“Anandamide, a major endocannabinoid, participates in energy metabolism homeostasis and neurobehavioral processes. In a secondary analyses of an open-label, randomized controlled trial, we investigated the long-term effect of aerobic exercise on resting plasma anandamide, and explored its relationship with changes in body weight, cardiorespiratory fitness, and mood status in healthy, physically inactive individuals. Thirty-four participants (age = 38 ± 11.5, BMI = 26.6 ± 3.6) were intention to treat-analysed (Exercise: n = 17; Control: n = 17). After intervention, there were significant decreases in plasma anandamide (p < .01), anger, anxiety, and body weight (all p < .05), whereas cardiorespiratory fitness increased (p < .05) in the exercise group. There were no significant changes in any variable for the control group. In the whole cohort, adjusted R2 of multiple linear regressions showed that 12.2% of change body weight was explained by changes in anandamide (β = 0.391, p = .033), while 27% of change in mood disturbance (β = 0.546, p = .003), and 13.1% of change in anger (β = 0.404, p = .03) was explained by changes in anandamide. Our data suggest that the weight loss and mood improvement through regular moderate exercise may involve changes in anandamide metabolism/signaling.” https://www.ncbi.nlm.nih.gov/pubmed/30578894 https://www.sciencedirect.com/science/article/abs/pii/S0031938418308254?via%3Dihub]]>
Tag Archives: Cannabinoids
Plants come to mind: Phytocannabinoids, endocannabinoids, and the control of seizures
Social isolation as a promising animal model of PTSD comorbid suicide: neurosteroids and cannabinoids as possible treatment options.
“Post-traumatic stress disorder (PTSD) is a psychiatric condition characterized by drastic alterations in mood, emotions, social abilities and cognition. Notably, one aspect of PTSD, particularly in veterans, is its comorbidity with suicide. Elevated aggressiveness predicts high-risk to suicide in humans and despite the difficulty in reproducing a complex human suicidal behavior in rodents, aggressive behavior is a well reproducible behavioral trait of suicide. PTSD animal models are based on a peculiar phenotype, including exaggerated fear memory, anxiety- and depressive-like behaviors associated with neurochemical dysregulations in emotional brain circuitry. The endocannabinoid and the neurosteroid systems regulate emotions and stress responses, and recent evidence shows these two systems are interrelated and critically compromised in neuropsychiatric disorders. For instance, levels of the neurosteroid, allopregnanolone, as well as those of the endocannabinoids, anandamide and its congener, palmitoylethanolamide are decreased in PTSD. Similarly, the endocannabinoid system and neurosteroid biosynthesis are altered in suicidal individuals. Selective serotonin reuptake inhibitors (SSRIs), the only FDA-approved treatments for PTSD and depression, fail to help half of the treatment-seeking patients. This highlights the need for developing biomarker-based efficient therapies. One promising hypothesis points to stimulation of allopregnanolone biosynthesis as a valid end-point to predict treatment response in PTSD patients. This review highlights running findings on the role of the endocannabinoid and neurosteroid systems in PTSD and suicidal behavior both in a preclinical and clinical perspective. A specific focus is given to predictive PTSD/suicide animal models. Ultimately, we discuss the idea that disruption of neurosteroid and endocannabinoid biosynthesis may offer novel promising biomarker candidates to develop new treatments for PTSD and, perhaps, suicidal behavior.” https://www.ncbi.nlm.nih.gov/pubmed/30586627 https://www.sciencedirect.com/science/article/pii/S0278584618305839?via%3Dihub]]>
Knowledge, Attitudes, and Perceptions of Cannabinoids in the Dermatology Community
“Recent research has identified potential uses of cannabinoids in dermatology, including psoriasis, atopic dermatitis, and wound healing.
This study examined dermatology providers’ knowledge, attitudes, and perceptions on therapeutic cannabinoids using a 20-question online survey.
