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The effects of cannabidiol and analgesic expectancies on experimental pain reactivity in healthy adults: A balanced placebo design trial

Please use this link to access this publication. Abstract Despite its frequent use for pain relief, no experimental pain research has tested the analgesic effects of cannabidiol (CBD) in humans. The goal of this study was to experimentally test the effects of CBD and expectancies for receiving CBD on human pain reactivity. Using a crossover, 2 × 2 factorial balanced placebo design, drug administration (given inactive substance or given active CBD) and verbal instruction sets (told inactive substance or told active CBD) were experimentally manipulated. Fifteen healthy adults each completed four separate experimental sessions. Participants were randomly assigned to different counterbalanced manipulation conditions at...
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Pilot clinical and pharmacokinetic study of Δ9-Tetrahydrocannabinol (THC)/Cannabidiol (CBD) nanoparticle oro-buccal spray in patients with advanced cancer experiencing uncontrolled pain

Abstract This pilot study aimed to assess the safety, tolerability, pharmacokinetics and exploratory analgesic effect of a novel water-soluble oro-buccal nanoparticle spray of a cannabis-based medicine (MDCNS-01) in patients with advanced incurable malignancy with unrelieved pain from opioid analgesic. The study was a non-blinded single arm 2 stage study. Stage I was a single escalating dose (n = 5) [2.5 mg Δ9-THC and 2.5 mg CBD) versus a 3-fold escalated dose. Stage II was an up-titrated dose in patients with advanced cancers and intractable pain (n = 25). During Stage I with an increased cannabis-based medicine dose, maximum observed plasma concentrations of cannabinoids were...
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Long-term and serious harms of medical cannabis and cannabinoids for chronic pain: a systematic review of non-randomised studies

Abstract Objective To establish the prevalence of long-term and serious harms of medical cannabis for chronic pain. Design Systematic review and meta-analysis. Data sources MEDLINE, EMBASE, PsycINFO and CENTRAL from inception to 1 April 2020. Study selection Non-randomised studies reporting on harms of medical cannabis or cannabinoids in adults or children living with chronic pain with ≥4 weeks of follow-up. Data extraction and synthesis A parallel guideline panel provided input on the design and interpretation of the systematic review, including selection of adverse events for consideration. Two reviewers, working independently and in duplicate, screened the search results, extracted data and assessed risk of bias. We used random-effects models for...
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Cannabinoids in Chronic Pain: Therapeutic Potential Through Microglia Modulation

Abstract Chronic pain is a complex sensory, cognitive, and emotional experience that imposes a great personal, psychological, and socioeconomic burden on patients. An estimated 1.5 billion people worldwide are afflicted with chronic pain, which is often difficult to treat and may be resistant to the potent pain-relieving effects of opioid analgesics. Attention has therefore focused on advancing new pain therapies directed at the cannabinoid system because of its key role in pain modulation. Endocannabinoids and exogenous cannabinoids exert their actions primarily through Gi/o-protein coupled cannabinoid CB1 and CB2 receptors expressed throughout the nervous system. CB1 receptors are found at key nodes along the pain...
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Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies

Abstract Cannabinoid co-administration may enable reduced opioid doses for analgesia. This updated systematic review on the opioid-sparing effects of cannabinoids considered preclinical and clinical studies where the outcome was analgesia or opioid dose requirements. We searched Scopus, Cochrane Central Registry of Controlled Trials, Medline, and Embase (2016 onwards). Ninety-two studies met the search criteria including 15 ongoing trials. Meta-analysis of seven preclinical studies found the median effective dose (ED50) of morphine administered with delta-9-tetrahydrocannabinol was 3.5 times lower (95% CI 2.04, 6.03) than the ED50 of morphine alone. Six preclinical studies found no evidence of increased opioid abuse liability with cannabinoid administration. Of five healthy-volunteer...
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Cannabinoid 1 and mu-Opioid Receptor Agonists Synergistically Inhibit Abdominal Pain and Lack Side Effects in Mice

Abstract While effective in treating abdominal pain, opioids have significant side effects. Recent legalization of cannabis will likely promote use of cannabinoids as an adjunct or alternative to opioids, despite a lack of evidence. We aimed to investigate whether cannabinoids inhibit mouse colonic nociception, alone or in combination with opioids at low doses. Experiments were performed on C57BL/6 male and female mice. Visceral nociception was evaluated by measuring visceromotor responses (VMR), afferent nerve mechanosensitivity in flat-sheet colon preparations, and excitability of isolated DRG neurons. Blood oxygen saturation, locomotion, and defecation were measured to evaluate side effects. An agonist of cannabinoid 1 receptor (CB1R), arachidonyl-2'-chloroethylamide...
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Cannabinoid CB1 Receptor Expression and Localization in the Dorsal Horn of Male and Female Rat and Human Spinal Cord

Abstract Cannabidiol (CBD), a non-psychotomimetic phytocannabinoid found in the Cannabis plant, has emerged as a potential therapeutic agent for psychostimulant use disorders. In recent work, we demonstrated that CBD is able to attenuate the expression of locomotor sensitization and the enhanced metabolic activity in the nucleus accumbens (NAc) generated by the combination of cocaine and caffeine. CDB interacts directly or indirectly with several molecular targets, so the underlying mechanisms of its beneficial effects are hard to determine. Here we used high-throughput RNA-sequencing in mice’s NAc after a sensitization protocol with combined cocaine plus caffeine and a CBD pre-treatment, to identify the major pathways and genes involved...
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Relief of nocturnal neuropathic pain with the use of cannabis in a patient with Fabry disease

Abstract Neuropathic pain is one of the most invalidating symptoms in patients with Fabry disease (FD), affecting their quality of life, it is linked to small fiber neuropathy and it may not respond to available disease specific treatments. We report the case of a 32 years old man with classic FD and severe neuropathic pain who, after the failure of several standard pharmaceutical approaches, was treated with medical cannabis with relief of nocturnal pain and sleep improvement.
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The endocannabinoid system and orofacial pains: updates and perspectives

ABSTRACT BACKGROUND AND OBJECTIVES: Since the relatively recent discovery of the endocannabinoid system (ECS) and its fundamental role in regulating other systems, the subject has aroused interest in all areas of health, including Dentistry. Among the possible uses and benefits of cannabinoids are their performance in pain and its predisposing or perpetuating factors, such as bruxism and sleep disorders. Although the literature is still scarce, the mechanisms of action and satisfactory results of cannabinoids and other cannabis derivatives in these situations already allow their safe prescription. The objective of this study was to verify the current evidence on the use of cannabis derivatives in...
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Chronic Cannabigerol as an Effective Therapeutic for Cisplatin-Induced Neuropathic Pain

Abstract Cannabigerol (CBG), derived from the cannabis plant, acts as an acute analgesic in a model of cisplatin-induced peripheral neuropathy (CIPN) in mice. There are no curative, long-lasting treatments for CIPN available to humans. We investigated the ability of chronic CBG to alleviate mechanical hypersensitivity due to CIPN in mice by measuring responses to 7 and 14 days of daily CBG. We found that CBG treatment (i.p.) for 7 and 14 consecutive days significantly reduced mechanical hypersensitivity in male and female mice with CIPN and reduced pain sensitivity up to 60–70% of baseline levels (p < 0.001 for all), 24 h after the last injection....
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