Use of nonprohibited hallucinogenic plants: increasing relevance for public health? A case report and literature review on the consumption of Salvia divinorum (Diviner's Sage)

INTRODUCTION:: We want to call attention to a mint plant, called diviner's sage ( Salvia divinorum), originally used in shamanic ceremonies of the Mazatec Indians of Mexico. On numerous websites of the internet, this ancient herbal drug and its extracts are offered as a legal means of widening individual awareness. Regarding its dose-response relationship, the active ingredient, salvinorin A, is one of the most potent naturally occurring hallucinogens. Laws on controlled substances, except for Finland, Denmark and Australia, do not prohibit cultivating, consuming or dealing with Salvia divinorum. Ingestion by smoking, vaporising or chewing, induces a short-lived inebriant state with intense, bizarre feelings of depersonalization. This article wants to be a signal for physicians or psychotherapists to take Salvia into consideration, when exploring young people for drug use. METHODS: We report the individual perceptions of a young man consuming Salvia divinorum. We review the scarce scientific literature and consider relevant internet websites. DISCUSSION: We define open issues for further investigations and try to discuss why Salvia divinorum may be of interest for teenagers and young adults in Europe.     

Salvia divinorum: An overview of the usage,misuse, and addiction processes

Salvia divinorum, a sage plant with leaves that can produce a psychoactive high, has been used for hundreds of years for its psycho‐mimetic effects in religious rituals in South America. Salvia has now become popular mainly with adolescents and young adults for the short‐lived relatively pleasant experiences many consider a “legal high” and its ready availability through Internet purchases. The main (psycho)active compound in salvia is Salvinorin A, a potent κ‐opioid agonist and although the short and long‐term effects have not been examined in sufficient detail, it is widely believed to have low addictive potential and low toxicity. Recent findings, however, seem to suggest that Salvinorin A can precipitate psychiatric symptoms and negatively affect cognition. Its ready availability and increasingly widespread use requires clinicians to have knowledge and awareness of its effects.     

Neuroimmune mechanisms of psychostimulant and opioid use disorders

Substance use disorders are global health problems with few effective treatment options. Unfortunately, most potential pharmacological treatments are hindered by abuse potential of their own, limited efficacy, or adverse side effects. As a consequence, there is a pressing need for the development of addiction treatments with limited abuse potential and fewer off target effects. Given the difficulties in developing new pharmacotherapies for substance use disorders, there has been growing interest in medications that act on non‐traditional targets. Recent evidence suggests a role for dysregulated immune signaling in the pathophysiology of multiple psychiatric diseases. While there is evidence that immune responses in the periphery and the central nervous system are altered by exposure to drugs of abuse, the contributions of neuroimmune interactions to addictive behaviors are just beginning to be appreciated. In this review, we discuss the data on immunological changes seen in clinical populations with substance use disorders, as well as in translational animal models of addiction. Importantly, we highlight those mechanistic findings showing causal roles for central or peripheral immune mediators in substance use disorder and appropriate animal models. Based on the literature reviewed here, it is clear that brain‐immune system interactions in substance use disorders are much more complex and important than previously understood. While much work remains to be done, there are tremendous potential therapeutic implications for immunomodulatory treatments in substance use disorders.     

Systematic Review of Clinical Trials Assessing Pharmacological Properties of Salvia Species on Memory,Cognitive Impairment and Alzheimer's Disease

