Buprenorphine Injections Effective on Opioid-Associated Euphoria and Withdrawal
Buprenorphine is an effective therapy for opioid use disorder and has a more favorable safety profile than methadone.
Once-weekly subcutaneous buprenorphine injections block the euphoric effects of opioids and suppress opioid withdrawal in patients with opioid use disorder (OUD) who are not seeking treatment for the disorder, according to a study published in JAMA Psychiatry.1
Buprenorphine is an effective therapy for OUD and has a more favorable safety profile than methadone.2 The primary benefits of buprenorphine in OUD include reducing opioid craving and opioid withdrawal and blocking the euphoric effects of opioids.3 However, the current formulation of buprenorphine, a daily sublingual tablet, carries the potential for abuse via injection or snorting, and overdose of oral buprenorphine has led to fatalities.4
CAM2038 is a subcutaneous buprenorphine formulation designed to curb the abuse potential of buprenorphine by requiring once-weekly injections and providing sustained release of the drug. Here, in a phase 2 study, researchers sought to evaluate the safety and efficacy of CAM2038 for blocking opioid-induced euphoria and suppressing opioid withdrawal in patients with OUD who were not seeking treatment.
During the qualification phase, hydromorphone was administered at doses of 0, 6, and 18 mg, and drug liking was measured with the visual analog scale (VAS). Peak VAS scores during the qualification phase were approximately 50, 80, and 90 mm for 0, 6, and 18 mg hydromorphone. The scores obtained during the qualification phase were used as comparators for drug liking scores during administration of CAM2038.
A total of 47 participants (mean age, 35.5 years; 76% men; 50% black) were selected during the qualification phase and were randomly assigned to receive 24 or 32 mg CAM2038, administered once weekly, for a total of 2 doses. After the initial dose of CAM2038, 4 sessions of hydromorphone challenges, during which 0, 6, and 18 mg hydromorphone was administered over the course of 3 days, were conducted over the course of 13 days.
Drug liking scores during the treatment phase for the 18- and 6-mg hydromorphone challenges were reduced 6- to 20-fold and 20- to 50-fold, respectively, in patients receiving 24 and 32 mg CAM2038 compared with scores obtained during the qualification phase. These effects were sustained through day 13.
Participants had to exhibit mild opioid withdrawal to be included in the study. Before CAM2038 administration, participants had a mean Clinical Opiate Withdrawal Scale score of 9.4. Both doses of CAM2038 nearly completely suppressed opioid withdrawal, with COWS scores ≤1 for the study duration.
The most common adverse events were constipation and injection-site pain. CAM2038 did not have adverse effects on oxygen saturation, respiratory rate, heart rate, or systolic blood pressure.
Summary and Clinical Applicability
Oral sublingual buprenorphine is an effective treatment for opioid dependency, but the potential for abuse and overdose limits its use. CAM2038, a once-weekly subcutaneous formulation of buprenorphine, produced rapid and sustained blockade of opioid-induced euphoria and suppression of opioid withdrawal in patients with OUD not seeking treatment.
"We've learned this therapy effectively blocks the effects of another opioid and produces sustained withdrawal suppression — two mechanisms by which a pharmacotherapy can lead to reduced illicit drug use," Dr Walsh said in a press release. "We can help more patients improve their health and psychosocial functioning if we reduce illicit drug use and drug injection behaviors. This study will be part of the submission for CAM2038 to be reviewed for approval by the Food and Drug Administration in the coming months. Sustained release formulations have the prospect of changing the treatment landscape, reaching more patients and reducing the risk of misuse and diversion of daily products."5
Limitations and Disclosures
This study did not include a control group that received placebo, which the researchers considered to be unsafe, given the high doses of opioids administered during the hydromorphone challenges.
This study was partially funded by Braeburn Pharmaceuticals.
- Walsh SL, Comer SD, Lofwall MR, et al. Effect of buprenorphine weekly depot (CAM2038) and hydromorphone blockade in individuals with opioid use disorder: a randomized clinical trial [published online June 22, 2017]. JAMA Psychiatry. doi: 10.1001/jamapsychiatry.2017.1874
- Walsh SL, Preston KL, Bigelow GE, Stitzer ML. Acute administration of buprenorphine in humans: partial agonist and blockade effects. J Pharmacol Exp Ther. 1995;274(1):361-372.
- Comer SD, Walker EA, Collins ED. Buprenorphine/naloxone reduces the reinforcing and subjective effects of heroin in heroin-dependent volunteers. Psychopharmacology (Berl). 2005;181(4):664-675. doi: 10.1007/s00213-005-0023-6
- Comer SD, Sullivan MA, Vosburg SK, et al. Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine-maintained intravenous heroin abusers. Addiction. 2010;105(4):709-718. doi: 10.1111/j.1360-0443.2009.02843.x
- University of Kentucky News. Injectable therapy blocks opioid euphoria, withdrawal symptoms in UK-led trial. https://uknow.uky.edu/research/injectable-therapy-blocks-opioid-euphoria-withdrawal-symptoms-uk-led-trial. Published June 23, 2017. Accessed July 11, 2017.