Peripheral, but not central effects of cannabidiol derivatives: mediation by CB(1) and unidentified receptors.

“Delta-9 tetrahydrocannabinol (Delta(9)-THC) and (-)-cannabidiol ((-)-CBD) are major constituents of the Cannabis sativa plant with different pharmacological profiles…

We tested a series of (+)- and (-)-CBD derivatives for central and peripheral effects in mice…

We suggest that (+)-CBD analogues have mixed agonist/antagonist activity in the brain.

Second, (-)-CBD analogues which are devoid of cannabinoid receptor affinity but which inhibit intestinal motility, suggest the existence of a non-CB(1), non-CB(2) receptor.

Therefore, such analogues should be further developed as antidiarrheal and/or antiinflammatory drugs.

We propose to study the therapeutic potential of (-)- and (+)-CBD derivatives for complex conditions such as inflammatory bowel disease and cystic fibrosis.”

http://www.ncbi.nlm.nih.gov/pubmed/15910887

Antipsychotic profile of cannabidiol and rimonabant in an animal model of emotional context processing in schizophrenia.

“Clinical and neurobiological findings suggest that cannabinoids and their receptors are implicated in schizophrenia. Cannabidiol (CBD), a non-psychotomimetic compound of the Cannabis sativa plant, has been reported to have central therapeutic actions, such as antipsychotic and anxiolytic effects…

Our results suggest a potential therapeutical effect of CBD and rimonabant to treat the emotional processing impairment presented in schizophrenia.

In addition, our results reinforce the anxiolytic profile of CBD.”

http://www.ncbi.nlm.nih.gov/pubmed/22716146

Protective Effects of Cannabidiol Against Hippocampal Cell Death and Cognitive Impairment Induced by Bilateral Common Carotid Artery Occlusion in Mice.

“The present study investigated whether cannabidiol (CBD), a major non-psychoactive constituent of marijuana, protects against hippocampal neurodegeneration and cognitive deficits induced by brain ischemia in adult mice…

These findings suggest a protective effect of CBD on neuronal death induced by ischemia and indicate that CBD might exert beneficial therapeutic effects in brain ischemia. The mechanisms that underlie the neuroprotective effects of CBD in BCCAO mice might involve the inhibition of reactive astrogliosis.”

http://www.ncbi.nlm.nih.gov/pubmed/24532152

Physiological intestinal oxygen modulates the Caco-2 cell model and increases sensitivity to the phytocannabinoid cannabidiol.

“The Caco-2 cell model is widely used as a model of colon cancer… these cells were more sensitive to cannabidiol-induced antiproliferative actions through changes in cellular energetics…

These effects could impact on its development as an anticancer therapeutic…”

http://www.ncbi.nlm.nih.gov/pubmed/24464350

5-Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid.

“It has been recently reported that cannabidiol (CBD), a non-psychoactive cannabinoid, is able to kill glioma cells, both in vivo and in vitro, independently of cannabinoid receptor stimulation.

…the present investigation indicates that CBD exerts its antitumoral effects through modulation of the LOX pathway and of the endocannabinoid system…”

http://www.ncbi.nlm.nih.gov/pubmed/18028339

Who Benefits Most from THC:CBD Spray? Learning from Clinical Experience.

“In this article, real-life data from clinical practice showing specific aspects relating to use of 9-delta-tetrahydocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex®) in patients with moderate to severe spasticity resistant to usual therapy will be presented…

These case reports highlight the diverse nature of the MS spasticity population and they show the possible usefulness of THC:CBD oromucosal spray in individual patients with moderate to severe spasticity resistant to existing therapies…

Perhaps the most important finding is the possibility of obtaining relevant improvements in QoL/ADL (quality of life/activities of daily living) in some patients with resistant MS spasticity, allowing them to engage back in physical and social activities.”

http://www.ncbi.nlm.nih.gov/pubmed/24457847

THC:CBD Spray and MS Spasticity Symptoms: Data from Latest Studies.

“New clinical experience with 9-delta-tetrahydocannabinol (THC) and cannabidiol (CBD) oromucosal spray (Sativex®)…

A randomized, placebo controlled long-term follow-up clinical trial with THC:CBD spray versus placebo demonstrated that it was not associated with cognitive decline, depression or significant mood changes…

THC:CBD oromucosal spray did not adversely influence standard driving ability in patients with moderate to severe MS spasticity…

Findings to date reinforce the efficacy and safety observed in Phase III clinical trials…

Importantly, no additional safety concerns were identified…

Thus, these new data support a positive benefit-risk relationship for THC:CBD oromucosal spray during longer-term use.”

http://www.ncbi.nlm.nih.gov/pubmed/24457846

Nabiximols as an Agonist Replacement Therapy During Cannabis Withdrawal: A Randomized Clinical Trial.

“The cannabis extract nabiximols (Sativex), developed as a multiple sclerosis treatment, offers a potential agonist medication for cannabis withdrawal…

Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal…

The data support further evaluation of nabiximols for management of cannabis dependence and withdrawal in treatment-seeking populations.”

http://www.ncbi.nlm.nih.gov/pubmed/24430917

The Novel Endocannabinoid Receptor GPR18 is Expressed in the Rostral Ventrolateral Medulla and Exerts Tonic Restraining Influence on Blood Pressure.

“Systemic administration of the GPR18 agonist abnormal cannabidiol (Abn CBD) lowers blood pressure (BP).

These findings are the first to demonstrate GPR18 expression in the RVLM, and to suggest sympathoinhibitory role for this receptor. The findings yield new insight into the role of a novel cannabinoid receptor (GPR18) in central BP control.”

http://www.ncbi.nlm.nih.gov/pubmed/24431468PR

A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment.

“Peripheral neuropathic pain (PNP) associated with allodynia poses a significant clinical challenge. The efficacy of Δ9 -tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray, a novel cannabinoid formulation, was investigated in this 15-week randomized, double-blind, placebo-controlled parallel group study…

These findings demonstrate that, in a meaningful proportion of otherwise treatment-resistant patients, clinically important improvements in pain, sleep quality and SGIC of the severity of their condition are obtained with THC/CBD spray. THC/CBD spray was well tolerated and no new safety concerns were identified.”

http://www.ncbi.nlm.nih.gov/pubmed/24420962