Salvia Studies Hold Promise for Addiction

But addictive drugs work by stimulating what scientists call mu opioid receptors. Salvinorin A works on the kappa opioid receptors, which have a depressive effect if activated. Today, we are facing a crisis in relation to the use and abuse of opiates and related molecules. In fact, new molecules are not being developed as analgesics, fundamentally because of the long time taken by the processes to position these new agents until they are properly marketed.

4 Drug sessions

Seated in a comfortable reclining lounger, the participant inhaled slowly for 40 s while the flask was heated, followed by a verbally cued exhale. For placebo sessions, the same protocol was followed but no salvinorin A was in the flask. The unblinded session monitor who heated the flask was obscured from the participant’s view (behind the divider), while the blinded staff member collected drug-strength ratings and all other pre- and post-session data from the participant. Both of these changes were correlated to some degree with motion, but there was evidence that motion may have attenuated some of these effects (see Supplementary Fig. S7 and S8). Further evidence that motion could not fully explain these effects comes from the fact that dFC of most between-network interactions was a consistently good predictor of SA effect on brain function, whereas eFC of only selective networks was predictive. Although the decreases in dFC were unexpected in light of the “entropy” produced by hallucinogens, ketamine was similarly found to attenuate but not increase dFC across the brain, especially in visual network interactions46.

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Divinorum, their metabolites, and semi-synthetic analogs in the last decade has shown their potential as an analgesic agent. Divinorum is normally ingested by chewing fresh leaves or drinking an infusion for treating GI disorders like abdominal swelling, diarrhea, and intestinal spasms, illnesses that course with chronic inflammation. During the last decade, different studies have focused on proving the effect of S. Often the quantity of salvinorin A in the leaves has been boosted by the addition of a concentrated extract of the compound. More than a dozen states have outright bans on the product, and eight others have restrictions such as prohibitions for minors. The U.S. Department of Justice’s Drug Enforcement Administration has included it in a list of “drugs and chemicals of concern,” but to date there is no federal prohibition against it.

Salvia divinorum: effects and use among YouTube users

Overall, these findings are strikingly similar to those of classic psychedelics and dissociative anesthetics. Once the inhalation procedure was sufficiently understood, a flask containing 15 µg/kg of SA was affixed to the delivery device (see Supplementary Information for description of drug and delivery device including analysis of tube deposition in Fig. S1). The inhalation procedure was then conducted during which an experimenter carefully moved the flames around the bottom of the flask and visually inspected that all SA was vaporized. Participants were then prompted by researchers to verbally rate the strength of subjective drug effects on a scale of 0 (no effect) to 10 (extreme, strongest imaginable) at 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, and 45 min post-inhalation.

• Similar to previous reports2,3, the average subjective drug strength rating from the practice session dropped by approximately half from the peak rating by 10 min (i.e., equivalent in time to halfway through each scan; Fig. 1a).
• The final sample of volunteers who both inquired and qualified for this study consisted only of males, thereby limiting generalizability.
• Salvinorin A works on the kappa opioid receptors, which have a depressive effect if activated.
• Divinorum for healing multiples conditions, including insect bites, eczema, candidiasis, cystitis, and menstrual cramps, and even depression or alcohol addiction.4 These multiple therapeutic targets implicate a complex pharmacology and mechanism of action for this mystical plant.
• However, because of the small sample and the healthy, hallucinogen-experienced status of participants, conclusions regarding safety are limited.

“We have done the first human study with the drug and it could be the first examination fo a whole new line of drugs that have a therapeutic potential.” Johnson said learning about salvia’s effects on the brain could lead to medical advances in the treatment of Alzheimer’s disease, chronic pain and, though it seems counterintuitive, drug addiction. Divinorum, SA, and their analogues decrease the pain induced by neuropathy and inflammation.

Subjective drug effects

These findings are somewhat at odds with the specificity of the entropic brain hypothesis, which emphasizes how classic psychedelics drive entropy in the DMN and other higher level networks that supposedly constrain the state-space of the brain40,41. By increasing DMN entropy, it has been proposed that psychedelics could loosen the inflexibility of behaviors in conditions such as depression and addiction. If such effects of classic psychedelics are important and related to therapeutic outcomes, then it could be inferred based on our findings that that such benefits extend to κ-opioid agonists. Indeed, SA and other κ-opioid agonists may be promising treatments for depression14,15 and cocaine addiction20 (but see66), and ibogaine, a compound with a much longer time course than SA and both κ-opioid and 5-HT2A agonist activity, is being explored for the treatment of addiction and mood disorders18,19.

