Cannabis Decreases Neuropathic Pain

Abstract

A randomized, placebo-controlled crossover trial utilizing vaporized cannabis containing placebo and 6.7% and 2.9% delta-9-tetrahydrocannabinol (THC) was performed in 42 subjects with central neuropathic pain related to spinal cord injury and disease. Subjects received two administrations of the study medication in a 4-hour interval. Blood samples for pharmacokinetic evaluation were collected, and pain assessment tests were performed immediately after the second administration and 3 hours later. Pharmacokinetic data, although limited, were consistent with literature reports, namely dose-dependent increase in systemic exposure followed by rapid disappearance of THC. Dose-dependent improvement in pain score was evident across all pain scale elements. Using mixed model regression, an evaluation of the relationship between plasma concentrations of selected cannabinoids and percent change in items from the Neuropathic Pain Scale was conducted. Changes in the concentration of THC and its nonpsychotropic metabolite, 11-nor-9-carboxy-THC, were related to percent change from baseline of several descriptors (eg, itching, burning, and deep pain). However, given the large number of multiple comparisons, false-discovery-rate-adjusted P-values were not significant. Plans for future work are outlined to explore the relationship of plasma concentrations with the analgesic response to different cannabinoids. Such an appraisal of descriptors might contribute to the identification of distinct pathophysiologic mechanisms and, ultimately, the development of mechanism-based treatment approaches for neuropathic pain, a condition that remains difficult to treat.

Authors: BL Wilsey, R Deutsch, E Samara, TD Marcotte, AJ Barnes, MA Huestis, D Le

Journal of Pain Research (2016) 9:587

Clinical Trials, Studies and Publications (click to access):

A preliminary evaluation of the relationship of cannabinoid blood concentrations with the analgesic response to vaporized cannabis.

Cannabis in Cancer Care

Abstract

Cannabis has been used in medicine for thousands of years prior to achieving its current illicit substance status. Cannabinoids, the active components of Cannabis sativa, mimic the effects of the endogenous cannabinoids (endocannabinoids), activating specific cannabinoid receptors, particularly CB1 found predominantly in the central nervous system and CB2 found predominantly in cells involved with immune function. Delta-9-tetrahydrocannabinol, the main bioactive cannabinoid in the plant, has been available as a prescription medication approved for treatment of cancer chemotherapy-induced nausea and vomiting and anorexia associated with the AIDS wasting syndrome. Cannabinoids may be of benefit in the treatment of cancer-related pain, possibly synergistic with opioid analgesics. Cannabinoids have been shown to be of benefit in the treatment of HIV-related peripheral neuropathy, suggesting that they may be worthy of study in patients with other neuropathic symptoms. Cannabinoids have a favorable drug safety profile, but their medical use is predominantly limited by their psychoactive effects and their limited bioavailability.
Authnors: DI Abrams, M Guzman
Clinical Pharmacology and Therapeutics (2015) 97:575

Clinical Trials, Studies and Publications (click to access):

Cannabis in Cancer Care

Use of cannabinoids in cancer care – palliative care

Commentary by Dr. SK Aggarwal on Cannabinoid Integrative Medicine (CIM) in oncologic palliative care.

Summary:

“Integrating CIM into oncologic palliative care promises to improve overall health-related quality of life, to provide further relief from distressing symptoms and spiritual suffering, and to bring hope to patients and families facing terminal illness.”

Author: SK Aggarwal

Current Oncology (2016) 23:S33-S36

Clinical Trials, Studies and Publications (click to access):

Use of cannabinoids in cancer care: palliative care.

Integrating Cannabis Into Clinical Cancer Care

Abstract

Cannabis species have been used as medicine for thousands of years; only since the 1940s has the plant not been widely available for medical use. However, an increasing number of jurisdictions are making it possible for patients to obtain the botanical for medicinal use.

For the cancer patient, cannabis has a number of potential benefits, especially in the management of symptoms. Cannabis is useful in combating anorexia, chemotherapy-induced nausea and vomiting, pain, insomnia, and depression. Cannabis might be less potent than other available antiemetics, but for some patients, it is the only agent that works, and it is the only antiemetic that also increases appetite. Inhaled cannabis is more effective than placebo in ameliorating peripheral neuropathy in a number of conditions, and it could prove useful in chemotherapy-induced neuropathy. A pharmacokinetic interaction study of vaporized cannabis in patients with chronic pain on stable doses of sustained-release opioids demonstrated no clinically significant change in plasma opiates, while suggesting the possibility of synergistic analgesia.

