Tag Archives: CBD

Antitumor Effects of Cannabidiol, a Nonpsychoactive Cannabinoid, on Human Glioma Cell Lines

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“Marijuana and its derivatives have been used in medicine for many centuries, and currently there is a renewed interest in the study of the therapeutic effects of cannabinoids…”

“Recently, cannabinoids (CBs) have been shown to possess antitumor properties. Because the psychoactivity of cannabinoid compounds limits their medicinal usage, we undertook the present study to evaluate the in vitro antiproliferative ability of cannabidiol (CBD), a nonpsychoactive cannabinoid compound, on U87 and U373 human glioma cell lines…”

“…the nonpsychoactive CBD was able to produce a significant antitumor activity both in vitro and in vivo, thus suggesting a possible application of CBD as an antineoplastic agent.”

“In conclusion, a cannabinoid-based therapeutic strategy for neural diseases devoid of undesired psychotropic side effects could find in CBD a valuable compound in cancer therapies along with the perspective of evaluating a synergistic effect with other cannabinoid molecules and/or with other chemotherapeutic agents as well as with radiotherapy. Whatever the precise mechanism underlying the CBD effects, the present results suggest a possible application of CBD as a promising, nonpsychoactive, antineoplastic agent.”

http://jpet.aspetjournals.org/content/308/3/838.full

Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L

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“The antidepressant action of cannabis as well as the interaction between antidepressants and the endocannabinoid system has been reported. This study was conducted to assess the antidepressant-like activity of Δ9-THC and other cannabinoids… Results of this study show that Δ9-THC and other cannabinoids exert antidepressant-like actions, and thus may contribute to the overall mood-elevating properties of cannabis.”

“Cannabis sativa L. is one of the most widely used plants for both recreational and medicinal purposes. To date a total of 525 natural constituents covering several chemical classes have been isolated and identified from C. sativa. The cannabinoids belong to the chemical class of terpenophenolics, of which 85 have been uniquely identified in cannabis, including the most psychoactive cannabinoid, Δ9-tetrahydrocannabinol (Δ9-THC). The most common natural plant cannabinoids (phytocannabinoids) are: Δ9-THC, cannabidiol (CBD), cannabigerol (CBG), cannabichromene (CBC), and cannabinol (CBN). Several of the identified cannabinoids are both chemically and pharmacologically poorly characterized due to insufficient isolated amounts; however, the pharmacology of Δ9-THC has been widely studied, and it is regarded as the main psychoactive constituent of cannabis.”

“The psychological and physiological effects of cannabis have been extensively characterized, including euphoria, analgesia, sedation, memory and cognitive impairment, appetite stimulation, and anti-emesis. Most of these effects have been primarily attributed to Δ9-THC. Major advances in the field of cannabinoid research were achieved following the unraveling of the molecular mechanism underlying the actions of Δ9-THC and the discovery of the endocannabinoid system. The endocannabinoid system is regarded as a neuromodulator, and is comprised of cannabinoid receptors (primarily CB1 and CB2 receptors), their endogenous ligands, and enzymes responsible for the synthesis and metabolism of these ligands.”

“In addition to the established effects of cannabis, it is well recognized that mood elevation is one of the components of the complex experience elicited by cannabis. Much of our knowledge regarding cannabis effect on mood and anxiety is based on individual reports following cannabis use for medicinal or recreational purposes. Several anecdotal reports describe the antidepressant effect of cannabis, with patients confirming beneficial outcomes from its use in primary or secondary depressive disorders…”

“In conclusion, our results show that phytocannabinoids, including Δ9-THC, CBD, and CBC, exert antidepressant-like actions in animal models of behavioral despair. The exact mechanism underlying such activity is still unclear and confounded by the fact that these compounds have varying binding profiles to the established cannabinoid CB1 as well as to non CB1 receptors. The results support the effect of phytocannabinoids on mood disorders and provide potential leads for further studies.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866040/

Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors

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 “Extracts of the Cannabis sativa plant elicit in humans a complex subjective experience that includes euphoria, heightened sensitivity to external stimuli and relaxation. This plant contains more than 400 different compounds, of which 66 are termed cannabinoids. Δ9-tetrahydrocannabinol (Δ9-THC), one of the major constituents of C. sativa extracts is thought to account for most of the effects of cannabis through the activation of cannabinoid CB1 receptors in the brain….The major endogenous agonists of the CB1 receptor are anandamide and 2-arachidonoyl glycerol, referred to as endocannabinoids…”

