Cannabinoids: Medical implications.

“Herbal cannabis has been used for thousands of years for medical purposes.

With elucidation of the chemical structures of tetrahydrocannabinol (THC) and cannabidiol (CBD) and with discovery of the human endocannabinoid system, the medical usefulness of cannabinoids has been more intensively explored.

While more randomized clinical trials are needed for some medical conditions, other medical disorders, like chronic cancer and neuropathic pain and certain symptoms of multiple sclerosis, have substantial evidence supporting cannabinoid efficacy.

While herbal cannabis has not met rigorous FDA standards for medical approval, specific well-characterized cannabinoids have met those standards.

Where medical cannabis is legal, patients typically see a physician who “certifies” that a benefit may result.

Physicians must consider important patient selection criteria such as failure of standard medical treatment for a debilitating medical disorder. Medical cannabis patients must be informed about potential adverse effects, such as acute impairment of memory, coordination and judgment, and possible chronic effects, such as cannabis use disorder, cognitive impairment, and chronic bronchitis.

Novel ways to manipulate the endocannbinoid system are being explored to maximize benefits of cannabinoid therapy and lessen possible harmful effects.

Key messages The medical disorders with the current best evidence that supports a benefit for cannabinoid use are the following: multiple sclerosis patient-reported symptoms of spasticity (nabiximols, nabilone, dronabinol, and oral cannabis extract), multiple sclerosis central pain or painful spasms (nabiximols, nabilone, dronabinol, and oral cannabis extract), multiple sclerosis bladder frequency (nabiximols), and chronic cancer pain/neuropathic pain (nabiximols and smoked THC).

Participating physicians should be knowledgeable about cannabinoids, closely look at the risk/benefit ratio, and consider certain important criteria in selecting a patient, such as: age, severity, and nature of the medical disorder, prior or current serious psychiatric or substance use disorder, failure of standard medical therapy as well as failure of an approved cannabinoid, serious underlying cardiac/pulmonary disease, agreement to follow-up visits, and acceptance of the detailed explanation of potential adverse risks.

The normal human endocannabinoid system is important in the understanding of such issues as normal physiology, cannabis use disorder, and the development of medications that may act as agonists or antagonists to CB1 and CB2.

By understanding the endocannabinoid system, it may be possible to enhance the beneficial effects of cannabinoid-related medication, while reducing the harmful effects.”

http://www.ncbi.nlm.nih.gov/pubmed/26912385

Medical cannabis: considerations for the anesthesiologist and pain physician.

“New regulations are in place at the federal and provincial levels in Canada regarding the way medical cannabis is to be controlled. We present them together with guidance for the safe use of medical cannabis and recent clinical trials on cannabis and pain.

Health Canada has approved a new regulation on medical marijuana/cannabis, the Marihuana for Medical Purposes Regulations: The production of medical cannabis by individuals is illegal. Health Canada, however, has licensed authorized producers across the country, limiting the production to specific licenses of certain cannabis products. There are currently 26 authorized licensed producers from seven Canadian provinces offering more than 200 strains of marijuana.

We provide guidance for the safe use of medical cannabis.

The recent literature indicates that currently available cannabinoids are modestly effective analgesics that provide a safe, reasonable therapeutic option for managing chronic non-cancer-related pain.

The science of medical cannabis and the need for education of healthcare professionals and patients require continued effort. Although cannabinoids work to decrease pain, there is still a need to confirm these beneficial effects clinically and to exploit them with acceptable benefit-to-risk ratios.”

http://www.ncbi.nlm.nih.gov/pubmed/26850063

CBD-enriched medical cannabis for intractable pediatric epilepsy: The current Israeli experience.

“To describe the experience of five Israeli pediatric epilepsy clinics treating children and adolescents diagnosed as having intractable epilepsy with a regimen of medical cannabis oil.

A retrospective study describing the effect of cannabidiol (CBD)-enriched medical cannabis on children with epilepsy.

The cohort included 74 patients (age range 1-18 years) with intractable epilepsy resistant to >7 antiepileptic drugs. Forty-nine (66%) also failed a ketogenic diet, vagal nerve stimulator implantation, or both.

They all started medical cannabis oil treatment between 2-11/2014 and were treated for at least 3 months (average 6 months).

The selected formula contained CBD and tetrahydrocannabinol at a ratio of 20:1 dissolved in olive oil. The CBD dose ranged from 1 to 20mg/kg/d. Seizure frequency was assessed by parental report during clinical visits.