Salvia officinalis L. and Salvia lavandulaefolia L. have a longstanding use as traditional herbal remedies that can enhance memory and improve cognitive functions. Pharmacological actions of S. officinalis and S. lavandulaefolia on healthy subjects and on patients suffering of cognitive decline have been investigated. Aim of this review was to summarize published clinical trials assessing effectiveness and safety of S. officinalis and S. lavandulaefolia in the enhancement of cognitive performance in healthy subjects and neurodegenerative illnesses. Furthermore, to purchase a more complete view on safety of S. officinalis and S. lavandulaefolia, we collected and discussed articles regarding toxicity and adverse reactions. Eight clinical studies investigating on acute effects of S. officinalis on healthy subjects were included in the review. Six studies investigated on the effects of S. officinalis and S. lavandaeluaefolia on cognitive performance in healthy subjects. The two remaining were carried out to study the effects of sage on Azheimer's disease. Our review shows that S. officinalis and S. lavandulaefolia exert beneficial effects by enhancing cognitive performance both in healthy subjects and patients with dementia or cognitive impairment and is safe for this indication. Unfortunately, promising beneficial effects are debased by methodological issues, use of different herbal preparations (extracts, essential oil, use of raw material), lack of details on herbal products used. We believe that sage promising effects need further higher methodological standard clinical trials.     

Abus de stéroïdes anabolisants androgènes et physiopathologie

Anabolic-androgenic steroids (AAS), including testosterone and its synthetic derivatives, are used illicitly to enhance athletic performance and physical appearance. Although little is known about AAS’ long-term actions, short-term side effects include a large array of adverse dose-dependent physiological and psychological consequences. Alongside elite athletes who take steroids for competitive purposes, many recreational gym members and non-competitive bodybuilders, who have little hope of financial gain or fame, also abuse of synthetic hormones to enhance their physique and gain social recognition. This worrisome phenomenon occurs on a global scale despite legal sanctions and health warnings. Inconsistencies in dosing strategies between clinical trials and the ASS real world use polypharmacy accounts for the fact that many studies have underestimated the true array of physio- and psychopathological side effects.     

The hallucinogenic herb Salvia divinorum and its active ingredient salvinorin A inhibit enteric cholinergic transmission in the guinea-pig ileum.

Salvia divinorum is a widespread hallucinogenic herb traditionally employed for divination, as well as a medicament for several disorders including disturbances of gastrointestinal motility. In the present study we evaluated the effect of a standardized extract from the leaves of S. divinorum (SDE) on enteric cholinergic transmission in the guinea-pig ileum. SDE reduced electrically evoked contractions without modifying the contractions elicited by exogenous acetylcholine, thus suggesting a prejunctional site of action. The inhibitory effect of SDE on twitch response was abolished by the opioid receptor antagonist naloxone and by the kappa-opioid antagonist nor-binaltorphimine, but not by naltrindole (a delta-opioid receptor antagonist), CTOP (a mu-opioid receptor antagonist), thioperamide (a H(3) receptor antagonist), yohimbine (an alpha(2)-receptor antagonist), methysergide (a 5-hydroxytryptamine receptor antagonist), N(G)-nitro-L-arginine methyl ester (an inhibitor of NO synthase) or apamin (a blocker of Ca(2+)-activated K(+) channels). Salvinorin A, the main active ingredient of S. divinorum, inhibited in a nor-binaltorphimine- and naloxone-sensitive manner electrically induced contractions. It is concluded that SDE depressed enteric cholinergic transmission likely through activation of kappa-opioid receptors and this may provide the pharmacological basis underlying its traditional antidiarrhoeal use. Salvinorin A might be the chemical ingredient responsible for this activity.     

Pharmacokinetics of the plant-derived kappa-opioid hallucinogen salvinorin A in nonhuman primates

Salvinorin A, a potent hallucinogen isolated from the leaves of Salvia divinorum, has gained popularity among adolescents in the USA. No detailed study of the pharmacokinetics has been conducted in vivo. The present study investigates the in vivo pharmacokinetics of salvinorin A (0.032 mg/kg, i.v. bolus) in rhesus monkeys (n=4, 2 male, 2 female). The elimination t(1/2) was rapid (56.6+/-24.8 min) for all subjects. Pharmacokinetic differences (distribution t(1/2), elimination t(1/2), and AUC) were observed between males and females, suggesting potential sex differences in its pharmacologic effects. Salvinorin B, the presumed major metabolite, is observed to accumulate ex vivo; however, in this study it never reached the limit of detection.     

