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