Category Archives: Endocannabinoid System

Cannabis, a complex plant: different compounds and different effects on individuals.

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“Cannabis is a complex plant, with major compounds such as delta-9-tetrahydrocannabinol and cannabidiol, which have opposing effects. The discovery of its compounds has led to the further discovery of an important neurotransmitter system called the endocannabinoid system.

This system is widely distributed in the brain and in the body, and is considered to be responsible for numerous significant functions.

There has been a recent and consistent worldwide increase in cannabis potency, with increasing associated health concerns. A number of epidemiological research projects have shown links between dose-related cannabis use and an increased risk of development of an enduring psychotic illness. However, it is also known that not everyone who uses cannabis is affected adversely in the same way.

What makes someone more susceptible to its negative effects is not yet known, however there are some emerging vulnerability factors, ranging from certain genes to personality characteristics.

 In this article we first provide an overview of the biochemical basis of cannabis research by examining the different effects of the two main compounds of the plant and the endocannabinoid system, and then go on to review available information on the possible factors explaining variation of its effects upon different individuals.”

http://www.ncbi.nlm.nih.gov/pubmed/23983983

Texas A&M Pharmacy Researcher Fights Cancer, Pain With New Cannabinoid Receptor Drug

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DrDaiLu

“Dr. Lu has been working to find new types of chemotherapeutic drugs that both kill pancreatic cancer and suppress the cancer pain at the same time by targeting a special G-protein coupled receptor that belongs to the biological system responsible for the effects of Tetrahydrocannabinol (THC), a compound derived from some varieties of cannabis (hemp) or made synthetically, that is the primary psychoactive agent in marijuana and hashish.

 Dr. Lu says pancreatic cancer cells have more type 2 cannabinoid receptors than do healthy cells.

 Consequently, drug molecules that selectively activate this receptor can induce cancer cell death without affecting normal pancreatic cells, noting that when given to mice with pancreatic tumors, the molecule prevented tumor growth and suppressed the spread of cancer to healthy organs.

 Meanwhile, this class of compounds also generates painkillers comparable to morphine’s pain killing effect…”

More: http://www.bionews-tx.com/news/2013/08/20/texas-am-pharmacy-researcher-fights-cancer-pain-with-new-cannabinoid-receptor-drug/

Cannabinoids may be a target for new strategies in cancer treatment

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“Cannabis-like substances that are produced by the body have both therapeutic and harmful properties, besides their well-known intoxicating effects, and the body’s cannabinoid system may be a target for new strategies in cancer treatment…

Cannabinoids have moreover been shown to affect the fate of cells. Cannabinoids protect some brain cells, whereas cells in certain types of brain tumors, such as glioma, are stimulated to commit controlled cell suicide (apoptosis)…

In summary, the findings of Sofia Gustafsson’s studies show that cannabinoids can be toxic for cancer cells… These findings are important for our knowledge both of the potential of the cannabinoid system as a target system for new strategies in cancer treatment…”

More: http://www.news-medical.net/news/20120229/Cannabinoids-may-be-a-target-for-new-strategies-in-cancer-treatment.aspx

More surprises lying ahead. The endocannabinoids keep us guessing.

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“The objective of this review is to point out some important facts that we don’t know about endogenous cannabinoids – lipid-derived signaling molecules that activate CB1 cannabinoid receptors and play key roles in motivation, emotion and energy balance. The first endocannabinoid substance to be discovered, anandamide, was isolated from brain tissue in 1992. Research has shown that this molecule is a bona fide brain neurotransmitter involved in the regulation of stress responses and pain, but the molecular mechanisms that govern its formation and the neural pathways in which it is employed are still unknown. There is a general consensus that enzyme-mediated cleavage, catalyzed by fatty acid amide hydrolase (FAAH), terminates the biological actions of anandamide, but there are many reasons to believe that other as-yet-unidentified proteins are also involved in this process. We have made significant headway in understanding the second arrived in the endocannabinoid family, 2-arachidonoyl-sn-glycerol (2-AG), which was discovered three years after anandamide. Researchers have established some of the key molecular players involved in 2-AG formation and deactivation, localized them to specific synaptic components, and showed that their assembly into a multi-molecular protein complex (termed the ‘2-AG signalosome’) allows 2-AG to act as a retrograde messenger at excitatory synapses of the brain. Basic questions that remain to be answered pertain to the exact molecular composition of the 2-AG signalosome, its regulation by neural activity and its potential role in the actions of drugs of abuse such as Δ9-THC and cocaine.”

http://www.ncbi.nlm.nih.gov/pubmed/23954677

CB1 and CB2 Cannabinoid Receptor Antagonists Prevent Minocycline-Induced Neuroprotection Following Traumatic Brain Injury in Mice.