Medicaid-covered alcohol and drug treatment use among people with intellectual disabilities: evidence of disparities

For some, community inclusion facilitates access to alcohol and drugs and, therefore, the potential for developing substance abuse disorders. However, little is known about substance abuse treatment use among people with intellectual disabilities. Using standardized performance measures, substance abuse treatment utilization was examined for Medicaid-covered people with intellectual disabilities and substance abuse (N=9,484) versus people without intellectual disabilities (N=915,070). The sociobehavioral model of healthcare use guides multivariate logistic regression analyses of substance abuse treatment utilization patterns, revealing disability-related disparities. Factors associated with utilization included being non-White, living in a nonurban area, having a serious mental illness, and living in a state with a generous Medicaid plan for substance abuse treatment. Implications relate to health policy, service delivery patterns, and the need for cross-system collaboration in the use of integrated treatment approaches.     

‘Higher education’ – substance use among Berlin college students

Berlin is internationally known for its intense nightlife associated with high rates of psychoactive substance use. Previous studies conducted in other cities indicated college students as a group at high risk for substance (mis‐)use that was associated with individual psychological and cognitive impairments as well as lower academic performance. The aim of this study was to provide detailed data about the substance use patterns of Berlin college students. In addition, major protective and risk factors were analysed. An online questionnaire assessing sociodemographic data and various relevant aspects of both legal and illegal substance use such as consumption pattern and frequency as well as risk‐taking behaviour was developed and distributed among colleges in Berlin. A sample of 9351 participants from 17 different colleges in Berlin completed the questionnaire. The study revealed high lifetime (69.3%), past year (45.9%) and past month (28.3%) prevalence of illicit substance use in the sample. Daily tobacco‐smoking, a mental disorder diagnosis, a positive screening for problematic consumption (Cage‐AID), bisexual orientation and living in open relationship were main factors positively associated with the prevalence and the extent of illicit substance use. Students in Berlin appear to show higher rates of illicit substance use than was previously reported for age‐matched individuals in the general German population and college students in other cities. Thus, they are a relevant target group for early prevention and intervention concerning substance use and abuse.     

The abuse potential of medications for attention-deficit/hyperactivity disorder: Recent advances in our understanding

Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric disorder that first presents in childhood and can cause impairment in social, emotional, and academic functioning. First-line treatment of ADHD is pharmacotherapy with stimulant medication. However, significant concerns about stimulants include their potential misuse or abuse. This review updates the reader on recent findings on the abuse potential of stimulants used to treat ADHD. Specific points of interest include the prevalence of misuse, risk factors associated with misuse, and implications of misuse on later substance use disorders.     

Sensitive periods of substance abuse: Early risk for the transition to dependence

Early adolescent substance use dramatically increases the risk of lifelong substance use disorder (SUD). An adolescent sensitive period evolved to allow the development of risk-taking traits that aid in survival; today these may manifest as a vulnerability to drugs of abuse. Early substance use interferes with ongoing neurodevelopment to induce neurobiological changes that further augment SUD risk. Although many individuals use drugs recreationally, only a small percentage transition to SUD. Current theories on the etiology of addiction can lend insights into the risk factors that increase vulnerability from early recreational use to addiction. Building on the work of others, we suggest individual risk for SUD emerges from an immature PFC combined with hyper-reactivity of reward salience, habit, and stress systems. Early identification of risk factors is critical to reducing the occurrence of SUD. We suggest preventative interventions for SUD that can be either tailored to individual risk profiles and/or implemented broadly, prior to the sensitive adolescent period, to maximize resilience to developing substance dependence. Recommendations for future research include a focus on the juvenile and adolescent periods as well as on sex differences to better understand early risk and identify the most efficacious preventions for SUD.     

