The invention generally relates to compositions and methods with covalently bound compounds, such as controlled substances covalently attached to a
chemical moiety, and
opioid antagonists or covalently bound
opioid antagonists to enhance
analgesic potency and / or attenuate one or more adverse effects of covalently bound compounds, including adverse
side effect(s) in humans such as
nausea,
vomiting, dizziness, headache,
sedation (
somnolence), physical dependence or pruritis. This invention relates to compositions and methods for selectively enhancing the
analgesic potency of a covalently bound compound and simultaneously attenuating anti-analgesia,
hyperalgesia, hyperexcitability, physical dependence and / or tolerance effects associated with the administration of a covalently bound compound. The methods of the invention comprise administering to a subject an
analgesic or sub-analgesic amount of a covalently bound compound and an amount of excitatory
opioid receptor antagonist such as
naltrexone or
nalmefene effective to enhance the analgesic
potency of a covalently bound compound and attenuate the anti-analgesia,
hyperalgesia, hyperexcitability, physical dependence and / or tolerance effects of covalently bound compound. The invention also relates to the addition of covalently-bound opioid antagonists to the compositions containing covalently bound compounds such that if the compositions are subjected to manipulation by illicit chemists, the
opioid antagonist is released effectively reducing or eliminating the euphoric effect of the covalently bound compounds.