Salvia divinorum

Abb. 1 zeigt die Strukturformel des Salvinorins A (Hauptwirkstoff) sowie die Anwendungsarten und die handelsüblichen Formen von Salvia divinorum.

Pharmacokinetics and Pharmacodynamics of Salvinorin A and Salvia divinorum: Clinical and Forensic Aspects

Salvia divinorum Epling and Játiva is a perennial mint from the Lamiaceae family, endemic to Mexico, predominantly from the state of Oaxaca. Due to its psychoactive properties, S. divinorum had been used for centuries by Mazatecans for divinatory, religious, and medicinal purposes. In recent years, its use for recreational purposes, especially among adolescents and young adults, has progressively increased. The main bioactive compound underlying the hallucinogenic effects, salvinorin A, is a non-nitrogenous diterpenoid with high affinity and selectivity for the κ-opioid receptor. The aim of this work is to comprehensively review and discuss the toxicokinetics and toxicodynamics of S. divinorum and salvinorin A, highlighting their psychological, physiological, and toxic effects. Potential therapeutic applications and forensic aspects are also covered in this review. The leaves of S. divinorum can be chewed, drunk as an infusion, smoked, or vaporised. Absorption of salvinorin A occurs through the oral mucosa or the respiratory tract, being rapidly broken down in the gastrointestinal system to its major inactive metabolite, salvinorin B, when swallowed. Salvinorin A is rapidly distributed, with accumulation in the brain, and quickly eliminated. Its pharmacokinetic parameters parallel well with the short-lived psychoactive and physiological effects. No reports on toxicity or serious adverse outcomes were found. A variety of therapeutic applications have been proposed for S. divinorum which includes the treatment of chronic pain, gastrointestinal and mood disorders, neurological diseases, and treatment of drug dependence. Notwithstanding, there is still limited knowledge regarding the pharmacology and toxicology features of S. divinorum and salvinorin A, and this is needed due to its widespread use. Additionally, the clinical acceptance of salvinorin A has been hampered, especially due to the psychotropic side effects and misuse, turning the scientific community to the development of analogues with better pharmacological profiles.

Overview of Salvia divinorum –Substance-induced psychosis

As per the literature, humans ingest a comprehensive range of food materials including drugs along with dietary supplements which are mainly derived through medicinal plant products and modifying the purpose of the central nervous system (CNS). These psychoactive based properties are mainly attributable to the existence of plant-derived secondary metabolites. Most of the cases or studies showed the effects of these phytochemicals derived from secondary metabolites on the human CNS might be linked either to their ecological roles or molecular along with biochemical based properties are reported in case of plants along with higher animals. One of the mental health disorders, psychosis where person losses its capacity of critical thinking, they perceive things differently as compared to the people around. They see or hear things that other people cannot see or hear (hallucination) or even believe things that are not true (delusion). There are so many synthetic psychosis inducer synthetic cannabinoids (SCs) as well as semi-synthetic and natural. Psychosis is a disorder which shows the effect for long-term or sometimes for the short term on an individual. In this review we will mainly look for natural psychosis inducers like Salvia divinorum and this plant may produce some secondary metabolites. Still, many of these are found to show an effect on human health in some or the other way which may range from hallucination to organ failure. These secondary metabolites affect the hippocampus region of the human brain, which is linked with memory. It is interesting to note how one chemical is used for an organism for protection and that one chemical act as a mind-altering chemical for the higher class of organism – the humans.

The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain

Salvinorin A (SA) is a κ-opioid receptor agonist and atypical dissociative hallucinogen found in Salvia divinorum. Despite the resurgence of hallucinogen studies, the effects of κ-opioid agonists on human brain function are not well-understood. This placebo-controlled, within-subject study used functional magnetic resonance imaging for the first time to explore the effects of inhaled SA on strength, variability, and entropy of functional connectivity (static, dynamic, and entropic functional connectivity, respectively, or sFC, dFC, and eFC). SA tended to decrease within-network sFC but increase between-network sFC, with the most prominent effect being attenuation of the default mode network (DMN) during the first half of a 20-min scan (i.e., during peak effects). SA reduced brainwide dFC but increased brainwide eFC, though only the former effect survived multiple comparison corrections. Finally, using connectome-based classification, most models trained on dFC network interactions could accurately classify the first half of SA scans. In contrast, few models trained on within- or between-network sFC and eFC performed above chance. Notably, models trained on within-DMN sFC and eFC performed better than models trained on other network interactions. This pattern of SA effects on human brain function is strikingly similar to that of other hallucinogens, necessitating studies of direct comparisons.