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Cannabinoid treatment for pain

Marjan de Vries, Dagmar C M van Rijckevorsel, Kris C P Vissers, Oliver H G Wilder-Smith, Harry van Goor
BACKGROUND & AIMS: Delta-9-tetrahydrocannabinol (THC) is the most abundant cannabinoid from the plant Cannabis sativa. There is only equivocal evidence that THC has analgesic effects. We performed a phase 2 controlled trial to evaluate the analgesic efficacy, pharmacokinetics, safety, and tolerability of an oral tablet containing purified THC in patients with chronic abdominal pain. METHODS: Sixty-five patients with chronic abdominal pain for 3 months or more (numeric rating scale scores of 3 or more) after surgery or due to chronic pancreatitis were randomly assigned to groups given the THC tablet or identical matching placebos for 50-52 days...
October 5, 2016: Clinical Gastroenterology and Hepatology
Jijun Xu, Yuying Tang, Mian Xie, Bihua Bie, Jiang Wu, Hui Yang, Joseph F Foss, Bin Yang, Richard W Rosenquist, Mohamed Naguib
Complex regional pain syndrome type 1 (CRPS-I) remains one of the most clinically challenging neuropathic pain syndromes and its mechanism has not been fully characterized. Cannabinoid receptor 2 (CB2) has emerged as a promising target for treating different neuropathic pain syndromes. In neuropathic pain models, activated microglia expressing CB2 receptors are seen in the spinal cord. Chemokine fractalkine receptor (CX3CR1) plays a substantial role in microglial activation and neuroinflammation. We hypothesized that a CB2 agonist could modulate neuroinflammation and neuropathic pain in an ischemia model of CRPS by regulating CB2 and CX3CR1 signaling...
September 26, 2016: European Journal of Neuroscience
Klaudyna Fidyt, Anna Fiedorowicz, Leon Strządała, Antoni Szumny
Natural bicyclic sesquiterpenes, β-caryophyllene (BCP) and β-caryophyllene oxide (BCPO), are present in a large number of plants worldwide. Both BCP and BCPO (BCP(O)) possess significant anticancer activities, affecting growth and proliferation of numerous cancer cells. Nevertheless, their antineoplastic effects have hardly been investigated in vivo. In addition, both compounds potentiate the classical drug efficacy by augmenting their concentrations inside the cells. The mechanisms underlying the anticancer activities of these sesquiterpenes are poorly described...
September 30, 2016: Cancer Medicine
James T Toguri, Meggie Caldwell, Melanie E M Kelly
The endocannabinoid system (ECS) has emerged as an important regulator of both physiological and pathological processes. Notably, this endogenous system plays a key role in the modulation of pain and inflammation in a number of tissues. The components of the ECS, including endocannabinoids, their cognate enzymes and cannabinoid receptors, are localized in the eye, and evidence indicates that ECS modulation plays a role in ocular disease states. Of these diseases, ocular inflammation presents a significant medical problem, given that current clinical treatments can be ineffective or are associated with intolerable side-effects...
2016: Frontiers in Pharmacology
Diego Lobos Urbina, José Peña Durán
Cannabinoids have been proposed for the treatment of patients with cancer pain, especially if standard treatment does not control symptoms. Using Epistemonikos database, which is maintained by searching 30 databases, we identified nine systematic reviews including seven trials that answer the question of interest, of which six are randomized trials. We performed a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded it is unclear whether cannabinoids decrease pain and improve quality of life in patients with refractory cancer pain because the certainty of the evidence is very low, and it probably increases adverse effects substantially...
2016: Medwave
Barth L Wilsey, Reena Deutsch, Emil Samara, Thomas D Marcotte, Allan J Barnes, Marilyn A Huestis, Danny Le
A randomized, placebo-controlled crossover trial utilizing vaporized cannabis containing placebo and 6.7% and 2.9% delta-9-tetrahydrocannabinol (THC) was performed in 42 subjects with central neuropathic pain related to spinal cord injury and disease. Subjects received two administrations of the study medication in a 4-hour interval. Blood samples for pharmacokinetic evaluation were collected, and pain assessment tests were performed immediately after the second administration and 3 hours later. Pharmacokinetic data, although limited, were consistent with literature reports, namely dose-dependent increase in systemic exposure followed by rapid disappearance of THC...
