Exposure to delta-9-tetrahydrocannabinol (THC) increases subsequent heroin taking but not heroin's reinforcing efficacy: a self-administration study in rats

Neuropsychopharmacology. 2004 Jul;29(7):1301-11. doi: 10.1038/sj.npp.1300431.


One concern about the widespread use of cannabis is that exposure to its active ingredient, delta-9-tetrahydrocannabinol (THC), might increase future reinforcing effects of other abused drugs such as heroin. In this study, we investigated the effects of pre-exposure to THC on subsequent intravenous self-administration of heroin by Sprague-Dawley rats. In one group of rats, we studied (1) acquisition of heroin self-administration behavior using a continuous-reinforcement (fixed-ratio (FR) 1) schedule, (2) heroin dose-response relationships using an FR1/variable-dose schedule, and (3) reinforcing efficacy of heroin using a progressive-ratio schedule. The number of rats pre-exposed to THC that subsequently learned to self-administer 50 microg/kg injections of heroin within 10 daily sessions did not differ from vehicle-pretreated controls. In contrast, rats pre-exposed to THC subsequently self-administered significantly more heroin injections per session and showed significantly shorter post-injection pauses over a range of heroin doses (12.5-100 microg/kg/injection) using the variable-dose schedule. Interestingly, the maximum effort rats would exert to receive an injection of the different doses of heroin under the progressive-ratio schedule was not altered by THC pre-exposure. In a second group of rats, we varied the 'price' of heroin (responses required/dose), by manipulating FR response requirements at different doses of heroin across sessions, to calculate demand and response output curves. Again, consumption was significantly higher in the THC-treated rats at the lowest prices of heroin (FR1/100 microg/kg and FR1/50 microg/kg) but there were no differences in the reinforcing efficacy of heroin between THC- and vehicle-pretreated rats. Altogether, these results demonstrate that pre-exposure to THC alters some pharmacological effects of heroin that determine frequency of heroin taking, but offer no support for the hypothesis that pre-exposure to THC alters heroin's efficacy as a reinforcer.

Publication types

  • Comparative Study

MeSH terms

  • Analgesics, Non-Narcotic / pharmacology*
  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Conditioning, Operant / drug effects
  • Dose-Response Relationship, Drug
  • Dronabinol / pharmacology*
  • Drug Administration Schedule
  • Drug Interactions
  • Heroin / administration & dosage*
  • Heroin Dependence
  • Narcotics / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley
  • Reinforcement Schedule
  • Reinforcement, Psychology*
  • Self Administration / methods


  • Analgesics, Non-Narcotic
  • Narcotics
  • Heroin
  • Dronabinol