Use patterns and self-reported effects of Salvia divinorum: an internet-based survey.

BACKGROUND There is growing use of Salvia divinorum (SD), a psychoactive plant that produces hallucinogen-like effects through a kappa opioid receptor (KOR) mechanism. Little is known about KOR agonist effects in humans and about users of SD. OBJECTIVES To characterize the reasons, methods, and reported consequences of SD use. METHODS Individuals reading SD-related pages of a drug-information website were invited to anonymously complete an online questionnaire if they had used SD. RESULTS Participants (N=500) were 92.6% male and 23.4 ± 8.7 (mean ± s.d.) years old. They had used a median of six times (range 1-250). 80.6% probably or definitely would use SD again. Most participants (92.6%) typically smoked or vaporized SD product. When smoked, the drug's main effects were estimated to last 14.1 ± 12.8 (range 0.5-120) minutes. When asked to compare SD effects to other methods of altering consciousness, the most common answer was that SD was unique (38.4%). 25.8% reported persisting (≥ 24 h) positive effects (often described as increased sense of well-being) on at least one occasion. 4.4% reported persisting negative effects (most often anxiety). CONCLUSIONS SD is typically smoked, acute effects are brief, and persistent adverse effects are uncommon. In addition to acute hallucinogenic effects, SD may produce subacute increases in subjective well-being. Such a subacute effect would be unusual for a drug that is used non-medically, as withdrawal from other drugs typically either does not affect mood or causes dysphoria. Findings from this convenience sample should be confirmed and extended using surveys of random samples and controlled clinical studies.

[1]  V. Chefer,et al.  Endogenous κ-Opioid Receptor Systems Regulate Mesoaccumbal Dopamine Dynamics and Vulnerability to Cocaine , 2005, The Journal of Neuroscience.

[2]  H. Emrich,et al.  Psychotomimesis mediated by kappa opiate receptors , 1986, Science.

[3]  M. Aceto,et al.  Effects of JDTic, a selective kappa-opioid receptor antagonist, on the development and expression of physical dependence on morphine using a rat continuous-infusion model. , 2005, European journal of pharmacology.

[4]  D. Cohen,et al.  Neuroendocrine and behavioral effects of the selective kappa agonist spiradoline in Tourette's syndrome: A pilot study , 1993, Psychiatry Research.

[5]  Bryan L. Roth,et al.  Salvinorin A: A potent naturally occurring nonnitrogenous κ opioid selective agonist , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[6]  N. Mello,et al.  Sex differences in opioid antinociception in rhesus monkeys: antagonism of fentanyl and U50,488 by quadazocine. , 2002, The journal of pain : official journal of the American Pain Society.

[7]  J. Levine,et al.  Gender difference in analgesic response to the kappa-opioid pentazocine , 1996, Neuroscience Letters.

[8]  M. Picker,et al.  Sex-related differences in mechanical nociception and antinociception produced by μ- and κ-opioid receptor agonists in rats , 2002 .

[9]  A. Zapata,et al.  Endogenous kappa opioid receptor systems modulate the responsiveness of mesoaccumbal dopamine neurons to ethanol. , 2006, Alcoholism, clinical and experimental research.

[10]  R. Spanagel,et al.  The Effects of Opioid Peptides on Dopamine Release in the Nucleus Accumbens: An In Vivo Microdialysis Study , 1990, Journal of neurochemistry.

[11]  Philip S. Portoghese,et al.  Antidepressant-Like Effects of κ-Opioid Receptor Antagonists in the Forced Swim Test in Rats , 2003, Journal of Pharmacology and Experimental Therapeutics.

[12]  T. Blackburn,et al.  κ‐Opioid‐induced changes in renal water and electrolyte management and endocrine secretion , 1989, British journal of pharmacology.

[13]  C. Gaveriaux-Ruff,et al.  Opioid receptor genes inactivated in mice: the highlights , 2002, Neuropeptides.

[14]  Cécile Béguin,et al.  Depressive-Like Effects of the κ-Opioid Receptor Agonist Salvinorin A on Behavior and Neurochemistry in Rats , 2006, Journal of Pharmacology and Experimental Therapeutics.

