Synergistic interactions of endogenous opioids and cannabinoid systems

Welch, Sandra P.; Eads, Micah

doi:10.1016/s0006-8993(99)01908-3

Cited by 152 publications

(84 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This result strongly supports a role of dynorphin, or other opioid peptides generated by the Pdyn gene, in THC analgesia. It is concordant with findings that have implicated the activation of -opioid and, preferentially, -opioid receptors in the antinociceptive mechanism of THC (Welch, 1993;Reche et al, 1996;Pugh et al, 1997;Welch and Eads, 1999). However, previous pharmacological studies of opioid-cannabinoid interactions in nociception were ambiguous.…”

Section: Discussionsupporting

confidence: 86%

“…The elucidation of these mechanisms is crucial for a better understanding of the processes involved in the initiation of cannabinoid abuse. THC, but not the endogenous cannabinoid anandamide, stimulates the release of the endogenous agonist dynorphin, which may contribute to the antinociceptive effects of THC (Welch and Eads, 1999;Houser et al, 2000). To determine whether dynorphin is also involved in the regulation of motivational effects of THC and morphine, we investigated whether the genetic deletion of dynorphin influences several acute and chronic responses of these two drugs.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Absence of Δ-9-Tetrahydrocannabinol Dysphoric Effects in Dynorphin-Deficient Mice

et al. 2001

View full text Add to dashboard Cite

The involvement of dynorphin on ⌬-9-tetrahydrocannabinol (THC) and morphine responses has been investigated by using mice with a targeted inactivation of the prodynorphin (Pdyn) gene. Dynorphin-deficient mice show specific changes in the behavioral effects of THC, including a reduction of spinal THC analgesia and the absence of THC-induced conditioned place aversion. In contrast, acute and chronic opioid effects were normal. The lack of negative motivational effects of THC in the absence of dynorphin demonstrates that this endogenous opioid peptide mediates the dysphoric effects of marijuana.Key words: cannabinoid; opioid; mice; mutation; withdrawal; addiction; place aversion Pharmacological and genetic evidence suggest important functional interactions between the endogenous brain cannabinoid and opioid systems (Hine et al

show abstract

Section: Discussionsupporting

confidence: 86%

mentioning

confidence: 99%

Absence of Δ-9-Tetrahydrocannabinol Dysphoric Effects in Dynorphin-Deficient Mice

et al. 2001

View full text Add to dashboard Cite

show abstract

“…Cannabinoid receptor agonists are associated with impaired performance in spatial learning and recognition memory tasks (Ferrari et al, 1999;Kosiorek et al, 2003;Takahashi et al, 2005), while cannabinoid receptor antagonists improve performance in cognitive tests (Lichtman, 2000;Wise et al, 2008;de Bruin et al, 2010). Cannabinoid ligands have also demonstrated antinociceptive effects in acute, inflammatory and neuropathic pain models (Finn and Chapman, 2004;Manzanares et al, 2006), and have a synergistic analgesic effect when coadministered with opioids (Welch and Eads, 1999). However, there is a paucity of studies directly investigating potential involvement of the endocannabinoid system in pain-related cognitive impairment.…”

Section: Neurotransmitters and Receptors In Pain And Cognitionmentioning

confidence: 99%

The effect of pain on cognitive function: A review of clinical and preclinical research

Moriarty

McGuire

Finn

2011

Progress in Neurobiology

874

710

View full text Add to dashboard Cite

Cognitive impairment is commonly associated with the pain experience. This impairment represents a major obstacle to daily activities and rehabilitation, especially in the chronic pain population. Here we review clinical and preclinical studies that have investigated pain-related alterations in cognition. These include impaired attentional, executive and general cognitive functioning. We describe the anatomical, neurochemical and molecular substrates common to both cognitive processing and supraspinal pain processing, and present the evidence for their involvement in pain-related cognitive impairment. We also examine the added complexity of cognitive impairment caused by analgesic medications and how this can further impact on morbidity in chronic pain patients. The need for a better understanding of the mechanisms of both pain-induced and treatment-related cognitive impairment is highlighted. Further research in this area will aid our understanding of patient symptoms and their underlying pathophysiology, ultimately leading to increased provision of guided therapy.

show abstract

“…Cannabinoids, such as THC, can stimulate the release of the endogenous KOR agonist dynorphin (Welch and Eads, 1999;Houser et al, 2000), which may contribute to their initial aversive effects. These dysphoric effects induced by the first administration of cannabinoids in rodents seem to be crucial to mask their rewarding properties in behavioral models.…”

Section: Introductionmentioning

confidence: 99%

Involvement of κ/Dynorphin System in WIN 55,212-2 Self-Administration in Mice

Mendizábal

Zimmer

Maldonado

2005

Neuropsychopharmacol

View full text Add to dashboard Cite

Self-administration procedures have not yet provided evidence that freely moving mice can reliably acquire and maintain an operant behavior to self-administer cannabinoid agonists. The aim of the present work was to establish a model of cannabinoid operant intravenous self-administration in freely moving mice given the relevance of this species for the use of genetically modified animals. In addition, the possible involvement of the k/dynorphin system in cannabinoid self-administration was evaluated by using pro-dynorphin knockout mice. Outbred CD1 wild-type mice as well as pro-dynorphin knockout and wild-type mice were trained to self-administer the cannabinoid receptor agonist WIN 55,212-2 under an FR1 schedule of reinforcement. Two cannabinoid training doses (6.25 and 12.5 mg/ kg/infusion) were used in the acquisition studies in outbred mice. Animals acquired a reliable operant responding to self-administer WIN 55,212-2 (12.5 mg/kg/infusion), but required as many as 15 sessions to attain this behavior. Interestingly, when a previous injection of WIN 55,212-2 (0.1 mg/kg, i.p.) was administered in the home-cage 24 h before the first session, mice acquired operant responding for cannabinoid self-administration by the fourth session. When the k-opioid agonist antagonist nor-binaltorphimine (5 mg/kg s.c.) was administered 4 h before the first session, the time required to acquire a reliable cannabinoid self-administration was also significantly reduced. Finally, a shift to the left in the dose-intake curve to self-administer WIN 55,212-2 was observed in pro-dynorphin knockout mice when compared to wild-type mice. These results indicate that the activation of the k/dynorphin opioid system after WIN 55,212-2 administration could counteract cannabinoid rewarding effects.

show abstract

Synergistic interactions of endogenous opioids and cannabinoid systems

Cited by 152 publications

References 32 publications

Absence of Δ-9-Tetrahydrocannabinol Dysphoric Effects in Dynorphin-Deficient Mice

Absence of Δ-9-Tetrahydrocannabinol Dysphoric Effects in Dynorphin-Deficient Mice

The effect of pain on cognitive function: A review of clinical and preclinical research

Involvement of κ/Dynorphin System in WIN 55,212-2 Self-Administration in Mice

Contact Info

Product

Resources

About