PubMed.gov is the US National Library of Medicine Nation Institutes of Health. Pubmed comprises more than 24 million citations for biomedical literaturs from MEDLINE, life science journals, and online books.
Cannabidiol: promise and pitfalls.
Abstract: Over the past few years, increasing public and political pressure has supported legalization of medical marijuana. One of the main thrusts in this effort has related to the treatment of refractory epilepsy-especially in children with Dravet syndrome-using cannabidiol (CBD). Despite initiatives in numerous states to at least legalize possession of CBD oil for treating epilepsy, little published evidence is available to prove or disprove the efficacy and safety of CBD in patients with epilepsy. This review highlights some of the basic science theory behind the use of CBD, summarizes published data on clinical use of CBD for epilepsy, and highlights issues related to the use of currently available CBD products. Cannabidiol is the major nonpsychoactive component of Cannabis sativa. Over the centuries, a number of medicinal preparations derived from C. sativa have been employed for a variety of disorders, including gout, rheumatism, malaria, pain, and fever. These preparations were widely employed as analgesics by Western medical practitioners in the 19(th) century (1). More recently, there is clinical evidence suggesting efficacy in HIV-associated neuropathic pain, as well as spasms associated with multiple sclerosis (1).
Blurred boundaries: the therapeutics and politics of medical marijuana.
Abstract: For 5 millennia, Cannabis sativa has been used throughout the world medically, recreationally, and spiritually. From the mid-19th century to the 1930s, American physicians prescribed it for a plethora of indications, until the federal government started imposing restrictions on its use, culminating in 1970 with the US Congress classifying it as a Schedule I substance, illegal, and without medical value. Simultaneous with this prohibition, marijuana became the United States' most widely used illicit recreational drug, a substance generally regarded as pleasurable and relaxing without the addictive dangers of opioids or stimulants. Meanwhile, cannabis never lost its cachet in alternative medicine circles, going mainstream in 1995 when California became the first of 16 states to date to legalize its medical use, despite the federal ban. Little about cannabis is straightforward. Its main active ingredient, δ-9-tetrahydrocannabinol, was not isolated until 1964, and not until the 1990s were the far-reaching modulatory activities of the endocannabinoid system in the human body appreciated. This system's elucidation raises the possibility of many promising pharmaceutical applications, even as draconian federal restrictions that hamstring research show no signs of softening. Recreational use continues unabated, despite growing evidence of marijuana's addictive potential, particularly in the young, and its propensity for inducing and exacerbating psychotic illness in the susceptible. Public approval drives medical marijuana legalization efforts without the scientific data normally required to justify a new medication's introduction. This article explores each of these controversies, with the intent of educating physicians to decide for themselves whether marijuana is panacea, scourge, or both. PubMed searches were conducted using the following keywords: medical marijuana, medical cannabis, endocannabinoid system, CB1 receptors, CB2 receptors, THC, cannabidiol, nabilone, dronabinol, nabiximols, rimonabant, marijuana legislation, marijuana abuse, marijuana dependence, and marijuana and schizophrenia. Bibliographies were hand searched for additional references relevant to clarifying the relationships between medical and recreational marijuana use and abuse.
Cannabinoid CB2 receptors in the gastrointestinal tract: a regulatory system in states of inflammation
Abstract: The emerging potential for the cannabinoid (CB) system in modulating gastrointestinal inflammation has gained momentum over the last few years. Traditional and anecdotal use of marijuana for gastrointestinal disorders, such as diarrhoea and abdominal cramps is recognized, but the therapeutic benefit of cannabinoids in the 21st century is overshadowed by the psychoactive problems associated with CB1 receptor activation. However, the presence and function of the CB2 receptor in the GI tract, whilst not yet well characterized, holds great promise due to its immunomodulatory roles in inflammatory systems and its lack of psychotropic effects. This review of our current knowledge of CB2 receptors in the gastrointestinal tract highlights its role in regulating abnormal motility, modulating intestinal inflammation and limiting visceral sensitivity and pain. CB2 receptors represent a braking system and a pathophysiological mechanism for the resolution of inflammation and many of its symptoms. CB2 receptor activation therefore represents a very promising therapeutic target in gastrointestinal inflammatory states where there is immune activation and motility dysfunction.
Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma.
Abstract: Delta(9)-Tetrahydrocannabinol (THC) exhibits antitumor effects on various cancer cell types, but its use in chemotherapy is limited by its psychotropic activity. We investigated the antitumor activities of other plant cannabinoids, i.e., cannabidiol, cannabigerol, cannabichromene, cannabidiol acid and THC acid, and assessed whether there is any advantage in using Cannabis extracts (enriched in either cannabidiol or THC) over pure cannabinoids. Results obtained in a panel of tumor cell lines clearly indicate that, of the five natural compounds tested, cannabidiol is the most potent inhibitor of cancer cell growth (IC(50) between 6.0 and 10.6 microM), with significantly lower potency in noncancer cells. The cannabidiol-rich extract was equipotent to cannabidiol, whereas cannabigerol and cannabichromene followed in the rank of potency. Both cannabidiol and the cannabidiol-rich extract inhibited the growth of xenograft tumors obtained by s.c. injection into athymic mice of human MDA-MB-231 breast carcinoma or rat v-K-ras-transformed thyroid epithelial cells and reduced lung metastases deriving from intrapaw injection of MDA-MB-231 cells. Judging from several experiments on its possible cellular and molecular mechanisms of action, we propose that cannabidiol lacks a unique mode of action in the cell lines investigated. At least for MDA-MB-231 cells, however, our experiments indicate that cannabidiol effect is due to its capability of inducing apoptosis via: direct or indirect activation of cannabinoid CB(2) and vanilloid transient receptor potential vanilloid type-1 receptors and cannabinoid/vanilloid receptor-independent elevation of intracellular Ca(2+) and reactive oxygen species. Our data support the further testing of cannabidiol and cannabidiol-rich extracts for the potential treatment of cancer.
