Cannabinoids: Current and Future Options to Treat Chronic and Chemotherapy-Induced Neuropathic Pain

Blanton, Henry L.; Brelsfoard, Jennifer M.; Deturk, Nathan; Pruitt, Kevin; Narasimhan, Madhusudhanan; Morgan, Daniel J.; Guindon, Josée

doi:10.1007/s40265-019-01132-x

Cited by 59 publications

(41 citation statements)

References 178 publications

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“…Cannabis -derived herbal extracts (CHEs) are increasingly popular for both human and animal use, with recent legalization of such products in Canada and some European countries and American states. There is significant interest in evaluating CHE products for a variety of applications in both human and animal health, including chronic osteoarthritis ( 1 , 2 ), epilepsy ( 3 , 4 ), neuropathic pain ( 5 ), and nausea/emesis ( 6 ). Substantial differences can exist between CHE formulations produced by licensed vs. unlicensed producers, with wide variations in cannabinoid composition and label accuracy ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic and Safety Evaluation of Various Oral Doses of a Novel 1:20 THC:CBD Cannabis Herbal Extract in Dogs

et al. 2020

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Objective: To determine the pharmacokinetics (PK) and safety of various oral doses of a Cannabis herbal extract (CHE) containing a 1:20 ratio of Δ9-tetrahydrocannabinol (THC):cannabidiol (CBD) in 13 healthy Beagle-cross dogs. Methods: Single-dose PK was assessed after oral administration of CHE at low, medium, or high doses [2, 5, or 10 mg CBD and 0.1, 0.25, or 0.5 mg THC per kg of body weight (bw), respectively; n = 6 per group]. Dogs were monitored for adverse events for up to 48 h post-dose. Evaluations of neurological signs, clinical laboratory abnormalities, and other adverse events were performed in two separate study phases: a multiple-dose phase with 12 dogs receiving five medium doses (5 mg CBD/kg bw) at 12 h intervals, and a single low-dose (2 mg CBD/kg bw), randomized, blinded, negative controlled study with 13 dogs. Results: Cannabinoids CBD, THC, CBC, and metabolites 6-OH-CBD, 7-OH-CBD, 11-OH-THC, and THC-COOH were quantified in plasma. CBD and THC were rapidly absorbed (mean T max of 1.9–2.3 h) and initially depleted rapidly (mean CBD T 1/2β of 2.3–2.6 h). A prolonged elimination phase (mean CBD T 1/2λ of 13.3–24.4 h) was observed. CBD and THC concentrations increased in a dose-dependent (non-linear) manner, with disproportionally greater cannabinoid exposure relative to the dose increase. Neurological signs (hyperesthesia or proprioceptive deficits) were noted in five of six dogs in the high-dose group, but only occasionally or rarely in the medium- and low-dose groups, respectively. Presence and severity of clinical signs correlated with plasma cannabinoid concentrations. Dogs appeared to develop a tolerance to cannabinoid effects after multiple CHE doses, with fewer neurological signs noted after the final (fifth) vs. first dose. No clinically meaningful changes in blood count or chemistry values occurred after multiple CHE doses. Clinical Significance: Dogs tolerated the 1:20 THC:CBD formulation well at low and medium doses, but clinically meaningful neurological signs were observed at high doses. Because of non-proportional increases in plasma cannabinoid concentrations with increasing doses, as well as potential differences in CHE product composition and bioavailability, the possibility of adverse events and dose regimen consistency should be discussed with dog owners.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetic and Safety Evaluation of Various Oral Doses of a Novel 1:20 THC:CBD Cannabis Herbal Extract in Dogs

et al. 2020

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“…Hence, CIPN and CIPN-related neuropathic pain episodes have become a significant clinical issue among cancer survivors [15]. In general, the prevalence of CIPN resulting from different antitumor drugs and doses varies significantly, with reported prevalence rates ranging from 19 to more [18][19][20][21]. GLT-1 glutamate transporter 1, GLAST GLutamate and ASpartate Transporter, GABA γ-aminobutyric acid, GAT GABA transporter, TLR toll-like receptor, Glu glutamate, PAC paclitaxel, VIN vincristine, OXA oxaliplatin, CIS cisplatin, BOR bortezomib, Na v voltage-gated sodium channels, Ca v voltage-gated calcium channels, K v voltage-gated potassium channels, TRPA1 Transient Receptor Potential Ankyrin-repeat 1 channel, TRPV Transient Receptor Potential Vanilloid channel, TRPM8 Transient Receptor Potential Melastatin 8 channel, iNOS inducible nitric oxide synthase, IL interleukin, TNFα tumor necrosis factor α, SARM1 sterile alpha and TIR motif-containing protein 1, NAD + nicotinamide adenine dinucleotide ◂ than 85% [17].…”

Section: Prevalence Of Cipn and Risk Factorsmentioning

confidence: 99%

Chemotherapy-induced peripheral neuropathy: part 1—current state of knowledge and perspectives for pharmacotherapy

Sałat

2020

Pharmacol. Rep

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Background Despite the increasing knowledge of the etiology of neuropathic pain, this type of chronic pain is resistant to available analgesics in approximately 50% of patients and therefore is continuously a subject of considerable interest for physiologists, neurologists, medicinal chemists, pharmacologists and others searching for more effective treatment options for this debilitating condition. Materials and methods The present review article is the first of the two articles focused on chemotherapy-induced peripheral neuropathy (CIPN). Results CIPN is regarded as one of the most common drug-induced neuropathies and is highly pharmacoresistant. The lack of efficacious pharmacological methods for treating CIPN and preventing its development makes CIPN-related neuropathic pain a serious therapeutic gap in current medicine and pharmacotherapy. In this paper, the most recent advances in the field of studies on CIPN caused by platinum compounds (namely oxaliplatin and cisplatin), taxanes, vinca alkaloids and bortezomib are summarized. Conclusions The prevalence of CIPN, potential causes, risk factors, symptoms and molecular mechanisms underlying this pharmacoresistant condition are discussed.

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“…There is increasing enthusiasm for the use of cannabinoids in the treatment of many chronic pain states. Agonism at CB1 and CB2 receptors has shown analgesia in rodent models of CIPN [129][130][131][132][133] but these findings have not translated into evidence of clinical efficacy. One published pilot study of nabiximols (THC:CBD mix) in 15 patients with CIPN 134 showed no significant improvement in pain, but a 2-point decrease over placebo was seen in five patients classified as "responders" 134 .…”

Section: Treatmentmentioning

confidence: 99%

Recent advances in understanding chemotherapy-induced peripheral neuropathy

Gordon-Williams

Farquhar-Smith

2020

F1000Res

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Chemotherapy-induced peripheral neuropathy (CIPN) is a common cause of pain and poor quality of life for those undergoing treatment for cancer and those surviving cancer. Many advances have been made in the pre-clinical science; despite this, these findings have not been translated into novel preventative measures and treatments for CIPN. This review aims to give an update on the pre-clinical science, preventative measures, assessment and treatment of CIPN.

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Cannabinoids: Current and Future Options to Treat Chronic and Chemotherapy-Induced Neuropathic Pain

Cited by 59 publications

References 178 publications

Pharmacokinetic and Safety Evaluation of Various Oral Doses of a Novel 1:20 THC:CBD Cannabis Herbal Extract in Dogs

Pharmacokinetic and Safety Evaluation of Various Oral Doses of a Novel 1:20 THC:CBD Cannabis Herbal Extract in Dogs

Chemotherapy-induced peripheral neuropathy: part 1—current state of knowledge and perspectives for pharmacotherapy

Recent advances in understanding chemotherapy-induced peripheral neuropathy

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