Impact of recreational and medicinal marijuana on surgical patients: A review.

American Journal of Surgery Home

“As medicinal and recreational marijuana use broadens across the United States, knowledge of its effects on the body will become increasingly important to all health care providers, including surgeons.

DATA SOURCES:

We performed a literature review of Pubmed for articles discussing the basic science related to cannabinoids, as well as articles regarding cannabinoid medications, and cannabis use in surgical patients.

CONCLUSIONS:

The primary components in the cannabis plant, tetrahydrocannabinol (THC) and cannabidiol (CBD), have been made available in numerous forms and formulations to treat multiple medical conditions, and recreational access to marijuana is increasing. Of particular importance to the surgeon may be their effects on prolonging intestinal motility, decreasing inflammation, increasing hunger, mitigating pain, and reducing nausea and vomiting. Perioperative use of medicinal or recreational marijuana will become increasingly prevalent, and the surgeon should be aware of the positive and negative effects of these cannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/30471810

https://www.americanjournalofsurgery.com/article/S0002-9610(18)31123-1/fulltext

A meta-analysis of the crash risk of cannabis-positive drivers in culpability studies-Avoiding interpretational bias.

Accident Analysis & Prevention

“Culpability studies, a common study design in the cannabis crash risk literature, typically report odds-ratios (OR) indicating the raised risks of a culpable accident. This parameter is of unclear policy relevance, and is frequently misinterpreted as an estimate of the increased crash risk, a practice that introduces a substantial “interpretational bias”.

RESULTS:

The model outperforms the culpability OR in bootstrap analyses. Used on actual study data, the average increase in crash risk is estimated at 1.28 (1.16-1.40). The pooled increased risk of a culpable crash is estimated as 1.42 (95% credibility interval 1.11-1.75), which is similar to pooled estimates using traditional ORs (1.46, 95% CI: 1.24-1.72). The attributable risk fraction of cannabis impaired driving is estimated to lie below 2% for all but two of the included studies.

CONCLUSIONS:

Culpability ORs exaggerate risk increases and parameter uncertainty when misinterpreted as total crash ORs. The increased crash risk associated with THC-positive drivers in culpability studies is low.”

https://www.ncbi.nlm.nih.gov/pubmed/30468948

https://www.sciencedirect.com/science/article/pii/S0001457518304706?via%3Dihub

The level of evidence of medical marijuana use for treating disabilities: a scoping review.

Publication Cover

“There is sufficient evidence that medical marijuana is effective in treating epileptic seizures and chronic pain.

Medical marijuana may improve the level of functioning and quality of life for individuals with certain disabilities.”

https://www.ncbi.nlm.nih.gov/pubmed/30456993

https://www.tandfonline.com/doi/abs/10.1080/09638288.2018.1523952?journalCode=idre20

Cannabis Systematics at the Levels of Family, Genus, and Species.

Cannabis and Cannabinoid Research cover image

“New concepts are reviewed in Cannabis systematics, including phylogenetics and nomenclature. The family Cannabaceae now includes CannabisHumulus, and eight genera formerly in the Celtidaceae. Grouping CannabisHumulus, and Celtis actually goes back 250 years. Print fossil of the extinct genus Dorofeevia (=Humularia) reveals that Cannabis lost a sibling perhaps 20 million years ago (mya). Cannabis print fossils are rare (n=3 worldwide), making it difficult to determine when and where she evolved. A molecular clock analysis with chloroplast DNA (cpDNA) suggests Cannabis and Humulus diverged 27.8 mya. Microfossil (fossil pollen) data point to a center of origin in the northeastern Tibetan Plateau. Fossil pollen indicates that Cannabis dispersed to Europe by 1.8-1.2 mya. Mapping pollen distribution over time suggests that European Cannabis went through repeated genetic bottlenecks, when the population shrank during range contractions. Genetic drift in this population likely initiated allopatric differences between European Cannabis sativa (cannabidiol [CBD]>Δ9-tetrahydrocannabinol [THC]) and Asian Cannabis indica (THC>CBD). DNA barcode analysis supports the separation of these taxa at a subspecies level, and recognizing the formal nomenclature of C. sativa subsp. sativa and C. sativa subsp. indica. Herbarium specimens reveal that field botanists during the 18th-20th centuries applied these names to their collections rather capriciously. This may have skewed taxonomic determinations by Vavilov and Schultes, ultimately giving rise to today’s vernacular taxonomy of “Sativa” and “Indica,” which totally misaligns with formal C. sativa and C. indica. Ubiquitous interbreeding and hybridization of “Sativa” and “Indica” has rendered their distinctions almost meaningless.”

https://www.ncbi.nlm.nih.gov/pubmed/30426073

https://www.liebertpub.com/doi/10.1089/can.2018.0039

Medical Cannabis: A plurimillennial history of an evergreen.