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“Traumatic brain injury (TBI) and its consequences represent one of the leading causes of death in young adults. This lesion mediates glial activation and the release of harmful molecules and causes brain edema, axonal injury, and functional impairment. Since glial activation plays a key role in the development of this damage, it seems that controlling it could be beneficial and could lead to neuroprotective effects. Recent studies show that minocycline suppresses microglial activation, reduces the lesion volume, and decreases TBI-induced locomotor hyperactivity up to 3 months. The endocannabinoid system (ECS) plays an important role in reparative mechanisms and inflammation under pathological situations by controlling some mechanisms that are shared with minocycline pathways. We hypothesized that the ECS could be involved in the neuroprotective effects of minocycline. To address this hypothesis, we used a murine TBI model in combination with selective CB1 and CB2 receptor antagonists (AM251 and AM630, respectively). The results provided the first evidence for the involvement of ECS in the neuroprotective action of minocycline on brain edema, neurological impairment, diffuse axonal injury, and microglial activation, since all these effects were prevented by the CB1 and CB2 receptor antagonists.”

http://www.ncbi.nlm.nih.gov/pubmed/23960212

Cannabinoids and glucocorticoids modulate emotional memory after stress.

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“Bidirectional and functional relationships between glucocorticoids and the endocannabinoid system have been demonstrated. Here, I review the interaction between the endocannabinoid and glucocorticoid/stress systems. Specifically, stress is known to produce rapid changes in endocannabinoid signaling in stress-responsive brain regions. In turn, the endocannabinoid system plays an important role in the downregulation and habituation of hypothalamic-pituitary-adrenocortical (HPA) axis activity in response to stress. Glucocorticoids also recruit the endocannabinoid system to exert rapid negative feedback control of the HPA axis during stress. It became increasingly clear, however, that cannabinoid CB1 receptors are also abundantly expressed in the basolateral amygdala (BLA) and other limbic regions where they modulate emotional arousal effects on memory.

 Enhancing cannabinoids signaling using exogenous CB1 receptor agonists prevent the effects of acute stress on emotional memory.

 I propose a model suggesting that the ameliorating effects of exogenously administered cannabinoids on emotional learning after acute stress are mediated by the decrease in the activity of the HPA axis via GABAergic mechanisms in the amygdala.”

http://www.ncbi.nlm.nih.gov/pubmed/23954749

Cannabinoid Receptor CB2 Modulates Axon Guidance.

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“Navigation of retinal projections towards their targets is regulated by guidance molecules and growth cone transduction mechanisms. Here, we present in vitro and in vivo evidences that the cannabinoid receptor 2 (CB2R) is expressed along the retino-thalamic pathway and exerts a modulatory action on axon guidance….

Overall, this study demonstrates that the contribution of endocannabinoids to brain development is not solely mediated by CB1R, but also involves CB2R.”

http://www.ncbi.nlm.nih.gov/pubmed/23951024

The endocannabinoid system as a possible target to treat both the cognitive and emotional features of post-traumatic stress disorder (PTSD).

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“Post-traumatic stress disorder (PTSD) is a psychiatric disorder of significant prevalence and morbidity, whose pathogenesis relies on paradoxical changes of emotional memory processing. An ideal treatment would be a drug able to block the pathological over-consolidation and continuous retrieval of the traumatic event, while enhancing its extinction and reducing the anxiety symptoms. While the latter benefit from antidepressant medications, no drug is available to control the cognitive symptomatology. Endocannabinoids regulate affective states and participate in memory consolidation, retrieval, and extinction. Clinical findings showing a relationship between Cannabis use and PTSD, as well as changes in endocannabinoid activity in PTSD patients, further suggest the existence of a link between endocannabinoids and maladaptive brain changes after trauma exposure. Along these lines, we suggest that endocannabinoid degradation inhibitors may be an ideal therapeutic approach to simultaneously treat the emotional and cognitive features of PTSD, avoiding the unwanted psychotropic effects of compounds directly binding cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/23950739

Effects of endocannabinoid and endovanilloid systems on aversive memory extinction.

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“In contextual fear conditioning animals have to integrate various elemental stimuli into a coherent representation of the condition and then associate context representation with punishment. Although several studies indicated the modulating role of endocannabinoid system (ECS) on the associative learning, ECS effect on contextual fear conditioning requires further investigations. The present study assessed the effects of the increased endocannabinoid anandamide (AEA) tone on acquisition, retrieval and extinction of the contextual fear conditioning…

 The present study indicates that ECS controls the extinction of aversive memories in the contextual fear conditioning.”

http://www.ncbi.nlm.nih.gov/pubmed/23948212

Activation of spinal cannabinoid cb2 receptors inhibits neuropathic pain in streptozotocin-induced diabetic mice.

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“The role of spinal cannabinoid systems in neuropathic pain of streptozotocin-induced diabetic mice was studied…

 … A low dose of WIN-55,212-2  significantly recovered the tail-flick latency in streptozotocin-induced diabetic mice… The selective cannabinoid CB2 receptor agonist L-759,656 also dose-dependently recovered the tail-flick latency in streptozotocin-induced diabetic mice…

 These results indicate that spinal cannabinoid systems are changed in diabetic mice and suggest that cannabinoid CB2 receptor agonists might have an ability to recover diabetic neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/23892011