Is Marijuana Harmless?

Marijuana (Cannabis sativa) is the illicit drug most commonly used by teenagers in the United States. Although cannabis is not as addictive as other substances, such as heroin and cocaine, cannabis-dependent individuals still greatly outnumber those reporting dependence on other illicit drugs and the number of people seeking treatment for cannabis dependence continues to increase yearly. Despite these facts, there is a growing perception, particularly in adolescents and young adults, that cannabis is ‘harmless’ and there is currently much debate as to whether cannabis should be legalized. Unfortunately, most of the discussion and policies being made regarding cannabis have been done without significant consideration of scientific data. Our studies directly address the question regarding the long-term impact on the brain as a consequence of cannabis exposure during adolescence, a period of dynamic brain development.

Translational studies carried out in our group with animal models and human subjects have begun to shed light on neuronal systems affected in adulthood as a consequence of developmental exposure to cannabis. For example, adolescent exposure to delta-tetrahydrocannabidiol (THC), the psychoactive component of cannabis, directly alters the expression of genes that regulate reward, decision-making and mood in brain regions intricately linked with addiction and related psychiatric disorders. Moreover, such animals as adults have increased self-administration of other drugs of abuse such as heroin in line with the so-called ‘gate-way’ hypothesis. Using molecular techniques that allow manipulation of genes in specific neuronal pathway in animal models, we have been able to prove a causal link between disturbance of these genes affected long-term by THC and enhanced drug intake.

It is important to note that not all individuals exhibit long-term sensitivity to developmental cannabis exposure. An important scientific question therefore focuses on what factors contribute to such individual differences. Our human studies have revealed that genetic mutations of genes previously identified in the animal models to be sensitive to the protracted effects of THC significantly associate with behavioral traits of inhibitory control and negative affective (anxiety/neuroticism). In addition, there is a synergistic interaction between mutation of these genes and negative affective trait that enhances the risk of cannabis dependence nearly 9-fold. Altogether, the accumulating data suggest that adolescent cannabis exposure does induce significant protracted effects suggestive of enhanced addiction vulnerability in later life, at least in certain subsets of individuals. Moreover, recent evidence has also begun to illuminate cross-generational effects on brain and behavior as a consequence of adolescent cannabis exposure on their adult children and grandchildren. As such, systematic scientific evidence to date suggests that the effects of cannabis are not benign.

Dr. Yasmin Hurd is Professor in the Departments of Psychiatry, Pharmacology and Systems Therapeutics, and Neuroscience.  She is the Chief of the Center of Excellence in Mood and Motivation in the Brain Institute and also serves as Chair of the Minority Health Research Committee (MHRC).

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