Cannabis and the Brain

MarijuanaMarijuana (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 pro- cess 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 schizo phrenia. 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 Sub- stances Act.

Then there are celebrity endorsements further clouding the already muddy debate surrounding marijuana. Even trusted medical figures are flip-flopping their stances. In March, for instance, celebrity neurosurgeon and former anti-marijuana backer Sanjay Gupta stated in his CNN blog, “It doesn’t have a high potential for abuse, and there are very legitimate medical applications [for it]. 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. In 2009, the National Eye Institute 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 man-made 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 Brain Health.

Recently, there’s been high demand for Charlotte’s Web, a strain of medical marijuana named after Charlotte Figi, a 5-year-old girl who suffered up to 300 grandmal seizures a week. Her mother decided to try medicinal marijuana as a last resort – two years later, Charlotte is mostly seizure free.

Unfortunately, medicinal cannabis use is overwhelmingly self- prescribed and therefore unregulated. “Dosage, frequency, delivery system and strain can make a huge difference in the therapeutic out- come,” says 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 psycho- logical. Still, many marijuana pro- ponents point out that socially acceptable drugs like cigarettes and alcohol are more dangerous and addictive.

In 2001, doctors from the University of Oxford found that up to 10 percent of users form a psychological dependence to it, 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.

Kids and teens

As children grow, their brains undergo continual transformation, forming and shedding huge numbers of neural connections for optimum performance in adult- hood. Study after study has shown that marijuana can interfere with this constant restructuring, particularly affecting brain areas that deal with memory and problem solving, which can affect cognition later in life.

Dr. Damon Raskin, director of the Cliffside Malibu addiction-treatment center in Southern California, says that because the brain doesn’t fully develop until around 25 to 26 years of age, marijuana can also lead to change in personality, judgment and reasoning skills. “Many adults appear to be able to use marijuana with relatively little harm,” he says. “But the same can’t be said of adolescents, who are about twice as likely as adults to become addicted to marijuana.”

But Dr. Sulak doesn’t see it this way. “The studies haven’t [proved] cannabis causes these outcomes, just that those with mental illness and impaired cognition are more likely to have tried cannabis in their youth than the rest of the population,” he says. “Contrary to the old ‘Just Say No’ campaigns (marijuana kills brain cells, etc.), cannabis has been [proved] to actually stimulate the growth of new brain cells and to enhance the connections between neurons.”


US states with legal cannabis: 2

US states with legal medical cannabis: 7

Number of daily or near daily users in the US: 3.6 million

Number of adults who use marijuana once a year: 5 percent

Number of cannabis-related arrests since 1993: 8,000,000

Estimated value of the marijuana market in the US: $35-45bn

Value of the legal marijuana market in 2013: $1.43bn

Estimated increase in 2014: 64 percent (to $2.34bn)

Rank of the US for people over age 15 who have used marijuana: 3rd (after New Zealand and Australia).