Designer drugs are made by slightly modifying the chemical structure of an existing drug to produce a new substance with similar pharmacologic effects.
Researchers at the University of Wisconsin-Madison and collaborators at the National Institute on Drug Abuse recently analyzed two of the most popular designer drugs – mephedrone and methylone, sold until recently as “bath salts.”
The two drugs were widely available on the Internet and at some “head” shops until they were banned last October, following reports describing serious cardiovascular and neurological problems, and even deaths.
The scientists compared the designer drugs to methamphetamine, or “speed,” and MDMA, or “ecstasy,” both of which have been extensively studied.
Methamphetamine is a stimulant used medically for the treatment of attention deficit hyperactivity disorder. It also suppresses appetite and produces euphoria. MDMA results in enhanced sensory perception, a general sense of well-being and access to deep emotions. MDMA has proven effective in relieving anxiety in studies involving soldiers and others with post-traumatic stress disorder (PTSD) and in terminal patients with end-of-life anxiety.
The studies, directed by Dr. Nicholas Cozzi, senior scientist and faculty associate in the Department of Cell and Regenerative Biology at the UW School of Medicine and Public Health, showed that, overall, both designer drugs resembled MDMA more than methamphetamine.
However, the experiments also showed that methylone, a derivative of MDMA, does not produce long-term depletion of serotonin in the brain, possibly the most problematic side effect associated with MDMA. Some people have described this depletion as a neurotoxic effect that may reduce the potential clinical value of MDMA.
“MDMA can be therapeutic, but the serotonin depletion is a concern,” says Cozzi, a pharmacologist and medicinal chemist. “Our study shows that methylone does not deplete serotonin like MDMA does. Further research will be needed to see if it has the same unique psychological effects as MDMA.”
Cozzi is interested in studying the way psychoactive drugs affect transporters that shuttle neurotransmitters such as serotonin, dopamine and norepinephrine in and out of synapses, the gaps between neurons where cell-to-cell communication occurs. The signal-carrying neurotransmitters play a key role in mood, emotion, appetite, motivation and reward – and behaviors that go with them.
Normally, transporters limit neurochemical signals by moving neurotransmitters from the synapse back into the cell. But methamphetamine and MDMA make transporters run in reverse, pumping neurotransmitters out of the cell and back into synapses.
As neurotransmitter levels in synapses rise, users feel the effects. And as those levels inside cells go down, long-term serotonin depletion can occur.
“Serotonin depletion seems to be related to a rise in core body temperature that produces hyperthermia, which has been implicated in some MDMA-related deaths.” Cozzi says.
In studies in test tubes and in awake, moving rats, the researchers found that both mephedrone and methylone acted on transporters in ways that most closely resembled MDMA. The results suggested that each compound evoked neurotransmitter release in similar ways, but with a larger effect on serotonin than dopamine.
High doses of the designer drugs did not produce severe hyperthermia or long-term changes in two related brain regions that MDMA produced. Both designer drugs also stimulated motor activity but were weaker than methamphetamine at doing this.
Several research groups have begun or are planning additional studies of methylone, says Cozzi.
“These studies may open the door for it becoming more acceptable for clinical use in treating anxiety or PTSD,” he says.
The research was published online in the journal Neuropsychopharmacology.
University of Wisconsin School of Medicine and Public Health