Marijuana compound may offer treatment for Alzheimer's disease
August 27, 2014
Science Daily/University of South Florida (USF Health)
Extremely low levels of the compound in marijuana known as delta-9-tetrahydrocannabinol, or THC, may slow or halt the progression of Alzheimer's disease, a recent study from neuroscientists at the University of South Florida shows.
Findings from the experiments, using a cellular model of Alzheimer's disease, were reported online in the Journal of Alzheimer's Disease.
Researchers from the USF Health Byrd Alzheimer's Institute showed that extremely low doses of THC reduce the production of amyloid beta, found in a soluble form in most aging brains, and prevent abnormal accumulation of this protein -- a process considered one of the pathological hallmarks evident early in the memory-robbing disease. These low concentrations of THC also selectively enhanced mitochondrial function, which is needed to help supply energy, transmit signals, and maintain a healthy brain.
"THC is known to be a potent antioxidant with neuroprotective properties, but this is the first report that the compound directly affects Alzheimer's pathology by decreasing amyloid beta levels, inhibiting its aggregation, and enhancing mitochondrial function," said study lead author Chuanhai Cao, PhD and a neuroscientist at the Byrd Alzheimer's Institute and the USF College of Pharmacy.
"Decreased levels of amyloid beta means less aggregation, which may protect against the progression of Alzheimer's disease. Since THC is a natural and relatively safe amyloid inhibitor, THC or its analogs may help us develop an effective treatment in the future."
The researchers point out that at the low doses studied, the therapeutic benefits of THC appear to prevail over the associated risks of THC toxicity and memory impairment.
Neel Nabar, a study co-author and MD/PhD candidate, recognized the rapidly changing political climate surrounding the debate over medical marijuana.
"While we are still far from a consensus, this study indicates that THC and THC-related compounds may be of therapeutic value in Alzheimer's disease," Nabar said. "Are we advocating that people use illicit drugs to prevent the disease? No. It's important to keep in mind that just because a drug may be effective doesn't mean it can be safely used by anyone. However, these findings may lead to the development of related compounds that are safe, legal, and useful in the treatment of Alzheimer's disease."
The body's own system of cannabinoid receptors interacts with naturally-occurring cannabinoid molecules, and these molecules function similarly to the THC isolated from the cannabis (marijuana) plant.
Dr. Cao's laboratory at the Byrd Alzheimer's Institute is currently investigating the effects of a drug cocktail that includes THC, caffeine as well as other natural compounds in a cellular model of Alzheimer's disease, and will advance to a genetically-engineered mouse model of Alzheimer's shortly.
"The dose and target population are critically important for any drug, so careful monitoring and control of drug levels in the blood and system are very important for therapeutic use, especially for a compound such as THC," Dr. Cao said.
https://www.sciencedaily.com/releases/2014/08/140827131801.htm
Synthetic Marijuana Compound Reduces Agitation, Improves Appetite in Alzheimer's Patients
August 21, 2003
Science Daily/Meridian Health System
Study results suggest dronabinol, a synthetic version of THC, the active ingredient in Cannabis sativa L (marijuana), may reduce agitation and lead to weight gain in patients with Alzheimer's disease, according to data presented today at the annual meeting of the International Psychogeriatric Association.
"Our research suggests dronabinol may reduce agitation and improve appetite in patients with Alzheimer's disease, when traditional therapies are not successful," said Joshua Shua-Haim, M.D., lead investigator in the study and medical director of the Meridian Institute for Aging, a continuum of senior health programs and services in Central New Jersey affiliated with Meridian Health System. "In the study, dronabinol appeared to be safe and effective for these patients. The results point to a promising direction for future research."
Dronabinol, marketed under the trade name Marinol, is synthetic delta-9-tetrahydrocannabinol (delta-9-THC). Delta-9-THC also is a naturally occurring component of Cannabis sativa L (marijuana). Dronabinol is the only cannabinoid approved by the U.S. Food and Drug Administration (FDA) and is indicated for the treatment of anorexia in patients with HIV/AIDS and for the treatment of nausea and vomiting associated with cancer chemotherapy.
An estimated four million Americans have Alzheimer's disease and the number will grow to 14 million by 2050, according to the Alzheimer's Association. In addition to memory loss, patients often experience agitation, loss of body weight, depression and restlessness.
Agitation is the most frequently encountered type of behavioral disturbance associated with Alzheimer's disease and affects an estimated 75 percent of people with the disease. Weight loss, a common problem in patients with Alzheimer's disease, is a predictive factor of mortality. Weight loss may derive from the deterioration of patients' cognitive abilities, resulting in an inability to recognize hunger and thirst.
"It's important to look at all the aspects of Alzheimer's disease that contribute to quality of life for patients, family members and caregivers," said Dr. Shua-Haim. "Agitation and weight loss are upsetting and stressful as the patient's needs become ever more demanding."
The study was a retrospective review and examined 48 patients (mean age = 77) residing in a dementia unit of an assisted living facility or a nursing home. All patients met the DSM-IV and NINCDS-ADRDA criteria for possible Alzheimer's disease and, according to their family or caregivers, had unsatisfactory control of their agitation. The mini mental status examination (MMSE), a test used to measure a person's basic cognitive skills, and an assessment of activities of daily living were used to evaluate patients prior to treatment with dronabinol and at one month. Patients initially received 5 mg/day of dronabinol in two doses. The treatment was titrated up to a maximum of 10 mg/day. In addition, all patients were treated with atypical neuroleptics and at least four medications to control behavior.
The evaluation by caregivers following one month of treatment found 31 patients (66 percent) experienced a significant improvement in agitation. Functional improvement was observed in 33 (69 percent) of the patients. Prior to the study, all patients experienced weight loss and had been diagnosed with anorexia. After treatment with dronabinol, all patients (100 percent) had gained weight. No adverse events, such as falls, syncope, seizures or exacerbation of agitation or depression, were reported as a result of treatment.
Meridian Health System is comprised of Jersey Shore Medical Center in Neptune, Medical Center of Ocean County in Brick, and Riverview Medical Center in Red Bank, in addition to long-term care and assisted living facilities, a home care agency, ambulatory care sites, ambulance services, and other related health services and affiliations throughout Monmouth and Ocean counties in New Jersey.
https://www.sciencedaily.com/releases/2003/08/030821072622.htm