Scientists from the Netherlands recently published the protocol for an upcoming study examining how CBD might be helpful in treating specific phobias. The endocannabinoid system is required for eliminating fearful memories, or at least making them palatable. But why have they only published their methods? It’s part of an ongoing movement to make science more accurate. Many statistical methods assume that the researchers plan all of their data analysis before looking at any of the data. Otherwise they might try to explain trends in the data, even spurious ones, based on their own biases. (This is called HARK-ing, or hypothesizing after results are known.) The researchers make their study more reliable by publishing their methods in advance.
What Do Vets Know About CBD?
A number of surveys have asked doctors what they know about cannabis and how comfortable they feel talking with patients about it. A similar survey was recently conducted about CBD and dogs among over 2000 veterinarians in the United States. Less than half of vets were comfortable talking to clients about CBD for pets. Among this group, vets were most comfortable recommending CBD for pain management, anxiety, and seizures in dogs. Young vets were much less likely to talk with clients about CBD or cannabis. Among those who had experience treating pets with CBD, the vast majority (~80%) did not feel that state veterinary organizations provide enough guidance on how to abide by state or federal laws. A similar proportion believed that from a moral and medical perspective, CBD should be allowed for pets. Only 16% of them supported the schedule 1 status of cannabis, and even fewer thought that CBD should remain a schedule 1 drug.
Low Dose THC Can Improve Cognition
THC and other cannabinoids are known to induce neurogenesis — the creation of new neurons — in the brain. There are reasons to believe that this can positively influence diseases like dementia or traumatic brain injury, as well as the ability to learn. Malaysian researchers recently probed the question, does THC improve cognition by inducing neurogenesis? Yes, but only at the right dose. When they applied a dose 6-7 times lower than is commonly used to study THC’s effect on memory, the rats learned from their environment more rapidly and showed signs of neurogenesis in a brain region called the hippocampus. The improvements were even greater after chronic treatment. Unfortunately, these sorts of animal studies are hard to interpret because of the number of factors involved. The results of experiments on THC and cognition may change if the animal is stressed in its learning environment, if mice are used rather than rats, if the dose is given at a different time, etc.
Ketamine Functions Through CB1
Ketamine is a dissociative anaesthetic that has shown some promise for treating severe depression. Historically, it has been used as a tranquilizer in veterinary medicine and as a recreational club drug. Low doses of ketamine prevent pain. Brazilian scientists recently provided evidence that this painkilling effect is partly mediated by the endocannabinoid system: When the scientists blocked the CB1 receptor, ketamine did not prevent pain. And when anandamide levels were boosted, the analgesic effect was potentiated. Previous research by this group showed that ketamine causes endocannabinoids to be released in certain parts of the brain. It will be interesting to see if the antidepressant effect of ketamine is also mediated by endocannabinoids — the primary action of ketamine is to inhibit a glutamate receptor called NMDA, which is intimately involved in long term potentiation (LTP). Cannabinoids also appear to influence depression by regulating LTP.
Lupus and ABHD6
Systemic lupus erythomatosus, often simply called lupus, is a severe autoimmune disorder where the immune system attacks the nucleus of cells — their genetic control center. Problems can be expressed anywhere in the body, though rashes in the skin, joints, and vital organs are most common. Treatment of lupus generally requires intense immunosuppresive drugs, often targeting inflammatory molecules called interferons. But these drugs make a person more susceptible to other diseases. Mutations in the gene encoding ABHD6, which breaks down the endocannabinoid 2-AG, are associated with lupus. Indian researchers probed this connection, suggesting that overactivity of ABHD6 limits the body’s ability to quell its overactive response to interferons. Normally 2-AG will activate CB2 receptors on immune cells, which seems to provide a tonic inhibition of interferon release.
Price Gouging on Life-Saving Medicine
The US is considered to have one of the least efficient medical systems among developed countries. This is particularly apparent when looking at the price of life-saving medications like insulin, the epipen, or the anti-malarial pyrimethamine. Doctors at the Mayo Clinic recently highlighted a case of price gouging on vitamin K1. Vitamin K1 can prevent death when someone accidentally consumes a rat poison like brodifacoum, which has recently been found in some illegal synthetic cannabinoid products. Although veterinary-grade vitamin K1 is sold for $0.61 per 50 mg tablet, the only product legally available to humans are 5 mg tablets costing $70.51 each. This is more than a 1000 fold discrepancy in price. The Mayo clinic doctors describe how initially treating patients for brodifacoum toxicity costs $5,000—$15,000, whereas it ought to be nearly free. As well, the poison remains in the body for months, so patients need ongoing treatment. But many people who use synthetic cannabinoids have limited or no medical coverage, which compounds with the exorbitant price to make life-saving medicine inaccessible.
