cannabinoid

Treating Cannabinoid Hyperemesis Syndrome with Benzodiazepines

Resolution of cannabinoid hyperemesis syndrome with benzodiazepines- a case series

In summary

A recent series of case studies has revealed the possible benefits of utilizing benzodiazepines to treat cannabinoid hyperemesis syndrome. Cannabis hyperemesis syndrome (CHS) is characterized by nausea, cyclic vomiting, and intense abdominal pain due to chronic cannabis consumption. Although CHS is now gaining recognition for how under-recognized the condition is, many patients suffering from CHS still suffer for long periods of time and have difficulty responding to traditional anti-emetics. Benzodiazepines, a common sleeping medication, were distributed to the four featured patients and appeared to provide rapid relief. Further research should focus on the development of a benzodiazepine-like substance that provides the same antiemetic effects while minimizing side effects. 

Benzodiazepines and benzodiazepine-like medications, such as Ambien (zolpidem tartrate), are known to have unsavory side-effects that can negate its benefits. Ambien specifically has been featured heavily in popular media due to the dangerous activities of patients utilizing Ambien for insomnia as some have caused serious accidents and even attempted murder. Considering the dangerous side-effects of such medications, those who report cannabis use or are screened and found to test positive for cannabis use should be advised to immediately cease all cannabis use and general anti-emetics should be attempted before benzodiazepines.

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Benjamin Caplan, MDTreating Cannabinoid Hyperemesis Syndrome with Benzodiazepines
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Sunk Cost Bias seen in Frequent Cannabis Users

Persisting on the Past- Cross-sectional and Prospective Associations Between Sunk Cost Propensity and Cannabis Use

Researchers have recently found that those diagnosed with cannabis use disorder are also likely to display sunk cost bias. Sunk cost bias is the overgeneralized tendency to persist based on past investment, in other words, the tendency to focus heavily on the past and perseverate more than their counterparts. In a two-part study, it was found that frequent cannabis use was positively associated with sunk cost bias and that sunk cost bias was able to predict frequent cannabis use in a separate cohort. This correlation may prove useful when developing a possible examination or screening test to determine the benefit of medical cannabis for individuals looking into cannabis-based treatments. 

Cannabis use may not be for everyone as cannabinoids can affect people differently depending on their general demeanor or perhaps some mechanism that has yet to be defined. The most abundant, and perhaps well studied, psychoactive cannabinoid in cannabis is ∆-9-tetrahydrocannabinol (THC), which can affect people with anxiety very differently. Occasionally, especially when patients are hesitant to use cannabis already, THC can actually exacerbate symptoms of anxiety and therefore may not serve as the most efficient treatment for some patients. The development of a screening technique to determine how cannabinoids will affect patients before they try cannabis is desperately needed to ensure the benefit of the consumer. 

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Benjamin Caplan, MDSunk Cost Bias seen in Frequent Cannabis Users
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Birth Defects Rose in Colorado Post-Cannabis Legalization

Cannabis teratology explains current patterns of Coloradan congenital defects- the contribution of increased cannabinoid exposure to rising teratological trends

In summary

Researchers have recently found that the frequency of major birth defects has increased in Colorado since the legalization of cannabis. It has been hypothesized that prenatal exposure to cannabis has caused these birth defects as the reported use of pain relievers, cocaine, alcohol, and tobacco did not increase. The specific birth defects that increased in frequency were atrial septal defect, spina bifida, microcephalus, Down’s syndrome, ventricular septal defect, and patent ductus arteriosus, but further research needs to be conducted to determine any causation. 

The effect of prenatal exposure to cannabis on birth rates, birth outcomes, and the health of the mother is rather uncertain. Studies focussing on cannabis use during pregnancy are limited and what little has been reported is inconsistent. Currently, governing bodies of obstetricians advise that pregnant mothers cease any cannabis use. 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, even if they are using cannabis because they are resistant to more common treatment methods. 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, MDBirth Defects Rose in Colorado Post-Cannabis Legalization
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The Relationship Between Cannabis and Nicotine may Reveal Novel Treatments

Acute separate and combined effects of cannabinoid and nicotinic receptor agonists on MMN-indexed auditory deviance detection in healthy humans

In Summary

Researchers have attempted to elucidate the relationship between nicotine and cannabis revealing a possible benefit for sensory and cognitive processes. A cannabinoid receptor 1 (CB1) agonist, nabilone, and nicotine were compared against each other and combined and compared with a placebo, resulting in the region and deviant-dependent effects. Temporal regions of the brain were not affected by coadministration of nabilone and nicotine, while frontal regions showed improved cognitive function. Future research should continue to develop therapies that combine CB1 agonist while minimizing the need for nicotine in order to develop therapies for the dysregulation of sensory and cognitive processes. 

So little is still understood about the interactions of the endocannabinoid system, nicotinic receptors, and the opioid system. If the mechanisms underlying these various systems were well understood perhaps novel therapies could be developed to aid in the treatment of substance abuse disorders. Cannabis poses much less risk for addiction than opioids or nicotine as cannabis does not enact upon the reward system. Cannabis holds promise to lessen the troubles associated with the opioid academic by treating current addicts and preventing future addiction by serving as an adjunct therapy. Further research is needed to validate these hypotheses, but the current data provides hope for more ethical treatment methods.

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Benjamin Caplan, MDThe Relationship Between Cannabis and Nicotine may Reveal Novel Treatments
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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 is 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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Further Evidence for Cannabis as an Adjunctive Therapy to Opioids

Effects of cannabinoid administration for pain- A meta-analysis and meta-regression

In Summary

A recent meta-analysis provided further evidence that cannabis can be used as a replacement and adjunctive therapy option for opioids. Across all of the studies, it was found that cannabis had a medium-to-large effect on the subjective pain felt. The included studies included a range of given doses, all reported in milligrams and were conducted in various pain models, including Human Immunodeficiency Virus, Cancer, Neuropathic Pain, Diabetes, and more. Further research is needed to standardize an appropriate dose for each condition and ensure the validity of such medications. 

