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The dopamine D3 receptor antagonist VK4-116 reduced oxycodone self-administration in rats, as well as drug-seeking behaviors after oxycodone reinstatement following withdrawal. VK4-116 did not interfere with oxycodone’s pain-relieving effects

In animal studies, α2δ-1 and its interactions with NMDA receptors in the spinal cord triggered the pain sensitivity and analgesic tolerance that occurs with chronic morphine treatment. Blocking the α2δ-1–NMDA interaction reduced opioid-induced hyperalgesia and analgesic tolerance.

An experimental compound with a dual action at two opioid receptors may provide powerful pain relief without many of opioids' harmful side effects.

Mindfulness-Oriented Recovery Enhancement (MORE) reduces opioid misuse among chronic pain patients. MORE shifts patients' attention away from drug cues and toward cues for natural rewards.

Among patients with chronic pain, those who reported less ability to tolerate physical or emotional distress were more likely to misuse opioid analgesics.