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Even One THC Hit Carries Risk for Inducing Psychosis

Meta-Analysis: Even One THC Hit Carries Risk for Inducing Psychosis
— Evidence suggested adding CBD does not ameliorate these effects

The psychoactive components of cannabis were linked to new-onset psychotic symptoms even at low doses, according to a systematic review and meta-analysis.

Across nine studies involving 196 healthy young adults, tetrahydrocannabinol (THC) was associated with significantly increased total symptom severity on the Brief Psychiatric Rating Scale compared with placebo (standardized mean change 1.10, 95% CI 0.92-1.28, P<0.0001) even at low doses, ranging from 1.25 mg to 10 mg, reported Oliver Howes, MD, PhD, of King’s College London, and colleagues.

Also, just one of four studies in which cannabidiol (CBD) was administered concurrently with THC found CBD administration reduced these symptoms, they wrote in the Lancet Psychiatry.

“Our findings highlight the risk of psychiatric symptoms after even a single dose of some THC-containing cannabis products,” Howes told MedPage Today in an email.

These findings add to the “growing scientific consensus” in support of the psychosis-cannabis link, an association that appears to be bidirectional, wrote Carsten Hjorthøj, PhD, and Christine Merrild Posselt, PhD, both of the University of Copenhagen in Denmark, in an accompanying commentary.

“In some people, cannabis leads to incident psychosis, whereas in other people, psychosis leads to incident cannabis use,” they wrote.

Hjorthøj and Posselt cautioned against extrapolating these findings to assume “single doses of THC will eventually lead to schizophrenia,” but also emphasized that “caution should not be thrown to the wind.”

For example, CBD in particular has been touted as a potential “wonder drug” with antipsychotic, anxiety-reducing effects, but the findings here suggest the usefulness of CBD and other cannabis extracts “might be somewhat exaggerated compared with what we can expect in clinical practice,” they continued.

This meta-analysis involved double-blind, placebo-controlled studies of healthy participants administered IV, oral, or inhaled THC with or without CBD. Individuals were generally in their mid-20s and predominantly male.

Of the 15 studies included, 13 were considered to have a “low” risk of bias and two studies had a “moderate” risk, as measured through the Newcastle Ottawa Scale. The authors calculated the SMR scores for “positive (including delusions and hallucinations), negative (such as blunted affect and amotivation), and general (including depression and anxiety) symptoms,” they explained.

Compared with placebo, THC was associated with significantly increased positive symptom severity scores in 14 studies (SMC 0.91, 95% CI 0.68-1.14, P<0.0001), negative symptom severity scores in 12 studies (SMC 0.78, 95% CI 0.59-0.97, P<0.0001), and general symptoms in eight studies (SMC 1.01, 95% CI 0.77-1.25, P<0.0001), researchers reported.

THC was also associated with increased total symptom severity versus placebo regardless of whether it was administered intravenously or inhaled (P=0.37), and regardless of whether participants were frequent or current cannabis users (P=0.73, P=0.95, respectively), the authors noted.

However, intravenous THC was associated with slightly “more pronounced” increased symptoms than inhalation, although this may be confounded by dose, they added.

The induction of psychotic symptoms was also lower in people with higher versus lower tobacco use, suggesting tobacco use may be a “protective factor,” the authors noted, although they cautioned against using tobacco to “counter” THC effects.

Howes told MedPage Today that “[another] possibility suggested by other evidence is that tobacco reduces the levels of the protein in the brain that THC binds to so it has less effect. This needs testing, and it is important that people don’t think tobacco will protect against the effects of THC containing cannabis.”

Many of the meta-regression analyses used involved fewer than 10 studies and were underpowered to detect small or moderate effects, which is a limitation, the authors noted. More participants were male than female, so the generalizability of these findings is also limited, they added. Researchers were additionally unable to differentiate the effects of THC on specific symptoms, like hallucinations or delusions.

As pot becomes legal, head shops can drop the smoke screen

Of course it was for marijuana. All of it. The cheapo metal one-hitters that are supposed to look like a cigarette. The glass shelves lined with pocket vaporizers. The $175 Magic Butter machine. All of it.

And at 12:01 a.m. on Thursday in Massachusetts, as recreational marijuana became legal, the shops that have been selling all this paraphernalia could finally end their long public wink, take down the “for tobacco use only” signs, and admit that their glass cases have always been filled with toys for getting high.

