Nabiximols for the Treatment of Cannabis Dependence: A Randomized Clinical Trial.

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“This study demonstrates that cannabinoid agonist treatment, in this case using nabiximols, in combination with psychosocial interventions is a safe approach for reducing cannabis use among individuals with cannabis dependence who are seeking treatment.”   https://www.ncbi.nlm.nih.gov/pubmed/31305874
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2737918
“nabiximols: An herbal preparation containing a defined quantity of specific cannabinoids formulated for oromucosal spray administration with potential analgesic activity. Nabiximols contains a standardized extract of tetrahydrocannabinol (THC), the non-psychoactive cannabinoid cannabidiol (CBD), other minor cannabinoids, flavonoids, and terpenes from two cannabis plant varieties.” https://www.cancer.gov/publications/dictionaries/cancer-drug/def/nabiximols
“Cannabis treatment counters addiction: First study of its kind. Trial shows cannabis replacement therapy can be effective” https://www.sciencedaily.com/releases/2019/07/190715114247.htm

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Cannabinoid receptors in osteoporosis and osteoporotic pain: a narrative update of review.

Journal of Pharmacy and Pharmacology banner“Osteoporosis is a skeletal disease with decreased bone mass and alteration in microarchitecture of bone tissue, and these changes put patients in risk of bone fracture. As a common symptom of osteoporosis and complication of osteoporotic fracture, chronic pain is a headache for clinicians. Nonsteroidal anti-inflammatory drugs (NSAIDs), selective COX-2 inhibitors and opioid drugs can temporarily reduce osteoporotic pain but have relevant side effects, such as addiction, tolerability and safety. The review summarized the recent advancements in the study of CB receptors in osteoporosis and osteoporotic pain and related mechanisms.

KEY FINDINGS:

Recent studies indicated the two nociceptive receptors, cannabinoid receptor (CB) and transient receptor potential vanilloid type 1 (TRPV1) channel, are co-expressed in bone cells and play important role in the metabolism of bone cells, suggesting that dualtargeting these 2 receptors/channel may provide a novel approach for osteoporotic pain. In addition, both CB receptor and TRPV1 channel are found to be expressed in the glial cells which play vital role in mediating inflammation, chronic pain and metabolism of bone cells, suggesting a role of glial cells inosteoporotic pain.

SUMMARY:

Multiple-targeting against glial cells, CB receptors and TRPV1 channel may be one effective therapeutic strategy for osteoporotic pain in the future, following the elucidation of the complicated mechanism.”

https://www.ncbi.nlm.nih.gov/pubmed/31294469

https://onlinelibrary.wiley.com/doi/full/10.1111/jphp.13135

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Use of Cannabis to Relieve Pain and Promote Sleep by Customers at an Adult Use Dispensary

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“Cannabis has been used for pain relief and to promote sleep for thousands of years. Over the past several decades in the United States (U.S.), a therapeutic role for cannabis in mainstream medicine has increasingly emerged. Medical cannabis patients consistently report using cannabis as a substitute for prescription medications. Both pain relief and sleep promotion are common reasons for cannabis use, and the majority of respondents who reported using cannabis for these reasons also reported decreasing or stopping their use of prescription or over-the-counter analgesics and sleep aids. While adult-use laws are frequently called “recreational,” implying that cannabis obtained through the adult use system is only for pleasure or experience-seeking, our findings suggest that many customers use cannabis for symptom relief.”

https://www.ncbi.nlm.nih.gov/pubmed/31264536

https://www.tandfonline.com/doi/full/10.1080/02791072.2019.1626953

“Cannabis Is An Effective Treatment Option For Pain Relief And Insomnia, Study Finds” https://www.inquisitr.com/5509672/cannabis-pain-medications-sleep/

“Marijuana Could Be The Alternative Pain Reliever Replacing Opioids”  https://www.medicaldaily.com/marijuana-alternative-pain-reliever-replacing-opioids-437974

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Cannabinoids reduce hyperalgesia and inflammation via interaction with peripheral CB1 receptors.

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“Central antinociceptive effects of cannabinoids have been well documented.

Our results indicate that cannabinoids produce antihyperalgesia via interaction with a peripheral CB1 receptor.

This hypothesis is supported by the finding that anandamide inhibited capsaicin-evoked release of calcitonin gene-related peptide from isolated hindpaw skin.

Collectively, these results indicate that cannabinoids reduce inflammation via interaction with a peripheral CB1 receptor.”