 Journal of Cellular Physiology banner“The history of Cannabis goes along that of humankind, as speculated based on geographical and evolutionary models together with historic data collected to date. Its medical use is several thousand years old, as attested both by archeobotanical evidence of Cannabis remains and written records found in ancient texts from the sacred Vedic foundational texts of Ayurvedic medicine (about 800 before current era [BCE]) to the first known Pharmacopoea, the Chinese “Shen Nung Pen Ts’ao Ching” (1 century BCE). In this paper, we retrace the history of Cannabis traveling through the key stages of its diffusion among the most important ancient cultures up to our days, when we are facing a renaissance of its medical employment. We report through the centuries evidence of its use in numerous pathologic conditions especially for its anti-inflammatory, antiseptic, and anticonvulsing properties that support the requirement to direct our present research efforts into the definitive understanding of its efficacy.”

https://www.ncbi.nlm.nih.gov/pubmed/30417354

https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.27725

Cannabigerol Action at Cannabinoid CB1 and CB2 Receptors and at CB1-CB2 Heteroreceptor Complexes.

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“Cannabigerol (CBG) is one of the major phytocannabinoids present in Cannabis sativa L. that is attracting pharmacological interest because it is non-psychotropic and is abundant in some industrial hemp varieties.

The aim of this work was to investigate in parallel the binding properties of CBG to cannabinoid CB1 (CB1R) and CB2 (CB2R) receptors and the effects of the compound on agonist activation of those receptors and of CB1-CB2 heteroreceptor complexes.

The results indicate that CBG is indeed effective as regulator of endocannabinoid signaling.”

https://www.ncbi.nlm.nih.gov/pubmed/29977202

https://www.frontiersin.org/articles/10.3389/fphar.2018.00632/full

Anti-inflammatory Properties of Cannabidiol, a Nonpsychotropic Cannabinoid, in Experimental Allergic Contact Dermatitis.

Journal of Pharmacology and Experimental Therapeutics

“Phytocannabinoids modulate inflammatory responses by regulating the production of cytokines in several experimental models of inflammation.

Cannabinoid type-2 (CB2) receptor activation was shown to reduce the production of the monocyte chemotactic protein-2 (MCP-2) chemokine in polyinosinic-polycytidylic acid [poly-(I:C)]-stimulated human keratinocyte (HaCaT) cells, an in vitro model of allergic contact dermatitis (ACD).

We investigated if nonpsychotropic cannabinoids, such as cannabidiol (CBD), produced similar effects in this experimental model of ACD.

We show that in poly-(I:C)-stimulated HaCaT cells, CBD elevates the levels of AEA and dose-dependently inhibits poly-(I:C)-induced release of MCP-2, interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α in a manner reversed by CB2 and TRPV1 antagonists 6-iodopravadoline (AM630) and 5′-iodio-resiniferatoxin (I-RTX), respectively, with no cytotoxic effect.

This is the first demonstration of the anti-inflammatory properties of CBD in an experimental model of ACD.”

https://www.ncbi.nlm.nih.gov/pubmed/29632236

http://jpet.aspetjournals.org/content/365/3/652.long

Cannabis Therapeutics and the Future of Neurology.

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“Neurological therapeutics have been hampered by its inability to advance beyond symptomatic treatment of neurodegenerative disorders into the realm of actual palliation, arrest or reversal of the attendant pathological processes.

While cannabis-based medicines have demonstrated safety, efficacy and consistency sufficient for regulatory approval in spasticity in multiple sclerosis (MS), and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges remain.