“I’m so sick of telling customers they can’t say bong, or marijuana. And I’ll be so glad to not have to say ‘tobacco’ anymore,” said Zelda Feinberg, throwing up huge, dramatic air quotes around the word “tobacco.” Feinberg is one of the cofounders of Buried Treasures, a “smoke shop” that has been pretending it had no idea what you were talking about with this weed stuff in various locations in Boston and Cambridge since 1983.

The “it’s for tobacco” deceit was a thin and often ludicrous charade carried out for decades by shops all over the state. With names like the Trippy Hippy, The Hempest, and Wild Side Smoke Shop, it’s unlikely anybody was fooled. But Massachusetts laws were clear — no sales of drug paraphernalia — and the penalties for violating them stiff, up to two years in prison or fines up to $5,000. So retailers strictly enforced the rules.

Customers who dared drop the “tobacco” ruse at her shop would usually get a warning, Feinberg said, and then the door. No talk of weed. And no using the “b word” — “bong just feels like a drug word,” Feinberg said. Customers were asked to call it a “water pipe” and pretend they were asking about the 4-foot, 4-inch chambered glass tower because they just weren’t getting enough out of their cigarettes.

“Now I don’t care what you call it. Call it a bong. Call it whatever you want,” said Feinberg, who said she stopped pretending about all of it after the ballot measure passed in November. For the first time in the shop’s 33-year history, they brought in apparel featuring the marijuana leaf. “Having that stuff in here feels like a big deal. We always had to be so careful.”

Upholding the “for tobacco use only” façade has always meant that it is somehow plausible that the product be usable for tobacco or some other legal pursuit. Could you use a glass pipe for tobacco? Most definitely. Could you eat a cookie made with tobacco butter? Technically, probably. Could you use the carbon-lined odor-absorbing messenger bag on sale at Buried Treasures for something other than transporting marijuana? Sure. Are there scenarios in which you’d want to disguise a cigarette by using a metal cigarette? Maybe so. And on and on. That has been the drill: Just pretend the items sold by the shop were for tobacco and everything was fine.

And now, well, it’s over. Right? Everyone can drop the act on Thursday? Just up the street from Buried Treasures in Allston, Richard Lamoretti, the owner of Fast Eddie’s Smoke Shop, still wasn’t ready to budge. “I’ve got a copy of the old laws around here somewhere,” he said, sifting through binders behind the counter. “The section on paraphernalia is like four pages long and whoever wrote it was good.”

He asked a Globe reporter to read him the new law, twice, which states that it is not a crime “for possessing, purchasing or otherwise obtaining or manufacturing marijuana accessories or for selling or otherwise transferring marijuana accessories to a person who is 21 years of age or older.”

His face continued to make clear that he was not sold.

“My current story is that this is all for tobacco use only,” he said.

On Thursday, would that change? Would he admit that nearly everything in his shop was for weed?

“You just told me that I can, right?” he asked, still with the suspicious face, triggering another assurance that no one here was a narc.

“I’ll tell you this, though,” he said finally. “We’re not going to have any huge jump in our business.”

And why is that?

“Because I don’t think we have many law-abiding citizens who have been sitting around waiting until it was legal to say the word bong.”

Stunning discovery: Marijuana may be harmful

Bad news, marijuana users: a new study claims that the drug isn’t as safe as you might think it is — and in one very key way is just as bad as tobacco smoke. The study, published in the Journal of the American Heart Association, states that second hand marijuana smoke is just as harmful as tobacco smoke on blood vessels, so you might want to think twice before you toke up.

In fact, it was actually a lot worse. Scientists exposed rats to both pot and tobacco smoke for one minute. Their blood vessels narrowed and it took 90 minutes to widen again for rats exposed to tobacco smoke — it took three times as long for rats exposed to marijuana smoke, according to the study.

The researchers decided to conduct this study because of what they felt was a lack of attention on the dangers of the actual smoking of marijuana versus just the drug itself. The study showed that, just like tobacco smoke, chronic marijuana smoking can narrow and harden your arteries which can lead to potentially deadly cardiovascular complications.

One minute of secondhand marijuana smoke impairs cardiovascular function

One minute of exposure to secondhand smoke (SHS) from marijuana diminishes blood vessel function to the same extent as tobacco, but the harmful cardiovascular effects last three times longer, according to a new study in rats led by UC San Francisco researchers.

