Investigation of cannabidiol gastro retentive tablets based on regional absorption of cannabinoids in rats.

European Journal of Pharmaceutics and Biopharmaceutics“The cannabis plant has been widely researched for many therapeutic indications and found to be effective in many chronic conditions such as epilepsy, neuropathic or chronic pain and more. However, biased opinion against compounds of the plant, regulatory as well as compounding challenges have led to very few approved medicinal products. Those formulations which are approved are dosed several times a day, creating an unmet need for controlled release (CR) formulations of cannabinoids. Conventional CR formulations rely on prolonged absorption including the colon. The purpose of this work is to investigate regional absorption of major cannabinoids THC and CBD from the colon and develop a suitable CR formulation. As hypothesized by researchers, THC and CBD have poor absorption from the colon compared to small intestine, suggesting that these compounds have a narrow absorption window. The suggested formulation examined in-vitro was a floating gastro retentive tablet based on egg albumin matrix, gas generating agents and surfactants. In-vivo investigation of CBD containing formulation in the freely moving rat model proved a prolonged absorption phase with a substantial increase in bioavailability compared to CBD solution. The findings of this paper answer a crucial question regarding potential application of CR dosage forms for cannabinoids and shed light on the regional intestinal absorption of these compounds. Ultimately, these results cement the way for future development of cannabinoid gastro retentive dosage forms.”

https://www.ncbi.nlm.nih.gov/pubmed/32422168

https://www.sciencedirect.com/science/article/abs/pii/S0939641120301375?via%3Dihub

Cannabidiol (CBD) as a treatment of acute and chronic back pain: A case series and literature review.

 Journal of opioid management (in SafetyLit)“Two patient case reports are presented describing the use of cannabidiol (CBD) for the symptomatic relief of a lumbar compression fracture and in the mitigation of thoracic discomfort and dysesthesia secondary to a surgically resected meningioma.

DISCUSSION:

CBD appears to have antisnociceptive and anti-inflammatory effects on opioid-naive patients with neuro-pathic and radicular pain. Of note, the patients in this case series used the same CBD cream: Baskin Essentials Body Wellness Cream (400 mg CBD per two oz.) Conclusion: Hemp-derived CBD in a transdermal cream provided significant symptom and pain relief for the patients described in this case series. Based on these results, we believe further investigation is warranted to see if CBD-containing products should have a more prominent role in the treatment of acute and chronic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/32421842

The molecular mechanisms that underpin the biological benefit of full spectrum cannabis extract in the treatment of neuropathic pain and inflammation.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease“Cannabis has been shown to be beneficial in the treatment of pain and inflammatory diseases.

The biological effect of cannabis is mainly attributed to two major cannabinoids, tetrahydrocannabinol and cannabidiol. In the majority of studies to-date, a purified tetrahydrocannabinol and cannabidiol alone or in combination have been extensively examined in many studies for the treatment of numerous disorders including pain and inflammation. However, few studies have investigated the biological benefits of full-spectrum cannabis plant extract.

Given that cannabis is known to generate a large number of cannabinoids along with numerous other biologically relevant products including terpenes, studies involving purified tetrahydrocannabinol and/or cannabidiol may not precisely consider the potential biological benefits of the full-spectrum cannabis extracts. This may be especially true in the role of cannabis as a treatment of pain and inflammation. Herein, we review the pre-clinical physiological and molecular mechanisms in biological systems that are affected by cannabis.”

https://www.ncbi.nlm.nih.gov/pubmed/32201189

“Full-spectrum cannabis extract demonstrates several convincing beneficial anti-inflammatory and analgesic effects in preclinical studies. Full-spectrum cannabis extract may represent a promising therapeutic agent that seems to benefit a variety of conditions associated with pain and inflammation.”

https://www.sciencedirect.com/science/article/abs/pii/S0925443920301162?via%3Dihub

Analgesic Effects of Cannabinoids for Chronic Non-cancer Pain: a Systematic Review and Meta-Analysis with Meta-Regression.

SpringerLink “There is growing interest in using cannabinoids for chronic pain.

We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the analgesic efficacy and adverse effects of cannabinoids for chronic non-cancer pain.

