IMPORTANCE Vaporization is an increasingly popular method for cannabis administration,and policy changes have increased adult access to cannabis drastically.Controlled examinations of cannabis vaporization among adults with infrequent current cannabis use patterns(>30 day ssince lastuse)are needed. OBJECTIVE: To evaluate the acute dose effects of smoked and vaporized cannabis using controlled administration methods. DESIGN,SETTING,AND PARTICIPANTS This within-participant,double-blind,crossover study was conducted from June 2016 to January 2017 at the Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, and included 17 healthy adults. Six smoked and vaporized outpatient experimental sessions (1-week wash out between sessions)were completed in clusters (order counterbalanced across participants);dose order was randomized within...

Cannabis sativa is the source of a unique set of compounds known collectively as plant cannabinoids or phytocannabinoids. This review focuses on the manner with which three of these compounds, ( )-trans-D9 -tetrahydrocannabinol (D9 -THC), ( )- cannabidiol (CBD) and ( )-trans-D9 -tetrahydrocannabivarin (D9 -THCV), interact with cannabinoid CB1 and CB2 receptors. D9 -THC, the main psychotropic constituent of cannabis, is a CB1 and CB2 receptor partial agonist and in line with classical pharmacology, the responses it elicits appear to be strongly influenced both by the expression level and signalling efficiency of cannabinoid receptors and by ongoing endogenous cannabinoid release. CBD displays unexpectedly high...

(−)δ 9 THC was found to significantly decrease the time it takes to fall asleep in physically healthy insomniacs. Once asleep, interruptions of sleep were not significantly altered over the whole night. The (−)δ 9 THC tended to be associated with some decrease in awakenings in the first half of the night. The primary side effect experienced by the subjects at all dose levels in the Pre­Sleep phase was temporal disorganization and mood alterations. There was an increase in intensity of side effects and number of subjects affected with increasing dosage. The most significant side effect, however, was a “hangover” phenomenon, or continued “high”...

This Phase I study aimed to assess the potential drug-drug interactions (pharmacokinetic [PK] and safety profile) of Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (Sativex®, nabiximols) in combination with cytochrome P450 (CYP450) inducer (rifampicin) or inhibitors (ketoconazole or omeprazole). Thirty-six healthy male subjects were divided into three groups of 12, and then randomized to one of two treatment sequences per group. Subjects received four sprays of THC/CBD (10.8/10 mg) alongside single doses of the CYP3A and 2C19 inducer rifampicin (600 mg), CYP3A inhibitor ketoconazole (400 mg) or CYP2C19 inhibitor omeprazole (40 mg). Plasma samples were analyzed for CBD, THC and its metabolite 11-hydroxy-THC (11-OH-THC). A single...

D9 -Tetrahydrocannabinol (THC) and other cannabinoids inhibit tumour growth and angiogenesis in animal models, so their potential application as antitumoral drugs has been suggested. However, the antitumoral effect of cannabinoids has never been tested in humans. Here we report the first clinical study aimed at assessing cannabinoid antitumoral action, specifically a pilot phase I trial in which nine patients with recurrent glioblastoma multiforme were administered THC intratumoraly. The patients had previously failed standard therapy (surgery and radiotherapy) and had clear evidence of tumour progression. The primary end point of the study was to determine the safety of intracranial THC administration. We also evaluated THC...

The plant cannabinoid Δ9-tetrahydrocannabinol and the endocannabinoid anandamide increase the amount of sleep via a CB1 receptor mediated mechanism. Here, we explored the use of a novel electroencephalogram (EEG) recording device based on wireless EEG microchip technology (Neurologger) in freely-moving rats, and its utility in experiments of cannabinoidsinduced alterations of EEG/vigilance stages. EEG was recorded through epidural electrodes placed above pre-frontal and parietal cortex (overlaying the dorsal hippocampus). As cannabinoids, we acutely administered the full synthetic CB1 receptor agonist, WIN55,212-2 (1 mg/kg), and the antagonist/inverse agonist, AM251 (2 mg/kg), either alone or together through the intraperitoneal route. WIN55,212-2 increased the total amount of NREM...

Background: Spasticity is a disabling complication of multiple sclerosis, affecting many patients with the condition. We report the first Phase 3 placebo-controlled study of an oral antispasticity agent to use an enriched study design. Methods: A 19-week follow-up, multicentre, double-blind, randomized, placebo-controlled, parallel-group study in subjects with multiple sclerosis spasticity not fully relieved with current antispasticity therapy, Subjects were treated with nabiximols, as add-on therapy, in a single-blind manner for 4 weeks, after which those achieving an improvement in spasticity of 20% progressed to a 12-week randomized, placebo controlled phase. Results: Of the 572 subjects enrolled, 272 achieved a 20% improvement after 4 weeks...

Charlotte, a little girl with SCN1A-confirmed Dravet syndrome, was recently featured in a special that aired on CNN. Through exhaustive personal research and assistance from a Colorado-based medical marijuana group (Realm of Caring), Charlotte’s mother started adjunctive therapy with a high concentration cannabidiol/D9 -tetrahydrocannabinol (CBD:THC) strain of cannabis, now known as Charlotte’s Web. This extract, slowly titrated over weeks and given in conjunction with her existing antiepileptic drug regimen, reduced Charlotte’s seizure frequency from nearly 50 convulsive seizures per day to now 2–3 nocturnal convulsions per month. This effect has persisted for the last 20 months, and Charlotte has been successfully weaned from her...

This study examines the current knowledge of physiological and clinical effects of tetrahydrocannabinol (THC) and cannabidiol (CBD) and presents a rationale for their combination in pharmaceutical preparations. Cannabinoid and vanilloid receptor effects as well as non-receptor mechanisms are explored, such as the capability of THC and CBD to act as anti-inflammatory substances independent of cyclo-oxygenase (COX) inhibition. CBD is demonstrated to antagonise some undesirable effects of THC including intoxication, sedation and tachycardia, while contributing analgesic, anti-emetic, and anti-carcinogenic properties in its own right. In modern clinical trials, this has permitted the administration of higher doses of THC, providing evidence for clinical efficacy and safety...

The object of the experiment was to verify whether cannabidiol (CBD) reduces the anxiety provoked by d9-THC in normal volunteers, and whether this effect occurs by a general block of the action of d9-THC or by a specific anxiolytic effect. Appropriate measurements and scales were utilized and the eight volunteers received, the following treatments in a double-blind procedure : 0.5 mg/kg d9-THC, 1 mg/kg CBD, a mixture containing 0.5 mg/kg d9-THC and 1 mg/kg CBD, and placebo and diazepam (10 mg) as controls. Each volunteer received the treatments in a different sequence. It was verified that CBD blocks the anxiety provoked by d9-THC, however...