Tag Archives: Cannabinoids

Pain and Depression: A Systematic Review.

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“Pain comorbid with depression is frequently encountered in clinical settings and often leads to significant impaired functioning. Given the complexity of comorbidities, it is important to address both pain and depressive symptoms when evaluating treatment options.

Overall, studies suggested that pain and depression are highly intertwined and may co-exacerbate physical and psychological symptoms. These symptoms could lead to poor physical functional outcomes and longer duration of symptoms. An important biochemical basis for pain and depression focuses on serotonergic and norepinephrine systems, which is evident in the pain-ameliorating properties of serotonergic and norepinephrine antidepressants.

Alternative pharmacotherapies such as ketamine and cannabinoids appear to be safe and effective options for improving depressive symptoms and ameliorating pain. In addition, cognitive-behavioral therapy may be a promising tool in the management of chronic pain and depression.

CONCLUSION:

The majority of the literature indicates that patients with pain and depression experience reduced physical, mental, and social functioning as opposed to patients with only depression or only pain. In addition, ketamine, psychotropic, and cognitive-behavioral therapies present promising options for treating both pain and depression.”

https://www.ncbi.nlm.nih.gov/pubmed/30407234

https://insights.ovid.com/crossref?an=00023727-201811000-00005

Cannabis and the Anxiety of Fragmentation-A Systems Approach for Finding an Anxiolytic Cannabis Chemotype.

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“Cannabis sativa is a medicinal herb with a diverse range of chemotypes that can exert both anxiolytic and anxiogenic effects on humans. Medical cannabis patients receiving organically grown cannabis from a single source were surveyed about the effectiveness of cannabis for treating anxiety.

Patients rated cannabis as highly effective overall for treating anxiety with an average score of 8.03 on a Likert scale of 0 to 10 (0 = not effective, 10 = extremely effective).

Patients also identified which strains they found the most or least effective for relieving their symptoms of anxiety. To find correlations between anxiolytic activity and chemotype, the top four strains voted most and least effective were analyzed by HPLC-MS/MS to quantify cannabinoids and GC-MS to quantify terpenes. Tetrahydrocannabinol (THC) and trans-nerolidol have statistically significant correlations with increased anxiolytic activity.

Guiaol, eucalyptol, γ-terpinene, α-phellandrene, 3-carene, and sabinene hydrate all have significant correlations with decreased anxiolytic activity. Further studies are needed to better elucidate the entourage effects that contribute to the anxiolytic properties of cannabis varieties.”

https://www.ncbi.nlm.nih.gov/pubmed/30405331

https://www.frontiersin.org/articles/10.3389/fnins.2018.00730/full

Efficacy of cannabinoids in paediatric epilepsy.

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Developmental Medicine & Child Neurology banner

“There are hundreds of compounds found in the marijuana plant, each contributing differently to the antiepileptic and psychiatric effects. Cannabidiol (CBD) has the most evidence of antiepileptic efficacy and does not have the psychoactive effects of ∆9 -tetrahydrocannabinol. CBD does not act via cannabinoid receptors and its antiepileptic mechanism of action is unknown. Despite considerable community interest in the use of CBD for paediatric epilepsy, there has been little evidence for its use apart from anecdotal reports, until the last year. Three randomized, placebo-controlled, double-blind trials in Dravet syndrome and Lennox-Gastaut syndrome found that CBD produced a 38% to 41% median reduction in all seizures compared to 13% to 19% on placebo. Similarly, CBD resulted in a 39% to 46% responder rate (50% convulsive or drop-seizure reduction) compared to 14% to 27% on placebo. CBD was well tolerated; however, sedation, diarrhoea, and decreased appetite were frequent. CBD shows similar efficacy to established antiepileptic drugs. WHAT THIS PAPER ADDS: Cannabidiol (CBD) shows similar efficacy in the severe paediatric epilepsies to other antiepileptic drugs. Careful down-titration of benzodiazepines is essential to minimize sedation with adjunctive CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/30402932

https://onlinelibrary.wiley.com/doi/full/10.1111/dmcn.14087

New insights on atherosclerosis: A cross-talk between endocannabinoid systems with gut microbiota.

