Transcript The Magic Mint - Stephanie Nichole Halbleib

The Magic Mint:
Salvia divinorum
By: Stephanie Halbleib
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Introduction
• Salvia divinorum is a native perennial shrub
to Mexico
– Hallucinogenic plant
– Lamiaceae mint family (sage, basil, etc.)
– Mazatec shamans
• Most potent naturally occurring
hallucinogen
• Legal in most states
– DEA states Salvia as a drug of
concern
Background
• Salvia was first documented in 1939
• Salvinorin A isolated in 1982 by X-ray
crystallography
• 1900s the psychoactive mechanism of
Salvia was identified
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Salvinorin A
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Active constituent
C23H28O8
Neoclerodane class of diterpenes
Is not an alkaloid
• Excreted through trichomes in
the leaves, forms a resin on the
leaves
• Responsible for observed
hallucinogen effects
• Kappa opioid receptor agonist
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Other Substituents
• Salvinorin B, C, D, E, & F, and divinaturin A, B, & C
• Neoclerodane diterpenoid structure
– Salvinorin B
• Lower concentrations
• Metabolite of salvinorin A
– Salvinorin C
• Weak affinity for kappa opioid receptor
• Lacks psychotropic effects
– Salvinorin D and G only
• Exhibit affinity for kappa opioid receptor
• Overall have shown no significant affinity
– Means no evidence to contribute psycho activity.
• Research focused on mechanism of salvinorin A
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History and Current Practices
• Traditionally
– Chewed, or drink juice of crushed leaves
– Induce visions in ceremonies
• Today
– Chewed, smoked, or tinctures
– Marijuana substitute
– 1.8 million have tried Salvia
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Opioid Receptor
• Opioid system controls pain, reward, and addictive
behaviors
• Three opioid receptors, mu, delta and kappa
• Activated endogenous by peptides (like endorphins), or
exogenously by alkaloid opiates (such as morphine)
• Signal transduction is theorized as follows:
– Activation is coupled to the G protein which increases
phosphodiesterase activity
– Breaks down cAMP, producing an inhibitory effect in neurons
– Also shown to be coupled to nitrogen type calcium ion channels
• Exact activation that Salvinorin A is unknown
Hallucinogens
• Distinct class of compounds categorized
by their chemical structure and
pharmacological actions
• Salvinorin A does not bind at 5HT2A
(serotonin) receptor
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Detection Methods
• Drug Urinalysis
– Two types of tests
• Drug screening and drug testing
– Looks for drug metabolites
– Marijuana has 31 different
metabolites (most common THCA)
– Salvia is undetectable
Detection Methods Cont.
• Extraction
– Organic solvents
extract salvinorin A and
pigments
– Activated charcoal,
centrifugation, and
evaporation reveals
purified salvinorin A
• Color test
– Indicate which type of
substance is present
(opium, barbiturates,
etc.)
– Cannabis uses the
Duquenois-Levine test
• (deep purple)
– No current color test for
Salvia (high amount,
Marquis Color test could
detect Salvinorin A
– Not 100% accurate
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Detection Methods Cont.
• Thin Layer Chromatography
– Confirm unknown substance with known Rf
values
– Researchers have been able to use this TLC to
show salvinorin A, B, C, and D are in the leaves
– Pinkish purple spots
– Cannabis, or Salvia?
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Detection Methods Cont.
• Gas Chromatography-Mass Spectrometry
– GC separates sample into individual compounds
– MS analyzes each compound
• Ionizing each compound to create fragments, then measured by
mass-to-charge ratios
– Salvia different organic solvents can be used (methanol
and chloroform)
– Salvinorin A is not
always the only
peak
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Potency and Methods of Use
• Amounts needed for hallucinogenic effect vary
•Dose of 200-600μ in humans
• Smoking
– Salvinorin A in leaves
– Lighter
• Type and temperature
– Inhaling smoke fully
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• Chewing
– Salvinorin A in leaves
– Contact with the
mucous lining
– Ingesting the leaves
Effects
• Impairs coordination, dream-like
awareness, body high, etc.
– Disappear when metabolized
• After effects-mentally refreshed,
headaches, nausea, etc.
– Disappear completely in about one day
• Does not seem to be toxic
– Mice vs. humans
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Role in Treatment
• Therapeutic Potential
– Shown to pharmacologically active on
inflamed gut and other inflamed tissues
– Could be useful for: Alzheimer's, depression,
schizophrenia, chronic pain, and AIDS/HIV
– Baggott’s survey and self-medication studies
have showed improved mood and
antidepressant effects
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Role in Treatment Cont.
• Drug Addiction
– Endogenous kappa opioid agonist is thought to be the
body's natural addiction control mechanism
– Kappa opioid receptor shown to influence stressinduced relapse drug seeking behavior
– Research suggest Salvia may help treat cocaine
addiction
• Rats had free access to cocaine until addicted
• Had choice of salvinorin A and cocaine.
• Rats stopped ingesting cocaine and had little signs of
withdraw
– Morphine
• Affects kappa and mu opioid receptors
• mu receptors are believed to cause opiate dependence
Discussion
• Sensitivity to salvinorin A vary
– Many factors
• Resin amounts
• Salvinorin A’s size
• Temperature and type of lighter
• More research is needed
Conclusion
• Further research
– Could provide insight into therapeutic potential of
kappa opioid receptor and Salvia in treatments
– On effects of salvinorin A can help to characterize
clinical toxicity and substance abuse
• Few human documented cases
– Salvia escapes traditional medical testing methods of
toxicology
• Could pose a problem
• No human case studies
• Many factors could effect potency levels
• Could other mint family species contain
salvinorin A, and lead to a Pandora's box?
QUESTONS
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References
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Vortherms, T.A.; Roth, B.L. Salvinorin A: From Natural Product to Human Therapeutics. Molecular Interventions 2006, 6,
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3 Lee, D.Y.; Yang, L.; Xu, W.; Deng, G.; Guo, L.; Liu-Chen, L.Y. Synthesis and Biological Evaluation of C-2 Halogenated
Analogs of Salvinorin A. Bioorganic Medicinal Chemistry Letters 2010, 20, 5749-5752.
4 Prisinzano, T.E. Psychopharmacology of the Hallucinogenic Sage Salvia divinorum. Life Science 2005, 78, 527-531.
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A Potent Naturally Occurring Nonnitrogenous κ Opioid Selective Agonist. Proc Natl Acad Sci (USA) 2002, 99, 11934-11939.
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Chromatography and Gas Chromatography/Mass Spectrometry. Journal of Forensic Science 2009, 45, 612-616.
12 Vohta, R.; Seefeld, A.; Cantrell, F.L.; Clark, R.F. Salvia Divinorum: Exposures Reported to a Statewide Poison Control
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16 Google images search (accessed April 22, 2011).
17 Wikipedia Salvia and Salvinorin A http://en.wikipedia.org/wiki/Salvinorin_A (accessed April 15, 20011).
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