CBD treatment yielded a significant positive effect on seizure load.

Most of the children (66/74, 89%) reported reduction in seizure frequency: 13 (18%) reported 75-100% reduction, 25 (34%) reported 50-75% reduction, 9 (12%) reported 25-50% reduction, and 19 (26%) reported <25% reduction. Five (7%) patients reported aggravation of seizures which led to CBD withdrawal.

In addition, we observed improvement in behavior and alertness, language, communication, motor skills and sleep. Adverse reactions included somnolence, fatigue, gastrointestinal disturbances and irritability leading to withdrawal of cannabis use in 5 patients.

CONCLUSIONS:

The results of this multicenter study on CBD treatment for intractable epilepsy in a population of children and adolescents are highly promising. Further prospective, well-designed clinical trials using enriched CBD medical cannabis are warranted.”

http://www.ncbi.nlm.nih.gov/pubmed/26800377

http://www.thctotalhealthcare.com/category/epilepsy-2/

The Use of Marijuana or Synthetic Cannabinoids for the Treatment of Headache

“Although marijuana is principally used as a psychoactive substance, it has also been used for medical and religious purposes for over 2000 years.

This review concluded that there was evidence of a positive and moderate short-term trend toward a reduction of pain.

There are a number of reasons why naturally occurring cannabis or cannabinoid drugs might have a pharmacologic effect on headache..

It has been suggested that one explanation for migraine and other headache disorders may be an underlying endocannabinoid deficiency.

…cluster headache attacks were relieved within 5 minutes by the inhalation of marijuana.

Subsequent treatment with dronabinol (THC) 5 mg orally also provided the patient relief within 15 minutes.”

http://www.medscape.com/viewarticle/738529_2

http://www.thctotalhealthcare.com/category/headachemigraine/

The effect of cannabis on regular cannabis consumers’ ability to ride a bicycle.

“To assess the effects of cannabis on the ability required to ride a bicycle, repetitive practical cycling tests and medical examinations were carried out before and after inhalative consumption of cannabis.

A maximum of three joints with body weight-adapted THC content (300 μg THC per kg body weight) could be consumed by each test subject.

Fourteen regular cannabis-consuming test subjects were studied (12 males, 2 females).

In summary, only a few driving faults were observed even under the influence of very high THC concentrations. A defined THC concentration that leads to an inability to ride a bicycle cannot be presented.

The test subjects showed only slight distinctive features that can be documented using a medical test routinely run for persons under suspicion of driving under the influence of alcohol or drugs.” http://www.ncbi.nlm.nih.gov/pubmed/26739323

“Alcohol-related deficits were already identifiable at very low blood alcohol concentrations (BAC)s. A significant increase in gross motoric disturbances compared to the soberness state did not regularly occur until a BAC of at least 0.8 g/kg was reached. At the BAC of 1.4 g/kg and above, no test subjects were able to achieve or surpass their sober driving results.”  http://www.ncbi.nlm.nih.gov/pubmed/25428289

“The practical ability to ride a bicycle was significantly reduced in the postalcoholic state… The relative cycling performance in the postalcoholic state was comparable to the rides under the influence of BAC of around 0.30 g/kg… it can be assumed that the direct influence of residual blood alcohol levels plays a minor role for the ability to ride a bicycle in the postalcoholic state. Instead, the side effects of the high amounts of alcohol that were consumed the night before are crucial.” http://www.ncbi.nlm.nih.gov/pubmed/25940454

“A defined THC concentration that leads to an inability to ride a bicycle cannot be presented.” http://www.ncbi.nlm.nih.gov/pubmed/26739323

Marijuana extract slashes pediatric seizures, landmark study confirms

Cannabis extract Epidiolex slashes seizures, a new study confirms.  (Photo by GW Pharmaceuticals)

“A batch of studies further confirms medical cannabis patients are right to try cannabidiol-rich marijuana products to treat intractable seizure disorders.

Three studies presented at the American Epilepsy Society’s 69th Annual Meeting in Philadelphia Dec. 7th found a marijuana-derived extract slashed pediatric seizures in half, and completely stopped seizures in nine percent of cases.”  http://blog.sfgate.com/smellthetruth/2015/12/15/marijuana-extract-slashes-pediatric-seizures-landmark-study-confirms/

“Study: marijuana medicine is safe, very effective on epilepsy” http://blog.sfgate.com/smellthetruth/2015/05/12/study-marijuana-medicine-is-safe-very-effective-on-epilepsy/

http://www.thctotalhealthcare.com/category/epilepsy-2/

Endocannabinoid Mechanisms Influencing Nausea.

