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Pot may be both good and bad, researchers say

Nov. 25, 2006
Special to World Science  

For scientists, as for so­ci­e­ty at large, ma­ri­jua­na has been among the most be­dev­il­ing of drugs. 

Some stud­ies have found that the il­lic­it sub­stance dam­ag­es the mem­o­ry. Oth­ers sug­gest that it does­n’t, or even that it’s ben­e­fi­cial for some con­di­tions, in­clud­ing Alz­hei­mer’s dis­ease. Through it all, the pub­lic clam­ors for an­swer­s—des­per­ate­ly needed to re­solve a decades-long, rau­cous de­bate over wheth­er pot is safe enough to be le­gal.

Leaves of the ma­ri­jua­na or Can­na­bis sa­ti­va plant (cour­te­sy Io­wa Dept. of Pub­lic Safe­ty)
A theory now emerg­ing from a re­search group pro­poses that the truth may be more com­plex than ei­ther side in that de­bate would have us be­lieve. Ma­ri­jua­na may have played a trick on us all, they sug­gest, by play­ing the roles of both health vil­lain and he­ro. 

In hefty doses, they ar­gue, its ac­tive in­gre­di­ent may pro­tect the brain ag­ainst var­i­ous types of da­m­age, where­as in ti­ny doses, harm­ful ef­fects would come through. 

The bad doses would be much low­er than those nor­mal­ly ob­tained from smok­ing a “joint,” ar­gues Yo­sef Sar­ne of Tel Aviv Uni­ver­si­ty in Is­ra­el, a mem­ber of the re­search team. On the oth­er hand, he notes, a large dose in­ev­i­ta­bly be­comes a small one as the body slow­ly clears it out—so per­haps a us­er can nev­er side­step the dan­gers com­plete­ly.

Sar­ne and five colleagues at the university pre­sented find­ings in sup­port of their hy­po­the­sis in the Nov. 6 is­sue of the re­search jour­nal Neu­ro­science Let­ters.

The ac­tive com­pound res­pon­si­ble for ma­ri­jua­na’s “high” is called del­ta nine te­t­ra­hy­dro­can­na­bi­nol, or THC. This and re­lat­ed com­pounds, in high doses, tend to re­strict the re­lease of a chem­i­cal called glu­ta­mate from brain cells, Sarne and col­leagues ar­gued. This ef­fect can be help­ful be­cause ex­cess re­lease of glu­ta­mate—which is also an es­sen­tial chem­i­cal mes­sen­ger in the brain—is im­pli­cat­ed in var­i­ous dis­or­ders, in­clud­ing Alzheimer’s. 

This, the scientists wrote, may ex­plain why THC-like com­pounds, called can­nabi­noids, help pro­tect brain cells in cases such as is­che­mia, or blocked blood ves­sels; ex­ci­to­tox­i­ci­ty, or over­sti­m­u­la­tion of nerve cells; and even phy­si­cal in­jur­ies.

Stud­ies sug­gest cannabi­noids tem­per glu­ta­mate re­lease by par­tially block­ing mo­lec­u­lar gate­ways in nerve cells, known as voltage-dependent cal­ci­um chan­nels, Sarne and col­leagues wrote. 

But ultra-low doses ap­pear to have the op­po­site ef­fect, they added.

Thus they proposed that “an acute treat­ment re­sults in a high con­cen­tra­tion of the drug close to the time of trau­ma and there­fore pro­tects the brain from the acute in­sult, while chron­ic treat­ment ex­poses the or­gan­ism to low con­cen­tra­tions of can­na­bi­noids for long pe­ri­ods of time.” Dur­ing that time, “mi­nor” nerve cell dam­age ac­cu­mu­lates.

In the stu­dy, Sarne and col­leagues in­jected mice with THC doses that they said were some 1,000 times low­er than what hu­mans would get from smok­ing a joint, tak­ing in­to ac­count body weight. The treat­ment sig­nif­i­cantly wors­ened the ro­dents’ per­for­mance on maze tests three weeks lat­er, com­pared to un­treat­ed mice, they wrote.

Ex­act­ly how the chem­i­cal dam­ag­es the brain re­mains un­clear, Sarne’s team wrote, as are the im­pli­ca­tions for hu­mans.

“Hu­man sub­jects may overcome such mi­nor deficits,” they wrote. Some brain im­ag­ing stud­ies have found that fre­quent smok­ers “can com­pen­sate for sub­tle cog­ni­tive deficits by en­list­ing larg­er brain re­gions or by re­cruit­ing ad­di­tion­al brain ar­eas.... Yet, such sub­tle deficits might emerge un­der cer­tain be­hav­ior­al or phys­i­o­lo­gi­cal con­di­tions.”

