In times of stressful situations, the body enters a “fight or flight” mode in order to fine-tune cognitive skills and movements, as well as to protect itself from perceived harm. During this process, certain brain chemicals such as endocannabinoids are released to help the body perform at optimal levels. Endocannabinoids play a crucial role in motor control, cognitive function, emotions, and behavior. Interestingly, studies show that cannabis or commonly known as marijuana, contains endocannabinoids and many different cannabinoids (chemicals that give marijuana its medicinal and recreational properties) which may have a positive effect on mice behavior. However, chronic marijuana use may lead to dependence and other adverse side effects.
What is Marijuana?
Marijuana originally comes from the Indian hemp plant. The leaves, stems, flowers, and seeds of this plant are dried and pressed into bars or sticks. When smoked, marijuana causes intoxication or makes users “high”, thus creating a mind-altering effect. The effect can be felt within minutes and is usually accompanied by increased heart rate, hallucination, reduced blood pressure, extreme happiness, impairment of concentration and memory, lessened coordination, increase in appetite, rapid breathing, intense laughter, and talkativeness.
The Behavior-Altering Effect of Marijuana on Mice
Aside from endocannabinoids, several other cannabinoids including delta-9-tetrahydrocannabinol, cannabichromene, and cannabidiol, also found in marijuana are known to affect brain function. Studies show that these chemicals might be the reason why marijuana has a beneficial effect on mice behavior.
The role of marijuana in mice behavior is well established. In one study, Bruijnzeel et al. investigated the effects of marijuana smoke on the behavior of rats in the small and large open field test and the elevated plus maze test. The small open field test is commonly used to assess the stimulant-like effects of a drug, whereas the large open field and elevated plus maze test measure locomotor activity as well as anxiety-like behavior in rats. Researchers observed that marijuana smoke exposure induced a brief increase in locomotor activity followed by a prolonged decrease in anxiety-like behaviors.
In another study, Cutler et al. investigated the effects of marijuana on social behavior of mice. At 12-14 weeks, subjects were transferred from stock boxes (each containing 25-30 males) to observation boxes where they were caged in pairs. After 4-7 days, one animal of each pair was injected with marijuana suspension and was placed in an unfamiliar cage to assess anxiety-like behavior and social behavior. Researchers observed that mice treated with marijuana suspension displayed less non-social activity.
The antidepressant action of marijuana has been investigated by El-Alfy et al. using the automated mouse forced swim test (FST) and tail suspension test (TST). FST involves placing a rat or mouse inside a
cylinder filled with water in order to assess its mobility and depression-like behavior, whereas TST involves hanging a rat or mouse in an apparatus to measure depression. Researchers observed that rat subjects injected with cannabinoids such as tetrahydrocannabinol, cannabichromene and cannabidiol displayed a significant decrease in immobility time both in the FST and TST, which is indicative of a potent antidepressant effect.
Similarly, a study by Zanelati et al. investigated the antidepressant effect of cannabidiol in male Swiss mice. Mice were treated with cannabidiol and imipramine (an antidepressant drug) prior to FST. Researchers observed that cannabidiol treatment reduced immobility time in the FST, as did the antidepressant imipramine. This result strongly suggests that marijuana contains a chemical that can induce antidepressant-like effects comparable to those of antidepressant drugs.
Other studies also show that marijuana may also be beneficial in mental health disorder aside from depression. In one study, Gomes et al. reported that administration of cannabinoids was able to decrease marble burying in mice. Marble burying is used to assess anxiety or obsessive-compulsive disorder (OCD) behavior, and is based on the observation that rats and mice will bury either harmful or harmless objects in their bedding during stressful situations. This result suggests that marijuana may have some potential efficacy in reducing obsessive-compulsive behavior.
How Marijuana Exerts its Behavior-Altering Effect
Marijuana acts on naturally occurring receptors in the brain known as cannabinoid receptors, which are involved in a variety of physiological processes including mood, memory, thinking skills, pain sensation, and appetite. Aside from this action, research shows that marijuana exerts its sensory and mood-altering effects within the brain through the following important mechanisms:
- It induces anti-anxiety and antipsychotic-like effects in animal models by activating the 5-HT1A receptors, which are found in brain regions involved in the control of mood, cognition, and memory. In addition, cannabinoids from marijuana also help facilitate the 5-HT1A receptor-mediated transmission of electrical signals from one nerve cell to another.
- It increases the levels of brain-derived neurotrophic factor (BDNF), a protein that promotes the survival of nerve cells (neurons).
Interestingly, studies show that alterations in the activation of the 5-HT1A receptors are associated with depression and other mental health disorders in humans. Furthermore, numerous studies have shown that in people with major depressive disorder, schizophrenia, addiction, and other psychiatric disorders, blood tests reveal lower levels of BDNF. Since cannabinoids from marijuana play a crucial role in the regulation of the activities of the 5-HT1A receptors and work to increase BDNF levels, there’s a strong possibility that marijuana may help improve behavioral symptoms associated with various mental health disorders.
Marijuana, Treatment and Addiction
Delta-9-tetrahydrocannabinol, or THC for short, is one of the chemicals present in marijuana that affects mental state and contributes to what makes it addictive. Experts believe that higher levels of THC and increased usage could increase the likelihood of drug dependence. This is because THC binds to and activates the cannabinoid receptors in the brain once it enters the bloodstream. This, in turn, stimulates the brain to release dopamine, a chemical that induces feelings of pleasure and reward. As a result, regular marijuana intake creates a sense of anticipation for more pleasure and reward, which ultimately leads to extreme craving for marijuana and the need for higher dosage to achieve the same effects.
While marijuana may produce therapeutic benefits when used as a form of treatment for depression and other mental health disorders, it must be used with extreme caution to prevent addiction and other adverse side effects. Therefore, patients who require medical marijuana treatment must be assessed for potential misuse, abuse, or addiction. In addition, careful examination of the history of substance use disorders and psychiatric illness must also be performed for patients to be eligible for medical marijuana treatment.
With its positive effects on a wide array of physiological processes including mood, thinking skills, and social interaction in mice, marijuana may potentially be a therapeutic option for various mental health disorders especially in patients with altered behavior. However, careful assessment must be performed to screen patients who will receive marijuana treatment to prevent the likelihood of drug dependence and other adverse side effects.
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