PubMed, EMBASE, Web of Science, Cochrane CENTRAL and clinicaltrials.gov were searched up to December 2018. Information on the type, dosage, route of administration, pain conditions, pain scores, and adverse events were extracted for qualitative analysis. Meta-analysis of analgesic efficacy was performed. Meta-regression was performed to compare the analgesic efficacy for different pain conditions (neuropathic versus non-neuropathic pain). Risk of bias was assessed by The Cochrane Risk of Bias tool, and the strength of the evidence was assessed using the Grade of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

Forty-three randomized controlled trials were included. Meta-analysis was performed for 33 studies that compared cannabinoids to placebo, and showed a mean pain score (scale 0-10) reduction of -0.70 (p < 0.001, random effect). Meta-regression showed that analgesic efficacy was similar for neuropathic and non-neuropathic pain (Difference = -0.14, p = 0.262).

Inhaled, oral, and oromucosal administration all provided statistically significant, but small reduction in mean pain score (-0.97, -0.85, -0.45, all p < 0.001). Incidence of serious adverse events was rare, and non-serious adverse events were usually mild to moderate. Heterogeneity was moderate.

The GRADE level of evidence was low to moderate. Pain intensity of chronic non-cancer patients was reduced by cannabinoids consumption, but effect sizes were small. Efficacy for neuropathic and non-neuropathic pain was similar.”

https://www.ncbi.nlm.nih.gov/pubmed/32172501

https://link.springer.com/article/10.1007%2Fs11481-020-09905-y

The role of the cannabinoid system in opioid analgesia and tolerance.

“Opioid receptor agonist drugs, such as morphine, are very effective for treating chronic and severe pain; but, tolerance can develop with long-term use. Although there is a lot of information about the pathophysiological mechanisms of opioid tolerance, it is still not fully clarified. Suggested mechanisms for opioid tolerance include opioid receptor desensitisation, reduction of sensitivity G-proteins, activation of mitogen-activated protein kinase (MAPK), altered intracellular signaling pathway including nitric oxide, and activation of mammalian target of rapamycin (mTOR).

One way to reduce opioid tolerance and increase the analgesic potential is to use low doses. Combination of cannabinoids with opioids has been shown to manifest reduce the opioid dose. Experimental studies revealed an interaction of the endocannabinoid system and opioid antinociception.

Cannabinoid and opioid receptor systems use common pathways in the formation of analgesic effect and demonstrate their activity via G protein coupled receptors (GPCR). Cannabinoid drugs modulate opioid analgesic activity at a number of distinct levels within the cell, ranging from direct receptor associations, to post-receptor interactions through shared signal transduction pathways.

This review summarizes the data indicating that with combining cannabinoids and opioids drugs may be able to produce long-term analgesic effects, while preventing the opioid analgesic tolerance.”

https://www.ncbi.nlm.nih.gov/pubmed/32167427

http://www.eurekaselect.com/180186/article

Antinociceptive and Immune Effects of Delta-9-tetrahydrocannabinol or Cannabidiol in Male Versus Female Rats with Persistent Inflammatory Pain.

Journal of Pharmacology and Experimental Therapeutics: 373 (1)

“Chronic pain is the most common reason reported for using medical cannabis.

The goal of this research was to determine if the two primary phytocannabinoids, THC and CBD, are effective treatments for persistent inflammatory pain.

These results suggest that THC may be more beneficial than CBD for reducing inflammatory pain, in that THC maintains its efficacy with short-term treatment in both sexes, and does not induce immune activation.

SIGNIFICANCE STATEMENT: CBDs and THCs pain-relieving effects are examined in male and female rats with persistent inflammatory pain to determine if individual phytocannabinoids could be a viable treatment for men and women with chronic inflammatory pain. Additionally, sex differences in the immune response to an adjuvant and to THC and CBD are characterized to provided preliminary insight into immune-related effects of cannabinoid-based therapy for pain.”

https://www.ncbi.nlm.nih.gov/pubmed/32179573

http://jpet.aspetjournals.org/content/early/2020/03/16/jpet.119.263319

A Review of Scientific Evidence for THC:CBD Oromucosal Spray (Nabiximols) in the Management of Chronic Pain.

“The 20% prevalence of chronic pain in the general population is a major health concern given the often profound associated impairment of daily activities, employment status, and health-related quality of life in sufferers. Resource utilization associated with chronic pain represents an enormous burden for healthcare systems. Although analgesia based on the World Health Organization’s pain ladder continues to be the mainstay of chronic pain management, aside from chronic cancer pain or end-of-life care, prolonged use of non-steroidal anti-inflammatory drugs or opioids to manage chronic pain is rarely sustainable.

As the endocannabinoid system is known to control pain at peripheral, spinal, and supraspinal levels, interest in medical use of cannabis is growing.