2016: Journal of Pain Research
Peng Liu, Wei Zhang, Shaobo Zhang, Yibao Zhang, Jing Wang
Endocannabinoids and cannabinoid receptors are expressed in various central pain modulation regions. They maintain in dynamic changes in the expression level and distribution under different pathological and physiological conditions. These changes possess advantage as well as disadvantage. Exogenous administration of endocannabinoids exerts analgesic effect in different pain models, which is mainly mediated by the cannabinoid CB1 and CB2 receptors. Inhibition of enzymes for degrading endocannabinoids in different pain models also shows analgesic effect due to the increased local levels of endocannabinoids...
August 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Ian A Clark, Bryce Vissel
The basic mechanism of the major neurodegenerative diseases, including neurogenic pain, needs to be agreed upon before rational treatments can be determined, but this knowledge is still in a state of flux. Most have agreed for decades that these disease states, both infectious and non-infectious, share arguments incriminating excitotoxicity induced by excessive extracellular cerebral glutamate. Excess cerebral levels of tumor necrosis factor (TNF) are also documented in the same group of disease states. However, no agreement exists on overarching mechanism for the harmful effects of excess TNF, nor, indeed how extracellular cerebral glutamate reaches toxic levels in these conditions...
2016: Journal of Neuroinflammation
Natalia Malek, Katarzyna Starowicz
Compared with acute pain that arises suddenly in response to a specific injury and is usually treatable, chronic pain persists over time, and is often resistant to medical treatment. Because of the heterogeneity of chronic pain origins, satisfactory therapies for its treatment are lacking, leading to an urgent need for the development of new treatments. The leading approach in drug design is selective compounds, though they are often less effective and require chronic dosing with many side effects. Herein, we review novel approaches to drug design for the treatment of chronic pain represented by dual-acting compounds, which operate at more than one biological target...
2016: Frontiers in Pharmacology
Roger L Bertholf, Rohit Sharma, Gary M Reisfield
Urine drug testing (UDT) has become an essential component in the management of patients prescribed opioid analgesics for the treatment of chronic non-malignant pain. Several laboratory methods are available to monitor adherence with the pharmacological regimen and abstinence from illicit or unauthorized medications. Immunochemical screening methods are rapid and economical, but they have limitations, including lack of specificity, and confirmatory methods are often necessary to verify presumptive positive results...
August 22, 2016: Journal of Analytical Toxicology
Alberto Gajofatto
INTRODUCTION: Nabiximols is a cannabinoid compound approved for the treatment of multiple sclerosis (MS)-related spasticity. However, additional symptoms, such as pain, urinary urgency and sleep disturbance, may benefit from treatment. CASE REPORT: The present report describes a patient with secondary progressive MS and severe lower limbs spasticity who was started on treatment with nabiximols. The patient also suffered from trigeminal neuralgia, which he was not treating due to inefficacy or side effects of all previously tried medications...
July 2016: Multiple Sclerosis and related Disorders
Q-Schick Auh, Yang Hyun Chun, Ohannes K Melemedjian, Youping Zhang, Jin Y Ro
Activation of opioid and cannabinoid receptors expressed in nociceptors induces effective antihyperalgesia. In this study, we examined whether combinations of opioid and cannabinoid receptor agonists directed at the injured site would enhance therapeutic effectiveness. Behavioral pharmacology experiments were performed to compare the effects of DAMGO, a selective agonist for μ-opioid receptor (MOR), ACPA, a specific agonist for CB1, and combinations of DAMGO and ACPA in attenuating complete Freund's adjuvant (CFA)-induced mechanical hyperalgesia in the rat hindpaw...
July 2016: Brain Research Bulletin
Osvaldo J M Nascimento, Bruno L Pessoa, Marco Orsini, Pedro Ribeiro, Eduardo Davidovich, Camila Pupe, Pedro Moreira Filho, Ricardo Menezes Dornas, Lucas Masiero, Juliana Bittencourt, Victor Hugo Bastos
Neuropathic pain (NP) is the result of a series of conditions caused by diseases or lesions to the somatosensory system. Due to the better understanding of NP pathophysiology previously unexplored therapies have been used with encouraging results. In this group, acetyl-L-carnitine, alpha-lipoic-acid, cannabinoids, clonidine, EMA401, botulinum toxin type A and new voltage-gated sodium channel blockers, can be included. Besides, changing paradigms may occur with the advent of optogenetics and a better understanding of epigenetic regulation...
