Animal Model

Cannabinoid Receptors in Brain Differ Due to Sex and Hormone Levels

March 13, 2020 Animal Model, CB1, Female Fertility

Male and Female Rats Differ in Brain Cannabinoid CB1 Receptor Density and Function and in Behavioural Traits Predisposing to Drug Addiction- Effect of Ovarian Hormones

In Summary

A recent study has revealed that cannabinoid receptor 1 (CB1) density and function depend on sex and hormone levels. Researchers have found that the effects of CB1 receptors in brain regions of female rats caused them to engage in behaviors that are associated with a higher risk for substance abuse disorders. Interestingly, female rats reported a lower density of CB1 receptors, suggesting that an increase in cannabis receptors may improve rats’ chances of developing a substance use disorder. Further studies need to be conducted in order to test the validity of these findings for human mammals considering the differences between the human and rat cannabinoid systems.

This study highlights the inconsistency between rat and human endocannabinoid systems. Rat models are commonly used to study biological processes for ethical, efficient, and economic reasons, but they are not always appropriate. Previous studies featured on this blog have reported fundamental differences in the endocannabinoid systems of rats and humans, suggesting that they may not provide valid evidence. Non-human mammalian models such as monkeys may provide more valid results when looking into the therapeutic effects of cannabinoids or interactions between opioid and cannabinoid systems.

The study is available for review or download here

Male-and-Female-Rats-Differ-in-Brain-Cannabinoid-CB1-Receptor-Density-and-Func-tion-and-in-Behavioural-Traits-Predisposing-to-Drug-Addiction-Effect-of-Ovarian-Hormones Download

View more studies like this in the CED Foundation Archive

To explore related information, click the keywords below:

Prenatal Exposure to Flavonoid Baicalein Shows Conflicting Results

March 1, 2020 Animal Model, Flavonoids

Baicalein, a flavonoid causes prolonged estrus and suppressed fertility output upon prenatal exposure in female mice

In Summary

Flavonoids are found in large quantities in flax seeds and plants including cannabis. There is conflicting evidence as to the effects of prenatal exposure to excessive quantities of flavonoids. The flavonoid baicalein has been used in Asian countries as herbal medicine to treat conditions including memory disorders, gastrointestinal dysfunction, and Parkinson’s disease. However, in excessive quantities, flavonoids have been shown to disrupt hormone production and function. Researchers interested in the effects of prenatal exposure to the baicalein administered the flavonoid to pregnant rats and observed effects on mothers and offspring. No signs of toxicity were observed. Exposed offspring weighed significantly less than control offspring, however, exposed female offspring also saw enhanced fertility .

The study is available for review or download here

View more studies like this in the CED Foundation Archive

To explore related information, click the keywords below:

Oleamide and the Endocannabinoid System Protect Against Excitotoxic Damage

February 27, 2020 Animal Model, endocannabinoid system

A Cannabinoid Receptor-Mediated Mechanism Participates in the Neuroprotective Effects of Oleamide Against Excitotoxic Damage in Rat Brain Synaptosomes and Cortical Slices

In Summary

Oleamide, an endocannabinoid-like compound, has been found to work with the endocannabinoid receptors to protect against excitotoxic damage. Utilizing tryptophan metabolite quinolinic acid to induces the overactivations of N-methyl-D-aspartate receptors (NMDAr), eliciting excitotoxic effects. Various doses of oleamide were given to excitotoxic rats, revealing that oleamide did provide protective effects. Further examination confirmed that oleamide served a protective role by working through the endocannabinoid system. Future research should examine other compounds that could enact neuroprotective effects through the endocannabinoid system.

Researchers continue to find novel targets for treatment within the endocannabinoid system. Although cannabis is not currently supported for medical use by the federal government the endocannabinoid system has far-reaching possibilities that can still be studied in the meantime. By using compounds like oleamide or other others that work on the endocannabinoid system researchers can determine new targets and therapeutic benefits of the endocannabinoid system.Researchers should continue to push for federally funded projects revolved around the endocannabinoid system as the underlying mechanism are still poorly understood considering the potential it holds.

