The neurobiology of cannabinoid analgesia

Walker, J. Michael; Hohmann, Andrea G.; Martin, William J.; Strangman, Nicole; Huang, Susan M.; Tsou, Kang

doi:10.1016/s0024-3205(99)00289-1

Cited by 132 publications

(75 citation statements)

References 22 publications

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“…The CB 1 receptor mediates several pharmacological effects and is an active target for therapeutic drug development (Howlett et al, 2002;Le Foll and Goldberg, 2005). Cannabinoid receptor ligands may be useful for the treatment of pain (Walker et al, 1999), nausea (Simoneau et al, 2001), appetite control (Gelfand and Cannon, 2006;Kirkham and Tucci, 2006), and smoking cessation (Gelfand and Cannon, 2006).…”

Section: Introductionmentioning

confidence: 99%

The PET Radioligand [11C]MePPEP Binds Reversibly and with High Specific Signal to Cannabinoid CB1 Receptors in Nonhuman Primate Brain

Yasuno

Brown

Zoghbi

et al. 2007

Neuropsychopharmacol

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The cannabinoid CB 1 receptor is one of the most abundant G protein-coupled receptors in the brain and is a promising target of therapeutic drug development. Success of drug development for neuropsychiatric indications is significantly enhanced with the ability to directly measure spatial and temporal binding of compounds to receptors in central compartments. We assessed the utility of a new positron emission tomography (PET) radioligand to image CB 1 receptors in monkey brain. showed that the majority (489%) of brain uptake in regions with high receptor densities was specific and reversibly bound to CB 1 receptors in the high binding regions. [ 11 C]MePPEP was rapidly removed from arterial plasma. Regional brain uptake could be quantified as distribution volume relative to the concentration of parent radiotracer in plasma. The P-glycoprotein (P-gp) inhibitor DCPQ ((R)-4- [(1a,6,10b)-1,1-dichloro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c]cyclohepten-6-yl]-[(5-quinolinyloxy)methyl]-1-piperazineethanol) did not significantly increase brain uptake of [ 11 C]MePPEP, suggesting it is not a substrate for this efflux transporter at the blood-brain barrier.[ 11 C]MePPEP is a radioligand with high brain uptake, high specific signal to CB 1 receptors, and adequately fast washout from brain that allows quantification with 11 C (half-life ¼ 20 min). These promising results in monkey justify studying this radioligand in human subjects.

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Section: Introductionmentioning

confidence: 99%

The PET Radioligand [11C]MePPEP Binds Reversibly and with High Specific Signal to Cannabinoid CB1 Receptors in Nonhuman Primate Brain

Yasuno

Brown

Zoghbi

et al. 2007

Neuropsychopharmacol

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“…Cannabinoid CB 2 receptors are found primarily on immune cells (Hohmann, 2002;Mbvundula et al, 2004). Cannabinoids attenuate behavioral responses to noxious stimuli and attenuate hyperalgesia produced by inflammation and nerve injury in animals (for review see (Hohmann, 2002;Martin and Lichtman, 1998;Walker et al, 1999) and humans (Karst et al, 2003). In preliminary studies, THC produced analgesia equivalent to that of codeine in patients with cancer pain (Noyes et al, 1975).…”

Section: Introductionmentioning

confidence: 99%

Acute and chronic administration of the cannabinoid receptor agonist CP 55,940 attenuates tumor-evoked hyperalgesia

Hamamoto

Giridharagopalan

Simone

2007

European Journal of Pharmacology

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Patients with cancer frequently report pain that can be difficult to manage. This study examined the antihyperalgesic effects of a cannabinoid receptor agonist, CP 55,940, in a murine model of cancer pain. Implantation of fibrosarcoma cells into and around the calcaneous bone in mice produced mechanical hyperalgesia (decreased paw withdrawal thresholds and increased frequency of paw withdrawals). On day 13 after implantation, mechanical hyperalgesia, nociception, and catalepsy were assessed. Mice were randomly assigned to receive CP 55,940 (0.01-3 mg/kg, i.p.) or vehicle and behavioral measures were redetermined. CP 55,940 dose-dependently attenuated tumor-evoked mechanical hyperalgesia. To examine the effect of catalepsy on the antihyperalgesic effect of CP 55,940, mice with tumor-evoked hyperalgesia were pretreated with the dopamine agonist apomorphine prior to administration of CP 55,940. Apomorphine attenuated the cataleptic effect of CP 55,940 but did not attenuate its antihyperalgesic effect. In a separate group of mice with tumorevoked hyperalgesia, administration of the dopamine antagonist spiperone produced catalepsy that was ~2.5 fold greater than that produced by CP 55,490. Whereas this dose of CP 55,940 completely reversed tumor-evoked mechanical hyperalgesia, spiperone only attenuated mechanical hyperalgesia by ~35%. Thus, the cataleptic effects of CP 55,940 did not fully account for its antihyperalgesic effect. The antihyperalgesic effect of CP 55,940 was mediated via the cannabinoid CB 1 but not CB 2 receptor. Finally, repeated administration of CP 55,940 produced a short-term and a longer term attenuation of tumor-evoked hyperalgesia. These results suggest that cannabinoids may be a useful alternative or adjunct therapy for treating cancer pain.

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“…Cannabinoid drugs exert potent analgesic effects in animals by interacting with cannabinoid CB receptor-type 1 receptors located in various pain-processing areas of the Ž central nervous system see Walker et al, 1999 for a . review .…”

Section: Introductionmentioning

confidence: 99%

Antinociceptive activity of the endogenous fatty acid amide, palmitylethanolamide

Calignano

Rana

Piomelli

2001

European Journal of Pharmacology

230

190

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The neurobiology of cannabinoid analgesia

Cited by 132 publications

References 22 publications

The PET Radioligand [11C]MePPEP Binds Reversibly and with High Specific Signal to Cannabinoid CB1 Receptors in Nonhuman Primate Brain

The PET Radioligand [11C]MePPEP Binds Reversibly and with High Specific Signal to Cannabinoid CB1 Receptors in Nonhuman Primate Brain

Acute and chronic administration of the cannabinoid receptor agonist CP 55,940 attenuates tumor-evoked hyperalgesia

Antinociceptive activity of the endogenous fatty acid amide, palmitylethanolamide

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