Historic psychedelic drug trials and the treatment of anxiety disorders

Abstract

Introduction: In this paper, we systematically review literature from 1940 to 2000 relating to the combined use of psychological therapies and psychedelic drugs in the treatment of ICD-10 anxiety disorders. Methods: The databases Ovid MEDLINE(R), PsycINFO, and Multidisciplinary Association for Psychedelic Studies (MAPS) were searched for case reports and trials involving humans in the treatment of ICD-10 anxiety and related disorders. Twentyfour studies are described; four describe anxiety symptoms in diverse patient groups, 14 studies describe historic diagnoses that usefully correspond with ICD-10 anxiety disorders, six studies pooled results or failed to detail results specific to contemporary ICD-10 anxiety disorders. Two of the 24 studies reported are individual case reports while two of them were inadequate in terms of the reporting of outcome measures. Thus 20 studies were ultimately included in the summary analysis. Results: Three of the 20 studies reviewed described improvements in anxiety by standardized measures (p < .05) and two studies found that this effect was dose related. Of the 20 studies included in the final analysis, 94 of 145 (65%) cases of "psychoneurotic anxiety reaction" as defined by Diagnostic and Statistical Manual of Mental Disorders-I showed improvement that ranged from moderate improvement to full recovery. Despite methodological inadequacies, the results from previous studies are encouraging and should be used to guide and inform further investigation. Conclusion: The majority of studies indicate that a combination of psychedelic drug administration and psychological therapy was most beneficial. We found no study suggesting that the pharmacological action of psychedelic drugs in isolation is sufficient.

Hallucinogenic/psychedelic 5HT2A receptor agonists as rapid antidepressant therapeutics: Evidence and mechanisms of action

“…Until their prohibition in the late 1960s/early 1970s, LSD, psilocybin, and mescaline were investigated in humans for the possible treatment of mood, anxiety, and substance use disorders (for reviews see: dos Santos and Hallak, 2020; McGlothlin and Arnold, 1971; Nichols, 2014, 2016; Nutt et al, 2020; Riedlinger and Riedlinger, 1994). Recent systematic reviews of studies in depression (Rucker et al, 2016), anxiety (Weston et al, 2020), substance use disorders (Krebs and Johansen, 2012), and in depression and anxiety associated with life-threatening diseases and cancer (Reiche et al, 2018) reported promising results from these early trials. Improvements often included fast and enduring symptom reduction (Krebs and Johansen, 2012; Reiche et al, 2018; Rucker et al, 2016; Weston et al, 2020).…”

“…Recent systematic reviews of studies in depression (Rucker et al, 2016), anxiety (Weston et al, 2020), substance use disorders (Krebs and Johansen, 2012), and in depression and anxiety associated with life-threatening diseases and cancer (Reiche et al, 2018) reported promising results from these early trials. Improvements often included fast and enduring symptom reduction (Krebs and Johansen, 2012; Reiche et al, 2018; Rucker et al, 2016; Weston et al, 2020). However, these previous studies often had methodological shortcomings, including broad definition of diagnoses, non-standardized procedures, varying drug doses, and lack of placebo and controls.…”

Editorial: Pharmacotherapy of Anxiety Disorders: Promises and Pitfalls

“…Several serotonergic agents that were originally investigated for depression have been studied and showed potential, but these trials did not lead to FDA approval and there are limited ongoing investigations. There are also trials of psilocybin and lysergic acid diethylamide (LSD) for anxiety but primarily in those with life-threatening diseases (like cancer) (17,18). Ketamine has been studied in a randomized controlled trial in SAD but there are no ongoing trials in anxiety disorders (19).…”

Psychedelics: Old drugs, new trips

“…It is generally unknown by whole generations of psychiatrists that the classical psychedelics d -lysergic acid diethylamide (LSD) and psilocybin were prescribable medicines in psychiatry throughout the USA and Europe until prohibition was effectively imposed on routine clinical use and most scientific research around 1970. Hundreds of papers were published on their clinical use, which we have synthesised in systematic reviews (Butler et al, 2020; Rucker et al, 2016; Weston et al, 2020) and narrative (Rucker et al, 2018).…”