Dataset Information

Pharmacokinetics of cannabichromene in a medical cannabis product also containing cannabidiol and Δ⁹-tetrahydrocannabinol: a pilot study.

ABSTRACT:

Purpose

Cannabichromene (CBC) is a phytocannabinoid commonly found in cannabis, yet its acute post-dose pharmacokinetics (PK) have not been examined in humans. This is a secondary data analysis from a trial investigating Spectrum Yellow oil, an oral cannabis product used for medical purposes that contained 20 mg cannabidiol (CBD), 0.9 mg Δ⁹-tetrahydrocannabinol (THC), and 1.1 mg CBC, per 1 mL of oil.

Methods

Participants (N = 43) were randomized to one of 5 groups: 120 mg CBD, 5.4 mg THC, and 6.6 mg CBC daily; 240 mg CBD, 10.8 mg THC, and 13.2 mg CBC daily; 360 mg CBD, 16.2 mg THC, and 19.8 mg CBC daily; 480 mg CBD, 21.6 mg THC, and 26.4 mg CBC daily; or placebo. Study medication was administered every 12 h for 7 days. Plasma CBC concentrations were analyzed by a validated two-dimensional high-performance liquid chromatography-tandem mass spectrometry assay.

Results

After a single dose and after the final dose, the C_max of CBC increased by 1.3-1.8-fold for each twofold increase in dose; the t_max range was 1.6-4.3 h. Based on the ratio of administered CBD, THC, and CBC to the plasma concentration, the dose of CBD was 18 times higher than the dose of CBC, yet the AUC_0-t of CBD was only 6.6-9.8-fold higher than the AUC_0-t of CBC; the dose of THC was similar to the dose of CBC, yet THC was quantifiable in fewer plasma samples than was CBC.

Conclusions

CBC may have preferential absorption over CBD and THC when administered together.

Trial registration

Australian New Zealand Clinical Trials Registry #ACTRN12619001450101, registered 18 October 2019.

SUBMITTER: Peters EN

PROVIDER: S-EPMC8748343 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:CD8+ T cells can contribute to neuroinflammation by secretion of inflammatory cytokines like interferon γ (IFNγ) and tumor necrosis factor α (TNFα). Astrocytes, a glial cell in the brain, can be stimulated by IFNγ and TNFα to secrete the inflammatory cytokines, monocyte chemotactic protein 1 (MCP-1), interleukin 6 (IL-6), and interferon-γ inducible protein 10 (IP-10). Δ9-Tetrahydrocannabinol (THC), the primary psychoactive cannabinoid in Cannabis sativa, possesses potent anti-inflammatory activity. The objective of this investigation was to assess the effects of THC treatment on CD8+ T cell-mediated activation of astrocytes. CD3/CD28/IFNα- stimulated CD8+ T cells were treated with vehicle (0.03% EtOH) or THC and cocultured with U251 astrocytes. IP-10+, MCP-1+, and IL-6+ astrocytes were quantified by flow cytometry. LegendPlex™ was used to measure cytokine secretion by CD8+ T cells and flow cytometry was employed to quantify IFNγ, TNFα, and lysosomal-associated membrane protein 1 (LAMP-1) expression. Recombinant TNFα and IFNγ were used to stimulate MCP-1, IP-10, IL-6 responses in U251 astrocytes, which were measured by flow cytometry. Treatment with THC reduced CD8+ T cell-mediated induction of IP-10 and IL-6 responses in U251 astrocytes but had no effect on MCP-1. THC treatment differentially affected T cell effector functions such that IFNγ and degranulation responses were sensitive to THC-mediated ablation while TNFα was not. Lastly, THC treatment reduced the IFNγ-induced IP-10 response but had no effect on TNFα-induced MCP-1 response in U251 astrocytes. The results suggest that cannabinoid treatment can selectively reduce certain CD8+ T cell responses that contribute to stimulation of astrocytes. Graphical Abstract Treatment with THC can abate CD8+ T cell-dependent neuroinflammatory processes by inhibiting CD8+ cell differentiation into effector cells, suppressing CD8+ effector cell function, and reducing activation of astrocytes by CD8+ T cell-derived inflammatory cytokines.

Dataset Information

Pharmacokinetics of cannabichromene in a medical cannabis product also containing cannabidiol and Δ⁹-tetrahydrocannabinol: a pilot study.

Purpose

Methods

Results

Conclusions

Trial registration

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Pharmacokinetics of cannabichromene in a medical cannabis product also containing cannabidiol and Δ9-tetrahydrocannabinol: a pilot study.

Purpose

Methods

Results

Conclusions

Trial registration

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Pharmacokinetics of cannabichromene in a medical cannabis product also containing cannabidiol and Δ⁹-tetrahydrocannabinol: a pilot study.