OPEN Foundation

F. Pellicer

Salvia divinorum: from recreational hallucinogenic use to analgesic and anti-inflammatory action

Abstract

Salvia divinorum is a herbal plant native to the southwest region of Mexico. Traditional preparations of this plant have been used in illness treatments that converge with inflammatory conditions and pain. Currently, S. divinorum extracts have become popular in several countries as a recreational drug due to its hallucinogenic effects. Its main active component is a diterpene named salvinorin A (SA), a potent naturally occurring hallucinogen with a great affinity to the κ opioid receptors and with allosteric modulation of cannabinoid type 1 receptors. Recent biochemical research has revealed the mechanism of action of the anti-inflammatory and analgesic effect of SA at the cellular and molecular level. Nevertheless, because of their short-lasting and hallucinogenic effect, the research has focused on discovering a new analogue of SA that is able to induce analgesia and reduce inflammation with a long-lasting effect but without the hallucinatory component. In this review, we explore the role of S. divinorum, SA and its analogues. We focus mainly on their analgesic and anti-inflammatory roles but also mention their psychoactive properties.

Coffeen, U., & Pellicer, F. (2019). Salvia divinorum: from recreational hallucinogenic use to analgesic and anti-inflammatory action. Journal of pain research12, 1069., 10.2147/JPR.S188619

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Salvinorin A reduces neuropathic nociception in the insular cortex of the rat

Abstract

BACKGROUND:
Neuropathic pain is one of the most important challenges in public health. The search for novel treatments is important for an adequate relief without adverse effects. In this sense salvinorin A (SA), the main diterpene of the medicinal plant Salvia divinorum is an important antinociceptive compound, which acts as a potent agonist of kappa opioid receptor (KOR) and cannabinoid CB1 receptors.
METHODS:
We evaluated nociceptive responses in a neuropathic pain model induced by the sciatic nerve ligature (SNL) in the right hind paw, after the microinjection of SA, Salvinorin B (SB), KOR and CB1 antagonists directly in the insular cortex (IC) in male wistar rats.
RESULTS:
We found a potent antinociceptive effect with the administration of SA. Moreover, this effect was blocked by the administration of a KOR antagonist as well as the administration of a CB1 antagonist.
CONCLUSION:
Salvinorin A has a potent antinociceptive effect when is administered centrally in the IC by the interaction with KOR and CB1 receptors.
SIGNIFICANCE:
We show evidence on the effectiveness of the administration of salvinorin A in the IC in a rodent model of neuropathic pain. These results support the use of novel compounds like SA as a therapeutic alternative for neuropathic pain relief.
Coffeen, U., Canseco‐Alba, A., Simón‐Arceo, K., Almanza, A., Mercado, F., León‐Olea, M., & Pellicer, F. (2017). Salvinorin A reduces neuropathic nociception in the insular cortex of the rat. European Journal of Pain. 10.1002/ejp.1120
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Neuropathic and inflammatory antinociceptive effects and electrocortical changes produced by Salvia divinorum in rats

Abstract

Ethnopharmacological relevance

Salvia divinorum is a medicinal plant traditionally used in hallucinogenic ethnopharmacological practices and for its analgesic and antinflammatory properties. Its active compounds include diterpenes known as salvinorins which act as potent κ opioid receptor agonists.

Aim of the study

Given its effects in acute animal models of pain, as well as its antinflammatory attributes, we decided to investigate the analgesic effects of an SD extract in neuropathic (sciatic loose nerve ligature) and inflammatory (intra plantar carrageenan) pain models in rats. We also determined in this study the electrocorticographic changes to correlate similar hallucinogenic state and behavior as those produced in humans.

Material and methods

Mechanical and thermonociceptive responses, plantar test and von Frey assay, respectively, were measured in adult Wistar rats 30 min, 3 h and 24 h after the intraperitoneal administration of saline or an hydroponic SD extract. We also evaluated carbamazepine and celecoxib, as gold reference drugs, to compare its antinociceptive effects.

Results

Our results showed that administration of SD extract induced antialgesic effects in both neuropathic and inflammatory pain models. All those effects were blocked by nor-binaltorphimine (a Kappa opioid receptor antagonist). Moreover, it was observed an increase of the anterior power spectral density and a decrease in the posterior region as electrocorticographic changes.