Aside from symptom management, an increasing body of in vitro and animal-model studies supports a possible direct anticancer effect of cannabinoids by way of a number of different mechanisms involving apoptosis, angiogenesis, and inhibition of metastasis. Despite an absence of clinical trials, abundant anecdotal reports that describe patients having remarkable responses to cannabis as an anticancer agent, especially when taken as a high-potency orally ingested concentrate, are circulating. Human studies should be conducted to address critical questions related to the foregoing effects.

Authors: DJ Abrams

Current Oncology (2016) 23:S8-S14

Clinical Trials, Studies and Publications (click to access):

Integrating cannabis into clinical cancer care.

 

Endocannabinoid signaling mediates oxytocin-driven social reward

Evidence that an oxytocin-dependent endocannabinoid
signal contributes to the regulation of social reward.
The results provide insights into the functions of oxytocin, a
neuropeptide crucial for social behavior, and its interactions
with other modulatory systems that regulate the rewarding
properties of social behavior. They further suggest that oxytocin-
driven anandamide signaling may be defective in autism
spectrum disorders, and that correcting such deficits might offer a
strategy to treat these conditions.

Authors: D Wei, D Dinh, D Lee, A Anguren, G Moreno-Sanz, C Gall, D Piomelli

Cannabis and Cannabinoid Research (2016)1:81-89

Clinical Trials, Studies and Publications (click to access):

Enhancement of Anandamide-Mediated Endocannabinoid Signalling Corrects Autism-Related Social Impairment

Alzheimer‘s Disease: Cannabinoids – Protecting against a toxic protein

Cannabinoids and other drugs that block inflammation in neurons could help thwart the progression of Alzheimer‘s disease. One of the hallmarks of this neurodegenerative disorder is the accumulation of clumps of amyloid-β protein within brain cells. Researchers led by David Schubert of the Salk Institute for Biological Studies in the USA used a tissue culture model to study the toxic effects of these protein aggregates. They determined that the production of amyloid-β initiates an inflammatory response that ultimately leads to neuronal death. However, the researchers also identified important protective mechanisms. For example, the brain produces compounds called endocannabinoids that help eliminate amyloid-β. Treatment with related chemical compounds like tetrahydrocannabinol–the active ingredient in marijuana–also reduced inflammation and prevented cell death, suggesting a potential avenue for preventing neurological damage from this devastating disease.

Authors: A Currais, O Quehenberger, AM Armando, D Daugherty, P Maher, D Schubert
npj Aging and Mechanisms of Disease (2016) 2: 16012

Clinical Trials, Studies and Publications (click to access):

Amyloid proteotoxicity initiate and inflammatory response blocked by cannabinoids

Deficits in cannabinoid signalling may contribute to social impairment in autism spectrum disorders.

It has been suggested that oxytocin can improve social, emotional and behavioral problems in autistic children although comprehensive clinical studies are still required. This article describes a mouse model where anandamide-mediated signalling of CB1 receptors controls social reward that is driven by oxytocin. These results suggest that anandamide, a THC analog, may offer an avenue to improve behavior in austism spectrum disorders.

Abstract:

Marijuana exerts profound effects on human social behavior, but
the neural substrates underlying such effects are unknown. Here
we report that social contact increases, whereas isolation decreases,
the mobilization of the endogenous marijuana-like neurotransmitter,
anandamide, in the mouse nucleus accumbens (NAc),
a brain structure that regulates motivated behavior. Pharmacological
and genetic experiments show that anandamide mobilization and
consequent activation of CB1 cannabinoid receptors are necessary and
sufficient to express the rewarding properties of social interactions,
assessed using a socially conditioned place preference test.We further
show that oxytocin, a neuropeptide that reinforces parental and
social bonding, drives anandamide mobilization in the NAc. Pharmacological
blockade of oxytocin receptors stops this response, whereas
chemogenetic, site-selective activation of oxytocin neurons in the
paraventricular nucleus of the hypothalamus stimulates it. Genetic or
pharmacological interruption of anandamide degradation offsets the
effects of oxytocin receptor blockade on both social place preference
and cFos expression in the NAc. The results indicate that anandamidemediated
signaling at CB1 receptors, driven by oxytocin, controls social
reward. Deficits in this signaling mechanism may contribute to
social impairment in autism spectrum disorders and might offer an
avenue to treat these conditions.

Authors: D Wei, D Lee, CD Cox, CA Karsten, O Penagarikano, DH Geschwind, CM Gall, D Piomelli

PNAS (2015) 112: 14084-14089

Clinical Trials, Studies and Publications (click to access):

Endocannabinoid signaling mediates oxytocin-driven social reward.

Cannabinoid and opioid interactions: implications for opiate dependence and withdrawal

Comprehensive review of cannabinoid-opioid interactions including background on opioid addiction, opioid withdrawal and cannabinoid modulation of the opioid system.