The study is available for review or download here

A-Cannabinoid-Receptor-Mediated-Mechanism-Participates-in-the-Neuroprotective-Effects-of-Oleamide-Against-Excitotoxic-Damage-in-Rat-Brain-Synaptosomes-and-Cortical-Slices Download

View more studies like this in the CED Foundation Archive

To explore related information, click the keywords below:

Snacking Reduces Stress?

January 6, 2020 Animal Model, Stress

Snacking Causes Long Term Attention of HPA Axis Stress Responses and Enhancement of Brain FosB/delta FosB Expression in Rats

In Summary

Researchers have found that snacking or consuming palatable foods reduces the amount of perceived stress that an individual experiences. Although this is well-known to most people intuitively, and common knowledge in anecdote, the physiological explanation for this finding has not been thoroughly investigated. In this review, it is clear that food interacts with the hypothalamic-pituitary-adrenal (HPA) axis and stress response, including markers of neuronal plasticity. The area that regulates stress and reward are both attenuated by palatable food, such as a sucrose drink. The dampening effect of the sucrose on the HPA axis and neuronal plasticity markers continued to be seen weeks after cessation of the sucrose, suggesting that snacking can have longterm effects on stress and the reward pathway.

This has interesting implications for a medication like cannabis, which includes elements that can either stimulate or reduce appetite. If consumers of cannabis are also snacking while they consume, this may cloud an accurate understanding of the stress-relieving aspects of cannabis

The paper is also stored HERE inside the CED Foundation Archive.

View this review (yellow link) or download: http://bit.ly/2ZlHQvJ

To explore related information, click the keywords below:

The Effects of Cannabinoid 1 Receptor on Memory

January 2, 2020 Animal Model, Cannabinoid 1 Receptor, Memory

A Meta-Analysis and Systematic Review Across Species

In Summary

A recent review has exposed the contrasting information found in human and mouse model studies that study cannabis-based medicines. Acute THC use impairs non-spatial memory in humans and monkeys but not in rodents. Previous research has shown that chronic cannabis use is correlated with lower cognitive function but a mechanism of action for the decline in cognitive function has yet to be identified, and several studies have pointed that the decline is short-lived, perhaps caused by acute intoxication. This study provides evidence for cannabis-based clinical trials due to THC’s species-specific effects on memory. More information is needed to examine the full effect of cannabis on human memory as animal models have now been proven to be inaccurate.

View this review (yellow link) or download:

The Effects of Cannabinoid 1 Receptor Compounds on Memory- A Meta-Analysis and Systematic Review Across Species Download

This paper is also stored HERE inside the CED Foundation Archive

To explore related information, click the keywords below:

Cannabinoid Receptors Play Important Roles in Anti-inflammation, Anti-depression, Immune modulation, and HIV support

September 11, 2019 Animal Model, Anti-inflammatory properties, Anxiety, Autoimmunity, Blood-Levels, Cannabinoids, Cannabis, Cannabis Science, CB1, CB2, Dementia, Depression, Future Medicine, History, Science

Cannabinoid receptor 2: Potential role in immunomodulation and neuroinflammation Review

Summary Info:

