The illicit recreational drugs cocaine, ecstasy and marijuana have pronounced effects upon sleep. Administration of cocaine increases wakefulness and suppresses REM sleep. Acute cocaine withdrawal is often associated with sleep disturbances and unpleasant dreams. Studies have revealed that polysomnographically assessed sleep parameters deteriorate even further during sustained abstinence, although patients report that sleep quality remains unchanged or improves. This deterioration of objective sleep measures is associated with a worsening in sleep-related cognitive performance. Like cocaine, 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") is a substance with arousing properties. Heavy MDMA consumption is often associated with persistent sleep disturbances. Polysomnography (PSG) studies have demonstrated altered sleep architecture in abstinent...

Purpose: The purpose of this study was to assess the effect on intraocular pressure (IOP) and the safety and tolerability of oromucosal administration of a low dose of delta-9-tetrahydrocannabinol (D-9-THC) and cannabidiol (CBD). Patients and Methods: A randomized, double-masked, placebocontrolled, 4 way crossover study was conducted at a single center, using cannabis-based medicinal extract of D-9-THC and CBD. Six patients with ocular hypertension or early primary open angle glaucoma received a single sublingual dose at 8 AM of 5 mg D-9-THC, 20 mg CBD, 40 mg CBD, or placebo. Main outcome measure was IOP. Secondary outcomes included visual acuity, vital signs, and psychotropic effects....

Cannabis contains various cannabinoids, two of which have almost opposing actions: D9-tetrahydrocannabinol (D9-THC) is psychotomimetic, whereas cannabidiol (CBD) has antipsychotic effects. Hair samples were analysed to examine levels of D9-THC and CBD in 140 individuals. Three clear groups emerged: ‘THC only’, ‘THC+CBD’ and those with no cannabinoid in hair. The THC only group showed higher levels of positive schizophrenia-like symptoms compared with the no cannabinoid and THC+CBD groups, and higher levels of delusions compared with the no cannabinoid group. This provides evidence of the divergent properties of cannabinoids and has important implications for research into the link between cannabis use and psychosis.

D9 -Tetrahydrocannabinol (D9 -THC) is the major psychoactive component of marijuana and elicits pharmacological actions via cannabinoid receptors. Anandamide (AEA) and 2-arachidonoyl-glycerol (2-AG) are endogenous ligands for cannabinoid receptors, which because of their structural similarities to arachidonic acid (AA), AEA, and 2-AG could serve as substrates for lipoxygenases and cyclooxygenases (COXs) that metabolize polyunsaturated fatty acids to potent bioactive molecules. In this study, we have compared the effects of D9 -THC, AEA, 2-AG, and another cannabinoid agonist, indomethacin morpholinylamide (IMMA), on lipopolysaccharide (LPS)- induced NO, IL-6, and PGE2 release from J774 macrophages. D9 -THC, IMMA, and AEA diminish LPS-induced NO and IL-6 production in...

Objective: Cannabis may alleviate some symptoms associated with multiple sclerosis (MS). This study investigated the effect of an orally administered standardized Cannabis sativa plant extract in MS patients with poorly controlled spasticity. Methods: During their inpatient rehabilitation programme, 57 patients were enrolled in a prospective, randomized, double-blind, placebo-controlled crossover study of cannabis-extract capsules standardized to 2.5 mg tetrahydrocannabinol (THC) and 0.9 mg cannabidiol (CBD) each. Patients in group A started with a drug escalation phase from 15 to maximally 30 mg THC by 5 mg per day if well tolerated, being on active medication for 14 days before starting placebo. Patients in group B...

Cyclooxygenase enzymes (COX-1 and COX-2) catalyse the production of prostaglandins from arachidonic acid. Prostaglandins are important mediators in the inflammatory process and their production can be reduced by COX-inhibitors. Endocannabinoids, endogenous analogues of the plant derived cannabinoids, occur normally in the human body. The Endocannabinoids are structurally similar to arachidonic acid and have been suggested to interfere with the inflammatory process. They have also been shown to inhibit cancer cell proliferation. Antiinflammatory effects of cannabinoids and endocannabinoids have been observed, however the mode of action is not yet clarified. Anti-inflammatory activity (i.e., inhibition of COX-2) is proposed to play an important role in the...

Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) occur naturally in marijuana (Cannabis) and may be formulated, individually or in combination in pharmaceuticals such as Marinol or Sativex. While it is known that these hydrophobic compounds can be transported in blood by albumin or lipoproteins, intracellular carrier have not been identified. Recent reports suggest that CBD and THC elevates the levels of the endocannabinoid anandamide (AEA) when administered to humans, suggesting that phytocannabinoids target cellular proteins involved in endocannabinoid clearance. Fatty acid binding proteins (FABPs) are intracellular proteins that mediate AEA transport to its catabolic enzyme fatty acid amide hydrolase (FAAH). By computational analysis and ligand displacement...

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...