Nabilone for the Management of Pain.

“Nabilone, a synthetic cannabinoid, is approved in many countries including, but not limited to, Canada, the United States, Mexico, and the United Kingdom for the treatment of severe nausea and vomiting associated with chemotherapy. Clinical evidence is emerging for its use in managing pain conditions with different etiologies. We review the efficacy and safety of nabilone for various types of pain as well as its abuse potential, precautions and contraindications, and drug interactions; summarize pertinent clinical practice guidelines; and provide recommendations for dosing, monitoring, and patient education.

Nabilone was most commonly used as adjunctive therapy and led to small but significant reductions in pain. The most common adverse drug reactions included euphoria, drowsiness, and dizziness. Nabilone was rarely associated with severe adverse drug reactions requiring drug discontinuation, and the likelihood of abuse was thought to be low. Although the optimal role of nabilone in the management of pain is yet to be determined, certain clinical practice guidelines consider nabilone as a third-line agent.”

http://www.ncbi.nlm.nih.gov/pubmed/26923810

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

THC:CBD Observational Study Data: Evolution of Resistant MS Spasticity and Associated Symptoms.

“The prospective observational MObility ImproVEment (MOVE) 2 study is collecting real-life clinical outcomes data on patients with treatment-resistant multiple sclerosis (MS) spasticity treated with THC:CBD oromucosal spray in routine clinical practice. The MOVE 2 study has been ongoing in Italy, involving more than 30 MS centres across the country, since 2013.

RESULTS:

In the Italian cohort, THC:CBD oromucosal spray was added mainly to oral baclofen. Similar to MOVE 2-Germany, during 3 months’ observation, treatment discontinuations were limited and patients recorded meaningful improvements on the patient-based 0-10 numerical rating scale and physician-rated modified Ashworth scale at mean daily doses that were about one-third lower than those used in the RCT. Also, similar to MOVE 2-Germany, the proportion of patients reporting adverse events was about one-third of the rate recorded in the RCT.

CONCLUSIONS:

While MOVE 2-Italy continues, this interim analysis has enabled us to better define the place in therapy of THC:CBD oromucosal spray within the context of daily management of our patients with MS spasticity.”

http://www.ncbi.nlm.nih.gov/pubmed/26901343

THC:CBD in Daily Practice: Available Data from UK, Germany and Spain.

“A retrospective registry study and a prospective safety study of THC:CBD oromucosal spray are reported.

…no evidence of addiction, abuse or misuse.

The homogeneity between these observational studies supports the interest in THC:CBD oromucosal spray for management of MS spasticity in daily practice.”

http://www.ncbi.nlm.nih.gov/pubmed/26901342

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Cannabis effects on driving longitudinal control with and without alcohol.

“Although evidence suggests cannabis impairs driving, its driving-performance effects are not fully characterized. We aimed to establish cannabis‘ effects on driving longitudinal control (with and without alcohol, drivers’ most common drug combination) relative to psychoactive ∆9 -tetrahydrocannabinol (THC) blood concentrations.

Current occasional (≥1×/last 3 months, ≤3 days per week) cannabis smokers drank placebo or low-dose alcohol, and inhaled 500 mg placebo, low (2.9%), or high (6.7%) THC vaporized cannabis over 10 min ad libitum in separate sessions (within-subject, six conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives 0.5-1.3 h post-inhalation. Blood and breath alcohol samples were collected before (0.17 and 0.42 h) and after (1.4 and 2.3 h) driving.

We evaluated the mean speed (relative to limit), standard deviation (SD) of speed, percent time spent >10% above/below the speed limit (percent speed high/percent speed low), longitudinal acceleration, and ability to maintain headway relative to a lead vehicle (headway maintenance) against blood THC and breath alcohol concentrations (BrAC).

THC was associated with a decreased mean speed, increased percent speed low and increased mean following distance during headway maintenance. BrAC was associated with increased SD speed and increased percent speed high, whereas THC was not.

Neither was associated with altered longitudinal acceleration.

A less-than-additive THC*BrAC interaction was detected in percent speed high (considering only non-zero data and excluding an outlying drive event), suggesting cannabis mitigated drivers’ tendency to drive faster with alcohol.

Cannabis was associated with slower driving and greater headway, suggesting a possible awareness of impairment and attempt to compensate.”

http://www.ncbi.nlm.nih.gov/pubmed/26889769

“Stoned Drivers Safer Than Drunk Drivers”                           http://americanlivewire.com/2015-02-15-stoned-drivers-safer-drunk-drivers/

Blockade of Nicotine and Cannabinoid Reinforcement and Relapse by a Cannabinoid CB1-Receptor Neutral Antagonist AM4113 and Inverse Agonist Rimonabant in Squirrel Monkeys.

