Category Archives: Uncategorized

Medical Marijuana: Just the Beginning of a Long, Strange Trip?

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Physical Therapy Journal

“Medical marijuana continues to gain acceptance and become legalized in many states. Various species of the marijuana plant have been cultivated, and this plant can contain up to 100 active compounds known as cannabinoids.

Two cannabinoids seem the most clinically relevant: Δ9-tetrahydrocannabinol (THC), which tends to produce the psychotropic effects commonly associated with marijuana, and cannabidiol (CBD), which may produce therapeutic effects without appreciable psychoactive properties.

Smoking marijuana, or ingesting extracts from the whole plant orally (in baked goods, teas, and so forth), introduces variable amounts of THC, CBD, and other minor cannabinoids into the systemic circulation where they ultimately reach the central and peripheral nervous systems.

Alternatively, products containing THC, CBD, or a combination of both compounds, can also be ingested as oral tablets, or via sprays applied to the oral mucosal membranes. These products may provide a more predictable method for delivering a known amount of specific cannabinoids into the body.

Although there is still a need for randomized controlled clinical trials, preliminary studies have suggested that medical marijuana and related cannabinoids may be beneficial in treating chronic pain, inflammation, spasticity, and other conditions seen commonly in physical therapist practice.

Physical therapists should therefore be aware of the options that are available for patients considering medical marijuana, and be ready to provide information for these patients.”

http://www.ncbi.nlm.nih.gov/pubmed/27660328

Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines

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“Cannabis sativa, commonly called hemp, has thousands of years-long history of medical use. Cannabis extracts were widely used in Europe and North America for their therapeutic value as sedatives, hypnotics, analgesics, muscle relaxants, and anticonvulsant agents. However, cannabis was removed from British and American Pharmacopoeias in 20th century, partially due to politic bias. Although prohibited, many patients were nevertheless self-medicating to obtain therapeutic benefits from cannabis for various conditions, including AIDS wasting syndrome, multiple sclerosis (MS) and spinal injuries. More recently, a growing interest in the therapeutic effects of cannabis has developed following the isolation of cannabinoids, the principal chemical compounds of cannabis, as well as the discovery of endocannabinoids and their cognate receptors in humans. These advances supported legalisation and wide-spread use of cannabis for therapeutic purposes in many countries.

There has been an escalating interest in the medicinal use of Cannabis sativa in recent years. Cannabis is often administered orally with fat-containing foods, or in lipid-based pharmaceutical preparations. However, the impact of lipids on the exposure of patients to cannabis components has not been explored. Therefore, the aim of this study is to elucidate the effect of oral co-administration of lipids on the exposure to two main active cannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In this study, oral co-administration of lipids enhanced the systemic exposure of rats to THC and CBD by 2.5-fold and 3-fold, respectively, compared to lipid-free formulations. In vitro lipolysis was conducted to explore the effect of lipids on the intestinal solubilisation of cannabinoids. More than 30% of THC and CBD were distributed into micellar fraction following lipolysis, suggesting that at least one-third of the administered dose will be available for absorption following co-administration with lipids. Both cannabinoids showed very high affinity for artificial CM-like particles, as well as for rat and human CM, suggesting high potential for intestinal lymphatic transport. Moreover, comparable affinity of cannabinoids for rat and human CM suggests that similar increased exposure effects may be expected in humans. In conclusion, co-administration of dietary lipids or pharmaceutical lipid excipients has the potential to substantially increase the exposure to orally administered cannabis and cannabis-based medicines. The increase in patient exposure to cannabinoids is of high clinical importance as it could affect the therapeutic effect, but also toxicity, of orally administered cannabis or cannabis-based medicines.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009397/

State Medical Marijuana Laws and the Prevalence of Opioids Detected Among Fatally Injured Drivers.

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“To assess the association between medical marijuana laws (MMLs) and the odds of a positive opioid test, an indicator for prior use.

State-specific estimates indicated a reduction in opioid positivity for most states after implementation of an operational MML,

CONCLUSIONS:

Operational MMLs are associated with reductions in opioid positivity among 21- to 40-year-old fatally injured drivers and may reduce opioid use and overdose.”

http://www.ncbi.nlm.nih.gov/pubmed/27631755

Preparation and Distribution of Cannabis and Cannabis-Derived Dosage Formulations for Investigational and Therapeutic Use in the United States.

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“Cannabis is classified as a schedule I controlled substance by the US Drug Enforcement Agency, meaning that it has no medicinal value. Production is legally restricted to a single supplier at the University of Mississippi, and distribution to researchers is tightly controlled. However, a majority of the population is estimated to believe that cannabis has legitimate medical or recreational value, numerous states have legalized or decriminalized possession to some degree, and the federal government does not strictly enforce its law and is considering rescheduling. The explosive increase in open sale and use of herbal cannabis and its products has occurred with widely variable and in many cases grossly inadequate quality control at all levels-growing, processing, storage, distribution, and use. This paper discusses elements of the analytical and regulatory system that need to be put in place to ensure standardization for the researcher and to reduce the hazards of contamination, overdosing, and underdosing for the end-user.”

http://www.ncbi.nlm.nih.gov/pubmed/27630566

Evaluation of Two Commercially Available Cannabidiol Formulations for Use in Electronic Cigarettes.