Previous research and characterization of cannabinoid receptors (CBs) have consistently demonstrated the therapeutic potential for many medical conditions. CB1, the receptor responsible for the intoxicating (and other psychoactive) effects of cannabis, has demonstrated the ability to modulate concentrations of certain other neurotransmitters, giving it the capability of acting as an antidepressant. Additionally, mice lacking CB1 receptors exhibited increased neurodegeneration, increased susceptibility for autoimmune encephalomyelitis, and inferior recovery to some traumatic nerve injuries. The CB2 receptor is generally attributed to support for modulating the immune system and calming some of the body’s natural, core inflammatory signaling systems. Activation of the receptor has been found to associate with neuroinflammatory conditions in the brain, and in appropriate circumstances, can result in the programming of cell death among some immune cells. This effect points toward a role in communication, inflammation and autoimmune diseases. Furthermore, evidence points to CB2 holding significant potential in HIV therapy. Binding partners of CB2 inhibit the HIV-1 infection and help to diminish HIV replication. Historically, these staggering findings have escaped traditional modern medical understanding. Further investigation into the therapeutic potential of cannabis, with respect to the treatment of inflammation, depression, autoimmune diseases, and HIV is at a minimum, clearly warranted for a more comprehensive understanding of effective medical therapy.

Dr Caplan and the #MDTake:

The main points here no longer seem to be investigational trends, but just pillars of Cannabis Medicine that are embarrassingly new, and poorly recognized by the modern medical establishment. While the bulk of consumers, including patients, may not engage with the science on a molecular basis, by iterative or intuitive science, individuals are diligently discovering what forms of cannabis serve their personal interests more effectively. This is, through a scientific lens, a trial-and-error adventure through products, which have various ratios of cannabinoid-receptor activation or inhibition, that ultimately achieves a similar result, which is a clinical relief for a particular ailment. Does the fact that the process does not begin with a clear understanding of the involved receptors and receptor modulators really matter? If one of the primary objectives of Medicine is to treat and/or ease suffering, and the products are built upon a bedrock of chemical safety (misuse, inappropriate, or misinformed production of products notwithstanding), it should not matter that people discover it by happy accident, or through more direct achievement.

View this review (yellow link) or download:

Cannabinoid receptor 2: Potential role in immunomodulation and neuroinflammation ReviewDownload

This paper is also stored here: http://bit.ly/34CN89F inside the CED Foundation Archive

To explore related information, click the keywords below:

California veterinarians & Cannabis

August 5, 2019 Animal Model, Anxiety, Arthritis, Business of Cannabis, California, Cannabinoids, Cannabis, Cannabis News, History, Law, Legislation, Los Angeles, Pets, Regulation, Stress, Veterinarians

Vets in CA can now discuss the use of cannabis for patients and their pets legally and soon, prescribe cannabis medication. Although there is still more much research to be done, adults can already legally buy products, so involving professional vets can help keep pets safe http://bit.ly/33dmbIK

The Effect of Cannabis Consumption on Sperm

July 31, 2019 Addiction, Adolescents, Adult, Adverse Effects, Animal Model, Behavior change, Dosing, Female Fertility, Future Medicine, Gender, Heavy Use, Impairment, Intimacy, Male Fertility, Occasional Use, Products, Stigma, THC

Impacts of cannabinoid epigenetics on human development- reflections on Murphy et. al. ‘cannabinoid exposure and altered DNA methylation in rat and human sperm’ epigenetics

An op-ed has praised the work published last year which exposed how pre-conception exposure to cannabis in males is related to alterations in epigenetic regulation of the central nervous and immune systems. Murphy et. al.’s paper ‘Cannabinoid exposure and altered DNA methylation in rat and human sperm,’ revealed that the sperm cells of men who have consumed cannabis are a key vector that may affect neuraxis, heart blood vessels, immune stimulation, secondary genomic instability, and carcinogenesis in the fetus offspring. The author of the response piece extrapolates the data collected by Murphy et. al. to conclude the genome-epigenome is extremely sensitive to environmental toxicants and that further research should examine the epigenomic toxicology of multiple cannabinoids.

