Cannabidivarin Rescues Memory Deficits in Mouse Model of Rett, Study Shows

Cannabidivarin, a non-psychotic compound found in cannabis, fully rescued memory deficits and delayed the appearance of neurological and motor defects in a mouse model of Rett syndrome (RTT), a study found.

The results, “Cannabidivarin completely rescues cognitive deficits and delays neurological and motor defects in male Mecp2 mutant mice,” were published in the Journal of Psychopharmacology.

Cannabinoids are a class of chemical substances that specifically act on cannabinoid receptors — cell surface receptors involved in physiological signals, including appetite, pain sensation, mood, and memory.

They are best known for their abundance in the cannabis plant; however, some are also naturally produced by the body. These are referred to as endocannabinoids. Others can be made artificially.

There are specific binding sites for cannabinoids in the body, predominantly in the brain (mostly CR1 receptors) and immune cells (mostly CR2 receptors), and to a lesser extent in other tissues.

In the brain, endocannabinoid signaling is primarily involved in functions such as memory, learning, emotions and appetite, but may also work to control movement and neuroinflammation, and to protect the brain from damage.

Because of their effects, cannabinoids have been increasingly suggested as potential treatments for many neurological conditions, including amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Parkinson’s disease.

Unlike tetrahydrocannabinol (THC), the main psychoactive component of cannabis, some cannabinoids have weak or no psychotropic activity, thus holding greater potential as therapeutic agents.

Cannabidiol (CBD) and cannabidivarin (CBDV), for instance, have been found to alleviate epilepsy and motor impairment, two conditions common in individuals with Rett, suggesting their potential as treatment options for the disease.

Based on previous promising results in mice showing that short treatment with cannabidivarin eased neurological and social deficits, researchers now tested the compound in a different mouse model of the disease, using a lifelong treatment schedule.

Researchers looked specifically at cannabidivarin’s effect on two neurological factors, brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1), whose reduced levels in the brain have been implicated in Rett syndrome, and have been seen as potential therapeutic targets.

The team treated 4-week-old mice with four different doses of purified cannabidivarin (0.2 mg/kg to 200 mg/kg), given daily over five weeks. Their behavior, cognitive deficits and neurological parameters were compared with untreated mice as well as healthy mice on the same treatment schedule.

The results showed that all cannabidivarin doses except the lowest one rescued Rett mice deficits in recognition memory (the ability to remember prior experiences) to the same levels of healthy mice.

The treatment also delayed the appearance of motor defects, including tremors, breathing and gait abnormalities, as well as behavioral symptoms.

At the molecular level, cannabidivarin was seen to normalize the brain levels of BDNF and IGF-1, and activate their signaling pathway in nerve cells.

These neurological improvements persisted even when mice were at an advanced stage of the disease (nine weeks of age).

Additionally, both CB1 and CB2 receptors in the brain, which are abnormally high during disease, were brought down by cannabidivarin treatment.

According to researchers, this study shows that chronic administration of cannabidivarin completely recovers memory deficits in mice with Rett-like disease, a durable beneficial effect that lasts through advanced stages of the disease.

“Regarding neurological and motor signs, our data support previous findings indicating that CBDV can ameliorate neurological and motor signs during an early symptomatic phase of the disease but highlight that this effect is only transient and is lost at advanced stages,” they said.

These findings encourage future studies to better understand the molecular mechanisms underlying cannabidivarin’s effects, as well as a more specific evaluation of its efficacy.