Evaluation of the preclinical analgesic efficacy of naturally derived, orally administered oil forms of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and their 1:1 combination.
Administration, Oral
Analgesics
/ administration & dosage
Animals
Biomarkers
/ metabolism
CD4-Positive T-Lymphocytes
/ drug effects
Cannabidiol
/ adverse effects
Dronabinol
/ administration & dosage
Drug Compounding
Drug Interactions
Female
Ganglia, Spinal
/ drug effects
Gene Expression Regulation
/ drug effects
Male
Oils
/ chemistry
Rats
Rats, Sprague-Dawley
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
31
01
2020
accepted:
20
05
2020
entrez:
5
6
2020
pubmed:
5
6
2020
medline:
25
8
2020
Statut:
epublish
Résumé
Chronic neuropathic pain (NP) is a growing clinical problem for which effective treatments, aside from non-steroidal anti-inflammatory drugs and opioids, are lacking. Cannabinoids are emerging as potentially promising agents to manage neuroimmune effects associated with nociception. In particular, Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and their combination are being considered as therapeutic alternatives for treatment of NP. This study aimed to examine whether sex affects long-term outcomes on persistent mechanical hypersensitivity 7 weeks after ceasing cannabinoid administration. Clinically relevant low doses of THC, CBD, and a 1:1 combination of THC:CBD extracts, in medium chain triglyceride (MCT) oil, were orally gavaged for 14 consecutive days to age-matched groups of male and female sexually mature Sprague Dawley rats. Treatments commenced one day after surgically inducing a pro-nociceptive state using a peripheral sciatic nerve cuff. The analgesic efficacy of each phytocannabinoid was assessed relative to MCT oil using hind paw mechanical behavioural testing once a week for 9 weeks. In vivo intracellular electrophysiology was recorded at endpoint to characterize soma threshold changes in primary afferent sensory neurons within dorsal root ganglia (DRG) innervated by the affected sciatic nerve. The thymus, spleen, and DRG were collected post-sacrifice and analyzed for long-term effects on markers associated with T lymphocytes at the RNA level using qPCR. Administration of cannabinoids, particularly the 1:1 combination of THC, elicited a sustained mechanical anti-hypersensitive effect in males with persistent peripheral NP, which corresponded to beneficial changes in myelinated Aβ mechanoreceptive fibers. Specific immune cell markers associated with T cell differentiation and pro-inflammatory cytokines, previously implicated in repair processes, were differentially up-regulated by cannabinoids in males treated with cannabinoids, but not in females, warranting further investigation into sexual dimorphisms that may underlie treatment outcomes.
Identifiants
pubmed: 32497151
doi: 10.1371/journal.pone.0234176
pii: PONE-D-20-02929
pmc: PMC7272035
doi:
Substances chimiques
Analgesics
0
Biomarkers
0
Oils
0
Cannabidiol
19GBJ60SN5
Dronabinol
7J8897W37S
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0234176Subventions
Organisme : CIHR
Pays : Canada
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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