Ayahuasca Research in Spain
The ayahuasca research effort we described in a previous MAPS Bulletin article has been progressing slowly but surely. Obtaining ayahuasca was the first difficulty we encountered, but thanks to the help of several people we are indebted to, we were kindly sent two 10 litre batches of ayahuasca by CEFLURIS in Brazil. Our ayahuasca (Santo Daime) batches were freeze-dried and analyzed for beta- carboline and DMT contents. The former were determined at our HPLC facilities, while the latter was quantified by James C. Callaway in Finland. We would also like to express our gratitude to him. Once this was done, freeze-dried ayahuasca was encapsulated in gelatin capsules. The handling of the freeze-dried material was another unexpected difficulty, as the material proved extremely hygroscopic even in an environment with controlled humidity. This complicated the manipulation of the powder, which was done in special plastic bags under dry nitrogen, and the storage of the prepared capsules, which have since been kept in a freezer at -20 ºC under dry nitrogen and protected from light.
Once we finally had the capsules ready, we began interviewing a number of local (Barcelona) ayahuasca users. We selected a group of six healthy male volunteers with previous experience with the tea, in order to conduct a pilot study. Even though we had first considered using 0.5 and 0.8 mg DMT/kg body weight doses, we decided to conduct a pilot study with three ayahuasca doses, containing respectively 0.5, 0.75 and 1.0 mg DMT/kg body weight. We administered the ayahuasca in a single- blind dose-escalating design. That is, subjects were told they would receive the doses in a randomized order. The investigator knew which doses were being given on each experimental day. They actually received the placebo on the first session, the lower dose on the second, the medium dose on the third and the higher dose on the fourth day of participation. This was done for safety reasons, in order to control for possible adverse reaction in the more stressing environment of a research lab. In this first pilot study the following measures were conducted: subjective effects were recorded by means of visual analogue scales (VAS), the Hallucinogen Rating Scale (HRS) and the Addiction Research Center Inventory (ARCI), a standard questionnaire used in the clinical evaluation of psychoactive drugs. Additionally, preliminary data on the prepulse inhibition of the startle response and the P50 event related potential (both putative measures of sensorimotor gating) were also obtained.
After completion of the pilot study we analyzed the subjective reports and reecorded cardiovascular measures. We are presently preparing a paper discussing the subjective effects reported by the subjects and the results of the preliminary tolerability analyses (cardiovascular measures, results from the biochemical and hematological determinations conducted after each experimental session). The pilot study developed without major problems, but one subject decided to withdraw after the second session, so we finished with only five volunteers. When the subjects were asked which doses they believed they had been given on each session, one subject mistook the lower dose with placebo. On the other hand, the higher dose was considered by all the remaining five participants as eliciting excessively intense effects. We decided thus to use a 0.6 DMT/kg body weight dose, that is a dose between the lower and medium doses of the pilot study, as the lower dose in the larger double blind study. As the higher dose of the final study, 0.85 mg DMT/kg body weight was chosen, between the medium and the higher doses administered in the pilot study. So the final ayahuasca doses employed were slightly different from those we reported in the MAPS article.
The experimental (clinical) part of the final double-blind trial is almost completed now. Finding volunteers with experience in hallucinogen use and meeting the inclusion criteria set in the study protocol proved difficult. As many as 90 subjects reached the psychiatric interview stage, but a large number were excluded later for minor physical health problems or decided not to participate when they were told they would have to spend ten hours in the lab on four different days, if they entered the study. In the end, we have been able to include 18 volunteers as we had planned. As we described in the MAPS Bulletin, the final double-blind trial included a large number of study variables: the performance of 30 lead EEG recordings, blood sampling, urine collection, etc. at different time points. We also incorporated the PPI and P50 measures mentioned above, which were not ready at our lab until some time after we wrote the MAPS article. This has all been a considerable amount of work, but it is now done and the prospect of soon beginning to analyze the data gathered is again stimulating.
As a final comment, we have now started working on a SPECT protocol in which ayahuasca will again be the center of our investigations. Before the protocol is sent to the Ethics Committee, we will concentrate on analyzing and publishing the data of the present study. This will doubtlessly facilitate the approval of a new ayahuasca project by the authorities.
Jordi Riba and Manel J. Barbanoj, MD, Ph.D.