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THC induced similar physiological effects on HIV transgenic rats and their controls without affecting HIV-induced deficits in effortful motivation.

Sunitha Vemuri, Samantha M. Ayoub, Arpi Minassian, Jared W Young

Journal of Cannabis Research January 2, 2026 DOI: 10.1186/s42238-025-00383-8 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Sample size 275
Population Adult female and male HIV-1 transgenic rats and wildtype littermate and Fischer344 control rats
Intervention delta-9-tetrahydrocannabinol (THC)
Dose 0, 0.3, 3 mg/kg
Duration 16 days of chronic THC treatment
Topics Cannabis
Keywords Apathy Exploration Hand Pain Phytocannabinoid
Key findings THC (3 mg/kg) reduced nociception, body temperature, locomotor and exploratory activity, and acute motivation across genotypes, with some sex-dependent effects, but chronic treatment did not affect motivation.

Abstract

Cannabinoids have proven to useful for attenuating adverse effects of HIV. People living with HIV use cannabis at higher rates, with evidence suggesting it alleviates physiological symptoms such as nausea, loss of appetite, etc.. Cannabis can alter physiology as well as essential behavioral functions such as motivation. This study investigated the effect of delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, on physiological responses and motivation in HIV-1 transgenic (tg) rats and their controls. In Experiment 1, adult female and male HIV-1tg (n = 46) rats and their controls (wildtype littermates [WT] and Fischer344 [F344] rats; n = 87) were tested for acute THC-induced (0, 0.3, 3 mg/kg) physiological effects using the cannabinoid tetrad assay: 1) nociception, 2) body temperature, and 3) locomotor and exploratory behavior. In Experiment 2, adult female and male HIV-1tg (n = 58) rats and controls (n = 84) were tested in the Progressive Ratio Breakpoint Task (PRBT) to assess effortful motivation at baseline, after acute THC, then chronic (16 days) THC treatment (0, 0.3, 3 mg/kg). Data collected was analyzed using separate univariate ANOVA test with group (HIV-1tg, WT, F344), drug (0, 0.3, 3 mg/kg THC) and sex (female and male) as fixed factors. Bonferroni adjustments were used to correct for multiple comparisons. THC (3 mg/kg) reduced nociception, temperature, and locomotor and exploratory activity across genotypes with some sex-dependent effects. Further, HIV-1tg and WT rats showed reduced motivation compared to F344 controls across PRBT testing timepoints. Acute 3 mg/kg THC reduced breakpoints but with no effects after chronic treatment. Hence, THC produces consistent physiological and motivational across HIV-1tg rats and their controls. Additionally, the HIV-1tg rat exhibited motivational deficits only when compared to the F344 but not WT controls, suggesting careful selections of control groups in future studies.

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Study Year Design Participants
Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors Mice 2015 Preclinical study
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Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Mice prenatally exposed to THC, including conditional CB1R knockout mice 2020 Animal experimental study
Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway Mice exposed to chronic THC early in life 2018 Animal experimental study
Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain Spontaneously hypertensive rats (SHRs) and Wistar rats 2014 Animal experimental study

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