Modulation of opioids via protection of anandamide degradation by fatty acid amide hydrolase.

Lack of involvement of the opioid system with the endocannabinoid, arachidonylethanolamide (anandamide) was possibly due to hydrolysis by fatty acid amide hydrolase (FAAH). Cyclohexylcarbamic acid 3'-carbamoyl-biphenyl-3-yl ester (URB597) is an inhibitor of FAAH, increases brain anandamide levels and enhances anandamide-induced antinociception in male ICR mice (25-30 g). The combination of URB597 (10 mg/kg, i.

Decreased basal endogenous opioid levels in diabetic rodents: effects on morphine and delta-9-tetrahydrocannabinoid-induced antinociception.

We have previously demonstrated synergy between morphine and Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in the expression of antinociception in acute pain models and in arthritic models of chronic pain. Our data has been extended to include acute pain in both diabetic mice and rats. In diabetic mice, Delta(9)-THC p.

The role of gonadal hormones on opioid receptor protein density in arthritic rats.

The purpose of this study was to evaluate the effects of the gonadal hormones on the opioid receptor protein levels of Freund's adjuvant-treated (arthritic) male and female Lewis rats. Following a paw pressure nociception assay, the midbrain and spinal cord tissues were collected for comparison of mu, delta, and kappa opioid receptor protein levels. The effects of Freund's adjuvant-induced hyperalgesia resulted in significantly decreased nociception thresholds in both males and females, compared to vehicle treated animals in the paw pressure test.

Chronic morphine treatment decreases the Cav1.3 subunit of the L-type calcium channel.

Voltage-gated L- and N-type calcium channels (VOCs) are implicated in the activity of morphine, but their contribution to the expression of opioid tolerance remains uncertain. L- and N-type VOCs are heteropentamers of alpha(1), alpha(2)delta, beta, and gamma subunits. The alpha(1) subunit forms both the ion pore and the binding site for ligands.

The antinociceptive effect of Delta9-tetrahydrocannabinol in the arthritic rat involves the CB(2) cannabinoid receptor.

Cannabinoid CB(2) receptors have been implicated in antinociception in animal models of both acute and chronic pain. We evaluated the role both cannabinoid CB(1) and CB(2) receptors in mechanonociception in non-arthritic and arthritic rats. The antinociceptive effect of Delta(9)-tetrahydrocannabinol (Delta(9)THC) was determined in rats following administration of the cannabinoid CB(1) receptor-selective antagonist, SR141716A, the cannabinoid CB(2) receptor-selective antagonist, SR144528, or vehicle.

Synergy between delta9-tetrahydrocannabinol and morphine in the arthritic rat.

We have shown in past isobolographic studies that a small amount of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) can enhance morphine antinociception in mice. However, previous studies of the Delta(9)-THC/morphine interaction were performed using normal mice or rats and evaluated acute thermal antinociception. Less is known about cannabinoid and opioid interactions involved in mechanical nociception and in chronic inflammatory pain models, such as Freund's complete adjuvant-induced arthritic model.

Non-cannabinoid CB1, non-cannabinoid CB2 antinociceptive effects of several novel compounds in the PPQ stretch test in mice.

The analgesic and anti-hyperalgesic effects of cannabinoid- and vanilloid-like compounds, plus the fatty acid amide hydrolase (FAAH) inhibitor Cyclohexylcarbamic acid 3'-carbamoyl-biphenyl-3-yl ester (URB597), and acetaminophen, were evaluated in the phenyl-p-quinone (PPQ) pain model, using different routes of administration in combination with opioid and cannabinoid receptor antagonists. All the compounds tested produced analgesic effects. Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide ((R)-methanandamide) were active by three routes of administration: i.

Time course of the enhancement and restoration of the analgesic efficacy of codeine and morphine by delta9-tetrahydrocannabinol.

Delta9-tetrahydrocannabinol (delta9-THC) synergizes with morphine and codeine by releasing endogenous opioids. These studies determined 1) the duration of enhancement of morphine and codeine by delta9-THC, 2) the effect of (delta9-THC on the time course of fully efficacious doses of the opioids, 3) restoration of efficacy of morphine and codeine by delta9-THC, and 4) duration of restoration. Sub-active combination doses of delta9-THC/morphine or delta9-THC/codeine are equivalent in duration of action and efficacy to high-dose opioids alone.