Although Salvia divinorum leaves were traditionally administered orally by the indigenous Mazatecs of Mexico for ritualistic purposes1, the plant is now recreationally administered via vaporization or combustion. When inhaled, SA can produce intense feelings of depersonalization and derealization accompanied by drastic perceptual changes, with effects beginning within a minute of inhalation and subsiding by 15 min2–4. Also like classic psychedelics16,17, other drugs with κ-opioid agonist activity such as ibogaine are being explored for their potential to treat addiction18,19, and SA, specifically, has shown efficacy in the treatment of preclinical models of cocaine abuse20. Unlike classic psychedelics, inhaled SA appears to be more incapacitating, causing unique alterations in interoception4, dense amnesia3, and more closely mimicking near-death experiences (similar to ketamine)21. One study reported SA experiences to be more similar to dreaming than experiences under other hallucinogens22 (cf. 23).

The microtorch was adjusted so that the flame was approximately 1.5 cm in length, and the tip of the flame was held in contact with the round-bottom flask. Using these procedures, inhalation of un-volatilized drug was unlikely because the salvinorin A residue left upon evaporation of acetone appeared strongly attached to the interior of the flask, and in tests with various rates of mechanical airflow (simulated inhalation) without heat, salvinorin A was observed to remain undisturbed. Tests with mechanical airflow and the application of the microtorch showed the method to result in the volatilization of salvinorin A with little scorching (small black marks presumably resulting from combustion).

• This technique identifies the connectivity measures (sFC, dFC, eFC) and network interactions most predictive of drug effects.
• These structural modifications of SA increase its efficacy and duration of action (for a complete review, see Roach and Shenvi).49 Some of these analogues have been proved in acute, inflammatory, and neuropathic pain models (Table 1, Figure 2).
• In order to reduce costs, a multi-session, crossover design was not implemented, which would have minimized possible expectancy and order effects.
• Where f(xi) is the discretized frequency distribution after binning and w is the bin width.

After a phone screen confirmed basic inclusion criteria (age, high-school-level education, and prior hallucinogen use), volunteers came to the laboratory for in-person screening. Participants were excluded who reported having a first or second degree relative with schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), or bipolar I or II disorder. Additional screening visits assessed general motivation for participation and established trust and rapport with the study staff.

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. Salvinorin A resulted in orderly dose- and time-related participant ratings of drug strength.

In conclusion, these results suggest the feasibility of future research examining the effects of salvinorin A, and potentially other high efficacy kappa agonists, in healthy hallucinogen-experienced participants. This study examined the overall psychological effects of inebriation facilitated by the naturally-occurring plant hallucinogen study of controversial hallucinogen salvia shows intense and novel effects in humans 12 07 2010 Salvia divinorum using a double-blind, randomized, placebo-controlled trial. Thirty healthy individuals self-administered Salvia divinorum via combustion and inhalation in a quiet, comfortable research setting. Experimental sessions, post-session interviews, and 8-week follow-up meetings were audio recorded and transcribed to provide the primary qualitative material analyzed here. Additionally, post-session responses to the Hallucinogen Rating Scale provided a quantitative groundwork for mixed-methods discussion. Qualitative data underwent thematic content analysis, being coded independently by three researchers before being collaboratively integrated to provide the final results.

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Practice sessions were repeated for five participants due to excessive movement under SA or not completing the inhalation procedure properly. Consistent with results from nonhuman animal research (Mowry et al. 2003), the present results suggest a safe physiological profile for salvinorin A at the studied doses, under controlled conditions, and in psychologically and physically healthy hallucinogen-experienced participants. Salvinorin A produced no significant changes in heart rate or blood pressure; no tremor was observed; and no adverse events were reported. However, because of the small sample and the healthy, hallucinogen-experienced status of participants, conclusions regarding safety are limited. For each session the round-bottom flask was heated from underneath with a butane microtorch with approximate flame temperature of 1,700 °C (model ST200T, Bernzomatic, Huntersville, NC).

“This is a landmark paper because it’s the first paper in which authentic salvinorin A was administered to human volunteers under controlled conditions, and it was shown to be hallucinogenic,” says psychiatrist and pharmacologist Bryan Roth of the University of North Carolina at Chapel Hill, who was not involved in the research. “All we had before were anecdotal reports, where people had bought salvia extract from their local smoke shop.” While the study is small and can’t vouch for the safety of salvia, the results lend some hard science to the current legislative fray around the substance, which is criminalized in some states but not regulated federally. M.K.D. collected data, analyzed data, produced figures, and wrote the manuscript. J.M.C. recruited participants, collected data, and contributed to writing the manuscript.

The tubing was replaced between participants but was not replaced for different sessions for the same participant. The resulting “pipe” was held stable by a ring stand clamp during administration, and the tube extended through a hole in a room divider toward the participant’s sitting area. Johnson and the Johns Hopkins team say that they undertook the research in an attempt to put some rigorous scientific information into current concerns over the growing recreational use of Salvia divinorum, which is an herb in the mint family. The plant, which has been used for centuries by shamans in Mexico for spiritual healing, is the target of increased nationwide legal efforts to restrict its availability and use. Though little is known about the compound’s effects in humans, some legislators have been spurred to action after watching one of thousands of online videos chronicling the uncontrolled behavior that sometimes follows its use.