Future Medicine

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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Benjamin Caplan, MDThe Endocannabinoid System’s Effect on the Cerebellum is a Drawback for Anti-Inflammatory Meds
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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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Benjamin Caplan, MDConsuming CBD with THC Decreases Systemic Availability of THC
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The Current Research on Cannabis-Alcohol Interactions and Risk Factors for Using Them Together

Title: Cannabis and Alcohol- From Basic Science to Public Policy

This new analysis summarizes the most recent preclinical trials and epidemiological studies concerning the interactions between cannabis and alcohol, as well as possible risk factors for co-use. Specific risk factors, such as frequency of use or belonging to particular groups, were found to be significant within studies (but not across separate studies.) The compiled data reveals that previous research is inconsistent and emphasizes the need for further research to elucidate at-risk populations.  


This article highlights a few secondary findings which all focus on the gaps in our knowledge concerning cannabis, of which there are many. There may be potential concerns with the integration of cannabis into modern culture, which has essentially normalized alcohol consumption. Future research will undoubtedly evaluate these concerns, and highlight potential advantages that cannabis consumption may offer as an alternative option.

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Benjamin Caplan, MDThe Current Research on Cannabis-Alcohol Interactions and Risk Factors for Using Them Together
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A Call for More Research: Adolescent Cannabis Use and Mental Health Risks

Title: Adolescent Cannabis Use and Risk of Mental Health Problems – The Need for Newer Data

Here, an article presenting a case, justifying the need for new research to determine how cannabis use in adolescents may affect their risk for mental health. Few recent studies have come out discussing mental health and adolescent use. This is problematic because, over the years, cannabis products have been curated to be significantly more potent than in the past. Considering how vulnerable the brain is, during adolescence, because it is still developing, longitudinal studies need to be conducted to fully elucidate the effects of cannabis on development. 


This review highlights how poorly adolescents consuming cannabis seem to be at titrating their dose, or correctly self-regulating consumption of cannabis. There is an overall need for greater education before cannabis is acquired, from a dispensary or otherwise. For adults and teens seeking to self-regulate their use of cannabis, irrespective of the consumption method, it is difficult to succeed, considering the gross lack of knowledge and sophistication around the dosage. The wide variability in choice and make-up of cannabis products, added to the complexity associated with how each patient may process the myriad of cannabinoids within the products consumed leads to a complexity of confounding variables, and here, a call for more studies to be conducted on more than just adolescents. 

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Benjamin Caplan, MDA Call for More Research: Adolescent Cannabis Use and Mental Health Risks
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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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Benjamin Caplan, MDCannabinoids and autoimmune diseases: A systematic review (Diabetes)
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Incidents of Driving Under the Influence of Drugs Reveals A Need for Stricter Regulations

Title: A review of drug abuse in recently reported cases of driving under the influence of drugs (DUID) in Asia, USA, and Europe

A recent literature review has found that the current driving regulations in Asia, Europe, and the US have not prevented cases of driving under the influence of drugs. The authors observed steady trends of incidences of driving under the influence in all three regions, despite legislature specifically enacted against such actions. In the literature, there is a consistent recommendation that drivers should be regularly tested, especially in the case of an accident, in order to gather more data on the role of drugs in traffic accidents. 


This review highlights the different illicit drugs that contribute to traffic accidents, depending on the region of the world. Cannabis is legal in certain areas of Europe, whereas it is still considered an illicit substance here in the US, and many other locations, worldwide. Looking at the differences in severity or circumstance of the accidents between the type of illicit drug used may provide data to create more beneficial regulations for each country. As the legal status of cannabis continues to evolve, and it becomes more common to find drivers on the road who have consumed a minimal amount of cannabis, new screening techniques will likely be developed to help the culture establish what it considers an “acceptable amount” of blood-borne cannabinoids to be.

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Benjamin Caplan, MDIncidents of Driving Under the Influence of Drugs Reveals A Need for Stricter Regulations
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The Endocannabinoid System may Provide Biomarkers for Endometrial Cancer

Title: Identification of Novel Predictive Biomarkers for Endometrial Malignancies- N-Acylethanolamines

A recent study has demonstrated that specific members of the endocannabinoid system may serve as potential biochemical markers for endometrial cancer. Elevated levels of two products of the endocannabinoid system (N-palmitoylethanolamine and N-arachidonoylethanolamine), reflect the production of endometrial tumors.

By screening for elevated levels of those substances, it may be easier for physicians to more quickly recognize the possible presence of endometrial tumors, leading to a potentially sooner diagnosis and intervention. Further research should be conducted to see if there is an even stronger connection between the dysregulation of the endocannabinoid system and endometrial cancer. 