“Nicotine, the main psychoactive component of tobacco, and (-)-Δ9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, play major roles in tobacco and marijuana dependence as reinforcers of drug-seeking and drug-taking behavior.

Drugs that act as inverse agonists of cannabinoid CB1 receptors in the brain can attenuate the rewarding and abuse-related effects of nicotine and THC…

Recently-developed CB1-receptor neutral antagonists may provide an alternative therapeutic approach to nicotine and cannabinoid dependence.

These findings point to CB1-receptor neutral antagonists as a new class of medications for treatment of both tobacco dependence and cannabis dependence.”

http://www.ncbi.nlm.nih.gov/pubmed/26888056

The Endocannabinoid System in the Retina: From Physiology to Practical and Therapeutic Applications.

“Cannabis is one of the most prevalent drugs used in industrialized countries.

The main effects of Cannabis are mediated by two major exogenouscannabinoids: ∆9-tetrahydroxycannabinol and cannabidiol. They act on specific endocannabinoid receptors, especially types 1 and 2.

Mammals are endowed with a functional cannabinoid system including cannabinoid receptors, ligands, and enzymes.

This endocannabinoid signaling pathway is involved in both physiological and pathophysiological conditions with a main role in the biology of the central nervous system.

As the retina is a part of the central nervous system due to its embryonic origin, we aim at providing the relevance of studying the endocannabinoid system in the retina. Here, we review the distribution of the cannabinoid receptors, ligands, and enzymes in the retina and focus on the role of the cannabinoid system in retinal neurobiology.

This review describes the presence of the cannabinoid system in critical stages of retinal processing and its broad involvement in retinal neurotransmission, neuroplasticity, and neuroprotection.

Accordingly, we support the use of synthetic cannabinoids as new neuroprotective drugs to prevent and treat retinal diseases.

Finally, we argue for the relevance of functional retinal measures in cannabis users to evaluate the impact of cannabis use on human retinal processing.”

http://www.ncbi.nlm.nih.gov/pubmed/26881099

Cannabinoids for the Treatment of Schizophrenia: An Overview.

“Δ9-tetrahydrocannabinol and its analogues are found to have particular application in psychiatry because of their antipsychotic properties suggesting a therapeutic use as neuroleptic agents in limiting psychotic diseases.

These treatments should not only aim to alleviate specific symptoms but also attempt to delay/arrest disease progression.

In the present review, we reported recent studies supporting the view that the cannabinoid signalling system is a key modulatory element in the activity of the striatum and temporal cortex that has been traditionally associated with psychosis and schizophrenia.

This idea is supported by different anatomical, electrophysiological, pharmacological and biochemical data.

Furthermore, these studies indicate that the cannabinoid system is impaired in different psychotic disorders, supporting the idea of developing novel pharmacotherapies with compounds that selectively target specific elements of the cannabinoid system.”

http://www.ncbi.nlm.nih.gov/pubmed/26845552

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

Metabolomics of Δ9-tetrahydrocannabinol: implications in toxicity.

“Cannabis sativa is the most commonly used recreational drug, Δ9-tetrahydrocannabinol (Δ9-THC) being the main addictive compound.

Biotransformation of cannabinoids is an important field of xenobiochemistry and toxicology and the study of the metabolism can lead to the discovery of new compounds, unknown metabolites with unique structures and new therapeutic effects.

The pharmacokinetics of Δ9-THC is dependent on multiple factors such as physical/chemical form, route of administration, genetics, and concurrent consumption of alcohol.

This review aims to discuss metabolomics of Δ9-THC, namely by presenting all known metabolites of Δ9-THC described both in vitro and in vivo, and their roles in the Δ9-THC-mediated toxic effects.

Since medicinal use is increasing, metabolomics of Δ9-THC will also be discussed in order to uncover potential active metabolites that can be made available for this purpose.”

http://www.ncbi.nlm.nih.gov/pubmed/26828228

Cannabinoids for pediatric epilepsy? Up in smoke or real science?

“Public interest in the use of “medical marijuana” for the treatment of childhood epilepsy has burgeoned in the last few years. This has occurred in parallel with a growing interest in “medical marijuana” in general. Physicians and pediatricians must balance their patients’ desire for immediate access to these products with the tenets of evidence-based medicine. This review discusses the biochemistry of cannabis products (the phytocannabinoids) setting this in the context of the endogenous endocannabinoid system. The differing and potentially modulating effects of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are reviewed. The evidence-base supporting or not the use of cannabis products for the treatment of neurological disease and specifically epilepsy is explored. The potential for adverse effects and particularly of neurotoxicity is addressed. Finally, public health and sociocultural implications are touched upon. Specific recommendations for interested physicians are provided including advocacy for patients and for a change in the “scheduling” of cannabis in order to better foster much-needed high-quality scientific research in this important area.”

http://www.ncbi.nlm.nih.gov/pubmed/26835389