No evidence for deleterious effects of psilocybin and MDMA on working memory or related neurophysiological activity in a non-clinical population: An uncontrolled exploratory study

Background: Research indicates psychedelics hold therapeutic potential, but possible deleterious effects have been insufficiently examined. We explored working memory (WM) performance and WM-related neurophysiological activity before and after exposure to psilocybin or 3,4-methylenedioxymethamphetamine (MDMA) in an uncontrolled study. Methods: Healthy participants were exposed to a single dose of psilocybin or MDMA (data analysed from 29 participants for each drug, with 16 receiving both drugs after >3-month washout). One to 16 days before and 5–16 days after dosing, participants completed a 3back WM task and eyes-closed resting with electroencephalography (EEG), plus a 3back during a 3-month remote follow-up. Results: After dosing, both groups showed increased alpha to gamma WM-related oscillatory power ( p < 0.001). After psilocybin, participants showed steeper WM-related aperiodic slopes ( p = 0.018), an effect maximal in occipital electrodes ( p < 0.001, Cohen’s d = 0.802, BF 10 = 155.138), and significant in occipital electrodes during resting ( p = 0.008). The MDMA group showed improved task accuracy in the post-dosing EEG session ( p = 0.005, Cohen’s d = 0.561, BF 10 = 7.809). Both groups showed improved accuracy at 3-months ( p -holm < 0.001, Cohen’s d = 0.678, BF 10 = 272.074). Conclusions: Our results are suggestive of enduring neurophysiological effects following a single dose of MDMA or psilocybin. Our results do not support concerns about cognitive impairments from single exposures to MDMA or psilocybin in controlled settings, suggesting clinical utility does not risk impairing WM. However, given the uncontrolled study design, future research is required to confirm our observations reflect drug-induced neurophysiological changes.