In a healthy animal, increased blood flow prompts arteries to widen, a process known as flow-mediated dilation (FMD). When FMD is compromised, as happens during SHS exposure, blood flow is impeded, and the risks of heart attack, atherosclerosis and other heart problems increase, said UCSF’s Matthew Springer, Ph.D., professor of medicine and senior author of the new study.

“Your blood vessels can carry more blood if they sense that they need to pass more blood to the tissues,” Springer said. “They dilate to allow more blood through. But that’s inhibited by exposure to smoke.”

Previous work by Springer and others has shown that as little as one minute of exposure to tobacco SHS diminishes FMD, but the effects of marijuana SHS hadn’t been examined. In the new research, published online in the July 27, 2016, issue of the Journal of the American Heart Association, a team of scientists in Springer’s laboratory measured rats’ FMD, which works similarly to FMD in humans, before and after exposure to both tobacco SHS and marijuana SHS.

The researchers found that rats exposed to marijuana SHS experienced a more than 50 percent reduction in FMD, similar to the reduction in artery function seen in both rats and humans exposed to tobacco smoke in previous studies. As with tobacco, the reduction occurred after just one minute of exposure to SHS from marijuana.

However, while rats exposed for one minute to tobacco SHS recover within 30 minutes – an observation that was reproduced in the new study – one minute of exposure to marijuana SHS still significantly affected FMD 90 minutes after the initial exposure.

Filling a void in secondhand smoke research

The research group used equipment designed to mechanically “smoke” cigarettes and fill a reservoir with the resulting smoke. In a series of experiments using marijuana ciagarettes, when the smoke in the collecting chamber was determined to be at a level roughly comparable to those found in restaurants that allow smoking, the rats were exposed to the marijuana smoke.

Using methodology that they developed for previous tobacco studies, the researchers temporarily blocked off blood flow to rats’ legs after they were exposed to SHS. They then let the blood rush back into the arteries and used ultrasound technology to measure the resulting widening of the femoral artery, a vessel similar to the human brachial artery of the arm, where FMD is typically measured in clinical studies.

The study fills a void in SHS research, as marijuana studies are difficult to undertake because of its illicit status and the numerous agencies, such as the Drug Enforcement Agency and the Food and Drug Administration, that must approve the use of the drug in experiments.

“The biggest reason that people believe marijuana secondhand smoke is harmless is because the public health community hasn’t had direct evidence of its harmful effects like it does with tobacco,” Springer said. “We hadn’t done the experiments, so I think there is definitely an underestimation of how harmful marijuana smoke is.”

To ensure the effect on FMD wasn’t a result of smoke from the rolling paper used in marijuana cigarettes or the cannabinoid compounds like tetrahydrocannabinol (THC, the main psychoactive substance in marijuana), the researchers also tested marijuana not rolled in paper and with cannabinoid compounds removed. Arterial function was still impaired in those situations, leading the team to conclude that smoke from burning marijuana plant matter itself caused the decline in FMD.

‘Just avoid smoke’

The rats were likely exposed to less SHS than people at certain rock concerts, such as one Springer attended in 2010, where there were so many people smoking marijuana that there was a haze in the air. This experience prompted his curiosity about whether marijuana SHS was really as benign as people made it out to be.

“It was really interesting to me, and distressing, because all these people in the stands would not tolerate it if the person next to them started smoking a cigarette,” Springer said, “but they were fine with the marijuana.”

Springer’s preliminary findings, presented at the November 2014 American Heart Association Annual Scientific Sessions, helped inspire California Assembly Bill 2300, a proposed law working its way through the State Legislature that would allow landlords to prohibit marijuana smoking —even for medicinal purposes—if smoking is already banned in their building. The medicinal use of marijuana complicates such public policy questions, Springer said, but he believes the current study solidifies the evidence that exposure to marijuana SHS carries risks.

“At this point, we’re saying that inhaling any smoke is detrimental to your health,” Springer said. “I think that people should avoid inhaling smoke whether it’s from tobacco or marijuana cigarettes, forest fires, barbecues—just avoid smoke.”

