“Marijuana use is independently associated with increased sexual frequency and does not appear to impair sexual function. A positive association between marijuana use and sexual frequency is seen in men and women across all demographic groups.” http://www.jsm.jsexmed.org/article/S1743-6095(17)31417-0/fulltext
Monthly Archives: October 2017
An Update on Non-CB1, Non-CB2 Cannabinoid Related G-Protein-Coupled Receptors
“The endocannabinoid system (ECS) has been shown to be of great importance in the regulation of numerous physiological and pathological processes. To date, two Class A G-protein-coupled receptors (GPCRs) have been discovered and validated as the main therapeutic targets of this system: the cannabinoid receptor type 1 (CB1), which is the most abundant neuromodulatory receptor in the brain, and the cannabinoid receptor type 2 (CB2), predominantly found in the immune system among other organs and tissues. Endogenous cannabinoid receptor ligands (endocannabinoids) and the enzymes involved in their synthesis, cell uptake, and degradation have also been identified as part of the ECS. However, its complex pharmacology suggests that other GPCRs may also play physiologically relevant roles in this therapeutically promising system. In the last years, GPCRs such as GPR18 and GPR55 have emerged as possible missing members of the cannabinoid family. This categorization still stimulates strong debate due to the lack of pharmacological tools to validate it. Because of their close phylogenetic relationship, the Class A orphan GPCRs, GPR3, GPR6, and GPR12, have also been associated with the cannabinoids. Moreover, certain endo-, phyto-, and synthetic cannabinoid ligands have displayed activity at other well-established GPCRs, including the opioid, adenosine, serotonin, and dopamine receptor families. In addition, the cannabinoid receptors have also been shown to form dimers with other GPCRs triggering cross-talk signaling under specific conditions. In this mini review, we aim to provide insight into the non-CB1, non-CB2 cannabinoid-related GPCRs that have been reported thus far. We consider the physiological relevance of these molecular targets in modulating the ECS.”
The Risks and Benefits of Cannabis in the Dermatology Clinic.
“Cannabis ( Cannabis sativa/indica), also known as marijuana, has been used for medicinal and recreational purposes for millennia.
There has been a recent trend to legalize the use of cannabis, as illustrated by the recent legalization votes in numerous states in the United States and legislation in Canada to allow recreational cannabis use. With this increasing consumption of cannabis, dermatologists will see increased pressure to prescribe cannabis and will see the side effects of cannabis use with greater frequency.
There are several approved medical indications for cannabis use, including psoriasis, lupus, nail-patella syndrome, and severe pain. In addition, very preliminary studies have suggested cannabis and its derivatives might have use in acne, dermatitis, pruritus, wound healing, and skin cancer.
In this review, we summarize some of the studies and reports regarding the medicinal uses of cannabis in the dermatology clinic and some of the side effects that might present more often to dermatologists as the use of cannabis increases.”
“Cannabinoid system in the skin – a possible target for future therapies in dermatology.” https://www.ncbi.nlm.nih.gov/pubmed/19664006
Sex-related marijuana expectancies as predictors of sexual risk behavior following smoked marijuana challenge.
“Findings suggest marijuana does not acutely increase risk for engaging in sexual risk behaviors.”
The use of cannabidiol for seizure management in patients with brain tumor-related epilepsy.
“Epilepsy, commonly encountered by patients with brain tumors, is often refractory to standard therapies. Our aim was to examine the safety and efficacy of pharmaceutical grade cannabidiol (CBD; Epidiolex, GW Pharmaceuticals) in those patients with epilepsy with concomitant tumors enrolled in The University of Alabama at Birmingham CBD Program (NCT02700412 and NCT02695537). Of the three patients with refractory seizures and a history of a primary brain tumor, two had improvement in seizure frequency and all three had improvement in seizure severity. These pilot results suggest that CBD should be further studied for the treatment of brain tumor-related epilepsy.”
https://www.ncbi.nlm.nih.gov/pubmed/29063814
http://www.tandfonline.com/doi/abs/10.1080/13554794.2017.1391294?journalCode=nncs20
Inspired by Mary Jane? Mechanisms underlying enhanced creativity in cannabis users.
“Previous research suggests cannabis may enhance some aspects of creativity, although the results remain somewhat equivocal. Moreover, it is unclear whether differences in cannabis users’ personalities may account for any potentially beneficial effects of cannabis on creativity. This study was designed to examine whether sober cannabis users demonstrate superior self-reported and objective creativity test performance relative to non-users, and to determine whether any of the Big 5 personality domains underlie these effects. A sample of sober cannabis users (n=412) and non-users (n=309) completed measures of cannabis consumption, personality, self-reported and objective creativity. Relative to non-users, sober cannabis users self-reported higher creativity, and performed significantly better on a measure of convergent thinking. Controlling for cannabis users’ higher levels of openness to experience abolished these effects. Therefore, while cannabis users appear to demonstrate enhanced creativity, these effects are an artifact of their heightened levels of openness to experience.”
https://www.ncbi.nlm.nih.gov/pubmed/29065317
http://www.sciencedirect.com/science/article/pii/S1053810017303744?via%3Dihub
Pharmacological augmentation of endocannabinoid signaling reduces the neuroendocrine response to stress.
