By Mark S. Gold, M.D. and Dr. Drew W. Edwards, EdD, MS


In part one, we culled the scientific literature and presented the best available research to bring forth the facts amid the current controversy. Framing the issue of cannabis use in terms of prevalence among children and teens, the neuroadaptive changes unique to adolescent brain development, and the long term cognitive and emotional deficits observed in those who are initiated early in life. [link to part one] The unprecedented correlation between cannabis use and mental illness, particularly depression, suicidality and psychosis and schizophrenia is cause for alarm and the reason the FDA requires all medicine to meet rigid safety standards.

“The consequences associated with frequent use of marijuana (as is the case for most teens and young adults) now include severe depressive state, suicidality, anxiety and psychosis that requires acute medical or psychiatric intervention.”

The research is clear, the life trajectory for children and teens who use cannabis is wrought with academic failure, psychopathology, underemployment, multiple failed relationships and decreased life expectancy.

In part two, we will delve deeper into the neurobiology of cannabis use, and explain the unique pharmacodynamics and pharmacokinetics of cannabis, in order to explain “WHY” cannabis has such unique, and deleterious effects. Part two will conclude with the challenges scientists face in understanding the endocannabinoid system and how to better educate parents and the public of the dangers unique to children and adolescence who live in a time, and in a society, that is, at best, ambivalent about this drug.

The neurobiology of cannabis

In 1964, the psychoactive ingredient of Cannabis sativa, Δ(9) tetrahydrocannabinol (THC), was isolated. In the late 1980’s and early 90’s researchers at Johns Hopkins discovered the endogenous counterpart of THC, collectively termed endocannabinoids and began to isolate them to understand their function. Anandamide is a naturally occurring, lipid endocannabinoid (endogenous cannabinoid) that functions as a neurotransmitter. Its natural receptors are found throughout the brain and body. Over the past 3 decades endocannabinoids have been recognized as key mediators of numerous aspects of human pathophysiology and thus have emerged as among the most widespread and versatile signaling molecules ever discovered. Most medications are mediated, to some degree through this system.

Specific functions of endocannabinoids mediate reward / pleasure, cognition (memory, executive function, focus, problem solving, concentration), movement, coordination, perception, and our sensation of time and space.

Usurping the Endocannabinoid System

Because THC is chemically similar to Anandamide, it can easily attach to cannabinoid receptors in the brain. But because it is a counterfeit to the anandamide, it corrupts the signal, and thus, the important functions of the endocannabinoid system throughout the brain and body.

Impaired Memory and Focus

Of particular interest is the effect of THC on the developing brain. For instance, THC binds to receptors on the hippocampus, which is designed to function much like the Random-Access- Memory (RAM) in a computer. The hippocampus, like a computer’s RAM, is responsible for coding, storing and retrieving memories. When impaired by THC, it fails to function properly. This was first observed in lab rats, while under the influence of THC and failed to navigate their way through a simple maze to find food and water, or escape. In contrast, the “sober” rats were able to learn, remember, store, and recall the information needed to find their way through the maze with relative ease. Human observational studies reveal much the same thing. Regular cannabis users struggle to recall previously learned information including common words used during a simple conversation. They often forget what they are saying, while they are saying it. So, they pause in mid-sentence and ask, “what was I saying”. Once “cued up” and reminded, they continue until the next time.

Marijuana also inhibits the normal function of the Orbitofrontal Cortex (OFC), an area directly behind the eyes, which serves to sustain and to shift our attention, and to create icons for new learning. The Pre-Frontal Cortex (PFC) houses our highest level or reasoning, problem solving and serves to mediate and inhibit hedonic signals from the midbrain. As a result of using marijuana, dopamine signals to the midbrain are enhanced while dopamine signals to the PFC are muted by marijuana. The result: Impaired cognitive function that interferes with the user’s ability to learn and perform complicated tasks, and apply sound reasoning in making important decisions in a timely manner.

The bottom line is clear. Adolescence who use marijuana regularly are at great risk for incurring detrimental and perhaps permanent neuroadaptations that can drastically alter the trajectory of their lives—while impairing their potential and capacity to be the very best version of themselves. Perhaps the most shocking evidence, is the quantitative drop in IQ among those who are initiated in their early or mid-teen years. These data explain the high level of school dropout, multiple failed relationships, and increased prevalence of dose dependent mental health problems. THC also binds to the cerebellum and the basal ganglia and thus, impairs balance and coordination, reaction time, and perceptions of time and space.Yet, for those who regularly use marijuana to get high, these side effects are dismissed as inconsequential because THC’s effect on the reward system in the midbrain is the brass ring, so to speak, because this is where the rewarding psychoactive effects, of the “high” occur.

