Influence of Pregabalin Maintenance on Cannabis Effects and Related Behaviors in Daily Cannabis Users

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Abstract

No medications are approved for cannabis use disorder (CUD), though a small clinical trial demonstrated that the voltage-dependent calcium channel (VDCC) ligand gabapentin reduced cannabis use in treatment seekers. VDCCs are modulated by cannabinoid (CB) ligands, and there are shared effects between CB agonists and VDCC ligands. This overlapping neuropharmacology and the initial clinical results supported the evaluation of pregabalin, a “next-generation” VDCC ligand, as a CUD medication. Two separate placebo-controlled, double-blind, counterbalanced, within-subjects human laboratory studies tested placebo and 300 (N = 2 females, 11 males; Experiment [EXP] 1) or 450 (N = 3 females, 11 males; EXP 2) mg/day pregabalin in cannabis users who were not seeking treatment or trying to reduce/quit their cannabis use. The protocol consisted of two outpatient maintenance phases (11 days in EXP 1 and 15 days in EXP 2) that concluded with four experimental sessions within each phase. During experimental sessions, maintenance continued, and participants completed two 2-day blocks of sampling and self-administration sessions to determine the reinforcing effects of smoked cannabis (0% and 5.9%delta9-tetrahydrocannabinol [THC]), as well as subjective, attentional bias, performance, and physiological responses. In addition, naturalistic cannabis use, side effects, sleep quality, craving, and other self-reported substance use were measured during pregabalin maintenance. Cannabis was self-administered and produced prototypical effects, but pregabalin generally did not impact the effects of cannabis or alter naturalistic use. These human laboratory results in cannabis users not trying to reduce/quit their use do not support the efficacy of pregabalin as a stand-alone pharmacotherapy for CUD.

Original languageEnglish
Pages (from-to)560-574
Number of pages15
JournalExperimental and Clinical Psychopharmacology
Volume30
Issue number5
DOIs
StatePublished - May 13 2021

Bibliographical note

Funding Information:
This research and the preparation of this article were supported by grants awarded to Dr. Joshua A. Lile (National Institute on Drug Abuse Grant R01 DA036550) as well as the University of Kentucky Center for Clinical and Translational Science (National Center for Advancing Translational Sciences grant UL1TR001998). These funding sources had no other role than financial support.

Publisher Copyright:
© 2021 American Psychological Association

Keywords

  • Attentional bias
  • Marijuana
  • Reinforcement
  • Self-administration
  • Subjective

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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