CB1

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.

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Cannabis Abuse May Be Caused By Genetic Factors

February 26, 2020 Alcohol, CB1, Smoking

CNR1 and FAAH variation and affective states induced by marijuana smoking

In Summary

Researchers have recently described how genetic variation determines individual mood state after the consumption of cannabis. The variation of genes may prove useful when attempting to understand either motivation for illicit cannabis use or risk for associated abuse behaviors. Researchers determined participants affect by utilizing tension-anxiety and confusion-bewilderment assessment in order two examine CRN1 and FAAH, two encoding factors for receptors of the endocannabinoid system. Further research should be conducted to elucidate the exact genetic variations so that the risk of abuse can be screened for in individuals.

The possibility of being able to screen for genetic variations within the endocannabinoid system that affect mood may prove useful when recommending cannabis to particularly anxious patients. ∆-9-tetrahydrocannabinol (THC) has been known to cause excess anxiety is some patients and exacerbate some mood symptoms. If physicians were able to screen for particularly whose anxiety would be exacerbated by certain cannabinoids then they may be able to help guide the patient towards other cannabinoids, like cannabidiol, or a different method of treatment entirely.

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CNR1-and-FAAH-variation-and-affective-states-induced-by-marijuana-smoking Download

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Cannabinoids Affect Your Sense of Smell

February 7, 2020 CB1, Sense of Smell

Cannabinoid Receptor-Mediated Modulation of Inhibitory Inputs to Mitral 3 Cells in the Main Olfactory Bulb

In Summary

A recent study has revealed that the endocannabinoid system regulates mitral cell activity in the olfactory bulb, affecting users’ sense of smell. Cannabinoids that agonize and antagonize cannabinoid receptor 1 (CB1) are able to regulate the threshold for odor stimulation and synaptic input, thereby modulating a users ability to smell various stimuli. This may aid people suffering from neuropathic pain caused by sensitivity to an array of odors such as perfume or household cleaners.

This article highlights how much more our community has to learn about the endocannabinoid system so that we can identify all of the possible therapeutic targets it provides. It is still uncertain whether or not cannabinoid 2 receptors are found within the central nervous system, specifically regions of the brain, which could provide more targets for the non-psychoactive components of cannabis, such as THC, another mechanism to work through. The more we learn about cannabis the more possibilities arise, calling for further research to be done.

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Further Evidence for Cannabis as Treatment of Neuropathic Pain

February 1, 2020 CB1, Neuropathy

Selective modulation of the cannabinoid type 1 (CB1) receptor as an emerging platform for the treatment of neuropathic pain

In Summary

A recent review has compiled further evidence for cannabis-based medicine as a treatment option for neuropathic pain. Studies suggest 1 in 10 Americans over the age of 30 suffer from neuropathic pain, frequently due to stroke, diabetes, or nerve trauma, and that pain greatly reduces their quality of life and productivity. The currently accepted treatment for neuropathic pain is various combinations of tricyclic antidepressants and anticonvulsants, however, the treatments are often ineffective, leaving patients in constant suffering. Cannabis has been shown to alleviate this pain in multiple studies but has had little impact on the community suffering from neuropathic pain due to select states legalizing its use and the lack of federally funded data.

This study highlights the possible implications of cannabis-use within the opioid-crisis. When antidepressants and anticonvulsants prove ineffective many patients use opioids as the second line of defense against pain, leading to addiction and abuse. Numerous studies have revealed the interaction between the endocannabinoid and opioid systems, highlighting cannabis as a possible remedy for the widespread opioid abuse, yet the legal status of cannabis limits naturalistic studies that would provide definite answers.