The insertion and transport of anandamide in synthetic lipid membranes are both cholesterol-dependent.
Abstract: Anandamide is a lipid neurotransmitter which belongs to a class of molecules termed the endocannabinoids involved in multiple physiological functions. Anandamide is readily taken up into cells, but there is considerable controversy as to the nature of this transport process (passive diffusion through the lipid bilayer vs. involvement of putative proteic transporters). This issue is of major importance since anandamide transport through the plasma membrane is crucial for its biological activity and intracellular degradation. The aim of the present study was to evaluate the involvement of cholesterol in membrane uptake and transport of anandamide
Conclusion: Our results demonstrate that cholesterol stimulates both the insertion of anandamide into synthetic lipid monolayers and bilayers, and its transport across bilayer membranes. In this respect, we suggest that besides putative anandamide protein-transporters, cholesterol could be an important component of the anandamide transport machinery. Finally, this study provides a mechanistic explanation for the key regulatory activity played by membrane cholesterol in the responsiveness of cells to anandamide.
Cannabis—A Valuable Drug That Deserves Better Treatment
Abstract: About 150 years ago, a French psychiatrist, J. J. Moreau, conducted a novel clinical experiment in which he administered hashish to humans. His volunteers, including Moreau himself, experienced “occurrences of delirium or of actual madness. …” He concluded that “There is not a single, elementary manifestation of mental illness that cannot be found in the mental changes caused by hashish. …”1 In contrast, most marijuana users today will presumably state that their senses appear enhanced, concomitant with an increase in relaxation and euphoria; while forgetfulness is enhanced, their focus on their surroundings is augmented.
Cannabis Use and Risky Behaviours and Harms: A Comparison of Urban and Rural Populations in Canada
Abstract: Cannabis is the most prevalent illicit substance used by Canadians 15 years of age and older (Health Canada, 2012a). Its use has been linked to a number of both short- and long-term health consequences, including depression, paranoia, cancer, learning problems, and memory and attention deficits (Kalant, 2004). While several studies examined the prevalence of cannabis use by age and sex, fewer studies have examined differences in cannabis use and its related harms and behaviours between urban and rural populations. The results of these studies are mixed; some studies indicate lower cannabis use rates among rural populations compared to urban (Gfroerer, Larson, & Colliver, 2007; Martino, Ellickson, & McCaffrey, 2008), while others suggest higher rates (Coomber et al., 2011). Still others found the rates of cannabis use to be similar between urban and rural populations (Centre for Addiction and Mental Health, 2012; Cronk & Sarvela, 1997; Scheer, Borden, & Donnermeyer, 2000). This paper fills an information gap by comparing contemporary national data on the prevalence of cannabis use and related behaviours and harms between urban and rural populations in Canada. It is intended for policy makers, substance use treatment and prevention program developers, and researchers. The information included in this report can inform efforts aimed at reducing the harms associated with cannabis use, as well as related risky behaviours.
In conclusion, the study failed to detect any meaningful differences between urban and rural populations, both in terms of their cannabis use and of related harms and risky behaviours. The prevalence of cannabis use, particularly among young Canadians, is concerning given its association with cognitive deficits, mental illness and future substance use. Equally concerning is the prevalence of driving after cannabis use as this practice can be just as dangerous as driving after alcohol use. Overall, our findings validate the need to target young people, especially young males, in an effort to reduce these behaviours and their associated harms.
The Inhibitory Effects of Cannabidiol on Systemic Malignant Tumors
Abstract: The recent article by Johnson et al.1 provided for highly stimulating reading. Cannabidiol may attenuate tumor growth in a number of other systemic malignancies. Decreased tumor growth in pulmonary malignancies is seen after administration of cannabidiol. Cannabidiol increases the expression of cyclooxygenase-2 within the cancerous cells.2 Cannabidiol also induces tissue inhibitor of metalloproteinase-1 synthesis and activity. Peroxisome proliferator-activated receptor-gamma expression is augmented at the same time.
Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol
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 was examined on the preneoplastic lesions (aberrant crypt foci), polyps and tumours induced by the carcinogenic agent azoxymethane (AOM) as well as in a xenograft model of colon cancer in mice.
Results: CBD BDS and CBD reduced cell proliferation in tumoral, but not in healthy, cells. The effect of CBD BDS was counteracted by selective CB1 and CB2 receptor antagonists. Pure CBD reduced cell proliferation in a CB1-sensitive antagonist manner only. In binding assays, CBD BDS showed greater affinity than pure CBD for both CB1 and CB2 receptors, with pure CBD having very little affinity. In vivo, CBD BDS reduced AOM-induced preneoplastic lesions and polyps as well as tumour growth in the xenograft model of colon cancer.
Conclusions: CBD BDS attenuates colon carcinogenesis and inhibits colorectal cancer cell proliferation via CB1 and CB2 receptor activation. The results may have some clinical relevance for the use of Cannabis-based medicines in cancer patients.