An anecdotal report of gynecomastia in chronic cannabis smokers [1] stimulated research into the effect of cannabis on male hormones [2,3]. A causal association between cannabis and gynecomastia was hypothesized based on the structural similarity of tetrahydrocannabinol (THC) and estradiol. Moreover, tetrahydrocannabinol was shown to directly stimulate development in rat breast tissue [4]. Although laboratory investigations on human subjects provided conflicting results regarding the effects of cannabis use on testosterone levels [2,3], one study failed to demonstrate any influence of intensive cannabis use on prolactin levels [2]. The present report is a case-control study of gynecomastia in a military population-US Army soldiers in Nuremberg,...

A hemp oil product (Hemp Liquid Gold TM) was purchased from a specialty food store. Fifteen milliliters was consumed by seven adult volunteers. Urine samples were taken from the subjects before ingestion and at 8, 24, and 48 h after the dose was taken. All specimens were screened by enzyme immunoassay with SYVA EMIT II THC 20, THC 50, and THC 100 kits. The tetrahydrocannabinol carboxylic acid (THCA) concentration was determined on all samples by gas chromatography-mass spectrometry (GC-MS) (5). A total of 18 postingestion samples were submitted. Fourteen of the samples screened above the 20-ng cutoff, seven were above the 50-ng cutoff, and...

Marijuana is one of the most abused drugs due to its psychotropic effects. Interestingly, it is also used for medicinal purposes. The main psychotropic component in marijuana, Δ 9 - tetrahydrocannabinol (THC), has also been shown to mediate potent anti-inflammatory properties. Whether the immunomodulatory activity of THC is mediated by epigenetic regulation has not been investigated previously. In this study, we employed ChIP-Seq technology to examine the in vivo effect of THC on global histone methylation in lymph node cells of mice immunized with a superantigen, staphylococcal enterotoxin B (SEB). We compared genome-wide histone H3K4, H3K27, H3K9, H3K36 trimethylation and H3K9 acetylation patterns in...

In this study, we report the isolation from canine intestines of 2-arachidonyl glycerol (2-Ara-Gl). Its structure was determined by mass spectrometry and by direct comparison with a synthetic sample. 2-Ara-Gl bound to membranes from cells transiently transfected with expression plasmids carrying DNA of either CB1 or CB2--the two cannabinoid receptors identified thus far--with Ki values of 472 +/- 55 and 1400 +/- 172 nM, respectively. In the presence of forskolin, 2-Ara-Gl inhibited adenylate cyclase in isolated mouse spleen cells, at the potency level of delta 9-tetrahydrocannabinol (delta 9-THC). Upon intravenous administration to mice, 2-Ara-Gl caused the typical tetrad of effects produced by THC: antinociception,...

Introduction: In recent research, orally administered cannabidiol (CBD) showed a relatively high incidence of somnolence in a pediatric population. Previous work has suggested that when CBD is exposed to an acidic environment, it degrades to D9 -tetrahydrocannabinol (THC) and other psychoactive cannabinoids. To gain a better understanding of quantitative exposure, we completed an in vitro study by evaluating the formation of psychoactive cannabinoids when CBD is exposed to simulated gastric fluid (SGF). Methods: Materials included synthetic CBD, D8 -THC, and D9 -THC. Linearity was demonstrated for each component over the concentration range used in this study. CBD was spiked into media containing 1% sodium...

Background: The two main constituents of cannabis, cannabidiol and D9 -tetrahydrocannabinol (THC), have opposing effects both pharmacologically and behaviourally when administered in the laboratory. Street cannabis is known to contain varying levels of each cannabinoid. Aims To study how the varying levels of cannabidiol and THC have an impact on the acute effects of the drug in naturalistic settings. Method: Cannabis users (n = 134) were tested 7 days apart on measures of memory and psychotomimetic symptoms, once while they were drug free and once while acutely intoxicated by their own chosen smoked cannabis. Using an unprecedented methodology, a sample of cannabis (as well...

Background: Neuroblastoma (nbl) is one of the most common solid cancers in children. Prognosis in advanced nbl is still poor despite aggressive multimodality therapy. Furthermore, survivors experience severe long-term multi-organ sequelae. Hence, the identification of new therapeutic strategies is of utmost importance. Cannabinoids and their derivatives have been used for years in folk medicine and later in the field of palliative care. Recently, they were found to show pharmacologic activity in cancer, including cytostatic, apoptotic, and antiangiogenic effects. Methods: We investigated, in vitro and in vivo, the anti-nbl effect of the most active compounds in Cannabis, Δ9-tetrahydrocannabinol (thc) and cannabidiol (cbd). We set out...

Previous studies have suggested that marijuana (cannabis sativa) and delta-9-tetrahydrocannabinol (D9-THC), the major psychoactive ingredient of marijuana, are effective in the therapy of tics and associated behavioral disorders in Tourette Syndrome (TS). Because there is also evidence that cannabis sativa may cause cognitive impairment in healthy users, we performed a randomized double-blind placebocontrolled crossover trial for D9-THC in 12 adult TS patients to investigate whether treatment of TS with a single dose of D9-THC at 5.0 to 10.0 mg causes significant side effects on neuropsychological performance. Using a variety of neuropsychological tests, we found no significant differences after treatment with D9-THC compared to placebo...

Abstract Purpose: Colon cancer is a major public health problem. Cannabis-based medicines are useful adjunctive treatments in cancer patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS, i.e. CBD botanical drug substance, on colorectal cancer cell proliferation and in experimental models of colon cancer in vivo. Methods: Proliferation was evaluated in colorectal carcinoma (DLD-1 and HCT116) as well as in healthy colonic cells using the MTT assay. CBD BDS binding was evaluated by its ability to displace [(3)H]CP55940 from human cannabinoid CB1 and CB2 receptors. In vivo, the effect of CBD BDS...

The cannabinoid receptor agonist delta9 -tetrahydrocannabinol (THC) enhances the antinociceptive effects of mu opioid receptor agonists, raising the possibility of using a combination of THC and opioids for treating pain. This study examined the effects of noncontingent and contingent administration of THC on i.v. heroin self-administration in rhesus monkeys. Self-administration of different unit doses of heroin (0.0001–0.1 mg/kg/infusion) generated a typical inverted U-shaped dose-response curve. In one experiment (n=4), noncontingent THC (0.1–1.0 mg/kg) dosedependently shifted the heroin dose-response curve downward in three monkeys and slightly leftward in one monkey. In a second experiment (n=4), monkeys could self-administer THC alone (0.0032–0.032 mg/kg/infusion), heroin alone, or...