The im­por­tance of this re­search goes “be­yond its sci­en­tif­ic sig­nif­i­cance,” the team wrote in a pre­vi­ous pa­per, pub­lished in the jour­nal Med­i­cal Hy­pothe­ses in 2004. “Can­na­bi­noids are the most wide­ly used drugs of abuse. In spite of the many re­ports on their long-term neu­ro­toxic ef­fects, can­na­bi­noids are still con­sid­ered by many as ‘safe soft drugs,’” and their ben­e­fi­cial ef­fects are of­ten cit­ed to back up claims for their long-term safe­ty.

Distinguishing these two modes of ac­tion may help edu­cate the pub­lic as to pot’s un­healthy con­se­quences, while clar­i­fy­ing the clin­i­cal ben­e­fits, they wrote. Can­na­bi­noids are used or un­der con­sid­er­a­tion for use, they not­ed, to fight pain and in­flam­ma­tion, to pre­vent vom­it­ing and nau­sea from chemoth­erapy, to stim­u­late ap­pe­tite in AIDS and an­o­rex­ia pa­tients, and to treat mus­cle spasms in mul­ti­ple scle­ro­sis.

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It's true, pot may have many benefits as well as downsides. Learn about marijuana and see why people are eager to dive into research to show how it can be used to benefit people with health ailments. Medicinal marijuana is a topic that is becoming more and more prominent so catch up on the latest news and issues associated with it.

For researchers, as for society at large, marijuana has been among the most bedeviling of drugs. Some studies have found that the illicit substance damages the memory. Others suggest that it doesn’t, or even that it may be beneficial for some conditions including Alzheimer’s disease. Through it all, the public clamors for answers—desperately needed to help resolve a decades-long, raucous debate over whether pot is safe enough to be legalized. A group of scientists now proposes that the answer may be more complex than either side in that debate would have us believe. Marijuana may have played a trick on us all, they suggest, playing the roles of both health villain and hero. In hefty doses, they argue, its active ingredient may help protect the brain against various types of damage. But in tiny doses, harmful effects come through, they add. Those damaging doses would be much lower than those normally taken in from smoking in a marijuana cigarette, argues Yosef Sarne of Tel Aviv University in Israel, a member of the research team. On the other hand, he adds, a large dose inevitably becomes a small one as the body clears it out—so perhaps a user can never sidestep the dangers completely. The team presented its findings in the Nov. 6 issue of the research journal Neuroscience Letters. The active compound that produces the “high” in marijuana is called delta nine tetrahydrocannibanol, or THC for short. This and related compounds, in high doses, tend to restrict the release of a chemical called glutamate from brain cells, Sarne and colleagues argued. This can be helpful because excess release of glutamate—otherwise a normal and essential chemical messenger in the brain—is implicated in various disorders, including Alzheimer’s. This may explain why compounds in the THC family, called cannabinoids, help protect brain cells in cases such as ischemia, or blocked blood vessels; excitotoxicity, or overstimulation of nerve cells; or blows to the head. Studies suggest that cannabinoids seem to suppress glutamate release by partially blocking molecular gateways in nerve cells, known as voltage-dependent calcium channels, Sarne and colleagues wrote. But ultra-low doses appear to have the opposite effect, they added. Thus the researchers hypothesized that “an acute treatment results in a high concentration of the drug close to the time of trauma and therefore protects the brain from the acute insult, while chronic treatment exposes the organism to low concentrations of cannabinoids for long periods of time.” During that time, “minor” nerve cell damage accumulates. In the Neuroscience Letters study, Sarne and colleagues injected mice with THC doses that they said were some 1,000 times lower, taking into account body weight, than what humans would get from smoking a joint. The treatment significantly worsened the rodents’ performance on maze tests three weeks later, compared to untreated mice, they wrote. Exactly how the chemical damages the brain remains unclear, Sarne’s team wrote, as are the implications for humans. “Human subjects may overcome such minor deficits,” they wrote. Some brain imaging studies have found that frequent smokers “can compensate for subtle cognitive deficits by enlisting larger brain regions or by recruiting additional brain areas.... Yet, such subtle deficits might emerge under certain behavioral or physiological conditions.” The importance of this research goes “beyond its scientific significance,” the team wrote in a previous paper, published in the journal Medical Hypotheses in 2004. “Cannabinoids are the most widely used drugs of abuse. In spite of the many reports on their long-term neurotoxic effects, cannabinoids are still considered by many as ‘safe soft drugs,’” and their beneficial effects are often cited to back up claims for their long-term safety. “The clear dissociation between these two modes of action, and the demonstration that cannabinoids induce long-term cognitive deficits, may help to draw the public awareness to the deleterious consequences” of chronic pot use, as well as clarifying the drug’s clinical benefits. Cannabinoids are used or under consideration for use, they noted, to fight pain and inflammation, prevent vomiting and nausea from chemotherapy, stimulate appetite in AIDS and anorexia patients, and to treat muscle spasms associated with multiple sclerosis.