Recent research has investigated drug combinations that enhance the analgesic effectiveness of their component substances. Many studies have examined the combination of opioids and psychostimulant drugs, such as amphetamine and methylphenidate. Despite the positive results reported in the literature, this combination is rarely used in clinical practice. The purpose of this paper is to review the literature on the opioid-amphetamine combination. Experiments with animal and human subjects provide convincing evidence that d-amphetamine or methylphenidate potentiate the analgesic effects of morphine. Psychostimulant drugs have been shown in animal studies to possess intrinsic analgesic properties and to have the ability to enhance the analgesic properties of opioids when both types of drugs are given in combination. Studies with human subjects have confirmed the enhancement of opioid analgesia by amphetamines and, in addition, have demonstrated that psychostimulant drugs produce a decrease in somnolence and an increase in general cognitive abilities. The greater cognitive alertness, moreover, allows the use of larger opioid doses, which can produce a substantial increase in analgesia. These results indicate another possible method to enhance the quality of life in patients with difficult pain problems. Although the enhanced cognitive effects are well established, the effects on pain need further study to determine the mechanisms of action and the drug combinations and administration patterns that would maximize their effects.
Dalal, S., & Melzack, R. (1998, October). Potentiation of opioid analgesia by psychostimulant drugs: A review. Journal of Pain and Symptom Management. https://doi.org/10.1016/S0885-3924(98)00084-0