The brain on cannabis

Research rushes to catch up with legalization

The brain on cannabis

Marijuana is set to become legal across Canada this week, and Canadians must be well equipped to confront any downstream effects this historic move may have. 

The Canadian Tobacco, Alcohol and Drugs Survey found 3.6 million — 12 per cent of Canadians — used cannabis in 2015. Of that population, 24 per cent said they used cannabis for medical purposes. 

Following legalization, individuals should be more cognizant of the effects of marijuana, and specifically ways in which it can affect the brain. 

What does marijuana do to your brain? 

The endocannabinoid system is a complex signaling system in the brain and surrounding tissues. Though it is not well understood, it has been shown to play a role in immune functions and the development of the nervous system. It is also the system that processes cannabis and plays a role in producing the associated neurological effects. 

The system consists of endocannabinoids, cannabinoid receptors, and enzymes that transform endocannabinoids in the body. 

Broadly, endocannabinoids like anandamide and 2-arachidonoylglycerol are a class of cannabinoids — chemicals present in cannabis — that bind to receptors in cells. Once bound, endocannabinoids act on CB1, a cannabinoid receptor that is found in the brain. 

Cannabidiol (CBD) and tetrahydrocannabinol (THC) are the two most well described cannabinoids in marijuana. 

NADIA BOACHIE AND KEITH CHENG/THE VARSITY

CBD does not produce any of the psychoactive effects, and has been found to block some of the effects of THC by interfering with CB1 receptors. 

Structurally, THC is similar to anandamide — a naturally occurring endocannabinoid — and has been shown to activate the endocannabinoid system. 

“[CB1 receptors] are found in many brain regions that control mood, appetite, memory etc. They inhibit the release of an inhibitor transmitter called GABA and this can lead to increased activity of certain brain excitation pathways,” U of T Professor Ruth Ross explained in an email. 

Ross’ research investigates the molecular pharmacology of cannabinoids. 

“There are many unanswered questions about the safety and efficacy of cannabis as a medicine and about the possible harms of cannabis ­— especially for certain people who may be vulnerable to these effects,” Ross added. “We desperately need more solid clinical data from double blind placebo controlled studies on safety and efficacy.” 

Marijuana in other areas of medicine

There is hope that medical research with cannabis and recreational users will benefit from its legalization. 

For example, Ross and her team are working on developing “medicines that target the endocannabinoid system for the treatment of liver disease, pain and brain disorders.”

Ross said that many medical claims are made about cannabis, but it can actually make some conditions worse. 

“It is almost unknown of any person who has overdosed on cannabis,” Andrea Furlan, Associate Professor in the Faculty of Medicine and Staff Physician and Senior Scientist at the Toronto Rehabilitation Institute, wrote to The Varsity. 

According to Ross, “Cannabis even at high doses does not have the type of physiologically dangerous effect that we might see with opioids, which cause respiratory depression and can cause death.” 

However, because of the psychoactive effects associated with marijuana, it could result in “acute psychosis, paranoia, anxiety, or fear,” and such effects could cause harm to individuals or those around them. 

Despite low chances of overdosing on marijuana, several studies have sought to compare long-term use of cannabis versus alcohol in the developing adolescent brain. One study concluded that “lasting effects of adolescent cannabis use can be observed on important cognitive functions and appear to be more pronounced than those observed for alcohol.”

The Canadian Institutes of Health Research is prioritizing research on neurodevelopment, prevention, harm and treatment of problematic cannabis use, potency and product safety, social determinants of health, relationship of cannabis use and mental health, potential applications of cannabis, and pain management. 

“We hope that with legalization there will be more scientists interested in this area, and that Canada will be a leader in research in the world,” Furlan said. 

The heart-stopping truth about smoking cessation drug

U of T prof finds varenicline to have adverse side effects

The heart-stopping truth about smoking cessation drug

As of 2014, approximately 5.4 million Canadians smoked daily or occasionally. The fight for smoking cessation has largely been made possible by varenicline, a prescription drug used to reduce the effects of nicotine.

A recent study spearheaded by Andrea Gershon, Lung Health Lead at the Institute for Clinical Evaluative Sciences (ICES) and an associate professor in U of T’s Department of Medicine, pointed to some alarming side effects of varenicline.

According to the study, the use of varenicline is associated with an increased number of serious cardiovascular events in the 12 weeks after starting varenicline use. The study reported a 34 per cent increase in risk of cardiovascular events in patients who had previously experienced cardiovascular episodes and a 12 per cent increase in those who had not.

In this study, serious cardiovascular events referred to heart-related conditions such as heart attacks, insufficient blood flow to the heart, heart failure, ischemic heart disease and stroke, abnormal heart beats, and peripheral vascular disease. The researchers also looked for possible neuropsychiatric effects of varenicline, but no serious effects were observed.

Approximately four patients out of 1,000 experience critical varenicline-induced cardiovascular events. Yet the difference between relative increased risk and absolute increased risk should be noted. “If the risk to begin with is pretty low, then [even with a high relative risk,] the absolute risk will also be low,” said Gershon.

The study was observational in nature, and Gershon took advantage of extensive patient data that was at her disposal. “Every time somebody goes to see a doctor or goes to the hospital, someone or some institution gets paid, and all that information is collected in the large health administrative databases.”

This data, run through the ICES, was collected prior to and after patients went on the medication, and then it was analyzed to determine the rate of incidence of cardiovascular events in patients.

This method was relatively beneficial due to the large sample size, which reduced bias. In general, using observational data can save time and money and increase the study’s scope.

There are, however, limitations — observational studies cannot determine causation. Observational data cannot determine whether patients were using other drugs to help quit smoking, or whether the patients quit smoking while taking varenicline.

Gershon stressed that this study addressed limitations commonly associated with an observational study, and she said that the paper underwent “a very strict peer review” process.

Though the study’s authors suggest that more research is required to confirm their findings, until evidence emerges to prove otherwise, it can be assumed that varenicline does increase the risk of cardiovascular events.

In a 2013 review published by the Cochrane Tobacco Addiction Group, varenicline was found to be the most effective drug for smoking cessation. Smokers were more than twice as likely to quit on varenicline than on a placebo, making it a commonly prescribed smoking cessation aid.

“I think quitting smoking is really important… the benefits of quitting smoking outweigh the risks of this medication,” said Gershon. “It’s complicated — just because somebody takes varenicline, that doesn’t mean they’ll be successful in quitting smoking. How motivated are they? How committed are they? What are their risk factors? It’s hardly an easy decision.”

Every patient is different and extraneous factors such as being predisposed to adverse cardiovascular events will influence how they will react to varenicline.