Interactions between cannabidiol and Δ9-THC during abstinence in morphine-dependent rats

Hine, Bromfield; Torrelio, Marina; Gershon, Samuel

doi:10.1016/0024-3205(75)90435-x

Cited by 34 publications

(19 citation statements)

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“…Consistent with this notion, gene-targeting experiments have shown attenuated naloxone-precipitated opioid withdrawal in morphinedependent CB1 knock-out mice (Ledent et al, 1999) and attenuated SR141716A-precipitated cannabinoid withdrawal in THCdependent mice lacking preproenkephalin gene . Pretreatment with THC (Hine et al, 1975;Valverde et al, 2001) or anandamide (Vela et al, 1995), have been also shown to decrease morphine withdrawal. Our finding that the disruption of a single opioid receptor gene has no major consequences on the somatic expression of THC withdrawal may indicate that concomitant changes in the activity of several opioid receptors are implicated in the expression of THC withdrawal.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the opioid antagonist naloxone precipitated a withdrawal syndrome in THC-tolerant rats (Kaymakcalan et al, 1977), whereas the cannabinoid antagonist SR171416A was able to precipitate abstinence in morphine-dependent rats (Navarro et al, 1998). Besides, the severity of opioid withdrawal was reduced by the administration of THC (Hine et al, 1975;Valverde et al, 2001) or the endogenous cannabinoid agonist anandamide (Vela et al, 1995). This bidirectional cross-dependence has been recently confirmed by using knock-out mice, because opioid dependence was reduced in mice lacking the CB1 cannabinoid receptor (Ledent et al, 1999), whereas cannabinoid dependence was reduced in mice lacking the preproenkephalin gene .…”

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confidence: 98%

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Motivational Effects of Cannabinoids Are Mediated by μ-Opioid and κ-Opioid Receptors

et al. 2002

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Repeated THC administration produces motivational and somatic adaptive changes leading to dependence in rodents. To investigate the molecular basis for cannabinoid dependence and its possible relationship with the endogenous opioid system, we explored ⌬9-tetrahydrocannabinol (THC) activity in mice lacking -, ␦-or -opioid receptor genes. Acute THCinduced hypothermia, antinociception, and hypolocomotion remained unaffected in these mice, whereas THC tolerance and withdrawal were minimally modified in mutant animals. In contrast, profound phenotypic changes are observed in several place conditioning protocols that reveal both THC rewarding and aversive properties. Absence of receptors abolishes THC place preference. Deletion of receptors ablates THC place aversion and furthermore unmasks THC place preference. Thus, an opposing activity of -and -opioid receptors in modulating reward pathways forms the basis for the dual euphoric-dysphoric activity of THC.

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Section: Discussionmentioning

confidence: 99%

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confidence: 98%

Motivational Effects of Cannabinoids Are Mediated by μ-Opioid and κ-Opioid Receptors

et al. 2002

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“…For example, in 1975 Hine et al [88] published the first study showing that natural cannabinoid agonists attenuate morphine withdrawal symptoms in rats. Other authors demonstrated cross-sensitization of locomotor activity in mice treated with opioids and cannabinoids [89].…”

Section: Parallelism and Functional Interac-tions Between The Cannabimentioning

confidence: 98%

Functional Interactions between Endogenous Cannabinoid and Opioid Systems: Focus on Alcohol, Genetics and Drug-Addicted Behaviors

López-Moreno¹,

López-Jiménez²,

Gorriti³

et al. 2010

CDT

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Although the first studies regarding the endogenous opioid system and addiction were published during the 1940s, addiction and cannabinoids were not addressed until the 1970s. Currently, the number of opioid addiction studies indexed in PubMed-Medline is 16 times greater than the number of cannabinoid addiction reports. More recently, functional interactions have been demonstrated between the endogenous cannabinoid and opioid systems. For example, the cannabinoid brain receptor type 1 (CB1) and mu opioid receptor type 1 (MOR1) co-localize in the same presynaptic nerve terminals and signal through a common receptor-mediated G-protein pathway. Here, we review a great variety of behavioral models of drug addiction and alcohol-related behaviors. We also include data providing clear evidence that activation of the cannabinoid and opioid endogenous systems via WIN 55,512-2 (0.4-10 mg/kg) and morphine (1.0-10 mg/kg), respectively, produces similar levels of relapse to alcohol in operant alcohol self-administration tasks. Finally, we discuss genetic studies that reveal significant associations between polymorphisms in MOR1 and CB1 receptors and drug addiction. For example, the SNP A118G, which changes the amino acid aspartate to asparagine in the MOR1 gene, is highly associated with altered opioid system function. The presence of a microsatellite polymorphism of an (AAT)n triplet near the CB1 gene is associated with drug addiction phenotypes. But, studies exploring haplotypes with regard to both systems, however, are lacking.

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“…One line of evidence particularly relevant to opioid abuse is the consistent findings that 1) CBD reduces morphine withdrawal symptoms (e.g., wet shakes, diarrhea, abnormal posture, ptosis, chewing, or teeth chattering) [74][75][76][77], and 2) even in combination with THC, CBD is capable of reducing abstinence scores to a greater extent than THC alone [74,75].…”

Section: Cbd In Preclinical Addiction Modelsmentioning

confidence: 99%

Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage

et al. 2015

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Multiple cannabinoids derived from the marijuana plant have potential therapeutic benefits but most have not been well investigated, despite the widespread legalization of medical marijuana in the USA and other countries. Therapeutic indications will depend on determinations as to which of the multiple cannabinoids, and other biologically active chemicals that are present in the marijuana plant, can be developed to treat specific symptoms and/or diseases. Such insights are particularly critical for addiction disorders, where different phytocannabinoids appear to induce opposing actions that can confound the development of treatment interventions. Whereas Δ 9 -tetracannabinol has been well documented to be rewarding and to enhance sensitivity to other drugs, cannabidiol (CBD), in contrast, appears to have low reinforcing properties with limited abuse potential and to inhibit drug-seeking behavior. Other considerations such as CBD's anxiolytic properties and minimal adverse side effects also support its potential viability as a treatment option for a variety of symptoms associated with drug addiction. However, significant research is still needed as CBD investigations published to date primarily relate to its effects on opioid drugs, and CBD's efficacy at different phases of the abuse cycle for different classes of addictive substances remain largely understudied. Our paper provides an overview of preclinical animal and human clinical investigations, and presents preliminary clinical data that collectively sets a strong foundation in support of the further exploration of CBD as a therapeutic intervention against opioid relapse. As the legal landscape for medical marijuana unfolds, it is important to distinguish it from Bmedical CBD^and other specific cannabinoids, that can more appropriately be used to maximize the medicinal potential of the marijuana plant.

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Interactions between cannabidiol and Δ9-THC during abstinence in morphine-dependent rats

Cited by 34 publications

References 19 publications

Motivational Effects of Cannabinoids Are Mediated by μ-Opioid and κ-Opioid Receptors

Motivational Effects of Cannabinoids Are Mediated by μ-Opioid and κ-Opioid Receptors

Functional Interactions between Endogenous Cannabinoid and Opioid Systems: Focus on Alcohol, Genetics and Drug-Addicted Behaviors

Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage

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