All posts tagged: CB1

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

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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Benjamin Caplan, MDNatural & Cannabinoid Changes in Dopamine: A key to the psychosis question?
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New Developments of Cannabinoid-Based Drugs

Title: Novel approaches in clinical development of cannabinoid drugs

A pamphlet has recently been published that highlights new approaches in the clinical development of cannabinoid-based therapies. The pamphlet begins with a look into how current cannabinoids affect patients based on gender, stress, physiological variations, and also delves into how cannabis works on the body in general.

A novel therapy that features an oral version of tetrahydrocannabinol (THC) and a synthetic activator of cannabinoid-receptor-1 (CB1) is explored in this piece and frames it to be a promising future therapy. The pharmacological properties of these two novel therapies were optimized during development after various analysis techniques, forming medications that the authors hope to see in future clinical trials. 

Although the authors remain hopeful that their cannabis-based therapies will reach clinical trials soon, trials featuring cannabinoids are difficult to test in a formal setting because of a dire lack of funding. The federal government still lists cannabis as a Schedule I substance, under the Controlled Substances Act, meaning that the federal government does not support the idea that cannabis has any medical use. Considering the legal status of cannabis, only privately-funded studies are able to take place, and unfortunately, that leaves cannabis research in an area of complete bias and prohibitively underfunded. Considering the massive literature supporting a myriad of novel therapeutic benefits, this is a costly reality to the health and well-being of millions.


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Benjamin Caplan, MDNew Developments of Cannabinoid-Based Drugs
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The Effect of Chronic Cannabis Use on Volumetric Alterations in Brain Regions

Title: Neuroanatomical alterations in people with high and low cannabis dependence

A recent article has been published revealing some volumetric alterations in specific brain regions in people who report dependence on cannabis. Magnetic resonance imaging revealed that the volume of certain regions, including the hippocampus, the cerebellum, and the caudate, in cannabis dependent users, were all reduced in size, relative to recreational cannabis users who did not use cannabis chronically. Future research will likely focus on the effects of the structural alterations on patients’ reward, stress, and addiction-relevant circuitry to examine the possible relevance of cannabis dependance on those circuits. 

There are certainly possibilities that suggest this volume difference could be of concern, but there are also a great number of explanations (more than likely) whereby this is related to another variable that we have not yet fully appreciated.

Currently, cannabis use is thought to have a little-to-no risk of addiction (beyond any “normal” product of medical value, such as coffee or eyeglasses), because it does not act directly on the reward circuit. Opioids have a high risk of addiction, and therefore a concerning safety profile, in part because of the direct effect of the opioid system on the reward pathway of the central and peripheral nervous systems. While the endocannabinoid system has been observed to act directly up the reward circuit, it does so in subtle, soft ways, making it an ideal adjunct therapy for opioids to help with pain management. Current research provides inconsistent results and appropriately emphasizes a need for more testing to validate the possibility of cannabis as a recommended pain medication. 

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This paper is also stored here:    http://bit.ly/2K5JNYn     inside the CED Foundation Archive

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Benjamin Caplan, MDThe Effect of Chronic Cannabis Use on Volumetric Alterations in Brain Regions
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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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This paper is also stored here:   http://bit.ly/2YfykgI      inside the CED Foundation Archive

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Benjamin Caplan, MDCB1 and CB2 receptors play differential roles in early zebrafish locomotor development
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Do-it-Yourself Cannabis-infused lubricants

Cannabis-infused lubricant can increase blood flow for men and create full-body experiences for women. Find out how to make your own infused lube at home with this video tutorial!

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Benjamin Caplan, MDDo-it-Yourself Cannabis-infused lubricants
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Video: The Endocannabinoid System

A simplified overview of the human side of the human-cannabis interaction system!

Built from the growing mountain of literature inside the CED Foundation Medical Cannabis Archive

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Benjamin Caplan, MDVideo: The Endocannabinoid System
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Hangovers Resulting from Drinking Negatively Impact Everyday Memory

Alcohol Hangover Has Detrimental Impact Upon Both Executive Function and Prospective Memory

A recent study revealed that alcohol hangovers negatively impact everyday memory, specifically executive function (EF) and prospective memory (PM). EF and PM are cognitive functions that underpin everyday memory; things such as remembering an appointment or where you placed your keys. Participants of the study who suffered from hangovers were able to recall significantly fewer items from memory tasks than their peers. The findings of this study may prove useful when looking into how alcohol and cannabis interact with patients.