Regulation, religious experience, and epilepsy: a lens on complementary therapies

Complementary and alternative medical (CAM) therapies include chiropractic, acupuncture and traditional Oriental medicine, massage therapy, and herbal remedies; mind-body therapies (such as meditative practices and visualization); and folk practices and religious healing. Of these, modalities based on spiritual healing create a number of conundrums for the clinician, including legal, regulatory, and ethical issues. Further, the historic relationship between the study of epilepsy and religious experience suggests particular, potential associations between CAM therapies (and especially spiritual healing) and care for epileptic patients. There are at least two dimensions to this exploration: first, the widespread use of spiritual healing for treatment of epilepsy; and second, the hypothesized connection between epileptic seizures and mystical states. A number of legal rules help address potential abuse of authority by health care professionals, and include: (1) medical licensure; (2) scope of practice; (3) professional discipline; (4) malpractice; and (5) fraud. This article offers a preliminary resource for clinicians interested in these topics.     

Recreational substance use patterns and co-morbid psychopathology in adults with intellectual disability

There is very limited evidence on the patterns of recreational substance use among adults with Intellectual Disabilities (ID) who have co-morbid mental health problems. In this study we collected clinical and socio-demographic information as well as data on substance use patterns for consecutive new referrals (N = 115) to specialist mental health services for adults with ID in South-East London. The data were recorded from active clinical case notes. About 15% of patients had a history of substance use, however only 8% were currently using substances. Alcohol was the most frequently used substance (80%) followed by cannabis (28%) and cocaine (12%). Overall, substance use was significantly more likely among male patients, those with a mild level of ID and those with a forensic history. Substance use was less likely among patients with autism and more likely among those with schizophrenia spectrum disorders. Logistic regression analyses revealed that those with a forensic history were about five times more likely to have current substance use problems. Male gender was the only predictor for legal substance (alcohol) use. Illicit substance use was about three times more likely among patients with schizophrenia spectrum disorders. The present results highlight the role of illicit substance use as a health risk factor for adults with ID as well as the need to increase awareness within specialist mental health services.     

Adolescents with Substance Diagnoses in an HMO: Factors Associated with Medical Provider Referrals to Substance Abuse and Mental Health Treatment

This study examines the factors related to referrals of adolescents with substance use disorders to substance abuse or mental health treatment by their medical providers. Administrative and chart review data from the membership of a large private health maintenance organization (HMO) were collected from a probability sample of 400 adolescents, ages 13-18, who were diagnosed with a substance use disorder in 1999. Logistic regression analyses examined referral to substance abuse treatment and referral to mental health treatment in the aggregate and stratified by gender. Documented use of both alcohol and another illicit drug, and legal problems increased likelihood of referral to substance abuse and mental health treatment, whereas diagnoses of alcohol and marijuana use disorders decreased likelihood of referral to substance abuse treatment. Mental health diagnoses played a limited role in both types of referrals, although specific psychosocial problems were associated with increased likelihood of referrals. Treatment history and location of first mention of problem were significant predictors of referral. There were no gender differences in referral rates to either substance abuse or mental health treatment; however predictors of referral differed by gender. These findings extend our knowledge about factors that influence clinicians' treatment referrals of adolescents with substance abuse diagnoses and have implications for influencing clinician referral behavior within health plans.     

Clinical importance of caffeine dependence and abuse

Caffeine is the most widely consumed psychoactive substance and is a legal stimulant that is readily available to children. Caffeine has occasionally been considered a drug of abuse and the potential for dependence on caffeine has been debated. Presently, due to a paucity of clinical evidence on caffeine dependence or abuse, no such diagnosis is included in the Diagnostic and Statistical Manual of Mental Disorder-fourth edition. The authors present two cases of abuse or dependence on the caffeine contained in 'eutrophic' (energy/nutritional) beverages or caffeine preparations, followed by a review of clinical studies demonstrating evidence that some people can manifest a clinical syndrome of caffeine dependence or abuse. The cases suggest that caffeine can produce a clinical dependence syndrome similar to those produced by other psychoactive substances and has a potential for abuse. In a recent study using a structured interview and the Diagnostic and Statistical Manual of Mental Disorder-fourth edition criteria for substance dependence and abuse, a subset of the general population was found to demonstrate caffeine dependence or caffeine abuse. Therefore, the authors propose that companies or businesses manufacturing or marketing caffeine or products containing caffeine must meet the following guidelines: (i) clearly indicate the caffeine content of products containing comparatively higher quantities of caffeine; (ii) warn that such products should be avoided by infants and children wherever possible, and inform adult consumers about the precise quantity of caffeine that is considered safe for consumption; and (iii) clearly state that consuming large quantities of caffeine and the long-term use of caffeine carry health risks.     

