27 April 2016 

Study finds sustained-release dexamfetamine is promising for reducing cocaine use

Depending on the circumstances, the use of street drugs can increase a person’s risk for exposure to germs, including bacterial infections and blood-borne viruses such as HIV and hepatitis C virus (HCV). In people with these viruses, exposure to street drugs also contributes to ill health. Therefore, researchers need to find ways to help substance users reduce their exposure to street drugs and, if possible, quit.

Heroin and cocaine

Several well-designed clinical trials have found that treatment with medically prescribed and supervised heroin can be useful for some people who are heroin-dependent and for whom methadone alone does not work. In these studies, researchers have found that heroin used in such circumstances has resulted in “improvements in mental status, physical health and social functioning.”

However, addiction specialists have found that “many heroin-dependent patients are also cocaine dependent.” In such cases of dual dependency, doctors have struggled to help patients sustain a decrease in cocaine usage. There have been many clinical trials of medicines to assess their potential for reducing cocaine dependence, but so far there is no therapy that has been licensed for this use.

Amphetamine-based therapy

Results from clinical trials suggest that some medicines that interact with the chemical messenger dopamine (used by cells in the brain and in other parts of the body to communicate) might be a useful path to pursue in the quest to reduce cocaine use and dependency. Researchers have been studying slow- or sustained-release forms of amphetamines for this purpose.

A team of researchers in the Netherlands has been exploring multiple approaches in its quest to help cocaine users reduce their use. In their latest report, published in the Lancet, the researchers analysed findings from a multicentre, randomized, placebo-controlled clinical trial of 12 weeks of daily, supervised, oral sustained-release dexamfetamine (60 mg/day) or placebo. All participants used crack cocaine and also received prescribed heroin and methadone.

The researchers found that participants who received sustained-release dexamfetamine used cocaine for significantly fewer days. Side effects were generally temporary and “well tolerated,” according to the researchers.

The study was relatively short and, although no one ceased cocaine consumption, its findings are promising and pave the way for further studies of dexamfetamine by itself and, perhaps in combination with other medicines.

Study details

A research team in the Netherlands is conducting studies of different interventions to try to help people decrease their use of cocaine. In one of those studies, researchers screened potential volunteers from “supervised, heroin-assisted treatment programmes” in Amsterdam, Rotterdam and The Hague. They recruited 73 people and randomly assigned them to the following groups:

  • sustained-release dexamfetamine – 38 people
  • fake dexamfetamine (placebo) – 35 people

Participants were recruited between August 2014 and February 2015. They took dexamfetamine or placebo under the observation of clinic staff.

The average profile of participants upon entering the study was as follows:

  • age – 49 years
  • 90% men, 10% women
  • years of cocaine use – 20 years
  • proportion with a positive urine test for cocaine on the first day of the study – 99%
  • number of days in the past month in which cocaine was used – 24 days
  • years of heroin use – 22 years
  • proportion with heavy alcohol use (five or more drinks daily) for at least one day in the past month – 34%
  • number of different anti-addiction treatments that participants had previously tried – seven

Researchers did not disclose if participants had chronic viral infections such as HIV or HCV.


Over the course of the study, the average number of (self-reported) days of cocaine use was distributed as follows:

  • dexamfetamine group – 45 days
  • placebo group – 61 days

This difference was statistically significant; that is, not likely due to chance alone.

Reduction in cocaine use occurred regardless of the city in which participants lived.

Participants who received dexamfetamine were more likely to be abstinent from cocaine for a period of time. The distribution of participants with the longest period of consecutive cocaine abstinence was as follows:

  • dexamfetamine group – 25 days
  • placebo group – 12 days

The proportions of participants who were able to stop taking cocaine for at least 21 days were as follows:

  • dexamfetamine group – 29%
  • placebo group – 6%

All of the above differences were statistically significant.

During the final four weeks of the study, researchers instituted twice-weekly urine screening for cocaine. Overall, the findings during this part of the study were broadly similar to those in the rest of the study, confirming decreased use of cocaine among participants who received dexamfetamine.

Adverse events

The distribution of adverse events was as follows:

  • dexamfetamine group – 74%
  • placebo group – 46%

According to the researchers, most side effects reported by dexamfetamine users “resolved before the end of the study.” Problems with sleep were the most common adverse event reported, distributed as follows:

  • dexamfetamine group – 34%
  • placebo group – 9%

The researchers did not find any serious side effects among participants who used dexamfetamine.

Points to consider

The present study took place in a supervised setting that required participants to visit a clinic daily. According to the researchers, this setting allowed clinic staff “to motivate [participants] and intensely monitor potential side effects.” Such a setting allowed the optimization of adherence.

The duration of the study was short, just 12 weeks. Given that many participants had been taking street drugs for years, it is unreasonable to expect that a short intervention would have resulted in the cessation of cocaine use. However, the study provides encouraging news for researchers who work in the field of addiction and the rationale for a longer and larger study.

Future research needs

According to Swiss addiction specialists who have reviewed the Dutch study, there is a need for at least the following:

  • confirmation of the study’s findings in other populations, including younger people and women
  • studies that help drug users with adherence to dexamfetamine who do not have the intense daily support received in the Dutch study
  • exploring the safety of higher doses of dexamfetamine in cocaine dependency
  • a combination of dexamfetamine with other potential anti-addiction agents to prolong periods off cocaine

In a separate report, Canadian addiction researchers have called for a “rigorous research programme” to explore the potential effect of cannabinoids (compounds found in marijuana) in people who use crack cocaine. They note that small observational studies from several countries reported that marijuana has been taken by drug users to help alleviate the harmful effects of crack cocaine—including paranoia, weight loss, craving, aggression and anxiety. Furthermore, in at least one of these reports, some crack cocaine users were able to overcome their addiction because of marijuana.

Bear in mind

According to Boston University addiction specialists and physicians Christine Pace and Jeffrey Samet:

“Studies suggest that [a person’s genes] may contribute as much as 40% to 60% of an individual’s risk for addiction. Environmental factors, particularly in childhood or adolescence, are also important, including age of first exposure to alcohol or drugs and adverse childhood experiences. Finally, substance use disorders are commonly associated with psychiatric comorbidities, including depression, anxiety and bipolar disorder. These conditions may contribute to an individual’s vulnerability to addiction; in addition, anxiety and depressive symptoms may be a consequence of long-term substance use.”

Given all of these factors, a combination of approaches to help people deal with addiction is necessary. Such approaches should try to address the issues—some of which are mentioned in the preceding paragraph—that underlie and drive addiction.


Pre-fix: A guide for people with Hep C or HIV who inject drugs

Prevention & Harm Reduction from Hepatitis C: An In-Depth Guide

Best Practice Recommendations for Canadian Harm Reduction Programs

—Sean R. Hosein


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