“Confounding variables underpin the association between cannabis use and cognitive function in psychotic disorders.
Taken together, it would appear that cannabis use or dependence has no additive effect on cognitive dysfunction in these disorders.”
Author Archives: David Worrell
Cannabinoids: is there a potential treatment role in epilepsy?
“Cannabinoids have been used medicinally for centuries, and in the last decade, attention has focused on their broad therapeutic potential particularly in seizure management.
While some cannabinoids have demonstrated anticonvulsant activity in experimental studies, their efficacy for managing clinical seizures has not been fully established.
This commentary will touch on our understanding of the brain endocannabinoid system’s regulation of synaptic transmission in both physiological and pathophysiological conditions, and review the findings from both experimental and clinical studies on the effectiveness of cannabinoids to suppress epileptic seizures.
At present, there is preliminary evidence that non-psychoactive cannabinoids may be useful as anticonvulsants, but additional clinical trials are needed to fully evaluate the efficacy and safety of these compounds for the treatment of epilepsy.”
Novel Triazolopyrimidine-Derived Cannabinoid Receptor 2 Agonists As Potential Treatment for Inflammatory Kidney Diseases.
“The cannabinoid receptor 2 (CB2) system is described to modulate various pathological conditions, including inflammation and fibrosis.
A series of new heterocyclic small-molecule CB2 receptor agonists were identified from a high-throughput screen…
A significant depletion of the three measured kidney markers indicated a protective role of CB2 receptor activation toward inflammatory kidney damage. Compound 39 was also protective in a model of renal fibrosis.
Oral treatment with 39 at 3 mg kg-1 per day significantly decreased the amount of fibrosis by ∼40 % which was induced by unilateral ureter obstruction.”
The GPR55 antagonist CID16020046 protects against intestinal inflammation.
“G protein-coupled receptor 55 (GPR55) is a lysophospholipid receptor responsive to certain cannabinoids.
The role of GPR55 in inflammatory processes of the gut is largely unknown. Using the recently characterized GPR55 inhibitor CID16020046, we determined the role of GPR55 in experimental intestinal inflammation and explored possible mechanisms of action…
Pharmacological blockade of GPR55 reduces experimental intestinal inflammation by reducing leukocyte migration and activation, in particular that of macrophages. Therefore, CID16020046 represents a possible drug for the treatment of bowel inflammation.”
ACEA (a highly selective cannabinoid CB1 receptor agonist) stimulates hippocampal neurogenesis in mice treated with antiepileptic drugs.
“Hippocampal neurogenesis plays a very important role in learning and memory functions.
In a search for best neurological drugs that protect neuronal cells and stimulate neurogenesis with no side effects, cannabinoids proved to be a strong group of substances having many beneficial properties.
The aim of this study was to evaluate the impact of ACEA (arachidonyl-2′-chloroethylamide – a highly selective cannabinoid CB1 receptor agonist) combined with a classical antiepileptic drug sodium valproate (VPA) on neural precursor cells’ proliferation and differentiation in the mouse brain.
VPA administered alone decreased the number of newly born neurons with no significant impact on neurogenesis.
These data provide substantial evidence that VPA administered chronically slightly decreases the proliferation and differentiation of newly born cells while combination of VPA+ACEA significantly increases the level of newborn neurons in the dentate subgranular zone.”
The levels of the endocannabinoid receptor CB2 and its ligand 2-arachidonoylglycerol are elevated in endometrial carcinoma.
“The endocannabinoid system plays protective roles against the growth and the spreading of several types of carcinomas.
Because estrogens regulate this system both in physiological states and cancer, in this paper we evaluated its involvement in endometrial carcinoma, a well-known estrogen-dependent tumor.
In conclusion, the endocannabinoid system seems to play an important role in human endometrial carcinoma, and modulation of CB(2) activity/expression may account for a tumor-suppressive effect.”
Endocannabinoid Signaling in Autism.
“Autism spectrum disorder (ASD) is a complex behavioral condition with onset during early childhood and a lifelong course in the vast majority of cases. To date, no behavioral, genetic, brain imaging, or electrophysiological test can specifically validate a clinical diagnosis of ASD. However, these medical procedures are often implemented in order to screen for syndromic forms of the disorder (i.e., autism comorbid with known medical conditions).
In the last 25 years a good deal of information has been accumulated on the main components of the “endocannabinoid (eCB) system”, a rather complex ensemble of lipid signals (“endocannabinoids”), their target receptors, purported transporters, and metabolic enzymes.
It has been clearly documented that eCB signaling plays a key role in many human health and disease conditions of the central nervous system, thus opening the avenue to the therapeutic exploitation of eCB-oriented drugs for the treatment of psychiatric, neurodegenerative, and neuroinflammatory disorders.
Here we present a modern view of the eCB system, and alterations of its main components in human patients and animal models relevant to ASD. This review will thus provide a critical perspective necessary to explore the potential exploitation of distinct elements of eCB system as targets of innovative therapeutics against ASD.”
Therapeutic potential of cannabis-related drugs.
“In this review, I will consider the dual nature of Cannabis and cannabinoids.
The duality arises from the potential and actuality of cannabinoids in the laboratory and clinic and the ‘abuse’ of Cannabis outside the clinic.
The therapeutic areas currently best associated with exploitation of Cannabis-related medicines include pain, epilepsy, feeding disorders, multiple sclerosis and glaucoma.
As with every other medicinal drug of course, the ‘trick’ will be to maximise the benefit and minimise the cost.
After millennia of proximity and exploitation of the Cannabis plant, we are still playing catch up with an understanding of its potential influence for medicinal benefit.”
COMPARATIVE EFFECTS OF PARATHION AND CHLORPYRIFOS ON ENDOCANNABINOID AND ENDOCANNABINOID-LIKE LIPID METABOLITES IN RAT STRIATUM.
“Parathion and chlorpyrifos are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE).
The endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) are endogenous neuromodulators that regulate presynaptic neurotransmitter release in neurons throughout the central and peripheral nervous systems.
Differential changes in extracellular and/or tissue levels of eCBs and eCBLs could potentially influence a number of signaling pathways and contribute to selective neurological changes following acute OP intoxications.”
Cannabidiol is a negative allosteric modulator of the type 1 cannabinoid receptor.
“Cannabidiol has been reported to act as an antagonist of cannabinoid agonists at type 1 cannabinoid receptors (CB1 ).
We hypothesized that cannabidiol can inhibit cannabinoid agonist activity through negative allosteric modulation of CB1…
Cannabidiol behaved as a non-competitive negative allosteric modulator of CB1 .
Allosteric modulation, in conjunction with non-CB1 effects, may explain the in vivo effects of cannabidiol.
Allosteric modulators of CB1 have the potential to treat central nervous system and peripheral disorders while avoiding the adverse effects associated with orthosteric agonism or antagonism of CB1.”