Legal challenges for substance abuse treatment during disasters

Certain groups with preexisting mental and behavioral health conditions, such as substance use disorders, may be especially vulnerable during and shortly after disasters. Researchers have found that substance abuse treatment programs and the individuals they serve experienced major disruptions after the September 11, 2001, attacks on the World Trade Center and the Pentagon and after Hurricane Katrina. This column considers legal challenges that may arise when a rapid influx of licensed providers is needed for substance abuse treatment during disasters and reviews specific legal issues that disasters may raise for opioid treatment programs. Opportunities to mitigate legal challenges and facilitate substance abuse treatment during disasters are discussed.     

Health correlates of recreational gambling in older adults

OBJECTIVE: Prior studies have found high rates of alcohol use and abuse/dependence, depression, bankruptcy, and incarceration associated with recreational gambling. Despite growing rates of recreational gambling in older adults, little is known regarding its health correlates in this age group. The objective of this study was to identify health and well-being correlates of past-year recreational gambling in adults age 65 years and older, compared to adults age 18-64 years. METHOD: The Gambling Impact and Behavior Study surveyed by telephone a nationally representative sample of 2,417 adults. Multivariate analyses were used to compare past-year recreational gamblers and nongamblers in the older and younger age groups on measures of alcohol use and abuse/dependence, substance abuse/dependence, depression, mental health treatment, subjective general health, incarceration, and bankruptcy. Additional analyses compared the gambling patterns in older and younger adult past-year recreational gamblers. RESULTS: After the effects of sociodemographic factors were controlled, older adult past-year recreational gamblers were more likely to report past-year alcohol use and better health than were older nongamblers. Multivariate analyses investigating interactions of gambling and age found that higher rates of good to excellent subjective general health in recreational gamblers were mainly attributable to the older age group. Older adult gamblers were more likely than younger adult gamblers to begin gambling after age 18 years, to gamble more frequently, and to report a larger maximum win. CONCLUSIONS: Recreational gambling patterns of older adults differ from those of younger adults. In contrast to findings in younger adults, recreational gambling in older adults is not associated with negative measures of health and well-being.     

Herbals and botanicals in geriatric psychiatry.

There is high prevalence of herbal medicine use among elderly people. Most patients do not reveal their herbal use to their physicians and pharmacists. The authors describe some commonly used herbal remedies in terms of their potential benefits and known adverse effects. The review also highlights the potentially serious risk of herb-drug interactions and discusses communication issues and regulatory concerns associated with use of herbal medicines. Health practitioners should remember to include herbal use history in their routine drug histories and remain informed of the beneficial and harmful effects of these treatments.     

Substance abuse in patients with schizophrenia

The comorbidity of schizophrenia and substance abuse has attracted increasing attention in the past years, with multiple potential links, including genetic vulnerability, neurobiological aspects, side effects of medications, and psychosocial factors being under discussion. The link between the use of substances and the development of psychoses is demonstrated by the high prevalence of substance abuse in schizophrenia. Apart from alcohol misuse, substances commonly abused in this patient group include nicotine, cocaine, and cannabis. In particular, heavy cannabis abuse has been reported to be a stressor eliciting relapse in schizophrenic patients. In general, substance use in psychosis is associated with poorer outcomes, including increased psychotic symptoms and poorer treatment compliance. Since both disorders have been observed to be closely interdependent, a particular treatment for schizophrenic patients with comorbidity of substance abuse is needed in order to provide more effective care. In this article, we discuss various potential modes of interaction and interdependence, and the possibility of embarking on new therapeutic paths for treating this particular population.