PMID- 33769105 OWN - NLM STAT- MEDLINE DCOM- 20211229 LR - 20220531 IS - 1532-2750 (Electronic) IS - 1098-612X (Print) IS - 1098-612X (Linking) VI - 23 IP - 12 DP - 2021 Dec TI - Safety and tolerability of escalating cannabinoid doses in healthy cats. PG - 1162-1175 LID - 10.1177/1098612X211004215 [doi] AB - OBJECTIVES: The aim of this study was to determine the safety and tolerability of escalating doses of orally delivered cannabis oils predominant in cannabidiol (CBD), tetrahydrocannabinol (THC), or both CBD and THC in healthy cats. METHODS: In this placebo-controlled, blinded study, 20 healthy adult cats were randomized to one of five treatment groups (n = 4 per group): two placebo groups (sunflower oil [SF] or medium-chain triglyceride oil [MCT]), or three plant-derived cannabinoid oil groups (CBD in MCT, THC in MCT or CBD/THC [1.5:1] in SF). Up to 11 escalating doses of each formulation were delivered orally via syringe to fasted subjects, with at least 3 days separating doses. Safety and tolerability were determined from clinical observations, complete blood counts (CBCs) and clinical chemistry. Plasma cannabinoids (CBD, THC) and metabolites (7-COOH-CBD, 11-OH-THC) were assessed. RESULTS: Titration to maximum doses of 30.5 mg/kg CBD (CBD oil), 41.5 mg/kg THC (THC oil) or 13.0:8.4 mg/kg CBD:THC (CBD/THC oil) was safely achieved in all subjects. All observed adverse events (AEs) were mild, transient and resolved without medical intervention. Gastrointestinal AEs were more common with formulations containing MCT. Constitutional (lethargy, hypothermia), neurologic (ataxia) and ocular (protrusion membrana nictitans) AEs were more common with oils containing THC (CBD/THC and THC oils). There were no clinically significant changes in CBC or clinical chemistry across treatment groups. Higher plasma levels of the cannabinoids and their metabolites following administration of the CBD/THC combination product are suggestive of a pharmacokinetic interaction. CONCLUSIONS AND RELEVANCE: This is the first feline study to explore the safety and tolerability of CBD and THC, alone and in combination, in a controlled research setting. These findings will inform veterinarians of the safety profile of cannabinoids, particularly when considering the potential therapeutic use of CBD in cats or recognizing clinical signs associated with accidental exposure to THC-containing products. FAU - Kulpa, Justyna E AU - Kulpa JE AUID- ORCID: 0000-0001-9823-235X AD - Canopy Animal Health, Research & Development, Canopy Growth Corporation, Smith Falls, ON, Canada. AD - Human and Animal Research Program, Canopy Growth Corporation, Smith Falls, ON, Canada. FAU - Paulionis, Lina J AU - Paulionis LJ AD - Canopy Animal Health, Research & Development, Canopy Growth Corporation, Smith Falls, ON, Canada. FAU - Eglit, Graham Ml AU - Eglit GM AD - Human and Animal Research Program, Canopy Growth Corporation, Smith Falls, ON, Canada. FAU - Vaughn, Dana M AU - Vaughn DM AD - Canopy Animal Health, Research & Development, Canopy Growth Corporation, Smith Falls, ON, Canada. AD - Human and Animal Research Program, Canopy Growth Corporation, Smith Falls, ON, Canada. LA - eng PT - Journal Article PT - Randomized Controlled Trial, Veterinary PT - Research Support, Non-U.S. Gov't DEP - 20210326 PL - England TA - J Feline Med Surg JT - Journal of feline medicine and surgery JID - 100897329 RN - 0 (Analgesics) RN - 0 (Cannabinoids) RN - 19GBJ60SN5 (Cannabidiol) RN - 7J8897W37S (Dronabinol) SB - IM MH - Analgesics MH - Animals MH - Cannabidiol/*administration & dosage/adverse effects MH - Cannabinoids/*administration & dosage/adverse effects MH - Cats MH - Dronabinol/administration & dosage/adverse effects PMC - PMC8637357 OTO - NOTNLM OT - Cannabidiol OT - cannabinoid administration and dosage OT - cannabinoid adverse effects OT - safety OT - tetrahydrocannabinol COIS- Conflict of interest: JK, GE and DV are employed by Canopy Growth Corporation. LP was previously employed by Canopy Growth Corporation. Staff at VivoCore, and not the authors, were responsible for study conduct and data collection. EDAT- 2021/03/27 06:00 MHDA- 2021/12/30 06:00 PMCR- 2021/12/02 CRDT- 2021/03/26 12:22 PHST- 2021/03/27 06:00 [pubmed] PHST- 2021/12/30 06:00 [medline] PHST- 2021/03/26 12:22 [entrez] PHST- 2021/12/02 00:00 [pmc-release] AID - 10.1177_1098612X211004215 [pii] AID - 10.1177/1098612X211004215 [doi] PST - ppublish SO - J Feline Med Surg. 2021 Dec;23(12):1162-1175. doi: 10.1177/1098612X211004215. Epub 2021 Mar 26.