Abstract Opioid receptor agonists are effective for treating pain; however, tolerance and dependence can develop with repeated use. Combining opioids with cannabinoids can enhance their analgesic potency, although it is less clear whether combined treatment alters opioid tolerance and dependence. In this study, four monkeys received 3.2 mg/kg morphine alone or in combination with 1 mg/kg Δ(9)-tetrahydrocannabinol (THC) twice daily; the antinociceptive effects (warm water tail withdrawal) of morphine, the cannabinoid receptor agonists WIN 55,212 [(R)-(1)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate] and CP 55,940 (2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-5-(2-methyloctan-2-yl)phenol), and the κ opioid receptor agonist U-50,488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzenacetamide methanesulfonate) were examined before, during, and after treatment. To determine whether concurrent THC treatment...

Lidocaine is clinically widely used as a local anesthetic inhibiting propagation of action potentials in peripheral nerve fibers. Correspondingly, the functional magnetic resonance imaging (fMRI) response in mouse brain to peripheral noxious input is largely suppressed by local lidocaine administered at doses used in a clinical setting. We observed, however, that local administration of lidocaine at doses 100 lower than that used clinically led to a significantly increased sensitivity of mice to noxious forepaw stimulation as revealed by fMRI. This hyperalgesic response could be confirmed by behavioral readouts using the von Frey filament test. The increased sensitivity was found to involve a type 1...

Background—Athletes with injury-related pain, especially National Football League (NFL) players, are at increased risk for opioid use and misuse which may result in medical, psychiatric and social problems. This is the first study to evaluate the intersection of sports pain and opioid use and misuse among former NFL players. Methods—A telephone survey of 644 retired NFL players from the 2009 Retired Players Association Directory was conducted (53.4% completion rate) from March to August 2010. Results—Over half (52%) used opioids during their NFL career with 71% reporting misuse. Additionally, 15% of NFL misusers currently misused vs. 5% among players who used just as prescribed during...

Cannabidiol (CBD), a major constituent of Cannabis, has been shown to be a powerful anti‐in‐ flammatory and anti‐anxiety drug, without exerting a psychotropic effect. However, when given either intraperitoneally or orally as a purified product, a bell‐shaped dose‐response was observed, which limits its clinical use. In the present study, we have studied in mice the anti‐inflammatory and anti‐nociceptive activities of standardized plant extracts derived from the Cannabis sativa L., clone 202, which is highly enriched in CBD and hardly contains any psychoactive ingredients. In stark contrast to purified CBD, the clone 202 extract, when given either intraperitoneally or orally, provided a clear correlation between...

Abstract Neuropathic pain affects between 5% and 10% of the US population and can be refractory to treatment. Opioids may be recommended as a second-line pharmacotherapy but have risks including overdose and death. Cannabis has been shown to be effective for treating nerve pain without the risk of fatal poisoning. The author suggests that physicians who treat neuropathic pain with opioids should evaluate their patients for a trial of cannabis and prescribe it when appropriate prior to using opioids. This harm reduction strategy may reduce the morbidity and mortality rates associated with prescription pain medications.

Background: Central pain in multiple sclerosis (MS) is common and often refractory to treatment. Methods: We conducted a single-center, 5-week (1-week run-in, 4-week treatment), randomized, double-blind, placebo-controlled, parallel-group trial in 66 patients with MS and central pain states (59 dysesthetic, seven painful spasms) of a whole-plant cannabis-based medicine (CBM), containing delta-9-tetrahydrocannabinol:cannabidiol (THC:CBD) delivered via an oromucosal spray, as adjunctive analgesic treatment. Each spray delivered 2.7 mg of THC and 2.5 of CBD, and patients could gradually self-titrate to a maximum of 48 sprays in 24 hours. Results: Sixty-four patients (97%) completed the trial, 34 received CBM. In week 4, the mean number of daily...

Abstract Cannabis extracts and synthetic cannabinoids are still widely considered illegal substances. Preclinical and clinical studies have suggested that they may result useful to treat diverse diseases, including those related with acute or chronic pain. The discovery of cannabinoid receptors, their endogenous ligands, and the machinery for the synthesis, transport, and degradation of these retrograde messengers, has equipped us with neurochemical tools for novel drug design. Agonist-activated cannabinoid receptors, modulate nociceptive thresholds, inhibit release of pro-inflammatory molecules, and display synergistic effects with other systems that influence analgesia, especially the endogenous opioid system. Cannabinoid receptor agonists have shown therapeutic value against inflammatory and neuropathic pains,...

Abstract Background Chronic neuropathic pain affects 1%–2% of the adult population and is often refractory to standard pharmacologic treatment. Patients with chronic pain have reported using smoked cannabis to relieve pain, improve sleep and improve mood. Methods Adults with post-traumatic or postsurgical neuropathic pain were randomly assigned to receive cannabis at four potencies (0%, 2.5%, 6% and 9.4% tetrahydrocannabinol) over four 14-day periods in a crossover trial. Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle, followed by a nine-day washout period. Daily average pain intensity was measured using an 11-point numeric rating...

Objectives—To identify the types and frequencies of pain treatments used by individuals with cerebral palsy (CP); examine the perceived effectiveness of these treatments; and identify the types of healthcare providers that were accessed for pain-related services. Design—A cross-sectional survey design was employed. 83 adults (mean age=40.3 years, SD=13.6) with CP indicated their pain location and intensity during the past 3 months. Next, they indicated their use of 24 different pain treatments and the effectiveness of each. Finally, participants indicated the frequency of pain-related healthcare visits to specific providers over the past 6 months. Results—63% of participants reported experiencing chronic pain and rated their pain...

Evidence for an analgesic interaction between delta-9-tetrahydrocannabinol (Δ9 -THC) and morphine was sought using an experimental pain model applied to normal volunteers. The study incorporated a double blinded, four treatment, four period, four sequence, crossover design. Subjects received Δ9 -THC 5 mg orally or placebo and 90 min later morphine 0.02 mg/kg intravenously or placebo. Fifteen minutes later subjects rated the pain associated with the application of thermal stimuli to skin using two visual analog scales, one for the sensory and one for the affective aspects of pain. Among sensory responses, neither morphine nor Δ9 -THC had a significant effect at the doses used,...