The effect of prenatal exposure to cannabis on birth rates, birth outcomes, and the health of the mother is still uncertain. Studies focussing on cannabis use during pregnancy are limited, and what little has been reported, is inconsistent. The featured article now brings to light that both parents may need to be cautious when attempting to conceive or when having unprotected sex as cannabis may affect both germ cells. Currently, governing bodies of obstetricians advise that pregnant mothers cease any cannabis use so if someone who needs cannabis for a medical purpose that improves their quality of life becomes pregnant they need to seek out alternative methods of treatment. Research is needed so that pregnant women can safely continue their medication or so that alternatives can be found so that women do not need to suffer for the duration of their pregnancy and possible breastfeeding period.

View this review (yellow link) or download:

Impacts of cannabinoid epigenetics on human development- reflections on Murphy et. al. ‘cannabinoid exposure and altered DNA methylation in rat and human sperm’ epigeneticsDownload

This paper is also stored here: http://bit.ly/2K42H1S inside the CED Foundation Archive

To explore related information, click the keywords below:

CB1 and CB2 receptors play differential roles in early zebrafish locomotor development

July 19, 2019 Adolescents, Adverse Effects, Aging, Animal Model, Behavior change, Blood-Levels, Cannabinoids, Cannabis Education, Cannabis Science, CB1, CB2, CBD, Crossover Study, Future Medicine, History, Impairment, Neuropathy, Placebo-Controlled

Scientists found that blocking CB1 receptors and CB2-receptors in young zebrafish resulted in morphological deficits, reductions in heart rate, and non-inflated swim bladders. These findings indicate that the endocannabinoid system is pivotal to the development of the locomotor system in zebrafish, and that disturbances to the endocannabinoid system in early life may have detrimental effects.

The translation of these effects to humans is obviously not direct, but it is important for science to learn about safety and expected effects, to examine how chemistry interacts in petri dishes, how basic organic/animal functions are impacted in a living thing, and when the time is appropriate, to then assess any effects in humans

View this review (yellow link) or download:

CB1 and CB2 receptors play differential roles in early zebrafish locomotor development Download

This paper is also stored here: http://bit.ly/2YfykgI inside the CED Foundation Archive

To explore related information, click the keywords below:

The Endocannabinoid System’s Effect on the Cerebellum is a Drawback for Anti-Inflammatory Meds

July 16, 2019 Adverse Effects, Animal Model, Anti-inflammatory properties, Behavior change, Cannabinoids, Cannabis, Cannabis Education, Cannabis Science, Coordination, Driving, Future Medicine, Heavy Use, Impairment, Jobs, Occasional Use, Overdose, Reaction Time, THC

Title: Monoacylglycerol lipase blockade impairs fine motor coordination and triggers cerebellar neuroinflammation through cyclooxygenase-2

Researchers are constantly considering how cannabis may impact the human brain, for better or worse. A recently published work points out a negative effect on the cerebellum, caused by the inhibition of the main enzyme that is used to break down the endocannabinoid “2- arachidonoylglycerol” (2-AG). By inhibiting the degradation of 2-AG, more of the endocannabinoid is allowed to remain in, and act upon, the human nervous system. This abundance of 2-AG results in reduced synthesis of prostaglandins, which produces an anti-inflammatory effect.

Unfortunately, the abundance of 2-AG also results in motor coordination deficits related to the effect on the cerebellum, but the addition of a cyclooxygenase-2 (COX-2) inhibitor (commonly found in many over-the-counter anti-inflammatory medications) reverses these cerebellar deficits.

This highlights the far-reaching capabilities of the endocannabinoid system and at least one powerful angle where researchers could develop medications to indirectly impact the endocannabinoid system. Cannabinoids are still a politically hot topic, but synthesizing drugs that alter the level of endogenous cannabinoids available in the body is an ideal way to study the endocannabinoid system and its therapeutic benefits, without engaging with the red tape that surrounds cannabis. The receptors mechanisms for the endocannabinoid system certainly warrants further investigation.

Tweet: Researchers have recently revealed the negative effects on the #cerebellum caused by the inhibition of the main enzyme utilized for the degradation of the #endocannabinoid 2- arachidonoylglycerol (#2-AG). Learn more at