Dr. Lii’s Research

Propofol-Enhanced Blinding to Test Psychedelics with Analgesic Potential

Abstract: This research aims to solve the critical issue of participant unblinding in randomized controlled trials (RCTs) involving psychedelic drugs with analgesic potential. Traditional methods fail to mask the intense subjective effects of these drugs, leading to unblinding and placebo-expectancy effects that compromise interpretability. To overcome these challenges, the PI will introduce propofol-enhanced blinding, which uses moderate sedation with propofol to obscure the subjective experience of psychedelic drugs, thus preserving the integrity of the blind. Ketamine will be used to test propofol-enhanced blinding due to its accessibility and potential for treating depression and chronic pain. The research will address three aims: Aim 1 will characterize the efficacy and safety of propofol-enhanced blinding in a double-blind, parallel-arm RCT of 32 adults with chronic pain and depression, who will each receive ketamine or placebo during propofol sedation.  Aim 2 will identify and address recruitment barriers, specifically pertaining to patient hesitancy, perceived safety concerns and burdens.  Aim 3 will assess the impact of patient expectations and opioid use on mood and pain outcomes, providing insights into placebo- and drug-specific mechanisms. Propofol-enhanced blinding will greatly enhance scientific rigor in psychedelic research, impacting multiple disciplines including pain medicine.  This study will establish the feasibility of propofol-enhanced blinding and lay the groundwork for future investigations into the mechanisms and efficacy of psychedelic treatments.