Springtime for psychopharmacology

Abstract

As we head into the (Northern Hemisphere) spring, the Journal publishes another set of papers which illustrate the robust health of the science of psychopharmacology. Once again, papers mostly focus on psychedelic drugs and related topics reflecting the zeitgeist (Young, 2022). de Wit et al. (2022) explore translational challenges and opportunities between clinical research and laboratory settings. Using 3,4-methylenedioxymethamphetamine (MDMA) as an example, the authors highlight the methodological differences in determining how drugs can elicit positive clinical outcomes and the psychological processes by which these occur. By dissecting the widely recognised concept of ‘set and setting’, the pertinent issues of expectancy effects, inter-individual subject characteristics and confounding influences of physical and social context are examined. The authors make practical recommendations, for example, the identification of standardised outcome measures that are appropriate for varied research settings. These suggestions should inform study design aimed at harmonising laboratory based and psychiatric research, in the pursuit of improved cognitive neuropsychological hypotheses in relation to clinical improvement. Schlag et al. (2022) review adverse effects associated with the classical psychedelics. They note minimal evidence for widely perceived risks such as neurotoxicity and abuse potential. While risks such as psychosis or self-harm may occur in individual cases, they can be minimised by informed patient selection and safe, controlled settings. The authors acknowledge that while some of our current understanding of the physiological and psychological risks of psychedelics comes from pre-prohibition research, modern scientific approaches (e.g. placebo-controlled, randomised, double-blind trials) can largely address these shortcomings. Providing relevant political and historical context, the authors highlight sensitivities required to develop novel treatments with substances that carry stigmatised histories. Ermakova et al. (2022) outline the key pharmacological and subjective characteristics of 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and explore potential for clinical utility. The short duration of action and minimal visual effects make it an attractive candidate for further study. The authors further note that increased rates of mystical experience and ego-dissolution, phenomena previously demonstrated to be related to positive, long-term clinical outcomes, are observed with 5-MeO-DMT administration. The currently available data suggest a similar risk profile to that of other classical psychedelics, further supporting the case for investigation of their clinical utility in psychiatry. Agin-Liebes et al. (2022) assessed changes in psychological flexibility, cognitive reappraisal and mood following ayahuasca use in a naturalistic (Shipibo) setting. Over a 3-month follow-up period, increased positive and negative affect and psychological flexibility were observed. Controlling for validity variables, the authors demonstrated that favourable changes in measures of anxiety and depression accrued for those with trait suggestibility and positive expectancies. The results support the integration of ‘third-wave’ psychological therapies, designed to target facets of emotion regulation parallel to psychological flexibility, such as Acceptance and Commitment Therapy (ACT), in psychedelicassisted therapy models. Uthaug et al. (2022) conducted the first epidemiological study on the use of mescaline, a psychoactive of the phenethylamine class found in numerous species of cacti, including San Pedro and Peyote. The authors note that mescaline use is infrequent, similar to that of 5-MeO-DMT. Findings include that the majority of users included used mescaline for spiritual purposes or to increase connectedness to nature, and suggest a low potential for abuse as with other psychedelics. Furthermore, respondents who reported prior psychiatric diagnoses, including depression, anxiety, substance misuse and post-traumatic stress disorder (PTSD) reported improvements in related symptoms. Family et al. (2022) conducted a Phase I, proof-of-concept study with lysergic acid diethylamide (LSD) that used both open-label and double-blind placebo-controlled design. The study evaluated the safety, tolerability, pharmacokinetics and subjective effects of 50, 75 and 100 μg of LSD in healthy volunteers. No serious adverse events were observed, with active doses of LSD eliciting greater subjective effects in comparison to placebo. This study represents an important first step in demonstrating feasibility of this novel intervention model and supporting the design of further trial protocols. Qualitative analysis of subjects’ narrative reports from this study was conducted by Springtime for psychopharmacology