“Topical cannabinoids are increasingly utilized by dermatology patients for a range of disorders; however, the acceptance of these over-the-counter products has far outpaced scientific investigation into their safety and efficacy. Here, we review the studies of topical cannabinoids in skin conditions and assess their current place in dermatology practice.”
https://www.ncbi.nlm.nih.gov/pubmed/28873100
“Cannabidiol (CBD) is one of the most important compounds in Cannabis sativa, lacks psychotropic effects, and possesses a high number of therapeutic properties including the amelioration of experimental autoimmune encephalomyelitis (EAE).
The aim of this study was to analyse the relative efficacy of CBD in adoptively transferred EAE (at-EAE), a model that allows better delineation of the effector phase of EAE.
Preventive intraperitoneal treatment with CBD ameliorated the clinical signs of at-EAE. CBD markedly improved the clinical signs of at-EAE and reduced infiltration, demyelination and axonal damage. The CBD-mediated decrease in the viability of encephalitogenic cells involves ROS generation, apoptosis and a decrease in IL-6 production and may contribute to the therapeutic effect of this compound.”
https://www.ncbi.nlm.nih.gov/pubmed/28867485
http://www.sciencedirect.com/science/article/pii/S0014488617302212
“Δ9-tetrahydrocannabinolic acid A (THCA-A) is the acidic precursor of Δ9-tetrahydrocannabinol (THC), the main psychoactive compound found in Cannabis sativa. THCA-A is biosynthesized and accumulated in glandular trichomes present on flowers and leaves, where it serves protective functions and can represent up to 90% of the total THC contained in the plant. THCA-A slowly decarboxylates to form THC during storage and fermentation and can further degrade to cannabinol. Decarboxylation also occurs rapidly during baking of edibles, smoking, or vaporizing, the most common ways in which the general population consumes Cannabis. Contrary to THC, THCA-A does not elicit psychoactive effects in humans and, perhaps for this reason, its pharmacological value is often neglected. In fact, many studies use the term “THCA” to refer indistinctly to several acid derivatives of THC. Despite this perception, many in vitro studies seem to indicate that THCA-A interacts with a number of molecular targets and displays a robust pharmacological profile that includes potential anti-inflammatory, immunomodulatory, neuroprotective, and antineoplastic properties. Moreover, the few in vivo studies performed with THCA-A indicate that this compound exerts pharmacological actions in rodents, likely by engaging type-1 cannabinoid (CB1) receptors. Although these findings may seem counterintuitive due to the lack of cannabinoid-related psychoactivity, a careful perusal of the available literature yields a plausible explanation to this conundrum and points toward novel therapeutic perspectives for raw, unheated Cannabis preparations in humans.”
“Anxiety and anxiety-like disorders describe many mental disorders, yet fear is a common overwhelming symptom often leading to depression. Currently two basic strategies are discussed to treat anxiety: pharmacotherapy or psychotherapy. In the pharmacotherapeutical clinical approach, several conventional synthetic anxiolytic drugs are being used with several adverse effects. Therefore, studies to find suitable safe medicines from natural sources are being sought by researchers. The results of a plethora experimental studies demonstrated that dietary phytochemicals like alkaloids, terpenes, flavonoids, phenolic acids, lignans, cinnamates, and saponins or various plant extracts with the mixture of different phytochemicals possess anxiolytic effects in a wide range of animal models of anxiety. The involved mechanisms of anxiolytics action include interaction with γ-aminobutyric acid A receptors at benzodiazepine (BZD) and non-BZD sites with various affinity to different subunits, serotonergic 5-hydrodytryptamine receptors, noradrenergic and dopaminergic systems, glutamate receptors, and cannabinoid receptors. This review focuses on the use of both plant-derived natural compounds and plant extracts with anxiolytic effects, describing their biological effects and clinical application.”
https://www.ncbi.nlm.nih.gov/pubmed/28863384
“Introduction: Cannabis biosynthesizes Δ9-tetrahydrocannabinolic acid (THCA-A), which decarboxylates into Δ9-tetrahydrocannabinol (THC). There is growing interest in the therapeutic use of THCA-A, but its clinical application may be hampered by instability. THCA-A lacks cannabimimetic effects; we hypothesize that it has little binding affinity at cannabinoid receptor 1 (CB1).
Results: The THCA-A reagent contained 2% THC. THCA-A displayed small but measurable binding at both hCB1 and hCB2, equating to approximate Ki values of 3.1μM and 12.5μM, respectively. THC showed 62-fold greater affinity at hCB1 and 125-fold greater affinity at hCB2. In efficacy tests, THCA-A (10μM) slightly inhibited forskolin-stimulated cAMP at hCB1, suggestive of weak agonist activity, and no measurable efficacy at hCB2.
Discussion: The presence of THC in our THCA-A certified standard agrees with decarboxylation kinetics (literature reviewed herein), which indicate contamination with THC is nearly unavoidable. THCA-A binding at 10μM approximated THC binding at 200nM. We therefore suspect some of our THCA-A binding curve was artifact-from its inevitable decarboxylation into THC-and the binding affinity of THCA-A is even weaker than our estimated values. We conclude that THCA-A has little affinity or efficacy at CB1 or CB2.
