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cbd neuropathy pubmed

The psychoactive and non-psychoactive constituents of cannabis, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have synergistic analgesic efficacy in animal models of neuropathic pain when injected systemically. However, the relevance of this preclinical synergy to clinical neuropathic pain studies is unclear because many of the latter use oral administration. We therefore examined the oral effectiveness of these phytocannabinoids and their interactions in a mouse chronic constriction injury (CCI) model of neuropathic pain. THC produced a dose-dependent reduction in mechanical and cold allodynia, but also induced side-effects with similar potency. CBD also reduced allodynia, albeit with lower potency than THC, but did not produce cannabinoid-like side-effects at any dose tested. Combination THC:CBD produced a dose-dependent reduction in allodynia, however, it displayed little to no synergy. Combination THC:CBD produced substantial, synergistic side-effects which increased with the proportion of CBD. These findings demonstrate that oral THC and CBD, alone and in combination, have analgesic efficacy in an animal neuropathic pain model. Unlike prior systemic injection studies, combination THC:CBD lacks analgesic synergy when delivered orally. Furthermore, both THC and combination THC:CBD display a relatively poor therapeutic window when delivered orally. This suggests that CBD provides a safer, albeit lower efficacy, oral treatment for nerve injury induced neuropathic pain than THC-containing preparations. This article is part of the special issue on ‘Cannabinoids’.

Cbd neuropathy pubmed

Repeated CBD treatment prevents SNI-induced…

TRPV 1 antagonism blocked the antinociceptive, but not the anxiolytic effects, of repeated…

Acute and repeated CBD administration on firing activity of DRN 5-HT neurons in naive rats. (A) Representation of coronal sections of the rat brain with the photomicrograph of the recording site in the DRN. Central gray dorsal (CGD); central gray lateral ventral (CGLV); aqueduct (Aq). The white arrow indicates the site of the electrode recording labeled with pontamine sky blue dye. (B) The typical spike waveform of 5-HT neuron. (C) Acute intravenous (i.v.) CBD administration decreases firing rate of DRN 5-HT neurons (n = 9), prevented by previous i.v. injection of WAY 100635 (WAY, n = 4) and CPZ (n = 4) but not by AM 251 (n = 4). Each point of the line represents mean ± SEM expressed as percentage of baseline before injections of veh, CBD, or antagonists. White arrow indicates the injection of veh, WAY, CPZ, or AM 251, and black arrow indicates the beginning of cumulative CBD injection. (D) WAY, CPZ, and AM 251 do not affect the basal 5-HT firing rate activity. (E-H) Representative firing rate histograms showing the acute response of 5-HT neurons to CBD alone (E) and with previous injection of WAY (F), CPZ (G), and AM 251 (H). Black arrows indicate sequence of a single injection of antagonists and of increasing doses of CBD. The cumulative doses are indicated on top of each arrow. Two-way ANOVA for RM followed by Bonferroni post hoc comparisons. *P < 0.05 and ***P < 0.001 vs veh; P < 0.001 vs CBD. (I) Mean firing DRN 5-HT activity of naive rats treated with veh (65 recorded neurons in 4 rats) or with CBD (5 mg/kg/day, subcutaneously [s.c.], for 7 days) (77 neurons recorded in 4 rats). Each bar represents mean ± SEM and each point represents a single neuron recorded in each group. The Student unpaired 2-tailed t test. ***P < 0.001 vs veh. (J) Simple linear regression analysis showing relationship between degree of suppression of 5-HT firing activity in the DRN and the dose of LSD administered i.v. in naive rats treated for 7 days with vehicle or CBD (5.0 mg/kg/day, s.c.). ANOVA, analysis of variance; CBD, cannabidiol; CPZ, capsazepine; DRN, dorsal raphe nucleus; N.S., not significant; RM, repeated measures.

Acute and repeated CBD administration…

Conflict of interest statement

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Clinical studies indicate that cannabidiol (CBD), the primary nonaddictive component of cannabis that interacts with the serotonin (5-HT)1A receptor, may possess analgesic and anxiolytic effects. However, its effects on 5-HT neuronal activity, as well as its impact on models of neuropathic pain are unknown. First, using in vivo single-unit extracellular recordings in rats, we demonstrated that acute intravenous (i.v.) increasing doses of CBD (0.1-1.0 mg/kg) decreased the firing rate of 5-HT neurons in the dorsal raphe nucleus, which was prevented by administration of the 5-HT1A antagonist WAY 100635 (0.3 mg/kg, i.v.) and the TRPV1 antagonist capsazepine (1 mg/kg, i.v.) but not by the CB1 receptor antagonist AM 251 (1 mg/kg, i.v.). Repeated treatment with CBD (5 mg/kg/day, subcutaneously [s.c.], for 7 days) increased 5-HT firing through desensitization of 5-HT1A receptors. Rats subjected to the spared nerve injury model for 24 days showed decreased 5-HT firing activity, mechanical allodynia, and increased anxiety-like behavior in the elevated plus maze test, open-field test, and novelty-suppressed feeding test. Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity. Antiallodynic effects of CBD were fully prevented by capsazepine (10 mg/kg/day, s.c., for 7 days) and partially prevented by WAY 100635 (2 mg/kg/day, s.c., for 7 days), whereas the anxiolytic effect was blocked only by WAY. Overall, repeated treatment with low-dose CBD induces analgesia predominantly through TRPV1 activation, reduces anxiety through 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.

5-HT 1A antagonism partially prevented antinociception and completely blocked the anxiolytic properties of…

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Repeated CBD treatment increases paw withdrawal threshold and prevents anxiety-like behavior in the…

TRPV 1 antagonism blocked the…

Recent findings: We examined current basic scientific research and data from recent randomized controlled trials (RCTs) evaluating medical cannabis for the treatment of neuropathic pain. These studies involved patients with diverse etiologies of neuropathic pain and included medical cannabis with different THC concentrations and routes of administration. Multiple RCTs demonstrated efficacy of medical cannabis for treating neuropathic pain, with number needed to treat (NNT) values similar to current pharmacotherapies. Although limited by small sample sizes and short duration of study, the evidence appears to support the safety and efficacy of short-term, low-dose cannabis vaporization and oral mucosal delivery for the treatment of neuropathic pain. The results suggest medical cannabis may be as tolerable and effective as current neuropathic agents; however, more studies are needed to determine the long-term effects of medical cannabis use. Furthermore, continued research to optimize dosing, cannabinoid ratios, and alternate routes of administration may help to refine the therapeutic role of medical cannabis for neuropathic pain.

Purpose of review: Many cultures throughout history have used cannabis to treat a variety of painful ailments. Neuropathic pain is a complicated condition that is challenging to treat with our current medications. Recent scientific discovery has elucidated the intricate role of the endocannabinoid system in the pathophysiology of neuropathic pain. As societal perceptions change, and legislation on medical cannabis relaxes, there is growing interest in the use of medical cannabis for neuropathic pain.

Keywords: CBD; Cannabinoid; Cannabis; Medical marijuana; Neuropathic pain; THC.