Meth Binge Puts Brain Chemistry at Stake

Availability of a raw methamphetamine ingredient in popular OTC products prompted national regulations to move products that contain pseudoephedrine behind the pharmacy counter.

Alongside the introduction of a meth-resistant pseudoephedrine formulation, this move has created roadblocks for illicit methamphetamine laboratories. Some areas of the country have even begun to promote meth-resistant pseudoephedrine in order to prevent the use of pharmacy-provided products as methamphetamine precursors. As a result, methamphetamine and its many consequences are of interest to pharmacists.

Methamphetamine causes dopamine to spike and creates an intense rush of pleasure or prolonged euphoria. With continued use, however, methamphetamine destroys dopamine receptors, making it impossible to feel pleasure. Pleasure centers appear to heal over time, but research has demonstrated that recovery can take years and cognitive damage may be permanent.

A new study published in Neuropharmacology described methamphetamine’s persistent striatal dopaminergic deficits in binge users who have used methamphetamine in the past. Although it was an animal study, previous research has indicated that animal models are predictive of methamphetamine’s effects in humans.

These and other investigators had previously demonstrated that a history of methamphetamine abuse creates intermediate neurochemical changes that may attenuate persistent dopaminergic deficits. The researchers allowed rats to self-administer methamphetamine or saline for 1 week. Sixteen hours after the final self-administration session, the researchers gave some rats a binge dose of methamphetamine or saline and sacrificed some rats without additional exposure.

Rats that received a binge dose of active drug and had self-administered methamphetamine had less compromised striatal dopamine (DA) content and striatal dopamine transporter (DAT) function than those that had not. In rats with no previous methamphetamine use, the binge methamphetamine treatment decreased DAT function and DA content, while rats with previous exposure had better DA content, but not DAT function.

Twenty-four hours after the binge methamphetamine treatment, rats with prior drug use had significantly less DAT function decline. DA content was approximately 25% higher in the group that self-administered methamphetamine, which implied tolerance to the drug’s neurotoxic effects within the striatum.

Although the study’s clinical implications remain unclear, it provided additional information about methamphetamine’s negative and potentially lifelong effects on the brain. This research looked at DA only, and pharmacists should note that methamphetamine’s many toxicities are cumulative.