Cannabis Considered: 50 Shades of Mary Jane


Marijuana (cannabis) is one of the most controversial and politicized controlled substances in the United States. It has many names — Mary Jane, pot, ganja, sativa, etc. — and stories about it ranging from positive to negative, depending on whom you ask, abound. The tide, however, seems to be turning in its favor as some states are legalizing the use of marijuana. This means that science has never been more important in investigating the impact cannabis has on our most complex organ — the brain.

The secret sauce of marijuana is a psychoactive compound, or cannabinoid, called tetrahydrocannabinol (THC). It produces distinct sensations when it binds to two different cannabinoid receptors, CB1 and CB2, in the brain and the body, respectively. Memory and spatial orientation may become affected when THC binds to CB1 receptors in the hippocampus, basal ganglia, cerebellum, and limbic system. Subsequently, pain sensation, appetite regulation, cardiovascular function, and a host of other processes are impacted when THC binds to CB2 receptors predominantly found in the immune system (especially the spleen) and the peripheral nervous system.

In both instances, THC also produces a high that results from elevated dopamine levels. This process is monitored by CB1 receptors in the nucleus accumbens, a key part of the brain’s reward circuit. Despite the fact that dopamine is called the “pleasure” or “reward” hormone, it’s nowhere near that simple. It plays a role in depression, psychosis, paranoia, and schizophrenia. Therefore, cannabis use can actually change a person’s natural mood balance.

Marijuana As Medicine

Whether marijuana is harmful or beneficial for the brain is unclear. Although scientific studies of cannabis and its effects seem to pop up daily, many of them tend to be inconclusive or in need of further evaluation. Neither do they reveal anything definitive about its long-term effects. As far as the government is concerned, marijuana is still a dangerous and illicit drug classified as a Schedule I substance — the FDA’s most restrictive class — under the Controlled Substances Act.

Then there are celebrity endorsements further clouding the already muddy debate surrounding marijuana. Even trusted medical figures are flip-flopping their stances. For instance, celebrity neurosurgeon and former anti-marijuana backer Dr. Sanjay Gupta states on his CNN blog, “It doesn’t have a high potential for abuse, and there are very legitimate medical applications. In fact, sometimes marijuana is the only thing that works.”

The political-punditry aspect surrounding this issue makes matters that much more confusing. Anyone with a political agenda can cherry-pick any number of studies to fit their position. The National Eye Institute has stated that none of the studies they’d supported since 1978 demonstrated that marijuana or any of its components could lower intraocular pressure as effectively as existing drugs could.

But Dr. James Giordano, chief of the neuroethics studies program at the Pellegrino Center for Clinical Bioethics and professor of integrative physiology in the department of biochemistry at Georgetown University, thinks there are clear medicinal benefits. “The neurochemical effects of cannabinoids alter the transmission of neural impulses in brain regions responsible for processing both the sensory and emotional aspects of pain,” he says. “[They also] appear to help treatment and management of chronic pain, anxiety disorders, loss of appetite, and maybe even agitation and anger management disorders.”

While there is some evidence to support the use of medicinal marijuana, current scientific research is simply the tip of the cannabis iceberg.

Cannabinoid Rising

So, if marijuana does have medicinal properties, can’t we identify the “good” chemicals and synthesize them in measured doses for the treatment of specific conditions? Actually, we can, and we have. Dronabinol, a manufactured form of THC, is a Schedule III drug — meaning, it’s available by prescription. But cannabinoid-type drugs aren’t perfect.

Some patients have said Marinol (a common brand name of dronabinol) produces a more acute psychedelic effect than cannabis. Doctors are trying to figure out if this has to do with the absence of the many non-THC cannabinoids that temper such a reaction in cannabis. “Determining how to harness the benefits while minimizing the risks still remains to be answered,” says Dr. Francesca Filbey, addiction researcher at the Center for BrainHealth.

Recently, there’s been high demand for Charlotte’s Web, a strain of medical marijuana named after Charlotte Figi, a young girl who suffered up to 300 grand mal seizures a week. Her mother decided to try medicinal marijuana as a last resort — and two years later, Charlotte was mostly seizure free. Charlotte died in 2020 at the age of 13 after hospitalization due to pneumonia.

“Dosage, frequency, delivery system, and strain can make a huge difference in the therapeutic outcome,” says Dr. Dustin Sulak, founder and medical director of Interg8 Health, a medical-marijuana and alternative-medicine practice. “My practice strongly emphasizes education to help patients navigate all these options. Each patient is a unique case and requires an individualized approach.”

Neurology specialist Dr. Marc Schlosberg adds, “Some strains have a much higher percentage of cannabinoids, which might have therapeutic uses without the cognitive consequences.”

Stop Anytime?

Few questions surrounding marijuana are as polarizing as the one about addiction and whether or not it’s even possible to become addicted to it. Marijuana doesn’t contain nicotine, the chemical that makes tobacco addictive, and addiction to it is mainly psychological. Still, many marijuana proponents point out that socially acceptable drugs like cigarettes and alcohol are more dangerous and addictive.

University of Oxford researchers found that up to 10% of users form a psychological dependence to marijuana, but there were no defined withdrawal behaviors. Just months later, in a study conducted by the University of Arkansas, “Marijuana Abstinence Effects in Marijuana Smokers Maintained in Their Home Environment,” doctors found “several specific effects of marijuana abstinence in heavy … users and showed they were reliable and clinically significant,” adding that the effects appeared similar to the behaviors observed during nicotine withdrawal.

Giordano thinks it’s just a question of management. “Pharmacologically, there’s some evidence sensitivity to cannabinoids can decrease to some extent with frequent and high-dose use,” he says. “There’s also evidence different preparations of marijuana have slightly different properties and effects so rotating or switching the strain might reduce or circumvent them. Unfortunately, there just aren’t enough adequately controlled studies to settle the issue.” To Filbey, it’s an opportunity. The changes to brain processes caused by marijuana (including any possible addiction) give clues to molecular effects that might be crucial. “We can leverage this information to develop treatment and intervention,” she says.

Indeed, we must conduct dispassionate study of this strange, beloved, and demonized weed.

This article is updated from its initial publication in Brain World Magazine’s print edition.

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