Behavioral and temperature effects of delta 9-tetrahydrocannabinol in human-relevant doses in rats.
Michael S Smirnov, Eugene A. Kiyatkin
Brain Research September 4, 2008 DOI: 10.1016/j.brainres.2008.06.069 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Male rats |
| Interventions | delta-9-tetrahydrocannabinol (THC) cocaine |
| Dose | THC 0.5, 2.0 and 8.0 mg/kg, ip; cocaine 1 mg/kg, iv |
| Topics | Cannabis |
| Key findings | Only the largest THC dose (8.0 mg/kg) clearly produced hypothermia, hypoactivity, and reduced locomotor and temperature responses to all stimuli; lower doses had weaker effects resembling diazepam. The authors suggest brain metabolic inhibition may underlie these effects and question whether THC's hypothermic action is specific to cannabinoid receptors or partly non-specific. |
Abstract
Marijuana smoking dramatically alters responses to various environmental stimuli. To study this phenomenon, we assessed how delta-9-tetrahydrocannabinol (THC), a primary psychoactive ingredient of marijuana, affects locomotor and brain (nucleus accumbens or NAcc), muscle and skin temperature responses to natural arousing stimuli (one-minute tail-pinch and one-minute social interaction with another male rat) and iv cocaine (1 mg/kg) in male rats. THC was administered at three widely varying doses (0.5, 2.0 and 8.0 mg/kg, ip), and the drug-induced changes in basal values and responses to stimuli were compared to those occurring following ip vehicle injections (control). Each stimulus in control conditions caused acute locomotor activation, a prolonged increase in brain and muscle temperature (0.6-1.0 degrees C for 20-50 min) and transient decrease in skin temperature (-0.6 degrees C for 1-3 min). While THC at any dose had a tendency to decrease spontaneous locomotion as well as brain and muscle temperatures, true hypothermia and hypoactivity as well as clearly diminished locomotor and temperature responses to all stimuli were only seen following the largest dose. In this case, temperature decreases in the NAcc were stronger than in the muscle, suggesting metabolic brain inhibition as the primary cause of hypoactivity, hypothermia and hyporesponsiveness. While weaker in strength and without associated vasodilatation, this response pattern is mimicked by general anesthetics, questioning to what extent the hypothermic action of THC is specific (i.e., mediated via endogenous cannabinoid receptors) or non-specific, reflecting drug interaction with membrane lipids or other receptors. In contrast, weaker behavioral and temperature effects of THC at lower doses resemble those of diazepam, whose locomotion- and temperature-decreasing effects are evident only in activated conditions, when rats are moving and basal temperatures are elevated.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 5
- Chronic Δ9-tetrahydrocannabinol treatment has dose-dependent effects on open field exploratory behavior and [3H] SR141716A receptor binding in the rat brain. Life Sciences August 15, 2023
- Cannabis: Drug of Abuse and Therapeutic Agent, Two Sides of the Same Coin. Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion 2023
- Clinical and Preclinical Evidence for Functional Interactions of Cannabidiol and Δ9-Tetrahydrocannabinol. Neuropsychopharmacology January 2018
- Adverse Reactions Associated With Cannabis Consumption as Evident From Search Engine Queries. JMIR public health and surveillance October 26, 2017
- Δ⁹Tetrahydrocannabinol impairs visuo-spatial associative learning and spatial working memory in rhesus macaques. Journal of Psychopharmacology October 2012