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endocannabinoid system mayo clinic

Potential Competing Interests: The authors report no competing interests.

Cannabidiol (CBD) oils are low tetrahydrocannabinol products derived from Cannabis sativa that have become very popular over the past few years. Patients report relief for a variety of conditions, particularly pain, without the intoxicating adverse effects of medical marijuana. In June 2018, the first CBD-based drug, Epidiolex, was approved by the US Food and Drug Administration for treatment of rare, severe epilepsy, further putting the spotlight on CBD and hemp oils. There is a growing body of preclinical and clinical evidence to support use of CBD oils for many conditions, suggesting its potential role as another option for treating challenging chronic pain or opioid addiction. Care must be taken when directing patients toward CBD products because there is little regulation, and studies have found inaccurate labeling of CBD and tetrahydrocannabinol quantities. This article provides an overview of the scientific work on cannabinoids, CBD, and hemp oil and the distinction between marijuana, hemp, and the different components of CBD and hemp oil products. We summarize the current legal status of CBD and hemp oils in the United States and provide a guide to identifying higher-quality products so that clinicians can advise their patients on the safest and most evidence-based formulations. This review is based on a PubMed search using the terms CBD, cannabidiol, hemp oil, and medical marijuana. Articles were screened for relevance, and those with the most up-to-date information were selected for inclusion.

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AU – Scharf, Eugene L.

T1 – Endocannabinoids and Stroke Prevention

T2 – Review of Clinical Studies

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AU – Ebbert, Jon O.

Research output : Contribution to journal › Review article › peer-review

N1 – Publisher Copyright: © 2020, Mary Ann Liebert, Inc., publishers.

The societal burden of ischemic stroke suggests a need for additional therapeutic categories in stroke prevention. Modulation of the endocannabinoid system (ECS) is a rational target for stroke prevention because of its effects on inflammation, vascular tone, and metabolic balance, all well-described stroke risk factors. In this article, we summarize the existing ECS clinical studies in human subjects’ research as they relate to conventional vascular risk factors associated with ischemic stroke. To date, 2-arachidonoylglycerol (2-AG) derivative endocannabinoids are consistently reported to be elevated in insulin resistance, whereas the N-arachidonoylethanolamine (AEA) endocannabinoid derivatives are elevated in obesity. The ECS role in metabolic health should examine the effects of 2-AG reduction and AEA augmentation as a means of stroke risk reduction. Cannabinoid receptors are reported on macrophages within atherosclerotic plaques and suggest a role for immunomodulation as a therapeutic for atherosclerosis through both peripheral immune cell CB1 antagonism and/or CB2 agonist. The effects of ECS on hypertension, smoking, physical activity, obstructive sleep apnea, heart failure, and atrial fibrillation are incompletely described and deserve further study. A limitation to ECS research is significant overlap with noncannabinoid molecular targets. Further exploration of the ECS needs to include the larger metabolomics context for a greater understanding of its therapeutic potential. Clinical translational studies in stroke prevention should be directed at ECS in metabolic balance and atherosclerosis.

Physiological Actions Mediated by Activation or Inhibition of Cannabinoid Receptors.

Based on relatively new but limited scientifically based literature, it is now only possible to speculate about mechanisms of action and what the future may hold for phytocannabinoids as effective analgesics across the vast and varied cohorts of people living with chronic pain. With that in mind, this review will proceed with a summary of what is known about different cannabinoid congeners on various types of pain (efficacy and tolerability) and the putative role of commonly available “generally regarded as safe” (GRAS) ingredients that may enhance the effectiveness of certain phytocannabinoids.

ENDOGENOUS CANNABINOIDS AND NOCICEPTION

For treating refractory cancer-related pain, there is mounting evidence that cannabinoids may be a useful addition to current analgesic treatments. However, to realize the full potential of cannabinoids suggested by preclinical data, it is likely that peripheral CB1 or CB2 receptors or modulation of endocannabinoids will have to be targeted to achieve analgesia without dose-limiting side effects.100, 101 So far, studies of the efficacy of CBD in cancer pain (as well as in neuropathic pain) have used insufficient doses of CBD (alone or in combination with THC) to determine efficacy.102 Part of this insufficiency may be due to the poor bioavailability of cannabinoids.103

Terpenes are quite potent and affect animal and even human behavior when inhaled in very low concentrations. They display unique therapeutic effects that may contribute meaningfully to the entourage effects of Cannabis-based medicinal extracts. Of particular interest are the phytocannabinoid–terpene interactions that could produce synergy with respect to treatment of pain and inflammation. Phytocannabinoid–terpene synergy increases the likelihood that an extensive pipeline of new therapeutic products is possible from this age-old plant.

CB1 and CB2 receptors inhibit adenylate cyclase via interactions at the G-protein complex. However, their activation and consequent inhibition of various ion channels differs.40 The key point is that differential binding of CB1 or CB2 receptors, either separately or in combination by their respective endogenous or exogenous ligands, leads to varied physiological effects ( Table 1 ), mediated via several neurotransmitters, including acetylcholine, glutamate, and dopamine.