Study co-authors from Springer’s UCSF lab are Xiaoyin Wang, M.D.; Ronak Derakhshandeh, MS; Jiangtao Liu, M.D.; Shilpa Narayan; Pooneh Nabavizadeh, M.D.; Stephenie Le; Olivia M. Danforth; Kranthi Pinnamaneni, M.D.; Hilda J. Rodriguez; Emmy Luu; and Richard E. Sievers. Other UCSF co-authors include Suzaynn F. Schick, Ph.D., assistant adjunct professor of medicine, and Stanton A. Glantz, Ph.D., professor of medicine.

The study was funded by the National Institutes of Health’s National Institute on Drug Abuse, and the Elfenworks Foundation.

For big marijuana, Grit win means money in the bank

Those with a stake in cannabis-related companies weren’t just hoping the Liberals would win the federal election, they were banking on it.

Legalized marijuana could be a budding into big business in Canada if the party follows through on its much-publicized campaign pledge, with one analysis projecting a $5 billion market for recreational weed.

The same analysis paints a picture of the path legalization will take, at first mimicking alcohol sales, then becoming subject to potential takeovers by Big Tobacco — a scenario that has long worried critics of Justin Trudeau’s legalization plan.

In a report published the morning after the Liberals cruised to a majority win at the polls, Bay St. investment dealer Dundee Capital Markets valued the current medicinal marijuana market at $80 million, projecting that number to balloon to $1.2 billion by 2024, with the number of licensed patients expected to increase tenfold over the next decade to as many as 450,000 cannabis card-carrying Canadians.

The market projection for recreational weed ranges from $1.5 billion to $5 billion annually.

And the biggest winners on election night, according to the report, were the pot producers already licensed to grow medical cannabis.

Chief among those is Canopy Growth Corp., which operates the Tweed plant in Smiths Falls as part of three properties totalling 500,000 sq. ft. of prime growing space, and the first licensed grower to go public on the stock exchange.

Current Liberal Party of Canada chief financial officer Chuck Rifici is the co-founder and former CEO of the company, and remains its largest shareholder.

The 7.8 million shares Rifici owns in the company netted him a cool $5 million in the days immediately following the election.

A federal Liberal party spokesman said he was not aware of any other high-level Liberal staffers or MPs with an ownership stake in marijuana companies.

A few notable politicians have previously jumped into the pot game shortly after leaving politics.

Former Ontario Health Minister George Smitherman sits on the board of medical marijuana company Thelon Capital, and David Caplan, his successor on the province’s health file, left Queen’s Park to join Nutritional High, a Toronto-based company developing edible cannabis products for the booming U.S. market in states where recreational weed is already legal.

The Dundee report said while the outgoing Conservative government established the current medicinal marijuana network in Canada, the legalization of recreational weed would have been “highly unlikely” had the Conservatives kept power.

But the report could also provide opponents with fodder, predicting Big Tobacco is “the likely candidate to take over large (medicinal marijuana) companies after recreational legalization has been rolled out.”

Dundee believes a “tipping point” could occur if tobacco companies are allowed to distribute marijuana, saying Big Tobacco has a “comparable” business model, the capability to market nationally, growing and manufacturing experience, and the need for new revenue streams.

“It’s no secret that Big Tobacco is hurting,” Salz wrote.

Canopy stock, which had been sluggish since its initial public offering in April 2014, has now been rising steadily since election night.

The report called Canopy “arguably the strongest and most recognizable potential ‘recreational’ brand in the industry,” and noted its “tremendous expansion potential” when advising investors to buy stock.—-Recreational????


But Canopy bested even Dundee’s forecasts, trading around $2.00 on Oct. 19, and peaking at $2.72 by Friday’s closing bell.

“The markets have performed extremely well, even from about a week before the election when it looked like the Liberals were pulling away,” said Salz, with cannabis-related stocks rallying between 20-30% in the days following the election. “The stocks have retained their gains and they’re trading better than they ever have, and there’s a lot more interest in the (marijuana) space ever since this election.”

Salz believes once legalized recreational marijuana becomes a reality — with the firm estimating that day is likely still 18 months to two years away — the markets will rally once again.

“Once you have more of a path towards a framework (of legal marijuana), the impact on these companies will be quite material, and the stocks will trade again on that,” said Salz.

Canopy hasn’t been resting on its laurels, instead following the post-election buzz with a series of announcements. Subsidiary Tweed announced it will sponsor the 2015 High Times Cannabis Cup in Jamaica, another country experiencing sweeping reforms to marijuana laws, and also launched a face-to-face customer service centre for inquiring Canadians. Last week, the company announced a $12.5 million equity deal with Dundee.