“An agonist that acts through a single receptor can activate numerous signaling pathways. Recent studies have suggested that different ligands can differentially activate these pathways by stabilizing a limited range of receptor conformations, which in turn preferentially drive different downstream signaling cascades. This concept, termed “biased signaling” represents an exciting therapeutic opportunity to target specific pathways that elicit only desired effects, while avoiding undesired effects mediated by different signaling cascades. The cannabinoid receptors CB1 and CB2 each activate multiple pathways, and evidence is emerging for bias within these pathways. This review will summarize the current evidence for biased signaling through cannabinoid receptor subtypes CB1 and CB2.”
“Acute kidney injury (AKI) is associated with a significantly increased risk of morbidity and mortality. Ischemia-reperfusion injury (IRI) is a major cause of AKI. In this study, we investigated the role of the endocannabinoid (EC) system in renal IRI using a well-established mouse model.
Results: Renal IRI was associated with significantly increased serum BUN and creatinine, increased tubular damage score, increased expression of renal markers of inflammation and oxidative stress and elevated renal 2-AG content. Pretreatment with JZL184 was associated with a significant increase in renal 2-AG content and there was also improved serum BUN, creatinine and tubular damage score. However, renal expression of inflammation and oxidative stress markers remained unchanged.
Conclusions: This is the first report documenting that renal IRI is associated with an increase in kidney 2-AG content. Further enhancement of 2-AG levels using JZL184 improved indices of renal function and histology, but did not lower renal expression of markers of inflammation and oxidative stress. Further studies are needed to determine the mechanisms responsible for the effects observed and the potential value of 2-AG as a therapeutic target in renal IRI.”
“A great need exists for the development of new medications to treat pain resulting from various disease states and types of injury. Given that the endogenous cannabinoid (ie, endocannabinoid) system modulates neuronal and immune cell function, both of which play key roles in pain, therapeutics targeting this system hold promise as novel analgesics.
Potential therapeutic targets include the cannabinoid receptors, type 1 and 2, as well as biosynthetic and catabolic enzymes of the endocannabinoids N-arachidonoylethanolamine and 2-arachidonoylglycerol. Notably, cannabinoid receptor agonists as well as inhibitors of endocannabinoid-regulating enzymes fatty acid amide hydrolase and monoacylglycerol lipase produce reliable antinociceptive effects, and offer opioid-sparing antinociceptive effects in myriad preclinical inflammatory and neuropathic pain models.
Emerging clinical studies show that ‘medicinal’ cannabis or cannabinoid-based medications relieve pain in human diseases, such as cancer, multiple sclerosis, and fibromyalgia.
Here, we examine the preclinical and clinical evidence of various endocannabinoid system targets as potential therapeutic strategies for inflammatory and neuropathic pain conditions.”
https://www.ncbi.nlm.nih.gov/pubmed/28857069
https://www.nature.com/npp/journal/vaop/naam/abs/npp2017204a.html
“The endocannabinoid system plays a regulatory role in a number of physiological processes and has been found altered in different pathological conditions, including movement disorders. The interactions between cannabinoids and dopamine in the basal ganglia are remarkably complex and involve both the modulation of other neurotransmitters (γ-aminobutyric acid, glutamate, opioids, peptides) and the activation of different receptors subtypes (cannabinoid receptor type 1 and 2).
In the last years, experimental studies contributed to enrich this scenario reporting interactions between cannabinoids and other receptor systems (transient receptor potential vanilloid type 1 cation channel, adenosine receptors, 5-hydroxytryptamine receptors). The improved knowledge, adding new interpretation on the biochemical interaction between cannabinoids and other signaling pathways, may contribute to develop new pharmacological strategies.
A number of preclinical studies in different experimental Parkinson’s disease (PD) models demonstrated that modulating the cannabinoid system may be useful to treat some motor symptoms. Despite new cannabinoid-based medicines have been proposed for motor and nonmotor symptoms of PD, so far, results from clinical studies are controversial and inconclusive. Further clinical studies involving larger samples of patients, appropriate molecular targets, and specific clinical outcome measures are needed to clarify the effectiveness of cannabinoid-based therapies.” https://www.ncbi.nlm.nih.gov/pubmed/28861502
“Cannabis is a psychoactive compound widely used along history for recreational and therapeutic purposes. Although many open questions remain, cannabis-based therapies have become increasingly common raising considerable interest in politics as well as in general public for legalization of medical cannabis.” http://online.liebertpub.com/doi/10.1089/can.2017.0002
“Headache disorders are common, debilitating, and, in many cases, inadequately managed by existing treatments. Although clinical trials of cannabis for neuropathic pain have shown promising results, there has been limited research on its use, specifically for headache disorders. This review considers historical prescription practices, summarizes the existing reports on the use of cannabis for headache, and examines the preclinical literature exploring the role of exogenous and endogenous cannabinoids to alter headache pathophysiology. Currently, there is not enough evidence from well-designed clinical trials to support the use of cannabis for headache, but there are sufficient anecdotal and preliminary results, as well as plausible neurobiological mechanisms, to warrant properly designed clinical trials. Such trials are needed to determine short- and long-term efficacy for specific headache types, compatibility with existing treatments, optimal administration practices, as well as potential risks.” https://www.ncbi.nlm.nih.gov/pubmed/28861505
“Preclinical studies examining the role of the endocannabinoid system in migraine pathogenesis also suggest a potential therapeutic value for cannabis in the treatment of headache. It has been postulated that a general deficiency in endocannabinoid tone could underlie headache disorders.” http://online.liebertpub.com/doi/10.1089/can.2016.0033