A study conducted on male Wistar rats found that once-daily administration of phytocannabinoids reduced voluntary alcohol intake. They tested three different compounds: cannabinol, tetrahydrocannabivarin, and cannabidiol, and found that they all reduced alcohol intake, although with different efficacy and side effects. The paper is alcohol and alcoholism.
Phytocannabinoids are naturally occurring compounds found in the cannabis plant that can interact with the endocannabinoid system and other biological systems in the body. “Phyto” means plant-based, so they are called “phyto” cannabinoids. The most well-known phytocannabinoids include tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), and tetrahydrocannabivarin (THCV), but the cannabis plant contains many others in small amounts.
Cannabinol, or CBN, is typically formed when THC breaks down with age, heat, or exposure to oxygen, so older cannabis material may contain more CBN. CBN is typically said to be mildly psychoactive, but much less so than THC. It is being studied for its possible effects on sleep, pain, and inflammation. Tetrahydrocannabivarin (THCV) is chemically related to THC, but can have different effects depending on the dose and situation. THCV has been studied for its possible role in appetite regulation, metabolism, glycemic control, and neurological effects, but strong clinical conclusions are still limited.
Cannabidiol (CBD) is a non-intoxicating phytocannabinoid that does not cause the “high” typically associated with THC. CBD is used to treat certain rare seizure disorders and is also widely marketed as a treatment for anxiety, sleep, pain, and inflammation, although evidence varies depending on the condition and product quality.
Study author Ieva Poceviciute and colleagues point out that the endocannabinoid system plays an important role in the development of alcohol use disorder. Studies have shown that synthetic substances that block or reduce the activity of CB1 receptors (a type of cannabinoid receptor) hold promise as new treatments for alcohol use disorder, but previous clinical trials of these drugs have failed due to severe psychiatric side effects. The authors sought to test whether naturally occurring non-psychoactive phytocannabinoids might be a safer alternative.
The endocannabinoid system is a body-wide signaling system of cannabinoid-like molecules, receptors, and enzymes that helps regulate functions such as mood, pain, appetite, sleep, memory, stress response, and inflammation. CB1 receptors are one of the main receptor types in this system and function as specialized molecules that detect specific types of signals and trigger a response within cells.
This study was conducted on male Wistar rats. All rats were group-housed from adolescence to adulthood. They had free access to standard laboratory rat chow and tap water.
To examine the effects of phytocannabinoids, CBN and THCV were dissolved in Tween 80 (a substance used to mix oil and water in food and pharmaceutical products) and diluted with 0.9% saline to a final Tween concentration of 4% and 5%, respectively. They were then injected into the peritoneum of rats in a volume of 2 ml/kg. CBD was suspended in 0.9% saline containing 0.5% methylcellulose and injected at a volume of 3 ml/kg.
To study the effects of phytocannabinoids on voluntary alcohol consumption, rats were allowed ad libitum access to water and 5% ethanol solution for 1 week. After this week, the alcohol concentration was increased to 8% for another week and finally to 10% for the remainder of the experiment (which lasted several months). Study authors measured alcohol and water intake weekly or daily.
The study authors excluded rats that did not drink much alcohol. Pharmacological intervention was performed only in rats that spontaneously ingested higher amounts of ethanol (at least 2 g/kg/day of ethanol). These rats were then randomly assigned to receive injections of different doses of CBN, THCV, CBD, or a placebo (an injection of a solution containing no phytocannabinoids) for three consecutive days.
During this time, the study authors measured various parameters such as the amount of alcohol the rats drank and their body weight. In one subgroup, motion sensors were used to track how much the rats moved over a 24-hour period. Those handling the rats did not know which groups of rats were receiving which treatments.
In another part of the study, the study authors tested the effects of these phytocannabinoids in a separate group of rats not given alcohol, measuring whether the compounds evoked emotion-like responses through the rats’ ultrasonic vocalizations. They treated high-frequency (50 kHz) calls as signs of positive emotional states, while low-frequency (22 kHz) calls were taken to signal negative emotional states such as distress.
Results showed that all three phytocannabinoids reduced voluntary alcohol consumption. However, there are differences in effectiveness and side effects. Treatment with CBN and THCV significantly reduced alcohol intake and alcohol preference, and the effects of CBN persisted for 3 days after the last injection. Both compounds had mild sedative effects, and the highest doses resulted in slight weight loss.
Surprisingly, CBD only had a small effect on alcohol consumption and had no effect on alcohol preference. Additionally, the rats’ movements were significantly reduced and their positive emotional state was reduced (50 kHz vocalizations were reduced). None of the compounds caused discomfort or pain (no 22 kHz vocalizations).
“We conclude that CBN and THCV have potential for the treatment of AUD (alcohol use disorder),” the study authors concluded.
This study contributes to scientific knowledge regarding the potential utility of phytocannabinoids in the treatment of alcohol use disorders. However, it is important to emphasize that this study was conducted in rats, not humans. Although rats and humans have many physiological similarities, they are still very different species. Therefore, the effects on the human body may not be the same.
The paper, “Effects of cannabinol, tetrahydrocannabivarin, and cannabidiol on voluntary alcohol intake” was authored by Ieva Poceviciute, Martynas Arbaciauskas, Rokas Buisas, Osvaldas Ruksenas, and Valentina Vengeliene.