“The Endocannabinoid System and Pain. Cannabis has been used for more than twelve thousand years and for many different purposes (i.e. fiber, medicinal, recreational). However, the endocannabinoid signaling system has only recently been the focus of medical research and considered a potential therapeutic target. Cannabinoid receptors and their endogenous ligands are present at supraspinal, spinal and peripheral levels. Cannabinoids suppress behavioral responses to noxious stimulation and suppress nociceptive processing through activation of cannabinoid CB1 and CB2 receptor subtypes. These studies suggest that manipulation of peripheral endocannabinoids may be promising strategy for the management of pain.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834283/

“The Analgesic Potential of Cannabinoids. Historically and anecdotally cannabinoids have been used as analgesic agents. Moreover, cannabinoids act synergistically with opioids and act as opioid sparing agents, allowing lower doses and fewer side effects from chronic opioid therapy. Thus, rational use of cannabis based medications deserves serious consideration to alleviate the suffering of patients due to severe pain.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728280/
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Cannabinoid receptor 1 (CB1R) expression in rat dental pulp

Oral Science International“Accumulating evidence supports the role of the cannabinoid system in providing an antinociceptive effect in various painful conditions.

This effect is mediated through the Cannabinoid receptor 1 (CB1R) expressed on nociceptive afferent nerve terminals.

To investigate whether this receptor plays a similar role in dental pain, we studied the presence and distribution of CB1R in rat dental pulp.

CB1R was present on nerve fibers in rat dental pulp and possibly plays a role in dental pain mechanisms.

Interestingly, CB1R has recently been demonstrated in human dental pulp.

This strongly suggests that CB1R could be a therapeutic target for dental pain management.”

https://www.sciencedirect.com/science/article/pii/S1348864312000031

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Cannabinoid receptor CB1-immunoreactive nerve fibres in painful and non-painful human tooth pulp.

Journal of Clinical Neuroscience Home“The cannabinoid receptor CB1 is involved in modulation of neuronal hypersensitivity and pain. The aim of this study was to evaluate CB1 receptor levels for the first time in dental pain. A total of 19 patients due for molar extraction were divided into two groups, those with existing dental pain (n=9), and those with no history of pain (n=10). Immunohistochemistry and computer image analysis was used to evaluate CB1-positive nerve fibres in tooth pulp, with neurofilament-immunostaining as a structural nerve marker. CB1-immunoreactive nerve fibres were scattered throughout the tooth pulp and often seen in nerve bundles, but the fibres did not penetrate the subodontoblastic layer. There was no statistically significant change in the CB1 nerve fibre percentage area in the painful group compared to the non-painful group (p=0.146); the neurofilament fibres were significantly reduced in the painful group compared to the controls (p=0.028), but there was no difference in the ratio of CB1 to neurofilaments between the two groups. Thus, CB1 expression is maintained by nerve fibres in painful human dental pulp, and peripherally-restricted CB1 agonists currently in development may advance the treatment of dental pain.”

https://www.ncbi.nlm.nih.gov/pubmed/20705472

https://www.jocn-journal.com/article/S0967-5868(10)00289-4/fulltext

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Omega-3 Endocannabinoid-Epoxides Are Novel Anti-inflammatory and Anti-Pain Lipid Metabolites (FS15-01-19).

Issue Cover“Omega-3 fatty acid derived endocannabinoids are metabolized by cytochrome P450s to form bioactive endocannabinoid epoxides that are anti-inflammatory.

RESULTS:

Cannabinoids are found in marijuana and also are produced naturally in the body from ω-3 and ω-6 fatty acids. Exocannabinoids in marijuana, are known to be responsible for some of its euphoric effects, but they also exhibit anti-inflammatory benefits. Our study revealed a cascade of enzymatic reactions that convert ω-3 fatty acids into anti-inflammatory endocannabinoid epoxides that act through the same receptors in the body as marijuana (PNAS 2017).

Endocannabinoids are ligands for cannabinoidreceptor 1 and 2 (CB1 and CB2). CB1 receptor agonists exhibit psychotropic properties while CB2 receptor agonists have anti-inflammatory effects. Consequently, there is a strong interest in the discovery of CB2 selective agonists to mitigate inflammatory pathologies. The work details the discovery and characterization of naturally occurring ω-3-derived endocannabinoid epoxides that are formed via enzymatic oxidation of ω-3 endocannabinoids by cytochrome P450 epoxygenases. These dual functional ω-3 endocannabinoid epoxides exhibit preference towards binding to CB2 receptor and are anti-inflammatory and vasodilatory and reciprocally modulate platelet aggregation. Some of the other regioisomers of ω-3 endocannabinoid epoxides are partial agonists of CB1 and stop tumor cell metastasis (J. Med. Chem 2018). By virtue of their physiological properties, they are expected to play important roles in neuroinflammation and pain.

