Salvia Divinorum

Salvia Divinorum

Psychosomatics 2012:53:277–279 Published by Elsevier Inc. on behalf of The Academy of Psychosomatic Medicine. Case Reports Salvia Divinorum Eric G. ...

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Psychosomatics 2012:53:277–279

Published by Elsevier Inc. on behalf of The Academy of Psychosomatic Medicine.

Case Reports Salvia Divinorum Eric G. Meyer, M.D., Brian W. Writer, D.O.

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alvia divinorum’s (Salvia) psychogenic properties were first utilized by the Mazateca to achieve ceremonial visions over a millennium ago.1 Colloquially referred to as Divine’s Sage, Seer’s Sage, Magic Mint, SkaPastora, and Sally-D,2 Salvia is an unregulated substance that is readily accessible to consumers. Traditionally consumed as a tea, Salvia is commonly dried and smoked or the raw leaves are chewed as a “quid.” Concentrated oil can also be administered sublingually.3 Although dosing varies between identically marketed packaging,4 studies have determined that Salvinorin A, the active component in Salvia, is effective at 200 –500 ␮g. This can be compared with lysergic acid diethylamide’s (LSD) effective dose of 20 –100 ␮q.2 Animal literature suggests that Salvinorin A, a transneoclerodane terpenoid,5 putatively enhances brain dopaminergic levels through partial agonist activation of ␬-opioid receptors6 while indirectly increasing cannabinoid activity via subsequent second messenger systems.7,8 Based on these activities, Salvinorin A has been theorized to produce potentially beneficial antidepressant and anxiolytic effects, along with a relatively less desirable neuropsychological profile consisting of mood, perceptual, and neurocognitive symptoms.9 The Drug Enforcement Agency has characterized Salvia’s neuropsychological profile to include “perceptions of bright lights, vivid colors and shapes, as well as body movements and body or object distortions. Other effects include dysphoria, uncontrolled laughter, a sense of loss of body, overlapping realities, and hallucinations . . . adverse physical effects may include incoordination, dizziness, and slurred speech.”2 The following case describes an individual who was admitted following a psychotic reaction to Salvia ingestion.

Case Reports

Mr. A, a 23-year-old white active duty military male, presented to the emergency department for evidence of Psychosomatics 53:3, May-June 2012

psychosis. Routine blood work, urine drug screen (Thermo Scientific CEDIA DAU Assay and Roche Diagnostics KIMS Assay), and vital signs were unremarkable. Evaluation by consultation psychiatry revealed paranoia and disorganized thinking with associated hypervigilance and mood lability. Physical exam was notable for ataxia. Mr. A reported smoking Salvia earlier that day. Given the history, Mr. A was admitted to inpatient psychiatry for further assessment and management. Inpatient evaluation the following morning revealed a complete resolution of the symptoms without interval psychotropic intervention. Mr. A demonstrated intact reality testing with good insight regarding his pre-admission circumstances and mental health difficulties. He recalled purchasing Salvia from a local gas station where the cashier had reportedly advised him of the “calming” properties of Salvia. Without any prior use or experience regarding Salvia, the patient smoked an unknown quantity of Salvia under the presumption that it would “calm” him. He instead experienced a rapid onset of psychosis and anxious dysphoria, which he described as an inability to distinguish whether he “was still alive or not,” which evoked fear, anxiety, and hypervigilance. Further interviewing and review of his medical record revealed no previous personal or family mental health difficulties. His medical history was likewise unremarkable. He denied current use of any prescriptions, over-thecounter medications, or illicit substances. Given his lack of ongoing mental health difficulties, Mr. A was discharged from the hospital within 24 hours of admission Received May 1, 2011; revised July 9, 2011; accepted July 11, 2011. From San Antonio Uniformed Services Health Education Consortium, San Antonio, TX (EGM, BWW); Teaching Fellow, Uniformed Services University of the Health Sciences, Bethesda, MD (EGM); Clinical Adjunct Faculty, University of Texas Health Science Center, San Antonio, TX (BWW). Send correspondence and reprint requests to Dr. Eric G. Meyer, Wilford Hall Medical Center, 59 MHS/SGOWV1, 2200 Bergquist Dr. Ste 1 Lackland AFB TX 78236-9908. e-mail: [email protected] Published by Elsevier Inc. on behalf of The Academy of Psychosomatic Medicine.

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Case Reports with a discharge diagnosis of Salvia divinorum-induced psychotic disorder. A review of his interval medical records following discharge revealed no further mental health difficulties over the ensuing 9 months.

