Abstract This study compared the efficacy of a tetrahydrocannabinol:cannabidiol (THC:CBD) extract, a nonopioid analgesic endocannabinoid system modulator, and a THC extract, with placebo, in relieving pain in patients with advanced cancer. In total, 177 patients with cancer pain, who experienced inadequate analgesia despite chronic opioid dosing, entered a two-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial. Patients were randomized to THC:CBD extract (n = 60), THC extract (n = 58), or placebo (n = 59). The primary analysis of change from baseline in mean pain Numerical Rating Scale (NRS) score was statistically significantly in favor of THC:CBD compared with placebo (improvement of −1.37 vs. −0.69), whereas the THC group showed a nonsignificant...

Please use this link to access this publication. Abstract Background Previous studies suggest that cannabidiol (CBD) may potentiate or antagonize Δ9-tetrahydrocannabinol’s (THC) effects. The current study examined sex differences in CBD modulation of THC-induced antinociception, hypolocomotion, and metabolism. Methods In Experiment 1, CBD (0, 10 or 30 mg/kg) was administered 15 min before THC (0, 1.8, 3.2, 5.6 or 10 mg/kg), and rats were tested for antinociception and locomotion 15–360 min post-THC injection. In Experiments 2 and 3, CBD (30 mg/kg) was administered 13 h or 15 min before THC (1.8 mg/kg); rats were tested for antinociception and locomotion 30–480 min post-THC injection (Experiment 2), or serum samples were taken 30–360 min post-THC injection to examine CBD modulation of THC metabolism (Experiment 3). Results In...

Please use this link to access this publication. Abstract Rationale The purpose of this study was to evaluate the potential of oral combined cannabis constituents to reduce nausea. Objective The objective of this study was to determine the effect of combining subthreshold oral doses of Δ9-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models of conditioned gaping. Material and methods The potential of intragastric (i.g.) administration of THC, CBDA, or combined doses, to interfere with acute nausea-induced conditioned gaping (acute nausea) or the expression of contextually elicited conditioned gaping (anticipatory nausea), was evaluated. Results For acute nausea, i.g. administration...

Please use this link to access this publication. Abstract Cannabis use has been associated with an increased risk to develop schizophrenia as well as symptom exacerbation in patients. In contrast, clinical studies have revealed an inverse relationship between the cerebrospinal fluid levels of the endocannabinoid anandamide and symptom severity, suggesting a therapeutic potential for endocannabinoid-enhancing drugs. Indeed, preclinical studies have shown that these drugs can reverse distinct behavioral deficits in a rodent model of schizophrenia. The mechanisms underlying the differences between exogenous and endogenous cannabinoid administration are currently unknown. Using the phencyclidine (PCP) rat model of schizophrenia, we compared the effects on neuronal activity...

Please use this link to access this publication. Abstract Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray was approved as add-on therapy for spasticity in patients with multiple sclerosis (MS). We show our 40-week postmarketing experience regarding efficacy and safety of THC/CBD spray in an Italian cohort of 102 MS patients. Patients were evaluated using the Expanded Disability Status Scale (EDSS) score, the Numerical Rating Scale (NRS) for spasticity, the Ambulation Index (AI), and Timed 25-Foot Walk (T25-FW) at the beginning of treatment and then every 3 months. After 4 weeks, if a clinically significant improvement in spasticity (at least 20% of baseline NRS score) was not...

Abstract Background: From the time Sativex (THC:CBD) oromucosal spray first became available in European Union countries in 2010 for the management of treatment-resistant multiple sclerosis (MS) spasticity, data from daily practice have been collected through various projects. Methods: A retrospective registry study and a prospective safety study of THC:CBD oromucosal spray are reported. Results: The most recent analysis of a retrospective registry established in the United Kingdom (UK), Germany and Switzerland, which collected safety data on more than 900 patients, has indicated a positive risk-benefit profile for THC:CBD oromucosal spray during long-term use. Long-term continuation rates were 68% (mean follow-up time 1 year) and the mean dose was 5.4...

Please use this link to access this publication. Abstract Rationale: Cannabis is mostly grown under illegal and unregulated circumstances, which seems to favour a product increasingly high in its main cannabinoid ∆-9-tetrahydrocannabinol (THC). ∆-9-tetrahydrocannabivarin (THCV) is a relatively untested cannabinoid which is said to be a cannabinoid receptor neutral antagonist, and may inhibit the effects of THC. Objectives: To explore the safety and tolerability of repeated THCV administration and its effects on symptoms normally induced by THC in a sample of healthy volunteers. Methods: Ten male cannabis users (<25 use occasions) were recruited for this within-subjects, placebo-controlled, double-blind, cross-over pilot study. 10mg oral pure...

Please use this link to access this publication. Abstract The effects of Δ9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, are a pressing concern for global mental health. Patterns of cannabis use are changing drastically owing to legalization, the availability of synthetic analogues (commonly termed spice), cannavaping and an emphasis on the purported therapeutic effects of cannabis. Many of the reinforcing effects of THC are mediated by the dopamine system. Owing to the complexity of the cannabinoid–dopamine interactions that take place, there is conflicting evidence from human and animal studies concerning the effects of THC on the dopamine system. Acute THC administration causes increased...

Please use this link to access this publication. Abstract Background and Objective Given that 29 U.S. states now have laws allowing medical marijuana use, this study examined mental and physical health correlates of medical versus nonmedical marijuana use among three age groups of adults (18–29, 30–49, and 50+). Methods Data came from the 2012–2013 National Epidemiologic Survey on Alcohol and Related Conditions (N = 36,309 respondents aged 18+). Logistic regression models were used to examine age group differences in associations of substance use and mental disorders and health conditions with medical versus nonmedical marijuana use. Results Of all respondents, 9.74% (N = 3,784) reported past-year marijuana use. Of...

Please use this link to access this publication. Abstract Plasmacytoid dendritic cells (pDCs) play a crucial role in host antiviral immune response through secretion of type I interferon. Interferon alpha (IFNα), a type I IFN, is critical for mounting the initial response to viral pathogens. A consequence of Human Immunodeficiency Virus-1 (HIV) infection is a decrease in both pDC number and function, but prolonged pDC activity has been linked with progression from HIV infection to the development of AIDS. Patients with HIV in the United States routinely use cannabinoid-based therapies to combat the side effects of HIV infection and antiretroviral therapy. However, cannabinoids, including...