Animal Model

Oleamide and the Endocannabinoid System Protect Against Excitotoxic Damage

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. 

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Benjamin Caplan, MDOleamide and the Endocannabinoid System Protect Against Excitotoxic Damage
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Snacking Reduces 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.

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Benjamin Caplan, MDSnacking Reduces Stress?
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The Effects of Cannabinoid 1 Receptor on 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.


brain and cannabis leaf

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Benjamin Caplan, MDThe Effects of Cannabinoid 1 Receptor on Memory
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Cannabinoid Receptors Play Important Roles in Anti-inflammation, Anti-depression, Immune modulation, and HIV support

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.

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Benjamin Caplan, MDCannabinoid Receptors Play Important Roles in Anti-inflammation, Anti-depression, Immune modulation, and HIV support
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California veterinarians & Cannabis

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

Benjamin Caplan, MDCalifornia veterinarians & Cannabis
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The Effect of Cannabis Consumption on Sperm

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. 

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Benjamin Caplan, MDThe Effect of Cannabis Consumption on Sperm
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CB1 and CB2 receptors play differential roles in early zebrafish locomotor development

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

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Benjamin Caplan, MDCB1 and CB2 receptors play differential roles in early zebrafish locomotor development
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The Endocannabinoid System’s Effect on the Cerebellum is a Drawback for Anti-Inflammatory Meds

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

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This paper is also stored here:    http://bit.ly/2Sh4JhA     inside the CED Foundation Archive

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Benjamin Caplan, MDThe Endocannabinoid System’s Effect on the Cerebellum is a Drawback for Anti-Inflammatory Meds
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Gauging Mice with CBD, part 2

A Forbes article shedding light on #CBD and its effects on the livers of mice. Dr Peter Grinspoon and Devitt-Lee wisely talk some sense around the lousy methods and insensible dosage used on mice to command sensational headlines. http://bit.ly/2XMP36W

The CED Foundation review of the topic: http://bit.ly/2jYOlFX

Benjamin Caplan, MDGauging Mice with CBD, part 2
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Cannabinoids and autoimmune diseases: A systematic review (Diabetes)

As it stands, there is no cure for Type 1 Diabetes Mellitus. But, some of us in the medical community are starting to wonder if cannabis could be a viable treatment option. Several studies already address this, with impressive findings, and now, A new mouse model study suggests that not only could CBD prevent Type 1 Diabetes, but it seems to also reduce symptoms after onset. 

Now researchers must determine the long term effects of CBD treatment. Watch a video summary below:

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This paper is also stored here:    http://bit.ly/2Y1paV5     inside the CED Foundation Archive

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Benjamin Caplan, MDCannabinoids and autoimmune diseases: A systematic review (Diabetes)
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