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Substitution profile of the cannabinoid agonist nabilone in human subjects discriminating δ9-tetrahydrocannabinol.
Clin Neuropharmacol. 2010 Sep-Oct; 33(5):235-42.CN

Abstract

OBJECTIVES

The central effects of Δ-tetrahydrocannabinol (Δ-THC), the primary active constituent of cannabis, are attributed to cannabinoid CB1 receptor activity, although clinical evidence is limited. Drug discrimination has proven useful for examining the neuropharmacology of drugs, as data are concordant with the actions of a drug at the receptor level. The aim of this study was to determine the profile of behavioral and physiological effects of the cannabinoid agonist nabilone in humans trained to discriminate Δ-THC.

METHODS

Six cannabis users learned to identify when they received oral Δ-THC (25 mg) or placebo and then received a range of doses of the cannabinoid agonists nabilone (1, 2, 3, and 5 mg) and Δ-THC (5, 10, 15, and 25 mg). The dopamine reuptake inhibitor methylphenidate (5, 10, 20, and 30 mg) was included as a negative control. Subjects completed the Multiple-Choice Procedure, and self-report, task performance, and physiological measures were collected.

RESULTS

Nabilone shared discriminative-stimulus effects with the training dose of Δ-THC, produced subject-rated drug effects that were comparable to those of Δ-THC, and increased heart rate. Methylphenidate did not engender Δ-THC-like discriminative-stimulus effects.

CONCLUSIONS

These data demonstrate that the interoceptive effects of nabilone are similar to Δ-THC in cannabis users. The overlap in their behavioral effects is likely due to their shared mechanism as CB1 receptor agonists. Given the relative success of agonist replacement therapy to manage opioid, tobacco, and stimulant dependence, these results also support the evaluation of nabilone as a potential medication for cannabis-use disorders.

Authors+Show Affiliations

Department of Behavioral Science, College of Medicine, University of Kentucky, Lexington, KY 40536-0086, USA. jalile2@email.uky.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

20838217

Citation

Lile, Joshua A., et al. "Substitution Profile of the Cannabinoid Agonist Nabilone in Human Subjects Discriminating Δ9-tetrahydrocannabinol." Clinical Neuropharmacology, vol. 33, no. 5, 2010, pp. 235-42.
Lile JA, Kelly TH, Hays LR. Substitution profile of the cannabinoid agonist nabilone in human subjects discriminating δ9-tetrahydrocannabinol. Clin Neuropharmacol. 2010;33(5):235-42.
Lile, J. A., Kelly, T. H., & Hays, L. R. (2010). Substitution profile of the cannabinoid agonist nabilone in human subjects discriminating δ9-tetrahydrocannabinol. Clinical Neuropharmacology, 33(5), 235-42. https://doi.org/10.1097/WNF.0b013e3181e77428
Lile JA, Kelly TH, Hays LR. Substitution Profile of the Cannabinoid Agonist Nabilone in Human Subjects Discriminating Δ9-tetrahydrocannabinol. Clin Neuropharmacol. 2010 Sep-Oct;33(5):235-42. PubMed PMID: 20838217.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Substitution profile of the cannabinoid agonist nabilone in human subjects discriminating δ9-tetrahydrocannabinol. AU - Lile,Joshua A, AU - Kelly,Thomas H, AU - Hays,Lon R, PY - 2010/9/15/entrez PY - 2010/9/15/pubmed PY - 2011/1/7/medline SP - 235 EP - 42 JF - Clinical neuropharmacology JO - Clin Neuropharmacol VL - 33 IS - 5 N2 - OBJECTIVES: The central effects of Δ-tetrahydrocannabinol (Δ-THC), the primary active constituent of cannabis, are attributed to cannabinoid CB1 receptor activity, although clinical evidence is limited. Drug discrimination has proven useful for examining the neuropharmacology of drugs, as data are concordant with the actions of a drug at the receptor level. The aim of this study was to determine the profile of behavioral and physiological effects of the cannabinoid agonist nabilone in humans trained to discriminate Δ-THC. METHODS: Six cannabis users learned to identify when they received oral Δ-THC (25 mg) or placebo and then received a range of doses of the cannabinoid agonists nabilone (1, 2, 3, and 5 mg) and Δ-THC (5, 10, 15, and 25 mg). The dopamine reuptake inhibitor methylphenidate (5, 10, 20, and 30 mg) was included as a negative control. Subjects completed the Multiple-Choice Procedure, and self-report, task performance, and physiological measures were collected. RESULTS: Nabilone shared discriminative-stimulus effects with the training dose of Δ-THC, produced subject-rated drug effects that were comparable to those of Δ-THC, and increased heart rate. Methylphenidate did not engender Δ-THC-like discriminative-stimulus effects. CONCLUSIONS: These data demonstrate that the interoceptive effects of nabilone are similar to Δ-THC in cannabis users. The overlap in their behavioral effects is likely due to their shared mechanism as CB1 receptor agonists. Given the relative success of agonist replacement therapy to manage opioid, tobacco, and stimulant dependence, these results also support the evaluation of nabilone as a potential medication for cannabis-use disorders. SN - 1537-162X UR - https://www.unboundmedicine.com/medline/citation/20838217/Substitution_profile_of_the_cannabinoid_agonist_nabilone_in_human_subjects_discriminating_δ9_tetrahydrocannabinol_ L2 - https://doi.org/10.1097/WNF.0b013e3181e77428 DB - PRIME DP - Unbound Medicine ER -