In this two-part blog post, I’m comparing two papers studying the psychological effects of Salvia divinorum consumption. Last week I summarised the findings of Gonzalez et al (2006), who analysed self-report questionnaires from 32 Salvia users. This week I’ll look at a slightly different study, where only four subjects are used, but the administration of Salvia is in total control of the authors. Comparing the two papers might shed some light on Salvia divinorum and the best method of studying its hallucinogenic effects.

Controlled administration study

Johnson et al (2011) set out to study Salvia in a controlled environment. This allows them not only to control the way Salvia is administered, but also to study the effects of Salvia at different doses. It also allows the authors to take several physiological measurements before, during and after Salvia use. The only downside is that the large time and effort requirements mean only four subjects could be used for the study.

Administering Salvia to participants

Johnson et al (2011) employed incredibly rigorous procedures to ensure that all their volunteers were physically and mentally healthy, including taking blood samples and consultation with a psychiatrist. Participants inhaled pure Salvinorin A, the active compound in Salvia divinorum, over several sessions spread over a few months. The participant was not aware of what exact dose of Salvia they were receiving, but knew that each session they would be receiving a slightly higher dose, up to a dose of 21µg (that's MICROgrams) per kilogram of body weight. At least once in every five trials the participant received a placebo dose; this provided the authors with a baseline to compare psychedelic effects to. During the process blood pressure and heart rate were recorded every two minutes, and participants were asked to rate the intensity of the experience every two minutes. After the effects had worn off, the patient was asked to rate the intensity of the overall experience, then filled in two rating scales to compare the effects of Salvia to other psychedelic drugs.

Results

Figure 1. Intensity of Salvia trips peaks at 2 minutes, at all doses. Intensity is reported by participants on a scale from 0 (no effect) to 10 (strongest effect possible) every two minutes after inhalation of Salvinorin A. Adapted from Johnson et al (2011).

Figure 2. Intensity of Salvia trips peaks at 2 minutes, at all doses. Intensity is reported by participants on a scale from 0 (no effect) to 10 (strongest effect possible) every two minutes after inhalation of Salvinorin A. Adapted from Johnson et al (2011).

At the end of the study, the authors found that the reported peak of Salvia effects was at 2 minutes after administration (see figure 1). As would be expected, the reported overall intensity of the trip increased with dose size (see figure 2). Higher doses also meant that participants were significantly more likely to rate the trip as positive, and participants very rarely rated trips as negative. Scores in both hallucinogenic rating scales showed that Salvia is very similar to classical psychedelics, especially psilocybin and DMT. However, whereas Gonzalez et al (2006) suggested the Salvia consumption resulted in a high loss of control, this study found that participants felt in control of their trips throughout the study.

Safety

Throughout all dose levels, blood pressure and heart rate remained unchanged, and at no point did participants suffer any ill effects or refuse to continue to higher doses. This provides evidence that Salvia is physiologically safe at these doses, and the authors even suggest that higher doses could be used in future studies.

Summary

The most significant finding of this study was that participants rarely reported negative effects, which seems to contradict previous studies. The authors of this study conclude that their subjects experienced only positive effects because A) they are experienced users of hallucinogens and fully prepared for an intense experience, and B) they are taking Salvia in a very safe, controlled and relaxing environment. This emphasises the importance of mind-set when taking Salvia; enter the experience with a positive frame of mind and in a safe, comfortable environment, and you will be much less likely to experience negative effects. Having a sitter present, as recommended for first time users, will help to alleviate any nervousness or anxiety.

Finally, the authors list a few things the participants mentioned when asked to narrate their experience. They were most likely to mention feelings of pressure on the body, and feelings of unusual movement, similar to previously reported effects of Salvia. The authors note how calm participants were during Salvia trips compared to the typical depictions of reactions in YouTube

Comparisons

Gonzalez et al (2006) employed a questionnaire-based method, while Johnson et al (2011) controlled the administration of Salvia while taking physiological measurements and constant questioning of the participants, in addition to a post-trip questionnaire.

Sample size

Gonzalez had 32 participants, Johnson only four. This highlights how much difficulty was involved in Johnson’s study; it’s much easier to recruit 32 Salvia users to fill out a questionnaire, than it is to recruit four completely physically and mentally healthy participants who are willing to give up a lot of their time over several weeks of study. But did the numbers really make a difference? Gonzalez did not manage to perform any statistical analysis on their results due to variability, even though they had a large sample size. Johnson, because they meticulously gathered so much data, managed to find statistical significance in several areas of measurement. I think this goes to show how scientific rigour can be more important than a large sample size. Having said that, a paper we reviewed in a previous blog post covering some different research on Salvia’s effects in humans managed to recruit 30 participants despite having similarly rigorous methods to Johnson et al; therefore the best of both worlds can definitely be achieved.

Volition

The studies did turn up some similar results; both showed that Salvia is similar to classical psychedelics, producing intense visuals. However, Gonzalez reported participants experiencing a loss of control in their trips, whereas Johnson did not find any significant change in feelings of control. I believe that the hallucinogen-experienced participants in Johnson’s study were prepared for a loss of control, and as such did not rate it highly. This shows a potential flaw in Johnson’s study; the participants may be too relaxed, and too experienced with hallucinogens, meaning that the potential negative effects a first time user might experience are not being recognised. If the subjects in Gonzalez’s study did not have a sitter present, or were in an unfamiliar or stressful environment, they would be much more likely to experience the loss of control of the Salvia trip as negative.

Control

The most important difference between the two papers is due to the ability of Johnson et al to control every aspect of Salvia administration. Johnson et al can vary the dose of Salvia and even use a placebo, allowing them to accurately compare Salvia’s effects to a baseline. Gonzalez et al, although providing us with a large quantity of trip reports and a nice idea of what to expect from a Salvia trip, have no way of controlling the dose or environment in which their participants have experienced Salvia.

Summary

It seems to me that the way forward in Salvia research is with studies where Salvia administration is controlled and measured in precise detail. Although these studies may have low sample sizes, they can gather much more data from every individual and study dose strengths and physiological responses. Questionnaire-based studies are great for providing us with a rough idea of Salvia’s effects, but when it comes to really understanding Salvia, more control over the psychedelic experience is crucial.

References

Gonzalez D, Riba J, Bouso JC, Gomez-Jarabo G & Barbanoj MJ (2006) Pattern of use and subjective effects of Salvia divinorum among recreational users. Drug and Alcohol Dependence 85:157-162

Johnson MW, MacLean KA, Reissig CJ, Prisinzano TE & Griffiths RR (2011) Human psychopharmacology and dose-effects of salvinorin A, a kappa-opioid agonist hallucinogen present in the plant Salvia divinorum. Drug and Alcohol Dependence 115:150-155