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“The incidence of atherosclerosis is increasing rapidly all over the world. Inflammatory processes have outstanding role in coronary artery disease (CAD) etiology and other atherosclerosis manifestations. Recently attentions have been increased about gut microbiota in many fields of medicine especially in inflammatory diseases like atherosclerosis. Ineffectiveness in gut barrier functions and subsequent metabolic endotoxemia (caused by rise in plasma lipopolysaccharide levels) is associated with low-grade chronic inflammation i.e. a recognized feature of atherosclerosis. Furthermore, the role of trimethylamine-N-oxide (TMAO), a gut bacterial metabolite has been suggested in atherosclerosis development. On the other hand, the effectiveness of gut microbiota modulation that results in TMAO reduction has been investigated. Moreover, considerable evidence supports a role for the endocannabinoid system (ECS) in atherosclerosis pathology which affects gut microbiota, but their effects on atherosclerosis are controversial. Therefore, we presented some evidence about the relationship between gut microbiota and ECS in atherosclerosis. We also presented evidences that gut microbiota modulation by pre/probiotics can have significant influence on the ECS.

Even though there are many questions which have been unanswered, studies demonstrated that mucosal barrier function disruption and subsequent gut microbiota-derived endotoxemia could contribute to cardiometabolic diseases pathogenesis. As well, number of studies revealed that TMAO in systemic circulation can activate macrophages which lead to cholesterol accumulation and subsequent foam cells formation in atherosclerotic lesions. On the other hand, accumulating evidence proposes that ECS involved in many physiological processes that are related to maintenance of gut-barrier function and inflammation regulation. Hence, although present literature review provides beneficial evidence in support of crosstalk between ECS and gut microbiota, additional studies are needed to clarify whether gut microbiota modulation can alter ECS tone and inflammation levels or not.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203867/

Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis.

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 Image result for drugs journal“Approximately one-third of patients with epilepsy presents seizures despite adequate treatment. Hence, there is the need to search for new therapeutic options. Cannabidiol (CBD) is a major chemical component of the resin of Cannabis sativa plant, most commonly known as marijuana. The anti-seizure properties of CBD do not relate to the direct action on cannabinoid receptors, but are mediated by a multitude of mechanisms that include the agonist and antagonist effects on ionic channels, neurotransmitter transporters, and multiple 7-transmembrane receptors. In contrast to tetra-hydrocannabinol, CBD lacks psychoactive properties, does not produce euphoric or intrusive side effects, and is largely devoid of abuse liability.

OBJECTIVE:

The aim of the study was to estimate the efficacy and safety of CBD as adjunctive treatment in patients with epilepsy using meta-analytical techniques.

METHODS:

Randomized, placebo-controlled, single- or double-blinded add-on trials of oral CBD in patients with uncontrolled epilepsy were identified. Main outcomes included the percentage change and the proportion of patients with ≥ 50% reduction in monthly seizure frequency during the treatment period and the incidence of treatment withdrawal and adverse events (AEs).

RESULTS:

Four trials involving 550 patients with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) were included. The pooled average difference in change in seizure frequency during the treatment period resulted 19.5 [95% confidence interval (CI) 8.1-31.0; p = 0.001] percentage points between the CBD 10 mg and placebo groups and 19.9 (95% CI 11.8-28.1; p < 0.001) percentage points between the CBD 20 mg and placebo arms, in favor of CBD. The reduction in all-types seizure frequency by at least 50% occurred in 37.2% of the patients in the CBD 20 mg group and 21.2% of the placebo-treated participants [risk ratio (RR) 1.76, 95% CI 1.07-2.88; p = 0.025]. Across the trials, drug withdrawal for any reason occurred in 11.1% and 2.6% of participants receiving CBD and placebo, respectively (RR 3.54, 95% CI 1.55-8.12; p = 0.003) [Chi squared = 2.53, degrees of freedom (df) = 3, p = 0.506; I2 = 0.0%]. The RRs to discontinue treatment were 1.45 (95% CI 0.28-7.41; p = 0.657) and 4.20 (95% CI 1.82-9.68; p = 0.001) for CBD at the doses of 10 and 20 mg/kg/day, respectively, in comparison to placebo. Treatment was discontinued due to AEs in 8.9% and 1.8% of patients in the active and control arms, respectively (RR 5.59, 95% CI 1.87-16.73; p = 0.002). The corresponding RRs for CBD at the doses of 10 and 20 mg/kg/day were 1.66 (95% CI 0.22-12.86; p = 0.626) and 6.89 (95% CI 2.28-20.80; p = 0.001). AEs occurred in 87.9% and 72.2% of patients treated with CBD and placebo (RR 1.22, 95% CI 1.11-1.33; p < 0.001). AEs significantly associated with CBD were somnolence, decreased appetite, diarrhea, and increased serum aminotransferases.