June 15, 2016: Neurology International
Mohammad Alsalem, Paul Millns, Ahmad Altarifi, Khalid El-Salem, Victoria Chapman, David A Kendall
BACKGROUND: Olvanil (NE 19550) is a non-pungent synthetic analogue of capsaicin, the natural pungent ingredient of capsicum which activates the transient receptor potential vanilloid type-1 (TRPV1) channel and was developed as a potential analgesic compound. Olvanil has potent anti-hyperalgesic effects in several experimental models of chronic pain. Here we report the inhibitory effects of olvanil on nociceptive processing using cultured dorsal root ganglion (DRG) neurons and compare the effects of capsaicin and olvanil on thermal nociceptive processing in vivo; potential contributions of the cannabinoid CB1 receptor to olvanil's anti-hyperalgesic effects were also investigated...
2016: BMC Pharmacology & Toxicology
Mohammad Hosein Farzaei, Roodabeh Bahramsoltani, Mohammad Abdollahi, Roja Rahimi
Irritable bowel syndrome (IBS) is the most common disorder referred to gastroenterologists and is characterized by altered bowel habits, abdominal pain, and bloating. Visceral hypersensitivity (VH) is a multifactorial process that may occur within the peripheral or central nervous systems and plays a principal role in the etiology of IBS symptoms. The pharmacological studies on selective drugs based on targeting specific ligands can provide novel therapies for modulation of persistent visceral hyperalgesia...
July 18, 2016: Journal of Neurogastroenterology and Motility
Brian Walitt, Petra Klose, Mary-Ann Fitzcharles, Tudor Phillips, Winfried Häuser
BACKGROUND: This review is one of a series on drugs used to treat fibromyalgia. Fibromyalgia is a clinically well-defined chronic condition of unknown aetiology characterised by chronic widespread pain that often co-exists with sleep problems and fatigue affecting approximately 2% of the general population. People often report high disability levels and poor health-related quality of life (HRQoL). Drug therapy focuses on reducing key symptoms and disability, and improving HRQoL. Cannabis has been used for millennia to reduce pain and other somatic and psychological symptoms...
2016: Cochrane Database of Systematic Reviews
C Fede, G Albertin, L Petrelli, M M Sfriso, C Biz, R De Caro, C Stecco
Cannabinoid receptors have been localized in the central and peripheral nervous system as well as on cells of the immune system, but recent studies on animal tissue gave evidence for the presence of cannabinoid receptors in different types of tissues. Their presence was supposed also in myofascial tissue, suggesting that the endocannabinoid system may help resolve myofascial trigger points and relieve symptoms of fibromyalgia. However, until now the expression of CB1 (cannabinoid receptor 1) and CB2 (cannabinoid receptor 2) in fasciae has not yet been established...
2016: European Journal of Histochemistry: EJH
Natalia Malek, Magdalena Kostrzewa, Wioletta Makuch, Agnieszka Pajak, Mateusz Kucharczyk, Fabiana Piscitelli, Barbara Przewlocka, Vincenzo Di Marzo, Katarzyna Starowicz
There is considerable evidence to support the role of anandamide (AEA), an endogenous ligand of cannabinoid receptors, in neuropathic pain modulation. AEA also produces effects mediated by other biological targets, of which the transient receptor potential vanilloid type 1 (TRPV1) has been the most investigated. Both, inhibition of AEA breakdown by fatty acid amide hydrolase (FAAH) and blockage of TRPV1 have been shown to produce anti-nociceptive effects. Recent research suggests the usefulness of dual-action compounds, which may afford greater anti-allodynic efficacy...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
L Mizera, G Gossrau, T Hummel, A Haehner
BACKGROUND: There is some evidence suggesting that analgesics have an impact on human chemosensory function, especially opioids and cannabinoids are known to interfere with olfactory function. However, largely unknown is the effect of a long-term use of analgesics on the intranasal trigeminal system so far. Here, we investigated olfactory function and the perception of intranasal trigeminal stimuli in pain patients with long-term use of analgesics compared to age-matched healthy controls...
June 20, 2016: European Journal of Pain: EJP
Samane Jahanabadi, Mohamad Reza Hadian, Javad Shamsaee, Seyed Mohammad Tavangar, Alireza Abdollahi, Ahmadreza Dehpour, Shahram Ejtemaei Mehr
OBJECTIVES: Diabetic neuropathy (DN) is a common complication of diabetes that leads to allodynia, impaired nerve conduction, and progressive sensory loss. The aim of this study was to observe the effect of a high-affinity cannabinoid receptors agonist, WIN 55,212-2, on thermal hyperalgesia, nerve conduction velocity and sciatic nerve histopathology in diabetic rats. MATERIALS AND METHODS: Diabetes was induced in rats using a single dose of streptozotocin (45 mg/kg IP)...
April 2016: Iranian Journal of Basic Medical Sciences
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