Effects of the synthetic cannabinoid receptor agonist JWH-018 on abuse-related effects of opioids in rhesus monkeys

Gerak, Lisa R.; Weed, Peter F.; Maguire, David R.

doi:10.1016/j.drugalcdep.2019.04.024

Cited by 11 publications

(5 citation statements)

References 34 publications

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“…Prior reports have demonstrated interactions between cannabinoids and opioids on measures of reward in rodents(Iyer et al, 2022; Mohammadkhani and Borgland, 2022), nonhuman primates(Beardsley et al, 2004; Maguire et al, 2013; Gerak et al, 2019) and humans(Cooper et al, 2018). It is therefore important to consider reward-related measures of Δ 9 -THC and oxycodone in a dose range that is therapeutically relevant.…”

Section: Discussionmentioning

confidence: 99%

“…A recent meta-analysis reported 3.5-fold reduction in the morphine dose required to produce analgesia when combined with Δ 9 -THC in rodent studies (Nielsen et al, 2022). This facilitation of antinociception is also observed in nonhuman primates (Maguire et al, 2013;Maguire and France, 2014;Maguire and France, 2018;Gerak et al, 2019;Nilges et al, 2020). In humans, combined treatment with oral oxycodone and smoked cannabis resulted in enhanced antinociception in the cold pressor test relative to either drug in isolation .…”

Section: Introductionmentioning

confidence: 92%

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Impact of Δ⁹-Tetrahydrocannabinol and oxycodone co-administration on measures of antinociception, dependence, circadian activity, and reward in mice

Slivicki,

Wang,

Nhat

et al. 2023

Preprint

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Oxycodone is commonly prescribed for moderate to severe pain disorders. While efficacious, long-term use can result in tolerance, physical dependence, and the development of opioid use disorder. Cannabis and its derivatives such as Δ9-Tetrahydrocannabinol (Δ9-THC) have been reported to enhance oxycodone analgesia in animal models and in humans. However, it remains unclear if Δ9-THC may facilitate unwanted aspects of oxycodone intake, such as tolerance, dependence, and reward at analgesic doses. This study sought to evaluate the impact of co-administration of Δ9-THC and oxycodone across behavioral measures related to antinociception, dependence, circadian activity, and reward in both male and female mice. Oxycodone and Δ9-THC produced dose-dependent antinociceptive effects in the hotplate assay that were similar between sexes. Repeated treatment (twice daily for 5 days) resulted in antinociceptive tolerance. Combination treatment of oxycodone and Δ9-THC produced a greater antinociceptive effect than either administered alone, and delayed the development of antinociceptive tolerance. Repeated treatment with oxycodone produced physical dependence and alterations in circadian activity, neither of which were exacerbated by co-treatment with Δ9-THC. Combination treatment of oxycodone and Δ9-THC produced CPP when co-administered at doses that did not produce preference when administered alone. These data indicate that Δ9-THC may facilitate oxycodone-induced antinociception without augmenting certain unwanted features of opioid intake (e.g. dependence, circadian rhythm alterations). However, our findings also indicate that Δ9-THC may facilitate rewarding properties of oxycodone at therapeutically relevant doses which warrant consideration when evaluating this combination for its potential therapeutic utility.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Impact of Δ⁹-Tetrahydrocannabinol and oxycodone co-administration on measures of antinociception, dependence, circadian activity, and reward in mice

Slivicki,

Wang,

Nhat

et al. 2023

Preprint

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“…We recently presented evidence that THC enhances the effects of oxycodone in an anti-nociception assay in rats and it also enhances the effects of a unit dose of oxycodone or heroin when self-administered (Nguyen et al 2019 ). Maguire and France have shown that the nature of the anti-nociceptive interaction (supra-additive, sub-additive, additive) between cannabinoids and opioids may depend on the specific drugs that are involved (Gerak et al 2019 ; Maguire and France 2018 ; Maguire et al 2013 ) which cautions against making generalizations across either class of substances, before specific data are available. In the case of both nociception and drug self-administration, the effects of opioids and cannabinoids are often in the same direction, i.e., anti-nociceptive (Li et al 2008 ; Lichtman and Martin, 1990 ; Manning et al 2001 ; Peckham and Traynor 2006 ; Wakley and Craft 2011 ) and rewarding (Blakesley et al 1972 ; Justinova et al 2003 ; Killian et al 1978 ; Panlilio et al 2010 ; Vendruscolo et al 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of combined THC and heroin vapor inhalation in rats

