This DEA ‘medication of concern’ may have health benefits

You may have encountered Salvia divinorum (ie, salvia) on the internet or heard about its sale at smoke shops. Although it is not regulated by the Controlled Substance Act, it is outlawed in certain states, and neither salvia, nor its active ingredient salvinorin A, has any formal medical indications. Certain vendors promote salvia as a legal alternative to other plant hallucinogens, including mescaline.

Salvia is a perennial herb in the mint family that is misused as a hallucinogenic recreational drug. It is native to Oaxaca, Mexico, and has a long history of use by the Mazatec Indians in ritual divination. Users can chew or smoke this drug for psychic effects including hallucinations; perceptions of bright lights, vivid colors, shapes, body movement, and object distortion; uncontrollable laughter; fear and panic; and sensations of overlapping realities. Physical effects include loss of coordination, slurred speech, and dizziness.

Although salvia is labeled a “drug of concern” by the DEA, it may have certain therapeutic uses, according to a growing body of research. Here’s a closer look.

Inflammation

As folk medicine, salvia has been used in the Mazatec culture to reduce abdominal swelling, diarrhea, and intestinal spasms. Research from the past decade supports these uses, according to the authors of a review published in the Journal of Pain Research.

In mouse models, salvinorin A inhibits gut motility during the inflammatory state. It also mitigates ileitis-induced hypermotility. Intriguingly, these effects may be mediated by cannabinoid 1 (CB1) receptors and kappa-opioid receptors (KORs). Furthermore, the peripheral action of salvinorin A involves the inhibition of leukotrienes and cytokines associated with inflammatory processes. Following peripheral inflammation, at the level of the enteric nervous system and in immune cells, KOR and CB1 receptors are localized and overexpressed.

Pain

Pain is one of the top patient complaints, and chronic pain can lead to many social and vocational detriments. The adverse effects and substantial costs of extant pain treatments make new pain agents a necessity. Recent research highlights the potential of salvia and its metabolites, as well as its semi-synthetic analogs, to treat pain.

“We found in a recent experiment that the direct microinjection of SA [salvinorin A] in this nucleus in deep cortical layers (V and VI) is capable of inducing a powerful antinociceptive effect in a model of neuropathic pain in rats,” wrote the authors of the aforementioned review. “This effect may be explained by the high affinity of this compound to KOR and also because of the allosteric modulation of the CB1 receptors.”

Neuropsychiatric illnesses

A more indirect use for salvia—vis-à-vis salvinorin A—could be the reverse engineering of agents used to treat neuropsychiatric conditions. In a review article published in Frontiers in Pharmacology, the authors postulate that “prolonged high efficacy signaling through KOPr results in behavioral and neurobiological effects associated with human neuropsychiatric conditions, especially depression-like and anxiety-like states, and specific addictions. Conversely, novel compounds with limited efficacy at KOPr (such as antagonists or appropriate partial agonists) or compounds with ‘biased’ KOPr signaling, could potentially have pharmacotherapeutic effects in mood, anxiety or addictive states.”

They added, “Exposure to stress or to drugs of abuse (eg, cocaine and other psychostimulants) results in an upregulation in KOPr/dynorphin activity, and this may underlie, in part, neurobiological and behavioral effects observed in these conditions.”

In other words, the structure of salvinorin A could serve as a new scaffold for medicinal chemistry approaches.

Bottom line

Despite warnings by the DEA, salvia, salvinorin A, and its derivatives may have therapeutic uses. To date, many studies have been in a preclinical context, thus clinical studies are likely needed. Nevertheless, it may be premature to discount the potential health benefits of this drug.