Lack of Psychostimulant Treatment Options: Answers in Salvia?

Pharmaceutical interventions for addiction have been making news headlines for quite some time now; especially the drug naloxone (Narcan) which has saved thousands of people from overdose deaths by reversing the effects of opioids almost instantly. There are numerous medications for alcoholism (most widely known being disulfiram, marketed under the brand name Antabuse) and even more medications are available for opioid addiction; some of the more well-known including methadone, buprenorphine (Subutex), and naltrexone (Revia, Vivitrol). Vivitrol has stirred up quite the frenzy because it is administered as an injection once a month, thereby ensuring improved treatment compliance since any pleasurable effects of heroin and other narcotics cannot be felt with naltrexone in one's system. This is important because drugs like Antabuse require daily dosing (unless implanted), and even the most motivated patients can struggle to comply with the dosing regimen.

So with all of this said, it may appear that our society is managing addiction right? Well, we have come a long way, and there is even research looking into "drug vaccines" as preventatives underway... however the overwhelming majority of the focus is on opioids and alcohol. Addiction to psychostimulants is also problematic and prevalent, but there are NO effective treatment options as of the date of this posting.

The good news is that research is being done, such as the work on nicotine being performed by Dr. Daniel McGehee at the University of Chicago. His experiments are modeled after prior work done by other researchers on cocaine with the somewhat surprising finding of "remarkable similarity in the mechanisms underlying synaptic plasticity induced by nicotine and cocaine in the ventral tegmental area (VTA)."

Nicotine structure

Cocaine structure

It is important to note that cocaine and nicotine act on different targets, however they both achieve the same effect of increasing dopamine levels in the VTA which has been shown to induce long-term potentiation (LTP). LTP means the brain synapses are strengthened and there is a long-lasting increase in signal transmission between neurons. LTP induction has been correlated with mechanisms of drugs of abuse. Dr. McGehee concluded his research article with the statement that "understanding the common receptors and signaling pathways [between cocaine and nicotine] may help identify more effective treatments for psychostimulant addiction."

This leads us into the discussion of interesting other compounds that have been brought up in the literature on addiction. There have been papers published regarding Ibogaine, a psychoactive substance extracted from an african shrub that has claims of modulating opiate tolerance. However, the focus of this post is on Salvia divinorum as a potential treatment option for stimulant abuse. Scientific American Mind published an article on August 11, 2015 (link below) on this subject. The article discusses studies involving rats whose results may point to Salvia disrupting many of cocaine's effects. The article states that Salvinorin-A, one of the more than dozen chemicals contained in the plant's leaves, is the most potent naturally occurring psychedelic known; it is approximately 10 times more potent than psilocybin (one of the two psychoactive substances found in magic mushrooms).

Structure of Salvinorin-A

Most importantly, Salvinorin-A is a selective kappa opioid receptor agonist which only affects dopamine and not serotonin. This is very unique because all other psychoactive compounds (LSD, magic mushrooms, MDMA, etc.) exert their psychedelic effects via activation of the serotonin system and do not affect kappa receptors at all. This property may be behind Salvia's anti-addiction claims because kappa and dopamine receptors act in opposite ways but are related complementary and work to maintain a sort of homeostasis. Stimulants increase the level of dopamine in the basal ganglia whereas Salvinorin-A reduces dopamine levels in parts of the basal ganglia. This is fairly early research, but it is nevertheless intriguing. This is especially true now because research on the various opioid receptors is increasingly focusing on the kappa receptors.

None of this serves as an endorsement for Salvia use, as it is itself known as a drug of abuse with its own set of side-effects and unknowns. Rather, in the very least, I hope it does serve as a reminder to keep an open mind, for we never really know where answers may lie; I can safely conclude that we do need more resources for those struggling with stimulant abuse and addiction in general. 

References: 

Addy, Peter H., and Ana E. Maqueda. "Traditional Medicine from Southern Mexico Offers Help with Addiction." Scientific American. Scientific American Mind 11 Aug. 2015. Web. http://www.scientificamerican.com/article/traditional-medicine-from-southern-mexico-offers-help-with-addiction/

Mao, Danyan, Keith Gallagher, and Daniel S. McGehee. "Nicotine Potentiation of Excitatory Inputs to Ventral Tegmental Area Dopamine Neurons." The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 31.18 (2011): 6710-20. Web.
http://www.jneurosci.org/content/31/18/6710.full

All images are from https://pubchem.ncbi.nlm.nih.gov