Salvinorin A: Effects, Uses, and Chemistry PDF

# Salvinorin A ## Introduction Salvinorin A is a psychoactive compound found in *Salvia divinorum*, a plant in the mint family known as "diviner's sage." This compound is stored in glandular trichomes, hair-like strands, similar to how phytocannabinoids are stored in the *Cannabis* plant. *Salvi...

# Salvinorin A ## Introduction Salvinorin A is a psychoactive compound found in *Salvia divinorum*, a plant in the mint family known as "diviner's sage." This compound is stored in glandular trichomes, hair-like strands, similar to how phytocannabinoids are stored in the *Cannabis* plant. *Salvia divinorum* is indigenous to Oaxaca, Mexico, where Mazatec shamans have used it for centuries in healing and divination ceremonies. The Mazatecs refer to it as the *leaf of prophecy* because of its ability to induce visions. The Mazatec shamans use *Salvia divinorum* to treat a variety of conditions, including: * Anemia * Diarrhea * Headache * Rheumatism * Swollen belly, which they attribute to a curse from black magic ## Effects of Salvinorin A Salvinorin A produces hallucinogenic and dissociative effects that have similarities to the effects of cannabis, ketamine, and high doses of classic hallucinogens. However, experienced hallucinogen users describe the effects of salvinorin A as unique and particularly intense. Salvinorin A is the first known diterpene hallucinogen. It is chemically distinct from other psychedelic compounds, such as LSD or mescaline, which are alkaloids. Dried *Salvia divinorum* leaves contain approximately 0.18% salvinorin A by weight, making it the most potent of the natural hallucinogens. As little as 200 micrograms (mg) can produce noticeable effects. This is comparable to the effective dose of synthetic or semisynthetic psychoactive drugs, such as LSD. ## Routes of Administration and Pharmacokinetics ### Traditional Use The Mazatecs traditionally use *Salvia divinorum* orally, either by chewing fresh leaves or by blending crushed leaves with water and drinking the mixture. ### Modern Recreational Use Modern recreational users typically smoke *Salvia divinorum* leaves using a pipe or bong, or by vaporizing the plant material. ### Absorption and Effects * **Buccal Membrane** * When administered sublingually, salvinorin A does not produce any effects, suggesting a lack of bioavailability through this route. * **Smoking:** * Effects are detected within approximately 5-10 minutes, build gradually, and are maintained for about 60 minutes. ## Neuropharmacology Salvinorin A is a highly selective kappa (κ)-opioid receptor agonist. It shares little structural similarity with other known κ-receptor ligands, such as dynorphin. While there is some evidence that salvinorin A may interact with other neurotransmitter systems, such as the mu (μ) opioid receptor and D₂ dopamine receptor, the evidence is not conclusive and requires further investigation. ## Effects of Salvinorin A on Animals Studies in rhesus monkeys have shown that salvinorin A produces a unique interoceptive profile, distinct from that of classic hallucinogens and dissociative agents. While the exact mechanisms are unclear, the effects appear to be primarily mediated through the κ-opioid receptor system. In rodents, salvinorin A produces: * Antinociception * Hyperthermia * Sedation * Facial relaxation * Motor incoordination * Reduced locomotor activity * Impaired spatial and episodic memory Though potent, salvinorin A has a relatively low level of toxicity. Acute or chronic exposure at doses exceeding those used by humans does not appear to produce toxic effects on the brain, liver, spleen, kidney, or bone marrow of mice. ## Effects of Salvinorin A on Humans Inhalation of smoked or vaporized salvinorin A produces a rapid onset of intense perceptual and mood effects that can be extremely pleasurable for some users while evoking feelings of anxiety and disorientation in others. ### Positive Effects * Altered state of consciousness and modified perception of external reality * Altered sense of time * Dissociation, depersonalization, and derealization (out-of-body experiences) * Spiritual experiences * Relaxation, dreaminess, and calm * Floating feeling * Improved mood and sense of well-being * Increased talkativeness and laughter * Heightened sense of creativity, insight, and self-confidence * Intense psychedelic effects * Synesthesia * Increased appreciation of aesthetics ### Negative Effects * Loss of control over experiences * Racing thoughts * Irritability, anxiety, panic attacks, terror * Acute psychosis and paranoia * Social withdrawal * Dysphoria * Physical exhaustion and drowsiness * Dizziness, headache, and sense of heaviness in the head * Mental fatigue, confusion, and disorientation * Psychomotor agitation * Temporary language impairment * Amnesia * Sweating, flushing, and chills * Nausea, vomiting, and abdominal pain ### Perceptual Alterations Salvinorin A produces profound perceptual alterations that can include: * Perceived changes in bodily form * Merging of objects with their surroundings * Relocation to a different place * Intensely colorful visions of objects and designs * Three-dimensional scenes * Cartoon-like imagery * Communication and interaction with otherworldly entities * Re-experiencing childhood memories ### Physiological Effects Salvinorin A has a safe physiological profile. It does not exert significant effects on heart rate or blood pressure. Its analgesic and anti-inflammatory properties suggest potential therapeutic value for chronic pain. ### Adverse Reactions There have been reports of individuals experiencing adverse reactions to salvinorin A that required them to visit a hospital emergency room. Often, these symptoms appear spontaneously, days after drug use, and are psychological in nature. These symptoms can resemble those of psychotic disorders, including: * Paranoia * Suspiciousness * Hallucinations * Blunted affect * Dysphoria * Thought blocking * Flight of ideas * Psychomotor agitation * Disorganization * Echolalia ### Tolerance and Withdrawal Repeated exposure to salvinorin A does not appear to lead to the development of tolerance. In fact, users report taking higher doses initially, and an intensification of drug effects with repeated use. This profile is distinct from nearly all other drugs, suggesting that the mechanism of action is unique. Symptoms of withdrawal are typically mild and may include headache, irritability, and insomnia. However, prolonged heavy use can lead to more severe symptoms, such as nausea, vomiting, diarrhea, and stomach pain. ## Conclusion Salvinorin A is a potent and complex psychoactive compound with a wide range of effects. While it can have a profound and pleasurable impact on some users, it can also evoke feelings of anxiety and disorientation in others. The long-term effects of repeated use are still not fully understood, as is the mechanism of action. More research is needed to fully understand the potential risks and benefits of this unique psychoactive substance.