The impact of gonadal hormones on cannabinoid dependence

Julie A Marusich; Rebecca M Craft; Timothy W Lefever; Jenny L Wiley

doi:10.1037/pha0000027

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The impact of gonadal hormones on cannabinoid dependence

Accepted manuscript

Open access

Peer reviewed

The impact of gonadal hormones on cannabinoid dependence

Julie A Marusich, Rebecca M Craft, Timothy W Lefever and Jenny L Wiley

Experimental and clinical psychopharmacology, Vol.23(4), pp.206-216

08/2015

DOI: https://doi.org/10.1037/pha0000027

Handle:

https://hdl.handle.net/2376/110268

PMCID: PMC4696547

PMID: 26237318

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Abstract

Marijuana Abuse - drug therapy

Substance Withdrawal Syndrome - etiology

Drug Tolerance

Body Weight - drug effects

Motor Activity - drug effects

Rats

Substance Withdrawal Syndrome - drug therapy

Pain Measurement - drug effects

Marijuana Abuse - complications

Sex Characteristics

Rats, Sprague-Dawley

Estrous Cycle - drug effects

Animals

Castration

Gonadal Hormones - therapeutic use

Time Factors

Reflex, Startle - drug effects

Hormone Replacement Therapy - methods

Dronabinol - toxicity

Disease Models, Animal

Cannabis is the most widely used illicit substance in the United States. Women report greater positive subjective effects of cannabis, and greater cannabis withdrawal compared to men. Female rodents are more sensitive than males to some acute effects of Δ⁹-tetrahydrocannabinol (THC), and females also develop greater tolerance to THC in some assays. The purpose of this study was to determine whether gonadal hormones modulate THC dependence in rats. Adult rats were gonadectomized (GDX) or sham-GDX, and hormone was replaced in half of the GDX rats of each sex (testosterone in males; estradiol and/or progesterone in females). THC (30 mg/kg) or vehicle was administered twice daily for 6.5 days, followed on the seventh day by vehicle or rimonabant challenge and assessment for withdrawal-related behaviors. Sham-GDX females developed greater tolerance than males to THC-induced hypothermia, and GDX females given progesterone showed greater tolerance to THC-induced locomotor suppression. Rimonabant precipitated withdrawal, as evidenced by increased somatic signs (forepaw tremors, licking) and increased startle amplitude. Testosterone in GDX males decreased withdrawal-induced licking. Estradiol and progesterone in GDX females increased withdrawal-induced chewing, and progesterone increased withdrawal-induced sniffing. These results suggest that estradiol and progesterone may promote the development of dependence, whereas testosterone may protect against dependence. While the present study indicates that testosterone and estradiol produce opposite effects on THC-induced behavior, estradiol appears to play a broader role than testosterone in modulating THC's behavioral effects.

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Title: The impact of gonadal hormones on cannabinoid dependence
Creators: Julie A Marusich - Center for Drug Discovery, RTI International
Rebecca M Craft - Department of Psychology, Washington State University
Timothy W Lefever - Center for Drug Discovery, RTI International
Jenny L Wiley - Center for Drug Discovery, RTI International
Publication Details: Experimental and clinical psychopharmacology, Vol.23(4), pp.206-216
Academic Unit: Psychology, Department of
Publisher: Amer Psychological Assoc; United States
Number of pages: 11
Grant note: R01 DA016644 / NIDA NIH HHS DA-016644 / NIDA NIH HHS
Identifiers: 99900547286101842
Language: English
Resource Type: Accepted manuscript