A proprietary blend of cannabis plant extracts containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) as the principal cannabinoids is formulated as an oromucosal spray (USAN name: nabiximols) and standardized to ensure quality, consistency and stability. This review examines evidence for THC:CBD oromucosal spray (nabiximols) in the management of chronic pain conditions.

Cumulative evidence from clinical trials and an exploratory analysis of the German Pain e-Registry suggests that add-on THC:CBD oromucosal spray (nabiximols) may have a role in managing chronic neuropathic pain, although further precise clinical trials are required to draw definitive conclusions.”

https://www.ncbi.nlm.nih.gov/pubmed/32104061

https://www.dovepress.com/a-review-of-scientific-evidence-for-thccbd-oromucosal-spray-nabiximols-peer-reviewed-article-JPR

“Smoked Cannabis Proven Effective In Treating Neuropathic Pain.” https://www.sciencedaily.com/releases/2007/10/071024141745.htm

“Marijuana Relieves Chronic Pain, Research Shows” https://www.webmd.com/pain-management/news/20100830/marijuana-relieves-chronic-pain-research-show#1

Cannabinoids in the Treatment of Back Pain.

Image result for neurosurgery journal“Marijuana is increasingly utilized for the treatment of multiple medical problems, including back pain, in the United States. Although there is strong preclinical evidence supporting the promise of cannabinoids in the treatment of back pain, there is a paucity of clinical data supporting their use in clinical practice. Opioids are an important medication for the treatment of acute and chronic back pain, but utilization of opioid-based regimens have likely contributed to the growing opioid epidemic. The significant risk of morbidity, mortality, and dependence secondary to opioid medications have increased the interest in nonopioid medications, including cannabinoid-based pain regimens, in treating back pain. This review will provide an overview on the pharmacology, drug delivery methods, clinical evidence, and safety considerations critical to understanding the potential role of cannabinoids in the treatment of back pain.”

https://www.ncbi.nlm.nih.gov/pubmed/32097466

https://academic.oup.com/neurosurgery/advance-article/doi/10.1093/neuros/nyz573/5758016

Cannabis and Pain Treatment-A Review of the Clinical Utility and a Practical Approach in Light of Uncertainty.

Logo of rmmj“Over the past decade the phenomenon of cannabis as a legitimate form of treatment for pain has overwhelmed the medical community, especially in the field of pain. From a status of a schedule 1 substance having no currently accepted medical use and being considered to have high potential for abuse, its use has mushroomed to over 50,000 legal medical users per year in Israel alone. There appear to be many reasons behind this phenomenon-medical, sociological, and economical. Thus, what is cannabis? An abusive substance or a medication? Should it be incorporated into current biomedical practice, and how should it be administered? Finally, what is the evidence for the beneficial and detrimental effects of cannabis? This article reviews and discusses the current literature regarding the beneficial and the detrimental effects of medical cannabis in the treatment of pain. We further discuss the problems and challenges facing the medical community in this domain and offer a practical approach to deal with these challenges.”

https://www.ncbi.nlm.nih.gov/pubmed/32017678

Cannabis and Cannabinoids in the Treatment of Rheumatic Diseases.

 Logo of rmmj“Chronic pain is a common complaint among patients, and rheumatic diseases are a common cause for chronic pain. Current pharmacological interventions for chronic pain are not always useful or safe enough for long-term use.

Cannabis and cannabinoids are currently being studied due to their potential as analgesics. In this review we will discuss current literature regarding cannabinoids and cannabis as treatment for rheumatic diseases.

Fibromyalgia is a prevalent rheumatic disease that causes diffuse pain, fatigue, and sleep disturbances. Treatment of this syndrome is symptomatic, and it has been suggested that cannabis and cannabinoids could potentially alleviate some of the symptoms associated with fibromyalgia. In this review we cite some of the evidence that supports this claim. However, data on long-term efficacy and safety of cannabinoid and cannabis use are still lacking.

Cannabinoids and cannabis are commonly investigated as analgesic agents, but in recent years more evidence has accumulated on their potential immune-modulatory effect, supported by results in animal models of certain rheumatic diseases. While results that demonstrate the same effect in humans are still lacking, cannabinoids and cannabis remain potential drugs to alleviate the pain associated with rheumatic diseases, as they were shown to be safe and to cause limited adverse effects.”

https://www.ncbi.nlm.nih.gov/pubmed/32017684