The response rate was 21% (n=531). Most responders thought cannabinoids should be legal for medical treatment (86%). Nearly all (94%) believed it is worthwhile to research dermatologic uses of cannabinoids. 55% reported at least one patient-initiated discussion about cannabinoids in the last year. Yet, 48% were concerned about a negative stigma when proposing cannabinoid therapies to patients. While most responders (86%) were willing to prescribe an FDA-approved cannabinoid as a topical treatment, fewer (71%) were willing to prescribe an oral form. 64% of respondents did not know that cannabidiol is not psychoactive and 29% did not know that tetrahydrocannabinol is psychoactive.
CONCLUSIONS:
Dermatology providers are interested in prescribing cannabinoids and patients are speaking about cannabinoids with their dermatologists. However, providers’ fund of knowledge on this subject is lacking. These results highlight the need for further education and research to detangle the dermatologic benefits and risks of cannabinoids.” https://www.ncbi.nlm.nih.gov/pubmed/30586258“Cannabinoid system in the skin – a possible target for future therapies in dermatology.” https://www.ncbi.nlm.nih.gov/pubmed/19664006
]]>An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia.
“In this experimental randomized placebo-controlled 4-way crossover trial, we explored the analgesic effects of inhaled pharmaceutical-grade cannabis in twenty chronic pain patients with fibromyalgia. We tested four different cannabis varieties with exact knowledge on their [INCREMENT]-tetrahydrocannabinol (THC), and cannabidiol (CBD) content: Bedrocan® (22.4 mg THC, < 1 mg CBD), Bediol® (13.4 mg THC, 17.8 mg CBD), Bedrolite® (18.4 mg CBD, < 1 mg THC) and a placebo variety without any THC or CBD. Following a single vapor inhalation, THC and CBD plasma concentrations, pressure and electrical pain thresholds, spontaneous pain scores and drug high were measured for 3 hours. None of the treatments had an effect greater than placebo on spontaneous or electrical pain responses, although more subjects receiving Bediol® displayed a 30% decrease in pain scores compared to placebo (90% vs. 55% of patients, p = 0.01), with spontaneous pain scores correlating with the magnitude of drug high (ρ = -0.5, p < 0.001). Cannabis varieties containing THC caused a significant increase in pressure pain threshold relative to placebo (p < 0.01). CBD inhalation increased THC plasma concentrations but diminished THC-induced analgesic effects, indicative of a synergistic pharmacokinetic but antagonistic pharmacodynamic interactions of THC and CBD. This experimental trial shows the complex behavior of inhaled cannabinoids in chronic pain patients with just small analgesic responses after a single inhalation. Further studies are needed to determine long-term treatment effects on spontaneous pain scores, THC-CBD interactions and the role of psychotropic symptoms on pain relief.” https://www.ncbi.nlm.nih.gov/pubmed/30585986 https://insights.ovid.com/crossref?an=00006396-900000000-98794]]>
Attenuation Effect of Cannabinoid Type 1 Receptor Activation on Methamphetamine-Induced Neurodegeneration and Locomotion Impairments among Male Rats.
“A number of neuroimaging studies on human addicts have revealed that abuse of Methamphetamine (METH) can induce neurodegenerative changes in various brain regions like the cerebral cortex and cerebellum. Although the underlying mechanisms of METH-induced neurotoxicity have been studied, the cellular and molecular mechanisms of METH-induced neurotoxicity remain to be clarified.
Previous studies implicated that cannabinoid type 1 receptors (CB1Rs) exert neuroprotective effects on several models of cerebral toxicity, but their role in METH-induced neurotoxicity has been rarely investigated. Moreover, the cerebellum was considered as a potential target to evaluate the effects of cannabinoids on locomotion activity as the CB1Rs are most widely distributed in the molecular layer of cerebellum. Therefore, the present study was carried out to evaluate whether neurodegeneration induced in the cerebellum tissue implicated in locomotion deficit induced by METH.
FINDINGS:
The results of the present study demonstrated that repeated exposure to METH increased cerebellar degeneration level as compared to the saline and dimethyl sulfoxide (DMSO) groups. In addition, METH-treated rats showed hyperactivity as compared to the saline and DMSO groups. Pretreatment with WIN significantly attenuated neurodegeneration and hyperactivity induced by METH.CONCLUSION:
The findings of this study provided evidence that CB1Rs may serve as a therapeutic strategy for attenuation of METH-induced locomotor deficits.” https://www.ncbi.nlm.nih.gov/pubmed/30574283 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294485/Cannabis for cancer – illusion or the tip of an iceberg: a review of the evidence for the use of Cannabis and synthetic cannabinoids in oncology.