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The Therapeutic Potential of Indenopyrazoles

January 10, 2020 Anti-inflammatory properties, Cannabinoids, CB1, CB2

An overview of the synthetic and medicinal perspectives of indenopyrazoles

In Summary:

Indenopyrazoles, molecules crucial to many biological signaling pathways, have been found to bind to cannabinoid receptors and seem to exhibit therapeutic properties in a variety of conditions. A review of studies on the molecule describes previously documented antimycobacterial, antipsychotic, anti-tumor, and anti-microbial properties, among others. The molecule has demonstrated moderate affinity for both cannabinoid-1 and cannabinoid-2 receptors, suggesting possible additional anti-inflammatory and anti-neurodegenerative capabilities related to the interactions with these receptors. Further research may uncover additional therapeutic applications and shed light on additional benefits of cannabinoid receptors.

Graphical abstract of actions of indenopyrazoles

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An overview on the synthetic and medicinal perspectives of indenopyrazolesDownload

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Cannabinoids Further Demonstrate Therapeutic Potential in Interactions with Adrenaline and Serotonin Systems

November 7, 2019 Adult, Behavior change, Biosynthesis, Cannabinoids, Cannabis, Cannabis Science, CB1, CB2, Depression, Future Medicine, Genetics, Mental Health, Neuropathy, Obesity, Pain, Schizophrenia

Regulation of noradrenergic and serotonergic systems by cannabinoids: relevance to cannabinoid-induced effects

In Summary:

Among many system-wide interactive effects, the noradrenergic and serotonergic hormone/signaling systems are responsible for pain, mood, arousal, wakefulness, learning, anxiety, and feelings of reward. A recent review dives deeper into the interactions between cannabinoids and these two systems: cannabinoids play roles in exciting, inhibiting, and regulating the nerve activity and feedback of both the noradrenergic and serotonergic systems. This data further underscores the therapeutic potential of cannabis for conditions such as depression, chronic pain, and insomnia, all of which are mediated, at least in part, by these systems. Further research may uncover more specific therapies targeted toward the noradrenergic and serotonergic systems and their interactions with cannabinoids.

Dr. Caplan and the #MDTake:

It would be shocking to imagine that, in addition to the usual fruits and vegetables on display at supermarkets, all of a sudden, there was a new category of healthy food. Similarly, the recognition that cannabinoids play a central role in animal physiology is embarrassingly recent. Surveying a sea of illnesses that have become increasingly common, over the last hundred years, before which cannabis was a common household product, also begs the question about a relationship between the circumstances. Might some of the common maladies of modern medicine be attributable to a cannabinoid deficiency syndrome?

A Schematic overview for regulation of NA/LC and 5-HT/DRN cells by the CB1 receptor

Neurochemical Evidence for cannabinoid-induced effects

Electrophysiological evidence for acute effects of cannabinoids on neuronal activity

Neurochemical evidence for cannabinoid-induced effects in the locus coeruleus

Functional evidence fo cannabinoid-induced effects

Electrophysiological evidence for acute effects of cannabinoids

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Regulation of noradrenergic and serotonergic systems by cannabinoids: relevance to cannabinoid-induced effectsDownload

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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.

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Cannabinoid receptor 2: Potential role in immunomodulation and neuroinflammation ReviewDownload

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Exciting New Cannabis Compound with Great Therapeutic Potential

August 30, 2019 Adverse Effects, Anti-inflammatory properties, Cannabinoids, Cannabis, Cannabis Science, CB1, Future Medicine, Products

Functionalized 6-(Piperidin-1-yl)-8,9-Diphenyl Purines as Peripherally Restricted Inverse Agonists of the CB1 Receptor

Summary information:

A recent study has developed a synthetic compound that can act as an inverse agonist (a reverse activator) of cannabinoid receptor 1 (CB1.) Considering how prevalent these receptors are in the body, this may serve as a useful treatment for a great many concerns that involve this receptor, and/or for altering the effects of other cannabinoid therapies. The developed compounds are orally bioavailable and peripherally selective for CB1, meaning they can be taken by mouth and can still have action in the periphery of the body, as opposed to simply at the brain’s receptors. The selectivity and therapeutic benefits of these novel compounds present a promising development for the potential treatment of metabolic syndrome, diabetes, liver diseases, and gastrointestinal disorders, to name but a few.