“One of the first recognized medical uses of Δ(9)-tetrahydrocannabinol was treatment of chemotherapy-induced nausea and vomiting.

Although vomiting is well controlled with the currently available non-cannabinoid antiemetics, nausea continues to be a distressing side effect of chemotherapy and other disorders.

Indeed, when nausea becomes conditionally elicited by the cues associated with chemotherapy treatment, known as anticipatory nausea (AN), currently available antiemetics are largely ineffective.

Considerable evidence demonstrates that the endocannabinoid system regulates nausea in humans and other animals.

In this review, we describe recent evidence suggesting that cannabinoids and manipulations that enhance the functioning of the natural endocannabinoid system are promising treatments for both acute nausea and AN.”

Metabolic Syndrome among Marijuana Users in the United States: An Analysis of National Health and Nutrition Examination Survey Data.

“Research on the health effects of marijuana use in light of its increased medical use and the current obesity epidemic is needed. Our objective was to explore the relationship between marijuana use and metabolic syndrome across stages of adulthood…

Current marijuana users had lower odds of presenting with metabolic syndrome than never users. Among emerging adults, current marijuana users were 54% less likely than never users to present with metabolic syndrome. Current and past middle-aged adult marijuana users were less likely to have metabolic syndrome than never users.

CONCLUSIONS:

Current marijuana use is associated with lower odds of metabolic syndrome across emerging and middle-aged US adults.”

http://www.ncbi.nlm.nih.gov/pubmed/26548604

The prescription of medical cannabis by a transitional pain service to wean a patient with complex pain from opioid use following liver transplantation: a case report.

Canadian Journal of Anesthesia/Journal canadien d'anesthésie

“The purpose of this case report is to describe a patient with a preoperative complex pain syndrome who underwent liver transplantation and was able to reduce his opioid consumption significantly following the initiation of treatment with medical cannabis.

CLINICAL FEATURES:

A 57-yr-old male with a history of hepatitis C cirrhosis underwent liver transplantation. Preoperatively, he was taking hydromorphone 2-8 mg⋅day-1 for chronic abdominal pain. Postoperatively, he was given intravenous patient-controlled analgesia through which he received hydromorphone 30 mg⋅day-1. Our multidisciplinary Transitional Pain Service was involved with managing his moderate to severe acute postsurgical pain in hospital and continued with weaning him from opioid medications after discharge. It was difficult to wean the patient from opioids, and he was subsequently given medical cannabis at six weeks postoperatively with remarkable effect. By the fifth postoperative month, his use of opioids had tapered to 6 mg⋅day-1 of hydromorphone, and his functional status was excellent on this regimen.

CONCLUSION:

Reductions in opioid consumption were achieved with the administration of medical cannabis in a patient with acute postoperative pain superimposed on a chronic pain syndrome and receiving high doses of opioids. Concurrent benefits of initiating medical cannabis may include improvements in pain profile and functional status along with reductions in opioid-related side effects. This highlights the potential for medical cannabis as an adjunct medication for weaning patients from opioid use.”

http://www.ncbi.nlm.nih.gov/pubmed/26507533

Peripherally Restricted Cannabinoids for the Treatment of Pain.

“The use of cannabinoids for the treatment of chronic diseases has increased in the United States, with 23 states having legalized the use of marijuana.

Although currently available cannabinoid compounds have shown effectiveness in relieving symptoms associated with numerous diseases, the use of cannabis or cannabinoids is still controversial mostly due to their psychotropic effects (e.g., euphoria, laughter) or central nervous system (CNS)-related undesired effects (e.g., tolerance, dependence).

A potential strategy to use cannabinoids for medical conditions without inducing psychotropic or CNS-related undesired effects is to avoid their actions in the CNS.

This approach could be beneficial for conditions with prominent peripheral pathophysiologic mechanisms (e.g., painful diabetic neuropathy, chemotherapy-induced neuropathy).

In this article, we discuss the scientific evidence to target the peripheral cannabinoid system as an alternative to cannabis use for medical purposes, and we review the available literature to determine the pros and cons of potential strategies that can be used to this end.”

http://www.ncbi.nlm.nih.gov/pubmed/26497478