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Benjamin Caplan, MDHangovers Resulting from Drinking Negatively Impact Everyday Memory
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Genes in the Endocannabinoid and Opioid Systems may Provide Biomarkers of Obesity

Title: Preclinical and Clinical Evidence for a Distinct Regulation of Mu Opioid and Type 1 Cannabinoid Receptor Genes Expression in Obesity

Researchers have recently found that alterations of the type 1 cannabinoid receptor gene (CNR1) and mu opioid receptor gene (OPRM1)  contribute to the development of obesity. This phenomenon was shown in rat models who were given a high-fat diet and humans currently dealing with obesity. Due to the possibility of the up-regulation of CNR1 and OPRM1 providing a mechanism for developing the obesity phenotype, those two genes could serve as biomarkers for obesity. Fortunately, the up-regulation of CNR1 and OPRM1 is reversible and may also provide a target for combatting obesity and encouraging weight loss in obese individuals. 

Highlighted here are the interactions of the endocannabinoid and opioid systems. Contradictory evidence concerning the interaction of the two systems has come out in recent years making it difficult to come to any conclusions. The endocannabinoid system has been thought to provide a safe and effective method for combatting the opioid crisis. Opioids are highly addictive and dangerous, but they are an efficient way to minimize pain which has kept them in mainstream medicine. Opioids have led to countless overdoses in recent decades causing researchers to search for a more ethical option for pain relief. Cannabis has a much better safety profile, poses no risk of overdose, and offers a welcome change of pace to traditional choices. Conclusive research is still needed to confirm, and reconfirm the details.

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

Benjamin Caplan, MDGenes in the Endocannabinoid and Opioid Systems may Provide Biomarkers of Obesity
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Cannabinoids Treat Chronic Gastrointestinal Disorders

Title: Nabilone administration in refractory chronic diarrhea- a case series

A new study reveals the efficacy of treating chronic gastrointestinal disorders with cannabinoids, such as Nabilone. Researchers followed case studies in which patients were given nabilone which greatly reduced symptoms of chronic diarrhea and weight gain, over a period of three months.

The cannabinoid treatment also reduced the abdominal pain felt by patients and improved their overall quality of life. Considering the favorable safety profile of cannabinoids and the effectiveness demonstrated in the patients, cannabinoids were deemed an appropriate and clinically beneficial method for the treatment of chronic gastrointestinal disorders, such as chronic diarrhea. 

Highlighted by this article are the many symptoms cannabis used to treat before the prohibition of cannabis and the scheduling of the medication under the Controlled Substances Act. Cannabis has been used in eastern medicine, for thousands of years, and used to be a prevalent medication in the late 19th and early 20th centuries, and has just recently been re-recognized as an option to treat anorexia associated with human immunodeficiency virus (HIV), nausea and vomiting due to chemotherapy, and various sleep disorders. Cannabis was once a well-recognized medication, but it has been mercilessly slandered by politicians. The rise and fall of cannabis have largely been politically driven pushes, and the plant and its effects deserve further study to examine the scope and efficacy of its therapeutic benefits. 

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This paper is also stored here:     http://bit.ly/2jP1ocV    inside the CED Foundation Archive

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Benjamin Caplan, MDCannabinoids Treat Chronic Gastrointestinal Disorders
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Consuming CBD with THC Decreases Systemic Availability of THC

Title: Model-based analysis on systemic availability of coadministered cannabinoids after controlled vaporized administration 

A new study revealed findings that vaporizing cannabidiol (CBD) with ∆-9-tetrahydrocannabinol (THC) lowers the systemic availability of THC.

Researchers analyzed the blood plasma level of CBD and THC in a randomized, double-blind study, and found that those who inhaled a high dose of CBD were found to have lower levels of THC. Frequent cannabis users were found to have only minorly decreased levels of THC in their plasma when high doses of CBD was coadministered. Future studies should be conducted to examine the validity of these results for other consumption methods. 

This work highlights how those who have consumed too much THC can combat some of the symptoms associated with THC by consuming CBD. Occasionally, cannabis users may overindulge in THC and feel anxiety, panic, or dizziness. One of the best ways to combat such overindulgence (and lower the effects of THC) is to consume a high dose of CBD. Other, non-cannabis related, methods are also commonly recommended, such as relaxation or food with high levels of the terpenes caryophyllene and limonene. When using cannabis it’s important to start low and go slow in order to minimize the possibility of overindulgence. 

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

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Benjamin Caplan, MDConsuming CBD with THC Decreases Systemic Availability of THC
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