Using 8-hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, most of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta 9-THC on 3 separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was used to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome,...

AIM Experimental pain models may help to evaluate the mechanisms of analgesics and target the clinical indications for their use. This review, the second in a series of two, addresses how the efficacy of non-opioid analgesics have been assessed in human volunteers using experimental pain models. METHODS A literature search was completed for randomized controlled studies that included human experimental pain models, healthy volunteers and non-opioid analgesics. RESULTS Nonsteroidal anti-inflammatory drugs worked against various types of acute pain as well as in hyperalgesia. Analgesia from paracetamol was difficult to detect in experimental pain and the pain needed to be assessed with very sensitive methods...

Abstract Gliomas constitute the most frequent and malignant primary brain tumors. Current standard therapeutic strategies (surgery, radiotherapy and chemotherapeutics, e.g., temozolomide, carmustin or carboplatin) for their treatment are only palliative and survival diagnosis is normally 6-12 months. The development of new therapeutic strategies for the management of gliomas is therefore essential. Interestingly, cannabinoids have been shown to exert antiproliferative effects on a wide spectrum of cells in culture. Of interest, cannabinoids have displayed a great potency in reducing glioma tumor growth either in vitro or in animal experimental models, curbing the growth of xenografts generated by subcutaneous or intratecal injection of glioma cells in...

Significant advances have increased our understanding of the molecular mechanisms of amyotrophic lateral sclerosis (ALS), yet this has not translated into any greatly effective therapies. It appears that a number of abnormal physiological processes occur simultaneously in this devastating disease. Ideally, a multidrug regimen, including glutamate antagonists, antioxidants, a centrally acting anti-inflammatory agent, microglial cell modulators (including tumor necrosis factor alpha [TNF-a] inhibitors), an antiapoptotic agent, 1 or more neurotrophic growth factors, and a mitochondrial function-enhancing agent would be required to comprehensively address the known pathophysiology of ALS. Remarkably, cannabis appears to have activity in all of those areas. Preclinical data indicate that cannabis...

The discovery of the endocannabinoid system (ECS; comprising of G-protein coupled cannabinoid 1 and 2 receptors, their endogenous lipid ligands or endocannabinoids, and synthetic and metabolizing enzymes, triggered an avalanche of experimental studies that have implicated the ECS in a growing number of physiological/pathological functions. They also suggested that modulating ECS activity holds therapeutic promise for a broad range of diseases, including neurodegenerative, cardiovascular and inflammatory disorders, obesity/metabolic syndrome, cachexia, chemotherapy-induced nausea and vomiting, tissue injury and pain, among others. However, clinical trials with globally acting CB1 antagonists in obesity/metabolic syndrome, and other studies with peripherally restricted CB1/2 agonists and inhibitors of the endocannabinoid...

Study Objective: Animal data suggest that ∆9 -TetraHydroCannabinol (∆9THC) stabilizes autonomic output during sleep, reduces spontaneous sleep-disordered breathing, and blocks serotonin-induced exacerbation of sleep apnea. On this basis, we examined the safety, tolerability, and efficacy of dronabinol (∆9THC), an exogenous Cannabinoid type 1 and type 2 (CB1 and CB2) receptor agonist in patients with Obstructive Sleep Apnea (OSA). Design and Setting: Proof of concept; single-center dose-escalation study of dronabinol. Participants: Seventeen adults with a baseline Apnea Hypopnea Index (AHI) ≥15/h. Baseline polysomnography (PSG) was performed after a 7-day washout of Continuous Positive Airway Pressure treatment. Intervention: Dronabinol was administered after baseline PSG, starting at...

In 2010 a review by Hazekamp and Grotenhermen covered controlled clinical trials of the years 2006-2009 on cannabis-based medicines, which followed the example of the review by Ben Amar (2006). The current review reports on the more recent clinical data available from 2010-2014. A systematic search was performed in the scientific database of PubMed, focused on clinical studies that were randomized, (double) blinded, and placebo-controlled. The key words used were: cannabis, marijuana, marihuana, hashish, cannabinoid(s), tetrahydrocannabinol, THC, CBD, dronabinol, Marinol, nabilone, Cannador, nabiximols and Sativex. For the final selection, only properly controlled clinical trials were retained. Open-label studies were excluded, except if they were...

The endocannabinoid system is implicated in a variety of physiological and pathological conditions (inflammation, immunomodulation, analgesia, cancer and others). The main active ingredient of cannabis, D9 -tetrahydrocannabinol (D9 -THC), produces its effects through activation of CB1 and CB2 receptors. CB1 receptors are expressed at high levels in the central nervous system (CNS), whereas CB2 receptors are concentrated predominantly, although not exclusively, in cells of the immune system. Endocannabinoids are endogenous lipid-signalling molecules that are generated in the cell membrane from phospholipid precursors. The two best characterized endocannabinoids identified to date are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Here we review the relationship between the endocannabinoid...