Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial.

“Clinical reports indicate that cannabinoids may alleviate pain in different pain conditions, including multiple sclerosis related pain…

Randomised double blind placebo controlled crossover trial… To evaluate the effect of the oral synthetic delta-9-tetrahydrocannabinol dronabinol on central neuropathic pain in patients with multiple sclerosis…

CONCLUSIONS:

Dronabinol has a modest but clinically relevant analgesic effect on central pain in patients with multiple sclerosis. Adverse events, including dizziness, were more frequent with dronabinol than with placebo during the first week of treatment.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC498019/

Gamma-irradiation enhances apoptosis induced by cannabidiol, a non-psychotropic cannabinoid, in cultured HL-60 myeloblastic leukemia cells.

“Two non-psychotropic cannabinoids, cannabidiol (CBD) and cannabidiol-dimethylheptyl (CBD-DMH), induced apoptosis in a human acute myeloid leukemia (AML) HL-60 cell line…

  Caspase-3 activation was observed after the cannabinoid treatment, and may represent a mechanism for the apoptosis.

Our data suggest a possible new approach to treatment of AML.”

http://www.ncbi.nlm.nih.gov/pubmed/14692532

Tetrahydrocannabinol inhibits adenyl cyclase in human leukemia cells.

“Delta 9-tetrahydrocannabinol has been shown to induce incomplete maturation in ML2 human leukemia cell lines.

We extend the observation of its induction of morphologic maturation to HL60 cells and of its induction of growth restriction to HL60 and K562 cells.

 We show that tetrahydrocannabinol reduces the cyclic AMP content of ML2 cells.

 Finally we demonstrate that this agent inhibits adenyl cyclase activity in ML2 cell membrane-enriched fractions.

This finding in myeloid cells is compatible with one hypothesis of cannabinoid action in neuronal cells.”

http://www.ncbi.nlm.nih.gov/pubmed/2154651

Cannabinoids induce incomplete maturation of cultured human leukemia cells.

“Monocyte maturation markers were induced in cultured human myeloblastic ML-2 leukemia cells after treatment for 1-6 days with 0.03-30 microM delta 9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana…

 Cannabinoids induce incomplete maturation of cultured human leukemia cells…

Findings obtained from this system may have important implications for studies of cannabinoid effects on normal human bone-marrow progenitor cells.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC298868/

Therapeutic potential of cannabinoid medicines.

Drug Testing and Analysis

“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.

The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.

In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24006213

http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract

Texas A&M Pharmacy Researcher Fights Cancer, Pain With New Cannabinoid Receptor Drug

DrDaiLu

“Dr. Lu has been working to find new types of chemotherapeutic drugs that both kill pancreatic cancer and suppress the cancer pain at the same time by targeting a special G-protein coupled receptor that belongs to the biological system responsible for the effects of Tetrahydrocannabinol (THC), a compound derived from some varieties of cannabis (hemp) or made synthetically, that is the primary psychoactive agent in marijuana and hashish.

 Dr. Lu says pancreatic cancer cells have more type 2 cannabinoid receptors than do healthy cells.

 Consequently, drug molecules that selectively activate this receptor can induce cancer cell death without affecting normal pancreatic cells, noting that when given to mice with pancreatic tumors, the molecule prevented tumor growth and suppressed the spread of cancer to healthy organs.

 Meanwhile, this class of compounds also generates painkillers comparable to morphine’s pain killing effect…”

More: http://www.bionews-tx.com/news/2013/08/20/texas-am-pharmacy-researcher-fights-cancer-pain-with-new-cannabinoid-receptor-drug/

Evaluation of the role of striatal cannabinoid CB1 receptors on movement activity of parkinsonian rats induced by reserpine.

“It has been observed cannabinoid CB1 receptor signalling and the levels of endocannabinoid ligands significantly increased in the basal ganglia and cerebrospinal fluids of Parkinson’s disease (PD) patients. These evidences suggest that the blocking of cannabinoid CB1 receptors might be beneficial to improve movement disorders as a sign of PD…

 These results support this theory that cannabinoid CB1 receptor antagonists might be useful to alleviate movement disorder in PD…”

http://www.ncbi.nlm.nih.gov/pubmed/23960729

GW Pharmaceuticals Announces Results of MS Spasticity Study Confirming Sativex Has No Long-Term Negative Effect on Cognition

“-Provides Further Evidence of Long-term Efficacy-

GW Pharmaceuticals, a biopharmaceutical company focused on discovering, developing and commercializing novel therapeutics from its proprietary cannabinoid product platform, announces top-line results from a 12 month placebo-controlled study of Sativex in patients with spasticity due to Multiple Sclerosis (MS).

The study results confirm the reassuring safety profile of Sativex and provide further evidence of long-term efficacy.”

More: http://finance.yahoo.com/news/gw-pharmaceuticals-announces-results-ms-060000735.html

Evaluation of the potential of the phytocannabinoids, cannabidivarin (CBDV) and Δ9 -tetrahydrocannabivarin (THCV), to produce CB1 receptor inverse agonism symptoms of nausea in rats.

“The cannabinoid 1(CB1 ) receptor inverse agonists/antagonists, rimonabant (SR141716, SR) and AM251, produce nausea and potentiate toxin-induced nausea by inverse agonism (rather than antagonism) of the CB1 receptor. Here, we evaluated two phytocannabinoids, cannabidivarin (CBDV) and Δ9 -tetrahydrocannabivarin (THCV) for their ability to produce these behavioural effects characteristic of CB1 receptor inverse agonism in rats.

…we investigated the potential of THCV and CBDV to produce conditioned gaping (measure of nausea-induced behaviour),..

THC, THCV  and CBDV suppressed LiCl-induced conditioned gaping, suggesting anti-nausea potential…

The pattern of findings indicates that neither THCV nor CBDV produced a behavioural profile characteristic of CB1 receptor inverse agonists.

As well, these compounds may have therapeutic potential in reducing nausea.”

http://www.ncbi.nlm.nih.gov/pubmed/23902479

Peripherally restricted CB1 receptor blockers.

“Antagonists (inverse agonists) of the cannabinoid-1 (CB1) receptor showed promise as new therapies for controlling obesity and related metabolic function/liver disease.

These agents, representing diverse chemical series, shared the property of brain penetration due to the initial belief that therapeutic benefit was mainly based on brain receptor interaction. However, undesirable CNS-based side effects of the only marketed agent in this class, rimonabant, led to its removal, and termination of the development of other clinical candidates soon followed. Re-evaluation of this approach has focused on neutral or peripherally restricted (PR) antagonists.

Supporting these strategies, pharmacological evidence indicates most if not all of the properties of globally acting agents may be captured by molecules with little brain presence. Methodology that can be used to eliminate BBB penetration and the means (in vitro assays, tissue distribution and receptor occupancy determinations, behavioral paradigms) to identify potential agents with little brain presence is discussed.

Focus will be on the pharmacology supporting the contention that reported agents are truly peripherally restricted. Notable examples of these types of compounds are: TM38837 (structure not disclosed); AM6545 (8); JD5037 (15b); RTI-12 (19).”

http://www.ncbi.nlm.nih.gov/pubmed/23902803