This review will examine the intriguing promise that recent discoveries regarding cannabis-based medicines offer to neurological therapeutics by incorporating the neutral phytocannabinoids tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), and cannabis terpenoids in the putative treatment of five syndromes, currently labeled recalcitrant to therapeutic success, and wherein improved pharmacological intervention is required: intractable epilepsy, brain tumors, Parkinson disease (PD), Alzheimer disease (AD) and traumatic brain injury (TBI)/chronic traumatic encephalopathy (CTE).

Current basic science and clinical investigations support the safety and efficacy of such interventions in treatment of these currently intractable conditions, that in some cases share pathological processes, and the plausibility of interventions that harness endocannabinoid mechanisms, whether mediated via direct activity on CB1 and CB2 (tetrahydrocannabinol, THC, caryophyllene), peroxisome proliferator-activated receptor-gamma (PPARγ; THCA), 5-HT1A (CBD, CBDA) or even nutritional approaches utilizing prebiotics and probiotics.

The inherent polypharmaceutical properties of cannabis botanicals offer distinct advantages over the current single-target pharmaceutical model and portend to revolutionize neurological treatment into a new reality of effective interventional and even preventative treatment.”

https://www.ncbi.nlm.nih.gov/pubmed/30405366

https://www.frontiersin.org/articles/10.3389/fnint.2018.00051/full

A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, Multiple Dose, and Food Effect Trial of the Safety, Tolerability and Pharmacokinetics of Highly Purified Cannabidiol in Healthy Subjects.

“A formal single ascending and multiple dose pharmacokinetic (PK) trial of cannabidiol (CBD) oral solution was required to determine the safety and tolerability of CBD, the maximum tolerated dose, and to examine the effect of food on CBD PK parameters.

OBJECTIVE:

This trial assessed the safety, tolerability and PK of CBD oral solution in healthy adult volunteers, as well as the effect of food on CBD PK parameters.

 CONCLUSION:

CBD was generally well tolerated. Most AEs were mild in severity; none were severe or serious. The safety and PK profile support twice-daily administration of CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/30374683

https://link.springer.com/article/10.1007%2Fs40263-018-0578-5

Medical Use of Cannabinoids.

“Cannabinoid receptors, endocannabinoids and the enzymes responsible for their biosynthesis and degradation constitute the endocannabinoid system. In recent decades, the endocannabinoid system has attracted considerable interest as a potential therapeutic target in numerous pathological conditions. Its involvement in several physiological processes is well known, such as in energy balance, appetite stimulation, blood pressure, pain modulation, embryogenesis, nausea and vomiting control, memory, learning and immune response, among others, as well as in pathological conditions where it exerts a protective role in the development of certain disorders. As a result, it has been reported that changes in endocannabinoid levels may be related to neurological diseases such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and multiple sclerosis, as well as anorexia and irritable bowel syndrome. Alterations in the endocannabinoid system have also been associated with cancer, affecting the growth, migration and invasion of some tumours. Cannabinoids have been tested in several cancer types, including brain, breast and prostate cancers. Cannabinoids have shown promise as analgesics for the treatment of both inflammatory and neuropathic pain. There is also evidence for a role of the endocannabinoid system in the control of emotional states, and cannabinoids could prove useful in decreasing and palliating post-traumatic stress disorder symptoms and anxiolytic disorders. The role of the endocannabinoid system in addictions has also been examined, and cannabinoids have been postulated as alternative and co-adjuvant treatments in some abuse syndromes, mainly in ethanol and opioid abuses. The expression of the endocannabinoid system in the eye suggests that it could be a potential therapeutic target for eye diseases. Considering the importance of the endocannabinoid system and the therapeutic potential of cannabinoids in this vast number of medical conditions, several clinical studies with cannabinoid-based medications are ongoing. In addition, some cannabinoid-based medications have already been approved in various countries, including nabilone and dronabinol capsules for the treatment of nausea and vomiting associated with chemotherapy, dronabinol capsules for anorexia, an oral solution of dronabinol for both vomiting associated with chemotherapy and anorexia, a Δ9-tetrahydrocannabinol/cannabidiol oromucosal spray for pain related to cancer and for spasticity and pain associated with multiple sclerosis, and an oral solution of cannabidiol for Dravet and Lennox-Gastaut syndromes. Here, we review the available efficacy, safety and tolerability data for cannabinoids in a range of medical conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/30374797

https://link.springer.com/article/10.1007%2Fs40265-018-0996-1