Control Conditions in Randomized Trials of Psychedelics: An ACTTION Systematic Review.

Objective: To systematically review control conditions of all available randomized psychedelic trials.Data Sources: We searched PubMed, PsycINFO, and EMBASE for randomized trials of psychedelics in humans from 1940 through May 2020 with no language restrictions. PRISMA guidelines were followed. (PROSPERO registration number: PROSPERO-CRD42020205341.).Study Selection: All randomized trials of psychedelics in humans from 1940 through May 2020 were included.Data Extraction: Two independent reviewers performed extraction. Extracted data included study design, demographics, blinding type, whether and how blind integrity was assessed, psychedelic used and dose, drug control condition and dose, type of non-drug control condition, number of dosing sessions, and recruitment source. Outcome data were not collected.Results: In total, 126 articles were included, encompassing 86 unique studies. Of studies with a drug control condition (80), 49 (61.2%) used an inert placebo control, 16 (20.0%) used active comparators, 12 (15.0%) used both, and 3 (3.8%) used only different active psychedelic doses as a control. Only 3 of 21 therapeutic trials compared the use of psychological support to a minimally supportive condition. The majority (81/86; 94%) of studies were blinded, though only 14 (17.3%) included blind assessment; only 8 of these 14 studies assessed participants' blinding. Blinding success, assessed in highly varied ways, was generally poor.Conclusions: Randomized psychedelic trials underutilize elements that would improve quality or provide important information: blind assessment, active drug controls, and testing psychological support against minimal-support conditions. Several queried categories, including blind integrity assessment and details of non-drug control conditions, were insufficiently reported by many reviewed studies. Recommendations are provided to improve trial methods.

E-cigarette Price Impacts legal and Black-Market Cigarette Purchasing Under a Hypothetical Reduced-Nicotine Cigarette Standard.

INTRODUCTION: The Tobacco Control Act gives the U.S. Food and Drug Administration authority to establish a reduced-nicotine content standard in combusted cigarettes. This future potential regulation may pose a significant public health benefit; however, black markets may arise to meet demand for normal-nicotine content cigarettes among smokers unwilling to transition to or use an alternative product. AIMS AND METHODS: We determined the behavioral-economic substitutability of illicit normal-nicotine content cigarettes and e-cigarettes for reduced-nicotine content cigarettes in a hypothetical reduced-nicotine regulatory market. Adult cigarette smokers were recruited online to complete hypothetical cigarette purchasing tasks for usual-brand cigarettes, reduced-nicotine content cigarettes, and illicit normal-nicotine content cigarettes, as well as a cross-commodity task in which reduced-nicotine content cigarettes were available across multiple prices and illicit cigarettes were concurrently available for $12/pack. Participants completed two three-item cross-commodity purchasing tasks in which e-cigarettes were available for $4/pod or $12/pod alongside reduced-nicotine content cigarettes and illicit cigarettes. RESULTS: Usual-brand cigarette purchasing was greater than illicit normal-nicotine content cigarettes and less than reduced-nicotine content cigarettes. In the cross-commodity purchasing tasks, illicit cigarettes and e-cigarettes both served as economic substitutes for reduced-nicotine content cigarettes; however, when e-cigarettes were available for $4/pod, they were purchased at greater levels than illicit cigarettes and resulted in greater reductions in reduced-nicotine content cigarettes purchasing than when available for $12/pod. CONCLUSIONS: These data suggest that some smokers are willing to engage in illicit cigarette purchasing in a reduced-nicotine regulatory environment, but e-cigarette availability at lower prices may reduce black-market engagement and shift behavior away from combusted cigarette use. IMPLICATIONS: E-cigarettes available at low, but not high, prices were stronger substitutes for legal, reduced-nicotine content cigarettes than illegal, normal-nicotine content cigarettes in a hypothetical reduced-nicotine tobacco market. Our findings suggest the availability of relatively inexpensive e-cigarettes may reduce illicit cigarette purchasing and combusted cigarette use under a reduced-nicotine cigarette standard.