has increased both in Europe and the United States.1 This substance is manufactured in illicit laboratories from a variety of organic ketone precursors. MDMA, which is structurally related both to the stimulant amphetamine and to the hallucinogen mescaline, promotes the release of both...
In a prospective study of 10 patients given d-lysergic acid diethylamide 25, there was no difference in frequency of chromosome breakage between samples obtained immediately before and 24 hours after treatment. In 11 patients, treated over periods ranging from 24 hours to eight years before sampling, the frequency of chromosomal breaks did not differ from that found in untreated controls. In an...
NO drug used by man has stimulated greater public-debate than lysergic acid diethylamide (LSD). This brief review of the current status of the drug will summarize its pharmacology, medical uses and dangers. No attempt will be made to analyze in detail its alleged benefits when taken indiscriminately or under uncontrolled circumstances; these include augmented aesthetic sensitivity, enhanced...
THE induction of chromosomal aberrations by exogenous agents, such as viruses, radiation and chemicals, is an area of active cytogenetic investigation.1 Recently, the psychotomimetic hallucinogen, lysergic acid diethylamide (LSD-25), has been added to the list of chemicals capable of causing abnormalities in the chromosomes of human leukocytes.2 , 3 Such preliminary studies report the in vitro...
MOST typically, medical research has proceeded from clinical observation to clinical investigation to laboratory experiment. Some of the striking exceptions to this pattern have been studies of a variety of pharmacologic agents that are capable of producing changes in psychic state. These drugs, first isolated or synthesized in the laboratory, occasionally create a new clinical syndrome or a...
DURING the last few years a great revival of interest has occurred in the search for a biochemical basis for schizophrenia and the other types of psychosis. There are several reasons for this. Modern laboratory technics permit the detection and accurate quantitation of substances in the blood and tissues for which satisfactory procedures were not available formerly. The discovery of a partially...