Salvinorin A

Discussion in 'Salvia divinorum' started by Alfa, Feb 5, 2004.

  1. Alfa

    Alfa Productive Insomniac Staff Member Administrator

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    [​IMG]Edited by: Alfa
     
  2. smartbee

    smartbee Gold Member

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    Does anybody know the dosage for using Salvanorin A, the duration by 250mcg was about one hour, 300 mcg also, even as 350 mcg and 375 mcg??
     
  3. scyrusurcys

    scyrusurcys Silver Member

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    I wouldn't think that the length of the trip would be extended as much
    as the INTENSITY would be increased. Also, I wouldn't try making
    yourself a lab-rat with those numbers and Salvinorin-A crystals.[​IMG]
     
  4. transit

    transit Newbie

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    <h3><center>
    <big>
    Salvia divinorum and Salvinorin A:
    new pharmacologic findings</big>

    by


    Daniel J. Siebert

    P.O. Box 661552.
    Los Angeles,
    CA 90066 USA

    Journal of Ethnopharmacology 43 (1994) 53-56


    </font></center></h3>
    <blockquote>








    The diterpene salvinorin A from Salvia divinorum
    (Epling and Jativa-M), in doses of 200-500 µg produces effects which
    are subjectively identical to those experienced when the whole herb is
    ingested. Salvinorin A is effectively deactivated by the
    gastrointestinal system, so alternative routes of absorption must be
    used to maintain its activity. Traditionally the herb is consumed
    either by chewing the fresh leaves or by drinking the juices of freshly
    crushed leaves. The effects of the herb when consumed this way depend
    on absorption of salvinorin A through the oral mucosa before the herb
    is swallowed.</font>



    Keywords. Salvia divinorum; Salvinorin A; Psychoactive plants; Psychoactive compounds







    </font><h3>1. Introduction</font></h3>

    Salvia divinorum
    is used by the Mazatec Indians of northeastern Oaxaca, Mexico primarily
    for its psychoactive effects which aid in ritual divination (Wasson,
    1962, 1963). It is also employed remedially to treat various health
    conditions (Valdes et al., 1983).
    </font>


    The first live specimens of S. divinorum
    were given to Carl Epling by R. Gordon Wasson in 1962 and were
    cultivated at the University of California in Los Angeles (Wasson,
    1962). Cuttings of this original clone were distributed to other
    botanical collections over the years and most of the plants in
    cultivation in the USA today originated from this original clone
    (Valdes et al.,
    1987). Recently, other clones have been appearing in collections. As of
    this writing there are at least four different clones present in public
    and private botanical collections in the USA.
    The chemistry of this plant has been investigated several times. The
    diterpenes salvinorin A and salvinorin B have been identified and
    characterized. Salvinorin A has been shown to be active in mice while
    salvinorin B was inactive. No human studies with these compounds have
    previously been reported (Ortega et al., 1982; Valdes et al., 1984).
    Trace amounts of other diterpenes have been detected but have not yet
    been characterized (Valdes et al., 1984).
    </font>


    There are
    two methods of ingestion traditionally employed: either the fresh whole
    leaves are masticated and swallowed or, alternatively, the leaves are
    crushed to extract the juices which are then drunk. Of these two
    methods, chewing of the leaves is most reliable and requires a smaller
    quantity of leaves. The liquid preparation is often ineffective and
    when it does produce effects they are usually much milder than those
    reported for chewing, even when substantially larger quantities of
    leaves are used in the preparation.
    </font>


    When the
    leaves are chewed whole they must first be chewed well enough to be
    easily swallowed and so spend quite some time in contact with the oral
    mucosa. When the leaf juice preparation is consumed it can be swallowed
    fairly quickly and consequently spends relatively little time in
    contact with the oral mucosa. The level of effects reported relates
    quite closely to the length of time the material spends in the mouth
    before being swallowed.
    </font>


    This
    presentation describes the effects of salvinorin A in humans, its
    deactivation by the gastrointestinal system and the essential role of
    the oral mucosa as an absorption site for salvinorin A from orally
    ingested leaves.</font>




    </font><h3>2. Materials and methods</font></h3>

    All plant material used in this study was propagated from the clone originally brought into the USA by R. Gordon Wasson in 1962.</font>



