Abstract
Chronic pain is a persistent and debilitating health problem. Although the use of analgesics such as opioids is useful in mitigating pain, their prolonged use is associated with unwanted effects including abuse liability. This study assesses the antinociceptive effect of combining subtherapeutic doses of two opioids (morphine or tramadol) with the synthetic cannabinoid CP55940 (2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan -2-yl)phenol). It also evaluates the associated adverse effects of these drugs and combinations. Adult male rats were injected with intraplantar complete Freund’s adjuvant (CFA) to produce mechanical allodyia. Antinociceptive effect of morphine, tramadol, the synthetic cannabinoid CP55940, or their combinations was evaluated three to nine days post-CFA injections. Intracranial self-stimulation (ICSS) was utilized to evaluate the abuse liability of these drugs or their combinations. All drugs alone produced a dose-dependent antinociceptive effect. Morphine produced minimal effect on ICSS, but both tramadol and CP55940 produced dose-dependent depression of ICSS. Morphine at a dose of 0.32 mg/kg enhanced the antinociceptive effects of CP55940, in that, CP55940 produced antinociception at a lower dose (0.1 mg/kg) when compared to the vehicle. The aforementioned combinations did not change CP55940-induced depression of ICSS. On the other hand, tramadol failed to enhance the antinociceptive effect of CP55940. Our data suggest that combining CP55940 with morphine, but not tramadol, shows a better antinociceptive profile with no additional risk of abuse liability, which represents a potential pain management approach.
Highlights
Opioids such as morphine are potent and widely used analgesics
Morphine and tramadol produced a significant antinociceptive effect when compared to the vehicle at 1–3.2 mg/kg and 10 mg/kg, respectively (Figure 1B,C)
This study examined the antinociceptive effect and abuse potential of the cannabinoid receptor 1 (CB1) agonist CP55940 in combination with two commonly used opioids: morphine tramadol
Summary
Opioids such as morphine are potent and widely used analgesics. They are considered to be the drugs of choice for the treatment of moderate to severe pain [1]. The analgesic potential of other compounds such as cannabinoids is being investigated for the clinical treatment of miscellaneous forms of pain, where conventional analgesics (e.g., opioids, tramadol, non-steroid anti-inflammatory drugs) have lower efficacy. Brain Sci. 2019, 9, 328 forms of inflammatory, neuropathic, or chronic pain conditions [3,4,5] In this regard, while preclinical studies have shown that several cannabinoid agonists have antinociceptive effects against both acute and chronic pain, clinical studies indicate that cannabinoids are more effective in the management of chronic pain [5]
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