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Preclinical studies on the reinforcing effects of cannabinoids. A tribute to the scientific research of Dr. Steve Goldberg

Abstract

Rationale

The reinforcing effects of most abused drugs have been consistently demonstrated and studied in animal models, although those of marijuana were not, until the demonstration 15 years ago that delta-9-tetrahydrocannabinol (THC) could serve as a reinforcer in self-administration (SA) procedures in squirrel monkeys. Until then, those effects were inferred using indirect assessments.

Objectives

The aim of this manuscript is to review the primary preclinical procedures used to indirectly and directly infer reinforcing effects of cannabinoid drugs.

Methods

Results will be reviewed from studies of cannabinoid discrimination, intracranial self-stimulation (ICSS), conditioned place preference (CPP), as well as change in levels of dopamine assessed in brain areas related to reinforcement, and finally from self-administration procedures. For each procedure, an evaluation will be made of the predictive validity in detecting the potential abuse liability of cannabinoids based on seminal papers, with the addition of selected reports from more recent years especially those from Dr. Goldberg’s research group.

Results and conclusions

ICSS and CPP do not provide consistent results for the assessment of potential for abuse of cannabinoids. However, drug discrimination and neurochemistry procedures appear to detect potential for abuse of cannabinoids, as well as several novel “designer cannabinoid drugs.” Though after 15 years transfer of the self-administration model of marijuana abuse from squirrel monkeys to other species remains somewhat problematic, studies with the former species have substantially advanced the field, and several reports have been published with consistent self-administration of cannabinoid agonists in rodents.

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Acknowledgments

This work was funded by the Medication Development Program, NIDA-IRP, NIH/DHHS.

I would like to thank Claudio Zanettini and Mark Coggiano for discussion of previous version of this review and Jonathan Katz for his extensive reading of the current version of this manuscript and his comments and suggestions.

Finally, I can never be thankful enough for crossing the scientific path of Dr. Steve Goldberg. There are not enough words I know (even in Italian) to express my gratitude for the many things I learned from Steve. We were a great team for about 16 years, even though I was a guest researcher in Steve’s Preclinical Pharmacology Section for only two of those years. Perhaps to make my feelings about our collaboration more understandable, Steve’s lab was for me like the Eagles’ Hotel California, “you can check out any time you like, but you can never leave.”

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Correspondence to Gianluigi Tanda.

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This study was supported by the Intramural Research Program, National Institute on Drug Abuse, NIH/DHHS.

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Tanda, G. Preclinical studies on the reinforcing effects of cannabinoids. A tribute to the scientific research of Dr. Steve Goldberg. Psychopharmacology 233, 1845–1866 (2016). https://doi.org/10.1007/s00213-016-4244-7

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Keywords

  • Cannabis
  • Delta-9-THC
  • Dopamine neurochemistry
  • Marijuana substance use disorders
  • Addiction
  • Self-administration
  • Drug discrimination
  • Place conditioning
  • Spice