Discussion

Recreational use of Salvia has increased over past years due to its perceived safety,10 increased availability, difficult-to-detect metabolites, and lack of federal regulation.2 In 2006, according to the Substance Abuse and Mental Health Services Administration (SAMHSA), approximately 1.8 million Americans over the age of 12 had used Salvia, with 756,000 reporting use within the past year. Young white males, defined as 18 to 25 years of age, were the most represented group with prevalence rates ranging from 4% to 7%.11 These rates mirror an increase in the misuse of medications, herbals, and other unregulated substances. Assessing Salvia’s safety can be difficult for typical consumers due to internet saturation with misinformation12 and limited available scientific literature. Relevant articles published between 1996 and June 2011 were identified using an Ovid MEDLINE search for the term “salvia divinorum.” The search detected 91 articles with five case studies, seven self-reported retrospective human studies, and no prospective human studies. The above search was supplemented with a cross reference of citations, which revealed one ahead-of-publication double-blind placebocontrolled prospective human trial that examined the effects of Salvia inhalation at various doses in a small number of subjects (n ⫽ 4) with previous hallucinogen use.13 Our literature review detected many neuropsychological similarities between Salvia and classic hallucinogenic (e.g., LSD or psilocybin) ingestion. This comparison is similar to the overall characterization as put forth by the only available human prospective trial.13 This study demonstrated that Salvinorin A inhalation significantly differed from placebo in regards to subsequent neuropsychological symptoms. These included somesthetic, mystical, and affective experiences, as well as perceptual and cognitive disturbances, as measured by the Hallucinogen Rating and Mysticism Scales, both of which have validated sensitivity for psilocybin ingestion. Likewise, a commonly reported subjective experience in the available literature was impaired reality testing including derealization14 and synesthesia.15 Although diuresis, hyperthermia, and nau278

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sea are not uncommon symptoms after Salvia use,14,16 they were not observed in our patient’s presentation. No evidence of tolerance or withdrawal symptoms appeared throughout our literature review. Reference material report that neuropsychological symptoms arise within 30 seconds of inhalation ingestion and 5–10 min after buccal absorption.15 The duration of effect is approximately 20 –30 min for inhalation versus 2 hours after buccal absorption. One study of users in an uncontrolled setting, accomplished via a review of YouTube videos, reports apparent symptom resolution occurring at an average of 8 min post-inhalation exposure.17 According to one animal study, although Salvinorin A’s serum half-life is 75 min, its central nervous system halflife is 36 minutes; this may be related to Salvia’s rapid breakdown by numerous oxidative enzymes and multidrug resistant protein, P-gp.18 Animal literature demonstrated peak concentrations throughout the brain 40 seconds after inhalation ingestion, with higher concentrations in the cerebellum and visual cortex.19 Interestingly, dosing has been shown to influence the intensity of the reaction but not the duration.13 Possibly related to intestinal inactivation, Salvia ingestion produces no neuropsychological symptoms. The safety and habit-forming potential of Saliva is debated. While Salvia’s putative dopaminergic modulation may confer a habit-forming risk, no study has been able to definitively characterize the long-term neuropsychological or behavioral profile of Salvia. However, one case study does describe a potential for persistent psychosis20 and, considering the pharmacodynamic and user-experiential similarities, one might infer a similar risk of emergent persistent psychosis with Salvia usage compared with cannabis or other traditional hallucinogenics. Despite this uncertainty, the popular press has at times asserted that Salvia may be safe10 and online pro-Salvia sources have claimed that the adverse neuropsychological profile and associated behavioral risk can be limited if Salvia is used in a quiet place with a trusted observer. However, it is improbable that observation alone would reliably provide an adequate safeguard for the potential neuropsychological sequelae and associated unforeseen consequences of ingestion. Our case was representative of the available literature in regards to user demographics, neuropsychological reaction, and resolution of symptoms. The patient’s response to Salvia ingestion resulted in a brief psychotic event that rapidly and fully resolved following a brief supportive inpatient mental health admission. One of the troubling aspects of this case, and perhaps most revealing of Salvia’s Psychosomatics 53:3, May-June 2012

Meyer and Writer inherent dangers, was the patient’s report that the strongest effects occurred while driving, which could have easily compromised his and others’ safety. Several states and the US military have already enacted regulatory efforts. Federal regulation of Salvia has also been pursued, as several other countries have already done. However, such regulations have proven difficult given Salvia’s ubiquitous availability, lack of screening tools, and continued uncertainty regarding definitive characterization of Salvinorin A’s long-term neuropsychological effects. Such uncertainty may be addressed with future improvements in detection, increased regulation, and methodologically sound prospective trials. In fact, a search of clinicaltrials.gov on 12 June 2011 for the term “Salvia di-

vinorum” produced two human randomized double-blinded, placebo controlled trials assessing tolerability and presence of psychosis following administration of Salvinorin A. An objective understanding of Salvia’s neuropsychological effects could empower regulatory efforts that might mitigate the possible consequences as observed in our case. Disclosure: The authors disclosed no proprietary or commercial interest in any product mentioned or concept discussed in this article. The opinions expressed in this document are solely those of the authors and do not represent an endorsement by or the views of the United States Air Force, the Department of Defense, or the United States Government.

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