This study highlights the far-reaching arms of the endocannabinoid system that are still so poorly understood. Until the federal government supports the research of cannabis and helps the general public to recognize it as a medically useful substance, research will continue to be limited and stifled. Government-sponsored research is required to boost the growing data that is currently limited by a reliance on private funding. State governments continue to legalize medical marijuana and recognize the medical and economic benefits of cannabis-based medicines. As local legislature demonstrates the success of medical cannabis programs, many patients continue to look to the federal government to follows suit, to further support our fellow citizens in need. 

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Benjamin Caplan, MDThe Endocannabinoid System may Provide Biomarkers for Endometrial Cancer
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Maintain a Balanced Diet when Consuming Oral Cannabidiol

Title: Food effect on pharmacokinetics of cannabidiol oral capsules in adult patients with refractory epilepsy

Researchers have recently revealed the importance of maintaining a balanced diet, when consuming cannabidiol (CBD). Consuming oral capsules containing CBD may be a more consistent method of consumption than blending CBD into liquids or solid foods, but unfortunately, capsules do not prevent a high degree of potential fluctuation of dosing. The fat content of a meal may vary widely, and so may change the active concentrations of CBD which become active in the bloodstream. In other words, the effects felt by a consumer may be either stronger or weaker, and differ in duration, related to the method of consumption, and the product make-up taken. Patients considering CBD as a therapeutic intervention, who also want a consistency of effect, would be wise to be mindful to maintain a diet with a balanced amount of fat (oils, butter, etc.) when consuming CBD capsules. 


This article highlights the variation of effects felt when altering consumption methods. For example, edibles and inhaled cannabinoids of the same dosage have extremely different effects, because of how they are processed in the body processes. When inhaled, tetrahydrocannabinol (THC) diffuses across structures in the lungs known as alveoli, and are then transmitted to circulate throughout the bloodstream. Edibles introduce THC into the system by first metabolizing with liver enzymes, resulting in an altered metabolite of THC circulating throughout the body. This subtly-altered metabolite of THC can be more potent than the starting material, although the onset is delayed due to the process of consumption, digestion, and metabolism. All consumers would do well to research their consumption method of choice and proceed carefully when switching between methods. 

Tweet: Researchers have recently revealed the importance of maintaining a balanced #diet when consuming #cannabidiol (#CBD). Learn more at

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Benjamin Caplan, MDMaintain a Balanced Diet when Consuming Oral Cannabidiol
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False Memory Formation Does not Differ between Cannabis Users and Controls

Title: False memory formation in cannabis users- a field study

This new study has revealed that although cannabis use does not increase the rate of false memory acquisition, cannabis use did increase the uncertainty of participants. It was also determined that intoxicated cannabis users were less accurate when recognizing true events, providing evidence that cannabis intoxication hinders memory formation.

This research provides a basis of knowledge for those interviewing people under the influence of cannabis for legal proceedings to determine the validity of their statements. If cannabis intoxication increases the uncertainty and liberal answers provided by users then their statements should be used sparingly or well-corroborated. 


This research highlights the importance of understanding cannabis for legal proceedings. More and more state governments are legalizing medical and recreational cannabis, each year, increasing the amount of those eligible to legally consume cannabis. As cannabis use continues to climb in popularity, witnesses or others interviewed in legal settings may not provide the most accurate information. Acute cannabis use should be a consideration related to legal proceedings so that the users’ statements can be weighed appropriately.  

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Benjamin Caplan, MDFalse Memory Formation Does not Differ between Cannabis Users and Controls
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The Endocannabinoid System May Play a Role in Autism Spectrum Disorders

Title: CB1 receptor antagonism in capuchin monkeys alters social interaction and aversive memory extinction

A recent study has revealed that the dysregulation of the endocannabinoid system may play a role in autism spectrum disorders (ASD). Using non-human primates, researchers were able to mimic some of the social impairment seen in autism models by antagonizing cannabinoid 1 receptors with synthetic cannabinoids. Future research may continue to show links between ASD and the endocannabinoid system, suggesting that cannabinoids may be used to treat the social impairments characteristic in ASD. 


This research highlights how the endocannabinoid system may provide novel targets for developing therapies for what have seemed, previously, to be treatment-resistant disorders. Autism is still not well-understood and has many false beliefs associated with it. By studying the possible role of the endocannabinoid systems in ASD, researchers may be able to shed light on the mechanism(s) underlining the disorders and develop targeted treatments that allow patients a degree of greater control over the symptoms.

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Benjamin Caplan, MDThe Endocannabinoid System May Play a Role in Autism Spectrum Disorders
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