Abstract: 

Withdrawal from opiates, such as heroin or oral narcotics, is characterized by a host of aversive
physical and emotional symptoms. High rates of relapse and limited treatment success rates for
opiate addiction have prompted a search for new approaches. For many opiate addicts, achieving
abstinence may be further complicated by poly-drug use and co-morbid mental disorders.
Research over the past decade has shed light on the influence of endocannabinoids on the opioid
system. Evidence from both animal and clinical studies point towards an interaction between these
two systems, and suggest that targeting the endocannabinoid system may provide novel
interventions for managing opiate dependence and withdrawal. This review will summarize the
literature surrounding the molecular effects of cannabinoids and opioids system on the locus
coeruleus-norepinephrine system, a key circuit implicated in the negative sequelae of opiate
addiction. A consideration of the trends and effects of marijuana use in those seeking treatment to
abstain from opiates in the clinical setting will also be presented. In summary, the present review
details how cannabinoid-opioid interactions may inform novel interventions in management of
opiate dependence and withdrawal.

Authors:  JL Sacavone, RC Sterling, EJ Van Brockstaele

Neuroscience (2013) 248: 637-654

 

Clinical Trials, Studies and Publications (click to access):

Cannabinoid and opioid interactions: implications for opiate dependence and withdrawal

 

Cannabis in Pain Treatment: Clinical and Research Considerations

In this article important considerations in the use of cannabis are presented to better prepare clinicians to care for patients who use if and needed directions for research are identified.

Abstract: Cannabinoids show promise as therapeutic agents, particularly as analgesics, but theirdevelopment and clinical use has been complicated by recognition of their botanical source, cannabis,as a substance of misuse. Although research into endogenous cannabinoid systems and potential cannabinoidpharmaceuticals is slowly increasing, there has been intense societal interest in making herbal(plant) cannabis available for medicinal use; 23 U.S. States and all Canadian provinces currently permituse in some clinical contexts. Whether or not individual professionals support the clinical use of herbalcannabis, all clinicians will encounter patients who elect to use it and therefore need to be prepared to

advise them on cannabis-related clinical issues despite limited evidence to guide care. Expanded
research on cannabis is needed to better determine the individual and public health effects of increasing
use of herbal cannabis and to advance understanding of the pharmaceutical potential of cannabinoids
as medications. This article reviews clinical, research, and policy issues related to herbal cannabis to support
clinicians in thoughtfully advising and caring for patients who use cannabis, and it examines obstacles
and opportunities to expand research on the health effects of herbal cannabis and cannabinoids.
Perspective: Herbal cannabis is increasingly available for clinical use in the United States despite
continuing controversies over its efficacy and safety. This article explores important considerations
in the use of plant Cannabis to better prepare clinicians to care for patients who use it, and identifies
needed directions for research.
ª 2016 by the American Pain Society

Authors: SR Savage, A Romero-Sandoval, M Schatman, M Wallace, G Fanciullo, B McCarberg and M Ware

The Journal of Pain (2016) 17:654-668

 

Clinical Trials, Studies and Publications (click to access):

Cannabis in Pain Treatment: Clinical and Research Considerations

 

 

 

 

The influence of cannabinoids on generic traits of neurodegeneration

Abstract:

Alzheimers-300x224In an increasingly ageing population, the incidence of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease are rising. While the aetiologies of these disorders are different, a number of common mechanisms that underlie their neurodegenerative components have been elucidated; namely neuroinflammation, excitotoxicity, mitochondrial dysfunction and reduced trophic support. Current therapies focus on treatment of the symptoms and attempt to delay the progression of these diseases but there is currently no cure. Modulation of the endogenous cannabinoid system is emerging as a potentially viable option in the treatment of neurodegeneration. Endocannabinoid signalling has been found to be altered in many neurodegenerative disorders. To this end, pharmacological manipulation of the endogenous cannabinoid system, as well as application of phytocannabinoids and synthetic cannabinoids have been investigated. Signalling from the CB1 and CB2 receptors are known to be involved in the regulation of Ca2+ homeostasis, mitochondrial function, trophic support and inflammatory status, respectively, while other receptors gated by cannabinoids such as PPARγ, are gaining interest in their anti-inflammatory properties. Through multiple lines of evidence, this evolutionarily conserved neurosignalling system has shown neuroprotective capabilities and is therefore a potential target for neurodegenerative disorders. This review details the mechanisms of neurodegeneration and highlights the beneficial effects of cannabinoid treatment.

Clinical Trials, Studies and Publications:

This review details the mechanisms of neurodegeneration and highlights the beneficial effects of cannabinoid treatment.