“It’s tricky, because you can potentially spare having to use high-dose opioids by adding gabapentin,” Dr. Walley observed. “So, as prescribers, you’re in a difficult position, because there’s a mixed message here: When gabapentin is combined with opioids, that’s when it’s dangerous – but that’s also when they’re potentially more effective for pain.”
Promethazine
This drug has a host of neurobiologic actions, which collectively provide sedative and antiemetic effects. Promethazine jacks up opioid-induced euphoria and alleviates withdrawal symptoms. It’s commonly detected in toxicology testing of patients on prescription opioids for chronic pain or on methadone therapy for opioid use disorder.
National Poison Data System figures show an unwelcome trend: A sharp uptick in promethazine abuse/misuse beginning in 2008, even while the total number of poisoning events of all kinds reported to the system began a steady decline (J Addict Med. 2015 May-Jun;9[3]:233-7).
Clonidine
This centrally acting alpha2-adrenoreceptor and imidazoline-receptor agonist is indicated for treatment of hypertension. However, it’s also extensively used off-label to treat anxiety, as well as for alcohol and opioid withdrawal symptoms. The problem is, clonidine boosts opioid-induced euphoria.