We are partnering with an Ayahuasca center in Brazil, where ayahuasca has been legal for ritualistic purposes since 2010. Our partner will recruit adults who have never taken ayahuasca before, screening people based on disease history, as is their standard practice. For safety, those with severe depression, or a family history of bipolar or schizophrenic disorders are not allowed to participate. Recruitment will happen on a rolling basis, as per the center’s status quo. Our goal is to recruit about ≈500 participants split across ≈15 sessions, averaging 33 participants per session. However, the final number of participants will hinge on how many first-timers the center can successfully recruit.
The randomization will be performed by our partner, and our only role is to administer the surveys. Participants will be randomly assigned to one of two groups upon arrival at the center: (i) take a regular dose of ayahuasca, offered in their usual ayahuasca sessions, with 3:1 concentration of ayahuasca:water, or (ii) take a less concentrated dose of ayahuasca, with 1:1 of concentration ayahuasca:water. To guarantee there is no selection into treatment, the study will be single-blinded (i.e. participants will not be informed about their treatment assignment until they fill out the last survey).
The sessions are preceded by a ≈15 minutes lecture given by the center’s owners. The lectures could be about either (i) happiness and pleasure or (ii) taming the mind. They will alternate which lectures are taught in each of the study sessions, allowing us to estimate suggestive effects of the lecture type on the nature of trips, and to explore treatment effect heterogeneity by lecture type.
We will also survey participants who booked a session but canceled or did not show up to the ceremony. For them, we will be interested in outcomes we measure at baseline, such as depression, (predicted) happiness, and work satisfaction. This group will be our “pure control group,” though given selection into the group, we will use a difference-in-difference approach for suggestive evidence of effects of the placebo relative to the pure control.
Randomization is stratified by sex, and it takes place when participants’ list for each study session has been closed (i.e. about one day before a study session). The center will perform the randomization by generating random numbers in a spreadsheet, allowing us to validate whether the randomization was implemented correctly.
August 29, 2023 AMENDMENT: We have successfully completed six study sessions following the design described above, in which participants were randomized into either (i) taking a regular ayahuasca dose or (ii) a diluted ayahuasca dose. Unexpectedly, we found that participants in the diluted dose group still experienced trip-related features of their ayahuasca experience. Relatedly, 26% of participants in the diluted dose group (N = 95) reported their ayahuasca experience was the single most meaningful in their life, compared with 0% of pure control participants (the “no shows”). This “placebo is treated” issue sharply reduces our first stage effects, reducing our statistical power to detect effects of ayahuasca.
After careful consideration and conversations with our partner center, they suggested we instead use an Amazonian tea called jurema for the placebo treatment, which has a similar color and taste as ayahuasca, but does not have any psychedelic component. We did two sessions with jurema (the first on June 30th, 2023 and the second one on August 11th, 2023), in which participants were randomized into (i) taking a regular ayahuasca dose, as before or (ii) taking a dose of jurema. Our first stage measures improved with the jurema as control: for example, only 14% of jurema-takers reported their participation in the ceremony to be the single most meaningful experience in their life, compared to 42% of regular ayahuasca takers, and 0% of the pure control group. Given this, we have decided to continue the study sessions using jurema as the placebo treatment, instead of the diluted dose of ayahuasca. The outcomes remain the same as before. We aim to reach ten or so sessions with the new jurema design (including the two completed so far), funding and partner permitting.