“It has recently been suggested that the endocannabinoid system may be involved in the pathophysiology of depression. This is supported by several pieces of evidence showing that endocannabinoids and CB1 receptors are widely distributed in brain areas that are often related to affective disorders and that their expression is regulated by antidepressant drugs. Moreover, administration of inhibitors of anandamide uptake or metabolism, as well as CB1 receptor agonists induces antidepressant-like effects in different animal models. In accordance with these preclinical results, many patients report benefits from cannabis use in depressive syndromes…”

“Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that induces anxiolytic- and antipsychotic-like effects in animal models. Effects of CBD may be mediated by the activation of 5-HT1A receptors. As 5-HT1A receptor activation may induce antidepressant-like effects, the aim of this work was to test the hypothesis that CBD would have antidepressant-like activity in mice as assessed by the forced swimming test. We also investigated if these responses depended on the activation of 5-HT1A receptors and on hippocampal expression of brain-derived neurotrophic factor (BDNF).”

“Conclusion and implications:

CBD induces antidepressant-like effects comparable to those of imipramine. These effects of CBD were probably mediated by activation of 5-HT1A receptors.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823358/

Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial.

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 “Patients with advanced cancer who have pain that responds poorly to opioid therapy pose a clinical challenge. Nabiximols (Nabiximols is the U.S. Adopted Name [USAN] for Sativex [GW Pharma Ltd, Wiltshire, U.K.], which does not yet have an INN), a novel cannabinoid formulation, is undergoing investigation as add-on therapy…

This study supports the efficacy and safety of nabiximols at the 2 lower-dose levels and provides important dose information for future trials.

 PERSPECTIVE: Nabiximols, a novel cannabinoid formulation, may be a useful add-on analgesic for patients with opioid-refractory cancer pain. A randomized, double-blind, placebo-controlled, graded-dose study demonstrated efficacy and safety at low and medium doses.”

http://www.ncbi.nlm.nih.gov/pubmed/22483680

Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain.

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“This study compared the efficacy of a tetrahydrocannabinol:cannabidiol (THC:CBD) extract, a nonopioid analgesic endocannabinoid system modulator, and a THC extract, with placebo, in relieving pain in patients with advanced cancer. This study shows that THC:CBD extract is efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids.”  http://www.ncbi.nlm.nih.gov/pubmed/19896326

“In conclusion, THC:CBD extract, a nonopioid analgesic, endocannabinoid system modulator, has been shown to be a useful adjunctive treatment for relief of pain in patients with advanced cancer who experience inadequate analgesia despite chronic opioid therapy. The reductions in pain scores were neither because of a change in opioid background medications nor because of an increase in use of breakthrough medication. Therefore, we can conclude that the observed reduction in pain scores is attributable to the positive analgesic effects of THC:CBD extract.” http://www.jpsmjournal.com/article/S0885-3924(09)00787-8/fulltext

An Open-Label Extension Study to Investigate the Long-Term Safety and Tolerability of THC/CBD Oromucosal Spray and Oromucosal THC Spray in Patients With Terminal Cancer-Related Pain Refractory to Strong Opioid Analgesics.

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  “Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group.

OBJECTIVES:

This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer.

CONCLUSION:

This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit.”

http://www.ncbi.nlm.nih.gov/pubmed/23141881

Treatment of Tourette syndrome with cannabinoids.

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Abstract

“Cannabinoids have been used for hundred of years for medical purposes. To day, the cannabinoid delta-9-tetrahydrocannabinol (THC) and the cannabis extract nabiximols are approved for the treatment of nausea, anorexia and spasticity, respectively. In Tourette syndrome (TS) several anecdotal reports provided evidence that marijuana might be effective not only in the suppression of tics, but also in the treatment of associated behavioural problems. At the present time there are only two controlled trials available investigating the effect of THC in the treatment of TS. Using both self and examiner rating scales, in both studies a significant tic reduction could be observed after treatment with THC compared to placebo, without causing significant adverse effects. Available data about the effect of THC on obsessive-compulsive symptoms are inconsistent. According to a recent Cochrane review on the efficacy of cannabinoids in TS, definite conclusions cannot be drawn, because longer trials including a large number of patients are missing. Notwithstanding this appraisal, by many experts THC is recommended for the treatment of TS in adult patients, when first line treatments failed to improve the tics. In treatment resistant adult patients, therefore, treatment with THC should be taken into consideration.”

http://www.ncbi.nlm.nih.gov/pubmed/23187140

Would some cannabinoids ameliorate symptoms of autism?