CONCLUSIONS:

Adjunctive CBD in patients with LGS or DS experiencing seizures uncontrolled by concomitant anti-epileptic treatment regimens is associated with a greater reduction in seizure frequency and a higher rate of AEs than placebo.”

https://www.ncbi.nlm.nih.gov/pubmed/30390221

Medical Use of Cannabinoids.

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“Cannabinoid receptors, endocannabinoids and the enzymes responsible for their biosynthesis and degradation constitute the endocannabinoid system. In recent decades, the endocannabinoid system has attracted considerable interest as a potential therapeutic target in numerous pathological conditions. Its involvement in several physiological processes is well known, such as in energy balance, appetite stimulation, blood pressure, pain modulation, embryogenesis, nausea and vomiting control, memory, learning and immune response, among others, as well as in pathological conditions where it exerts a protective role in the development of certain disorders. As a result, it has been reported that changes in endocannabinoid levels may be related to neurological diseases such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and multiple sclerosis, as well as anorexia and irritable bowel syndrome. Alterations in the endocannabinoid system have also been associated with cancer, affecting the growth, migration and invasion of some tumours. Cannabinoids have been tested in several cancer types, including brain, breast and prostate cancers. Cannabinoids have shown promise as analgesics for the treatment of both inflammatory and neuropathic pain. There is also evidence for a role of the endocannabinoid system in the control of emotional states, and cannabinoids could prove useful in decreasing and palliating post-traumatic stress disorder symptoms and anxiolytic disorders. The role of the endocannabinoid system in addictions has also been examined, and cannabinoids have been postulated as alternative and co-adjuvant treatments in some abuse syndromes, mainly in ethanol and opioid abuses. The expression of the endocannabinoid system in the eye suggests that it could be a potential therapeutic target for eye diseases. Considering the importance of the endocannabinoid system and the therapeutic potential of cannabinoids in this vast number of medical conditions, several clinical studies with cannabinoid-based medications are ongoing. In addition, some cannabinoid-based medications have already been approved in various countries, including nabilone and dronabinol capsules for the treatment of nausea and vomiting associated with chemotherapy, dronabinol capsules for anorexia, an oral solution of dronabinol for both vomiting associated with chemotherapy and anorexia, a Δ9-tetrahydrocannabinol/cannabidiol oromucosal spray for pain related to cancer and for spasticity and pain associated with multiple sclerosis, and an oral solution of cannabidiol for Dravet and Lennox-Gastaut syndromes. Here, we review the available efficacy, safety and tolerability data for cannabinoids in a range of medical conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/30374797

https://link.springer.com/article/10.1007%2Fs40265-018-0996-1

Synthetic cannabinoids nano-micelles for the management of triple negative breast cancer.

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 Journal of Controlled Release

“Triple-negative breast cancer (TNBC) is a highly heterogeneous disease with poor prognosis and inadequate therapeutic outcome. This contribution reports the use of a cannabinoid derivative, WIN55,212-2 (WIN) on the growth of TNBC in a 4T1 syngeneic mouse model.

To reduce the well-known psychoactive side effects of cannabinoids, we prepared a nanomicellar formulation of WIN (SMA-WIN). In vivo biodistribution, in silico ADME predictions, anticancer activity, and psychoactive effect of WIN and SMA-WIN studies suggest that SMA-WIN formulation can reduce to greater extent tumor growth with milder psychoactive side effects when compared to free drug.