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“Since 24 states and the District of Columbia have legalized marijuana in some form, suppliers of legal marijuana have developed Cannabis sativa products for use in electronic cigarettes (e-cigarettes).

Personal battery powered vaporizers, or e-cigarettes, were developed to deliver a nicotine vapor such that smokers could simulate smoking tobacco without the inherent pathology of inhaled tobacco smoke. The liquid formulations used in these devices are comprised of an active ingredient such as nicotine mixed with vegetable glycerin (VG) and/or propylene glycol (PG) and flavorings.

A significant active ingredient of C. sativa, cannabidiol (CBD), has been purported to have anti-convulsant, anti-nociceptive, and anti-psychotic properties. These properties have potential medical therapies such as intervention of addictive behaviors, treatments for epilepsy, management of pain for cancer patients, and treatments for schizophrenia.

However, CBD extracted from C. sativa remains a DEA Schedule I drug since it has not been approved by the FDA for medical purposes.

Two commercially available e-cigarette liquid formulations reported to contain 3.3 mg/mL of CBD as the active ingredient were evaluated. These products are not regulated by the FDA in manufacturing or in labeling of the products and were found to contain 6.5 and 7.6 mg/mL of CBD in VG and PG with a variety of flavoring agents. Presently, while labeled as to content, the quality control of manufacturers and the relative safety of these products is uncertain.”

http://www.ncbi.nlm.nih.gov/pubmed/27621706

Maternal Marijuana Use and Adverse Neonatal Outcomes: A Systematic Review and Meta-analysis.

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“To estimate whether marijuana use in pregnancy increases risks for adverse neonatal outcomes and clarify if any increased risk is attributable to marijuana use itself or to confounding factors such as tobacco use.

CONCLUSION:

Maternal marijuana use during pregnancy is not an independent risk factor for adverse neonatal outcomes after adjusting for confounding factors.

Thus, the association between maternal marijuana use and adverse outcomes appears attributable to concomitant tobacco use and other confounding factors.”

http://www.ncbi.nlm.nih.gov/pubmed/27607879

“Using Pot While Pregnant Not Tied to Birth Risks. Smoking marijuana during pregnancy doesn’t appear to increase the risk of preterm birth or other harmful birth outcomes, a new review study suggests.” http://www.livescience.com/56036-marijuana-pregnant-preterm-birth-risk.html

“Marijuana Is Safe During pregnancy, Experts Do Not Encourage. Marijuana does not increase pregnancy risk according to new research. It does not have a negative outcome when it comes to premature birth and low birth weight. Still, experts do not encourage marijuana use during pregnancy.” http://www.scienceworldreport.com/articles/47194/20160910/marijuana-safe-during-pregnancy-experts-encourage.htm

Cannabis for Cognitive Enhancement as a New Coping Strategy? Results From a Survey of Students at Four Universities in Germany.

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“Cognitive Enhancement (CE) is often discussed in relation to stimulant drugs, such as amphetamines (AMPH).

However, there is some evidence that cannabis (CAN) can be used for CE.

A survey was taken of 1,538 students at four German universities.

A considerable number of students report having used CAN for CE.”

http://www.ncbi.nlm.nih.gov/pubmed/27607062

Spontaneous Cannabinoid Receptor 2 (CB2) Expression in the Cochlea of Adult Albino Rat and Its Up-Regulation after Cisplatin Treatment

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“We provide evidence for the presence of cannabinoid CB2 receptors in some cellular types of the cochlea of the adult albino rat. Cannabinoids and their receptors are increasingly being studied because of their high potential for clinical use. As a hyperspecialized portion of the peripheral nervous system, study of the expression and function of cannabinoid receptors in the hearing organ is of high interest. Stria vascularis and inner hair cells express CB2 receptor, as well as neurites and cell bodies of the spiral ganglion. Cellular types such as supporting cells and outer hair cells, in which the expression of other types of functional receptors has been reported, do not significantly express CB2 receptors in this study. An up-regulation of CB2 gene expression was detected after an ototoxic event such as cisplatin treatment, probably due to pro-inflammatory events triggered by the drug. That fact suggests promising potential of CB2receptor as a therapeutic target for new treatments to palliate cisplatin-induced hearing loss and other ototoxic events which triggers inflammatory pathways.”  http://www.ncbi.nlm.nih.gov/pubmed/27564061

“In conclusion, evidence for the presence of cannabinoid CB2 receptor by immunohystochemistry and by RT-qPCR was provided. An immunolabeling of CB2 antibodies in four structures of the adult rat cochlea was found. That was, stria vascularis, inner hair cells, auditory afferent nerves and cell bodies of the spiral ganglion. Up-regulation of CB2 gene expression in animals exposed to CDDP treatment was also detected, when compared with healthy animals. This fact was partially supported by the higher immunofluorescence observed in the stria vascularis of CDDP-treated animals if compared with the healthy ones. These results suggest a considerable promising potential of CB2 receptor as a target of new treatments against CDDP-induced ototoxicity, and probably against other inflammatory diseases in the inner ear. Further research is needed to determine the functionality of CB2receptors in the organ of Corti and the potential therapeutic role of agonists and antagonists of these receptors.”  http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161954

“Study: Cannabinoids a Potential Treatment Option for Chemotherapy-Induced Hearing Loss” http://www.theweedblog.com/study-cannabinoids-potential-treatment-option-chemotherapy-induced-hearing-loss/