    2.1. Salvia divinorum leaves</font>



    In order to investigate the relative importance of the oral mucosa as an absorption site for the active principals in S. divinorum
    leaves, the following experiments were carried out by six volunteers
    using ten large fresh leaves each (approximately 30 g total) which had
    been homogenized with 100 ml water using a blender. Each experiment was
    separated by several days.</font><blockquote>
    (A) The
    material was swallowed as quickly as possible with the intention of
    quickly bypassing the oral mucosa; then the mouth was immediately
    rinsed with water to wash away any residual material that might be
    clinging to the oral mucosa. None of the volunteers reported any
    noticeable effects when the material was ingested in this manner.</font>


    (B) The
    material was held in the mouth for 10 min without swallowing; then the
    entire contents were spit out. This method proved consistently
    effective with all of the volunteers reporting very definite
    psychoactive effects.



    </font></blockquote>

    2.2. Salvinorin A</font>



    Salvinorin
    A was isolated following the method of Valdes (Valdes et al., 1984).
    The identity of this material was verified by comparison with an
    authentic sample of salvinorin A using TLC, melting point and NMR.
    </font>


    Salvinorin
    A has previously been shown to be active in mice but it has remained
    uncertain whether this compound is responsible for the psychoactive
    effects produced in humans. In order to determine this, salvinorin A
    was administered to a group of 20 volunteers.
    </font>


    When
    salvinorin A was encapsulated and swallowed in doses as high as 10 mg
    there was no detectable activity. Experiments with the leaves indicate
    that the active principle of the plant is deactivated by the
    gastrointestinal system. To test for activity of salvinorin A,
    alternative routes of ingestion were attempted. Salvinorin A is not
    water soluble so injection was not attempted.
    </font>


    Absorption
    through the oral mucosa. A 2-mg quantity of salvinorin A was dissolved
    in 1 ml anhydrous ethyl alcohol then sprayed on the inner surfaces of
    the mouth using an aspirator. The material proved to be active; however
    only a small percentage is absorbed this way before it gets dispersed
    by salivary flow. Consequently this method was inefficient and results
    were inconsistent.
    </font>


    Inhalation
    of the vaporized compound. The material was placed on a piece of
    aluminum foil. A butane micro torch was then held beneath the foil
    until the material was seen to vaporize. As soon as this began, the
    vapors were inhaled through a 15-mm glass tube.
    </font>


    Inhalation
    of the vapors produced by heating salvinorin A proved to be the most
    efficient method of ingestion tested. When 200-500 µg of salvinorin A
    is vaporized and inhaled the subjective effects produced are identical
    to those typically produced by the fresh herb. Doses up to 2.6 mg were
    tested in this manner. Typically threshold effects are noted at about
    200 g.</font>




    2.3. Effects</font>



    When
    salvinorin A is absorbed through the oral mucosa the first effects are
    usually experienced in 5-10 min. The strength of the effects builds
    very quickly over a few minutes, maintaining a plateau for about 1 h.
    The effects gradually subside over another l-h period. The evolution of
    effects over time is identical to that of orally ingested S. divinorum leaves.

    </font>


    When
    salvinorin A is vaporized and inhaled the full effects are experienced
    in about 30 s. There is almost no transition period experienced. The
    strongest effects last 5-10 min and then gradually subside over about
    20-30 min. As dosage increases above 1 mg the duration of the effects
    are somewhat increased. A similar evolution of effects is reported for
    smoked S. divinorum leaves.

    </font>


    The oral
    mucosa apparently acts as a time release buffer, slowly diffusing
    salvinorin A into the blood stream; hence when consumed orally, the
    effects begin more gradually, last longer and subside over a longer
    period of time than when the material is vaporized and inhaled.
    Although variable in duration, the effects experienced have the same
    overall characteristics regardless of the route of absorption used.
    </font>


    The nature
    of the effects experienced depends on many factors including dose, set
    and setting. Frequently people report having seen visions of people,
    objects, and places. With doses above 1 mg, out of body experiences are
    frequent. Occasionally individuals get up and move about with no
    apparent awareness of their movements or behavior. Some individuals
    speak gibberish during the most intense phase of the experience, others
    laugh hysterically.
    </font>