CONCLUSIONS:

This finding demonstrates how omega-3 fatty acids can produce some of the same medicinal qualities as marijuana, but without a psychotropic effect. In summary, the ω-3 endocannabinoid epoxides are found at concentrations comparable to those of other endocannabinoids and are expected to play critical roles during inflammation in vivo.”

https://www.ncbi.nlm.nih.gov/pubmed/31223777

https://academic.oup.com/cdn/article/3/Supplement_1/nzz031.FS15-01-19/5518049

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Preparation of bivalent agonists for targeting the mu opioid and cannabinoid receptors.

European Journal of Medicinal Chemistry

“In order to obtain novel pharmacological tools and to investigate a multitargeting analgesic strategy, the CB1 and CB2 cannabinoid receptor agonist JWH-018 was conjugated with the opiate analgesic oxycodone or with an enkephalin related tetrapeptide. The opioid and cannabinoid pharmacophores were coupled via spacers of different length and chemical structure. In vitro radioligand binding experiments confirmed that the resulting bivalent compounds bound both to the opioid and to the cannabinoid receptors with moderate to high affinity. The highest affinity bivalent derivatives 11 and 19 exhibited agonist properties in [35S]GTPγS binding assays. These compounds activated MOR and CB (11 mainly CB2, whereas 19 mainly CB1) receptor-mediated signaling, as it was revealed by experiments using receptor specific antagonists. In rats both 11 and 19 exhibited antiallodynic effect similar to the parent drugs in 20 μg dose at spinal level. These results support the strategy of multitargeting G-protein coupled receptors to develop lead compounds with antinociceptive properties.”

https://www.ncbi.nlm.nih.gov/pubmed/31220675

https://www.sciencedirect.com/science/article/pii/S0223523419304477?via%3Dihub

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Opioid-Sparing Effects of Cannabinoids on Morphine Analgesia: Participation of CB1 and CB2 Receptors.

British Journal of Pharmacology banner“Much of the opioid epidemic arose from abuse of prescription opioid drugs.

This study sought to determine if the combination of a cannabinoid with an opioid could produce additive or synergistic effects on pain, allowing reduction in the opioid dose needed for maximal analgesia.

CONCLUSIONS AND IMPLICATIONS:

The ability of a cannabinoid to produce an additive or synergistic effect on analgesia when combined with morphine varies with the pain assay and may be mediated by CB1 or CB2 receptors. These results hold the promise of using cannabinoids to reduce the dose of opioids for analgesia in certain pain conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/31218677

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14769

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Antitumor Cannabinoid Chemotypes: Structural Insights.

Image result for frontiers in pharmacology“Cannabis has long been known to limit or prevent nausea and vomiting, lack of appetite, and pain. For this reason, cannabinoids have been successfully used in the treatment of some of the unwanted side effects caused by cancer chemotherapy.

Besides their palliative effects, research from the past two decades has demonstrated their promising potential as antitumor agents in a wide variety of tumors.

Cannabinoids of endogenous, phytogenic, and synthetic nature have been shown to impact the proliferation of cancer through the modulation of different proteins involved in the endocannabinoid system such as the G protein-coupled receptors CB1, CB2, and GRP55, the ionotropic receptor TRPV1, or the fatty acid amide hydrolase (FAAH).

In this article, we aim to structurally classify the antitumor cannabinoid chemotypes described so far according to their targets and types of cancer. In a drug discovery approach, their in silico pharmacokinetic profile has been evaluated in order to identify appropriate drug-like profiles, which should be taken into account for further progress toward the clinic.

This analysis may provide structural insights into the selection of specific cannabinoid scaffolds for the development of antitumor drugs for the treatment of particular types of cancer.” https://www.ncbi.nlm.nih.gov/pubmed/31214034

“The first report on the antitumor activity of phytocannabinoids was published over four decades ago. During these last years, significant research has been focused on the therapeutic potential of cannabinoids to manage palliative effects in cancer patients. Besides such palliative applications, some cannabinoids have shown anticancer properties. Since inflammation is a common risk factor for cancer, and some cannabinoids have shown anti-inflammatory properties, they could play a role in chemoprevention.” https://www.frontiersin.org/articles/10.3389/fphar.2019.00621/full
“Antitumor effects of THC.” http://www.ncbi.nlm.nih.gov/pubmed/11097557
“Antitumor effects of cannabidiol” http://www.ncbi.nlm.nih.gov/pubmed/14617682
“Anti-tumour actions of cannabinoids.” https://www.ncbi.nlm.nih.gov/pubmed/30019449
“Extensive preclinical research has demonstrated that cannabinoids, the active ingredients of Cannabis sativa, trigger antitumor responses in different models of cancer.” https://www.ncbi.nlm.nih.gov/pubmed/29940172
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