ArticlePharmacological research2015
Repeated administration of phytocannabinoid Δ(9)-THC or synthetic cannabinoids JWH-018 and JWH-073 induces tolerance to hypothermia but not locomotor suppression in mice, and reduces CB1 receptor expression and function in a brain region-specific manner.
Article in Pharmacological research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 49 citations in OpenAlex.
- Don't Sweat It: Cannabinoid CB1 Receptors Reduce Sweating in a Mouse Model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- In vivo evaluation of synthetic cannabinoid JWH-018 derivatives as potential new psychoactive substances.Scientific reports · 2026Article
- The SigmaPharmacological reports : PR · 2026Article
- The role of the kynurenine pathway in conditioned place aversion induced by synthetic cannabinoid CP-55940.Behavioral and brain functions : BBF · 2026Article
- Endocannabinoid signaling in stress, nausea, and vomiting.Neurogastroenterology and motility · 2025Review
- Evidence for enduring cardiac and multiorgan toxicity after repeated exposure to the synthetic cannabinoid JWH-018 in male rats.Toxicology · 2024Article
- Timeframe Analysis of Novel Synthetic Cannabinoids Effects: A Study on Behavioral Response and Endogenous Cannabinoids Disruption.International journal of molecular sciences · 2024Article
- Effects of cannabinoid agonists and antagonists in male rats discriminating the synthetic cannabinoid AM2201.European journal of pharmacology · 2023Article
- Investigating the Effects of Exogenous and Endogenous 2-Arachidonoylglycerol on Retinal CB1 Cannabinoid Receptors and Reactive Microglia in Naive and Diseased Retina.International journal of molecular sciences · 2023Article
- Similar 5F-APINACA Metabolism between CD-1 Mouse and Human Liver Microsomes Involves Different P450 Cytochromes.Metabolites · 2022Article
- Cannabinoid tetrad effects of oral Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in male and female rats: sex, dose-effects and time course evaluations.Psychopharmacology · 2022Article
- Biomarkers of the Endocannabinoid System in Substance Use Disorders.Biomolecules · 2022Review
- A Model of Combined Exposure to Nicotine and TetrahydrocannabinolFrontiers in neuroscience · 2022Article
- Synthetic cannabinoid JWH-073 alters both acute behavior andFrontiers in psychiatry · 2022Article
- Glucocorticoids, Stress and Delta-9 Tetrahydrocannabinol (THC) during Early Embryonic Development.International journal of molecular sciences · 2021Review
- Quantitation of Synthetic Cannabinoid Receptor Agonists in Postmortem Blood Using a Single Point Calibration.Academic forensic pathology · 2021Article
- Metabolism, CB1 cannabinoid receptor binding and in vivo activity of synthetic cannabinoid 5F-AKB48: Implications for toxicity.Pharmacology, biochemistry, and behavior · 2020Article
- Role of the stress response and the endocannabinoid system in ΔPsychopharmacology · 2020Article
- Cannabinoid Hyperemesis Syndrome: A Review of Potential Mechanisms.Cannabis and cannabinoid research · 2020Review
- Nausea-Induced Conditioned Gaping Reactions in Rats Produced by High-Dose Synthetic Cannabinoid, JWH-018.Cannabis and cannabinoid research · 2020Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
These studies probed the relationship between intrinsic efficacy and tolerance/cross-tolerance between ∆(9)-THC and synthetic cannabinoid drugs of abuse (SCBs) by examining in vivo effects and cellular changes concomitant with their repeated administration in mice. Dose-effect relationships for hypothermic effects were determined in order to confirm that SCBs JWH-018 and JWH-073 are higher efficacy agonists than ∆(9)-THC in mice. Separate groups of mice were treated with saline, sub-maximal hypothermic doses of JWH-018 or JWH-073 (3.0mg/kg or 10.0mg/kg, respectively) or a maximally hypothermic dose of 30.0mg/kg ∆(9)-THC once per day for 5 consecutive days while core temperature and locomotor activity were monitored via biotelemetry. Repeated administration of all drugs resulted in tolerance to hypothermic effects, but not locomotor effects, and this tolerance was still evident 14 days after the last drug administration. Further studies treated mice with 30.0mg/kg ∆(9)-THC once per day for 4 days, then tested with SCBs on day 5. Mice with a ∆(9)-THC history were cross-tolerant to both SCBs, and this cross-tolerance also persisted 14 days after testing. Select brain regions from chronically treated mice were examined for changes in CB1 receptor expression and function. Expression and function of hypothalamic CB1Rs were reduced in mice receiving chronic drugs, but cortical CB1R expression and function were not altered. Collectively, these data demonstrate that repeated ∆(9)-THC, JWH-018 and JWH-073 can induce long-lasting tolerance to some in vivo effects, which is likely mediated by region-specific downregulation and desensitization of CB1Rs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.