“Activation of the hypothalamic-pituitary-adrenal axis (HPA) is critical for survival when the organism is exposed to a stressful stimulus. The endocannabinoid system (ECS) is currently considered an important neuromodulator involved in numerous pathophysiological processes and whose primary function is to maintain homeostasis. In the tissues constituting the HPA axis, all the components of the ECS are present and the activation of this system acts in parallel with changes in the activity of numerous neurotransmitters, including nitric oxide (NO). NO is widely distributed in the brain and adrenal glands and recent studies have shown that free radicals, and in particular NO, may play a crucial role in the regulation of stress response. Our objective was to determine the participation of the endocannabinoid and NOergic systems as probable mediators of the neuroendocrine HPA axis response to a psychophysical acute stress model in the adult male rat. Animals were pre-treated with cannabinoid receptors agonists and antagonists at central and systemic level prior to acute restraint exposure. We also performed in vitro studies incubating adrenal glands in the presence of ACTH and pharmacological compounds that modifies ECS components. Our results showed that the increase in corticosterone observed after acute restraint stress is blocked by anandamide administered at both central and peripheral level. At hypothalamic level both cannabinoid receptors (CB1 and CB2) are involved, while in the adrenal gland, anandamide has a very potent effect in suppressing ACTH-induced corticosterone release that is mainly mediated by vanilloid TRPV1 receptors. We also observed that stress significantly increased hypothalamic mRNA levels of CB1 as well as adrenal mRNA levels of TRPV1 receptor. In addition, anandamide reduced the activity of the nitric oxide synthase enzyme during stress, indicating that the anti-stress action of endocannabinoids may involve a reduction in NO production at hypothalamic and adrenal levels. In conclusion, an endogenous cannabinoid tone maintains the HPA axis in a stable basal state, which is lost with a noxious stimulus. In this case, the ECS dampens the response to stress allowing the recovery of homeostasis. Moreover, our work further contributes to in vitro evidence for a participation of the endocannabinoid system by inhibiting corticosterone release directly at the adrenal gland level.”
https://www.ncbi.nlm.nih.gov/pubmed/29065362
http://www.psyneuen-journal.com/article/S0306-4530(17)30614-5/fulltext
Phytocannabinoids modulate emotional memory processing through interactions with the ventral hippocampus and mesolimbic dopamine system: implications for neuropsychiatric pathology.
“Growing clinical and preclinical evidence suggests a potential role for the phytocannabinoid cannabidiol (CBD) as a pharmacotherapy for various neuropsychiatric disorders. In contrast, delta-9-tetrahydrocannabinol (THC), the primary psychoactive component in cannabis, is associated with acute and neurodevelopmental propsychotic side effects through its interaction with central cannabinoidtype 1 receptors (CB1Rs). CB1R stimulation in the ventral hippocampus (VHipp) potentiates affective memory formation through inputs to the mesolimbic dopamine (DA) system, thereby altering emotional salience attribution. These changes in DA activity and salience attribution, evoked by dysfunctional VHipp regulatory actions and THC exposure, could predispose susceptible individuals to psychotic symptoms. Although THC can accelerate the onset of schizophrenia, CBD displays antipsychotic properties, can prevent the acquisition of emotionally irrelevant memories, and reverses amphetamine-induced neuronal sensitization through selective phosphorylation of the mechanistic target of rapamycin (mTOR) molecular signaling pathway. This review summarizes clinical and preclinical evidence demonstrating that distinct phytocannabinoids act within the VHipp and associated corticolimbic structures to modulate emotional memory processing through changes in mesolimbic DA activity states, salience attribution, and signal transduction pathways associated with schizophrenia-related pathology.”
[Cannabinoid receptor system regulates ion channels and synaptic transmission in retinal cells].
“Endocannabinoid receptor system is extensively expressed in the vertebrate retina. There are two types of cannabinoid receptors, CB1 and CB2. Activation of these two receptors by endocannabinoids N-arachidonoylethanolamide (anandamine, AEA) and 2-arachidonyl glycerol (2-AG) regulates multiple neuronal and glial ion channels, thus getting involved in retinal visual information processing. In this review, incorporating our results, we discuss the modulation of cannabinoid CB1 and CB2 receptors on retinal neuronal and glial ion channels and retinal synaptic transmission.”
The Synthetic Cannabinoid WIN 55,212-2 Elicits Death in Human Cancer Cell Lines.
“Studies have revealed that cancer might be treated with cannabinoids since they can influence cancer cell survival. These findings suggest an alternative treatment option to chemo- and radiotherapy, that are associated with numerous adverse side-effects for the patients.
MATERIALS AND METHODS:
Viability staining was conducted on lung cancer, testicular cancer and neuroblastoma cells treated with different concentrations of the synthetic cannabinoid WIN 55,212-2 and the percentage of dead cells was compared. Activity of apoptosis-related enzymes was investigated by the presence of DNA ladder in gel electrophoresis.
RESULTS:
Treatment with different WIN 55,212-2 concentrations led to a significant dose-dependent reduction of cell viability. A DNA ladder was observed after WIN 55,212-2 treatment of testicular cancer and lung cancer cells.
CONCLUSION:
The application of WIN 55,212-2 was found to trigger cell death in the investigated cell lines. The decline in lung cancer and testicular cancer cell viability seems to have been caused by apoptosis. These findings may contribute to development of alternative cancer therapy strategies.”