Quick Hits

Welcome to Project CBD Quick Hits, where we collect some of the most interesting and informative tidbits of research into cannabis over the past week.

Lupus and ABHD6

Posted: February 24, 2019

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

Posted: February 22, 2019
Hoarding money

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

Posted: February 20, 2019

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

Posted: February 20, 2019
Marijuana leaf and handcuffs

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

Posted: February 20, 2019
stop sign and crossing guard

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

Posted: February 20, 2019

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.

Who's in My Entourage?

Posted: February 20, 2019
Image of PPAR-Gamma molecule

The entourage effect was a term first used to describe the various endocannabinoids that work together. Recent research emphasizes how two of these chemicals (OEA and PEA) exert subtle anti-inflammatory and antidepressant effects through a receptor called PPAR-alpha. PPAR-alpha regulates gene expression. Many plant cannabinoids - including CBD and THCA - activate the related protein, PPAR-gamma. OEA and PEA are chemically very similar to anandamide and all three are primarily broken down by the same enzyme, FAAH. The medical effects of FAAH inhibitors are probably due, in large part, to the elevation of these endogenous entourage chemicals.

CBD vs. Methamphetamine

Posted: February 11, 2019

Little needs to be said about the devastating impact methamphetamine abuse can have. It is a highly addictive substance whose use can lead to transient psychotic behavior and long-term cognitive problems. As part of an Iranian researcher’s PhD thesis, two scientists demonstrate that CBD can reduce the likelihood of methamphetamine relapse, even while one deals with stresses like sleep deprivation. This is particularly important because drug withdrawal often causes temporary insomnia, yet many of the medications that induce sleep are highly addictive. The researchers injected CBD directly into rats’ brain and measured the conditioned place preference for meth - a common preclinical predictor of addiction and relapse - under different experimental conditions. The implications for humans are, of course, speculative as of now.

Safer Sex

Posted: February 11, 2019
Image of a lab technician at work

Much funding has been devoted to studying drug use and risky sexual practices. While this is a serious issue that should be addressed, such research has been misused to stigmatize marginalized groups. It is used to justify greater enforcement of racist drug laws in communities of color by insinuating that poor black women are misusing their autonomy, and hence need to be forced into rehabilitation programs for their own good. But even the premise may be wrong among cannabis users. Researchers in Los Angeles have recently shown that, among homosexual men, cannabis users are safer about sex and have dramatically lower rates of STIs compared with people not using illicit drugs or using other illegal drugs.

Cannabis for Weight Loss

Posted: February 11, 2019
Image of doctor measuring BMI

In spite of the munchies, using THC-rich cannabis is associated with lower weight and a smaller risk for Type II diabetes. This is well substantiated by human epidemiology and research. But it naively seems to contradict quite a bit of preclinical research on the role of the endocannabinoid system in metabolism, which has shown that activating the CB1 receptor promotes weight gain and reduces insulin sensitivity. Researchers at Indiana University suggest one explanation in a new paper, based on the fact that the modern western diet incorporates much fewer omega-3 fatty acids than omega-6. Omega-6 fatty acids are precursors to endocannabinoids, and so the imbalance in the Western diet may lead to overactivity at CB1 in metabolic tissues. Heavy or long-term cannabis use could desensitize the CB1 receptor, offsetting the effect of the elevated levels of endocannabinoids from diet. This is a plausible explanation, although other reasons have been proposed as well. According to the scientists, “Once patients become aware that the side effects of medical Cannabis may include weight loss and reduced risk of obesity-associated medical conditions, [the] shift toward medical Cannabis is likely to accelerate. Available data suggests that this will save many lives, not only from reduced rates of obesity-related chronic illness, but also from reduced deaths from pharmaceutical overdose” [emphasis added]. That’s certainly food for thought.