Finally, the effects of WIN and SMA-WIN in combination with doxorubicin (Doxo), an established chemotherapeutic agent for the treatment of TNBC, were investigated in vitro and in vivo. SMA-WIN in combination with Doxo showed therapeutic efficacy and was able to reduce the tumor volume of TNBC murine model drastically. Moreover, SMA-WIN, while favoring drug tumor accumulation, minimized the adverse psychoactive effects that have impeded the use of this agent in the clinic.

To our knowledge, this is the first report for the assessment of cannabinoid nanoparticles in vivo for the treatment of TNBC and its enhanced anticancer effect at low doses with Doxo. These findings suggest a new therapeutic strategy in the management of TNBC.”

https://www.ncbi.nlm.nih.gov/pubmed/30367922

https://www.sciencedirect.com/science/article/pii/S0168365918306114?via%3Dihub

What do Cochrane systematic reviews say about the use of cannabinoids in clinical practice?

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SciELO - Scientific Electronic Library Online

“The therapeutic effects of cannabinoid compounds have been the center of many investigations.

This study provides a synthesis on all Cochrane systematic reviews (SRs) that assessed the use of cannabinoids as a therapeutic approach.

CONCLUSIONS:

This review identified eight Cochrane systematic reviews that provided evidence of unknown to moderate quality regarding the use of cannabinoids as a therapeutic intervention. Further studies are still imperative for solid conclusions to be reached regarding practical recommendations.”

 https://www.ncbi.nlm.nih.gov/pubmed/30365598
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-31802018005016102&lng=en&tlng=en

Assessment of Efficacy and Tolerability of Medicinal Cannabinoids in Patients With Multiple Sclerosis: A Systematic Review and Meta-analysis

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“Are medicinal cannabinoids effective and well tolerated in the treatment of multiple sclerosis?

Findings  In this systematic review and meta-analysis of 17 randomized clinical trials including 3161 patients, cannabinoids were significantly associated with efficacy for subjective spasticity, pain, and bladder dysfunction compared with placebo. Cannabinoids had a higher risk of adverse events and withdrawals due to adverse events, with no statistically significant differences found for serious adverse events.

Meaning  Cannabinoids appear to be safe regarding serious adverse events, but their clinical benefit may be limited.

Cannabinoids have antispastic and analgesic effects.

The results suggest a limited efficacy of cannabinoids for the treatment of spasticity, pain, and bladder dysfunction in patients with MS. Therapy using these drugs can be considered as safe.”

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2706499

“MEDICAL MARIJUANA USES: CANNABIS MAY EASE SYMPTOMS OF MULTIPLE SCLEROSIS” https://www.newsweek.com/medical-marijuana-may-ease-symptoms-multiple-sclerosis-1170416

The Role of Cannabis in the Management of Inflammatory Bowel Disease: A Review of Clinical, Scientific, and Regulatory Information: Commissioned by the Crohn’s and Colitis Foundation.

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Oxford University Press

“There is significant interest among patients and providers in using cannabis (marijuana) and its derivatives to treat a number of chronic illnesses, including inflammatory bowel disease. Despite the Schedule I classification of cannabis by the federal government, state governments have sought ways to make cannabis available for specific medical conditions, and some states have legalized cannabis outright. This white paper summarizes the preclinical data, clinical data, safety data, and the regulatory landscape as they apply to medical cannabis use in inflammatory bowel disease. Animal models of cannabinoid chemistry and physiology give evidence of anti-inflammatory, antidiarrheal, and nociceptive-limiting properties. Human studies have found benefit in controlling symptoms and improving quality of life, but no studies have established true disease modification given the absent improvement in biomarker profiles or endoscopic healing. Finally, this review describes the legal, regulatory, and practical hurdles to studying the risks and benefits of medical cannabis in the United States.”

https://www.ncbi.nlm.nih.gov/pubmed/30358848

https://academic.oup.com/ibdjournal/advance-article-abstract/doi/10.1093/ibd/izy319/5144402?redirectedFrom=fulltext