“A flowering plant of variegated ingredients and psychoactive qualities, Cannabis has long been used for medicinal and recreational purposes.
Regulatory approvals have been gained across a broad range of palliative and therapeutic indications, and in some cases, included in standard treatment guidelines.
Areas covered: The use of Cannabis and cannabinoid-based-medicines in oncology is summarized in this article. Cannabinoids were classified according to natural and synthetic subtypes and their mechanisms of action expounded. The variability of available products is discussed in the clinical context and data regarding chemotherapy-induced nausea and vomiting, cancer-related pain, anorexia, insomnia and anxiety are presented.
Moreover, immunological and antineoplastic effects in preclinical and clinical trials are addressed. Concepts such as synergism or opposition with conventional treatment modalities, sequence of administration and dosage, molecular cross-talk and malignancy-cannabinoid congruence, are explored. Finally, side-effects, limitations in trial design and legislation barriers are related.
Expert opinion: Sufficient evidence supports use of Cannabis for palliative indications in oncology, however, patients should be carefully selected, guided and followed. Promising research suggests potent antineoplastic activity, but more data must be accrued before conclusions can be drawn.”
https://www.ncbi.nlm.nih.gov/pubmed/30572744
https://www.tandfonline.com/doi/abs/10.1080/13543784.2019.1561859?journalCode=ieid20
“Previous studies have shown that a cytosine (C) to thymine (T) single nucleotide polymorphism (SNP) of the human cannabinoid receptor 1 (CNR1) gene is associated with positive emotional processing.
C allele carriers are more sensitive to positive emotional stimuli including happiness. The effects of several gene polymorphisms related to sensitivity to emotional stimuli, such as that in the serotonin transporter gene-linked polymorphic region (5HTTLPR), on emotional processing have been reported to differ among cultures-e.g., between those that are independent and interdependent. Thus, we postulated that the effects of the CNR1 genotype on happiness might differ among different cultures because the concept of happiness varies by culture.
We recruited healthy male and female young adults in Japan, where favorable external circumstances determine the concept of happiness, and Canada, where the concept of happiness centers on positive inner feelings, and compared the effects of the CNR1 genotype on both subjective happiness levels (self-evaluation as being a happy person) and situation-specific happiness (happy feelings accompanying various positive events) by using a questionnaire.
We found that the effect of CNR1 on subjective happiness was different between the Japanese and Canadian groups. The subjective happiness level was the highest in Japanese individuals with the CC genotype, whereas in Canadian participants, it was the highest in individuals with the TT genotype. Furthermore, the effects of CNR1 genotype on situation-specific happiness were also different between the groups. Happiness accompanied with being surrounded by happy people was the highest among Japanese individuals with the CC genotype, whereas among Canadian individuals, it was the highest in TT genotype carriers.
These findings suggest that culture and CNR1 polymorphism interact to influence the perception of happiness.”
“The lack of good diagnostic/prognostic biomarkers and the often late presentation of endometrial cancer (EC) hinders the amelioration of the morbidity and mortality rates associated with this primarily estrogen-driven disease, a disease that is becoming more prevalent in the population.
Previous studies on the expression of the classical cannabinoid receptors, CB1 and CB2, suggest these could provide good diagnostic/prognostic biomarkers for EC but those observations have been contradictory. In this study, we sought to resolve the inconsistency of CB1 and CB2 expression levels in different EC studies.
To that end, we used qRT-PCR and immunohistochemistry (IHC) for CB1 and CB2 in endometrial biopsies from women with or without EC and found that transcript levels for both CB1 and CB2 were significantly decreased by 90 and 80%, respectively in EC. These observations were supported by histomorphometric studies where CB1 and CB2 staining intensity was decreased in all types of EC.
These data suggest that the loss of both types of CB receptors is potentially involved in the development of or progression of EC and that CB1 and CB2 receptor expression could serve as useful histological markers and therapeutic targets in the treatment of or prevention of EC.”