A preclinical study found that repeated CBG treatment prevented a long-term recognition memory impairment induced by MK-801 in male rats, an experimental model used to study cognitive deficits relevant to schizophrenia. The effect did not appear to involve restoring reduced BDNF protein levels, though changes in TrkB messenger RNA point to a possible mechanism that will require further research.

CBG (cannabigerol), the precursor molecule from which THC and CBD are formed in the cannabis plant, and a cannabinoid far less studied than either of them, has just given researchers another reason to pay attention.

A preclinical study published online ahead of print by Pharmacology Biochemistry and Behavior found that CBG prevented a long-term memory deficit in male rats treated with MK-801, a compound commonly used in experimental models of cognitive impairments associated with schizophrenia.

Does that mean CBG improves memory in people with schizophrenia? No, but the results offer an interesting clue about a problem for which there are still no approved treatments: the cognitive deficits that can accompany the disorder.

CBG and a Memory Problem

Schizophrenia affects about 23 million people worldwide, or roughly one in 345, according to the World Health Organization, and can cause persistent difficulties across a range of cognitive functions.

These impairments can affect memory, attention, learning and executive function, and can have real-world consequences for a person’s ability to study, work, maintain relationships or live independently. The authors of the new study describe the pharmacological options for treating them as limited, note that some research finds all antipsychotics have minimal effect on cognitive function, and cite estimates that 30% to 35% of patients with schizophrenia are treatment-resistant.

That’s where the new study comes in. It was carried out by researchers at the Instituto de Investigaciones Biológicas Clemente Estable and the Universidad de la República, in Uruguay, together with colleagues at Phytoplant Research, the Universitat de Vic-Universitat Central de Catalunya, the University of Barcelona and Spain’s Biomedical Research Networking Center in Mental Health.

To study CBG’s potential effects, the researchers used MK-801, a substance that blocks certain NMDA receptors in the brain. In animals, this compound can cause cognitive impairments that mimic some of the deficits observed in schizophrenia, which is why it is commonly used as an experimental model.

The study used 67 adult male Wistar rats, bred and housed at the institute’s facilities in Montevideo. The researchers gave them repeated doses of CBG at 10 mg/kg, and some of the animals then received a single 0.1 mg/kg dose of MK-801, while others received a control solution. Then came the test.

Did the Rats Remember What They Had Seen?

To measure memory, the researchers used a fairly intuitive test known as novel object recognition.

First, the rats are exposed to certain objects. The following day, one of them is replaced with a new one.

Normally, if an animal remembers what it saw before, it spends more time exploring the new object. If it fails to distinguish between the old and new objects, that may indicate impaired recognition memory.

That is exactly what happened in the rats that received only MK-801: they stopped showing a preference for the new object.

By contrast, the rats that had received CBG retained that ability, even after receiving MK-801.

According to the authors, CBG prevented the long-term recognition memory impairment caused by the experimental compound.

The researchers also had to rule out a much less exciting explanation: that the treated rats were simply moving around more and therefore spent more time exploring. According to the study, neither MK-801 nor CBG nor the combination affected locomotor activity. MK-801 did reduce rearing, the behavior of standing up on the hind legs, but the authors report that this did not change how long the animals spent exploring the objects.

Things Got a Little Stranger Inside the Brain

The researchers also tried to determine how that effect might be occurring.

One of the main suspects was BDNF, a protein associated with brain plasticity, learning and memory.

MK-801 reduced BDNF protein levels in two regions involved in these processes: the hippocampus and the medial prefrontal cortex. If CBG was preventing the cognitive impairment, one logical possibility was that it might also restore those BDNF levels. But it didn’t.

Even though the rats maintained their performance on the memory test, CBG did not restore the BDNF protein levels reduced by MK-801.

Then another clue emerged: the combination of CBG and MK-801 significantly increased messenger RNA expression for TrkB, a receptor closely involved in BDNF signaling, in the medial prefrontal cortex.

In very simplified terms, CBG appeared to influence part of the molecular machinery involved in memory, but not through the most obvious mechanism the researchers expected to find.

The authors suggest that TrkB signaling may contribute to the observed effect through a mechanism independent of direct changes in BDNF.

Promising, Yes; a Treatment, Not Yet

The study was conducted exclusively in male rats. The researchers did not test different CBG doses or dosing schedules, and they have not yet confirmed whether the changes observed in TrkB messenger RNA extend to the protein level.

Also, MK-801 does not give rats “schizophrenia.” It is an experimental tool that mimics certain cognitive deficits relevant to the study of specific aspects of the disorder.

For that reason, the results do not show that CBG treats schizophrenia, improves memory in human patients or should be used clinically for that purpose.

What they do show is something much narrower and, for that very reason, still interesting: in this preclinical model, CBG was able to preserve a form of memory that MK-801 had impaired.

And for a cannabinoid that remains far less studied than its more famous relatives, that is enough to justify a second look.

Disclosure: the study was funded by Uruguayan public science programs, including MEC-DICYT and PEDECIBA. The cannabigerol was donated by Phytoplant Research S.L.U., a Spanish cannabis research company, and two of the paper’s authors, Carlos Ferreiro-Vera and Verónica Sánchez de Medina, work for the company, according to its competing interest declaration.

Editor’s note: this article describes findings in animals. Preclinical research is an early step and does not establish that a compound is safe or effective in people. Nothing here is medical advice, and no one should change or stop a prescribed treatment based on it.

