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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.

FDA Trouble Ahead For Vaporizer Stocks?

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Swiss boffins create cannabis e-cigarette

Swiss scientists have created a cannabis e-cigarette, intended for medical use, that is safer than a joint and better than a pill, they said on Thursday.

“Therapeutic cannavaping”, they argued, should be examined as an alternative to existing medical treatments which can come in the form of a syrup, pill, mouth spray, skin patch, suppository, or a plain-old spliff.

The team copied an improvised method popular among marijuana afficionados using butane gas to extract and concentrate cannabinoids — the active, high-causing compounds of cannabis.

“We were inspired by what is done illegally, underground, on the web fora,” study co-author Vincent Varlet, a biochemist and toxicologist from the University Centre of Legal Medicine in Lausanne, told AFP.

“Normally, they use this form of cannabinoids to get high. Based on what is done illegally, we found that it could be interesting” for the medical field.

The method yields super-concentrated “dabs” of butane hash oil (BHO) comprising about 70-80 percent THCa, the precursor of THC or tetrahydrocannabinol, which is the psychoactive ingredient. THCa is transformed into THC at high heat.

Usually the dabs are burnt and the fumes inhaled. But for the study, the team mixed their activated BHO paste into commercially-available e-cigarette liquid at different concentrations — three, five or ten percent.

They then put “vaping machines” to work: sucking at the e-cigarettes and blowing out vapour, which was measured for its THC content, according to results published in the nature journal Scientific Reports.

“Cannavaping appears to be a gentle, efficient, user-friendly and safe alternative method for cannabis smoking for medical cannabis delivery,” the team concluded with a nod to “the creativity of cannabis users”.

It was also more reliable than consuming cannabinoid pills or foods which are poorly and erratically absorbed, said Varlet.

Safer pain relief?

Battery-powered e-cigarettes heat up liquids containing artificial flavourings, with or without nicotine, to release a vapour which is inhaled and exhaled much like smoke.

They are touted as safer than the real thing, and an aide for giving up cancer-causing tobacco — which is also an ingredient of the traditional cannabis joint.

Cannabis-infused e-liquids are advertised online, along with a rash of recipes for making your own.

Medical marijuana can be legally prescribed in some countries for pain relief, appetite stimulation, nausea reduction or the relief of muscle spasms.

A challenge, said Varlet, was to keep cannabis intended for therapeutic use out of the hands of recreational high-seekers.

One way to do that was to have legal drugs with microdoses of cannabinoids.

“We have calculated that to have the same dose of what is present in a real cigarette joint… with tobacco, we have to vape between 80-90 puffs” of the 10-percent BHO liquid, said Varlet.

“Eighty puffs constitutes a rebuttal to getting high,” he added, when a few drags from a joint will do.

“The take-home message of our article is that vaping is less harmful than smoking, so you can be sure that cannavaping is less harmful than cannabis smoking for medical purposes,” said Varlet, adding there was no plan to patent or sell the product.

“Today, we have set the cat among the pigeons. This is just the first step, and we need to see how the scientific community is going to welcome this kind of possibility.”

Vaping Could Make Medical Pot Healthier

A new type of smoking called “cannavaping” — using e-cigarettes for vaping cannabis — may help people use marijuana for medical reasons, according to a small, early study.

Smoking conventional marijuana cigarettes may lead a person to inhale high amounts of the toxic contaminants that are released when marijuana is burned, the researchers said. In contrast, cannavaping might provide a way to avoid inhaling high levels of these contaminants, the researchers said. Among these contaminants are carcinogenic compounds called polycyclic aromatic hydrocarbons, the researchers said.

Vaping involves heating a liquid to its boiling point and then inhaling the vapors; conventional smoking involves burning a substance, such as marijuana, and then inhaling the smoke.

“Vaporization should lead to a lower toxic burden than combustion [burning],” lead study author Vincent Varlet, an analytical chemist at the University Centre of Legal Medicine in Lausanne, Switzerland, told Live Science. “Vaporization constitutes a safer approach of cannabis administration than cannabis smoking.”

There are also devices available that can vaporize marijuana and are designed to sit on a tabletop, but e-cigarettes may be more user-friendly, the researchers said. Both e-cigarettes and tabletop vaporizing devices are likely to be less harmful than marijuana joints, the investigators said.

In the study, researchers looked at the plausibility and efficiency of cannabis vaping as an alternative to smoking the substance for medical reasons. The scientists extracted active compounds in marijuana called cannabinoids and made an oil that they concentrated in an e-liquid, which is a type of liquid used in e-cigarettes.

However, they found that the concentration of the oil they made in the study was not sufficient. About 100 puffs on an e-cigarette would have been needed to induce the same therapeutic effects as those provided by intravenous administration of THC, one of marijuana’s most powerful compounds, the researchers said. More research on the preparation and optimization of such liquid is needed, they said.

However, cannavaping might still one day provide a safer alternative to smoking cannabis, because it does not require heating the cannabis to the high temperatures reached when it is burned, the researchers found. That process leads to the inhalation of high levels of contaminants, the scientists found.

“Cannavaping appears to be a gentle, efficient, user-friendly and safe alternative method for cannabis smoking for medical cannabis delivery,” they wrote in the study, published today (May 25) in the journal Scientific Reports. [4 Myths About E-Cigarettes]

Cannavaping may also offer an alternative to ingesting marijuana by eating products such as brownies or candies. When marijuana is consumed in this way, it is metabolized before it enters a person’s bloodstream and its therapeutic ingredients may therefore become less active, Varlet said. This diluting effect does not occur with cannavaping, which allows the inhaled therapeutic compounds to enter the bloodstream directly, he said.

