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Vol. LXVI, No. 17
August 15, 2014
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NIDA’s Huestis Warns of Adverse Cognitive Effects of Marijuana; Some Therapeutic Uses Seen

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NIDA’s Dr. Marilyn Huestis discusses potential therapeutic uses, and dangers, of marijuana.
NIDA’s Dr. Marilyn Huestis discusses potential therapeutic uses, and dangers, of marijuana.

A Lipsett Amphitheater full of eager attendees listened intently, some of them perhaps hoping to hear validating evidence of the merits of marijuana. But the jury’s still out: while marijuana has some therapeutic potential, more research is needed. What we do know, said Dr. Marilyn Huestis, chief of the chemistry and drug metabolism section at the National Institute on Drug Abuse, is that the harmful effects of marijuana last longer than you may realize. The primary psychoactive chemical in marijuana, Δ-9-tetrahydrocannabinol (THC), is stored in the body after chronic, frequent marijuana use.

The national debate over marijuana’s safety rages on. Medical marijuana is legal in 23 states and the District of Columbia. This year, Colorado and Washington legalized marijuana outright. About 12 percent of Americans age 12 and older reported using marijuana in the past year, according to a survey by the Substance Abuse and Mental Health Services Administration. But is cannabis consumption safe?

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“We know there are therapeutic benefits, but we haven’t been able to separate the psychoactive effects from the therapeutic benefits,” said Huestis at a July 22 lecture titled, “Marijuana: From the Street to the Clinic.” The talk was sponsored by NCCAM and the NIH natural products special interest group.

Effects on the Brain

Marijuana comes from the Cannabis sativa plant, which for thousands of years has been valued for its medicinal and euphoric effects. Today we know that cannabis contains more than 530 chemicals, including 109 cannabinoids, explained Huestis. THC binds to cannabinoid receptors throughout the brain and affects all aspects of brain function, including executive function (paying attention, memory and learning, decision-making); emotion, coordination and motor control, appetite and pain sensation. Smoking or inhaling marijuana sends a concentrated dose into the lungs and quickly releases THC into the brain, causing a rapid onset of effects.

Recent surveys show that the perceived danger of using marijuana is down among adolescents. Yet studies reveal that marijuana negatively affects brain development and is associated with decreased IQ, especially in kids who start using pot when they’re younger than 15. Huestis said persistent marijuana use from childhood to middle age can cause significant neurological decline.

In one study of adult chronic daily marijuana smokers conducted by Huestis and her team, 28 men and women ages 19-38 abstained from marijuana in a closed clinical setting. Blood and urine samples were collected daily.

“The problem with pot medicalization is the public infers that marijuana use is not associated with significant or lasting harm,” said Huestis.

“The problem with pot medicalization is the public infers that marijuana use is not associated with significant or lasting harm,” said Huestis.

Photos: Ernie Branson

“The data rocked the toxicology world,” said Huestis. Within 19 hours, 13 people tested negative. Of the 15 people who tested positive for THC after the first test, all but 5 had 1 or more blood samples come up negative and then turn positive days later. In fact, more people tested positive on day 5 than on day 4.

“We in the field had really underestimated the cannabinoids that build up in people,” said Huestis. “What you have is this slow release of THC from the tissues and it goes on for a very long period in chronic, frequent smokers.”

In this study, interestingly, the 5 people whose blood tested THC-positive during the first 7 days were all women and urine tested positive 6 days longer in women than in men. “This [study] is critical for treatment programs because you have people assuming that if someone is still positive, they’re actually still using the drug, but we show they stay positive for long periods of time.”

Huestis described measuring cannabinoid (CB) receptor density in the brain of these individuals when they first entered the research unit and after 28 days of sustained abstinence. Her team found significantly reduced density of CB receptors in specific brain regions known to be important areas where marijuana has effects. After 28 days with no marijuana, the receptor density returned to normal, showing chronic, frequent smokers have effects of marijuana long after their last use due to the large body burden of THC.

Studies show conflicting results about lasting cognitive impairments from marijuana use. In some studies, the heaviest users have irreversible loss of cognitive performance. Other studies show impairment for more than a week but then cognitive function improved or returned to normal after a month. In a recent NIDA-NIMH collaborative study of infrequent marijuana smokers, THC could be found in the blood a month later in some participants.

Driving While Stoned

If THC can remain in the body after 30 days of abstinence, “this creates a huge problem with driving under the influence,” said Huestis. Multi-site studies over the past decade have shown an increased risk of car crashes if THC is at all measurable in the body. Her studies found significant psychomotor impairment in chronic daily marijuana users that lasted at least 3 weeks after sustained abstinence from the drug.

What will happen on the road if marijuana becomes legal in other places? In Colorado, the chief toxicologist reported a 25 percent increase in driving under the influence of marijuana cases in the first 6 weeks after the drug’s legalization.

Huestis and colleagues are currently studying the effects of marijuana with and without low-dose alcohol in the National Advanced Driving Simulator at the University of Iowa. Data are being analyzed to gauge the effects of marijuana on decision-making, divided attention, concentration, reaction time and vehicle control, among other parameters—all integral abilities for safe driving.

Medical Marijuana

But the news is not all negative. Marijuana does have therapeutic benefits. CB receptors are the most common G-protein coupled receptors present in the brain, offering many therapeutic targets. Some of the most promising applications are to ease pain in cancer patients, relieve neuropathic pain and spasms in multiple sclerosis and reduce vomiting following cancer medications. For more than a decade, scientists have been studying marijuana’s potential to help treat severe nausea, inflammation, seizures and glaucoma and to manage symptoms associated with AIDS and other diseases. Currently, a new cannabis-based extract nasal spray to relieve cancer pain is in phase 3 clinical trials.

“The problem with pot medicalization is the public infers that marijuana use is not associated with significant or lasting harm,” said Huestis. Meanwhile, the composition and purity of active components can vary and often don’t meet Food and Drug Administration standards, she said. While Huestis said she supports research on therapeutic uses, she advocates using purified, FDA-approved compounds that are dispensed properly to meet therapeutic standards and said an alternate administration route other than smoking is needed.

With the increased availability and potency of marijuana come increased health and accident risk. Yet more people are becoming desensitized to the dangers of cannabis use. Huestis advocates for more defined behavioral and biological markers of impairment, improved public education about marijuana’s risks and more science-based drug legislation.

“Where I hope we can go is a much more balanced approach,” said Huestis. “We need to enable and expand cannabinoid research on many different effects in the body—neurocognitive, psychomotor, reproductive and genetic. We [also] need well-controlled research on the potential therapeutic benefits to develop safe, effective medications and delivery systems and enable availability of efficacious medications to legitimate patients.”


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