    Certain
    themes are common to many of the visions and sensations described. The
    following is a listing of some of the more common themes:
    </font>
    1. Becoming objects (yellow plaid French fries, fresh paint, a drawer, a pant leg, a Ferris wheel, etc.).</font>

    2. Visions of various two dimensional surfaces, films and membranes.</font>

    3. Revisiting places from the past, especially childhood.</font>


    4. Loss of the body and/or identity.</font>


    5. Various sensations of motion, or being pulled or twisted by forces of some kind.</font>


    6. Uncontrollable hysterical laughter.</font>


    7. Overlapping realities. The perception that one is in several locations at once.
      </font>

    Some of
    the effects appear to parallel those of other hallucinogens (i.e. the
    depersonalization experienced with ketamine, the rapid onset of effects
    and short duration of smoked DMT). The volunteers who were experienced
    with other hallucinogens all agreed that despite some similarities, the
    content of the visions and the overall character of the experience is
    quite unique.</font>




    2.4. Receptor Site Screening and MAO Inhibition</font>


    A sample
    of salvinorin A was submitted to NovaScreen™ for receptor site
    screening. At screening concentrations of 10-5 M there was no
    significant inhibition (i.e. 50% or less) for the following sites.</font><blockquote>
    Neurotransmitters:
    Adenosine, alpha 1, alpha 2, beta, dopamine 1, dopamine 2, GABA-A,
    GABA-B, serotonin 1, serotonin 2, muscarinic 3, NMDA, kainate,
    quisqualate, glycine (stry sens.).</font>



    Regulatory sites: Benzodiazepine(centrl), glycine (stry insens.), PCP, MK-801.</font>


    Brain/gut peptides:
    angiotensin Ty2, arg-vasopressin Vl, bombesin, CCK central, CCK
    peripheral, substance P, substance K, NPY, neurotensin, somatostatin,
    VIP.</font>


    Growth factors and peptides: ANF I, EGF, NGF.</font>


    Ion channels: Calcium (type N), calcium (type T and L), chloride, potassium (low conduct).</font>


    Second messengers: Forskolin, phorbol ester, inositol triphosphate.</font>


    Monoamine oxidase inhibition: Monoamine oxidase A, monoamine oxidase B.
    </font></blockquote>




    </font><h3>3. Discussion and conclusions</font></h3>

    When S. divinorum
    leaves are consumed, either by chewing the fresh leaves or by retaining
    the leaf juices in the mouth, enough of the highly active compound
    salvinorin A is absorbed through the oral mucosa and into the blood
    stream to produce a psychoactive effect. Swallowing of the herb is
    unnecessary and its effects are increased by lengthening the amount of
    time that the herb remains in the mouth. When the leaf juices are
    quickly swallowed, minimizing contact with the oral mucosa, the only
    route of absorption is though the gastrointestinal system where
    salvinorin A is deactivated before entering the blood stream. When pure
    salvinorin A is encapsulated and swallowed it is inactive even at
    relatively large doses, but when absorbed through the oral mucosa or
    vaporized and inhaled is extremely active. It is likely that if
    salvinorin A were administered by injection, it would prove to be
    active at even lower doses than those described in this paper.
    </font>


    Salvinorin
    A is the first entheogenic diterpene reported and is active in humans
    at extraordinarily low doses. It does not appear to affect any of the
    receptor sites affected by other hallucinogens. Further research into
    the methods of action and possible medicinal values of this and similar
    compounds may prove to be quite rewarding.</font>




    Acknowledgments</font>



    I am
    grateful to Dr Leander Valdes III for supplying a reference sample of
    salvinorin A, and Dr David Nichols for his role in the receptor site
    screening of salvinorin A through his NIMH-funded research program.</font>




    References</font>



    Ortega, A., Blount, J.F. and Manchand, P.S. (1982) Salvinorin. a new lrans-neoclerodane diterpene from Salvia divinorum (Labiatae). Journal of the Chemical Society. Perkin Trans-actions 1: Organic and Bio-Organic Chemistry 2505-2508.</font>