Dr Caplan’s Input:

We have CB1 receptors from head-to-toe, through every organ, and just about everywhere in the body. This article highlights a few interesting points. While we have compounds which can activate a target cannabinoid receptor, the action in this review is actually stimulating an opposite impact (activating the opposite action, or an “inverse agonist” effect.) Also, the concept of targeting central (at the brain) vs peripheral (everywhere else) has not been well-addressed yet in Cannabis Medicine. If we can separate the two targets easily, the options for applications of cannabinoid therapies multiplies, as does the opportunity to eliminate undesirable effects.

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Functionalized 6-(Piperidin-1-yl)-8,9-Diphenyl Purines as Peripherally Restricted Inverse Agonists of the CB1 ReceptorDownload

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Cannabinoid Receptors Regulating the Function of Opioid Receptors

August 26, 2019 Abuse, Addiction, Behavior change, Cannabinoids, Cannabis, Cannabis Science, CB1, Future Medicine, Illicit Drug Use, Opiates, Overdose

Constitutive Activity of the Cannabinoid CB1 Receptor Regulates the Function of Co-expressed Mu Opioid Receptors

Summary info:

Cannabinoid receptors have been found to regulate the function of co-expressed mu-opioid receptors. Researchers have found data that indicates the constitutive activity within the cannabinoid system reduced the capacity of expressed mu-opioid receptor functions. This research brings to light the possible benefits of modulating opioid consumption with cannabis-based medicines.

Dr Caplan Discussion Points:

One of the interesting discussion points in this paper is a close look at the effects of the CB1 receptor and its capacity to reduce the function of some mu-opioid receptors, through a mechanism different than naloxone. This suggests some appropriate optimism for cannabinoid-based tools in the battle against the worldwide opioid epidemic.

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Constitutive Activity of the Cannabinoid CB1 Receptor Regulates the Function of Co-expressed Mu Opioid Receptors Download

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Natural & Cannabinoid Changes in Dopamine: A key to the psychosis question?

August 25, 2019 Adolescents, Adult, Adverse Effects, Agitation, Anxiety, Behavior change, Cannabinoids, Cannabis, Cannabis Science, Cannabis Use Disorder (CUD), CB1, CED Foundation, Cognition, Dopamine, Psychosis, Schizophrenia

Comparing dopaminergic dynamics in the dorsolateral striatum between adolescent and adult rats- Effect of an acute dose of WIN55212-2

Brief summary:

A recent study has exposed an age-dependent mechanism within the dopaminergic system that relies on cannabinoid receptor 1 (CB1). Adult and adolescent dopamine levels were examined in the presence of a CB1 agonist and increased levels of extracellular dopamine were found in adolescents. This study reveals the different effects cannabis-based medicine has depended on the age of the patient and warrants future research to ensure cannabis has the desired therapeutic effect on patients.

Dr Caplan Discussion Points:

This adds a helpful layer of insight to the way an animal model of dopamine changes over time, as well as its interaction with exogenous cannabinoids. This sheds light on the natural evolution of the dopamine control system (irrespective of how it interacts with endocannabinoids), and it also points to how cannabinoids may be involved.

This helps to educate the discussion about how psychosis and cannabis use may interact. There is a long-held understanding that dopamine abnormalities in the specific parts of the brain (mesolimbic and prefrontal brain regions) exist in schizophrenia. More recently, research has also strongly suggested that other neurotransmitters, including glutamate, GABA, acetylcholine, and serotonin are also involved in schizophrenia (and, coincidentally, there is also interaction with these other neurotransmitters from various components of cannabis). Nonetheless, this study simply suggests that, by nature, basal dopamine levels increase during adolescence. Also, the study points out that some cannabinoids boost basal levels too. It seems logical to suggest that excessive dopamine may create a problematic force of additional tipping toward illness, within individuals for whom a congenital predisposition toward illness exists.

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Comparing dopaminergic dynamics in the dorsolateral striatum between adolescent and adult rats- Effect of an acute dose of WIN55212-2 Download

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