by James J. Galligan, Ph.D., Associate Chair,
Department of Pharmacology and Toxicology

There has been a recent surge in reports of use and abuse of bath salts as psychoactive drugs that provide a cheap and easily accessible “high” (see for example: ‘Bath Salts’ A Growing Drug Problem, Officials Say‘).

There are many bath salts provided by different commercial suppliers and many of these products contain mephedrone and methylenedioxypyrovalerone.  Subjects abusing these products have reported psychedelic experiences and amphetamine-like stimulant responses (see links below).

Abusers have also reported episodes of self-mutilation while under the influence of these substances.  There is now a growing movement to ban mephedrone and methylenedioxypyrovalerone but the Food and Drug Administration reports that it will take sometime before the regulations can be developed and implemented.

What are mephedrone and methylenedioxypyrovalerone (MDPV) and how do they produce their psychostimulant effects?

Mephedrone (4-methylmethcathinone) is derived from cathionine, the active ingredient in the African Khat plant (SpringerLink – Psychopharmacology, Online First™).  Although mephedrone is a relatively recent addition to the drug of abuse portfolio in the U.S. it has been popular for sometime in the United Kingdom.  Cathionine and mephedrone have amphetamine-like effects on the brain and the peripheral nervous system.  These effects include stimulation of release of the neurotransmitters dopamine and norepinephrine in the brain.  Dopamine is a neurotransmitter in the brain’s reward pathways while norepinephrine is a neurotransmitter in brain areas that control attention and appetite.  These effects account for the addictive (reward), stimulant and appetite suppressing properties of amphetamine-like drugs.  Mephedrone users also report rapid heart rate and this effect is caused by norepinephrine release from the nerves that supply the heart.  Norepinephrine speeds up heart rate.

bath salts

Methylenedioxypyrovalerone is contained in some bath salts - and is easily obtained via the internet

MDPV is also a cathionine derivative with pharmacological properties similar to mephedrone.  Both of these substances can be purchased over the internet, but recent analysis of these substances from different suppliers has revealed a wide range of purity.  This is part of the danger associated with mephedrone and MDPV abuse, the buyer is never quite sure what he/she is purchasing and ingesting.  Another substantial concern is that the interaction of these drugs with other drugs of abuse is unknown.  This is a problem because most drug abusers or polysubstance abusers.  Drug-drug interactions can cause unpredictable psychoactive or toxic responses.

So, clichés are clichés for a reason: let the buyer beware.

Additional information:

by James J. Galligan, Ph.D., Associate Chair,
Department of Pharmacology and Toxicology

The fall semester has started at MSU and I am fully immersed in a course I teach on drug abuse and  jama-logoaddiction.  This has brought my focus to news items related to drug addiction and its treatment. An article published in the September 9 issue of the Journal of the American Medical Association provides some interesting new data that may be related to drug addiction, motivation and mental illness.

Attention deficit hyperactivity disorder (ADHD) is an illness in which some children and adults have difficulty focusing on single tasks. It has always been puzzling that the drug most commonly used to treat ADHD is an amphetamine-like drug called methylphenidate (Ritalin). Why would we use a stimulant drug to treat an illness already associated with hyperactivity? Well, the study referenced above may have helped solve this puzzle.

Positron Emission Tomography (PET)

Positron Emission Tomography (PET)

The investigators used positron emission tomography to study the activity of dopamine neurons in the brains of normal subjects and ADHD patients. Specifically, they looked at dopamine neurons in the mesolimbic dopamine pathway. The mesolimbic dopamine pathway is part of the brain’s reward system as it becomes active when we perform enjoyable tasks, such as eating, or when we feel good about an accomplishment. This is also the brain pathway that is hijacked by addictive drugs like amphetamine, cocaine, heroin and nicotine. The study revealed that ADHD patients had impaired dopamine signaling in the mesolimbic dopamine pathway. This would cause ADHD patients to experience reduced rewards for performing tasks successfully and perhaps this is why ADHD patients have difficulty concentrating and completing tasks.

The results of the study are important for a number of reasons. Firstly, the results provide new information about the abnormalities in brain function that may be responsible for ADHD. Secondly, these data help to explain the paradoxical benefits of a stimulant drug for treatment of hyperactivity. As methylphenidate causes an increase in dopamine mediated neurotransmission, methylphenidate may boost activity in the endogenous reward system making it easier for the ADHD patient to experience the reward associated with task completion. Lastly, these data may also help to explain the increased incidence of drug addiction and obesity in ADHD patients. If their endogenous reward system is impaired, these subjects may seek out addictive drugs which activate the reward pathways. This might also explain the overeating that leads to obesity in some ADHD patients.

If there is reduced reward associated with eating, the ADHD patient might overeat in an effort to compensate for the reduced reward associated with feeding. This new information may not only help to treat ADHD, it may also lead to new treatments for drug addiction and obesity.

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