The authors take care to emphasize the need for alternative pain therapies for opioids that are safer and more economically responsible. Currently, pain-related costs from patients, caretakers, and healthcare facilities continue to grow beyond $600-billion annually, as more people grow dependent on opioids. Cannabis is much more cost-effective, and even if it does not entirely replace opioid therapies and is simply an adjunct therapy, it has the potential to greatly reduce the amount of opioid prescribed and lower the necessary dose. Opioids are highly addictive whereas cannabis has a much better safety profile, yet cannabis is still deemed medically irrelevant by the federal government. More research needs to be conducted to reduce the chance of addiction, the opioid crisis in general, and reduce the economic burden of pain-related costs in the United States. 

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Benjamin Caplan, MDFurther Evidence for Cannabis as an Adjunctive Therapy to Opioids
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The Pain-Relieving Effects of Tetrahydrocannabinol Differ Depending on Age

Age-Related Differences in Δ9-TetrahydrocannabinolInduced Antinociception in Female and Male Rats

In Summary

Researchers have recently found that the antinociceptive effects of ∆-9-tetrahydrocannabinol (THC) differ depending on the age of the subject. While examining the effects of THC on the nociceptive receptors of rats it was found that the THC was not as effective of a pain reliever in adolescent rats as it was in adult rats. It was determined that although adolescent and adult rats metabolize the cannabinoid differently it is not the cause of the differences in THC’s effect on nociception. Further research is needed to determine the mechanism that underlies the difference in age-dependent effects. 

This article brings to light the issues of dosing between age and gender. Clinical trials often occur in a population of healthy young men and are rarely dosed specifically for women. By noting the differences in effect and metabolism of drugs depending on sex and age clinical trials need to be broadened to accurately dose drugs for all users. Although the featured study was conducted in mouse models it provides evidence that the effects of cannabis are age-dependent and should be a serious consideration for researchers moving forward with the development of cannabis-based therapies. 

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Benjamin Caplan, MDThe Pain-Relieving Effects of Tetrahydrocannabinol Differ Depending on Age
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A Cannabinoid-Like Compound Modulates Neuronal Excitability, May Reduce Seizures

The Cannabinoid-Like Compound, VSN16R, Acts on Large Conductance, Ca2 -Activated K  Channels to Modulate Hippocampal CA1 Pyramidal Neuron Firing

In Summary

Researchers have recently found a cannabinoid-like compound, VSN16R, which is able to modulate Ca2+– activated potassium channels and may reduce seizure severity. By hyperpolarizing the neurons through the opening of Ca2+– activated potassium channels VSN16R ultimately results in the reduction of hyperexcitability seen in individuals who suffer from seizures. The compiled data reveals that cannabinoids or compounds structurally similar to cannabinoids may prove useful in the treatment of seizures or epileptic disorders, similar to the cannabinol-based Epidiolex® medication for rare forms of epilepsy, reducing the chance of a seizure or minimizing its duration. Further research is needed to aid the development of more readily available cannabis-based therapies for seizure activity and more general forms of epilepsy. 

Highlighting in this article are the options for treatment that the endocannabinoid system provides us, even in the absence of naturally occurring cannabinoids. If structurally similar compounds like VSN16R are able to be synthesized and proven effective, it could mean novel therapies could be developed even while red tape surrounds cannabis. The endocannabinoid system affects a myriad of systems within the human body and is severely under-researched considering its potential. Epidiolex® is the only cannabinoid-based medication currently approved by the federal government but cannabis has shown promise in so many other areas where the current treatment is either ineffective or lacking. Research utilizing the endocannabinoid system as a target should continue and be pushed to the forefront of the medical community.

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Benjamin Caplan, MDA Cannabinoid-Like Compound Modulates Neuronal Excitability, May Reduce Seizures
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Further Evidence For Cannabis as an Effective Pain Reliever

Effects of Cannabinoid Administration for Pain- A Meta-Analysis and Meta-Regression

In Summary

A recent meta-analysis has found that cannabis is an effective treatment for those dealing with chronic pain. Researchers analyzed studies that compared cannabinoid-based therapies to placebos, concluding that those therapies served as an effective replacement or adjunctive therapy for more common pain relievers, such as opioids. Some studies included in the analysis disqualified the effectiveness of cannabinoids due to the psychoactive effects of tetrahydrocannabinol (THC) but the featured piece suggests future work should aim to synthesize cannabinoids that highlight cannabis’s analgesic effects while minimizing any psychoactive effects. Future research needs to discover more about the endocannabinoid mechanism within the body before this can occur. 

The authors take care to emphasize the need for alternative pain therapies for opioids that are safer and more economically responsible. Currently, pain-related costs from patients, caretakers, and healthcare facilities continue to grow beyond $600-billion annually, as more people grow dependent on opioids. Cannabis is much more cost-effective, and even if it does not entirely replace opioid therapies and is simply an adjunct therapy, it has the potential to greatly reduce the amount of opioid prescribed and lower the necessary dose. Opioids are highly addictive whereas cannabis has a much better safety profile, yet cannabis is still deemed medically irrelevant by the federal government. More research needs to be conducted to reduce the chance of addiction, the opioid crisis in general, and reduce the economic burden of pain-related costs in the United States.





The Study is available for review or download here

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Benjamin Caplan, MDFurther Evidence For Cannabis as an Effective Pain Reliever
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