As I mentioned in my last post about Salvia divinorum Research, I was going to take a look at some papers on Salvia divinorum and summarise them here. Well, here we go!

The following post is a summary of a paper published last year in the journal Psychopharmacology entitled "Acute and post-acute behavioral and psychological effects of salvinorin A in humans", by Peter H Addy.

Introduction

The paper begins with a bit of background on Salvinorin-A, the active compound in Salvia divinorum. Unlike "classic" hallucinogens such as psilocin, LSD, etc, salvinorin-A does not bind to the 5-HT2A receptor, but instead binds specifically to the kappa opioid receptor. In the body, very little is known about the effects produced by the kappa opioid receptor, but synthetic drugs that bind to it tend to cause dysphoria (ie the opposite of euphoria, so not very nice), hallucinations and other effects we'd associate with Salvia divinorum including perceived distortions in space and time and uncontrollable laughter.

Up to the point this paper was published, the author mentions the four clinical studies of Salvia divinorum on humans, only one of which was a placebo-controlled study (where an inactive dose or dummy substance is used as well), however, this particular study only had four participants - such a small sample size is too small to draw any major generalised conclusions from. There has also been relatively little research done on the subjective experiences from Salvia divinorum use, or the after-effects of use in humans.

Method

This study used a "double-blind, placebo-controlled, randomized methodology" to asses acute changes in behaviour and self-reported effects, as well as longer term effects, in a group of 30 participants who have taken hallucinogens before on at least one occasion. Previous studies have shown no significant cardiovascular effects, but things like blood pressure, temperature and other vital signs were also recorded before and after the salvia divinorum was consumed. Behaviour of participants was recorded by an observer during the experiment, participants were then interviewed shortly after their experience and asked to fill out the "Hallucinogenic Rating Scale" which was designed to assess the experience as felt by the participants. 8 weeks after the experiment had finished, participants were interviewed again to look for any longer term effects.

The Salvia divinorum was consumed by self-administered smoking of either 25mg of (effectively) 10x extract or 25mg of plain Salvia divinorum leaf (which has already been shown to have no noticeable effects with such a small quantity). There were two sessions for each participant: in the first they were given either the active dose or the placebo dose, and then the opposite for the second session. This was done at random, so neither the participant nor the researchers involved knew if the participant was receiving the active dose to ensure there was no bias.

An hour after the dose/placebo was inhaled, each participant filled out the Hallucinogenic Rating Scale, which is a 126-item questionnaire which was originally designed to assess the psychoactive effects of DMT, which has since been adapted to assess other hallucinogens including pilocybin, MDMA, ketamine and salvinorin-A in that previous study mentioned previously. The scale is categorised into six "clusters", each of which is rated from one to four. These clusters are defined as follows:

  1. Somaesthesia — interoceptive, visceral, and cutaneous/tactile effects
  2. Affect — emotional/affective responses
  3. Perception — visual, auditory, gustatory, and olfactory experiences
  4. Cognition — alterations in thought processes or content
  5. Volition — a change in capacity to willfully interact with themselves, the environment, or certain aspects of the experience
  6. Intensity—strength of the various aspects of the experience.

Results

On average, participants started talking 11.6 times on an active dose and only 9.9 times on the placebo; laughed 3.9 times on an active dose and only 1.2 times on the placebo and moved 8.8 times on the active dose and only 4.9 times on the placebo. Participants were also encouraged to hold the hand of the observer if they felt anxious, afraid, confused or overwhelmed during the experience - this happened on average 0.5 times on the active dose and 0 times on the placebo.

All six clusters from the Hallucinogenic Rating Scale were significantly increased with the active dose. The graph below shows the results for each cluster (as defined above) on both the active dose and the placebo.

Hallucinogenic Rating Scale: Salvinorin-A

Participants were also asked if there experience on Salvia divinorum resembled any of the following experiences. The percentage of participants agreeing it was similar is also given:

  • Dreaming: 43%
  • LSD: 13%
  • Psilocybin: 10%
  • Marijuana: 10%
  • Meditation/trance/yoga: 7%
  • Ketamine/DXM: 7%

Half of participants said that their experience was unlike anything they'd previously experienced.

Twenty participants (87%) reported after-effects in the 24 hours following the sessions, which were more positive than negative. 18 reports positive reports talked about reflection, empathy, intuition and awareness of beauty, while nine negative reports mentioned headaches, fatigue and difficulty concentrating. The following table summarises these reports:

NumberPercentEffect
20 87 Total
5 22 Reflective, curious
5 22 More emotionally sensitive or empathic
4 17 General positive aftereffects (e.g., awe of reality; laughter; euphoric, antidepressant; calm, relaxed, peaceful, happy)
3 13 Headache
3 13 Fatigue
3 13 Difficulty concentrating
2 9 More intuitive (e.g., with self, with clients)
2 9 Feelings of floating or lightness
2 9 More aware of beauty

Sixteen participants went on to report after-effects lasting more than 24 hours, but only three people listed anything negative. These reports are summarised below:

NumberPercentEffect
16 70 Total
5 22 Positive changes in relationships with living family members
5 22 Reflecting on and integrating their experience
4 17 General positive changes in themselves (e.g., general sense of well-being; aligned with the stars and wholesome feelings; more grounded, present; calming, focusing)
3 13 Negative effects (e.g., headache for 3 days; unsure of things; ears popping, ready to cry, lack of patience)
2 13 Increased empathy or sensitivity (with children, with intimate partner)
2 13 Receiving lessons (e.g., about intimate partner, about working with psychotic clients)
2 9 Positive changes in relationships with others (e.g., deceased mother, a saint)

Discussion

The author draws a number of comparisons between these results and previous studies on Salvia divinorum and other drugs. The results differ slightly from the study mentioned previously with only four participants, but this is to be expected with a larger sample size. Results from the Hallucinogenic Rating Scale for Salvinorin-A are similar to intravenous ketamine for the somaesthesia, perception, cognition and affect clusters, and similar to intravenous DMT for the volition and intensity clusters, however the author notes that there is little comparable effect between these same substances when taken orally, so these similarities in experience could very well be down to the route of administration rather than the substances themselves. The rapid onset of effects from smoked Salvia divinorum are a likely parallel for the rapid onset of effects from intravenous drug use.

In 1994, Daniel Siebert identified several themes from the Salvia divinorum experience:

  • becoming objects
  • visions of various two-dimensional surfaces, films and membranes
  • loss of the body and/or identity
  • various sensations of motion, or being pulled or twisted by forces of some kind
  • uncontrollable hysterical laughter
  • overlapping realities
  • revisiting places from the past, especially childhood


All but the last theme were reported by the participants of this study.

So, all things considered this is the most scientifically valid investigation into the effects of Salvia divinorum that we have. There are of course several limitations to this study, but there are more limitations to the studies published previously and this investigation does well to improve upon them.

For a more technical description of the methods, results and limitations, read the original paper: http://www.ncbi.nlm.nih.gov/pubmed/21901316