et al. 2021

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Rationale Opioids are effective medications, but they have several key limitations including the development of tolerance, establishment of dependence, diversion for non-medical use, and the development of addiction. Therefore, any drugs which act in an additive or synergistic fashion with opioids to address medical applications have the potential to reduce opioid-related harms. Objectives To determine if heroin and Δ 9 -tetrahydrocannabinol (THC) interact in an additive or independent manner to alter nociception, body temperature, and spontaneous locomotor activity when inhaled or injected. Methods Groups of female and male rats, implanted with radiotelemetry transmitters, were exposed to vapor generated from heroin (50 mg/mL in propylene glycol vehicle; PG), THC (50 mg/mL), or the combination for assessment of effects on temperature and activity. Thermal nociception was assessed with a warm water tail-withdrawal assay. Results Heroin inhalation increased temperature and activity whereas THC inhalation decreased temperature and activity in both female and male Sprague–Dawley rats. Effects of combined inhalation were in opposition, and additional experiments found the same outcome for the injection of heroin (0.5 mg/kg, s.c.) and THC (10 mg/kg, i.p.) alone and in combination. In contrast, the co-administration of heroin and THC by either inhalation or injection produced additive effects on thermal nociception in both male and female Sprague–Dawley and Wistar rats. Conclusions This study shows that additive effects of THC with an opioid on a medical endpoint such as analgesia may not generalize to other behavioral or physiological effects, which may be a positive outcome for unwanted side effects.

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“…Although others have applied effect‐addition analysis to evaluate the effects of drug mixtures in reinstatement procedures (e.g., Gerak et al, 2019; Self et al, 1996), we have recently used dose‐addition analyses to define the nature of drug–drug interactions in drug‐primed reinstatement. In these studies, mixtures of MDPV + caffeine exhibited a supraadditive interaction, suggesting that mixtures of MDPV + caffeine were more effective at reinstating responding than either drug alone (Doyle et al, 2021).…”

Section: Figurementioning

confidence: 99%

Application of dose‐addition analyses to characterize the abuse‐related effects of drug mixtures

Doyle

Gannon

Mesmin

et al. 2022

J Exper Analysis Behavior

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Polysubstance use makes up a majority of drug use, yet relatively few studies investigate the abuse‐related effects of drug mixtures. Dose‐addition analyses provide a rigorous and quantitative method to determine the nature of the interaction (i.e., supraadditive, additive, or subadditive) between two or more drugs. As briefly reviewed here, studies in rhesus monkeys have applied dose‐addition analyses to group level data to characterize the nature of the interaction between the reinforcing effects of stimulants and opioids (e.g., mixtures of cocaine + heroin). Building upon these foundational studies, more recent work has applied dose‐addition analyses to better understand the nature of the interaction between caffeine and illicit stimulants such as MDPV and methamphetamine in rats. In addition to utilizing a variety of operant procedures, including drug discrimination, drug self‐administration, and drug‐primed reinstatement, these studies have incorporated potency and effectiveness ratios as a method for both statistical analysis and visualization of departures from additivity at both the group and individual subject level. As such, dose‐addition analyses represent a powerful and underutilized approach to quantify the nature of drug–drug interactions that can be applied to a variety of abuse‐related endpoints in order to better understand the behavioral pharmacology of polysubstance use.

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Effects of the synthetic cannabinoid receptor agonist JWH-018 on abuse-related effects of opioids in rhesus monkeys

Cited by 11 publications

References 34 publications

Impact of Δ⁹-Tetrahydrocannabinol and oxycodone co-administration on measures of antinociception, dependence, circadian activity, and reward in mice

Impact of Δ⁹-Tetrahydrocannabinol and oxycodone co-administration on measures of antinociception, dependence, circadian activity, and reward in mice

Effects of combined THC and heroin vapor inhalation in rats

Application of dose‐addition analyses to characterize the abuse‐related effects of drug mixtures

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Effects of the synthetic cannabinoid receptor agonist JWH-018 on abuse-related effects of opioids in rhesus monkeys

Cited by 11 publications

References 34 publications

Impact of Δ9-Tetrahydrocannabinol and oxycodone co-administration on measures of antinociception, dependence, circadian activity, and reward in mice

Impact of Δ9-Tetrahydrocannabinol and oxycodone co-administration on measures of antinociception, dependence, circadian activity, and reward in mice

Effects of combined THC and heroin vapor inhalation in rats

Application of dose‐addition analyses to characterize the abuse‐related effects of drug mixtures

Contact Info

Product

Resources

About

Impact of Δ⁹-Tetrahydrocannabinol and oxycodone co-administration on measures of antinociception, dependence, circadian activity, and reward in mice

Impact of Δ⁹-Tetrahydrocannabinol and oxycodone co-administration on measures of antinociception, dependence, circadian activity, and reward in mice