Background: The use of medical cannabis is increasing, most commonly for pain, anxiety and depression. Emerging data suggest that use and abuse of prescription drugs may be decreasing in states where medical cannabis is legal. The aim of this study was to survey cannabis users to determine whether they had intentionally substituted cannabis for prescription drugs. Methods: A total of 2,774 individuals were a self-selected convenience sample who reported having used cannabis at least once in the previous 90 days. Subjects were surveyed via an online anonymous questionnaire on cannabis substitution effects. Participants were recruited through social media and cannabis dispensaries in Washington State....

Cannabidiol (CBD) is a major, biologically active, but psycho-inactive component of cannabis. In this cell culture-based report, CBD is shown to displace the agonist, [3H]8-OHDPAT from the cloned human 5-HT1a receptor in a concentration-dependent manner. In contrast, the major psychoactive component of cannabis, tetrahydrocannabinol (THC) does not displace agonist from the receptor in the same micromolar concentration range. In signal transduction studies, CBD acts as an agonist at the human 5-HT1a receptor as demonstrated in two related approaches. First, CBD increases [35S]GTPcS binding in this G protein coupled receptor system, as does the known agonist serotonin. Second, in this GPCR system, that is negatively...

Context: Marijuana smoke contains many of the same constituents as tobacco smoke, but whether it has similar adverse effects on pulmonary function is unclear. Objective: To analyze associations between marijuana (both current and lifetime exposure) and pulmonary function. Design, Setting, and Participants: The Coronary Artery Risk Development in Young Adults (CARDIA) study, a longitudinal study collecting repeated measurements of pulmonary function and smoking over 20 years (March 26, 1985-August 19, 2006) in a cohort of 5115 men and women in 4 US cities. Mixed linear modeling was used to account for individual age-based trajectories of pulmonary function and other covariates including tobacco use, which...

Aims: This study tested whether adolescents who used cannabis or met criteria for cannabis dependence showed neuropsychological impairment prior to cannabis initiation and neuropsychological decline from before to after cannabis initiation. Design: A longitudinal co-twin control study. Setting and Participants: Participants were 1,989 twins from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of twins born in England and Wales from 1994-1995. Measurements: Frequency of cannabis use and cannabis dependence were assessed at age 18. Intelligence quotient (IQ) was obtained at ages 5, 12, and 18. Executive functions were assessed at age 18. Findings: Compared with adolescents who did not...

Objectives. Marijuana is the most commonly used illicit drug during pregnancy. Due to high lipophilicity, cannabinoids can easily penetrate physiological barriers like the human placenta and jeopardize the developing fetus. We evaluated the impact of cannabidiol (CBD), a major non-psychoactive cannabinoid, on P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) expression, and P-gp function in a placental model, BeWo and Jar choriocarcinoma cell lines (using P-gp induced MCF7 cells (MCF7/P-gp) for comparison). Study design. Following the establishment of the basal expression of these transporters in the membrane fraction of all three cell lines, P-gp and BCRP protein and mRNA levels were determined following chronic...

It is now well established that the psychoactive effects of Cannabis sativa are primarily mediated through neuronal CB1 receptors, while its therapeutic immune properties are primarily mediated through CB2 receptors. Two endocannabinoids, arachidonoylethanolamide and 2-arachidonoylglycerol, have been identifi ed, their action on CB1 and CB2 thoroughly characterized, and their production and inactivation elucidated. However, many signifi cant exceptions to these rules exist. Here we review the evidence suggesting that cannabinoids can modulate synaptic transmission, the cardiovascular system, and the immune system through receptors distinct from CB1 and CB2, and that an additional “ independent ” endocannabinoid signaling system that involves palmitoylethanolamide may exist.

The effect of cannabimimetic agents on the function of immune cells such as T and B lymphocytes, natural killer cells and macrophages has been extensively studied over the past several decades using human and animal paradigms involving whole animal models as well as tissue culture systems. From this work, it can be concluded that these drugs have subtle yet complex effects on immune cell function and that some of the drug activity is mediated by cannabinoid receptors expressed on the various immune cell subtypes. However, the overall role of the cannabinoid system of receptors and ligands in human health and disease is still unclear...

The active component of marijuana, D9 -tetrahydrocannabinol, activates the CB1 and CB2 cannabinoid receptors, thus mimicking the action of endogenous cannabinoids. CB1 is predominantly neuronal and mediates the cannabinoid psychotropic effects. CB2 is predominantly expressed in peripheral tissues, mainly in pathological conditions. So far the main endocannabinoids, anandamide and 2-arachidonoylglycerol, have been found in bone at ‘brain’ levels. The CB1 receptor is present mainly in skeletal sympathetic nerve terminals, thus regulating the adrenergic tonic restrain of bone formation. CB2 is expressed in osteoblasts and osteoclasts, stimulates bone formation, and inhibits bone resorption. Because low bone mass is the only spontaneous phenotype so far reported...

A central tenet underlying the use of botanical remedies is that herbs contain many active ingredients. Primary active ingredients may be enhanced by secondary compounds, which act in beneficial synergy. Other herbal constituents may mitigate the side effects of dominant active ingredients. We reviewed the literature concerning medical cannabis and its primary active ingredient, Δ9-tetrahydrocannabinol (THC). Good evidence shows that secondary compounds in cannabis may enhance the beneficial effects of THC. Other cannabinoid and non-cannabinoid compounds in herbal cannabis or its extracts may reduce THC-induced anxiety, cholinergic deficits, and immunosuppression. Cannabis terpenoids and flavonoids may also increase cerebral blood flow, enhance cortical activity, kill...

Many constituents of cannabis exhibit beneficial anti-inflammatory properties, such as 9-tetrahydrocannabinol (THC) in marijuana and gamma-linolenic acid (GLA) in hemp seed oil. The effects of these cannabis constituents on eicosanoid metabolism is reviewed. THC and GLA modulate the arachidonic acid cascade, inhibiting the production of series 2 prostaglandins and series 4 leukotrienes. Cannabinoid receptor- as well as non-receptor-mediated signal transduction pathways appear to be involved. It is proposed that THC acts as a selective cyclooxygenase-2 (COX-2) inhibitor.