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Marijuana and antidepressants don't mix

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01/24/2001 - Updated 02:20 PM ET

Marijuana and antidepressants don't mix

By Mike Falcon, Spotlight Health

With medical adviser Stephen A. Shoop, M.D.
Mike Tyson.

Five weeks before his most recent bout, heavyweight boxer Mike Tyson told reporters that he takes Zoloft, a popular antidepressant categorized as a selective serotonin reuptake inhibitor (SSRI). SSRIs keep the behavior-modulating neurotransmitter serotonin in brain circulation. Certainly Tyson's behavior could use some modulating influences: The fighter served time on a rape conviction and has been involved in violent altercations outside the ring. He also has been known to make outrageous press pronouncements, and his SSRI revelation was no exception. "I'm on the Zoloft to keep me from killing y'all," he said with a grin. If he was joking, no one was laughing.
Read more

* Tyson's failed drug test


* Dr. Abraham Kryger: Marijuana Mental Disturbances

Then came the bulletin that Tyson's October 2000 post-fight urine sample tested positive for marijuana, according to a member of the state of Michigan Board in Control of Athletics who was quoted in the Detroit News. The prospect of Iron Mike under the influence of both pot and pills added a new dimension of volatility to his reputation that was hardly needed.

Although Tyson claims he discontinues Zoloft before fights, the one-two combination of antidepressants and marijuana — even if ingestion is separated by weeks — could make even the toughest customer punchy or worse, doctors say.

The mixture "is a cocktail which can confound and confuse even the most determined and experienced psychiatrist," says Dr. Gabriel Nahas, pharmacology research professor at New York University Medical Center, and editor of Marijuana and Medicine, the topic's definitive text. "The effects on the patient can be very confusing, disorienting, and dangerous."

Mystery mix

It's a common, but probably severely under-reported psychoactive drug concoction, according to Dr. Abraham Kryger, a Monterey, Calif., family physician who has written and lectured extensively on the topic. "Because marijuana still has a stigma surrounding it, there are patients who have been prescribed antidepressants, including the newer SSRIs, who simply do not tell their physicians that they smoke marijuana, even if their doctor asks them."

As a result, he says, "Physicians see side effects which may or may not be due to the anti-depressant alone."

Marijuana is what pharmacologists call a "dirty" drug. It contains not only psychoactive tetrahydrocannabinol (THC), but 65 other cannabinoids which may modulate THC's effects and produce others of their own. It's therefore impossible to precisely define the effects produced by cross-medicating marijuana with antidepressants.

"We are a long way from knowing everything about marijuana alone," says Dr. Istvan Boksay, chief of psychiatry at the Aging and Dementia Research Center and a research pharmacologist at NYU Medical Center.

Pros and cons

Marijuana's medical benefits continue to be hotly debated. There is no shortage of studies proving its effectiveness in treating nausea, glaucoma and intra-ocular eye pressure, migraine headaches, suppressed appetite in AIDS patients, and specific types of pain. Some studies also suggest applications in movement and neurologic disorders.

Other drugs, or a synthetic form of THC called Marinol (dronabinol), sometimes perform as well or better in controlled studies, sometimes not.

"That brings us squarely back to whether it's the THC in marijuana or other modulating influences at work," says Boksay. "In either event, synthetic THC does not share all the properties of the naturally occurring THC in marijuana, and we're not sure why. There are some significant parallels, but they are not identical."

Marijuana's drawbacks, particularly in self-medicators, are equally well documented. According to Nahas, these include:

Addictive effects — While the debate rages on as to what constitutes addiction, "Nobody can argue that habitual use of marijuana does not exist," says Nahas.

Memory impairment — "How many stoners does it take to open an automobile door?" goes the well-worn joke at Marijuana Anonymous meetings. Answer: "Honey, me and Bill and Ed and Joe can't find any of our car keys."

Distance and time distortion — Spatial relationships become confused. Driving becomes dangerous.

Behavioral responses — From social interactions to "the appropriate response to an extremely wide range of stimulus demands, all can be impaired by marijuana," says Nahas.

Amotivational syndrome — "This is caused by the temporary low levels of testosterone produced by marijuana," says Boksay. You don't feel like doing much, with the exception of eating.

Disease — Some researchers, including Nahas, find marijuana implicated in a wide variety of diseases, from cancer to immune system response. Among the newest and most troubling: "Marijuana can change male and female reproductive function in an irreversible fashion, through the destruction of gametes in both men and women," says Nahas.

Still, many don't consider marijuana a serious health hazard. "Compared to so many other drugs, marijuana remains relatively innocuous in the minds of most," says Kryger. "But you should be careful in assessing psychoactive drug interactions, no matter which side of the marijuana 'fence' you're on."


According to Nahas' Marijuana and Medicine, these are some of the possible interactions between marijuana and various anti-depressants:

Tricyclics — "Additive tachycardia, " or accelerated heartbeat, hypertension, and drowsiness. Transient delirium and cognitive problems were also observed in four children.

SSRIs — "(One) case report of severe mania with psychosis on fluoxetene (Luvox) shortly after smoking marijuana. THC may inhibit serotonin uptake and increase its synthesis," says the text.

Still, the connection between marijuana and serotonin is speculative and hinges on the word "may," emphasizes Boksay.

"The cannanboid receptors in the brain are not SSRI-mediated and not serotonin-mediated, " he adds. Marijuana can, however, affect norepinephrine and dopamine, two other neurotransmitters that influence mood.

But neurotransmitter interactions and interdependence have yet to be completely defined. Add antidepressants plus marijuana and its 66 cannabinoids and you've got a mystery stew for the brain.

Not all SSRIs are affected equally by marijuana, Boksay emphasizes. Paxil and Prozac, for example, have greater inhibitory effects on an enzyme in the liver's P450 system, which metabolizes many drugs. Taking SSRIs could prolong the excretion of marijuana from the body.

"Tyson's a big guy, so it's possible that he may have not taken marijuana for several weeks, or even over a month," says Boksay. "He may have been honest when he said he didn't use marijuana for a long time."

At least one major drug testing authority agrees. "SSRIs can and will elevate levels of THC in urine because the SSRIs are being preferentially excreted before the THC," observes Dr. Lester Lee, former head of the United States Olympic Committee's drug testing arm and director of Arista Medical in Huntington Beach, Calif. "Someone previously testing at levels of 50-100 nanograms of THC may wind up testing at 100-400."

But all the experts absolutely agree on two points. Taking prescription antidepressants and simultaneously self-medicating with marijuana is not a good idea. And not telling the physician who prescribes your antidepressants that you use marijuana is simply a poor and potentially dangerous decision.

* Spotlight Health index

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