    Valdes, L.J. III., Diaz J.L. and Ara G. Paul. (1983) Ethnopharmacology of Ska Maria Pastora (Salvia divinorum Epling and Jativa-M.). Journal of Ethnopharmacology 7, 287-312.</font>


    Valdes, L.
    J.III., Butler, W.M., Hatfield, G.M., Paul. A.G. and Koreeda, M. (1984)
    Divinorin A, a psychotropic terpenoid, and divinorin B from the
    hallucinogenic mint Salvia divinorum. Journal of Organic Chemistry 49, 4716-4720.</font>


    Valdes, L.J. III., Hatfield, G.M., Paul, A.G.and Koreeda M. (1987) Studies of Salvia divinorum (Lamiaceae), an hallucinogenic mint from the Sierra Mazateca in Oaxaca. Central Mexico. Economic Botany 41(2), 283-291.</font>


    Wasson, R.G. (1962) A new Mexican psychotropic drug from the mint family. Botanical Museum Leaflets Harvard University 20 77-84.</font>


    Wasson, R.G. (1963) Notes on the present status of ololuiqui and the other hallucinogens of Mexico. Botanical Museum Leaflets Harvard University 20, 161 - 193.

    </font></blockquote>
     
  5. transit

    transit Newbie

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    <ul>
    <center>Dosage and Method of Administration</font></font></center><center></center><center>
    <hr size="5" width="80%"></center>
    [/list]

    </font>Salvinorin A can be efficiently consumed by inhaling the vaporized
    crystalline powder, or by smoking, providing the crystalline powder has
    been placed on a substrate such as dried Salvia divinorum leaf. Used in
    this manner, the effects of salvinorin A can be distinctly felt from as
    little as 200 to 500 mcg. Most who have tried salvinorin A have reported
    'full" effects at a range between 800 and 1200 mcg. The distinction of
    "full" effects is arbitrary, as the intensity and diversity of the experience
    increases with the dosage. It should also be noted that as with any substance,
    there are a few people who will be unusually sensitive to salvinorin A,
    and will require a smaller amount to produce the same level of effects.

    </font>


    Ott has indicated that salvinorin A can also be taken sublingually,
    and is active in even smaller doses, with as little as 100 to 250 mcg.
    producing noticeable effects. Ott used a solution of salvinorin A in acetone
    in his sublingual tests, and also reported that DMSO can be used as a solvent
    for this purpose. By comparison, the most potent previously known natural
    psychedelics, 5-MeO-DMT and psilocin. are typically used in doses of 5
    to 10 mg. Salvinorin A is approximately 10 times the potency of these compounds,
    and nearly as potent as the semi-synthetic psychedelic, LSD.

    </font>


    The effects of salvinorin A intensify sharply as the dose is increased,
    as has been noted by several people who have used over 1 mg. A few have
    tried doses around 2 mg., and had experiences of ferocious intensity which
    they had no desire to repeat. The largest single dose reported is Siebert's
    initial smoking of approximately 2 mg. of salvinorin A.

    </font>


    Most of the early experiments with salvinorin A were performed by inhaling
    the vaporized crystal using the following technique. The salvinorin A was
    placed on the center of a piece of thick aluminum foil, which was heated
    from below with a butane micro-torch or "jet flame" lighten As the salvinorin
    A turned to a white vapor, the vapors were inhaled through a 15mm diameter
    glass tube. This technique requires careful performance. If one inhales
    before the crystal has been melted, the solid material wilt be taken into
    the mouth and will not produce the desired effects. However, if one waits
    more than a moment after the vapor begins to appear, it will disperse and
    be lost to the atmosphere. There were several reported misfires from people
    who were not successful in this procedure. Some of these people suspected
    the substance was not very potent, increased the dose, and were quite shocked
    by the intensity of what they were subsequently propelled into.