[15]  P. Rubin,et al.  The cardiovascular and central nervous system effects in the human of U-62066E , 1994, European Journal of Clinical Pharmacology.

[16]  A. Sedman,et al.  Diuretic Effects, Pharmacokinetics, and Safety of a New Centrally Acting Kappa‐Opioid Agonist (CI‐977) in Humans , 1994, Journal of clinical pharmacology.

[17]  L. Bierut,et al.  Association of the κ-opioid system with alcohol dependence , 2006, Molecular Psychiatry.

[18]  G. Bigelow,et al.  Enadoline, a selective kappa opioid agonist: comparison with butorphanol and hydromorphone in humans , 2001, Psychopharmacology.

[19]  James E Lange,et al.  Salvia divinorum: effects and use among YouTube users. , 2010, Drug and alcohol dependence.

[20]  L. Bierut,et al.  Association of the kappa-opioid system with alcohol dependence. , 2006, Molecular psychiatry.

[21]  Jennifer M. Mitchell,et al.  A single injection of the kappa opioid antagonist norbinaltorphimine increases ethanol consumption in rats , 2005, Psychopharmacology.

[22]  E. Butelman,et al.  The plant-derived hallucinogen, salvinorin A, produces κ-opioid agonist-like discriminative effects in rhesus monkeys , 2004, Psychopharmacology.

[23]  Eric J. Nestler,et al.  Inhibition of cAMP Response Element-Binding Protein or Dynorphin in the Nucleus Accumbens Produces an Antidepressant-Like Effect , 2002, The Journal of Neuroscience.

[24]  F. Simonin,et al.  Decreased oral self-administration of alcohol in kappa-opioid receptor knock-out mice. , 2005, Alcoholism, clinical and experimental research.

[25]  Paul Ernsberger,et al.  Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[26]  J. Pintar,et al.  Prior Activation of Kappa Opioid Receptors by U50,488 Mimics Repeated Forced Swim Stress to Potentiate Cocaine Place Preference Conditioning , 2006, Neuropsychopharmacology.

[27]  Elissa J. Chesler,et al.  The melanocortin-1 receptor gene mediates female-specific mechanisms of analgesia in mice and humans , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[28]  R. Pavarin.  Substance use and related problems: a study on the abuse of recreational and not recreational drugs in Northern Italy. , 2006, Annali dell'Istituto superiore di sanita.

[29]  J. Wyatt,et al.  Using the Internet for Surveys and Health Research , 2002, Journal of medical Internet research.

[30]  Carlo Petrini,et al.  Informed consent in experimentation involving mentally impaired persons: ethical issues. , 2010, Annali dell'Istituto superiore di sanita.

[31]  E. Nestler,et al.  Altered Responsiveness to Cocaine and Increased Immobility in the Forced Swim Test Associated with Elevated cAMP Response Element-Binding Protein Expression in Nucleus Accumbens , 2001, The Journal of Neuroscience.

[32]  Amy E. Miller,et al.  Evaluation of Herbal Dietary Supplements Marketed on the Internet for Recreational Use , 2005, The Annals of pharmacotherapy.

[33]  Mark S. Schmidt,et al.  Pharmacokinetics of the plant‐derived κ‐opioid hallucinogen salvinorin A in nonhuman primates , 2005 .

[34]  R. Clark,et al.  Salvia divinorum: exposures reported to a statewide poison control system over 10 years. , 2011, The Journal of emergency medicine.

[35]  R. Craft,et al.  Sex differences in opioid antinociception: kappa and 'mixed action' agonists. , 2001, Drug and alcohol dependence.

[36]  C. Epling,et al.  A New Species of Salvia from Mexico , 1962, Botanical Museum leaflets, Harvard University.

[37]  M. Picker,et al.  Sex-related differences in mechanical nociception and antinociception produced by mu- and kappa-opioid receptor agonists in rats. , 2002, European journal of pharmacology.

[38]  R. Craft,et al.  Sex differences in opioid antinociception: κ and ‘mixed action’ agonists , 2001 .

[39]  D J Siebert,et al.  Salvia divinorum and salvinorin A: new pharmacologic findings. , 1994, Journal of ethnopharmacology.

