“Cannabinoids and opioids produce antinociceptive synergy. Cannabinoids such as Δ-9-tetrahydrocannabinol (THC) release endogenous opioids and endocannabinoids such as anandamide (AEA) also alter endogenous opioid tone. Opioids and cannabinoids bind distinct receptors that co-localize in areas of the brain involved with the processing of pain signals. Therefore, it is logical to look at interactions of these two systems in the modulation of both acute and chronic pain. This review summarizes the data indicating that with cannabinoid/opioid therapy one may be able to produce long-term antinociceptive effects at doses devoid of substantial side effects, while preventing the neuronal biochemical changes that accompany tolerance. The clinical utility of modulators of the endocannabinoid system as a potential mimic for THC-like drugs in analgesia and tolerance-sparing effects of opioids is a critical future direction also addressed in the review.” https://www.tandfonline.com/doi/abs/10.1080/09540260902782794]]>
Category Archives: Endocannabinoid System
The role of cannabinoid signaling in acute and chronic kidney diseases.
“The endogenous cannabinoids anandamide and 2-arachidonoylglycerol bind to the cannabinoid receptors of type 1 and 2. These receptors are also the binding sites for exogenous, both natural and synthetic, cannabinoids that are used for recreation purposes.
Until recently, cannabinoids and cannabinoid receptors have attracted little interest among nephrologists; however, a full endocannabinoid system (ECS) is present in the kidney and it has recently emerged as an important player in the pathogenesis of diabetic nephropathy, drug nephrotoxicity, and progressive chronic kidney disease.
This newly established role of the ECS in the kidney might have therapeutic relevance, as pharmacological modulation of the ECS has renoprotective effects in experimental animals, raising hope for future potential applications in humans.
In addition, over the last years, there has been a number of reported cases of acute kidney injury (AKI) associated with the use of synthetic cannabinoids that appear to have higher potency and rate of toxicity than natural Cannabis. This poorly recognized cause of renal injury should be considered in the differential diagnosis of AKI, particularly in young people.
In this review we provide an overview of preclinical evidence indicating a role of the ECS in renal disease and discuss potential future therapeutic applications.”
https://www.ncbi.nlm.nih.gov/pubmed/29706358
[The impact of cannabinoids on the endocrine system].
“Cannabinoids are naturally occurring compounds, derivatives of Indian hemp, in which tetrahydrocannabinol (THC) is the most important. Marijuana, hashish and hash oil are among those most commonly used in the group.
Cannabinoids (marjhuana and hashish) have been used throughout recorded history as effective drugs in treating various diseases and conditions such as: malaria, hypertension, constipation, bronchial asthma, rheumatic pains, and as natural pain relief in labour and joint pains.
Marijuana acts through cannabinoid receptors CB 1 and CB2. Both receptors inhibit cAMP accummulation (through Gi/o proteins) and stimulate mitrogen- activated protein kinase. CB1 rceptors are located in CNS and in adipose tissue, digestive tract, muscles, heart, lungs, liver, kidneys, gonads, prostate gland and other peripheral tissues. CB2 cannabinoid receptors are located in the peripheral nervous system (at the ends of peripheral nerves), and on the surfaces of the cells of the immunological system.
The discovery of endogenous cannabinoids has contributed to a better understanding of their role in the regulation of the intake of food, energetic homeostasis and their significant influence on the endocrine system.”
“The nucleus accumbens (NAc) is a critical component of the reward circuitry, and dysfunction of the NAc may account for anhedonia and other symptoms of depression.
The endocannabinoid (eCB) system regulates mood, emotion, motivation, appetite, body weight, and cognition.
Here, we investigated whether alterations in endocannabinoid (eCB) signaling in the NAc contribute to depression-like behaviors induced by chronic unpredictable stress (CUS) in mice.
These results suggest that downregulation of eCB signaling in the NAc occurs after CUS and contributes to the pathophysiology of depression.”
“Δ9-THC and cannabidiol (CBD) are two main 
“In the last decades, the endocannabinoid system has attracted a great interest in medicine and cancer disease is probably one of its most promising therapeutic areas.
On the one hand, endocannabinoid system expression has been found altered in numerous types of tumours compared to healthy tissue, and this aberrant expression has been related to cancer prognosis and disease outcome, suggesting a role of this system in tumour growth and progression that depends on cancer type.
On the other hand, it has been reported that 
“The endocannabinoid (eCB) system plays a key role in many physiological and pathological conditions and its dysregulation has been described in several rheumatological and autoimmune diseases. Yet, its possible alteration in systemic lupus erythematosus (SLE) has never been investigated.
Here, we aimed filling this gap in plasma and peripheral blood mononuclear cells (PBMCs) of patients with SLE and age- and sex- matched healthy subjects (HS).
In conclusion, our results demonstrate, for the first time, an alteration of eCB system in SLE patients. They represents the first step toward the understanding of the role of eCB system in SLE that likely suggest DAGL and 2-AG as potential biomarkers of SLE in easily accessible blood samples.
Our data provides proof-of-concept to the development of