Areas of the brain and function impaired by THC

High Octane Weed

Higher Potency Marijuana is particularly harmful to the developing brain. But it’s not just the potency, it’s also the ratio between THC and CBD. For example, street marijuana in the 1980’s contained approximated 50% THC and 50% CBD. We now understand that CBD is the healthy and protective constituent of cannabis. In contrast, today’s street marijuana is 90% THC and 10 % CBD, which produces an intense high, but also does more damage to the functionality of the brain, e.g., the neurotransmission of anandamide is corrupted by THC, thus inhibiting the role of anandamide in numerous somatic systems. To put it bluntly, CBD has numerous protective and beneficial effects, whereas THC simply gets you high. The only medicinal benefit of smoking THC is to reduce nausea and some neurogenic pain associated with late stage cancer and the effects of chemotherapy. Yet, it very well may be that the CBD is responsible for the positive effects observed in palliative care. Even if THC may temporarily mediate some forms of pain, the damage done, especially to the young and relatively healthy users far outweighs any known benefit of smoking a psychoactive substance associated with addiction, depression, cognitive decline, suicidality, anxiety, multiple failed relationships, and psychosis.

Marijuana use and Depression and Suicidality

The single most controversial question is the effect of cannabis use on mental health. Lev-Ran and colleagues evaluated 14 studies with a total of 76,058 participants in a meta-analysis. The odds ratio (OR) for depression among cannabis users’ vs nonusers was 1.17 (95% confidence interval [CI], 1.05-1.30). There was also evidence of a dose-response effect between marijuana use and the risk for depression. Heavy cannabis users had a higher OR for depression of 1.62 (95% CI, 1.21-2.16) compared with nonusers. The positive association between cannabis and a higher risk for depression was noted across different age groups.

After adjusting for co variates and using regression analysis, the research revealed that both early and frequent cannabis use is “robustly associated” with depression as well as suicidal thoughts and behaviors, with adjusted ORs ranging from 1.28 to 2.38. These significant associations persist, even when the researchers excluded lifetime never-users of cannabis from the analysis. Frequent users were twice as likely to report suicidal ideation and attempt than were lifetime but less-frequent users.

Why Crude Phytocannabinoid should never be a “medicine?

Unlike drugs approved by the Food and Drug Administration, “dispensary marijuana” has no quality control, no standardized composition or recommended dosage for specific medical conditions. It has no prescribing information or no high-quality studies of effectiveness or safety. The FDA is not opposed to approving cannabinoids as medicines, as it has already approved two cannabinoid medications and is poised to approve a CBD based anti-seizure medication shortly. Specifically, R=researchers at Nationwide Children’s Hospital and the Ohio State University College of Medicine in Columbus have demonstrated that CBD may provide tremendous benefits for children suffering from a severe form of epilepsy called Lennox- Gastaut Syndrome (LGS). The researchers noted “CBD looks like an important molecule for reducing seizures among children and adults with epilepsy possibly other medical conditions”.

Knowing that the science does not support the claims that THC is a harmless drug with multiple medicinal value, the pro cannabis lobby set their sights on the ballot box. Backed by millions of Madison Avenue marketing dollars, they have prevailed in several states and are targeting many more.

As scientists, we are excited about the potential of cannabis derived medicines, especially from CBD, which has no psychoactive effects. This is important because the best available research informs that THC is associated with numerous deficits including cognitive impairment, lower IQ, neuroadaptation, passed in utero to an unborn child, depression, suicidality, anxiety disorder, psychosis, schizophrenia and a shorter life expectancy.

As scientists, we are excited about the potential of cannabis derived medicines, especially from CBD, which has no psychoactive effects. This is important because the best available research informs that THC is associated with numerous deficits including cognitive impairment, lower IQ, neuroadaptation, passed in utero to an unborn child, depression, suicidality, anxiety disorder, psychosis, schizophrenia and a shorter life expectancy.

Marijuana is a dangerous and addictive drug. Additional cannabinoids and constituents of cannabis may be approved for humans in the near future, but only after rigorous scrutiny by the FDA for a specific disease, with a specific dosing and high safety parameters.

Mark S. Gold, MD, Chairman of the RiverMend Health Scientific Advisory Boards, is an award-winning expert on the effects of opiates, cocaine, food and addiction on the brain. His work over the past 40 years has led to new treatments for addiction and obesity which are still in widespread use today. He has authored over 1000 medical articles, chapters, abstracts, journals, and twelve professional books on a wide variety of psychiatric research subjects, including psychiatric comorbidity, detox and addiction treatment practice guidelines.

Dr. Drew Edwards is a behavioral medicine / addictive disease researcher, clinician, author, medical writer, and clinical consultant. He has published over 250 peer-reviewed and popular articles on behavioral medicine obesity, addictive disease, parenting and youth culture, as well books on childhood depression, and instilling selfesteem in children. He is a graduate of the University of Minnesota, received his Master of Science from the University of No. Florida and earned his doctorate at Nova Southeastern University.