Is Salvia dangerous? Bias in research.

Is Salvia dangerous? Bias in research.

Public awareness of Salvia divinorum is always growing; mostly thanks to scaremongering media reports about the new ‘legal high’ that is threatening our safety. Unfortunately, the majority of instances of Salvia use we hear about in the media focus on reckless or irresponsible use of the plant. What we don’t hear a lot about is the Legal Highs Dangers Killer Plantsresponsible use of Salvia, or the amazing medical potential of the plant. Hundreds of scientists are currently studying Salvia in the hope of finding a cure for addiction, or developing groundbreaking new painkillers. It’s important that the people in government who are responsible for drug policy are aware of the scientific community’s consensus about Salvia, rather than basing their decisions entirely on biased media reports.

Here I’ll present two very recent, very different papers on Salvia divinorum. The first (Winslow and Mahendran 2014) presents a case study of one person who took what may have been Salvia in an irresponsible way, and use it to claim that Salvia is a harmful drug of abuse. The second (Serra et al. 2015) undertakes a thorough and controlled study of the effects of Salvinorin A on rats, in an attempt to understand the potential dangers of Salvia as a drug of abuse.

Winslow & Mahendran 2014

Singapore drug policy

This report is published in the Singapore Medical Journal. Singapore is notorious for handing out practically medieval punishments for being in possession of or testing positive for tiny amounts of drugs. Drug abuse rates are incredibly low in Singapore, which is a good thing. But this draconian system punishes people for even one-time use of relatively safe drugs such as marijuana and MDMA. It’s likely that SMJ editors have little interest in supporting a progressive and rational drug policy; most papers in the journal address the treatment of abusers. However taking this approach can mean harmless and beneficial drugs are disregarded, assumed to be drugs of abuse just like the rest.

Salvia: an unknown drug?

In this case report, the authors seem quick to claim that Salvia is unknown to the medical literature, stating that there is ‘scarce information about its psychoactive effects in medical literature’. This is simply not true; a literature search yields dozens of papers compiling accounts of the ‘acute phase experiences’ of Salvia divinorum, some of which I have discussed previously in this blog. The authors state: ‘To the best of our knowledge, the present report is the first report to describe the vivid hallucinatory experiences associated with the use of Salvia’. Not quite!  

 

No proof it’s Salvia!

The man at the center of this ‘case report’ bought ‘Salvia’ online, although the authors say it was sold as ‘plant food’. It’s not clear what proof the authors have that this was genuine Salvia, especially if it was labeled as something else. We also have no idea what strength of extract the Salvia was. The user smoked a ‘small amount’ of the substance in a joint, and experienced ‘terrifying’ hallucinations for ’12-14’ minutes. The authors note that these effects are ‘unusual compared to those previously reported’, and I agree! Firstly, the vaporisation temperature of Salvinorin A is extremely high, and smoking extract through a joint will usually only produce very mild effects. Additionally, Salvinorin A is very short-acting in the brain, and when smoked will only exert its effects for around 5 minutes. Finally the hallucinatory effects were quite a bit more intense than the typical experience; the user reported furniture coming to life and talking to him, and experiencing scary auditory hallucinations.

Uncontrolled use

Even if this substance was Salvia, it could have been taken irresponsibly. Although the user had a ‘history of drug abuse’, he possibly had no experience with psychedelics. He also may not have had a sober sitter present, and may not have been in a comfortable environment. All of these uncontrolled factors mean that the authors can’t definitively say that this substance was Salvia or that it was taken in a representative manner.

Mental health?

The authors go on to cite several other case studies that present the emergence of negative effects on mental health after repeated Salvia use; however in all these cases underlying mental health problems were thought to be a large factor. However they do inadvertently present an area where research is lacking; no large-scale long-term study has been performed on the effects of repeated Salvia divinorum use.

Overall this case report is based on the testimony of one man and should not have been presented in a medical journal. Papers like this are damaging; they are using pseudoscience to spread unreliable information that may influence unfair drug policies.

Serra et al, 2015

Two months after the publication of Winslow & Mahendran’s paper, Serra and her group at the University of Cagliari presented a study of the abuse potential of Salvinorin A. Previous studies had shown that Salvinorin A has the potential to raise dopamine levels in rat brains, and since drugs that affect dopamine levels are known to be particularly prone to causing addiction, Serra’s group wanted to see if Salvia could be addictive.

Testing addiction

The group decided to use a tried and tested method of determining a substance’s addictive potential. Intra-venous self administration (IVSA) has long been used to study what substances rats and mice can become addicted to. IVSA involves training a rodent to press levers in a room. The rodent is given a reward (food or milk) every time it presses either one of the levers. One of the levers also delivers, through an intravenous catheter, the drug under investigation. If the rodent likes this drug, it will prefer pressing this lever. If the rodent maintains this preference over many trials and many days, it indicates that the drug has addictive potential. If the rodent shows no preference between levers, it means the drug probably doesn’t have addictive potential.

No Preference for Salvia Develops in Rat Models

Results: no abuse potential

In this study, the IVSA trials were undertaken on two different strains of rats. Neither strain showed a preference for the Salvinorin A lever after 20 days of training. Therefore the authors conclude that Salvinorin A is probably not a drug of abuse at low doses (0.5 and 1ug/kg). The authors of this study also tried to look at dopamine levels in these rats, however failed to significantly change dopamine levels at any dose of Salvinorin A. Therefore it is possible that these rats are immune to any dopamine-altering effects of Salvinorin A at these doses. The authors point out that others have found differences in drug-related behaviour between different strains of rats, and so the strains they used in this study may not be ideal.

Of course, it’s a large jump to relate these findings directly to humans. If different strains of rats experience Salvinorin A differently, how can we expect humans to be similar? We aren’t even sure if these doses of Salvinorin A (around 1ug/kg) can be directly compared to a typical human recreational dose (around 5ug/kg). However, rats have shown to be capable of becoming addicted to cocaine and heroin, so it is reasonable to assume there are some parallels between how rats and humans react to drugs of abuse. This study at least provides compelling evidence that Salvia has little risk of abuse.

What next?

There is still much research to be done. Before Salvinorin A can be used to safely develop painkillers or anti-addiction medication, it must be fully profiled. What is lacking in the literature is a long-term study on the effects of excessive Salvia consumption to physiology and psychology.

An informed, rational and progressive drug policy requires a strong and thorough background of scientific research. All current research has shown that Salvia is a safe drug, with little or no abuse potential, but with great medical and scientific potential. Salvinorin A has a lot to offer the scientific community and perhaps society as a whole, and it’s the responsibility of scientists to study the drug thoroughly and without bias.

References

Serra V, Fattore L, Scherma M, Collu R, Spano MS, Fratta W, Fadda P (2015) Behavioural and neurochemical assessment of salvinorin A abuse potential in the rat. Psychopharmacology 232(1):91-100.

Winslow M, Mahendran R (2014) From divination to madness: features of acute intoxication with Salvia use. Singapore medical journal 55(4):e52-53.