Source link

Headlines around the world tied a captain’s positive marijuana test to a terrifying midair plunge. He wasn’t the one flying. The first officer was at the controls, and Airbus says the aircraft registered pressure losses across all three hydraulic systems and that key flight controls stopped responding for four seconds. Every one of those headlines was technically true. Together, they told a story the investigation hasn’t established.

You have probably seen some version of this story by now. An Air India jet flying from Phuket to Delhi dropped roughly 300 feet in cruise, injured 24 people, and its captain later tested positive for marijuana.

Both of those things are true.

Here is what a great many of those headlines left out. The captain who tested positive was not the pilot flying the airplane when it happened. According to his own account to investigators, first reported by Hindustan Times, he was not in his seat. He was standing behind the first officer, and when the aircraft moved, it threw him to the cockpit floor.

The first officer was the one at the controls.

What Happened at 36,000 Feet

Air India flight AI2379, an Airbus A320neo registered VT-EXO, left Phuket on the morning of August 4 with 137 passengers and eight crew members. At around 9:33 a.m. India time, cruising near 36,160 feet over the Odisha coast, the aircraft lost roughly 300 feet of altitude. Twenty passengers and four cabin crew members were hurt. The plane stayed airborne for about another hour and a half and landed safely in Delhi.

Air India first described the event as turbulence. It later dropped that description and called it a sudden loss of altitude. Indian authorities classified it as a serious incident, and the Aircraft Accident Investigation Bureau is investigating with technical help from Airbus and France’s BEA.

The aircraft’s Centralised Fault Display System log, reviewed by Hindustan Times, recorded nine warning messages inside a single minute at around 9:32 a.m. Low pressure in the Green, Blue and Yellow hydraulic systems. Low reservoir levels in Yellow and Blue. An autopilot disconnect. An elevator flight-control fault.

An A320 has three independent hydraulic systems for a reason. They are what move the surfaces that point the airplane up, down and sideways. All three registered pressure loss in quick succession. The Airbus analysis, described by The Tribune, puts it down to the second: one system failed just before 9:32:44 a.m., the other two failed at 9:32:45, and all three came back seven seconds later.

Inside the cockpit

The first officer is flying the aircraft. The captain, acting as pilot monitoring, is standing behind the first officer’s seat after a trip to the washroom, discussing the air conditioning system.

9:32:44 a.m. IST. One hydraulic system fails. One second later, the other two go. Nine warnings hit in under a minute. The autopilot disconnects.

The aircraft pitches upward. For roughly four seconds, per Airbus, the elevators and ailerons are unusable.

The first officer applies full nose-down input. Airbus says there is “no direct response” from the flight-control surfaces.

Seven seconds after the first failure, all three systems are back. The aircraft drops roughly 300 feet. The captain is thrown to the cockpit floor.

That sequence comes from Airbus’s own preliminary assessment, written in response to a request from Air India and reviewed by Reuters. The manufacturer has not determined why the hydraulic pressure dropped. It has asked the airline to test the hydraulic systems and the sensors that monitor them, to pull some of those sensors for inspection, and to check the aircraft for structural damage, because the jet took forces beyond its specified limits during the drop. It also wants maintenance records covering the previous month and fuller accounts from both pilots.

Reuters also reported, plainly, that no link has been established between the captain’s test result and the loss of altitude.

Everything the Captain Is Facing

None of the above is a defense of Sudeep Vashistha, and this piece is not going to pretend otherwise.

A post-flight screening returned a non-negative result. A confirmatory test came back positive for cannabis. Investigators questioned him for over an hour. He told them he had been struggling to sleep for some time because of personal circumstances, that he had not slept well during the Phuket layover, and that he was taking medication prescribed by his family doctor for the problem. He also told them he had slept for 30 to 35 minutes during the flight itself.

Both pilots have been pulled from the flying roster pending the outcome of the investigation. Air India began mandatory psychoactive substance screening for its entire pilot workforce on August 13, across the mainline carrier and Air India Express, going further than what the Directorate General of Civil Aviation currently requires.

Whether a captain running on very little sleep, taking medication whose disclosure status remains unclear, and with cannabis metabolites in his system should have been in that cockpit at all is a serious question. Investigators have every reason to ask it. Air India has every reason to answer it.

It is a different question from what made the airplane drop.

Technically True Is Not the Same as True

Look at how the story got packaged. A plane dropped 300 feet. A pilot tested positive for marijuana. Put those two sentences next to each other, in that order, under one headline, and the reader does the rest of the work without being asked.

Nobody had to write the word “caused.” The arrangement said it.

Imagine a car crashes and the owner is drunk. Now imagine he was in the passenger seat and his sober brother was driving. “Car Owner Was Drunk When Vehicle Crashed” is a true sentence. It is also a sentence that leaves a reader believing something the reporter knows is not the case.

There is a second thing worth saying, and it is the point cannabis consumers have been making for decades in every context from job applications to custody hearings. A positive result for cannabis metabolites establishes exposure. It does not establish when, and it does not establish impairment at any particular moment. That is a real limitation of the test and it is well understood.

But that argument is not even necessary here, which is what makes this case unusual. You do not have to litigate toxicology. You only have to ask who was holding the controls.

Maybe Sudeep Vashistha had no business anywhere near that cockpit on August 4. Investigators will decide that, and they should. Maybe his test result will end up mattering to the final report.

But if a positive marijuana test was important enough to put in the headline, who was actually flying the airplane was important enough to mention.

Source link