Microdosing of scopolamine as a “cognitive stress test”: Rationale and test of a very low dose in an at‐risk cohort of older adults
Peter J. Snyder, Yen Ying Lim, Rachel Schindler, Brian R. Ott, Stephen Salloway, Lori Daiello, Christine Getter, Catherine M. Gordon, Paul Maruff
Alzheimer s & Dementia March 1, 2014 DOI: 10.1016/j.jalz.2014.01.009 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 26 |
| Population | Healthy older adults aged 55-75 years with two risk factors for Alzheimer's disease but low cortical amyloid burden |
| Intervention | Scopolamine |
| Dose | 0.20 mg subcutaneously |
| Duration | Assessments at baseline and 1, 3, 5, 7, and 8 hours postinjection |
| Measures | Groton Maze Learning Test (GMLT) |
| Topics | Microdosing |
| Key findings | A 0.20 mg subcutaneous dose of scopolamine reliably impaired cognition at 3 hours postdose, with moderate effects on Groton Maze Learning Test total errors, rule-break errors, and composite score (d ≈ 0.50), and full recovery within 5 hours. The authors argue this supports scopolamine as a 'cognitive stress test' paradigm for identifying preclinical Alzheimer's disease. |
Abstract
Abstract:
Background: Abnormal β‐amyloid (Aβ) is associated with deleterious changes in central acetylcholinergic tone in the very early stages of Alzheimer's disease (AD), which may be unmasked by a cholinergic antagonist. We aimed to establish an optimal “microdose” of scopolamine for the development of a “cognitive stress test.”
Methods: Healthy older adults (n = 26, aged 55–75 years) with two risk factors for AD, but with low cortical Aβ burden, completed the Groton Maze Learning Test (GMLT) at baseline and then received scopolamine (0.20 mg subcutaneously). Participants were reassessed at 1, 3, 5, 7, and 8 hours postinjection.
Results: There were significant differences, of a moderate magnitude, in performance between baseline and 3 hours postinjection for total errors, rule break errors, and the GMLT composite (d ≈ 0.50) that were all unrelated to body mass.
Conclusions: A very low dose of scopolamine leads to reliable cognitive impairment at 3 hours postdose (Tmax) and full cognitive recovery within 5 hours, supporting its use as a prognostic test paradigm to identify individuals with potential preclinical AD. This paradigm is being implemented in a larger cohort of healthy adults, with high or low Aβ, to identify pharmacodynamic differences between groups.
Comparable studies
Other observational and cohort studies on microdosing, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Microdosing psychedelics: personality, mental health, and creativity differences in microdosers Respondents recruited from online forums | 2019 | Observational study | |
| Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing Individuals planning a weekly microdosing regimen | 2021 | Prospective observational study | n = 81 |
| Might Microdosing Psychedelics Be Safe and Beneficial? An Initial Exploration. More than a thousand individuals from 59 countries | 2019 | Observational cohort | n = 1,000 |
| Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls Psilocybin microdosers and non-microdosing comparators | 2022 | Naturalistic observational study | n = 1,133 |
| Nonlinear Pharmacokinetics of Oral Quinidine and Verapamil in Healthy Subjects: A Clinical Microdosing Study Healthy subjects | 2011 | Observational cohort |