[40]  C. Gaveriaux-Ruff,et al.  Exploring the opioid system by gene knockout , 2002, Progress in Neurobiology.

[41]  Donald J. Abraham,et al.  Burger's medicinal chemistry, drug discovery, and development , 2010 .

[42]  K. Wiren,et al.  Anticonvulsive effects of kappa-opioid receptor modulation in an animal model of ethanol withdrawal. , 2006, Genes, brain, and behavior.

[43]  G. Gründer,et al.  Toxic psychosis after intake of the hallucinogen salvinorin A. , 2008, The Journal of clinical psychiatry.

[44]  William M. Butler,et al.  Divinorin A, a psychotropic terpenoid, and divinorin B from the hallucinogenic Mexican mint, Salvia divinorum , 1984 .

[45]  K. Hanes.  Antidepressant effects of the herb Salvia divinorum: a case report. , 2001, Journal of clinical psychopharmacology.

[46]  W. Martin,et al.  Studies of the dependence-producing potential of the narcotic antagonist 2-cyclopropylmethyl-2'-hydroxy-5,9-dimethyl-6,7-benzomorphan (cyclazocine, WIN-20,740, ARC II-c-3). , 1965, The Journal of pharmacology and experimental therapeutics.

[47]  E. Butelman,et al.  Unconditioned Behavioral Effects of the Powerful κ-Opioid Hallucinogen Salvinorin A in Nonhuman Primates: Fast Onset and Entry into Cerebrospinal Fluid , 2009, Journal of Pharmacology and Experimental Therapeutics.

[48]  Takemi Yoshida,et al.  Determination of salvinorin A and salvinorin B in Salvia divinorum-related products circulated in Japan. , 2008, Forensic science international.

[49]  Joanna S. Fowler,et al.  Pharmacokinetics of the potent hallucinogen, salvinorin A in primates parallels the rapid onset and short duration of effects in humans , 2008, NeuroImage.

[50]  Alfredo Ortega,et al.  Salvinorin, a new trans-neoclerodane diterpene from Salvia divinorum(Labiatae) , 1982 .

[51]  Sundeep Singh.  Adolescent salvia substance abuse. , 2007, Addiction.

[52]  J. Clapp,et al.  College student use of Salvia divinorum. , 2008, Drug and alcohol dependence.

[53]  Mark S. Schmidt,et al.  Pharmacokinetics of the plant-derived kappa-opioid hallucinogen salvinorin A in nonhuman primates. , 2005, Synapse.

[54]  A. D. Marderosian,et al.  High performance liquid chromatographic quantification of salvinorin a from tissues ofsalvia divinorum epling & játiva-m , 1999 .

[55]  O. Hayden Griffin,et al.  Salvia Divinorum Use among a College Student Sample , 2008, Journal of drug education.

[56]  R. Langs,et al.  RETROSPECTIVE ALTERATIONS OF THE LSD‐25 EXPERIENCE , 1964, The Journal of nervous and mental disease.

[57]  K. Wiren,et al.  Anticonvulsive effects of κ‐Opioid receptor modulation in an animal model of ethanol withdrawal , 2006 .

[58]  Yan Zhang,et al.  Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats. , 2003, The Journal of pharmacology and experimental therapeutics.

[59]  V. O’Keane,et al.  Enhancement of the Prolactin Response to d-Fenfluramine in Drug-Naive Schizophrenic Patients , 1996, British Journal of Psychiatry.

[60]  Bryan L Roth,et al.  Salvinorin A, an Active Component of the Hallucinogenic Sage Salvia divinorum Is a Highly Efficacious κ-Opioid Receptor Agonist: Structural and Functional Considerations , 2004, Journal of Pharmacology and Experimental Therapeutics.

[61]  W. Uhl,et al.  Influence of asimadoline, a new kappa-opioid receptor agonist, on tubular water absorption and vasopressin secretion in man. , 2000, British journal of clinical pharmacology.

[62]  J. Riba,et al.  Pattern of use and subjective effects of Salvia divinorum among recreational users. , 2006, Drug and alcohol dependence.