Historic psychedelic drug trials and the treatment of anxiety disorders
Abstract: 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.
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. Twenty-four 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.
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.
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.
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The classical psychedelics comprise three main chemical classes: organic tryptamines (psilocybin and dimethyltryptamine [DMT] with ayahuasca being the combination of DMT and a monoamine oxidase inhibitor), the phenethylamines (mescaline), and the semisynthetic ergolines (lysergic acid diethylamide [LSD]; Geyer, Nichols, & Vollenweider, 2009). It is now accepted that the prototypic “psychedelic experience” arises from agonism at the serotonin 2A receptor subtype (5-HT2AR; Madsen et al., 2019; Vollenweider, Vollenweider-Scherpenhuyzen, Bäbler, Vogel, & Hell, 1998).
In the last decade, results from a number of studies on the safety and therapeutic potential of psychedelics hold significant promise for a range of conditions, including anxiety disorders. Recent, well designed studies exploring the safety of these substances suggest that psychedelics may impact on depressive symptoms as well as anxiety associated with life-threatening diseases (Carhart-Harris et al., 2016; Gasser et al., 2014; Griffiths et al., 2016; Grob et al., 2011; Palhano-Fontes et al., 2019; Ross et al., 2016).
In this paper, we systematically review literature from 1940 to 2000 regarding the use of psychedelic drugs in the treatment of ICD-10 anxiety disorders so any supporting evidence can inform future research into the use of psychedelics for treating anxiety disorders.
ICD-10 describes phobic and “other anxiety disorders” under “neurotic, stress related, and somatoform disorders.” The grouping “other anxiety disorders” encompasses panic, generalized anxiety disorder (GAD), and mixed anxiety and depressive disorder (World Health Organization [WHO], 1992). In the United Kingdom, anxiety disorders grouped with posttraumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD) are the most frequently diagnosed psychiatric conditions with 10% of the population having a “disabling anxiety disorder” at some stage in their life (Fineberg et al., 2013). Despite significant prevalence, many go undetected (Hirschfeld, 2001) and those identified receive far less attention than other areas of mental health (Kessler et al., 2005; Kroenke, Spitzer, Williams, Monahan, & Löwe, 2007)....[Full Article]