Vapor inhalation of cannabidiol (CBD) in rats - PubMed (original) (raw)

Vapor inhalation of cannabidiol (CBD) in rats

Mehrak Javadi-Paydar et al. Pharmacol Biochem Behav. 2019 Sep.

Abstract

Rationale: Cannabidiol (CBD), a compound found in many strains of the Cannabis genus, is increasingly available in e-cigarette liquids as well as other products. CBD use has been promoted for numerous purported benefits which have not been rigorously assessed in preclinical studies.

Objective: To further validate an inhalation model to assess CBD effects in the rat. The primary goal was to determine plasma CBD levels after vapor inhalation and compare that with the levels observed after injection. Secondary goals were to determine if hypothermia is produced in male Sprague-Dawley rats and if CBD affects nociception measured by the warm water tail-withdrawal assay.

Methods: Blood samples were collected from rats exposed for 30 min to vapor generated by an e-cigarette device using CBD (100, 400 mg/mL in the propylene glycol vehicle). Separate experiments assessed the body temperature response to CBD in combination with nicotine (30 mg/mL) and the anti-nociceptive response to CBD.

Results: Vapor inhalation of CBD produced concentration-related plasma CBD levels in male and female Wistar rats that were within the range of levels produced by 10 or 30 mg/kg, CBD, i.p. Dose-related hypothermia was produced by CBD in male Sprague-Dawley rats, and nicotine (30 mg/mL) inhalation enhanced this effect. CBD inhalation had no effect on anti-nociception alone or in combination with Δ9-tetrahydrocannabinol inhalation.

Conclusions: The vapor-inhalation approach is a suitable pre-clinical model for the investigation of the effects of inhaled CBD. This route of administration produces hypothermia in rats, while i.p. injection does not, at comparable plasma CBD levels.

Keywords: 5-HT1a; E-cigarette; Hemp; Hypothermia; Nociception.

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Figures

Figure 1:

Timeline depicting the course of experiments conducted in each cohort of rats.

Figure 2:

A, B) Mean plasma concentration of CBD following vapor inhalation for 30 minutes in groups of A) female (N=8), and B) male (N=8), Wistar rats. A significant difference between concentrations, within each sex, is indicated with *, and a significant difference between timepoints after vapor initiation is indicated with #. C, D) Mean plasma concentration of CBD following i.p. injection in the same groups. Collapsed across sex, a significant difference between doses is indicated with &, and a significant difference between timepoints after vapor initiation with $.

Figure 3:

Mean (N=8; SEM) body temperature and activity following inhalation of the PG vehicle, cannabidiol (CBD; 100, 400 mg/mL) for 30 minutes by male Wistar rats. Shaded symbols indicate a significant difference from the Baseline (Base), within treatment condition and open symbols represent a significant difference from the baseline and the respective time-point after PG inhalation. A significant difference between CBD (100 mg/mL) and CBD (400 mg/mL) indicated by *, a significant difference from PG2 with # and a difference from PG1 with $.

Figure 4:

Mean (N=8; SEM) A, B) body temperature and C, D) activity following inhalation of cannabidiol CBD (100 mg/mL) or THC (100 mg/mL), by male Wistar rats, with pre-inhalation injection with WAY 100,635 (0.1, 1.0 mg/mg, i.p.). Shaded symbols indicate a significant difference from the Baseline (Base), within treatment condition A significant difference between CBD and THC with saline pretreatment is indicated by *, with 0.1 mg/kg WAY pretreatment by # and with 1.0 mg/kg WAY pretreatment by &.

Figure 5:

Mean (N=8; SEM) A, B) body temperature and C, D) activity rates following injection of 8-OH-DPAT (0.1 mg/kg, i.p.) 15 minutes after pre-treatment with A, C) WAY-100,635 (0.0, 0.1, 1.0 mg/mg, i.p.) or B,D) SB-269970 (0.0, 0.1, 1.0 mg/mg, i.p.) in male Wistar rats. Open symbols indicate a significant difference from the Baseline (Base) within treatment condition and from each of the other pre-treatments at the respective time post-injection. A significant difference between Saline and 0.1 mg/kg WAY pretreatment is indicated with *.

Figure 6:

Mean (N=7; SEM) A, B) body temperature and C, D) activity following inhalation of the PG vehicle, cannabidiol (CBD), Nicotine (NIC; 30 mg/mL) or the CBD/NIC combination for 30 minutes by male Sprague-Dawley rats. The panels present the experiments with the A, C) CBD (100 mg/mL) and B, D) CBD (400 mg/mL) concentrations. Shaded symbols indicate a significant difference from the Baseline (Base), within treatment condition and open symbols represent a significant difference from the baseline and the respective time-point after PG inhalation. A significant difference from all other treatment conditions at a given time-point is indicated with *, a significant difference across CBD concentration is indicated with & and a significant difference between CBD alone and CBD+ Nicotine is indicated with #.

Figure 7:

Mean (N=7; SEM) A) body temperature and B) activity rate following inhalation of CBD 100 mg/mL for 30 minutes after i.p. injection of WAY 100635 (0.1, 1.0 mg/kg) or the Saline vehicle by male Sprague-Dawley rats. The arrow indicates the time of the pre-inhalation injection. Shaded symbols indicate a significant difference from the Pre-inhalation time-point, within treatment condition. Significant difference between all conditions is indicated with &, between the WAY 1.0 and the Saline pre-injection with *.

Figure 8:

Mean (±SEM) tail withdrawal latency before (Pre) and after (Post) vapor inhalation for 30 minutes by male Wistar rats. Conditions included CBD (50, 400 mg/mL), THC (25, 50, 100 mg/mL) and the CBD (200 mg/mL)/THC (50 mg/mL) combination. A significant difference between Pre-vapor and Post-vapor is indicated with *, and a significant difference between inhalation conditions after vapor inhalation is indicated with #.

References

1. Arkell TR, Lintzeris N, Kevin RC, Ramaekers JG, Vandrey R, Irwin C, Haber PS, McGregor IS, 2019. Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition. Psychopharmacology (Berl) May 1. doi: 10.1007/s00213-019-05246-8. -DOI -PMC -PubMed
1. Barata L, Arruza L, Rodriguez MJ, Aleo E, Vierge E, Criado E, Sobrino E, Vargas C, Ceprian M, Gutierrez-Rodriguez A, Hind W, Martinez-Orgado J, 2019. Neuroprotection by cannabidiol and hypothermia in a piglet model of newborn hypoxic-ischemic brain damage. Neuropharmacology 146, 1–11. -PubMed
1. Bloom AS, Johnson KM, Dewey WL, 1978. The effects of cannabinoids on body temperature and brain catecholamine synthesis. Res Commun Chem Pathol Pharmacol 20(1), 51–57. -PubMed
1. Boggs DL, Nguyen JD, Morgenson D, Taffe MA, Ranganathan M, 2018. Clinical and Preclinical Evidence for Functional Interactions of Cannabidiol and Delta(9)-Tetrahydrocannabinol. Neuropsychopharmacology 43(1), 142–154. -PMC -PubMed
1. Bourque A, 2018, How Hemp And The Farm Bill May Change Life As You Know It. Forbes https://www.forbes.com/sites/andrebourque/2018/12/17/how-hemp-and-the-fa...

Vapor inhalation of cannabidiol (CBD) in rats - PubMed (original) (raw)