The researchers noted that they tested only one type of e-cigarette in the new study, and other brands that are available may produce different levels of certain impurities.

‘Cannavaping’ could see e-cigarettes used to deliver medicinal cannabis

Vaping medicinal cannabis would be healthier than smoking the drug with tobacco, researchers claim, and allow regular microdoses not possible with pills

Electronic cigarettes can be a safe and effective way to deliver cannabis for medicinal purposes, according to researchers in Switzerland.

Scientists at the University of Lausanne created cannabis-laden oils for e-cigarettes and found that vaping the infusions could deliver useful levels of the active ingredients found in cannabis.

The team claims that “therapeutic cannavaping”, would be healthier than smoking the drug with tobacco, and would allow users to have regular microdoses of the drug’s active ingredients throughout the day, which is not possible with pills containing cannabis extracts.

“This could be a great approach to using these kinds of cannabinoids,” said Vincent Varlet, who took part in the work. “The aim is not to get high, the aim is to get cured.”

Varlet and others used butane gas to extract the active substances, called cannabinoids, from cannabis to create concentrated butane hashish oil. They then tested how well the oil was atomised in e-cigarettes on the market.

Writing in the journal Scientific Reports, the researchers describe how e-cigarettes can deliver therapeutic doses of cannabinoids without getting people stoned. “Cannavaping appears to be a gentle, efficient, user-friendly and safe alternative method for cannabis smoking for medical cannabis delivery,” they say.

In the course of their experiments, the scientists found that butane hashish oil is not very soluble in the liquid refills used in commercial e-cigarettes, leading them to suspect that the risks of people abusing the drug through vaping are low.

“I think it’s a great idea, but this would be illegal in the UK,” said David Nutt, head of neuropsychopharmacology at Imperial College, London. In Britain, cannabinoids in vapable oil form would likely be considered “controlled drugs” under the Misuse of Drugs Act, or psychoactive substances under the Psychoactive Substances Act, which comes into force in the UK today. “I hope parliament makes cannabis a medicine soon,” Nutt added.

But Michael Bloomfield, a clinical lecturer in psychiatry at University College London, has concerns about vaping cannabis oil. “We really need more studies and to look at whether cannabis through e-cigarettes can be use for medicinal purposes,” he said. “From a harm reduction point of view, cannavaping sounds like it may be a good thing, but if this is going to be used as a medicine, it has to go through all the same checks and balances as other medicines.”

“Branding cannabis use through an electronic cigarette as ‘therapeutic cannavaping’ is worrying given that proper randomised controlled trials need to be conducted on any medical intervention to demonstrate their effectiveness, something that is currently lacking in much of the ‘medical marijuana’ market,” he said.

Another concern, he added, was the use of flavoured cannabis e-cigarettes that might become popular with younger people, who appear most at risk from some of the harms linked to heavy, long-term use of cannabis.

Smoke without fire – Japan becomes test ground for real tobacco e-cigarette

Two tobacco giants are seeing strong demand for their reboots of the e-cigarette in Japan, with Philip Morris International (PM.N) twice postponing a nationwide rollout and Japan Tobacco (2914.T) suspending shipments – both due to supply shortages.

Japan has become a key testing ground for the two companies and their new, real tobacco esmokes as they grapple with shrinking demand for traditional cigarettes in other developed countries.

Philip Morris, the world’s largest tobacco company, has postponed the nationwide rollout of its iQOS to April 18.

“We believe that the success of iQOS commercialisation in Japan will accelerate its global expansion,” Philip Morris Japan president Paul Riley told Reuters.

Japan Tobacco CEO Mitsuomi Koizumi told an earnings briefing in February: “We have very high expectations for growth of the so-called tobacco vapour category in five years or so from now.”

The iQOS is a tobacco stick that is heated just enough to produce an aerosol but not combust. The company is betting the presence of real tobacco will make it more satisfying to smokers than existing e-cigarettes.

The new device, priced at 9,980 yen (£62.5), appears similar to other e-cigarettes in that it is pen-shaped and battery-powered, and is heated to release tobacco vapour.

A key distinction is the refills, sold as Marlboro HeatSticks. Most e-cigarettes sold elsewhere use nicotine-laced liquid, which is heavily regulated in Japan. A pack of 20 HeatSticks sells for 460 yen, the same as regular Marlboro cigarettes.

Philip Morris has introduced the products in major cities in Switzerland, Italy and other countries, but Japan is the first country it plans a nationwide release.

The company had originally planned to sell the product throughout Japan on March 1, but postponed the launch to the end of the month due to a potential supply shortage after it saw stronger-than-expected sales in 12 prefectures where it has been test marketing.

The company estimates the market share of Marlboro HeatSticks reached 2.4 percent in Tokyo at the end of January.

Japan Tobacco, which commands about 60 percent of Japan’s cigarette market and is the world’s third-largest tobacco maker, has also got in on the action by acquiring two overseas ecigarette makers in the past two years.

In Japan, it has launched the Ploom TECH, priced at 4,000 yen and sold with 460-yen packs of five capsules. Ploom TECH’s selling point is that vapour generated from a liquid cartridge passes through the capsules’ granulated tobacco, creating a taste the company says is close to the real thing.

“There is definitely a need for products that are smokeless but are still satisfying as cigarettes,” said Masanao Takahashi, director at Japan Tobacco’s emerging products marketing division.

Like iQOS, Ploom TECH’s initial launch in the southern Japanese city of Fukuoka proved so popular that the shipment of the device were suspended after a week due to a supply shortage.

It is currently working on a nationwide launch and is also eyeing a global expansion later this year.