A common and potentially toxic additive called levamisole increases the addiction potential of cocaine by making the stimulant drug more rewarding to the brain, research from the Temple University School of Medicine indicates. Like virtually all other addictive substances, cocaine makes its inroads by producing highly rewarding sensations in a part of the human brain known informally as the pleasure center. In a study published in February 2015 in the journal Drug and Alcohol Dependence, Temple researchers used laboratory testing on rats to assess the impact of a common additive called levamisole on cocaine’s ability to trigger rewarding sensations inside the brain. These researchers concluded that the presence of levamisole may make cocaine substantially more enticing to users.
When cocaine reaches the pleasure center, it triggers an increase in the levels of a chemical called dopamine. In turn, heightened levels of dopamine boost activity in the pleasure center and lead to the onset of an extremely rewarding sensation called euphoria. Euphoria is commonly most intense for new users of the drug; unfortunately, new users often consciously or unconsciously attempt to capitalize on this fact by consuming the drug repeatedly over time. However, when cocaine repeatedly barrages the pleasure center, this brain area changes its baseline function and eventually comes to rely on the presence of the drug to feel “normal.” The initiation of this brain change marks the beginning of physical cocaine dependence. In real-world terms, physically dependent cocaine use and cocaine addiction are one in the same. Addicted cocaine users have a condition called stimulant use disorder, which covers all forms of stimulant-related addiction. Non-addicted, dysfunctional cocaine abusers also qualify for a stimulant use disorder diagnosis, as do non-addicted, dysfunctional consumers of other stimulant substances such as amphetamine or methamphetamine. While all habitual cocaine use can trigger the onset of addiction, habitual consumption of the highly processed form of the drug known as “crack” may shorten the pathway to addiction by a substantial amount of time.
Levamisole is a de-wormer that veterinarians use to combat animal parasites. In the past, some doctors also used the substance as a treatment for colorectal cancer and arthritis, although such applications are no longer legal in the U.S. Levamisole is found in approximately 80 percent of all cocaine sold in America; in this role, it nominally acts primarily as a filler or additive designed to add bulk. Human consumption of levamisole can lead to the development of a potentially lethal white blood cell disorder called neutropenia, as well as a related condition called agranulocytosis and cases of toxic overdose.
Impact on Cocaine’s Addiction Potential
In the study published in Drug and Alcohol Dependence, the Temple University researchers used laboratory experiments on rats to explore the impact that levamisole has on the amount of reward produced by cocaine consumption, as well as on the amount of central nervous system stimulation triggered by the presence of the drug. The researchers initiated this project, in part, out of a belief that there must be some underlying explanation for the widespread addition of levamisole to batches of cocaine. The researchers also wanted to know if levamisole has drug effects beyond its influence on cocaine-related reward and central nervous system stimulation. The researchers gave a group of rats a low dose of cocaine combined with a much smaller dose of levamisole. They compared the rewarding effects of this substance combination to the rewarding effects of cocaine alone, as well as to the rewarding effects of a placebo dose of saline solution. The researchers concluded that, at very low doses, neither cocaine nor levamisole had an impact on the animals’ pleasure centers. However, when identical low doses of the two substances were combined, they did produce a rewarding drug effect in this brain area. The researchers used levamisole and somewhat larger doses of cocaine to test these substances’ combined impact on the central nervous system. They concluded that levamisole/cocaine produces greater activation of this system than cocaine alone, at least until doses of cocaine rise above a certain size. The study’s authors also found that levamisole has a minor drug effect inside the brain when not used in combination with cocaine. Overall, they believe that the presence of levamisole in cocaine noticeably contributes to the amount of addiction-promoting reward produced by this drug.