    </font>


    I came across a simpler procedure for this process, which is to use
    a conventional hash oil pipe. A hash oil pipe is made by creating a bubble
    or bowl at one end of a glass tube, with an opening at the top. Although
    hash oil is no longer commonly available4 these pipes can occasionally
    be found in stores. A hash oil pipe allows better visibility of the melting
    and vaporization, and better confinement of the vaporized material against
    escaping without being inhaled. Even with a hash oil pipe the technique
    requires precision. The use of a micro-torch or "jet flame" lighter is
    essential, not only due to salvinorin A's high boiling point, but also
    because a conventional lighter will coat the outside of the pipe in carbon,
    obscuring visibility of the melting/vaporization process. I found that
    the flame must be continually moved over the bottom of the bowl until the
    material has melted. These torches are hot enough to cause the bowl to
    quickly expand and buckle if the flame is kept at one point on the bowl.
    This causes the solid salvinorin A crystals to disperse over a large area
    inside the bowl, which does not allow for efficient vaporization. It is
    important that only self-extinguishing torches or lighters are used in
    this process, as salvinorin A takes effect very rapidly. One does not want
    to be traveling through hyperspace while a lit torch is burning at their
    side.

    </font>


    Recently salvinorin A has been distributed in another form which is
    much easier to use. The material I've used contains 1 mg. of salvinorin
    A, dissolved onto 25 mg. of dried and powdered Salvia divinorum leaf. This
    concentrate formulation is much easier to handle than the pure crystalline
    form. The concentrate formulation may be smoked in a regular pipe using
    a regular lighter. However, a dedicated pipe should be used for smoking
    salvinorin A, as subsequent smoking of other herbs in the same pipe may
    induce an unwanted journey. Individual doses can now be reasonably measured
    on a scale with 10 mg. (1/100 of a gram) resolution, such as the Ohaus
    Centogram quad- beam balance. I've prepared 1 mg. doses of salvinorin A
    by first weighing 50 mg. of the salvinorin A on Salvia divinorum leaf concentrate,
    and then visually dividing this amount into two equal piles. Anyone working
    with this material should be acutely aware that even small variations in
    the dose size can produce dramatic increases in the intensity of the experience.
    Pure crystalline salvinorin A requires a sophisticated analytical balance
    for the measurement of individual doses. I have used the salvinorin A on
    Salvia divinorum leaf formulation several times now, and have noticed no
    difference between this and vaporizing the same amount of material in pure
    crystalline form.

    </font>


    Siebert also performed tests using other methods of administering pure
    salvinorin A. This included placing salvinorin A in the mouth, and dissolving
    salvinorin A in a solvent and spraying into the nose. The effectiveness
    of these methods varied widely with repeated applications of the same method.
    In some cases a large percentage of the material taken seemed to make its
    way into the bloodstream, at other times only minimal effects were produced.
    This presented a significant risk. If the dose was increased to the point
    where one would normally achieve "full" effects, (equivalent to smoking
    1 mg.) there was a risk of absorbing a larger percentage of the material
    which could produce an experience of shocking intensity. This possibility
    led Siebert to suspend his research in this area.

    </font>
    There are currently a number of people in the psychedelic community
    experimenting with different methods of ingesting Salvia divinorum, including
    the oral administration of a crude extract. It is likely that a reliable
    method will soon be developed which allows one to experience fuller effects
    than can be easily obtained through chewing the whole leaves, but without
    the intensity and sudden onset of smoked salvinorin A.
    </font>
     
  6. LeadCenobite

    LeadCenobite Newbie

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    That was a nice read! I really want to try salvia orally now. I am a little hesitant knowing that the effects last like 5 times longer though. The 10 minute trip is intense enough for me as it is. I must try it!
     
  7. genaro

    genaro Iridium Member

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    I've been searching for a few mg of this stuff during a long time... Edited by: genaro
     
  8. transit

    transit Newbie

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    Come on genaro. </span>You’ve
    been around here long enough to know better.
    </span>Read the rules:


    </span>•Discussion
    of sources / commercial suppliers are only allowed in the Sources forum.</span>
    </span>
     
  9. DJ-666

    DJ-666 Mercury Member

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    Whats the best and effective way to consume Salvinorin A in his purest form without heating and then inhaling the vapours?


    SWIM heared of "Salvinorin A blotters" but how are they made? Due to the very very small doses, is there made a f.e.ethanol/Salvinorin solution and then droped on the blotter so that there is f.e. 1mg of salvinorin on it??? And then putting it on your tongue?