Conclusion

The present investigation give evidence that SD is capable to reduce algesic response associated to neuropathic and inflammatory nociception. This study support therapeutic alternatives for a disabling health problem due to the long term pain with high impact on population and personal and social implications.

Simón-Arceo, K., González-Trujano, M. E., Coffeen, U., Fernández-Mas, R., Mercado, F., Almanza, A., … & Pellicer, F. (2017). Neuropathic and inflammatory antinociceptive effects and electrocortical changes produced by Salvia divinorum in rats. Journal of Ethnopharmacology206, 115-124. 10.1016/j.jep.2017.05.016
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Neuropathic and inflammatory antinociceptive effects and electrocortical changes produced by Salvia divinorum in rats

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:
Salvia divinorum is a medicinal plant traditionally used in hallucinogenic ethnopharmacological practices and for its analgesic and antinflammatory properties. Its active compounds include diterpenes known as salvinorins which act as potent κ opioid receptor agonists.
AIM OF THE STUDY:
Given its effects in acute animal models of pain, as well as its antinflammatory attributes, we decided to investigate the analgesic effects of an SD extract in neuropathic (sciatic loose nerve ligature) and inflammatory (intra plantar carrageenan) pain models in rats. We also determined in this study the electrocorticographic changes to correlate similar hallucinogenic state and behavior as those produced in humans.
MATERIAL AND METHODS:
Mechanical and thermonociceptive responses, plantar test and von Frey assay, respectively, were measured in adult Wistar rats 30min, 3h and 24h after the intraperitoneal administration of saline or an hydroponic SD extract. We also evaluated carbamazepine and celecoxib, as gold reference drugs, to compare its antinociceptive effects.
RESULTS:
Our results showed that administration of SD extract induced antialgesic effects in both neuropathic and inflammatory pain models. All those effects were blocked by nor-binaltorphimine (a Kappa opioid receptor antagonist). Moreover, it was observed an increase of the anterior power spectral density and a decrease in the posterior region as electrocorticographic changes.
CONCLUSION:
The present investigation give evidence that SD is capable to reduce algesic response associated to neuropathic and inflammatory nociception. This study support therapeutic alternatives for a disabling health problem due to the long term pain with high impact on population and personal and social implications.
Simón-Arceo, K., González-Trujano, M. E., Coffeen, U., Fernández-Mas, R., Mercado, F., Almanza, A., … & Pellicer, F. (2017). Neuropathic and inflammatory antinociceptive effects and electrocortical changes produced by Salvia divinorum in rats. Journal of Ethnopharmacology206, 115-124. 10.1016/j.jep.2017.05.016
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Depressant Effects of Salvia divinorum Involve Disruption of Physiological Sleep

Abstract

Although Salvia divinorum is traditionally known as a ‘mind-altering’ or psychoactive herb used, among others things, as a tranquilizer, this property has not been validated with regard to its efficacy and safety. The objective of this study is to provide evidence for the sedative effects of S. divinorum and discriminate the nature of the responsible constituents by examining different experimental models. A battery of tests, including the open-field, hole-board, exploration cylinder, plus-maze and sodium pentobarbital-induced hypnosis potentiation, were used in mice after administration of non-polar, medium polar and/or polar extracts of the plant (10, 30 and 100 mg/kg). Polysomnographic analysis in rats receiving an active medium polar extract (10 and 100 mg/kg) containing salvinorins was also assessed to study the effects of this plant on sleep architecture. All tested extracts produced significant sedative-like responses, although those of the medium polar extract were more pronounced in mice. The sedative effect of this latter extract, which contains a mixture of salvinorins, caused fragmented sleep architecture in rats by diminishing rapid eye movement (REM) sleep and increased the quiet awake stage at 10 and 100 mg/kg. Our results provide evidence that S. divinorum exhibits sedative-like depressant properties that alter physiological sleep architecture.

González‐Trujano, M. E., Brindis, F., López‐Ruiz, E., Ramírez‐Salado, I., Martínez, A., & Pellicer, F. (2016). Depressant Effects of Salvia divinorum Involve Disruption of Physiological Sleep. Phytotherapy Research. http://dx.doi.org/10.1002/ptr.5617

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