CBD vs. Alcohol
An unfortunate slogan of the cannabis legalization movement has been “Regulate cannabis like alcohol.” But cannabis, unlike alcohol, is not associated with domestic violence, sexual assault, liver toxicity, cancers, neurodegeneration, and the list goes on. Cannabinoids can, in fact, attenuate many of these issues, as described in a recent review. A group of Canadian scientists systematically reviewed publications about CBD as a drug for people abusing alcohol. They conclude that CBD does not cause harm in humans and does not interact negatively with alcohol. Animal studies suggest that CBD protects against many specific problems, including wet-brain seizures during alcohol withdrawal, neurodegeneration (which leads to aggression and cognitive impairment), inflammation, liver toxicity, and steatosis. CBD also appears to diminish some of the addictive qualities of alcohol. As the scientists note, the major limitation is a lack of clinical studies. Not every beneficial effect of CBD in animal models will apply to humans, but if even a few of these effects pan out it will be significant for alcoholics and heavy drinkers. Currently, there are two medications commonly prescribed to heavy drinkers, naltrexone and acamprosate. But these drugs are only effective in about 10-12% of people. Programs like Alcoholics Anonymous appear more useful than these medications, but still leave many people without sufficient support to quit and stay sober.
No Argument Here
Possession of cannabis in the UK is currently punishable by up to 5 years in prison and an unlimited fine. On January 23, 2019, the Royal College of Psychiatrists in London attempted to hold a debate on the British laws that criminalize cannabis use. But it didn’t take place because none of the psychiatrists present were willing to argue for criminalization. Instead of a debate, David Nutt of the Imperial College of London gave a speech. Nutt highlighted – as many have before him – how criminalizing the use of any drug worsens the lives of both casual users and addicts. He also noted that fears of cannabis in the UK are overblown: “[D]espite a 20-fold increase in cannabis use over the past 50 years, prevalence and incidence of schizophrenia … [has] not increased anywhere near in step.” It is unlikely that these facts will sway the opinion of British regulators. After Nutt criticized the UK’s unscientific classification of drugs back in 2009, he was fired from chairing the Advisory Council on the Misuse of Drugs. Many other organizations, including the Royal Society for Public Health, the Royal College of Physicians, and the British Medical Journal also currently support decriminalizing all drugs.
Driving on 4/20
Driving accidents cause about 60,000 deaths in the US each year, and nearly all of these are due to driver errors. Regulators are still trying to understand the risks associated with driving while high. Canadian epidemiologist recently analyzed data from the stoner holiday 4/20, finding that there was up to a 12% increase in the number of fatal accidents that that day. This is within typical daily variations, suggesting that, if there is an increase in crash risk, it is small. The study aligns with a recent meta-analysis from Norwegian epidemiologist Ole Rogeberg, which deconstructs how the metrics used in traffic research exaggerate the danger of cannabis. The average person who gets high on cannabis before driving appears to have a 30% increase in the likelihood of crashing. (By comparison, driving with a passenger increases the crash risk by 60%, twice as much as cannabis.) Any increase in crash risk should be factored into regulations on cannabis, but fear about cannabis and driving seem to be more motivated by a political ideology of criminalizing cannabis use rather than genuine concerns for safety.
Ibuprofen as a FAAH Inhibitor
Nonsteroidal antiinflammatory drugs (NSAIDs) are one of the most common classes of painkillers, which includes aspirin, ibuprofen, celecoxib, and other pharmaceuticals. Their primary target is an enzyme called cyclooxygenase-2 (COX-2), which metabolizes many lipids (including endocannabinoids!) into a class of inflammatory molecules called prostaglandins. The side effects of NSAIDs are largely due to the inhibition of the related COX-1 enzyme, which can cause significant gastrointestinal problems. But ibuprofen distinguishes itself from other NSAIDs because it is also a FAAH inhibitor, meaning it slows the breakdown of anandamide and related molecules, including PEA and OEA. (These molecules are called fatty-acid ethanolamines.) A new paper by Italian chemists examines the molecular structure of ibuprofen, and explains how slight changes to ibuprofen’s structure can strengthen its ability to inhibit FAAH. Studying the so-called “structure-activity relationship” of existing drugs, as these scientists have done, aids the development of new pharmaceuticals.