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“Cannabidiol (CBD) is a major nonpsychotropic constituent of cannabis sativa, which unlike the other major constituent delta9-tetrahydrocannabinol (delta9-THC), is virtually inactive at both of its central nervous system receptors. In one study, cell-based calcium mobilization and electrophysiological assays were used to identify and characterize several novel cannabinoid TRPV2 agonists in cultured rat dorsal root ganglion neurons. Among these, CBD was found to be the most robust and potent, followed by delta9-THC and cannabinol. Those cannabinoids may, accordingly, possess the ability, due to their action as TRPV2 agonists, to increase the release of both oxytocin and vasopressin enhancing the stimulation of oxytocin receptor and V1a receptors at the same time. CBD displays a plethora of other actions including anticonvulsive, sedative, hypnotic, antipsychotic, anti-inflammatory and neuroprotective properties. CBD and delta9-THC are components of drugs commercialized, in certain countries, as treatments for neuropathic pain, overactive bladder, and spasticity in patients suffering from multiple sclerosis. Thus, despite their action on oxytocin and vasopressin release, CBD and delta9-THC may help in improving symptoms of ASD by their sedative, antipsychotic, anticonvulsant and tranquilizing effects. In addition, the cannabinoid system has already been shown to be implicated in social behavior in rats.
 
The administration of cannabinoids for children and adolescents suffering from ASD is a controversial legal and ethical issue. Instead, those cannabinoids may be tested when administered to animals presenting autistic symptoms. Animal models of autistic symptoms exist especially in rodents that have their oxytocin and/or vasopressin function impaired such as mice or rats lacking the oxytocin or vasopressin gene or one of their receptors]. Whenever cannabinoids were found efficient in animal models of autism, the rationale supporting their efficacy may outweigh their legal and ethical adversities, when administered to children in the setting of randomized controlled studies.”
 

Inhibition of Human Neutrophil Chemotaxis by Endogenous Cannabinoids and Phytocannabinoids: Evidence for a Site Distinct from CB1 and CB2

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   “Here, we show a novel pharmacology for inhibition of human neutrophil migration by endocannabinoids, phytocannabinoids, and related compounds. The endocannabinoids virodhamine and N-arachidonoyl dopamine are potent inhibitors of N-formyl-l-methionyl-l-leucyl-l-phenylalanine-induced migration of human neutrophils…”

   “This study reveals that certain endogenous lipids, phytocannabinoids and related ligands are potent inhibitors of human neutrophil migration, and it implicates a novel pharmacological target distinct from cannabinoid CB1 and CB2 receptors; this target is antagonized by the endogenous compound N-arachidoloyl l-serine. These findings corroborate the emerging clinical and animal model data demonstrating that the nonpsychoactive phytocannabinoid, CBD and its structural analogs are effective in alleviating arthritis. Furthermore, our findings have implications for the potential pharmacological manipulation of elements of the endocannabinoid system for the treatment of various inflammatory conditions.”

http://molpharm.aspetjournals.org/content/73/2/441.long

Non-CB1, non-CB2 receptors for endocannabinoids, plant cannabinoids, and synthetic cannabimimetics: focus on G-protein-coupled receptors and transient receptor potential channels.

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Abstract

“The molecular mechanism of action of Delta(9)-tetrahydrocannabinol (THC), the psychotropic constituent of Cannabis, has been a puzzle during the three decades separating its characterization, in 1964, and the cloning, in the 1990s, of cannabinoid CB1 and CB2 receptors. However, while these latter proteins do mediate most of the pharmacological actions of THC, they do not seem to act as receptors for other plant cannabinoids (phytocannabinoids), nor are they the unique targets of the endogenous lipids that were originally identified in animals as agonists of CB1 and CB2 receptors, and named endocannabinoids. Over the last decade, several potential alternative receptors for phytocannabinoids, endocannabinoids, and even synthetic cannabimimetics, have been proposed, often based uniquely on pharmacological evidence obtained in vitro. In particular, the endocannabinoid anandamide, and the other most abundant Cannabis constituent, cannabidiol, seem to be the most “promiscuous” of these compounds. In this article, we review the latest data on the non-CB1, non-CB2 receptors suggested so far for endocannabinoids and plant or synthetic cannabinoids, and lay special emphasis on uncharacterized or orphan G-protein-coupled receptors as well as on transient receptor potential channels.”

http://www.ncbi.nlm.nih.gov/pubmed/19847654