Analysis of the Psychoactive Terpenoid Salvinorin A Content in Five Salvia divinorum Herbal Products

William R. Wolowich, PharmD; Alisha M. Perkins, MD; John J. Cienki, MD


Pharmacotherapy. 2006;26(9):1268-1272. 

In This Article


The objective of this study was to analyze for comparison a variety of salvia products that are easily available to the public and are advertised to be pure and to contain a specific concentration of salvia's active ingredient, salvinorin A. Among the five samples obtained, the salvinorin A concentration ranged from 0.126-1.137 mg/g. This was comparable to previous research using the same extraction and analytical methods to examine salvia botanical samples in which the salvinorin A content ranged from 0.63-3.70 mg/g.[20] The actual concentration found in each sample did not coincide with the advertised 1x concentration. An average 1x potency claimed in a users group discussion blog is equivalent to 2.5mg/g.[13,14]

In our study, the sample labeled 1x contained a higher concentration than one of the samples falsely labeled 5x. The 1x sample contained 0.4 mg/g, which is 16% of the average 2.5 mg/g. The 20x sample contained only 1% of the claimed concentration. A screen for controlled substances and pharmaceuticals revealed that two samples of crushed leaves obtained on the Internet contained vitamin E, and the 10x extract obtained from a head shop was adulterated with caffeine.

The general public has become increasingly aware of salvia since June 1, 2002, when Australia became the first country to ban salvia and salvinorin A. In late 2002, a California Congressman unsuccessfully introduced a bill in the House of Representatives to schedule salvia as a controlled substance. The DEA has indicated on its Web site that salvia is a drug of concern and is evaluating the plant for possible scheduling. Under Louisiana Act 159, a total of 40 plants, including Salvia divinorum, are illegal if sold for human consumption; Salvia divinorum was outlawed in Missouri in the fall of 2005. New York is considering a bill that would place heavy civil penalties on the sale of the drug; Illinois also is considering regulating the drug's use. In January 2006, the Swedish government declared its intention to make salvinorin A and all plants containing the substance illegal, and in March 2006 the law was enacted.[2]

The popularity of salvia is growing, as gauged by hits from search engines on Internet sites. A Yahoo search for Salvia divinorum in 2003 yielded 100 hits; an identical Yahoo search in March 2006 yielded 881,000 hits.

Practitioners need to be aware of this compound when treating individuals with unusual intoxication, and especially Internet-savvy teenagers. The human toxidrome associated with salvia is expected to be similar to that seen with other hallucinogens, except that the duration of the effects is much shorter. In fact, the duration of action is so short that a patient who sought medical attention would probably be lucid by the time help arrived. The intensity of the psychological effect is dose dependent, however, and high doses can produce extreme effects, such as depersonalization, with loss of reality intense enough that users have unintentionally harmed themselves.[15]

In one study, investigators intending to study the human pharmacokinetics of salvinorin A asked volunteers-all of whom had experience with hallucinogens-to smoke salvia.[21] The volunteers became so intoxicated 30 seconds after inhaling that drawing blood was considered hazardous. After regaining lucidity 20 minutes later, they refused to have blood drawn and, presumably, refused any further participation in the experiment.

In a pharmacokinetic study involving nonhuman primates, two-compartment behavior was exhibited after the animals were administered an intravenous 0.032-mg/kg bolus of salvinorin A, which should result in approximately the same disposition as smoking salvia.[22] The rapid distribution phase was essentially complete 5 minutes after administration of the bolus. The overall elimination half-life was 37.9 and 80.0 minutes in male and female primates, respectively. The rapid onset and short duration of effect reported in humans make it likely that the pharmacokinetics are similar in humans. Interactions between salvinorin A and other agents have not been reported. For a prolonged effect, salvinorin A has been used in combination with other recreational drugs such as cannabis.

To our knowledge, no studies of human toxicity with salvia have been published. A placebo-controlled study of acute and long-term toxicity in rats examined the effect of salvinorin A by intraperitoneal injection at doses of 400, 800, 1600, 3200, and 6400 µg/kg/day for 14 days.[23] No histologic evidence of liver, spleen, kidney, bone marrow, or brain tissue damage was found. The doses used in this study were 100-1000 times the dose range of 200-500 µg found hallucinogenic in humans. The authors concluded that salvinorin A has relatively low toxicity compared with other hallucinogens, especially amphetamine derivatives such as MDMA. In addition, the authors warned that psychological effects are not assessed in a rat model, and in humans, these effects could be the stimulus for an episode of panic that could cause myocardial ischemia.

A rat model used to screen for efficacy of antidepressant drugs also was used to investigate salvinorin A.[10] Results of the forced swim test, intracranial self-stimulation, and locomotor activity suggested that salvinorin A produced depressant effects. National Public Radio recently reported the case of a salvia user who committed suicide.[24] An expert interviewed expressed concern that salvia is being marketed to teenagers and young adults as producing a marijuana-like high. The expert also stated that salvia should be regulated like alcohol and should be kept strictly off-limits to teenagers, as suicide rates are high among adolescents and teenagers.[25] The potential for depression caused by salvia consumption must also be considered and needs further investigation.


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